
Relationship between subclinical cardiac troponin I elevation and culprit lesion characteristics assessed by optical coherence tomography in patients undergoing elective percutaneous coronary intervention.
Lee Tetsumin,Murai Tadashi,Yonetsu Taishi,Suzuki Asami,Hishikari Keiichi,Kanaji Yoshihisa,Matsuda Junji,Araki Makoto,Niida Takayuki,Isobe Mitsuaki,Kakuta Tsunekazu
Circulation. Cardiovascular interventions
BACKGROUND:The prevalence of subclinical, cardiac troponin I (cTnI) elevation in stable patients undergoing elective percutaneous coronary intervention and its relationship to culprit lesion characteristics assessed by optical coherence tomography (OCT) are unknown. METHODS AND RESULTS:We studied 206 native de novo culprit coronary lesions from 206 patients with stable angina pectoris who underwent OCT before elective percutaneous coronary intervention. Patients were divided into 2 groups according to the presence (cTnI group; n=47; 22.8%) or absence (non-cTnI group; n=159; 77.2%) of cTnI ≥0.03 ng/mL at admission. The clinical and OCT findings were compared between these 2 groups. No significant difference was found in the clinical presentation between the groups except for the serum C-reactive protein levels and presence of multivessel disease. By OCT, cTnI elevation was associated with the presence of thin-cap fibroatheromas, a greater lipid arc, and a longer lipid length. In a multivariable analysis, the presence of positive C-reactive protein levels (odds ratio, 4.38; 95% confidence interval, 1.90-10.08; P=0.001) and OCT-derived thin-cap fibroatheromas (odds ratio, 2.89; 95% confidence interval, 1.22-6.86; P=0.016) were independent predictors of cTnI elevation. Periprocedural myocardial injury, defined as postpercutaneous coronary intervention peak cTnI levels >1.0 ng/mL (5× the upper reference limit), occurred more often in patients with cTnI elevation at admission (cTnI group: 41% versus non-cTnI group: 18%; P=0.001). CONCLUSIONS:The presence of subclinical cTnI elevation at admission was not uncommon and was associated with OCT-derived unstable plaque morphology in patients undergoing elective percutaneous coronary intervention, and may help to identify patients with stable angina pectoris at high risk for periprocedural myocardial injury.
10.1161/CIRCINTERVENTIONS.114.001727
Comparison of circulating dendritic cell and monocyte subsets at different stages of atherosclerosis: insights from optical coherence tomography.
Zhuang Jianhui,Han Yang,Xu Dachun,Zhu Guofu,Singh Shekhar,Chen Luoman,Zhu Mengyun,Chen Wei,Xu Yawei,Li Xiankai
BMC cardiovascular disorders
BACKGROUND:While specific patterns of circulating dendritic cells (DCs) and monocytes are associated with the incidence of coronary artery disease, the characterization of circulating DC and monocyte subsets in patients with different stages of atherosclerosis remains unclear. METHODS:Forty-eight patients with unstable angina pectoris (UAP) diagnosed by angiography were enrolled. Likewise, 31 patients with ST-segment elevation myocardial infarction (STEMI) were enrolled and confirmed with the presence of thrombosis by angiography. Plaque features of 48 UAP patients were evaluated at the culprit lesions by OCT. Circulating myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and monocyte subsets were analyzed using flow cytometry. RESULTS:The proportions and absolute counts of mDC2s, which specifically express CD141 and possess the ability to activate CD8+ T lymphocytes, significantly decreased in patients with UAP and STEMI when compared with controls (0.08 × 10 ± 0.05 × 104/ml and 0.08 × 10 ± 0.06 × 104/ml vs. 0.11 × 10 ± 0.06 × 104/ml, p = 0.027). On the other hand, patients with UAP and STEMI had significantly higher proportions and counts of Mon2 subsets. In the OCT subgroup, patients with thin-cap fibroatheroma (TCFA) had higher proportions and absolute number of Mon2 (11.96% ± 4.27% vs. 9.42% ± 4.05%, p = 0.034; 5.17 × 104/ml ± 1.92 × 104/ml vs. 3.53 × 104/ml ± 2.65 × 104/ml, p = 0.045) than those without TCFA. However, there was no remarkable difference in mDC2s between patients with and without TCFA. CONCLUSIONS:Circulating Mon2 appears to be a promising marker for the severity of atherosclerotic plaque.
10.1186/s12872-017-0702-3
Assessment of carotid plaque neovascularization using quantitative analysis of contrast-enhanced ultrasound imaging is useful for risk stratification in patients with coronary artery disease.
Nakamura Jun,Nakamura Takamitsu,Deyama Juntaro,Fujioka Daisuke,Kawabata Ken-ichi,Obata Jun-ei,Watanabe Kazuhiro,Watanabe Yosuke,Kugiyama Kiyotaka
International journal of cardiology
BACKGROUND:Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization, a feature of unstable atherosclerotic plaques. This study examined whether assessment of intra-plaque neovascularization of the carotid artery using CEUS provides prognostic information in patients with coronary artery disease (CAD). METHODS:A total of 206 patients with stable CAD underwent a CEUS examination of the carotid artery and were followed up prospectively for <38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (uAP) requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque was quantified by calculating the mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. RESULTS:During the follow-up period, 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazard analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.13; 95% CI, 1.05-1.21; p<0.001). The addition of the plaque enhanced intensity to traditional risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.62, p=0.001; and IDI 0.106, p=0.002). CONCLUSIONS:The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD.
10.1016/j.ijcard.2015.05.107
Elevated plasma levels of Mac-2 binding protein predict poor cardiovascular outcomes in patients with acute coronary syndrome.
Xie Hao,Zhang Zhun,Chen Liming,Zhang Pu,Cui Yuqi,Liu Hang,Ma Hongrui,Jiang Yufan,Wang Ying,Yang Le,Wu Hongpeng,Cui Lianqun
Coronary artery disease
BACKGROUND:Mac-2 binding protein (M2BP) is an inflammatory glycoprotein associated with carotid atherosclerosis and all-cause mortality in patients with suspected coronary artery diseases. We aimed to explore the potential association of plasma M2BP levels with unstable plaque morphology and cardiovascular outcomes in patients with acute coronary syndrome (ACS). PATIENTS AND METHODS:We compared plasma M2BP levels among three groups: 216 patients with ACS, 82 patients with stable angina pectoris, and 50 controls. Angiographic analyses of complex lesions were carried out in patients with ACS and they were followed up prospectively for 12 months for the occurrence of major adverse cardiovascular outcomes (MACEs). RESULTS:Patients with ACS showed significantly higher plasma levels of M2BP than patients with stable angina pectoris (P<0.001) and controls (P<0.001). M2BP levels correlated positively with the presence (P<0.001) and extent (P=0.005) of complex lesions. During follow-up, 45 (20.8%) cases of MACEs occurred. Survival analysis indicated that high M2BP levels were associated with a poor prognosis (log-rank P=0.008). After Cox multivariate adjustment, plasma M2BP levels remained an independent predictor of MACEs either as a continuous variable (hazard ratio: 1.178, 95% confidence interval: 1.093-1.270, P<0.001) or as a categorical variable (hazard ratio: 2.783, 95% confidence interval: 1.433-5.404, P=0.002). CONCLUSION:Plasma M2BP levels might be predictive of unstable plaque and were associated independently with poor cardiovascular outcomes in patients with ACS.
10.1097/MCA.0000000000000540
Correlation between genetic polymorphism of matrix metalloproteinase-9 in patients with coronary artery disease and cardiac remodeling.
Yu Qibin,Li Hanmei,Li Linlin,Wang Shaoye,Wu Yongbo
Pakistan journal of medical sciences
OBJECTIVE:To explore the correlation between genetic polymorphism of matrix metalloproteinase-9 (MMP-9) in patients with coronary artery disease (CAD) and cardiac remodeling. METHODS:A total of 272 subjects who received coronary angiography in our hospital from July 2008 to September 2013 were selected, including 172 CAD patients (CAD group) and another 100 ones (control group). Both groups were subjected to MMP-9 and ultrasonic detections to determine vascular remodeling and atherosclerotic plaques. C1562G polymorphism of MMP-9 gene was detected, and correlation with vascular remodeling and atherosclerotic plaque was analyzed. RESULTS:Serum MMP-9 level of CAD group (330.87±50.39 ng/ml) was significantly higher than that of control group (134.87±34.02 ng/ml) (P<0.05). Compared with control group, CAD group had significantly higher intima-media thickness, and significantly lower systolic peak velocity, mean systolic velocity and end-diastolic velocity (P<0.05). Total area of stenotic blood vessels was 67.34±22.98 mm(2), while that of control blood vessels was 64.00±20.83 mm(2). G/G, G/C and C/C genotype frequencies of MMP-9 differed significantly in the two groups (P<0.05). G and C allele frequencies of CAD group (70.9% and 29.1%) were significantly different from those of control group (50.0% and 50.0%) (P<0.05). G/G, G/C and C/C genotypes were manifested as lipid-rich, fibrous and calcified or ulcerated plaques respectively. Total area of stenotic blood vessels of G/G genotype significantly exceeded those of G/C and C/C genotypes (P<0.05), whereas the latter two had no significant differences. CONCLUSION:CAD promoted 1562C-G transformation of MMP-9 gene into genetic polymorphism, thus facilitating arterial remodeling and increasing unstable atherosclerotic plaques.
10.12669/pjms.313.7229
Kindlin 3 (FERMT3) is associated with unstable atherosclerotic plaques, anti-inflammatory type II macrophages and upregulation of beta-2 integrins in all major arterial beds.
Oksala Niku,Pärssinen Jenita,Seppälä Ilkka,Klopp Norman,Illig Thomas,Laaksonen Reijo,Levula Mari,Raitoharju Emma,Kholova Ivana,Sioris Thanos,Kähönen Mika,Lehtimäki Terho,Hytönen Vesa P
Atherosclerosis
BACKGROUND:Kindlins (FERMT) are cytoplasmic proteins required for integrin (ITG) activation, leukocyte transmigration, platelet aggregation and thrombosis. Characterization of kindlins and their association with atherosclerotic plaques in human(s) is lacking. METHODS AND RESULTS:Exploratory microarray (MA) was first performed followed by selective quantitative validation of robustly expressed genes with qRT-PCR low-density array (LDA). In LDA, ITGA1 (1.30-fold, p = 0.041) and ITGB3 (1.37-fold, p = 0.036) were upregulated in whole blood samples of patients with coronary artery disease (CAD) compared to healthy controls. In arterial plaques, both robustly expressed transcript variants of FERMT3 (MA: 5.90- and 3.4-fold; LDA: 3.99-fold, p < 0.0001 for all) and ITGB2 (MA: 4.81- and 4.92-fold; LDA: 5.29-fold, p < 0.0001 for all) were upregulated while FERMT2 was downregulated (MA: -1.61-fold; LDA: -2.88-fold, p < 0.0001 for both). The other integrins (ITGA1, ITGAV, ITGB3, ITGB5) were downregulated. All these results were replicated in at least one arterial bed. The latter FERMT3 transcript variant associated with unstable plaques (p = 0.0004). FERMT3 correlated with M2 macrophage markers and in hierarchical cluster analysis clustered with inflammatory and macrophage markers, while FERMT2 correlated with SMC-rich plaque markers and clustered with SMC markers. In confocal immunofluorescence analysis, FERMT3 protein colocalized with abundant CD68-positive cells of monocytic origin in the atherosclerotic plaques, while co-localization of FERMT3 with HHF35 indicative of smooth muscle cells was low. CONCLUSIONS:Kindlin-3 (FERMT3) is upregulated in atherosclerotic, especially unstable plaques, mainly in cells of monocytic origin and of M2 type. Simultaneous upregulation of ITGB2 suggests a synergistic effect on leukocyte adherence and transmigration into the vessel wall.
10.1016/j.atherosclerosis.2015.06.058
A vascular biology network model focused on inflammatory processes to investigate atherogenesis and plaque instability.
De León Héctor,Boué Stéphanie,Schlage Walter K,Boukharov Natalia,Westra Jurjen W,Gebel Stephan,VanHooser Aaron,Talikka Marja,Fields R Brett,Veljkovic Emilija,Peck Michael J,Mathis Carole,Hoang Vy,Poussin Carine,Deehan Renee,Stolle Katrin,Hoeng Julia,Peitsch Manuel C
Journal of translational medicine
BACKGROUND:Numerous inflammation-related pathways have been shown to play important roles in atherogenesis. Rapid and efficient assessment of the relative influence of each of those pathways is a challenge in the era of "omics" data generation. The aim of the present work was to develop a network model of inflammation-related molecular pathways underlying vascular disease to assess the degree of translatability of preclinical molecular data to the human clinical setting. METHODS:We constructed and evaluated the Vascular Inflammatory Processes Network (V-IPN), a model representing a collection of vascular processes modulated by inflammatory stimuli that lead to the development of atherosclerosis. RESULTS:Utilizing the V-IPN as a platform for biological discovery, we have identified key vascular processes and mechanisms captured by gene expression profiling data from four independent datasets from human endothelial cells (ECs) and human and murine intact vessels. Primary ECs in culture from multiple donors revealed a richer mapping of mechanisms identified by the V-IPN compared to an immortalized EC line. Furthermore, an evaluation of gene expression datasets from aortas of old ApoE-/- mice (78 weeks) and human coronary arteries with advanced atherosclerotic lesions identified significant commonalities in the two species, as well as several mechanisms specific to human arteries that are consistent with the development of unstable atherosclerotic plaques. CONCLUSIONS:We have generated a new biological network model of atherogenic processes that demonstrates the power of network analysis to advance integrative, systems biology-based knowledge of cross-species translatability, plaque development and potential mechanisms leading to plaque instability.
10.1186/1479-5876-12-185
Cholesterol-crystalized coronary atheroma as a potential precursor lesion causing acute coronary syndrome: a case report.
European heart journal. Case reports
BACKGROUND:Histopathological studies have reported the presence of cholesterol crystals in the culprit lesion in patients with sudden cardiac death. Given that cholesterol crystals themselves promote pro-inflammatory cascades, they may destabilize atherosclerotic plaques, leading to the occurrence of acute coronary events. CASE SUMMARY:A 60-year-old man presented with ST-segment elevation myocardial infarction. Emergent coronary angiography revealed a severely stenotic lesion (=culprit lesion) and another non-obstructive lesion in the proximal and middle segments of the left anterior descending artery (LAD), respectively. Optical coherence tomography (OCT) imaging showed that both lesions exhibited lipid-rich plaque with cholesterol crystals, and the non-obstructive lesion in the mid-LAD did not have a thin fibrous cap (its thickness = 230 μm). A drug-eluting stent was successfully implanted at the culprit lesion in the proximal LAD. On non-contrast T1-weighted magnetic resonance imaging performed 10 days after percutaneous coronary intervention (PCI), a high-intensity signal was identified at the non-obstructive mid-LAD lesion. This lesion was medically managed with aspirin, clopidogrel, and rosuvastatin due to the absence of myocardial ischaemia. However, 12 months after PCI, the patient was hospitalized again due to unstable angina pectoris. Coronary angiography revealed substantial progression of the mid-LAD lesion. Optical coherence tomography imaging prior to the second PCI showed a severely narrowed lesion containing cholesterol crystals and covered by organized thrombus. This lesion harbored an extensive amount of lipidic materials on near-infrared spectroscopy (maximum 4-mm lipid core burden index = 809). DISCUSSION:In our case, atherosclerotic plaques containing cholesterol crystals was associated with the occurrence of acute coronary syndrome. Our findings suggest that plaque with cholesterol crystals is a potential precursor to future acute coronary events.
10.1093/ehjcr/ytz128
Correlation between osteocalcin-positive endothelial progenitor cells and spotty calcification in patients with coronary artery disease.
Zhang He,Wang Li-jun,Si Dong-lei,Wang Chuan,Yang Jing-ci,Jiang Ping,Du Chao,Wang Jian-jun
Clinical and experimental pharmacology & physiology
Immature endothelial progenitor cells (EPC) carrying osteocalcin (OCN) might mediate vascUlar calcification in coronary artery disease (CAD). Spotty calcification within atherosclerotic plaque is associated with cardiovascular events. The aim of the present study was to assess the correlation between immature EPC levels and spotty calcification in CAD patients. In the 224 CAD patients studied, 76 had acute myocardial infarction (AMI), 102 had unstable angina pectoris (UAP), and 46 had stable angina pectoris (SAP). The levels of OCN-positive (OCN+) EPC were analysed by flow cytometry. The status of spotty calcification was determined by cardiac computed tomography angiography. OCN+ EPC and calcium deposits were significantly increased in acute coronary artery syndrome (ACS) when compared with those in SAP patients. Positive correlation was also revealed between the number of OCN+ EPC and the frequency of spotty calcification and levels of serum high-sensitivity C-reactive protein (hs-CRP) and serum alkaline phosphatase in AMI and UAP patients. In summary, the number of OCN+ EPC is positively related to the frequency of spotty calcification in ACS patients. Serum hs-CRP and serum alkaline levels are thought to contribute to the elevation of OCN+ EPC.
10.1111/1440-1681.12366
High Plasma Levels of Legumain in Patients with Complex Coronary Lesions.
Umei Tomohiko C,Kishimoto Yoshimi,Aoyama Masayuki,Saita Emi,Niki Hanako,Ikegami Yukinori,Ohmori Reiko,Kondo Kazuo,Momiyama Yukihiko
Journal of atherosclerosis and thrombosis
AIM:The degradation of the vascular extracellular matrix is important for atherosclerosis. The cysteine protease legumain was shown to be upregulated in atherosclerotic plaques, especially unstable plaques. However, no study has reported blood legumain levels in patients with coronary artery disease (CAD). METHODS:We investigated plasma legumain and C-reactive protein (CRP) levels in 372 patients undergoing elective coronary angiography. RESULTS:CAD was found in 225 patients. Compared with patients without CAD, those with CAD had higher CRP levels (median 0.60 [0.32, 1.53] vs. 0.46 [0.22, 0.89] mg/L, P<0.001), but no difference was found in legumain levels between patients with and without CAD (median 5.08 [3.87, 6.82] vs. 4.99 [3.84, 6.88] ng/mL). A stepwise increase in CRP was found depending on the number of >50% stenotic vessels: 0.55 mg/L in 1-vessel, 0.71 mg/L in 2-vessel, and 0.86 mg/L in 3-vessel diseases (P<0.001). However, legumain did not differ among 1-, 2-, and 3-vessel diseases (5.20, 4.93, and 5.01 ng/mL, respectively). Of 225 patients with CAD, 40 (18%) had complex lesions. No difference was found in CRP levels between patients with CAD with and without complex lesions (0.60 [0.34, 1.53] vs. 0.60 [0.32, 1.51] mg/L). Notably, legumain levels were higher in patients with CAD with complex lesions than without such lesions (6.05 [4.64, 8.64] vs. 4.93 [3.76, 6.52] ng/mL, P<0.01). In multivariate analysis, legumain levels were not a factor for CAD, but were a factor for complex lesions. The odds ratio for complex lesions was 2.45 (95% CI=1.26-4.79) for legumain >5.5 ng/mL. CONCLUSION:Plasma legumain levels were associated with the presence of complex coronary lesions.
10.5551/jat.52027
Usefulness of Coronary Atheroma Burden to Predict Cardiovascular Events in Patients Presenting With Acute Coronary Syndromes (from the PROSPECT Study).
Shan Peiren,Mintz Gary S,McPherson John A,De Bruyne Bernard,Farhat Naim Z,Marso Steven P,Serruys Patrick W,Stone Gregg W,Maehara Akiko
The American journal of cardiology
We investigated the relation between overall atheroma burden and clinical events in the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study. In PROSPECT, 660 patients (3,229 nonculprit lesions with a plaque burden ≥ 40% and complete intravascular ultrasound data) were divided into tertiles according to baseline percent atheroma volume (PAV: total plaque/vessel volume). Patients were followed for 3.4 years (median); major adverse cardiac events (MACE: death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization because of unstable or progressive angina) were adjudicated to either culprit or nonculprit lesions. Compared with patients in low or intermediate PAV tertiles, patients in the high PAV tertile had the greatest prevalence of plaque rupture and radiofrequency thin-cap fibroatheroma (VH-TCFA) and the highest percentage of necrotic core volume; they were also more likely to have high-risk lesion characteristics: ≥ 1 lesion with minimal luminal area ≤ 4 mm(2), plaque burden >70%, and/or VH-TCFA. Three-year cumulative nonculprit lesion-related MACE was greater in the intermediate and high tertiles than in the low tertile (6.3% vs 14.7% vs 15.1%, low vs intermediate vs high tertiles, p = 0.009). On Cox multivariable analysis, insulin-dependent diabetes (hazard ratio [HR] 3.98, p = 0.002), PAV (HR 1.06, p = 0.03), and the presence of ≥1 VH-TCFA (HR 1.80, p = 0.02) were independent predictors of nonculprit MACE. In conclusion, increasing baseline overall atheroma burden was associated with more advanced, complex, and vulnerable intravascular ultrasound lesion morphology and independently predicted nonculprit lesion-related MACE in patients with acute coronary syndromes after successful culprit lesion intervention.
10.1016/j.amjcard.2015.08.038
[Management of hypercholesterolemia in patients with acute coronary syndrome: current mechanisms and future perspectives].
Lettino Maddalena
Giornale italiano di cardiologia (2006)
Acute coronary syndromes (ACS) are a major health problem both in industrialized countries and in developing ones, and a leading cause of death and disability. The pathogenesis of ACS is multifactorial and complex, with approximately 65-70% of cases caused by the abrupt occlusion of a coronary vessel. This usually occurs as a result of thrombus formation over a vulnerable, lipid-rich atherosclerotic plaque, which undergoes rupture or erosion. High levels of LDL-cholesterol (LDL-C) are a well known risk factor for the development of atherosclerosis, and the reduction in plasma LDL-C is a fundamental treatment both in primary and secondary prevention. Statins are the most extensively used lipid-lowering drugs. They have been associated with reduced progression of coronary atherosclerosis and a decreased incidence of new ACS episodes or post-ACS major cardiovascular events. For ACS patients, the European Society of Cardiology (ESC) has suggested an early treatment - starting with the acute phase - together with a well defined target value of LDL-C level, which should be achieved during the follow-up. While statin therapy has significantly lowered cardiovascular risk, several cardiovascular events are still not prevented and a residual risk remains also after intensive therapy. In addition, a significant proportion of high-risk patients do not achieve the LDL-C target recommended by the ESC guidelines or present with statin intolerance, which does not allow a continuative and effective treatment. This is the main reason why innovative lipid-lowering therapies might become a new opportunity in ACS patients. The recently published results of the IMPROVE-IT trial have shown that the association statin + ezetimibe is superior to statin alone in preventing cardiovascular death, non-fatal myocardial infarction, rehospitalization for unstable angina, coronary revascularization and stroke in a population of medium to high-risk patients stabilized after ACS. Monoclonal antibodies targeting human PCSK9 are currently being tested on top of statins in patients with ACS, to investigate their superiority in reducing major cardiovascular adverse events as compared with statins alone at the maximally tolerated dose. The results, expected for 2017, will hopefully benefit the treatment of patients in secondary prevention and contribute to a better outcome of ACS patients worldwide.
10.1714/2254.24282
Circulating Endothelial Progenitor Cells were Increased in Patients with Thin-Cap Fibroatheroma.
Tan Qiang,Wang Qingsheng,Zhang Shuangyue,Qi Ximing,Li Yang
Clinical laboratory
BACKGROUND:We used virtual histology-intravascular ultrasound (VH-IVUS) to evaluate the relationship between circulating endothelial progenitor cells (EPC) and thin-cap fibroatheroma (TCFA). METHODS:This study included 52 patients with unstable angina who underwent coronary angiography and IVUS examination. Patients were divided into a TCFA group (n = 21) or a non-TCFA group (n = 31) based on VH-IVUS performance. Before angiography, peripheral blood levels of EPC were measured by flow cytometry. TCFA was defined as a necrotic core (NC) ≥ 10% of the plaque area without overlying fibrous tissue in the presence of ≥ 40% plaque burden. RESULTS:Levels of circulating EPCs were 72.45 ± 31.73 (count/105) in the TCFA group and 23.93 ± 11.87 (count/ 105) (p < 0.01). Mean levels of CRP were 0.38 ± 0.21 mg/L in the TCFA group and 0.23 ± 0.17 mg/L (p < 0.01). Levels of EPCs correlated positively with necrotic core volume(r = 0.421, p = 0.005), CRP (r = 0.405, p = 0.011) and negatively with fibrous tissue volume(r = -0.411, p = 0.009). In multivariate logistic regression analysis, level of EPC (OR: 1.815, 95% CI: 1.12 - 2.798, p = 0.016), plaque burden (OR: 1.26, 95% CI: 1.07 - 1.86, p = 0.027), and CRP (OR; 1.14, 95% CI: 0.74 - 1.56, p = 0.029) were independent predictors of TCFA. CONCLUSIONS:Circulating EPCs were increased in patients with TCFA, level of EPCs could predict the presence of TCFA.
10.7754/Clin.Lab.2016.160505
The Incremental Prognostic Value of Cardiac Computed Tomography in Comparison with Single-Photon Emission Computed Tomography in Patients with Suspected Coronary Artery Disease.
Lee Heesun,Yoon Yeonyee E,Park Jun-Bean,Kim Hack-Lyoung,Park Hyo Eun,Lee Seung-Pyo,Kim Hyung-Kwan,Choi Su-Yeon,Kim Yong-Jin,Cho Goo-Yeong,Zo Joo-Hee,Sohn Dae-Won
PloS one
BACKGROUND:Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT. MATERIALS AND METHODS:A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies). RESULTS:During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001). CONCLUSION:Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS.
10.1371/journal.pone.0160188
In vivo evaluation of fibrous cap thickness by optical coherence tomography for positive remodeling and low-attenuation plaques assessed by computed tomography angiography.
Sato Akira,Hoshi Tomoya,Kakefuda Yuki,Hiraya Daigo,Watabe Hiroaki,Kawabe Masayuki,Akiyama Daiki,Koike Akira,Aonuma Kazutaka
International journal of cardiology
BACKGROUND:Coronary plaques with positive remodeling (PR) and low-attenuation plaques (LAP) by computed tomography angiography (CTA) might be associated with plaque vulnerability. The purpose of this study was to assess the relation between coronary plaques with PR and LAP by CTA and fibrous cap thickness measured by optical coherence tomography (OCT). METHODS:We used CTA and OCT to assess 102 coronary plaques in patients with coronary artery disease (unstable angina pectoris, n=24; stable angina pectoris, n=78). Plaque characteristics were divided into three groups: 2-feature-positive plaques (PR and LAP; n=32), 1-feature-positive plaques (PR or LAP; n=20), and 2-feature-negative plaques (neither PR nor LAP; n=50). PR was defined as remodeling index (RI) of >1.05 and LAP was defined as CT density value <50HU. RESULTS:There were significant differences between the three plaque groups with respect to fibrous cap thickness measured by OCT: 76±24μm in 2-feature-positive plaques, 154±51μm in 1-feature-positive plaques, and 192±49μm in 2-feature-negative plaques (P<0.001). The RI (1.21±0.06, 1.14±0.05, P=0.011) and the presence of thin cap fibroatheroma (TCFA) (<70-μm thickness) (75%, 15%, P=0.001) were significantly higher in UAP than in SAP patients with 2-feature-positive plaques, whereas fibrous cap thickness (68.9±24.1, 92.1±21.9μm, P<0.001) was lower in the UAP patients. In UAP patients, the presence of ring-like enhancement showed higher accuracy of 88% for detection of TCFA. CONCLUSIONS:Coronary PR and LAP by CTA were associated with the degree of fibrous cap thickness measured by OCT. CTA can non-invasively provide promising information on plaque vulnerability by identifying coronary plaque with PR and LAP, especially ring-like enhancement.
10.1016/j.ijcard.2015.01.021
Direct relationship of local C-reactive protein production and lipid pool characterized by integrated backscatter intravascular ultrasound: a preliminary observation.
Kobayashi Yuhei,Okura Hiroyuki,Kume Teruyoshi,Miyamoto Yoshinori,Yamada Ryotaro,Kobayashi Yukari,Fukuhara Kenzo,Koyama Terumasa,Neishi Yoji,Yoshida Kiyoshi
Coronary artery disease
BACKGROUND:Local production of C-reactive protein (CRP) in human coronary arterial plaque was reported as a possible marker for local inflammation and vulnerable plaque. Integrated backscatter intravascular ultrasound (IB-IVUS) plaque tissue characterization may detect vulnerable plaque with high local plaque inflammation. Thus, the aim of this study was to clarify the relationship between IB-IVUS-based plaque characteristics and local high-sensitivity C-reactive protein (hs-CRP) production in stable and unstable plaque. METHODS AND RESULTS:Eighteen patients (nine unstable angina/non-ST-segment elevation myocardial infarction and nine stable angina) were prospectively enrolled. Using the microcatheter, blood samples from the proximal and distal sites of the culprit lesion were obtained to measure local CRP production. Translesional hs-CRP was defined as distal hs-CRP minus proximal hs-CRP of the culprit lesion. Gray-scale and IB-IVUS analyses were carried out at the target lesion. The translesional hs-CRP level tended to be higher in the unstable angina group than in the stable angina group (0.026 ± 0.033 vs. 0.003 ± 0.007 mg/dl, P = 0.050). Gray-scale IVUS-derived indices did not correlate with translesional hs-CRP. However, % lipid pool area by IB-IVUS correlated positively (r = 0.54, P = 0.02) and % fibrosis area correlated negatively with the translesional hs-CRP level (r = -0.52, P = 0.03). CONCLUSION:Lipid pool area detected by IB-IVUS is correlated positively with the translesional hs-CRP level.
10.1097/MCA.0000000000000250
Elevated Serum Angiopoietin-like Protein 2 in Patients with Acute Coronary Syndrome.
Wang Zhiqing,Zheng Haotian,Chen Hao,Lin Xueping,Chen Juan,Wang Li,Bao Weiwei,Lin Xianliang,Huang Mingfang,Luo Zhurong
Archives of medical research
BACKGROUND AND AIMS:Angiopoietin-like protein 2 (Angptl2) is regarded as a proinflammatory factor in the pathogenesis of atherosclerosis and is expressed at high levels in patients with coronary artery disease. However, direct evidence of Angptl2 in acute coronary syndrome (ACS) is lacking. Our study was designed to investigate a possible relationship between serum Angptl2 and ACS. METHODS:We evaluated 251 consecutive patients undergoing coronary angiography, consisting of 132 patients with ACS (unstable angina pectoris n = 60, acute myocardial infarction n = 72), 50 patients with stable angina pectoris, and 69 control patients. Serum Angptl2 concentration was measured in peripheral venous blood by an enzyme-linked immunosorbent assay. RESULTS:Serum Angptl2 levels were significant higher in patients with ACS than in those with stable angina (p <0.05) or controls (p <0.001). The difference between angplt2 levels in unstable angina and acute myocardial infarction subgroups was statistically insignificant (p = 0.831). In multivariable logistic regression models, using quartiles of Angptl2, Angptl2 was closely associated with ACS following adjustment of age, gender, established risk factors and high sensitivity C-reactive protein levels (odds ratio for quartile 4 vs. quartile 1: 10.182, 95% confidence interval 2.440-42.485, p = 0.001). CONCLUSIONS:Serum Angptl2 is a new candidate biomarker for risk stratification of ACS.
10.1016/j.arcmed.2015.05.003
Characterization of high-intensity plaques on noncontrast T1-weighted magnetic resonance imaging by coronary angioscopy.
Oshita Akira,Kawakami Hideo,Miyoshi Toru,Seike Fumiyasu,Matsuoka Hiroshi
Journal of cardiology
BACKGROUND:A recent study showed that coronary high-intensity plaques (HIPs) visualized by noncontrast T1-weighted imaging (T1WI) in cardiac magnetic resonance were associated with coronary events. We used coronary angioscopy to analyze HIP plaque morphology. METHODS AND RESULTS:A total 17 lesions from 17 patients with stable or unstable angina pectoris were evaluated at the culprit lesion by noncontrast T1WI using 1.5-T magnetic resonance; of them, nine (53%) were HIPs and eight (47%) were non-HIPs, and all were analyzed by coronary angioscopy. We assessed the existence of thrombus and plaque yellow color grade (YG). YG was assessed visually according to a four-grade scale: 0, white; 1, light yellow; 2, yellow; 3, intense yellow. The frequency of thrombus was significantly higher in HIPs than in non-HIPs (89% vs. 25%, respectively; p=0.007). YG was significantly more frequent in HIPs than in non-HIPs (2.2±0.4 vs. 0.7±0.7, respectively; p=0.01). CONCLUSIONS:These data indicated that HIPs on noncontrast T1WI were associated with the presence of high-grade yellow plaque with thrombus.
10.1016/j.jjcc.2017.04.009
Myxomavirus anti-inflammatory chemokine binding protein reduces the increased plaque growth induced by chronic Porphyromonas gingivalis oral infection after balloon angioplasty aortic injury in mice.
Lucas Alexandra R,Verma Raj K,Dai Erbin,Liu Liying,Chen Hao,Kesavalu Sheela,Rivera Mercedes,Velsko Irina,Ambadapadi Sriram,Chukkapalli Sasanka,Kesavalu Lakshmyya
PloS one
Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virus-derived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE-/- mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P<0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P<0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE-/- mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine proteases significantly reduced arterial plaque growth, suggesting a central role for chemokine-mediated inflammation after BA in P. gingivalis infected mice.
10.1371/journal.pone.0111353
Wnt5a-induced Wnt1-inducible secreted protein-1 suppresses vascular smooth muscle cell apoptosis induced by oxidative stress.
Mill Carina,Monk Bethan Alice,Williams Helen,Simmonds Steven John,Jeremy Jamie Yancey,Johnson Jason Lee,George Sarah Jane
Arteriosclerosis, thrombosis, and vascular biology
OBJECTIVE:Apoptosis of vascular smooth muscle cells (VSMCs) contributes to thinning and rupture of the atherosclerotic plaque fibrous cap and is thereby associated with myocardial infarction. Wnt protein activation of β-catenin regulates numerous genes that are associated with cell survival. We therefore investigated Wnt/β-catenin survival signaling in VSMCs and assessed the presence of this pathway in human atherosclerotic plaques at various stages of the disease process. APPROACH AND RESULTS:Wnt5a induced β-catenin/T-cell factor signaling and retarded oxidative stress (H₂O₂)-induced apoptosis in mouse aortic VSMCs. Quantification of mRNA levels revealed a >4-fold (P<0.05; n=9) increase in the expression of the Wnt/β-catenin responsive gene, Wnt1-inducible secreted protein-1 (WISP-1), which was dependent on cAMP response element-binding protein and sustained in the presence of H₂O₂. Exogenous WISP-1 significantly reduced H₂O₂-induced apoptosis by 43% (P<0.05; n=3) and was shown using silencing small interfering RNA, to be important for Wnt5a-dependent survival responses to H₂O₂ (P<0.05; n=3). WISP-1 protein levels were significantly lower (≈50%) in unstable atherosclerosis compared with stable plaques (n=11 and n=14). CONCLUSIONS:These results indicate for the first time that Wnt5a induces β-catenin survival signaling in VSMCs via WISP-1. The deficiency of the novel survival factor, WISP-1 in intimal VSMCs of unstable coronary plaques, suggests that there is altered Wnt/β-catenin/ T-cell factor signaling with progressive atherosclerosis, and restoration of WISP-1 protein might be an effective stabilization factor for vulnerable atherosclerotic plaques.
10.1161/ATVBAHA.114.303922
Prognostic Value of sLOX-1 Level in Acute Coronary Syndromes Based on Thrombolysis in Myocardial Infarction Risk Score and Clinical Outcome.
Mashayekhi Sina,Ziaee Mojtaba,Garjani Alireza,Sarbakhsh Parvin,Ghaffari Samad
The Journal of emergency medicine
BACKGROUND:Biomarkers possess important diagnostic and prognostic value in acute coronary syndromes (ACSs). Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) is one of the markers involved in atherosclerotic plaque vulnerability and rupture. OBJECTIVE:This study aimed to evaluate the prognostic value of sLOX-1 through its correlation with Thrombolysis in Myocardial Infarction (TIMI) risk score and its possible association with clinical outcomes in 2 major spectrums of ACS. METHODS:A prospective cross-sectional study was planned, and 320 patients who underwent diagnostic coronary angiography were selected (in first 24 h after coronary angiography): those with documented ST elevation myocardial infarction or unstable angina/non-ST elevation myocardial infarction. sLOX-1 was measured immediately after administration in the emergency department. The TIMI risk score was calculated separately for both groups. In hospital death, heart failure and recurrent infarction were considered major adverse cardiac events. RESULTS:There was a significant positive correlation between sLOX-1, TIMI risk score, major adverse cardiac events, and heart failure. The optimal cutoff value of sLOX-1 to predict clinical endpoints was 1.75 ng/mL in patients with ST elevation myocardial infarction and 1.35 ng/mL in patients with unstable angina/non-ST elevation myocardial infarction. CONCLUSIONS:Circulating sLOX-1 could be used as a biomarker to predict major adverse cardiac events in patients with ACS and may be clinically useful in the triage and management of these patients.
10.1016/j.jemermed.2018.06.018
Interleukin-6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial.
Journal of the American Heart Association
BACKGROUND:Interleukin-6 (IL-6) is an inflammatory cytokine implicated in plaque instability in acute coronary syndrome (ACS). We aimed to evaluate the prognostic implications of IL-6 post-ACS. METHODS AND RESULTS:IL-6 concentration was assessed at baseline in 4939 subjects in SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52), a randomized trial of darapladib in patients ≤30 days from ACS. Patients were followed for a median of 2.5 years for major adverse cardiovascular events; cardiovascular death, myocardial infarction, or stroke) and cardiovascular death or heart failure hospitalization. Primary analyses were adjusted first for baseline characteristics, days from index ACS, ACS type, and randomized treatment arm. For every SD increase in IL-6, there was a 10% higher risk of major adverse cardiovascular events (adjusted hazard ratio [adj HR] 1.10, 95% confidence interval [CI] 1.01-1.19) and a 22% higher risk of cardiovascular death or heart failure (adj HR 1.22, 95% CI 1.11-1.34). Patients in the highest IL-6 quartile had a higher risk of major adverse cardiovascular events (adj HR Q4:Q1 1.57, 95% CI 1.22-2.03) and cardiovascular death or heart failure (adj HR 2.29, 95% CI 1.6-3.29). After further adjustment for biomarkers (high-sensitivity C-reactive protein, lipoprotein-associated phospholipase A activity, high-sensitivity troponin I, and B-type natriuretic peptide), IL-6 remained significantly associated with the risk of major adverse cardiovascular events (adj HR Q4:Q1 1.43, 95% CI 1.09-1.88) and cardiovascular death or heart failure (adj HR 1.79, 95% CI 1.22-2.63). CONCLUSIONS:In patients after ACS, IL-6 concentration is associated with adverse cardiovascular outcomes independent of established risk predictors and biomarkers. These findings lend support to the concept of IL-6 as a potential therapeutic target in patients with unstable ischemic heart disease.
10.1161/JAHA.117.005637
Elevation of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes.
Pan Wei,Yu Jingjia,Shi Ruizheng,Yan Lei,Yang Tianlun,Li Yuanjian,Zhang Zhuohua,Yu Guolong,Bai Yongping,Schuchman Edward H,He Xingxuan,Zhang Guogang
Coronary artery disease
BACKGROUND:Although there are several reported evidences for a pathogenic role of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide and secretory acid sphingomyelinase (S-SMase) activity in patients with acute coronary syndromes (ACS) have not been evaluated. METHODS AND RESULTS:A total of 304 CAD patients and 52 healthy individuals were divided into four groups: control group (n=52), stable angina pectoris (SAP) group (n=98), unstable angina pectoris (UAP) group (n=92), and acute myocardial infarction (AMI) group (n=114). Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI compared with those in the control and SAP participants. Plasma ceramide levels and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were significantly higher than those in the control and SAP participants. Elevation in plasma ceramide levels in patients with UAP and AMI was sustained until a day after percutaneous coronary intervention or day 7, respectively. Moreover, in patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual decrease toward the SAP range up to a day after percutaneous coronary intervention. In patients with AMI, elevation in S-SMase activity showed a peak on day 3. CONCLUSION:Serial changes in plasma ceramide and S-SMase activity were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.
10.1097/MCA.0000000000000079
Sodium-fluoride PET-CT for the non-invasive evaluation of coronary plaques in symptomatic patients with coronary artery disease: a cross-correlation study with intravascular ultrasound.
Li Li,Li Xiang,Jia Yongping,Fan Jiamao,Wang Huifeng,Fan Chunyu,Wu Lei,Si Xincheng,Hao Xinzhong,Wu Ping,Yan Min,Wang Ruonan,Hu Guang,Liu Jianzhong,Wu Zhifang,Hacker Marcus,Li Sijin
European journal of nuclear medicine and molecular imaging
OBJECTIVES:The aim of this study was to evaluate the F-sodium fluoride (F-NaF) coronary uptake compared to coronary intravascular ultrasound (IVUS) in patients with symptomatic coronary artery disease. BACKGROUND:F-NaF PET enables the assessment of vascular osteogenesis by interaction with surface hydroxyapatite, while IVUS enables both identification and quantification of intra-plaque components. METHODS:Forty-four patients with symptomatic coronary artery disease were included in this prospective controlled trial, 32 of them (30 patients with unstable angina and 2 patients with stable angina), representing the final study cohort, got additional IVUS. All patients underwent cardiac F-NaF PET/CT and IVUS within 2 days. F-NaF maximum tissue-to-blood ratios (TBR) were calculated for 69 coronary plaques and correlated with IVUS plaque classification. RESULTS:Significantly increased F-NaF uptake ratios were observed in fibrocalcific lesions (meanTBR = 1.42 ± 0.28), thin-cap atheroma with spotty calcifications (meanTBR = 1.32 ± 0.23), and thick-cap mixed atheroma (meanTBR = 1.28 ± 0.38), while fibrotic plaques showed no increased uptake (meanTBR = 0.96 ± 0.18). The F-NaF uptake ratio was consistently higher in atherosclerotic lesions with severe calcification (meanTBR = 1.34 ± 0.22). The regional F-NaF uptake was most likely localized in the border region of intensive calcification. Coronary lesions with positive F-NaF uptake showed some increased high-risk anatomical features on IVUS in comparison to F-NaF negative plaques. It included a significant severe plaque burden (70.1 ± 13.8 vs. 61.0 ± 13.8, p = 0.01) and positive remodeling index (1.03 ± 0.08 vs. 0.99 ± 0.07, p = 0.05), as well as a higher percentage of necrotic tissue (37.6 ± 13.3 vs. 29.3 ± 15.7, p = 0.02) in positive F-NaF lesions. CONCLUSIONS:F-NaF coronary uptake may provide a molecular insight for the characterization of coronary atherosclerotic lesions. Specific regional uptake is needed to be determined by histology.
10.1007/s00259-018-4122-0
Optical Coherence Tomography Assessment of Morphological Characteristics in Suspected Coronary Artery Disease, but Angiographically Nonobstructive Lesions.
Yamamoto Myong Hwa,Maehara Akiko,Song Lei,Matsumura Mitsuaki,Chin Chee Yang,Losquadro Monica,Sosa Fernando A,Mintz Gary S,Shlofmitz Richard A
Cardiovascular revascularization medicine : including molecular interventions
BACKGROUND/PURPOSE:We sought to evaluate the morphological characteristics of nonobstructive coronary lesions in patients with ischemic symptoms and/or signs. MATERIALS/METHODS:We used optical coherence tomography (OCT) to assess the presumed culprit lesion in 142 patients with suspected coronary artery disease in whom coronary angiography showed no lesion with a diameter stenosis ≥50%. Patients with a clinical diagnosis of acute coronary syndrome (ACS, n = 31, including 2 ST-elevation myocardial infarction, 9 non-ST-elevation myocardial infarction, and 20 unstable angina pectoris) were compared to those with stable coronary artery disease (CAD) (n = 111) including 79 patients with stable angina and 32 patients with silent ischemia (positive non-invasive stress test only). RESULTS:The overall prevalence of thrombus, plaque rupture, intimal laceration, or calcified nodule in the combined groups was 23.2% (33/142) including 15 thrombus, 12 plaque rupture, 9 calcified nodule, and 8 intimal laceration (not mutually exclusive) without differences between ACS and stable CAD patients. Also the prevalence of thin-cap fibroatheroma was not significantly different between ACS and stable patients (12.9% vs 6.3%, p = 0.22). Minimum lumen area (3.1 mm [2.3, 4.1] versus 3.2 mm [2.4, 4.7], p = 0.7) and area stenosis (49.9% [37.1, 56.4] versus 48.1% [37.8, 55.8], p = 0.9) were similar between ACS and stable CAD patients. CONCLUSION:In patients presenting with ischemic symptoms and/or signs, but angiographically nonobstructive culprit lesions, approximately 25% had abnormal findings by OCT-whether patients presented with acute/unstable or stable CAD.
10.1016/j.carrev.2018.07.011
Differences in coronary artery disease by CT angiography between patients developing unstable angina pectoris vs. major adverse cardiac events.
Schlett Christopher L,Nance John W,Schoepf U Joseph,O'Brien Terrence X,Ebersberger Ullrich,Headden Gary F,Hoffmann Udo,Bamberg Fabian
European journal of radiology
OBJECTIVE:CT angiography (CTA) has prognostic value in patients. But it is unknown whether differences in atherosclerosis by CTA predict the development of unstable angina pectoris (UAP) vs. major adverse cardiac events (MACE). METHODS:We followed patients undergoing CTA as part of their acute chest pain work-up. Primary outcome was the development of UAP or MACE (cardiac death, myocardial infarction, revascularization) during a minimum follow-up of 12-months. CTAs were assessed for extent and composition of coronary plaque and stenosis. Ordinal regression with a 3-level outcome (no events, UAP, MACE) was applied. RESULTS:Among 315 patients, 22 developed UAP and 31 MACE. While UAP patients had higher atherosclerosis burden with respect to all assessed features compared to patients with no events (p ≤ 0.02), only mixed plaque extent was significantly different between UAP and MACE patients (p=0.02). The odds ratio was 4.55 for being in a higher disease-level comparing patients with low extent to those with no mixed plaque, and 3.02 comparing patients with high to those with low. These findings remained after adjustments for potential confounders. CONCLUSION:The extent of mixed coronary plaque is different between patients who develop UAP vs. MACE, supporting the hypothesis that it is a more culprit morphology.
10.1016/j.ejrad.2014.04.005
Echolucency of carotid plaque is useful for assessment of residual cardiovascular risk in patients with chronic coronary artery disease who achieve LDL-C goals on statin therapy.
Uematsu Manabu,Nakamura Takamitsu,Sugamata Wataru,Kitta Yoshinobu,Fujioka Daisuke,Saito Yukio,Kawabata Ken-Ichi,Obata Jun-Ei,Watanabe Yosuke,Watanabe Kazuhiro,Kugiyama Kiyotaka
Circulation journal : official journal of the Japanese Circulation Society
BACKGROUND:Ultrasound assessment of either intima-media thickness (IMT) or plaque echolucency of the carotid artery provides prognostic information on coronary events. This study examined the hypothesis that IMT and plaque echolucency of the carotid artery may remain useful for prediction of coronary events in patients with coronary artery disease (CAD) after achievement of LDL-C goals on statin therapy. METHODS AND RESULTS:Ultrasound assessment of carotid maximum IMT (maxIMT) and plaque echolucency with integrated backscatter (IBS) analysis was performed in 357 chronic CAD patients with LDL-C <100mg/dl on statin therapy. All patients were prospectively followed up until the occurrence of one of the following coronary events: cardiac death, non-fatal myocardial infarction, or unstable angina pectoris requiring unplanned revascularization. During a mean follow-up of 32±18 months, 33 coronary events occurred. On multivariate Cox proportional hazards analysis, plaque echolucency (lower IBS value) was a significant predictor of coronary events (HR, 0.44; 95% CI: 0.29-0.73; P=0.009), whereas maxIMT was not. The addition of plaque echolucency to traditional risk factors improved net reclassification improvement (NRI) and integrated discrimination improvement (IDI; NRI, 0.59; P=0.0013; and IDI, 0.075; P=0.0009). CONCLUSIONS:Measurement of echolucency of the carotid artery was useful for assessment of residual coronary risk in CAD patients after LDL-C goal attainment on statin treatment.
A Dual-Modality Hybrid Imaging System Harnesses Radioluminescence and Sound to Reveal Molecular Pathology of Atherosclerotic Plaques.
Scientific reports
Atherosclerosis is a progressive inflammatory condition caused by an unstable lesion, called thin-cap fibro atheromata (TCFA) that underlies coronary artery disease (CAD)-one of the leading causes of death worldwide. Therefore, early clinical diagnosis and effective risk stratification is important for CAD management as well as preventing progression to catastrophic events. However, early detection could be difficult due to their small size, motion, obscuring F-FDG uptake by adjacent myocardium, and complex morphological/biological features. To overcome these limitations, we developed a catheter-based Circumferential-Intravascular-Radioluminescence-Photoacoustic-Imaging (CIRPI) system that can detect vulnerable plaques in coronary arteries and characterizes them with respect to pathology and biology. Our CIRPI system combined two imaging modalities: Circumferential Radioluminescence Imaging (CRI) and PhotoAcoustic Tomography (PAT) within a novel optical probe. The probe's CaF:Eu based scintillating imaging window provides a 360° view of human (n = 7) and murine carotid (n = 10) arterial plaques by converting β-particles into visible photons during F-FDG decay. A 60× and 63× higher radioluminescent signals were detected from the human and murine plaque inflammations, respectively, compared to the control. The system's photoacoustic imaging provided a comprehensive analysis of the plaque compositions and its morphologic information. These results were further verified with IVIS-200, immunohistochemical analysis, and autoradiography.
10.1038/s41598-018-26696-8
Comparison of the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by tissue characterization using serial virtual histology intravascular ultrasound.
Nozue Tsuyoshi,Yamamoto Shingo,Tohyama Shinichi,Fukui Kazuki,Umezawa Shigeo,Onishi Yuko,Kunishima Tomoyuki,Sato Akira,Nozato Toshihiro,Miyake Shogo,Takeyama Youichi,Morino Yoshihiro,Yamauchi Takao,Muramatsu Toshiya,Hibi Kiyoshi,Terashima Mitsuyasu,Michishita Ichiro
Heart and vessels
Thin-cap fibroatheroma (TCFA) is the most common type of vulnerable plaque and is the precursor of plaque rupture. However, rupture of a TCFA is not the only mechanism underlying thrombus formation or acute coronary syndrome. Although statin therapy changes the composition of coronary artery plaques, the effects of statins, particularly different types of statins, on plaque phenotype have not been fully examined. This study compared the effects of pitavastatin versus pravastatin on coronary artery plaque phenotype assessed by virtual histology (VH) intravascular ultrasound (IVUS) in patients with angina pectoris (AP). Coronary atherosclerosis in nonculprit lesions was evaluated using VH-IVUS at baseline and 8 months after statin therapy; analyzable IVUS data were obtained from 83 patients with stable AP (39 patients treated with pitavastatin and 44 with pravastatin) and 36 patients with unstable AP (19 patients treated with pitavastatin and 17 with pravastatin). Pitavastatin had a strong effect on reducing pathologic intimal thickening (PIT), especially in patients with unstable AP, but had no impact on VH-TCFA or fibroatheroma (FA). By contrast, pravastatin had weak effects on reducing PIT, VH-TCFA, or FA. Increases in the number of calcified plaques were observed for both statins. In conclusion, pitavastatin and pravastatin changed coronary artery plaque phenotype as assessed by VH-IVUS in patients with AP. However, the effects of these statins on coronary artery plaque phenotype were different.
10.1007/s00380-013-0453-8
[Computed Tomography in the Evaluation of Coronary Atherosclerotic Plaques: Comparison With Intravascular Ultrasound].
Veselova T N,Shabanova M S,Mironov V M,Merkulova I N,Ternovoy S K
Kardiologiia
PURPOSE:Determination of computed tomography angiography (CTA) informativeness in assessment of state of atherosclerotic coronary plaque (ACP) and identification of signs of its instability compared with intravascular ultrasound (IVUS). MATERIALS AND METHODS:Coronary CTA was carried out in 52 patients with clinical presentation of non-ST elevation (NSTE) acute coronary syndrome on the first day of hospitalization. ACPs were identified in 32 of 52 patients (61.5%). IVUS was performed in 32 patients (mean age 58+/-11.4 years, 27 men, 5 women, 22 with unstable angina, 10 with NSTE myocardial infarction) and 50 plaques in 45 coronary arteries were characterized (39 with spectral analysis of IVUS data). All data were compared with the results of coronary CTA. RESULTS:Sensitivity and specificity of CTA in the detection of stenosis >50% were 97.67 and 71.40%, respectively. Correlation analysis showed a high comparability of methods in determining plaque burden (r=0.80, 95% confidence interval [CI] 0.67 - 0.88, p<0.0001), plaque length (r=0.75, 95%CI 0.60 - 0.85, p<0.0001), and remodeling index (r=0.62, 95%CI 0.40 - 0.77, p<0.0001). Threshold value for "low-density areas" of plaques typical for thin cap fibroatheroma was less or equal 41 Hounsfield units (sensitivity 82%; specificity 86%; area under the curve 0.824; 95% CI 0.615 - 0.947, p<0.0005). CONCLUSION:Coronary CT is a non-invasive method for rapid characterization of ACP. CT results correlate well with IVUS data, including identification of such important signs of plaque instability as presence of "low-density zone" and positive remodeling at the plague level.
Significant association among residual SYNTAX score, non-culprit major adverse cardiac events, and greyscale and virtual histology intravascular ultrasound findings: a substudy from the PROSPECT study.
Fujino Akiko,Kadohira Tadayuki,Redfors Björn,Maehara Akiko,Serruys Patrick W,Mintz Gary S,Stone Gregg W,Généreux Philippe
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
AIMS:Residual SYNTAX score (rSS) is known to be associated with cardiac events. We sought to investigate the association between rSS and greyscale and virtual histology (VH)-intravascular ultrasound (IVUS) plaque morphology, and the association between rSS and non-culprit-related major adverse cardiac events (MACE) using data from the PROSPECT study. METHODS AND RESULTS:A total of 697 patients with acute coronary syndromes were enrolled in the PROSPECT study. Three-vessel greyscale and VH-IVUS were performed. Among them, 688 patients with paired baseline SS or SYNTAX score and rSS were identified and divided into three groups - rSS=0 (n=184), 0 <rSS ≤8 (n=364), and rSS >8 (n=140). MACE was defined as the composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalisation for unstable or progressive angina. There was a significant difference in the three-year non-culprit-related MACE rates among the three groups (5.7% versus 11.9% versus 19.7%, lowest to highest rSS; p=0.004) mainly due to rehospitalisation for unstable or progressive angina. On multivariable analysis, patients with ≥1 lesion with plaque burden ≥70% or ≥1 lesion with a minimum lumen area ≤4 mm2 and total dense calcium volume per patient were significantly correlated with rSS. Insulin-treated diabetes mellitus, rSS, and patients with ≥1 lesion with plaque burden ≥70% were independent predictors of non-culprit-related MACE. CONCLUSIONS:Plaque morphology based on greyscale IVUS and VH-IVUS was significantly correlated with rSS, and rSS and plaque burden ≥70% independently predicted non-culprit-related MACE.
10.4244/EIJ-D-18-00681
Prognostic value of the high-mobility group box-1 in young patients with chest pain.
Haghjooy-Javanmard Shaghayegh,Sadeghi Masoumeh,Safavi Shiva,Gheraati Maryam,Dana Nasim
ARYA atherosclerosis
BACKGROUND:Atherosclerosis is accepted as an inflammatory disease. Evidence suggests that inflammation evoked by injury plays a pathogenic role in all stages of atherosclerosis. This study aimed to investigate whether the high-mobility group box-1 (HMGB1) a proinflammatory cytokine/nuclear protein, which is derived from both injured endothelium and activated macrophages/monocytes, could contribute to the progression of atherosclerosis and other cardiovascular diseases. METHODS:This study was designed as case-control. A total of 135 patients who referred to the hospital due to angina pectoris had the diagnosis of unstable angina and were candidates of angiography were recruited in this study. Forty patients who had coronary artery disease confirmed by angiography were considered as case group and control group consists of 40 persons who had no plaque, and 55 persons were excluded according to the exclusion criteria. At first, a questionnaire was filled for each patient including demographic factors and their medical history. Then a blood sample was taken to assess the level of HMGB1. Data were analyzed using SPSS, Student's independent t-test, and chi-square tests. RESULTS:The mean plasma level of HMGB1 in the case group was 27.1 ± 2.9 ng/ml, while it was 19.6 ± 1.9 ng/ml in control groups (P = 0.03). The odds ratio for coronary artery plaque associated with high (> 15.03 ng/ml) levels of HMGB1 was 2.50 (95% confidence interval, 1.02-6.17, P = 0.03). CONCLUSION:Increased plasma HMGB1 concentration may be associated with an increased risk of coronary atherosclerosis.
Lysophosphatidic Acid Is Associated with Atherosclerotic Plaque Instability by Regulating NF-κB Dependent Matrix Metalloproteinase-9 Expression via LPA in Macrophages.
Gu Chun,Wang Fang,Zhao Zhenwen,Wang Hongyue,Cong Xiangfeng,Chen Xi
Frontiers in physiology
Lysophosphatidic acid (LPA), one of the simplest phospholipid signaling molecules, participates in formation and disruption of atherosclerotic plaque. Matrix metalloproteinases (MMPs) contribute to atherosclerotic plaque rupture by involving in extracellular matrix (ECM) degradation and then thinning fibrous cap. Our previous study demonstrated that macrophage-derived MMP-9 was associated with coronary plaque instability, but the relationship between LPA and MMP-9 remains unclear. The present work therefore aimed at elucidating association between LPA and MMP-9 and the regulation mechanism of LPA on MMP-9 in macrophages. We found that plasma LPA and MMP-9 levels were correlated positively ( = 0.31, < 0.05) and both elevated significantly in patients with acute myocardial infarct (AMI). Consistent with peripheral blood levels, histochemical staining indicated that autotaxin (ATX), LPA-producing ectoenzyme, and MMP-9 were expressed frequently in the necrotic core and fibrous cap of human unstable plaques, which might increase the instability of plaque. Experiments were done with THP-1-derived macrophages and showed that LPA enhanced the expression, secretion and activity of MMP-9 in a time- and dose-dependent manner. Induction of LPA on pro-MMP-9 and active-MMP-9 was confirmed in human peripheral blood monocyte-derived macrophages. PDTC, NF-κB inhibitor, but not inhibitor of AP-1 and PPARγ, effectively prevented LPA-induced MMP-9 expression and NF-κB p65 siRNA decreased MMP-9 transcription, confirming that LPA might induce MMP-9 elevation by activating NF-κB pathway. In addition, knockdown of LPA attenuated LPA-induced MMP-9 expression and nucleus p65 levels. These findings revealed that LPA upregulated the expression of MMP-9 through activating NF-κB pathway in the LPA dependent manner, hence blocking LPA receptors signaling may provide therapeutic strategy to target plaque destabilization.
10.3389/fphys.2017.00266
Risk classification of highly sensitive troponin I predict presence of vulnerable plaque assessed by dual source coronary computed tomography angiography.
Liu Ting,Wang Guan,Li Peiling,Dai Xu
The international journal of cardiovascular imaging
Patients presenting to the emergency department with acute chest pain, negative conventional troponin and electrocardiogram require serial testing to rule out acute coronary syndrome (ACS). We studied the association of highly sensitive troponin (hsTn) I with vulnerable plaque features as detected by coronary dual source computed tomography angiography (DSCTA) and determined whether hsTn I at the time of presentation combined with early DSCTA could improve classification of patients as high-risk or low risk for ACS. We included 220 patients with acute chest pain, negative electrocardiogram and conventional troponin who underwent DSCTA and had hsTn I measured at the time of presentation. The patients were categorized as having hsTn I below the limit of detection (low risk), intermediate and above the 99th percentile (high risk). Readers assessed DSCTA qualitatively for the presence of significant CAD (≥50% stenosis), calcified and non-calcified coronary plaque, and vulnerable plaque features (positive remodeling, low CT attenuation plaque, napkin-ring sign, spotty calcium). The mean age of the population was 50.3 ± 8.2 years (43% women). ACS during the index hospitalization occurred in 36 (16.3%) patients (myocardial infarction n = 8, unstable angina pectoris n = 28). HsTn I was below the limit of detection, intermediate, and above 99th percentile in 39 (17.7%), 139 (86.9%), and 42 (19.1%) patients, respectively. Across the categories of low risk, intermediate and high risk of hsTn I, there was increase in prevalence of ≥50% stenosis (0, 11.5, and 61.9% of patients; p < 0.001), any plaque (35.9, 51.1, and 85.7% of patients; p < 0.001) and high-risk plaque (0, 36.0, and 85.7% of patients; p < 0.001). None of the patients in low risk HsTn I group had ACS. ACS occurred in 10.1% of the intermediate hsTn I group and in 52.3% of the patients with high risk hsTnI group. Severity of stenosis and presence of vunerable plaque as detected by DSCTA are associated with increasing levels of hsTn I. DSCTA at the time of presentation with the assessment for both stenosis and high-risk plaque improved the diagnostic accuracy for ACS in the intermediate hsTn I group patients.
10.1007/s10554-017-1174-3
Intravascular evaluation of coronary atherosclerotic lesions among Egyptian diabetic patients with acute coronary syndromes.
Laimoud Mohamed,Faris Farouk,Elghawaby Helmy
The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology
BACKGROUND:Coronary artery disease is one of the main causes of death in diabetes mellitus (DM). Egypt was listed among the world top 10 countries regarding the number of diabetic patients by the International Diabetes Federation (IDF). AIM OF WORK:Assessment of the extent of coronary atherosclerotic disease and lesion tissue characterization among diabetic compared to non-diabetic Egyptian patients. METHODOLOGY:IVUS studies of 272 coronary lesions in 116 patients presented with unstable angina were examined. The patients were divided into two groups: diabetic group (50 patients with 117 lesions) and non-diabetic group (66 patients with 155 lesions). RESULTS:As compared to the non-diabetic group, the diabetic patients were more dyslipidemic (84% vs 39.4%, p = 0.001) with higher total cholesterol level (194.6 ± 35.3 vs 174.4 ± 28.5 mg/dl, p = 0.001) and higher LDL-C (145.3 ± 27.1 vs 123.2 ± 31.4, p = 0.001). Regarding lesions characteristics, the diabetic group had longer lesions (19.4 ± 7.4 vs 16.3 ± 7.9 mm, p = 0.002) with higher plaque burden (60.8 ± 15.3 vs 54.8 ± 14.0, p 0.002) and more area stenosis percentage (60.8 ± 15.6 vs 55.6 ± 14.1, p = 0.008). Structurally, the diabetic group lesions had more lipid content (19.8 ± 8.8 vs 16.8 ± 8.7, p = 0.008) and more necrotic core (17.6 ± 7.4 vs 14.7 ± 4.8, p = 0.008) but less calcification (6.9 ± 3.6 vs 11.8 ± 6.3, p = 0.001). The RI was negative in both groups, 0.95 ± 0.13 in the diabetic group vs 0.98 ± 0.19 in non-diabetic group (p = 0.5). Within the diabetic group lesions, the dyslipidaemic subgroup had more lipid content (23. ± 5.2 vs 14.6 ± 8.6, p = 0.01) but less fibrotic component (48.6 ± 4.7 vs 59.1 ± 13.6%, p = 0.01) and less calcification (10.9 ± 6.8% vs 14.07 ± 3.8%, p = 0.02) as compared to the nondyslipidaemic subgroup. CONCLUSIONS:Diabetic patients with coronary atherosclerosis in Egypt have longer lesions with higher plaque burden and more percent area stenosis with negative remodeling index. The diabetic lesions had more lipid content and more necrotic core but less calcification.
10.1016/j.ehj.2018.10.003
[Noninvasive Methods of Detection of Vulnerable Atherosclerotic Plaques in Coronary Arteries].
Tagieva N R,Shakhnovich R M,Veselova T N
Kardiologiia
In most cases direct cause of acute coronary syndrome and sudden death is an intracoronary thrombus formed on a surface of unstable atherosclerotic plaque (UAP). The following are main characteristics of UAP: active inflammation; large lipid rich nucleus occupying a40% of plaque volume; thin (< 65 mm) fibrous cap; erosions of intima over plaque; tear of plaque cap; superficially located calcium nodules; intraplaque hemorrhage. Visualization of UAP in coronary arteries is a very important direction in diagnostics. During recent years both invasive and noninvasive methods of detection of UAP have been actively developed. In this review we present main noninvasive techniques used for detection of UAP: multislice computed tomography, magnetic resonance tomography, positron emission tomography and single-photon emission computed tomography. In the review we have covered main advantages and limitations of each invasive method of UAP detection and delineated perspectives of development of this direction.
10.18565/cardio.2015.5.80-88
Galectin-3 binding protein plasma levels are associated with long-term mortality in coronary artery disease independent of plaque morphology.
Gleissner Christian A,Erbel Christian,Linden Fabian,Domschke Gabriele,Akhavanpoor Mohammadreza,Doesch Andreas O,Buss Sebastian J,Giannitsis Evangelos,Katus Hugo A,Korosoglou Grigorios
Atherosclerosis
BACKGROUND AND AIMS:Galectin-3 binding protein (Gal-3BP) is a secreted protein associated with inflammation and carotid atherosclerosis. We hypothesized that high Gal-3BP levels may indicate unfavorable plaque morphology and outcome in coronary artery disease (CAD). METHODS:Gal-3BP plasma levels were measured by ELISA in 233 patients (63 ± 10 years, 50.2% male) undergoing computed coronary angiography tomography (CCTA). RESULTS:In 149 patients, CCTA confirmed CAD (stenosis grade >20%). Mean Gal-3BP plasma levels were 5.9 ± 2.7 μg/mL and did not differ between patients with or without CAD. Over a follow-up time of up to 4.4 years (median 2.5 years), there were 17 cases of revascularization, five cases of myocardial infarction, and five deaths (four non-cardiac, one fatal myocardial infarction). Kaplan-Meier analysis revealed that high Gal-3BP levels were significantly associated with long-term mortality (p < 0.001). Cox proportional hazards regression analysis showed that this association was independent of cardiovascular risk factors (HR 1.238, 95%-CI 1.012-1.514, p = 0.038). After adjustment for troponin T and C-reactive protein (hs-CRP) levels, significance was lost (p = 0.123). Further analysis revealed that Gal-3BP levels were significantly related to body mass index and hs-CRP levels indicating an association with metabolic and inflammatory distress. There was no correlation between Gal-3BP and calcium score, plaque volume, or vascular remodeling. CONCLUSIONS:While high Gal-3BP plasma levels are associated with long-term mortality, we could not confirm it as a marker of cardiac mortality or unstable plaque morphology.
10.1016/j.atherosclerosis.2016.06.002
F-sodium fluoride positron emission tomography for molecular imaging of coronary atherosclerosis based on computed tomography analysis.
Kitagawa Toshiro,Yamamoto Hideya,Toshimitsu Shinya,Sasaki Ko,Senoo Atsuhiro,Kubo Yumiko,Tatsugami Fuminari,Awai Kazuo,Hirokawa Yutaka,Kihara Yasuki
Atherosclerosis
BACKGROUND AND AIMS:We aimed at evaluating the relation of F-sodium fluoride (F-NaF) uptake on positron emission tomography (PET) to coronary atherosclerosis detected and assessed by computed tomography (CT). METHODS:Thirty-two patients with one or more coronary atherosclerotic lesions detected on cardiac CT underwent F-NaF PET/CT. Each coronary atherosclerotic lesion was evaluated on CT angiography for plaque types (calcified plaque [CP], non-calcified plaque [NCP], partially calcified plaque [PCP]), and the presence of CT-based high-risk features (minimum CT density <30 Hounsfield units and vascular remodeling index >1.1). Focal F-NaF uptake of each lesion was quantified using maximum tissue-to-background ratio (TBR). RESULTS:A total of 111 lesions were studied. In a patient-based analysis, logarithmically transformed coronary calcium score correlated positively with maximum TBR per patient, and 15 patients with myocardial infarction or unstable angina history showed a higher maximum TBR per patient than those without (1.36 ± 0.15 versus 1.15 ± 0.15, p = 0.0006). In a lesion-based analysis, PCP showed a higher TBR than CP and NCP (1.17 ± 0.19 versus 1.00 ± 0.24 and 0.92 ± 0.18, respectively, p < 0.0001), and the lesions with high-risk features had a higher TBR than those without (1.20 ± 0.21 versus 1.02 ± 0.20, p = 0.0011). CONCLUSIONS:Coronary arterial F-NaF uptake is related to total plaque burden, coronary event history, and specific features of coronary atherosclerosis based on CT analysis. F-NaF PET/CT, in combination with cardiac CT, may provide a new molecular imaging approach to identify high-risk patients and coronary atherosclerotic lesions.
10.1016/j.atherosclerosis.2017.04.024
Evaluation of Serum Pregnancy Associated Plasma Protein-A & Plasma D-Dimer in Acute Coronary Syndrome.
Nichenametla Gautam,Thomas Vivian Samuel
Journal of clinical and diagnostic research : JCDR
INTRODUCTION:Acute coronary syndrome (ACS), a spectrum comprising unstable angina pectoris, ST Elevated Myocardial Infarction (STEMI) & Non ST Elevated Myocardial Infarction (NSTEMI) is the major cause of presentation in Emergency Department today. Though ECG and cardiac enzymes are used for diagnosis, they mislead the diagnosis sometimes and delay in treatment initiation. This leads us to search certain new parameters which reflect the pathophysiology of ACS. Markers of plaque stability like Pregnancy Associated Plasma Protein-A and D-Dimer, a marker of ongoing thrombosis are found to be better markers in early diagnosis. AIM:To evaluate the diagnostic competence of PAPP-A and D-Dimer in acute coronary syndrome over CK-MB and to compare with the inflammatory marker High Sensitive C-Reactive Protein (hs-CRP) which is associated with atherosclerosis. MATERIALS AND METHODS:Fifty patients presenting with acute onset of chest pain to Emergency Department with or without ECG changes served as cases and 50 healthy people served as controls. Serum PAPP-A is measured by Enzyme Linked Immunosorbent Assay (ELISA), D-Dimer and hs-CRP by using Latex Turbidimetry method. RESULTS:A statistical significant difference of PAPP-A and D-Dimer was noted between the ACS and controls (p < 0.001) whereas CK-MB shows no much difference (p 0.09). Statistically significant positive correlation is noted between parameters. CONCLUSION:PAPP-A marker of plaque instability and D-Dimer marker of ongoing thrombosis are raised in acute coronary syndrome and thus can be considered as one of the marker in ACS for diagnosis.
10.7860/JCDR/2016/14432.7011
Percutaneous coronary intervention for a Chinese familial hypercholesterolemia homozygous under the guidance of optical coherence tomography.
Liu Zesen,Peng Jie,Wang Shilong,Jiang Tao,Zhang Weicong,Zhang Chun,Chen Yan,Meng Kang,Lin Jie
Atherosclerosis. Supplements
Homozygous familial hypercholesterolemia developed into severe cardiovascular consequences early. Untreated HoFH usually cannot survive over 30 years old. Acute coronary syndrome(ACS) caused by plaque rupture is one of the main causes of death in HoFH. As the highest resolution intravascular imaging technique, optical coherence tomography(OCT) can clearly show the thickness and structural characteristics of atherosclerotic plaque caps. In this study, a Chinese male HoFH received percutaneous coronary intervention for unstable angina. After analyzed his genetic and follow-up data, OCT was performed during interventional therapy. Multiple lipid rich plaques accompanied with inflammatory cell infiltration and a thin-cap fibroatheroma(TCFA) were noted, which reflected the vulnerability of plaques. The utility of OCT had certain guiding significance for strategy of interventional therapy and the long-term drug management. And this case suggested that it was important to undergo OCT examination for patients with HoFH who required percutaneous coronary intervention.
10.1016/j.atherosclerosissup.2019.01.004
Association between P-selectin glycoprotein ligand-1 and pathogenesis in acute coronary syndrome assessed by optical coherence tomography.
Ozaki Yuichi,Imanishi Toshio,Teraguchi Ikuko,Nishiguchi Tsuyoshi,Orii Makoto,Shiono Yasutsugu,Shimamura Kunihiro,Ishibashi Kohei,Tanimoto Takashi,Yamano Takashi,Ino Yasushi,Yamaguchi Tomoyuki,Kubo Takashi,Akasaka Takashi
Atherosclerosis
OBJECTIVE:Although monocytes appear to be actively involved in the onset of acute coronary syndrome (ACS), they are heterogenous in human peripheral blood. How up-regulation of monocyte subsets leads to coronary plaque rupture followed by thrombus formation remains unclear. Recent studies have shown that P-selectin glycoprotein ligand-1 (PSGL-1) is involved in monocyte activation in patients with thrombus formation. We therefore investigated the relationship between the expression of PSGL-1 on monocyte subsets and thrombus formation using frequency-domain optical coherence tomography (FD-OCT) in patients with ACS. METHODS:We enrolled a total of 100 individuals in this study: patients with acute myocardial infarction (AMI, n=25), unstable angina pectoris (UAP, n=20), or stable angina pectoris (n=35) who underwent coronary angiography, and control subjects (n=20). Three monocyte subsets (CD14++CD16-, CD14++CD16+, and CD14+CD16+) and the expression of PSGL-1 were measured by flow cytometry. In patients with AMI and UAP, FD-OCT was performed before percutaneous coronary intervention. RESULTS:Circulating peripheral CD14++CD16+ monocytes expressed PSGL-1 more frequently than CD14++CD16- and CD14+CD16+ monocytes in patients with ACS. The expression of PSGL-1 on circulating peripheral CD14++CD16+ monocytes was significantly elevated in patients with AMI compared with the other 3 groups. Moreover, the expression levels of PSGL-1 on CD14++CD16+ monocytes were significantly higher in patients with plaque rupture or intracoronary thrombus assessed by FD-OCT. CONCLUSION:Up-regulation of PSGL-1 on CD14++CD16+ monocytes may be a crucial role in plaque rupture and thrombus formation.
10.1016/j.atherosclerosis.2013.12.052
Correlation analysis of levels of adiponectin and matrix metalloproteinase-9 with stability of coronary heart disease.
Li Ya
Technology and health care : official journal of the European Society for Engineering and Medicine
OBJECTIVE:To analyze the changes of adiponection (ANP) and matrix metalloproteinase-9 (MMP-9) in patients with coronary heart diseases (CHD) of different types, to investigate the correlation between these changes and stability of coronary artery plague. METHODS:Inpatients of our hospital were divided into 56 cases with acute myocardial infarction (AMI), 56 cases with unstable angina pectoris (UA), 54 cases with stable angina pectoris (SA), and 60 cases with CHD excluded by using coronary arteriongraphy as the control group. Changes of ANP and MMP-9 were determined, and the correlation was analyzed. RESULTS:1. ANP and MMP-9 levels in CHD group were higher than those of control group (P < 0.01). 2. Serum ANP and MMP-9 levels in AMI and UA groups were significantly higher than those in control group and SA group (P < 0.05). 3. MMP-9 level in AMI group was significantly higher than that in UA group (P < 0.01). CONCLUSION:1. Increased ANP and MMP-9 levels are the independent risk factors of CHD; 2. Increased levels of ANP and MMP-9 in patients with CHD suggest instability of atherosclerotic plaque.
10.3233/thc-150937
A Proteomic Study of Atherosclerotic Plaques in Men with Coronary Atherosclerosis.
Stakhneva Ekaterina M,Meshcheryakova Irina A,Demidov Evgeny A,Starostin Konstantin V,Sadovski Evgeny V,Peltek Sergey E,Voevoda Michael I,Chernyavskii Alexander M,Volkov Alexander M,Ragino Yuliya I
Diagnostics (Basel, Switzerland)
BACKGROUND:To study the changes in protein composition of atherosclerotic plaques at different stages of their development in coronary atherosclerosis using proteomics. METHODS:The object of research consisted of homogenates of atherosclerotic plaques from coronary arteries at different stages of development, obtained from 15 patients. Plaque proteins were separated by two-dimensional electrophoresis. The resultant protein spots were identified by the matrix-assisted laser desorption ionization method with peptide mass mapping. RESULTS:Groups of differentially expressed proteins, in which the amounts of proteins differed more than twofold ( < 0.05), were identified in pools of homogenates of atherosclerotic plaques at three stages of development. The amounts of the following proteins were increased in stable atherosclerotic plaques at the stage of lipidosis and fibrosis: vimentin, tropomyosin β-chain, actin, keratin, tubulin β-chain, microfibril-associated glycoprotein 4, serum amyloid P-component, and annexin 5. In plaques at the stage of fibrosis and calcification, the amounts of mimecan and fibrinogen were increased. In unstable atherosclerotic plaque of the necrotic-dystrophic type, the amounts of human serum albumin, mimecan, fibrinogen, serum amyloid P-component and annexin were increased. CONCLUSION:This proteomic study identifies the proteins present in atherosclerotic plaques of coronary arteries by comparing their proteomes at three different stages of plaque development during coronary atherosclerosis.
10.3390/diagnostics9040177
The potential inhibitory effects of miR‑19b on vulnerable plaque formation via the suppression of STAT3 transcriptional activity.
Li Sufang,Geng Qiang,Chen Hong,Zhang Jing,Cao Chengfu,Zhang Feng,Song Junxian,Liu Chuanfen,Liang Wenqing
International journal of molecular medicine
Atherosclerotic plaque growth requires angiogenesis, and acute coronary syndrome (ACS) is usually triggered by the rupture of unstable atherosclerotic plaques. Previous studies have identified typically circulating microRNA (miRNA/miR) profiles in patients with ACS. miRNAs serve important roles in the pathophysiology of atherosclerotic plaque progression. The present study aimed to investigate the potential role and mechanism of miR‑19b in plaque stability. miRNA array data indicated that 28 miRNAs were differentially expressed in the plasma of patients with unstable angina (UA; n=12) compared with in control individuals (n=12), and miR‑19b exhibited the most marked upregulation. Circulating miR‑19b levels were further validated in another independent cohort, which consisted of 34 patients with UA and 24 controls, by quantitative polymerase chain reaction. Gene Ontology annotations of the predicted target genes of miR‑19b suggested that miR‑19b may be involved in endothelial cell (EC) proliferation, migration and angiogenesis, which was confirmed by Cell Counting kit‑8, wound healing and tube formation assays in the present study. Finally, the present study indicated that miR‑19b may suppress signal transducer and activator of transcription 3 (STAT3) tyrosine phosphorylation and transcriptional activity in ECs, as determined by western blot analysis and luciferase reporter assay. In conclusion, the present study revealed that increased miR‑19b expression may delay unstable plaque progression in patients with UA by inhibiting EC proliferation, migration and angiogenesis via the suppression of STAT3 transcriptional activity.
10.3892/ijmm.2017.3263
In Vivo Translation of the CIRPI System: Revealing Molecular Pathology of Rabbit Aortic Atherosclerotic Plaques.
Zaman Raiyan T,Yousefi Siavash,Chibana Hidetoshi,Ikeno Fumiaki,Long Steven R,Gambhir Sanjiv S,Chin Frederick T,McConnell Michael V,Xing Lei,Yeung Alan
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Thin-cap fibroatheroma (TCFA) are the unstable lesions in coronary artery disease that are prone to rupture, resulting in substantial morbidity and mortality worldwide. However, their small size and complex morphologic and biologic features make early detection and risk assessment difficult. We tested our newly developed catheter-based ircumferential-ntravascular-adioluminescence-hotoacoustic-maging (CIRPI) system in vivo to enable detection and characterization of vulnerable plaque structure and biology in rabbit abdominal aorta. The CIRPI system includes a novel optical probe combining circumferential radioluminescence imaging and photoacoustic tomography (PAT). The probe's CaF:Eu-based scintillating imaging window captures radioluminescence images (360° view) of plaques by detecting β-particles during F-FDG decay. A tunable laser-based PAT characterizes tissue constituents of plaque at 7 different wavelengths-540 and 560 nm (calcification), 920 nm (cholesteryl ester), 1040 nm (phospholipids), 1180 nm (elastin/collagen), 1210 nm (cholesterol), and 1235 nm (triglyceride). A single B-scan is concatenated from 330 A-lines captured during a 360° rotation. The abdominal aorta was imaged in vivo in both atherosclerotic rabbits (Watanabe Heritable Hyper Lipidemic [WHHL], 13-mo-old male, = 5) and controls (New Zealand White, = 2). Rabbits were fasted for 6 h before 5.55 × 10 Bq (1.5 mCi) of F-FDG were injected 1 h before the imaging procedure. Rabbits were anesthetized, and the right or left common carotid artery was surgically exposed. An 8 French catheter sheath was inserted into the common carotid artery, and a 0.035-cm (0.014-in) guidewire was advanced to the iliac artery, guided by x-ray fluoroscopy. A bare metal stent was implanted in the dorsal abdominal aorta as a landmark, followed by the 7 French imaging catheters that were advanced up to the proximal stent edge. Our CIRPI and clinical optical coherence tomography (OCT) were performed using pullback and nonocclusive flushing techniques. After imaging with the CIRPI system, the descending aorta was flushed with contrast agent, and OCT images were obtained with a pullback speed of 20 mm/s, providing images at 100 frames/s. Results were verified with histochemical analysis. Our CIRPI system successfully detected the locations and characterized both stable and vulnerable aortic plaques in vivo among all WHHL rabbits. Calcification was detected from the stable plaque (540 and 560 nm), whereas TCFA exhibited phospholipids/cholesterol (1040 nm, 1210 nm). These findings were further verified with the clinical OCT system showing an area of low attenuation filled with lipids within TCFA. PAT images illustrated broken elastic fiber/collagen that could be verified with the histochemical analysis. All WHHL rabbits exhibited sparse to severe macrophages. Only 4 rabbits showed both moderate-to-severe level of calcifications and cholesterol clefts. However, all rabbits exhibited broken elastic fibers and collagen deposition. Control rabbits showed normal wall thickness with no presence of plaque tissue compositions. These findings were verified with OCT and histochemical analysis. Our novel multimodality hybrid system has been successfully translated to in vivo evaluation of atherosclerotic plaque structure and biology in a preclinical rabbit model. This system proposed a paradigm shift that unites molecular and pathologic imaging technologies. Therefore, the system may enhance the clinical evaluation of TCFA, as well as expand our understanding of coronary artery disease.
10.2967/jnumed.118.222471
[Vascular Calcification - Pathological Mechanism and Clinical Application - . The significance of arterial calcification in unstable plaques].
Inaba Mayumi,Ueda Makiko
Clinical calcium
Plaque rupture or erosion with subsequent thrombus formation is the principal mechanism underlying the sudden onset of acute coronary syndromes. Plaque inflammation and increased oxidative stress play important roles in the pathogenesis of plaque destabilization. Macrophages, T lymphocytes, and neutrophils are the dominant types of inflammatory cells at human coronary unstable plaques, such as ruptured plaques or eroded plaques. Calcification is a common finding in human atherosclerotic lesions, and arterial calcification is generally classified into calcification within an atherosclerotic plaque, and Mönckeberg's medial calcific sclerosis characterized by calcific deposits within the media of small and medium-sized muscular arteries. It has been reported that a spotty pattern of calcification is associated with coronary unstable ruptured plaques in patients with acute myocardial infarction. Patients undergoing hemodialysis (HD) have a high prevalence of arterial calcification and cardiovascular events. We recently demonstrated that plasma oxidized low density lipoprotein (LDL) levels significantly increased after a single HD session. This HD session-related increase in plasma oxidized LDL levels could contribute to the progression and acceleration of atherosclerosis and arterial calcification, leading to the development of cardiovascular events in HD patients.
CliCa1505679686
Almanac 2013: Acute coronary syndromes.
Meier Pascal,Lansky Alexandra J,Baumbach Andreas
Acta cardiologica
Unstable coronary artery plaque is the most common underlying cause of acute coronary syndromes (ACS) and can manifest as unstable angina, non-ST segment elevation infarction (NSTE-ACS), and ST elevation myocardial infarction (STEMI), but can also manifest as sudden cardiac arrest due to ischaemia induced tachyarrhythmias. ACS mortality ha decreased significantly over the last few years, especially from the more extreme manifestations of ACS, STEMI, and cardiac arrest. This trend is likely to continue based on recent therapeutic progress which includes novel antiplatelet agents such as prasugrel, ticagrelor, and cangrelor.
10.2143/AC.69.1.3011351
Alternatively spliced tissue factor promotes plaque angiogenesis through the activation of hypoxia-inducible factor-1α and vascular endothelial growth factor signaling.
Giannarelli Chiara,Alique Matilde,Rodriguez David T,Yang Dong Kwon,Jeong Dongtak,Calcagno Claudia,Hutter Randolph,Millon Antoine,Kovacic Jason C,Weber Thomas,Faries Peter L,Soff Gerald A,Fayad Zahi A,Hajjar Roger J,Fuster Valentin,Badimon Juan J
Circulation
BACKGROUND:Alternatively spliced tissue factor (asTF) is a novel isoform of full-length tissue factor, which exhibits angiogenic activity. Although asTF has been detected in human plaques, it is unknown whether its expression in atherosclerosis causes increased neovascularization and an advanced plaque phenotype. METHODS AND RESULTS:Carotid (n=10) and coronary (n=8) specimens from patients with stable or unstable angina were classified as complicated or uncomplicated on the basis of plaque morphology. Analysis of asTF expression and cell type-specific expression revealed a strong expression and colocalization of asTF with macrophages and neovessels within complicated, but not uncomplicated, human plaques. Our results showed that the angiogenic activity of asTF is mediated via hypoxia-inducible factor-1α upregulation through integrins and activation of phosphatidylinositol-3-kinase/Akt and mitogen-activated protein kinase pathways. Hypoxia-inducible factor-1α upregulation by asTF also was associated with increased vascular endothelial growth factor expression in primary human endothelial cells, and vascular endothelial growth factor-Trap significantly reduced the angiogenic effect of asTF in vivo. Furthermore, asTF gene transfer significantly increased neointima formation and neovascularization after carotid wire injury in ApoE(-/-) mice. CONCLUSIONS:The results of this study provide strong evidence that asTF promotes neointima formation and angiogenesis in an experimental model of accelerated atherosclerosis. Here, we demonstrate that the angiogenic effect of asTF is mediated via the activation of the hypoxia-inducible factor-1/vascular endothelial growth factor signaling. This mechanism may be relevant to neovascularization and the progression and associated complications of human atherosclerosis as suggested by the increased expression of asTF in complicated versus uncomplicated human carotid and coronary plaques.
10.1161/CIRCULATIONAHA.114.006614
Early diagnostic value of circulating microRNAs in patients with suspected acute myocardial infarction.
Li Long,Li Sufang,Wu Manyan,Chi Cheng,Hu Dan,Cui Yuxia,Song Junxian,Lee Chongyou,Chen Hong
Journal of cellular physiology
BACKGROUND/AIMS:Evidence has shown that several microRNAs (miRNAs) may be involved in coronary plaque rupture and local thrombus. However, the diagnostic ability of these miRNAs in acute myocardial infarction (AMI) is less known. The aim of this study is to explore the diagnostic value of these circulating miRNAs in patients presenting with acute chest pain in the emergency department. METHODS AND RESULTS:In a nested case-control study, 140 of 1,206 patients finally diagnosed with AMI were matched with 70 unstable angina and 70 noncardiac chest pain patients. Five candidate miRNAs (miR-483-5p, miR-155-5p, miR-451, miR-19b, and miR-223) were selected for validation. Among them, miR-19b, miR-223, and miR-483-5p were significantly higher in AMI patients compared with those without AMI. A multivariate analysis showed that these miRNAs were independent predictors of AMI. The overall areas under the receiver operating curves (AUCs) for miR-19b, miR-223, and miR-483-5p were 0.74, 0.65, and 0.70, respectively. However, serial sampling in AMI patients showed that these miRNAs already peaked on admission, which was earlier than troponin I. Among 170 patients with a negative troponin result at presentation, a panel of three miRNAs improved the discrimination ability to a clinical model. In 119 patients presenting within 3 hr after chest-pain onset, the diagnostic accuracy of each miRNAs was higher than Point of care (POC) troponin assay. And a panel of these miRNAs had an AUC of 0.92. CONCLUSION:Circulating miR-19b, miR-223, and miR-483-5p may provide clinically useful information for diagnosis in the early phases of AMI.
10.1002/jcp.28045
Nox4 NADPH oxidase contributes to smooth muscle cell phenotypes associated with unstable atherosclerotic plaques.
Xu Shaoping,Chamseddine Ali H,Carrell Samuel,Miller Francis J
Redox biology
Plaque instability associated with acute coronary syndromes results in part from apoptosis and senescence of cells within the atherosclerotic (AS) lesion. Increased cellular oxidative stress has been proposed to contribute to plaque progression and changes in composition, leading to plaque instability. Our objective was to examine the role of NADPH oxidase in smooth muscle cell (SMC) phenotypes associated with an unstable plaque. Aortae were isolated from pre-lesion (8 weeks of age) and post-lesion (35 weeks of age) hypercholesterolemic mice (ApoE(-/-)/LDLR(-/-), AS), and age-matched normal C57BL/6J mice. We observed an age-dependent increase in reactive oxygen species (ROS) in aorta from AS mice, with evidence for elevated ROS prior to lesion development. Whereas macrophage infiltration was restricted to the lesion, oxidized lipids extended beyond the plaque and into the vessel wall. Consistent with these findings, we observed dynamic changes in the expression of NADPH oxidases in AS vessels. Specifically, Nox1 expression was increased early and decreased with lesion progression, while induction of Nox4 was a late event. Nox2 and p22(phox) were elevated throughout lesion development. Similar to observations in aortae, SMCs isolated from the lesion of AS aortae had decreased Nox1 and increased Nox4 levels as compared to SMCs from normal mice. AS SMCs demonstrated increased generation of ROS, cell cycle arrest, evidence of senescence, and increased susceptibility to apoptosis. Overexpression of Nox4 in normal SMCs recapitulated the phenotypes of the AS SMCs. We conclude that increased expression of Nox4 in AS may drive SMC phenotypes that lead to the plaque instability and rupture responsible for myocardial infarction and stroke.
10.1016/j.redox.2014.04.004
The prognostic value of various carotid ultrasound parameters in patients at high and very high cardiovascular risk.
International journal of cardiology
BACKGROUND:According to the current guidelines the visualization of atherosclerotic plaques in the carotid arteries is the only option that carotid ultrasound provides for the assessment of cardiovascular risk (CVR). The direction devoted to the development and implementation of markers based on the quantification of atheroma, is promising. The aim of the study was to evaluate the prognostic value of various carotid ultrasound parameters in patients at high and very high CVR. METHODS:Patients at high and very high CVR were included. All patients underwent carotid ultrasound. We evaluated carotid intima-media thickness (cIMT), carotid plaque, carotid plaque score (cPS) and carotid total plaque area (cTPA). The combined endpoint was cardiovascular death, non-fatal myocardial infarction or unstable angina, non-fatal stroke and coronary revascularization. RESULTS:The study included 100 patients. The duration of the follow-up period was 24.4 (14.1-34.3) months. Endpoint events occurred in 34.0% patients. cIMT and cPS were not significantly associated with the risk of cardiovascular events. The presence of carotid plaque in accordance with Cox regression after adjusting for possible confounders was associated with an increase in the relative risk of cardiovascular events by 10.5 times (95% CI 1.27-86.5; p = 0.008). CTPA ≥69 mm according to adjusted analysis was associated with an increase in the risk of cardiovascular events by 5.86 times (95% CI 2.09-16.4; p = 0.001). CONCLUSION:In patients at high and very high CVR among carotid atherosclerosis markers only carotid plaque and cTPA had an independent predictive value regarding the development of adverse cardiovascular events.
10.1016/j.ijcard.2019.06.038
Elastin fragmentation in atherosclerotic mice leads to intraplaque neovascularization, plaque rupture, myocardial infarction, stroke, and sudden death.
Van der Donckt Carole,Van Herck Jozef L,Schrijvers Dorien M,Vanhoutte Greetje,Verhoye Marleen,Blockx Ines,Van Der Linden Annemie,Bauters Dries,Lijnen Henri R,Sluimer Judith C,Roth Lynn,Van Hove Cor E,Fransen Paul,Knaapen Michiel W,Hervent Anne-Sophie,De Keulenaer Gilles W,Bult Hidde,Martinet Wim,Herman Arnold G,De Meyer Guido R Y
European heart journal
AIMS:There is a need for animal models of plaque rupture. We previously reported that elastin fragmentation, due to a mutation (C1039G(+/-)) in the fibrillin-1 (Fbn1) gene, promotes atherogenesis and a highly unstable plaque phenotype in apolipoprotein E deficient (ApoE(-/-)) mice on a Western-type diet (WD). Here, we investigated whether plaque rupture occurred in ApoE(-/-)Fbn1(C1039G+/-) mice and was associated with myocardial infarction, stroke, and sudden death. METHODS AND RESULTS:Female ApoE(-/-)Fbn1(C1039G+/-) and ApoE(-/-) mice were fed a WD for up to 35 weeks. Compared to ApoE(-/-) mice, plaques of ApoE(-/-)Fbn1(C1039G+/-) mice showed a threefold increase in necrotic core size, augmented T-cell infiltration, a decreased collagen I content (70 ± 10%), extensive neovascularization, intraplaque haemorrhage, and a significant increase in matrix metalloproteinase-2, -9, -12, and -13 expression or activity. Plaque rupture was observed in 70% of ascending aortas and in 50% of brachiocephalic arteries of ApoE(-/-)Fbn1(C1039G+/-) mice. In ApoE(-/-) mice, plaque rupture was not seen in ascending aortas and only in 10% of brachiocephalic arteries. Seventy percent of ApoE(-/-)Fbn1(C1039G+/-) mice died suddenly, whereas all ApoE(-/-) mice survived. ApoE(-/-)Fbn1(C1039G+/-) mice showed coronary plaques and myocardial infarction (75% of mice). Furthermore, they displayed head tilt, disorientation, and motor disturbances (66% of cases), disturbed cerebral blood flow (73% of cases; MR angiograms) and brain hypoxia (64% of cases), indicative of stroke. CONCLUSIONS:Elastin fragmentation plays a key role in plaque destabilization and rupture. ApoE(-/-)Fbn1(C1039G+/-) mice represent a unique model of acute plaque rupture with human-like complications.
10.1093/eurheartj/ehu041
The Correlation of Serum Myeloid-Related Protein-8/14 and Eosinophil Cationic Protein in Patients with Coronary Artery Disease.
Xia Guo-lian,Wang Yun-kai,Huang Zhao-quan
BioMed research international
OBJECTIVE:To investigate the changes in serum Myeloid-Related Protein 8/14 (MRP8/14) and Eosinophil Cationic Protein (ECP) levels in patients with different types of coronary artery diseases (CAD) and assess the value of MRP8/14 and ECP detection in predicting CAD. METHODS:178 patients were divided into CAD group including unstable angina pectoris (UAP), acute myocardial infarction (AMI), and stable angina pectoris (SAP). Thirty-six individuals with normal coronary artery served as the control group. Serum MRP8/14 and ECP were measured by ELISA. The severity of coronary artery stenosis was assessed by the numbers of involved coronary artery branches and the sum of Gensini scores. RESULTS:The MRP8/14 levels were significantly higher in AMI and UAP group than SAP and control group (P < 0.05). The levels of MRP8/14 in AMI group were also obviously higher than UAP group (P < 0.05). The ECP levels were obviously increased in AMI group, but there was no difference between SAP and UAP group (P > 0.05). The ECP was significantly increased in three impaired coronary arteries and obviously correlated with Gensini score (P < 0.01), whereas the MRP8/14 was obviously positively correlated with CRP (P < 0.01). CONCLUSIONS:Increased MRP8/14 levels suggest the instability of the atherosclerotic plaque. ECP reflects the severity of coronary arteries stenosis, predicting atherosclerosis burden. They may become the new biomarkers of CAD.
10.1155/2016/4980251
Potential contribution of virtual histology plaque composition to hemodynamic-morphologic dissociation in patients with non-ST elevation acute coronary syndrome.
Hüseyinova Güneş,Aslanger Emre,Çakır Ozan,Atıcı Adem,Panç Cafer,Demirkıran Ahmet,Sürmen Semih,Sarıkaya Remzi,Erdoğan Onur,Gölcük Ebru,Umman Sabahattin,Sezer Murat
International journal of cardiology
OBJECTIVE:Histologic plaque characteristics may influence the hemodynamic effect generated by physiologically significant unstable coronary lesions where plaque content and surface related factors are expected to contribute to the maximum translesional pressure drop. In this study, we aimed to identify local lesion specific virtual histological characteristics that may potentially affect hemodynamic outcome measures. METHODS:Forty-eight consecutive patients with non-ST-elevation acute coronary syndrome (NSTEACS) having paired hemodynamic and morphological data were enrolled. A dual sensor guide-wire was used for the assessment of fractional flow reserve (FFR) and stenosis resistance (HSR) in the culprit vessel. Virtual histology intravascular ultrasound imaging was performed after obtaining hemodynamic data. RESULTS:In a hemodynamically significant lesion subset (FFR<0.75 [n=34]), after controlling for lesion length, MLA and coronary artery compliance, FFR correlated with necrotic core (NC) area (r=-0.423, p=0.028) at MLA and NC volume (r=-0.497, p=0.008) and dense calcium (DC) volume (r=-0.332, p=0.03) across the entire lesion segment. Likewise, NC (r=-0.544, p=0.005) and DC (r=0.376, p=0.03) areas at MLA and NC (r=0.545, p=0.005) and DC (r=0.576, p=0.003) volumes across the entire lesion segment were associated with HSR in the hemodynamically significant lesion group (HSR>0.80 [n=33]). However, no correlation has been observed between intracoronary hemodynamic end-points and plaque components in hemodynamically insignificant lesions. CONCLUSIONS:This study demonstrated that for a given coronary stenosis geometry and arterial compliance, plaque composition may influence hemodynamic outcome measures in functionally significant stenoses in patients with NSTEACS.
10.1016/j.ijcard.2015.03.316
Clinical significance of optical coherence tomography-guided angioplasty on treatment selection.
Huang Jianfeng,Belmadani Kamal,Chatot Marion,Ecarnot Fiona,Chopard Romain,Wang Manhong,Cai Xu,Schiele Francois,Meneveau Nicolas
Experimental and therapeutic medicine
The present study aimed to observe whether optical coherence tomography (OCT)-guided angioplasty is able to provide useful clinical information beyond that obtained by angiography as well as provide recommendations for physicians that may improve treatment selection. This prospective study included 83 patients with coronary artery disease (>18 years) undergoing coronary angiography (CAG) for ST-elevation myocardial infarction (n=13), non-ST-elevation myocardial infarction (n=19), stable angina (n=22), unstable angina (n=10), silent ischemia (n=11), or elective percutaneous coronary intervention (n=8). Following the initial CAG (CAG-pre), the patients underwent OCT before angioplasty (OCT-pre, 24 patients), after angioplasty (OCT-post, 22 patients), or both (37 patients). The thrombus burden, calcification and plaque dissection or rupture were compared between the OCT-pre and CAG-pre recordings. Following angioplasty, stent malapposition, suboptimal stent deployment, suboptimal stent lesion coverage, and edge dissection were compared between OCT-post and CAG-post alone. Among the 83 patients, 45.7% had single-vessel and 54.3% had multiple-vessel disease. OCT pre- and post-angioplasty revealed significantly more information on the procedure than CAG alone. This clinical information changed the clinical strategies in 41/83 (49.4%) patients, including 58 modifications of therapeutic strategy (69.9%, 58/83): Thrombus aspiration in 2 cases (2.4%), administration of glycoprotein IIb/IIIa inhibitors in 8 cases (9.6%), additional balloon inflation in 23 cases (27.7%), additional stent implantation in 17 cases (20.5%), avoiding stent implantation in 4 cases (4.8%), collateral intervention in 2 cases (2.4%), and guidewire reposition in 2 cases (2.4%). In conclusion, OCT-pre and OCT-post provided additional clinical information beyond that obtained by angiography alone, which resulted in modification of the treatment strategies in half of the included patients.
10.3892/etm.2018.6237
Cholesterol crystal as a new feature of coronary vulnerable plaques: An optical coherence tomography study.
Nishimura Satoshi,Ehara Shoichi,Hasegawa Takao,Matsumoto Kenji,Yoshikawa Junichi,Shimada Kenei
Journal of cardiology
BACKGROUND:Previous pathohistological studies demonstrated that cholesterol crystals (CCs) are frequently observed in atherosclerotic plaques, and are usually present abundantly in vulnerable plaques. However, the role of CCs in plaque destabilization, as well as their origin and composition, is unknown. Optical coherence tomography (OCT) imaging system is a high-resolution imaging device, which allows the in vivo identification of CCs accumulating within atherosclerotic plaques. The aim of this study was to investigate the relationship between the presence of CCs, other plaque morphologies assessed by OCT, and patients' clinical characteristics including acute coronary syndrome (ACS). METHODS AND RESULTS:Preinterventional OCT images of 173 patients with either ACS or stable angina pectoris were studied. Of 173 lesions in the patients, 66 (38%) had CCs within the culprit lesion segment and 107 (62%) had non-CC lesions. Multivariate analysis revealed that low high-density lipoprotein cholesterol levels, diabetes mellitus, the presence of plaque rupture, intimal vasculature, and thrombus were independent factors associated with CCs. Moreover, the frequency of CCs increased in proportion to the accumulation of the number of components of their vulnerable plaque features within the culprit lesion segment. Compared with the plaques without thrombus, CCs were present at shallower locations in those with thrombus. CONCLUSIONS:This study demonstrates the potential correlation between the clinical metabolic disorder and vulnerable morphological features of culprit lesions to the presence of CCs in patients with stable and unstable coronary syndromes. These observations of CCs by using in vivo plaque imaging could provide incremental value to OCT evaluation of atherosclerotic plaques.
10.1016/j.jjcc.2016.04.003
Incremental Prognostic Value of Coronary Computed Tomography Angiography: High-Risk Plaque Characteristics in Asymptomatic Patients.
Takamura Kazuhisa,Fujimoto Shinichiro,Kondo Takeshi,Hiki Makoto,Kawaguchi Yuko,Kato Etsuro,Daida Hiroyuki
Journal of atherosclerosis and thrombosis
AIM:Coronary computed tomography angiography (CCTA) findings of positive remodeling (index >1.1) and low-attenuation plaque (<30 Hounsfield units) are recognized as CT-verified high-risk plaque (CT-HRP). Therefore, we investigated the incremental prognostic value of evaluation of plaque characteristics using CCTA in asymptomatic patients. METHODS:Overall, 495 consecutive patients without any known coronary artery disease who underwent CCTA were included in this study. Patients who underwent revascularization within 30 days of CCTA or had scans with poor image quality were excluded. Clinical follow-up data (716.5±262.6 days) were available for 339 patients, who were analyzed for the current study. Framingham risk score (FRS), coronary artery calcium score (CACS), and CT-HRP were investigated as predictors of cardiac events by multivariable analysis using Cox proportional hazard model. Improvement of predictive accuracy by including CT findings was evaluated from reclassification [net reclassification indices (NRI) and integrated discrimination improvement (IDI)] standpoints. RESULTS:During the follow-up period, 9 cardiac events (cardiac death: 0, nonfatal myocardial infarction: 2, hospitalization for unstable or progressive angina: 7) occurred. Multivariate Cox proportional hazard analysis demonstrated that CACS (HR, 13.23; 95% CI, 1.62-107.78, p<0.0164) and CT-HRP (HR, 11.27; 95% CI, 1.24-102.12, p<0.0321) were the independent predictors of cardiac events. NRI was 0.9556 (p<0.0007) and IDI was 0.2582 (p<0.0203), and the diagnostic performance improved by CT-HRP added to the combination of CACS and FRS. CONCLUSION:Although the cardiac event rate was low, the evaluation of CCTA plaque characteristics may provide incremental prognostic value to CACS in asymptomatic patients.
10.5551/jat.39115
MicroRNA-21 is a unique signature associated with coronary plaque instability in humans by regulating matrix metalloproteinase-9 via reversion-inducing cysteine-rich protein with Kazal motifs.
Fan Xuesong,Wang Enshi,Wang Xianyun,Cong Xiangfeng,Chen Xi
Experimental and molecular pathology
BACKGROUND:Coronary atherosclerotic unstable plaque is one of the leading causes of cardiovascular death. Macrophage-derived matrix metalloproteinase (MMP) 9 is considered for degrading extracellular matrix and collagen, thereby thinning the fibrous cap in plaques. miR-21 is implicated to play an important role in the progression of atherosclerosis. Nevertheless, miR-21 as the biomarker for coronary atherosclerotic unstable plaque remains unknown. We aimed to investigate the prediction role of miR-21 for unstable plaque by pathway study of miR-21 on MMPs and its inhibitor RECK in macrophages. METHODS:Expression of miR-21 in macrophages and serum miR-21 as well as MMP-9 was measured in patients with coronary non-calcified plaque, calcified plaque and controls. In vitro experiment was done in human macrophages by over-expressing miR-21 or down-regulating RECK. The regulation of RECK and MMP-9 by miR-21 was evaluated by western blotting and siRNA strategy. RESULTS:Patients with non-calcified coronary artery lesions had significantly higher miR-21 in macrophages and lower miR-21 serum levels compared to the control and calcified plaque patients. At the same time, the serum levels of MMP-9 were significantly elevated in non-calcified patients. Experiments in vitro indicated that over-expressing miR-21 could induce the expression and secretion of pro-MMP-9 and active-MMP-9 in human macrophages via targeting gene RECK, and knocking down RECK expression by specific siRNA can resemble that of miR-21 over-expression. CONCLUSIONS:miR-21 might be a biomarker for plaque instability by suppressing target gene RECK to promote the expression and secretion of MMP-9 in macrophages.
10.1016/j.yexmp.2014.02.009
Association of Circulating IGFBP1 Level with the Severity of Coronary Artery Lesions in Patients with Unstable Angina.
Zheng Wei,Lai Yayu,Jin Peng,Gu Wenzhu,Zhou Qi,Wu Xiaojing
Disease markers
Local IGFBP1 level was reported to affect the development of coronary artery plaque. This study investigated the association of circulating IGFBP1 level with the severity of coronary artery lesions in patients with unstable angina. In 112 consecutive patients with clinically diagnosed unstable angina, admitted from July 2014 to July 2015, we studied the correlations of circulating IGFBP1 and the severity of coronary artery disease (CAD). All patients underwent scheduled coronary angiography, and 67 cases were diagnosed with critical and 45 with noncritical CAD. Of the 67 critical CAD patients, 41 (61.19%) presented with multivessel and 26 (38.81%) with single-vessel lesions. IGFBP1 levels were higher in patients with multivessel than those with single-vessel lesions. Moreover, the IGFBP1 level was positively correlated with the GRACE score. Among clinical variables, the IGFBP1 level was correlated with HDL-C. IGFBP1 alone (cutoff 20.86 ng/ml) demonstrated a sensitivity of 0.448 and specificity of 0.933 in predicting CAD. Combination of IGFBP1 and HDL-C had a sensitivity of 0.821 and specificity of 0.800 in predicting CAD. Circulating IGFBP1 level positively correlated with the severity of CAD. IGFBP1, when combined with HDL-C, might be useful in screening for high risk CAD patients.
10.1155/2017/1917291
Indoleamine 2,3-dioxygenase 1 in coronary atherosclerotic plaque enhances tissue factor expression in activated macrophages.
Research and practice in thrombosis and haemostasis
BACKGROUND:Recent clinical studies have found that changes in the kynurenine (Kyn) pathway of tryptophan (Trp) metabolism are associated with cardiovascular events. However, the roles of the Kyn pathway on vascular wall thrombogenicity remain unknown. Indoleamine 2,3-dioxygenase 1 (IDO1) is a rate-limiting enzyme of the Kyn pathway. OBJECTIVE:The present study aimed to localize IDO1 in human coronary atherosclerotic plaques from patients with angina pectoris and define its role in plaque thrombogenicity. METHODS:Immunohistochemical methods were applied to localize IDO1 in coronary atherosclerotic plaques from patients with stable (SAP) and unstable (UAP) angina pectoris. The role of IDO1 in tissue factor (TF) expression was investigated in THP-1 macrophages activated by interferon (IFN)γ and tissue necrosis factor (TNF)α. RESULTS:We localized IDO1 mainly in CD68-positive macrophages within atherosclerotic plaques, and in close association with TF. Areas that were immunopositive for IDO1, TF, and CD3-positive T lymphocytes were significantly larger in plaques from patients with UAP than SAP. Macrophages activated by IFNγ and TNFα upregulated IDO1 expression, increased the Kyn/Trp ratio and enhanced TF expression and activity, but not TF pathway inhibitor expression. The IDO1 inhibitor epacadostat significantly reduced the Kyn/Trp ratio, TF expression and activity, as well as NF-κB (p65) binding activity in activated macrophages. Inhibition of the aryl hydrocarbon receptor that binds to Kyn, also reduced Kyn-induced TF expression in activated macrophages. CONCLUSION:Indoleamine 2,3-dioxygenase 1 expressed in coronary atherosclerotic plaques might contribute to thrombus formation through TF upregulation in activated macrophages.
10.1002/rth2.12128
The Role of Insulin-Like Growth Factor-1 and Pregnancy-Associated Plasma Protein-A in Diagnosis of Acute Coronary Syndrome and Its Related Morbidities.
Advanced journal of emergency medicine
INTRODUCTION:Pregnancy-associated plasma protein-A (PAPP-A) is a metalloproteinase that plays a role in atherosclerotic plaque destabilization. In recent studies, insulin-like growth factor-1 (IGF-1) has been introduced as a mediator of atherosclerosis. PAPP-A and IGF-1 level may be important diagnostic indicators of acute coronary syndrome (ACS). OBJECTIVE:The present study tried to assess the diagnostic role of IGF-1 and PAPP-A biomarkers in ACS spectrum. METHODS:The serum level of IGF-1, PAPP-A and troponin I was determined in 121 consecutive patients with ACS. Relationships were assessed by t-test, ANOVA and the non-parametric equivalent. Accuracy of biomarkers was measured by the area under the ROC curve (AUC) and optimal cut-off points to diagnose STEMI and NSTEMI using Youden index. RESULTS:In patients with acute ST segment elevation myocardial infarction (STEMI), all of these three biomarkers were significantly higher than those in patients with unstable angina (P= 0.028 for IGF-1, P<0.001 for PAPP-A and Troponin-I). Mean level of IGF-1 in patients with renal failure was significantly higher than that in patients without renal failure (137.9±35.1 vs 105.1±46.9, P=0.003), but PAPP-A and serum Troponin-I level had no significant difference in renal failure groups (P>0.05). ROC curve analysis showed that after Troponin-I, PAPP-A was a good discriminator between patients with STEMI and patients with unstable angina (AUC=0.79). Optimum cut-off value for PAPP-A was found to be 89.2 ng/ml, with sensitivity and specificity of 66.7% and 83.8%, respectively. CONCLUSION:PAPP-A can be a novel biomarker for both identification of patients with STEMI and risk stratification in patients with ACS.
10.22114/ajem.v0i0.200
Efficacy of Carotid Endarterectomy for Mild (<50%) Symptomatic Carotid Stenosis with Unstable Plaque.
Kashiwazaki Daina,Shiraishi Keitaro,Yamamoto Shusuke,Kamo Tetsuhiro,Uchino Haruto,Saito Hisayasu,Akioka Naoki,Kuwayama Naoya,Noguchi Kyo,Kuroda Satoshi
World neurosurgery
BACKGROUND:Carotid endarterectomy (CEA) is known to reduce stroke risk in patients with symptomatic, moderate to severe carotid stenosis but has no apparent impact in patients with symptomatic, mild (less than 50%) carotid stenosis. However, recent development of noninvasive imaging modalities has shown that a certain subgroup of patients are at high risk for further ischemic events despite antiplatelet therapy. This study, therefore, aimed to clarify the patients' clinical features and explore the impact of CEA for them. METHODS:This prospective cohort study included 74 patients who underwent CEA for symptomatic carotid stenosis between April 2012 and December 2016. Of these, 16 (22%) had mild (less than 50%) carotid stenosis. Their demographic, radiologic, intraoperative, and pathologic findings were precisely analyzed, and their outcome after CEA was examined for 38.5 ± 13.3 months. RESULTS:Of these 16 patients, 12 had already been treated with antiplatelets against previous ischemic cerebrovascular or coronary artery diseases. Plaque magnetic resonance imaging revealed that all patients had vulnerable plaque, including lipid-rich plaque (n = 6) and intraplaque hemorrhage (n = 10). Intraoperative observations confirmed this. Histologic analysis revealed that inflammatory cells and fragile angiogenesis were widely found in the specimens. Only 1 patient experienced transient (less than 30 days) neurologic deficit after CEA, and none of them repeated cerebrovascular events during the follow-up period. CONCLUSIONS:It is not rare the patients who are at high risk for subsequent ischemic events because of vulnerable plaque despite mild (less than 50%) carotid stenosis. Magnetic resonance imaging is quite useful to noninvasively detect such vulnerable plaque. CEA is a promising procedure to treat these patients.
10.1016/j.wneu.2018.09.013
Impact of positive and negative lesion site remodeling on clinical outcomes: insights from PROSPECT.
Inaba Shinji,Mintz Gary S,Farhat Naim Z,Fajadet Jean,Dudek Dariusz,Marzocchi Antonio,Templin Barry,Weisz Giora,Xu Ke,de Bruyne Bernard,Serruys Patrick W,Stone Gregg W,Maehara Akiko
JACC. Cardiovascular imaging
OBJECTIVES:This study investigated coronary artery remodeling patterns associated with clinical outcomes. BACKGROUND:In the prospective, multicenter PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree: An Imaging Study in Patients With Unstable Atherosclerotic Lesions) study, reported predictors of nonculprit lesion (NCL) major adverse cardiac events (MACE) were an intravascular ultrasound (IVUS) minimal lumen area (MLA) ≤4 mm(2), a plaque burden ≥70%, and a IVUS-virtual histology (VH) thin-cap fibroatheroma (TCFA), but not lesion site remodeling. METHODS:Overall, 697 consecutive patients with an acute coronary syndrome were enrolled and underwent 3-vessel gray-scale and IVUS-VH; 3,223 NCLs were identified by IVUS. The remodeling index (RI) was calculated as the external elastic membrane area at the MLA site divided by the average of the proximal and distal reference external elastic membrane areas. First, one third of the patients were randomly selected to determine RI cutoffs related to NCL MACE (development cohort). Receiver-operating characteristic analysis showed that there were 2 separate cut points that predicted NCL MACE: RI = 0.8789 and RI = 1.0046 (area under the curve = 0.663). These cut points were used to define negative remodeling as an RI <0.88, intermediate remodeling as an RI of 0.88 to 1.00, and positive remodeling as an RI >1.00. Second, we used the remaining two-thirds of patients to validate these cut points with respect to lesion morphology and clinical outcomes (validation cohort). RESULTS:Kaplan-Meier curve analysis in the validation cohort showed that NCL MACE occurred more frequent (and equally) in negative and positive remodeling lesions compared with intermediate remodeling lesions. In this cohort, negative remodeling lesions had the smallest MLA, positive remodeling lesions had the largest plaque burden, and VH TCFA, especially VH TCFA with multiple necrotic cores, was most common in negatively remodeling lesions. CONCLUSIONS:The present study showed the novel concept that positive and negative lesion site remodeling was associated with unanticipated NCL MACE in the PROSPECT study. ( PROSPECT:An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466).
10.1016/j.jcmg.2013.10.007
Prevalence of M4 macrophages within human coronary atherosclerotic plaques is associated with features of plaque instability.
Erbel Christian,Wolf Antonia,Lasitschka Felix,Linden Fabian,Domschke Gabriele,Akhavanpoor Mohammadreza,Doesch Andreas O,Katus Hugo A,Gleissner Christian A
International journal of cardiology
BACKGROUND:The platelet chemokine CXCL4 induces monocyte differentiation resulting in a macrophage phenotype called "M4", which co-expresses CD68, MMP7, and S100A8. We hypothesized that M4 macrophages are associated with plaque destabilization. METHODS:Atherosclerotic arteries were obtained from explanted hearts of patients with severe coronary artery disease (CAD, n = 32) and of patients with dilated cardiomyopathy and no or mild CAD (controls, n = 19). Coronary arteries were stained with H&E, and immuno-fluorescence was performed against CD68, MMP7, and S100A8. RESULTS:Both CD68(+) macrophages representing the entire macrophage population and MMP7(+)S100A8(+)CD68(+) M4 macrophages could be reproducibly identified within all arterial layers. The average proportion of the M4 macrophage phenotype amongst all CD68(+) macrophages was 31.7 ± 16.2%. The highest number of M4 macrophages was found in the adventitia, followed by the intima. CD68(+) and M4 macrophage numbers were significantly higher in patients with severe CAD. The presence of M4 macrophages within the intima and the media was significantly associated with plaque instability as determined by Stary class. Multivariate analysis showed a highly significant contribution of cardiovascular risk factors (P = 0.008) to plaque instability, while only trends were observed for age (P = 0.060) and intimal prevalence of M4 macrophages (P = 0.098). CONCLUSIONS:We demonstrate for the first time that M4 macrophages can be reproducibly found in coronary artery plaques. The prevalence of M4 macrophages is associated with indexes of plaque instability, most likely representing a surrogate marker of inflammatory activity. These findings suggest a pathogenetic role of M4 macrophages in vulnerable atherosclerotic plaques.
10.1016/j.ijcard.2015.03.151
Circulating microRNAs as potential biomarkers for unstable angina.
Liu Jun,Li Su-Fang,Lee Chong-You,Song Jun-Xian,Zhang Feng,Cui Yu-Xia,Chen Hong
International journal of clinical and experimental pathology
BACKGROUND:Chest pain is a typical presentation in the emergency department (ED), often due to acute coronary syndrome. Accurate and fast identification is crucial. The diagnosis and proper treatment of unstable angina (UA) can reduce the chance of acute myocardial infarction, and reduce high mortality and morbidity rates. However there is a lack of reliable and valid biomarkers in the diagnosis of UA. This study investigated the usefulness of circulating microRNAs (miRNAs) for differentiating UA from non-ischemic chest pain (NICP) in the ED. Methods The expressions of circulating miRNAs in patients with UA were evaluated relative to individuals with NICP (control subjects). Circulating miR-21, miR-25, miR-92a, miR-106b, miR-126* and miR-451 levels were measured in 98 patients with UA and 95 control subjects in the ED. To investigate the underlying functions of miRNAs in UA, bioinformatic analysis of validated miRNAs was conducted. RESULTS:Circulating miRNAs were upregulated in UA compared with the control group. The combination of the modified HEART score (m-HS) and miR-25 (AUC 0.901, NRI 0.096) could better distinguish UA than m-HS alone. Bioinformatic analysis indicated that miRNAs may take part in platelet activation, cGMP-PKG signaling pathways etc. Conclusion: The circulating levels of miRNAs (miR-21, miR-25, miR-106b, miR-126*) are significantly higher in UA patients compared with patients with NICP, and the addition of the m-HS that combined ECG, age, risk factors and troponin is useful to detect or rule out UA. The associated signaling pathways are involved in the pathogenesis of vulnerable plaque.
Modified platelet deposition on matrix metalloproteinase 13 digested collagen I.
Journal of thrombosis and haemostasis : JTH
BACKGROUND:Atherothrombosis underlies acute coronary syndromes, including unstable angina and acute myocardial infarction. Within the unstable plaque, monocytes express collagenolytic matrix metalloproteinases (MMPs), including MMP-13, which degrades fibrous collagen. Following rupture, vessel wall components including degraded collagen are exposed to circulating platelets. Platelet receptors then mediate the recruitment and activation of platelets to form a thrombus, blocking blood flow and resulting in myocardial infarction and sudden death. OBJECTIVES:Here we aim to provide information on the effects of collagen degradation on platelet adhesion and thrombus formation. METHODS:Using increasing concentrations of MMP-13, we induced progressive degradation of fibrous and monomeric collagen I, visualized by electrophoresis, and then investigated the capacity of the resulting fragments to support static platelet adhesion and thrombus formation in whole flowing blood. RESULTS:Both integrin and glycoprotein VI-dependent interactions with fibrous collagen underpin high levels of platelet adhesion under both conditions, with little obvious effect of MMP-13 treatment. Static platelet adhesion to monomeric collagen was strongly α2β1-dependent regardless of degradation status. Under flow conditions, partially degraded monomeric collagen supported increased thrombus deposition at 10 μg mL(-1) MMP-13, falling close to background when collagen degradation was complete (100 μg mL(-1) MMP-13). CONCLUSIONS:New binding activities come into play after partial digestion of collagen monomers, and net platelet-reactivity through all axes is abolished as degradation becomes more complete.
10.1111/jth.13166
Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease.
Kim Kichun,Lim Cheong,Kim Gilhyang,Chung Jin-Haeng,Cho Young-Seok,Cho Jun Hwan,Seo Jae-Bin,Chung Woo-Young,Oh Se-Jin,Choi Jae-Sung,Kim Jun-Sung,Park Jin Joo,Suh Jung-Won,Youn Tae-Jin,Chae In-Ho,Choi Dong-Ju
Annals of vascular surgery
BACKGROUND:The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. METHODS:Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n = 20), surgical endarterectomy (n = 9), or bypass surgery (n = 19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). RESULTS:Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4 ± 13.9 vs. 47.2 ± 13.6 U/L, P = 0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. CONCLUSIONS:Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.
10.1016/j.avsg.2019.11.004
Quantitative assessment of tissue prolapse on optical coherence tomography and its relation to underlying plaque morphologies and clinical outcome in patients with elective stent implantation.
Sugiyama Tomoyo,Kimura Shigeki,Akiyama Daiki,Hishikari Keiichi,Kawaguchi Naohiko,Kamiishi Tetsuo,Hikita Hiroyuki,Takahashi Atsushi,Isobe Mitsuaki
International journal of cardiology
BACKGROUND:Tissue prolapse (TP) is sometimes observed after percutaneous coronary intervention (PCI), but its clinical significance remains unclear. We investigated the relationship between TP volume on optical coherence tomography (OCT) after PCI and underlying plaque morphologies and the impact of TP on clinical outcomes. METHODS:We investigated 178 native coronary lesions with normal pre-PCI creatine kinase-myocardial band (CK-MB) values (154 lesions with stable angina; 24 with unstable angina). TP was defined as tissue extrusion from stent struts throughout the stented segments. All lesions were divided into tertiles according to TP volume. The differences in plaque morphologies and 9-month clinical outcomes were evaluated. RESULTS:TP volume was correlated with lipid arc (r=0.374, p<0.0001) and fibrous cap thickness (r=-0.254, p=0.001) at the culprit sites. The frequency of thin-cap fibroatheroma (TCFA) was higher in the largest TP tertile (≥ 1.38 mm(3)) (p=0.015). In multivariate analysis, right coronary artery lesion (odds ratio [OR]: 2.779; p=0.005), lesion length (OR: 1.047; p=0.003), and TCFA (OR: 2.430; p=0.022) were related to the largest TP tertile. Lesions with post-PCI CK-MB elevation (>upper reference limit) had larger TP volume than those without (1.28 [0.48 to 3.97] vs. 0.70 [0.16 to 1.64] mm(3), p=0.007). The prevalence of cardiac events during the 9-month follow-up was not significantly different according to TP volume. CONCLUSIONS:TP volume on OCT was related to plaque morphologies and instability, and post-PCI myocardial injury, but not to worse 9-month outcomes.
10.1016/j.ijcard.2014.07.005
[Invasive methods of detection of unstable atherosclerotic plaques in coronary arteries].
Tagieva N P,Shakhnovich R M,Mironov V M,Ruda M Ia
Kardiologiia
In most cases direct cause of acute coronary syndrome and sudden death is an intracoronary thrombus formed on a surface of unstable atherosclerotic plaque (UAP). The following are main characteristics of UAP: active inflammation; large lipid rich nucleus occupying a 40% of plaque volume; thin (< 65 mm) fibrous cap; erosions of intima over plaque; tear of plaque cap; superficially located calcium nodules; intraplaque hemorrhage. Visualization of UAP in coronary arteries is a very important direction in diagnostics. During recent years both invasive and noninvasive methods of detection of UAP have been actively developed. In this review we present main invasive techniques used for detection of UAP: intravascular ultrasound study with virtual histology; optical coherent tomography; near-infrared spectroscopy; thermography; intravascular magnetic resonance imaging; direct visualization by angioscopy. In the review we have covered main advantages and limitations of each invasive method of UAP detection and delineated perspectives of development of this direction.
10.18565/cardio.2014.11.46-56
Automated characterisation of lipid core plaques in vivo by quantitative optical coherence tomography tissue type imaging.
Gnanadesigan Muthukaruppan,Kameyama Takeyoshi,Karanasos Antonios,van Ditzhuijzen Nienke S,van der Sijde Johannes N,van Geuns Robert-Jan,Ligthart Jurgen,Witberg Karen,Ughi Giovanni J,van der Steen Antonius F,Regar Evelyn,van Soest Gijs
EuroIntervention : journal of EuroPCR in collaboration with the Working Group on Interventional Cardiology of the European Society of Cardiology
AIMS:Qualitative criteria for plaque tissue characterisation by OCT are well established, but quantitative methods lack systematic validation in vivo. High optical attenuation coefficient µt has been associated with unstable plaque features, such as lipid core. The purpose of this study was to validate optical coherence tomography (OCT) attenuation imaging for tissue characterisation in vivo, specifically to detect lipid core in coronary atherosclerotic plaques, and to evaluate quantitatively the ability of OCT attenuation imaging to differentiate thin-cap (TCFA) and thick-cap fibroatheroma (FA). METHODS AND RESULTS:We prospectively enrolled 85 patients undergoing imaging of a native coronary segment by both OCT and near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS). Ninety-eight NIRS-positive 4 mm plaque segments were selected and matched to the OCT data. Two experienced OCT readers classified the plaque type using OCT criteria. A cap thickness of 65 μm was used to differentiate TCFA and FA. We computed an index of plaque attenuation (IPA) in the 4 mm blocks, and assessed the association of this index with plaque type. IPA differentiated between TCFA and FA (AUC=0.82 in ROC analysis; p<0.0001). LCBI was numerically, but not significantly, higher in TCFA compared to FA (p=0.097). CONCLUSIONS:IPA is an unbiased reproducible measure of tissue optical properties. The fraction of pixels with attenuation coefficient ≥11 mm-1 can identify TCFA.
10.4244/EIJ-D-15-00320
Association between serum lipoprotein-associated phospholipase A2, ischemic modified albumin and acute coronary syndrome: a cross-sectional study.
Yang Fumeng,Ma Liping,Zhang Lili,Wang Yilian,Zhao Changxin,Zhu Wenjun,Liang Wei,Liu Qian
Heart and vessels
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a newly emerging biomarker with strong pro-inflammatory effects, and is an independent risk predictor of atherosclerotic plaque rupture and thrombosis. In addition, ischemic modified albumin (IMA) is another important marker for the evaluation of myocardial ischemia, and has been approved by the U.S. Food and Drug Administration. The objective of this study was to investigate serum Lp-PLA2 and IMA in the early diagnosis, progression and prognosis of acute coronary syndrome (ACS). Serum Lp-PLA2 and IMA were detected using an AU5800 automatic biochemical analyzer in samples from 180 patients with ACS [n = 60 with unstable angina pectoris (UA), n = 56 with non-ST segment elevation myocardial infarction (NSTEMI), and n = 64 with ST segment elevation myocardial infarction (STEMI)] and 60 healthy control subjects. The relationship between Lp-PLA2 and IMA with Gensini score and the number of coronary artery lesions was explored, and logistic regression was conducted to identify risk factors for major adverse cardiovascular events (MACE). Serum Lp-PLA2 and IMA were significantly higher in all ACS subgroups compared to the control group (P < 0.05), were positively associated with the severity of ACS based on the Gensini score (P < 0.05), and were significantly higher in patients with double- and triple-vessel lesions compared to those with single-vessel lesions and healthy controls (P < 0.05). Logistic regression identified Lp-PLA2, IMA, and troponin I levels as independent risk factors for MACE. Lp-PLA2 and IMA were predictive of the degree of myocardial ischemia in patients with ACS, and may provide important clinical significance for the early diagnosis of ACS and the choice of treatment strategy.
10.1007/s00380-019-01403-3
Curcumin inhibits EMMPRIN and MMP-9 expression through AMPK-MAPK and PKC signaling in PMA induced macrophages.
Cao Jiatian,Han Zhihua,Tian Lei,Chen Kan,Fan Yuqi,Ye Bozhi,Huang Weijian,Wang Changqian,Huang Zhouqing
Journal of translational medicine
In coronary arteries, plaque disruption, the major acute clinical manifestations of atherosclerosis, leads to a subsequent cardiac event, such as acute myocardial infarction (AMI) and unstable angina pectoris (UA). Numerous reports have shown that high expression of MMP-9 (matrix metalloproteinase-9), MMP-13 (matrix metalloproteinase-13) and EMMPRIN (extracellular matrix metalloproteinase induce) in monocyte/macrophage results in the plaque progression and destabilization. Curcumin exerts well-known anti-inflammatory and antioxidant effects and probably has a protective role in the atherosclerosis. The purpose of our study was to investigate the molecular mechanisms by which curcumin affects MMP-9, MMP13 and EMMPRIN in PMA (phorbol 12-myristate 13-acetate) induced macrophages. Human monocytic cells (THP-1 cells) were pretreated with curcumin or compound C for 1 h, and then induced by PMA for 48 h. Total RNA and proteins were collected for real-time PCR and Western blot analysis, respectively. In the present study, the exposure to curcumin resulted in attenuated JNK, p38, and ERK activation and decreased expression of MMP-9, MMP-13 and EMMPRIN in PMA induced macrophages. Moreover, we demonstrated that AMPK (AMP-activated protein kinase) and PKC (Protein Kinase C) was activated by PMA during monocyte/macrophage differentiation. Furthermore, curcumin reversed PMA stimulated PKC activation and suppressed the chronic activation of AMPK, which in turn reduced the expression of MMP-9, MMP-13 and EMMPRIN. Therefore, it is suggested that curcumin by inhibiting AMPK-MAPK (mitogen activated protein kinase) and PKC pathway may led to down-regulated EMMPRIN, MMP-9 and MMP-13 expression in PMA-induced THP-1 cells.
10.1186/s12967-014-0266-2
Incremental prognostic value of coronary computed tomographic angiography high-risk plaque characteristics in newly symptomatic patients.
Fujimoto Shinichiro,Kondo Takeshi,Takamura Kazuhisa,Baber Usman,Shinozaki Tomohiro,Nishizaki Yuji,Kawaguchi Yuko,Matsumori Rie,Hiki Makoto,Miyauchi Katsumi,Daida Hiroyuki,Hecht Harvey,Stone Gregg W,Narula Jagat
Journal of cardiology
BACKGROUND:The incremental prognostic value of the plaque features in coronary computed tomographic angiography (CTA) has not been well assessed. This study was designed to determine whether CTA high-risk plaques have prognostic value incremental to the Framingham risk score (FRS) and the severity of luminal obstruction. METHODS:A total of 628 newly symptomatic patients without known coronary artery disease underwent CTA. They were followed for a median of 677 days during which there were 26 cardiac events, including cardiac death, acute myocardial infarction, and hospitalization for unstable angina. Incremental prognostic value of adding plaque characteristics to the number of diseased vessels and the FRS was evaluated using 3 Cox models and net reclassification indexes. RESULTS:The discrimination index was significantly increased by adding the number of diseased vessels to the FRS (change in c-statistic from 65.8% to 78.6%, p=0.028) but not significantly by further adding plaque characteristics (change in c-statistic from 78.6% to 80.0%, p=0.812). However, improved model-fitting by adding plaque characteristics into the linear combination with risk score and the number of diseased vessels (p=0.007 from likelihood ratio test) and the lowest value of Akaike's information criteria of that model indicated that plaque characteristics improved both predictive accuracy and discrimination perspective. More subjects reclassified by plaque characteristics were moved to directions consistent with their subsequent cardiac event status than in an inconsistent direction. CONCLUSIONS:Evaluation of CTA plaque characteristics may provide incremental prognostic value to the number of diseased vessels and the FRS.
10.1016/j.jjcc.2015.07.018
Correlation of serum high-sensitivity C-reactive protein and interleukin-6 in patients with acute coronary syndrome.
Wang X H,Liu S Q,Wang Y L,Jin Y
Genetics and molecular research : GMR
Serum high-sensitivity C-reactive protein (hs-CRP) is a sensitive indicator of inflammation, which is closely related with the progress of plaque formation. Interleukin-6 (IL-6) is one of the inflammatory markers of local coronary plaque and the peripheral blood cycle, promoting the occurrence of atherosclerosis development and plaque rupture. In this study, the correlation of hs-CRP and IL-6 was investigated in patients with acute coronary syndrome (ACS). Sixty cases of ACS, including 33 cases of acute myocardial infarction (AMI) and 27 cases of unstable angina pectoris (UAP), 45 cases of stable angina pectoris (SAP), and 45 healthy people (HG) were enrolled in study. The serum hs-CRP and serum IL-6 levels were tested by the immune turbidimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. The differences among groups and their correlations were evaluated. Results showed that the serum hs-CRP and IL-6 concentrations of the AMI and UAP groups were significantly higher than those of the SAP and HG groups, respectively (P<0.01), and those of the AMI group were significantly higher than those of the UAP group (P<0.05). The serum hs-CRP and IL-6 levels of the ACS group were positively correlated (r=0.836). The serum hs-CRP and IL-6 levels could be used to determine the stability of plaque, and have some relevance in the ACS process, showing great value in judgments of ACS prognosis.
10.4238/2014.June.9.11
Role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism.
Zhong Z X,Li B,Li C R,Zhang Q F,Liu Z D,Zhang P F,Gu X F,Luo H,Li M J,Luo H S,Ye G H,Wen F L
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
Our aim was to investigate the role of chemokines in promoting instability of coronary atherosclerotic plaques and the underlying molecular mechanism. Coronary angiography and intravascular ultrasound (IVUS) were performed in 60 stable angina pectoris (SAP) patients and 60 unstable angina pectoris (UAP) patients. The chemotactic activity of monocytes in the 2 groups of patients was examined in Transwell chambers. High-sensitivity C-reactive protein (hs-CRP), monocyte chemoattractant protein-1 (MCP-1), regulated on activation in normal T-cell expressed and secreted (RANTES), and fractalkine in serum were examined with ELISA kits, and expression of MCP-1, RANTES, and fractalkine mRNA was examined with real-time PCR. In the SAP group, 92 plaques were detected with IVUS. In the UAP group, 96 plaques were detected with IVUS. The plaques in the UAP group were mainly lipid 51.04% (49/96) and the plaques in the SAP group were mainly fibrous 52.17% (48/92). Compared with the SAP group, the plaque burden and vascular remodeling index in the UAP group were significantly greater than in the SAP group (P<0.01). Chemotactic activity and the number of mobile monocytes in the UAP group were significantly greater than in the SAP group (P<0.01). Concentrations of hs-CRP, MCP-1, RANTES, and fractalkine in the serum of the UAP group were significantly higher than in the serum of the SAP group (P<0.05 or P<0.01), and expression of MCP-1, RANTES, and fractalkine mRNA was significantly higher than in the SAP group (P<0.05). MCP-1, RANTES, and fractalkine probably promote instability of coronary atherosclerotic plaque.
10.1590/1414-431X20144195
Clinical implications of tenascin-C and OX40 ligand in patients with acute coronary syndrome.
Yang Jin-Hu,Ren Feng
Biomedical reports
Acute coronary syndrome (ACS) typically occurs when coronary artery disease results in the obstruction of the coronary arteries. Tenascin-C (TNC) and OX40 ligand (OX40L) were shown to be involved in the pathogenesis of atherosclerosis. In this study, 50 healthy controls and 170 patients, including 50 patients with stable angina (SA), 70 with unstable angina and 50 with acute myocardial infarction, were evaluated to assess serum TNC and plasma OX40L levels. The serum TNC levels were measured by a quantitative automated particle-enhanced immunonephelometric assay. ELISA was used to determine the expression levels of OX40L. All the coronary stenoses with a ≥30% diameter reduction were assessed by angiographic coronary stenosis morphology. The patients with ACS exhibited a significant increase in TNC expression levels (39.39±19.80 ng/ml) compared to the levels in the control and SA groups (28.65±12.32 ng/ml, P<0.01 and 31.22±18.92 ng/ml, P<0.05, respectively). The levels of OX40L were also found to be higher in patients with ACS (38.59±15.76 ng/ml) compared to those in the control and SA groups (19.42±11.19 ng/ml, P<0.001 and 21.52±10.30 ng/ml, P<0.001, respectively). The TNC and OX40L levels were positively correlated with each other (r=0.68; P<0.001) and with fibrinogen levels (r=0.76 and r=0.45, respectively; P<0.001). A positive correlation was also observed between the expression of TNC and OX40L and complex coronary stenosis (r=0.69 and r=0.55, respectively; P<0.001). We concluded that TNC and OX40L may act synergistically in coronary plaque formation and may be also be involved in the pathogenesis of coronary lesions. Patients with ACS exhibited increased TNC and OX40L expression levels, which may have created a prothrombotic milieu, aggravating the development of atherosclerosis and the instability of atherosclerotic plaques. Therefore, the expression of TNC and OX40L may be a valuable marker for predicting the severity of ACS.
10.3892/br.2013.195
[Correlation between serum inflammatory cytokine levels and fibrous cap thickness of fibrofatty plaque in coronary culprit lesions].
Zhong Y,Ye F,You W,Wu Z M
Zhonghua xin xue guan bing za zhi
To identify the correlation between serum inflammatory cytokine levels including high sensitive C reactive protein (hs-CRP) and lipoprotein associated phospholipase (Lp-PLA2) and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions. Clinical data of 117 patients with selective coronary artery angiography diagnosed coronary artery disease admitted to our hospital from January 2015 to January 2016 were retrospective analyzed. According to type of coronary disease, patients were divided into 3 subgroups: SAP group (containing 47 stable angina patients), UAP group (containing 52 unstable angina patients), and NSTEMI group(containing 18 acute non ST segment elevation myocardial infarction patients). Serum hs-CRP and Lp-PLA2 levels were measured before subsequent procedures. The characteristics of the culprit lesions were detected by optical coherence tomogarpgy(OCT) before interventional treatment, and the correlation between hs-CRP and Lp-PLA2 and the fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were analyzed. (1) The serum levels of hs-CRP (2.13(1.04, 4.75)μg/L vs. 1.02(0.60, 1.29)μg/L and 1.30(1.03, 1.96)μg/L, all <0.05) and Lp-PLA2 ((394.8±61.4)mg/L vs. (140.1±40.4)mg/L and (284.5±93.6)mg/L, all <0.05) were significantly higher in NSTEMI group than in SAP group and UAP group, and serum levels of hs-CRP and Lp-PLA2 were significantly higher in UAP group than in SAP group (all <0.05). (2)The fibrous cap thickness of fibrofatty plaque in coronary culprit lesions were smaller in NSTEMI group and UAP group than in SAP group(50(50, 60)μm and 60(50, 90)μm vs. 130(80, 190)μm, all <0.05), and there was no significantly difference between NSTEMI group and UAP group(>0.05). Proportion of thin-cap fibroatheroma plaque(82.35%(14/18) vs. 19.15%(9/47) and 63.46%(33/52), all <0.05), plaque rupture(55.56%(10/18)vs. 6.38%(3/47) and 28.85%(15/52), all <0.05) and thrombosis(33.33%(6/18) vs. 4.26%(2/47) and 9.26%(5/52), all <0.05) were significantly higher in NSTEMI group than in SAP group and UAP group. Proportion of calcifiacation in plaque was lower in NSTEMI group than in SAP group (11.11%(2/18)vs. 42.55%(20/47), <0.05), and there was no significantly difference between NSTEMI group and UAP group(>0.05). (3) Pearson correlation analysis showed that serum levels of hs-CRP(=-0.233, <0.05) and Lp-PLA2(=-0.465, <0.01)were negatively correlated with fibrous cap thickness of fibrofatty plaques. Spearman correlation analysis showed that serum levels of hs-CRP were positively correlated with plaque rupture(=0.409, <0.01) and thrombosis (=0.227, <0.05), and serum levels of Lp-PLA2 were also positively correlated with plaque rupture(=0.499, <0.01) and thrombosis(=0.263, <0.01). (4)Multiple logistic regression analysis showed that serum levels of Lp-PLA2 at baseline was independently related to thin-cap fibroatheroma plaque(=1.017, <0.01). The serum levels of hs-CRP and Lp-PLA2 in NSTEMI patients are much higher than that in SAP and UAP patients, higher in UAP patients than in SAP patients. Prevalence of thin-cap fibroatheroma plaque, plaque rupture and thrombosis was significantly higher in the NSTEMI patients, while the prevalence of calcification in plaque is more often in SAP patients. Increased serum levels of Lp-PLA2 are independent risk factor of thin-cap fibroatheroma plaque formation.
10.3760/cma.j.issn.0253-3758.2017.07.004
Noncanonical NF-κB signaling in microvessels of atherosclerotic lesions is associated with inflammation, atheromatous plaque morphology and myocardial infarction.
Atherosclerosis
BACKGROUND AND AIMS:Neovascularization is associated with atherosclerotic plaque instability and increased chance of myocardial infarction (MI). Patients with chronic inflammatory diseases (CID) have increased risk of atherosclerosis, and evidence demonstrates that NF-κB inducing kinase (NIK)-mediated noncanonical NF-κB signaling in endothelial cells (EC) is linked to inflammation and angiogenesis. Here, we hypothesized NIK may also be activated in EC of atherosclerotic lesion microvessels. METHODS:Using cohorts of atherosclerotic lesions from coronary and carotid arteries, we quantified NIK expression in plaque microvessels and compared it to pathological markers, including inflammatory cell content, plaque characteristics and MI. Differences in gene transcripts were evaluated between stable and ruptured lesions. RESULTS:NIKEC were present in both coronary and carotid lesions. In CID patients, plaques with stenosis >40% had an increased number of NIKEC and higher content of immune cells (p < .05) as compared to controls. Immune cells per NIKEC were also greater in CID patients (p < .05), with pronounced differences as stenosis increased. In unstable lesions, NIKEC were elevated as were EC expressing CXCL12 (p < .05). NIKEC were increased in lesions with lipid content >40% (p < .05) and more abundant in coronary artery lesions implicated in MI (p < .05). These vessels also associated with atheromatous rather than fibrous plaque morphology (p < .05). Transcriptomic profiling demonstrated components of noncanonical NF-κB pathway were also upregulated in ruptured plaques (p < .05). CONCLUSIONS:NIKEC associate with chronic inflammation in advanced lesions and are linked to markers of local inflammation, lipid content, unstable plaque phenotype and development of MI. Therefore, targeting noncanonical NF-κB signaling may hold therapeutic potential for patients with atherosclerosis and cardiovascular disease.
10.1016/j.atherosclerosis.2018.01.032
Optical Coherence Tomography-Defined Plaque Vulnerability in Relation to Functional Stenosis Severity and Microvascular Dysfunction.
Usui Eisuke,Yonetsu Taishi,Kanaji Yoshihisa,Hoshino Masahiro,Yamaguchi Masao,Hada Masahiro,Fukuda Tadashi,Sumino Yohei,Ohya Hiroaki,Hamaya Rikuta,Kanno Yoshinori,Yuki Haruhito,Murai Tadashi,Lee Tetsumin,Hirao Kenzo,Kakuta Tsunekazu
JACC. Cardiovascular interventions
OBJECTIVES:This study sought to investigate the relationship of unstable plaque features with physiological lesion severity and microvascular dysfunction. BACKGROUND:The functional severity of epicardial lesions and microvascular dysfunction are both related to adverse clinical outcomes. METHODS:We investigated 382 de novo intermediate and severe coronary lesions in 340 patients who underwent optical coherence tomography, fractional flow reserve (FFR), and index of microcirculatory resistance (IMR) examinations. Lesions were divided into tertiles based on either FFR or IMR values. The optical coherence tomography findings were compared among the tertiles of FFR and IMR. Each tertile was defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74 ≤ FFR ≤0.81), and FFR-T3 (FFR >0.81); and IMR-T1 (IMR ≥25), IMR-T2 (15 < IMR <25), and IMR-T3 (IMR ≤15). RESULTS:No significant relationship was observed between FFR and IMR. The prevalence of optical coherence tomography-defined thin-cap fibroatheroma (TCFA) was significantly greater in IMR-T1 than in IMR-T2 and IMR-T3. An overall significant difference in the prevalence of TCFAs was detected among FFR tertiles, although no pairwise comparison revealed statistical significance. The prevalence of ruptured plaque was significantly greater in IMR-T1 than in IMR-T2 and IMR-T3, although no significant difference was observed between FFR tertiles. Multivariate analysis showed that FFR and IMR were independent predictors of the prevalence of TCFAs (odds ratio: 0.036; 95% confidence interval: 0.004 to 0342; p = 0.004; and odds ratio: 1.034; 95% confidence interval: 1.014 to 1.054; p = 0.001, respectively). CONCLUSIONS:Lower FFR and higher IMR values were independent predictors of the presence of a TCFA in angiographically intermediate-to-severe stable lesions or nonculprit lesions in acute coronary syndrome.
10.1016/j.jcin.2018.07.012
Change of Inflammatory Factors in Patients with Acute Coronary Syndrome.
Chinese medical journal
BACKGROUND:Acute coronary syndrome (ACS) is closely related to unstable plaques and secondary thrombosis. The inflammatory cells in plaques and their inflammatory products may be the cause for plaque instability and ruptures. The study aimed to disclose the changes of inflammatory factors including serum intracellular adhesion molecule-1 (ICAM-1), chitinase-3-like protein 1 (YKL-40), and lipoprotein-associated phospholipase A2 (Lp-PLA2) in patients with ACS and its clinical significance. METHODS:A total of 120 patients with coronary heart disease (CHD) were categorized into 2 groups: 69 with ACS and 51 with stable angina pectoris (SAP); 20 patients with chest pain and normal angiography served as a control group. The 120 patients with CHD were categorized into single-vessel disease group, double-vessel disease group, and three-vessel disease group based on the number of coronary artery stenosis. The severity of coronary artery stenosis was quantified based on coronary angiography using Gensini score. They were further divided into mild CHD group with its Gensini score <26 (n = 36), moderate CHD group with its Gensini score being 26-54 (n = 48) and severe CHD group with its Gensini score >54 (n = 36). Serum levels of ICAM-1, YKL-40, and Lp-PLA2 of different groups were determined by enzyme-linked immunosorbent assay. Correlation between ICAM-1, YKL-40, Lp-PLA2, and Gensini score was analyzed. RESULTS:The levels of serum inflammatory factors ICAM-1, YKL-40, and Lp-PLA2 were significantly higher in the ACS group than those in control group and SAP group (all P < 0.05); and compared with control group, no significant difference was observed in terms of the serum ICAM-1, YKL-40, and Lp-PLA2 levels in the SAP group (P > 0.05).The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, single-vessel disease group, double-vessel disease group, and three-vessel disease group (all P > 0.05). The levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not significantly different among control group, mild CHD group (Gensini score <26), moderate CHD group (Gensini score 26-54), and severe CHD group (Gensini score >54) (all P > 0.05). Nonparametric Spearman correlation analysis showed that the levels of serum ICAM-1, YKL-40, and Lp-PLA2 were not correlated with the Gensini score in CHD patients (r = 0.093, r = -0.149, and r = -0.085, all P > 0.05; respectively). CONCLUSIONS:The serum levels of ICAM-1, YKL-40, and Lp-PLA2 were correlated with different clinical types of CHD, but not well correlated the severity and extent of artery stenosis, suggesting that ICAM-1, YKL-40, and Lp-PLA2 might be involved in occurrence of instability of atherosclerotic plaque, and might reflect the severity of CHD mostly through reflecting the plaque stability.
10.4103/0366-6999.233953
Spectroscopic intravascular photoacoustic imaging of lipids in atherosclerosis.
Jansen Krista,van der Steen Antonius F W,Wu Min,van Beusekom Heleen M M,Springeling Geert,Li Xiang,Zhou Qifa,Shung K Kirk,de Kleijn Dominique P V,van Soest Gijs
Journal of biomedical optics
The natural history of atherosclerosis is marked by changes in the lipid biochemistry in the diseased arterial wall. As lesions become more vulnerable, different cholesterol species accumulate in the plaque. Understanding unstable atherosclerosis as a pharmacological and interventional therapeutic target requires chemically specific imaging of disease foci. In this study, we aim to image atherosclerotic plaque lipids and other vessel wall constituents with spectroscopic intravascular photoacoustics (sIVPA). sIVPA imaging can identify lipids in human coronary atherosclerotic plaque by relying on contrast in the near-infrared absorption spectra of the arterial wall components. Using reference spectra acquired on pure compounds, we analyzed sIVPA data from human coronary plaques ex vivo, to image plaque composition in terms of cholesterol and cholesterol ester content. In addition, we visualized the deeper lying connective tissue layers of the adventitia, as well as the fatty acid containing adipose cells in the peri-adventitial tissue. We performed simultaneous coregistered IVUS imaging to obtain complementary morphological information. Results were corroborated by histopathology. sIVPA imaging can distinguish the most prevalent lipid components of human atherosclerotic plaques and also visualize the connective tissue layers of the adventitia and the fatty acid containing adipose cells in the peri-adventitial tissue.
10.1117/1.JBO.19.2.026006
Altered human neutrophil FcγRI and FcγRIII but not FcγRII expression is associated with the acute coronary event in patients with coronary artery disease.
Zhao Na,Mi Lan,Zhang Yaping,Li Na,Xu Jiaojiao,Xia Dongyu,Wang Junkui,Wu Yue,Liu Xiaojun
Coronary artery disease
OBJECTIVE:Neutrophils enhancing atherosclerotic plaque instability have been observed in patients with acute coronary syndrome (ACS). Generally, activation of neutrophils in lesions depends on the interaction of Fcγ receptors (FcγRs) with immunoglobulin G antibodies in immune complexes. However, altered FcγR expression on neutrophils of patients with ACS is unknown. We aimed to evaluate changes in FcγR expression on neutrophils of patients with ACS. METHODS:We enrolled 106 patients who were divided into four groups: acute myocardial infarction (AMI), unstable angina (UA), stable angina, and normal coronary arteries. The expressions of FcγRI, FcγRII, and FcγRIII on neutrophils and related upstream ligand and downstream molecules were measured by flow cytometry and enzyme-linked immunosorbent assay. RESULTS:The expression of unbound FcγRI was significantly decreased in AMI and UA patients and that of unbound FcγRIII was significantly decreased in AMI patients, with no difference in the expression of unbound FcγRII among the four groups. In contrast, plasma levels of antioxidized LDL antibody, myeloperoxidase, matrix metalloproteinase-9, and neutrophil gelatinase-associated lipocalin were significantly greater in AMI and UA than in stable angina and normal coronary arteries patients. CONCLUSION:Unbound FcγRI and FcγRIII expression was decreased on neutrophils of patients with ACS, which reflects a potential role of disturbed FcγRI and FcγRIII expression in the destabilization of atherosclerotic plaque. Our findings may provide insight into the mechanism underlying culprit plaque-relevant activation of neutrophil FcγRs in ACS patients.
10.1097/MCA.0000000000000425
Frequency Analysis of the Photoacoustic Signal Generated by Coronary Atherosclerotic Plaque.
Daeichin Verya,Wu Min,De Jong Nico,van der Steen Antonius F W,van Soest Gijs
Ultrasound in medicine & biology
The identification of unstable atherosclerotic plaques in the coronary arteries is emerging as an important tool for guiding percutaneous coronary interventions and may enable preventive treatment of such plaques in the future. Assessment of plaque stability requires imaging of both structure and composition. Spectroscopic photoacoustic (sPA) imaging can visualize atherosclerotic plaque composition on the basis of the optical absorption contrast. It is an established fact that the frequency content of the photoacoustic (PA) signal is correlated with structural tissue properties. As PA signals can be weak, it is important to match the transducer bandwidth to the signal frequency content for in vivo imaging. In this ex vivo study on human coronary arteries, we combined sPA imaging and analysis of frequency content of the PA signals. Using a broadband transducer (-3-dB one-way bandwidth of 10-35 MHz) and a 1-mm needle hydrophone (calibrated for 1-20 MHz), we covered a large frequency range of 1-35 MHz for receiving the PA signals. Spectroscopic PA imaging was performed at wavelengths ranging from 1125 to 1275 nm with a step of 2 nm, allowing discrimination between plaque lipids and adventitial tissue. Under sPA imaging guidance, the frequency content of the PA signals from the plaque lipids was quantified. Our data indicate that more than 80% of the PA energy of the coronary plaque lipids lies in the frequency band below 8 MHz. This frequency information can guide the choice of the transducer element used for PA catheter fabrication.
10.1016/j.ultrasmedbio.2016.03.015
Coronary Computed Tomography (CT) Angiography as a Predictor of Cardiac and Noncardiac Vascular Events in Asymptomatic Type 2 Diabetics: A 7-Year Population-Based Cohort Study.
Halon David A,Azencot Mali,Rubinshtein Ronen,Zafrir Barak,Flugelman Moshe Y,Lewis Basil S
Journal of the American Heart Association
BACKGROUND:Type 2 diabetics are at increased risk for vascular events, but the value of further risk stratification for coronary heart disease (CHD) in asymptomatic subjects is unclear. We examined the added value of coronary computed tomography angiography over clinical risk scores (United Kingdom Prospective Diabetes Study), and coronary artery calcium in a population-based cohort of asymptomatic type 2 diabetics. METHODS AND RESULTS:Subjects (n=630) underwent baseline clinical assessment and computed tomography angiography (64-slice scanner). Plaque site, volume, calcific content, and arterial remodeling were recorded using dedicated software. Coronary, macrovascular, and microvascular-related events were assessed over 6.6±0.6 (mean±SD) (range 5.4-7.5) years and all CHD events were adjudicated. Discrimination of CHD events (cardiovascular death, myocardial infarction, unstable angina, or new-onset angina requiring intervention) (n=41) was improved by addition of total plaque burden to the clinical risk and coronary artery calcium scores combined (C=0.789 versus 0.763, P=0.034) and further improved by addition of an angiographic score (C=0.824, P=0.021). Independent predictors of a CHD event were United Kingdom Prospective Diabetes Study risk score (hazard ratio 1.3 per 10% 10-year risk, P=0.003) and the angiographic score (hazard ratio 3.2 per quartile, P<0.0001). Classification was improved over that by United Kingdom Prospective Diabetes Study and coronary artery calcium scores alone (overall net reclassification improvement 0.24). In subjects with coronary plaque (N=500), mild plaque calcification independently predicted a CHD event (hazard ratio 3.0, P=0.02). Computed tomography angiography predicted combined macrovascular but not microvascular-related events. CONCLUSIONS:Computed tomography angiography provides additional prognostic information in asymptomatic type 2 diabetics not obtainable from clinical risk assessment and coronary artery calcium alone.
10.1161/JAHA.116.003226
Local carotid atherosclerotic plaque proteins for the identification of circulating biomarkers in coronary patients.
Malaud Eric,Merle Delphine,Piquer Dominique,Molina Laurence,Salvetat Nicolas,Rubrecht Laetitia,Dupaty Emilie,Galea Pascale,Cobo Sandra,Blanc Aurélie,Saussine Max,Marty-Ané Charles,Albat Bernard,Meilhac Olivier,Rieunier Francois,Pouzet Agnes,Molina Franck,Laune Daniel,Fareh Jeannette
Atherosclerosis
OBJECTIVE:To identify circulating biomarkers that originate from atherosclerotic vulnerable plaques and that could predict future cardiovascular events. METHODS:After a protein enrichment step (combinatorial peptide ligand library approach), we performed a two-dimensional electrophoresis comparative analysis on human carotid plaque protein extracts (fibrotic and hemorrhagic atherosclerotic plaques). In silico analysis of the biological processes was applied on proteomic data. Luminex xMAP assays were used to quantify inflammatory components in carotid plaques. The systemic quantification of proteins originating from vulnerable plaques in blood samples from patients with stable and unstable coronary disease was evaluated. RESULTS:A total of 118 proteins are differentially expressed in fibrotic and hemorrhagic plaques, and allowed the identification of three biological processes related to atherosclerosis (platelet degranulation, vascular autophagy and negative regulation of fibrinolysis). The multiplex assays revealed an increasing expression of VEGF, IL-6, IL-8, IP-10 and RANTES in hemorrhagic as compared to fibrotic plaques (p<0.05). Measurement of protein expressions in plasmas from patients with stable and unstable coronary disease identified a combination of biomarkers, including proteins of the smooth muscle cell integrity (Calponin-1), oxidative stress (DJ-1) and inflammation (IL-8), that allows the accurate classification of patients at risk (p=0.0006). CONCLUSION:Using tissue protein enrichment technology, we validated proteins that are differentially expressed in hemorrhagic plaques as potential circulating biomarkers of coronary patients. Combinations of such circulating biomarkers could be used to stratify coronary patients.
10.1016/j.atherosclerosis.2013.12.019
Atomic Force Microscopy Study of Atherosclerosis Progression in Arterial Walls.
Timashev Peter S,Kotova Svetlana L,Belkova Galina V,Gubar'kova Ekaterina V,Timofeeva Lidia B,Gladkova Natalia D,Solovieva Anna B
Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada
Cardiovascular disease remains the leading cause of mortality worldwide. Here we suggest a novel approach for tracking atherosclerosis progression based on the use of atomic force microscopy (AFM). Using AFM, we studied cross-sections of coronary arteries with the following types of lesions: Type II-thickened intima; Type III-thickened intima with a lipid streak; Type IV-fibrotic layer over a lipid core; Type Va-unstable fibrotic layer over a lipid core; Type Vc-very thick fibrotic layer. AFM imaging revealed that the fibrotic layer of an atherosclerotic plaque is represented by a basket-weave network of collagen fibers and a subscale network of fibrils that become looser with atherosclerosis progression. In an unstable plaque (Type Va), packing of the collagen fibers and fibrils becomes even less uniform than that at the previous stages, while a stable fibrotic plaque (Vc) has significantly tighter packing. Such alterations of the collagen network morphology apparently, led to deterioration of the Type Va plaque mechanical properties, that, in turn, resulted in its instability and propensity to rupture. Thus, AFM may serve as a useful tool for tracking atherosclerosis progression in the arterial wall tissue.
10.1017/S1431927616000039
Atherosclerosis imaging to refine cardiovascular risk assessment in diabetic patients: Computed tomography and positron emission tomography applications.
Raggi Paolo
Atherosclerosis
The lifetime cardiovascular risk of a diabetic patient is approximately 4-5 times higher than that of an age and sex matched individual without diabetes mellitus. Despite the well-publicized cardiovascular risk equivalence of diabetes mellitus, it has become apparent that not all diabetic patients are equally at high-risk and many patients may have a level of risk similar to that of the general population. Cardiovascular imaging has been employed to address the dilemma of a more accurate risk stratification of diabetic patients. Two randomized clinical trials aiming at uncovering the presence of unknown obstructive coronary artery disease (CAD) gave disappointing results. In fact, the number of patients with inducible myocardial ischemia and/or severe obstructive disease was lower than expected and the overall outcome was not improved after having brought the existence of CAD to light. Other techniques that may help identify a diabetic patient susceptible to suffer future events have therefore being explored. In this review we discuss two imaging tools that provide anatomical and functional information on pre-clinical coronary atherosclerosis: computed tomography for calcium scoring, and plaque characterization and myocardial ischemia detection and positron emission tomography using tracers to identify functionally unstable plaques. Despite the availability of several imaging techniques there remain numerous questions as to the utility of imaging to define risk in diabetes mellitus and an optimal approach has yet to be found.
10.1016/j.atherosclerosis.2018.02.021
Prognostic value of calcium score and coronary flow velocity reserve in asymptomatic diabetic patients.
Dikic Miodrag,Tesic Milorad,Markovic Zeljko,Giga Vojislav,Djordjevic-Dikic Ana,Stepanovic Jelena,Beleslin Branko,Jovanovic Ivana,Mladenovic Ana,Seferovic Jelena,Ostojic Miodrag,Arandjelovic Aleksandra
Cardiovascular ultrasound
BACKGROUND:The risk stratification of patients with diabetes mellitus (DM) is a major objective for the clinicians, and it can be achieved by coronary flow velocity reserve (CFVR) or with coronary artery calcium score (CS). CS evaluates underlying coronary atherosclerotic plaque burden and CFVR estimates both presence of coronary artery stenosis and microvascular function. Consequently, CFVR may provide unique risk information beyond the extent of coronary atherosclerosis. AIM:Our aim is to assess joint prognostic value of CFVR and CS in asymptomatic DM patients. MATERIALS AND METHODS:We prospectively included 200 asymptomatic patients (45,5 % male, mean age 57,35 ± 11,25), out of which, there were 101 asymptomatic patients with DM and 99 asymptomatic patients without DM, but with one or more conventionally risk factors for coronary artery disease. We analyzed clinical, biochemical, metabolic, inflammatory parameters, CS by Agatston method, transthoracic Doppler echocardiography CFVR of left anterior descending artery and echocardiographic parameters. RESULTS:Total CS and CS LAD were significantly higher, while mean CFVR was lower in diabetics compared to the nondiabetics. During 1 year follow-up, 24 patients experienced cardio-vascular events (one cardiovascular death, two strokes, three myocardial infarctions, nine new onsets of unstable angina and nine myocardial revascularizations): 19 patients with DM and five non DM patients, (p = 0,003). Overall event free survival was significantly higher in non DM group, compared to the DM group (94,9 % vs. 81,2 %, p = 0,002 respectively), while the patients with CS ≥200 and CFVR <2 had the worst outcome during 1 year follow up in the whole study population as well as in the DM group. At multivariable analysis CFVR on LAD (HR 12.918, 95 % CI 3.865-43.177, p < 0.001) and total CS (HR 13.393, 95 % CI 1.675-107.119, p = 0.014) were independent prognostic predictors of adverse events in DM group of patients. CONCLUSION:Both CS and CFVR provide independent and complementary prognostic information in asymptomatic DM patients. When two parameters are analyzed together, the risk stratification ability improves, even when DM patients are analyzed together with non DM patients. As a result, DM patients with CS ≥200 and CFVR <2 had the worst outcome. Consequently, the use of two tests identified subset of patients who can derive the most benefit from the intensive prevention measures.
10.1186/s12947-015-0035-2
Predictors of Plaque Rupture Within Nonculprit Fibroatheromas in Patients With Acute Coronary Syndromes: The PROSPECT Study.
Zheng Bo,Mintz Gary S,McPherson John A,De Bruyne Bernard,Farhat Naim Z,Marso Steven P,Serruys Patrick W,Stone Gregg W,Maehara Akiko
JACC. Cardiovascular imaging
OBJECTIVES:The study sought to examine the relative importance of lesion location versus vessel area and plaque burden in predicting plaque rupture within nonculprit fibroatheromas (FAs) in patients with acute coronary syndromes. BACKGROUND:Previous studies have demonstrated that plaque rupture is associated with larger vessel area and greater plaque burden clustering in the proximal segments of coronary arteries. METHODS:In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study 3-vessel grayscale and radiofrequency-intravascular ultrasound was performed after successful percutaneous coronary intervention in 697 patients with acute coronary syndromes. Untreated nonculprit lesion FAs were classified as proximal (<20 mm), mid (20 to 40 mm), and distal (>40 mm) according to the distance from the ostium to the maximum necrotic core site. RESULTS:Overall, 74 ruptured FAs and 2,396 nonruptured FAs were identified in nonculprit vessels. The majority of FAs (73.6%) were located within 40 mm of the ostium, and the vessel area and plaque burden progressively decreased from proximal to distal FA location (both p < 0.001). In a multivariate logistic regression model, independent predictors for plaque rupture included the distance from the ostium to the maximum necrotic core site per millimeter (odds ratio [OR]: 0.86; 95% confidence interval [CI]: 0.76 to 0.98; p = 0.02), plaque burden per 10% (OR: 2.05; 95% CI: 1.63 to 2.58; p < 0.0001), vessel area per mm(2) (OR: 1.14; 95% CI: 1.11 to 1.17; p < 0.0001), calcium (OR: 0.09; 95% CI: 0.05 to 0.18; p < 0.0001), and right coronary artery location (OR: 2.16; 95% CI: 1.25 to 3.27; p = 0.006). By receiver-operating characteristic analysis, vessel area correlated with plaque rupture stronger than either plaque burden (p < 0.001) or location (p < 0.001). CONCLUSIONS:Large vessel area, plaque burden, proximal location, right coronary artery location, and lack of calcium were associated with FA plaque rupture. The present study suggests that among these variables, vessel area may be the strongest predictor of plaque rupture among non-left main coronary arteries. ( PROSPECT:An Imaging Study in Patients With Unstable Atherosclerotic Lesions [PROSPECT]; NCT00180466).
10.1016/j.jcmg.2015.06.014
Ultrasonic Transducer-Guided Electrochemical Impedance Spectroscopy to Assess Lipid-Laden Plaques.
Ma Jianguo,Luo Yuan,Sevag Packard René R,Ma Teng,Ding Yichen,Abiri Parinaz,Tai Yu-Chong,Zhou Qifa,Shung Kirk K,Li Rongsong,Hsiai Tzung
Sensors and actuators. B, Chemical
Plaque rupture causes acute coronary syndromes and stroke. Intraplaque oxidized low density lipoprotein (oxLDL) is metabolically unstable and prone to induce rupture. We designed an intravascular ultrasound (IVUS)-guided electrochemical impedance spectroscopy (EIS) sensor to enhance the detection reproducibility of oxLDL-laden plaques. The flexible 2-point micro-electrode array for EIS was affixed to an inflatable balloon anchored onto a co-axial double layer catheter (outer diameter = 2 mm). The mechanically scanning-driven IVUS transducer (45 MHz) was deployed through the inner catheter (diameter = 1.3 mm) to the acoustic impedance matched-imaging window. Water filled the inner catheter to match acoustic impedance and air was pumped between the inner and outer catheters to inflate the balloon. The integrated EIS and IVUS sensor was deployed into the ex vivo aortas dissected from the fat-fed New Zealand White (NZW) rabbits (n=3 for fat-fed, n= 5 normal diet). IVUS imaging was able to guide the 2-point electrode to align with the plaque for EIS measurement upon balloon inflation. IVUS-guided EIS signal demonstrated reduced variability and increased reproducibility ( < 0.0001 for magnitude, < 0.05 for phase at < 15 kHz) as compared to EIS sensor alone ( < 0.07 for impedance, < 0.4 for phase at < 15 kHz). Thus, we enhanced topographic and EIS detection of oxLDL-laden plaques via a catheter-based integrated sensor design to enhance clinical assessment for unstable plaque.
10.1016/j.snb.2016.04.179
Matrix Metalloproteinase 9 as a Predictor of Coronary Atherosclerotic Plaque Instability in Stable Coronary Heart Disease Patients with Elevated Lipoprotein(a) Levels.
Ezhov Marat,Safarova Maya,Afanasieva Olga,Mitroshkin Maksim,Matchin Yuri,Pokrovsky Sergei
Biomolecules
We sought to investigate whether levels of matrix metalloproteinases (MMPs) and their inhibitors predict coronary atherosclerotic plaque instability, as assessed by intravascular ultrasound (IVUS) virtual histology during coronary angiography. Blood samples were collected before angiography in 32 subjects (mean age 56 ± 8 years) with stable coronary heart disease (CHD) and elevated lipoprotein(a) (Lp(a), 94 ± 35 mg/dL). Levels of high-sensitivity C-reactive protein (hsCRP), apolipoprotein B100 (apoB100), MMP-7, MMP-9, tissue inhibitor of metalloproteinases (TIMP)-1, and TIMP-2 were determined using commercially available enzyme-linked immunosorbent assay kits. Results. The morphology of a total of sixty coronary lesions was assessed by virtual histology IVUS imaging. Eleven (18%) plaques in nine (28%) patients were classified as plaques with an unstable phenotype or a thin-cap fibroatheroma. Age, low-density lipoprotein cholesterol, apoB100, MMP-7, and MMP-9 levels were positively associated with necrotic core volume. Conversely, there was a negative relationship between MMP-7 and -9 levels and fibrous and fibro-fatty tissue volume. Multivariate regression analysis revealed that MMP-9 is a strong independent predictor of atherosclerotic plaque instability in stable CHD patients. In stable CHD patients with elevated Lp(a), MMP-9 levels are positively associated with the size of the necrotic core of coronary atherosclerotic plaques.
10.3390/biom9040129
Detection of positively remodeled coronary artery lesions by multislice CT and its impact on cardiovascular future events.
Galal Haitham,Rashid Tarek,Alghonaimy Wesam,Kamal Diaa
The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology
BACKGROUND:Positive arterial remodeling may be a characteristic of early proliferative lesions. The study was done to identify the different morphological characteristics of the positively remodeled coronary lesions, and causing non-significant arterial stenosis, as detected by multislice computed tomography coronary angiography (MSCT CA) and its predictors of cardiovascular clinical events at 90-day follow-up. The study included 55 patients who were candidate for MSCT CA and found to have a single-vessel disease with less than 70% stenosis positively remodeled lesions. The most expansive or solitary lesion was selected for each patient. Positive remodeling defined as remodeling index (RI) > 1.05. We followed the patients clinically for 90 days. RESULTS:Twenty-four patients had a history of acute coronary syndrome at initial presentation with normal LV systolic function for all studied patients. Dyslipidemia was found in 37 patients (67.3%) while diabetes was found in 29 patients (52.7%). The majority of the lesions were found in the proximal LAD (43.6%). The mean calculated remodeling index was 1.41 ± 0.25. At the end of 90 days, 25 patients had clinical events in the form of unstable coronary syndromes, coronary interventions, or coronary angiography related to the index lesion. The predictors of clinical events were duration of DM, higher degree of luminal narrowing, calculated wall/lumen area percentage, plaque burden, plaque-specific calcification, and total calcium score at remodeling site as well as a lower percentage of low-attenuation plaque area. The mean calculated wall/lumen area percentage was 263.72 ± 122.71%. A cut-off value of > 226% was found a predictor for clinical events. The mean plaque burden percentage was 69.72 ± 9.71%, a value of > 69% was found a predictor for clinical events. Both values had a sensitivity of 68% and specificity of 86.6% and PPV of 81%. Positively remodeled lesions with a high RI > 1.4 were correlated with patients who had acute coronary syndrome on their initial presentation. CONCLUSION:Different morphological characteristics of positively remodeled non-occlusive atherosclerotic plaques as detected by multislice CT coronary angiography may be good potential predictors of future cardiovascular events.
10.1186/s43044-019-0029-8
Predictive Value of Age- and Sex-Specific Nomograms of Global Plaque Burden on Coronary Computed Tomography Angiography for Major Cardiac Events.
Naoum Christopher,Berman Daniel S,Ahmadi Amir,Blanke Philipp,Gransar Heidi,Narula Jagat,Shaw Leslee J,Kritharides Leonard,Achenbach Stephan,Al-Mallah Mouaz H,Andreini Daniele,Budoff Matthew J,Cademartiri Filippo,Callister Tracy Q,Chang Hyuk-Jae,Chinnaiyan Kavitha,Chow Benjamin,Cury Ricardo C,DeLago Augustin,Dunning Allison,Feuchtner Gudrun,Hadamitzky Martin,Hausleiter Joerg,Kaufmann Philipp A,Kim Yong-Jin,Maffei Erica,Marquez Hugo,Pontone Gianluca,Raff Gilbert,Rubinshtein Ronen,Villines Todd C,Min James,Leipsic Jonathon
Circulation. Cardiovascular imaging
BACKGROUND:Age-adjusted coronary artery disease (CAD) burden identified on coronary computed tomography angiography predicts major adverse cardiovascular event (MACE) risk; however, it seldom contributes to clinical decision making because of a lack of nomographic data. We aimed to develop clinically pragmatic age- and sex-specific nomograms of CAD burden using coronary computed tomography angiography and to validate their prognostic use. METHODS AND RESULTS:Patients prospectively enrolled in phase I of the CONFIRM registry (Coronary CT Angiography Evaluation for Clinical Outcomes) were included (derivation cohort: n=21,132; 46% female) to develop CAD nomograms based on age-sex percentiles of segment involvement score (SIS) at each year of life (40-79 years). The relationship between SIS age-sex percentiles (SIS%) and MACE (all-cause death, myocardial infarction, unstable angina, and late revascularization) was tested in a nonoverlapping validation cohort (phase II, CONFIRM registry; n=3030, 44% female) by stratifying patients into 3 SIS% groups (≤50th, 51-75th, and >75th) and comparing annualized MACE rates and time to MACE using multivariable Cox proportional hazards models adjusting for Framingham risk and chest pain typicality. Age-sex percentiles were well fitted to second-order polynomial curves (men: =0.86±0.12; women: =0.86±0.14). Using the nomograms, there were 1576, 965, and 489 patients, respectively, in the ≤50th, 51-75th, and >75th SIS% groups. Annualized event rates were higher among patients with greater CAD burden (2.1% [95% confidence interval: 1.7%-2.7%], 3.9% [95% confidence interval: 3.0%-5.1%], and 7.2% [95% confidence interval: 5.4%-9.6%] in ≤50th, 51-75th, and >75th SIS% groups, respectively; <0.001). Adjusted MACE risk was significantly increased among patients in SIS% groups above the median compared with patients below the median (hazard ratio [95% confidence interval]: 1.9 [1.3-2.8] for 51-75th SIS% group and 3.4 [2.3-5.0] for >75th SIS% group; <0.01 for both). CONCLUSIONS:We have developed clinically pragmatic age- and sex-specific nomograms of CAD prevalence using coronary computed tomography angiography findings. Global plaque burden measured using SIS% is predictive of cardiac events independent of traditional risk assessment. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01443637.
10.1161/CIRCIMAGING.116.004896
Impact of Diabetes Control on Subclinical Atherosclerosis: Analysis from Coronary Computed Tomographic Angiography Registry.
Park Gyung Min,Lee Chang Hoon,Lee Seung Whan,Yun Sung Cheol,Kim Young Hak,Kim Yong Giun,Won Ki Bum,Ann Soe Hee,Kim Shin Jae,Yang Dong Hyun,Kang Joon Won,Lim Tae Hwan,Koh Eun Hee,Lee Woo Je,Kim Min Seon,Park Joong Yeol,Kim Hong Kyu,Choe Jaewon,Lee Sang Gon
Diabetes & metabolism journal
BACKGROUND:There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis. METHODS:We analyzed 6,434 consecutive asymptomatic individuals without previous history of coronary artery disease who underwent coronary computed tomographic angiography (CCTA) (mean age, 53.7±7.6 years and 4,694 men [73.0%]). The degree and extent of subclinical coronary atherosclerosis were assessed by CCTA, and ≥50% diameter stenosis was defined as significant. A cardiac event was defined as a composite of all-cause death, myocardial infarction, unstable angina, or coronary revascularization. Study participants were categorized as normal (=5,319), controlled diabetes (glycosylated hemoglobin [HbA1c] <7%, =747), or uncontrolled diabetes (HbA1c ≥7%, =368), respectively. RESULTS:Compared with normal individuals, there were no statistically significant differences in the risk of for any atherosclerotic plaque (odds ratio [OR], 1.16; 95% confidence interval [CI], 0.98 to 1.38; =0.086) and significant coronary artery stenosis (OR, 1.08; 95% CI, 0.82 to 1.42; =0.583) in controlled diabetic individuals. In contrast, uncontrolled diabetic individuals had consistently higher risks of any atherosclerotic plaque (OR, 2.16; 95% CI, 1.70 to 2.75; <0.001) and significant coronary artery stenosis (OR, 3.34; 95% CI, 2.52 to 4.43; <0.001) than normal individuals. During a follow-up of median 5.4 years, there was no significant difference in cardiac events between normal and controlled diabetic individuals (=0.365). However, uncontrolled diabetes was associated with an increased risk of cardiac events compared with normal individuals (<0.001) and controlled diabetic individuals (=0.023). CONCLUSION:Asymptomatic uncontrolled diabetes was associated with significant subclinical coronary atherosclerosis with subsequent high risk for cardiac events.
10.4093/dmj.2019.0073
Clinical outcome in patients with acute coronary syndrome and outward remodeling is associated with a predominant inflammatory response.
Madrid-Miller Alejandra,Chávez-Sánchez Luis,Careaga-Reyna Guillermo,Borrayo-Sánchez Gabriela,Chávez-Rueda Karina,Montoya-Guerrero Silvestre Armando,Abundes Velazco Arturo,Ledesma-Velasco Mariano,Legorreta-Haquet María Victoria,Blanco-Favela Francisco
BMC research notes
BACKGROUND:Pro-inflammatory molecules and low-density lipoproteins play essential roles in the atherosclerosis. The aim of our study was to establish an association among the cytokines secreted by peripheral blood mononuclear cells and the serum concentration in patients with unstable angina and coronary outward remodeling before and after percutaneous coronary intervention. The clinical and coronary responses were evaluated 6 months after the procedure. FINDINGS:Twenty-two patients with unstable angina were evaluated prior to after percutaneous coronary intervention and 6 months after procedure by coronary intravascular ultrasound. Eleven of the patients had recurrent angina, while 9 presented restenosis and an increase in the percentage of total plaque area. These 11 patients displayed higher levels of C-reactive protein than those without coronary events (1.27 vs. 0.43 mg/dl, respectively; p = 0.029) and a tendency to increase levels of interleukin (IL)-8 and transforming growth factor-β1, but lower levels of IL-10 (52.09 vs. 141.5 pg/ml, respectively; p = 0.035). Activated peripheral blood mononuclear cells from patients with restenosis presented higher levels of proliferation, CD86 expression and higher IL-1, and increased IL-10 compared to those in patients without restenosis. CONCLUSIONS:Patients with unstable angina and coronary outward remodeling who displayed a pro-inflammatory response experienced recurrent coronary events and an increased percentage of total plaque area. In contrast, better outcomes were observed in patients with anti-inflammatory responses. This response could be secondary to low-density lipoproteins.
10.1186/1756-0500-7-669
APOA1 and APOB polymorphisms and apolipoprotein concentrations as biomarkers of risk in acute coronary syndrome: Relationship with lipid-lowering therapy effectiveness.
Casillas-Muñoz Fidel,Valle Yeminia,Muñoz-Valle José Francisco,Martínez-Fernández Diana Emilia,Reynoso-Villalpando Gabriela Lizet,Flores-Salinas Héctor Enrique,Llamas-Covarrubias Mara Anaís,Padilla-Gutiérrez Jorge Ramón
Medicina clinica
BACKGROUND AND OBJECTIVE:Lipid metabolism alterations contribute to acute coronary syndrome (ACS). rs670, rs5070 and rs693 polymorphisms have shown to modify the risk of cardiovascular disease. Apolipoprotein A-I (ApoA-I) plays a major role in reverse cholesterol transport; apolipoprotein B (ApoB) contributes to accumulation of cholesterol in the plaque. The aim of this study was to investigate the association of rs670 and rs5070 polymorphisms of APOA1 and rs693 polymorphism of APOB with ACS and circulating levels of its proteins and find if ApoB/ApoA-I could be implemented as an independent parameter of risk for cardiovascular disease and as a biomarker of lipid-lowering therapy effectiveness in Mexican population. METHODS:Three hundred patients with ACS and 300 control subjects (CS) were included. RESULTS:Neither genotype nor allele frequencies of rs670, rs5070 and rs693 polymorphisms showed statistical differences between groups. Serum levels of ApoA-I (195 vs. 161.4mg/dL; P<.001) and ApoB (167 vs. 136.9mg/dL; P<.001) were significantly higher in CS compared with ACS; however, there was no genetic association. Unstable angina patients showed the highest ApoA-I levels (males: 176.3mg/dL; females: 209.1mg/dL). CONCLUSION:The rs670, rs5070 and rs693 polymorphisms are not genetic susceptibility factors for ACS in Mexican population and had no effect on their apolipoprotein concentrations. In our population, ApoA-I, ApoB and HDL-C could be better biomarkers of cardiovascular risk and could indicate if statins doses reduce atherogenic particles properly.
10.1016/j.medcli.2017.07.026
Atherosclerotic plaque metabolism in high cardiovascular risk subjects - A subclinical atherosclerosis imaging study with F-NaF PET-CT.
Oliveira-Santos Manuel de,Castelo-Branco Miguel,Silva Rodolfo,Gomes Andreia,Chichorro Nuno,Abrunhosa Antero,Donato Paulo,Pedroso de Lima João,Pego Mariano,Gonçalves Lino,Ferreira Maria João
Atherosclerosis
BACKGROUND AND AIMS:Atherosclerotic plaque molecular imaging with F-sodium fluoride (NaF) in positron emission tomography with computed tomography (PET-CT) provides potential discrimination between active unstable microcalcification and established dormant calcification. We aimed to study F-NaF atherosclerotic plaque uptake in high cardiovascular (CV) risk participants and its associations with CV risk factors, coronary calcium score and thoracic fat volume. METHODS:High CV risk hypertensive individuals from a single centre were prospectively scanned with F-NaF-PET-CT in the coronary, aortic and carotideal arteries. Atherosclerotic plaque F-NaF uptake was expressed as Corrected Uptake per Lesion (CUL): maximum standard uptake value in each vascular territory subtracted by mean blood pool activity. RESULTS:Mean age was 64 years, 56% male and 96% Caucasian (n = 25). Ninety six per cent of the subjects showed F-NaF uptake in the aorta (CUL 0.9 ± 0.3), 40% in the carotid arteries (median CUL 0.0, IQR 0.0-0.7) and 64% in the coronary arteries (0.4, IQR 0.0-0.6). Individuals with ≥ five risk factors (60%) had increased overall F-NaF uptake (1.1 ± 0.3 vs. 0.7 ± 0.3, p < 0.01), which was positively correlated with predicted fatal CV risk - SCORE (r = 0.49, p = 0.01). There was no correlation between F-NaF uptake in the coronary arteries and calcium score (p = 0.87). Thoracic fat was moderately correlated with overall CUL (r = 0.41, p = 0.04). CONCLUSIONS:In a high CV risk group, F-NaF atherosclerotic plaque uptake was related to the burden of CV risk factors and thoracic fat volume, but there was no association between coronary uptake and calcium score.
10.1016/j.atherosclerosis.2017.03.014
Effect of tube potential and luminal contrast attenuation on atherosclerotic plaque attenuation by coronary CT angiography: In vivo comparison with intravascular ultrasound.
Matsumoto Hidenari,Watanabe Satoshi,Kyo Eisho,Tsuji Takafumi,Ando Yosuke,Otaki Yuka,Cadet Sebastien,Slomka Piotr J,Berman Daniel S,Dey Damini,Tamarappoo Balaji K
Journal of cardiovascular computed tomography
BACKGROUND:It has been shown that CT attenuation of noncalcified plaques depends on luminal contrast attenuation (LCA). Although tube potential (kilovolt [kV]) has been shown to exert influence on plaque attenuation through LCA as well as its direct effects, in-vivo studies have not investigated plaque attenuation at lower tube potentials less than 120 kV. We sought to evaluate the effect of kV and LCA on thresholds for lipid-rich and fibrous plaques as defined by intravascular ultrasound (IVUS). METHODS:CT attenuation of IVUS-defined plaque components (lipid-rich, fibrous, and calcified plaques) were quantified in 52 consecutive patients with unstable angina, who had coronary CT angiography performed at 100 kV (n = 25) or 120 kV (n = 27) using kV-adjusted contrast protocol prior to IVUS. CT attenuation of plaque components was compared between the two groups. RESULTS:LCA was similar in the 100-kV and 120-kV groups (417.6 ± 83.7 Hounsfield Units [HU] vs 421.3 ± 54.9 HU, p = 0.77). LCA correlated with CT attenuation of lipid-rich (r = 0.49, p = 0.001) and fibrous plaques (r = 0.32, p < 0.05), but not with that of calcified plaques (r = 0.04, p = 0.81). When plaque attenuation was normalized to LCA, lipid-rich (0.087 ± 0.036, range -0.012-0.147) and fibrous plaque attenuation (0.234 ± 0.056, range 0.153-0.394) were distinct (p < 0.001) with no overlap for both kV groups. CT attenuation was not significantly different between 100-kV and 120-kV groups for lipid-rich (34.0 ± 21.5 vs 39.3 ± 12.9, p = 0.33) or fibrous plaques (95.4 ± 19.1 vs 97.6 ± 22.0, p = 0.75). CONCLUSION:Plaque attenuation thresholds for non-calcified plaque components should be adjusted based on LCA. Further adjustment may not be required for different tube potentials.
10.1016/j.jcct.2019.02.004
Coronary-Heart-Disease-Associated Genetic Variant at the COL4A1/COL4A2 Locus Affects COL4A1/COL4A2 Expression, Vascular Cell Survival, Atherosclerotic Plaque Stability and Risk of Myocardial Infarction.
Yang Wei,Ng Fu Liang,Chan Kenneth,Pu Xiangyuan,Poston Robin N,Ren Meixia,An Weiwei,Zhang Ruoxin,Wu Jingchun,Yan Shunying,Situ Haiteng,He Xinjie,Chen Yequn,Tan Xuerui,Xiao Qingzhong,Tucker Arthur T,Caulfield Mark J,Ye Shu
PLoS genetics
Genome-wide association studies have revealed an association between coronary heart disease (CHD) and genetic variation on chromosome 13q34, with the lead single nucleotide polymorphism rs4773144 residing in the COL4A2 gene in this genomic region. We investigated the functional effects of this genetic variant. Analyses of primary cultures of vascular smooth muscle cells (SMCs) and endothelial cells (ECs) from different individuals showed a difference between rs4773144 genotypes in COL4A2 and COL4A1 expression levels, being lowest in the G/G genotype, intermediate in A/G and highest in A/A. Chromatin immunoprecipitation followed by allelic imbalance assays of primary cultures of SMCs and ECs that were of the A/G genotype revealed that the G allele had lower transcriptional activity than the A allele. Electrophoretic mobility shift assays and luciferase reporter gene assays showed that a short DNA sequence encompassing the rs4773144 site interacted with a nuclear protein, with lower efficiency for the G allele, and that the G allele sequence had lower activity in driving reporter gene expression. Analyses of cultured SMCs from different individuals demonstrated that cells of the G/G genotype had higher apoptosis rates. Immunohistochemical and histological examinations of ex vivo atherosclerotic coronary arteries from different individuals disclosed that atherosclerotic plaques with the G/G genotype had lower collagen IV abundance and thinner fibrous cap, a hallmark of unstable, rupture-prone plaques. A study of a cohort of patients with angiographically documented coronary artery disease showed that patients of the G/G genotype had higher rates of myocardial infarction, a phenotype often caused by plaque rupture. These results indicate that the CHD-related genetic variant at the COL4A2 locus affects COL4A2/COL4A1 expression, SMC survival, and atherosclerotic plaque stability, providing a mechanistic explanation for the association between the genetic variant and CHD risk.
10.1371/journal.pgen.1006127
Prevalence, impact, and predictive value of detecting subclinical coronary and carotid atherosclerosis in asymptomatic adults: the BioImage study.
Baber Usman,Mehran Roxana,Sartori Samantha,Schoos Mikkel Malby,Sillesen Henrik,Muntendam Pieter,Garcia Mario J,Gregson John,Pocock Stuart,Falk Erling,Fuster Valentin
Journal of the American College of Cardiology
BACKGROUND:Although recent studies suggest that measuring coronary artery calcification (CAC) may be superior to indirect atherosclerotic markers in predicting cardiac risk, there are limited data evaluating imaging-based biomarkers that directly quantify atherosclerosis in different vascular beds performed in a single cohort. OBJECTIVES:The BioImage Study (A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population) sought to identify imaging biomarkers that predict near-term (3-year) atherothrombotic events. METHODS:The BioImage Study enrolled 5,808 asymptomatic U.S. adults (mean age: 69 years, 56.5% female) in a prospective cohort evaluating the role of vascular imaging on cardiovascular risk prediction. All patients were evaluated by CAC and novel 3-dimensional carotid ultrasound. Plaque areas from both carotid arteries were summed as the carotid plaque burden (cPB). The primary endpoint was the composite of major adverse cardiac events (MACE) (cardiovascular death, myocardial infarction, and ischemic stroke). A broader secondary MACE endpoint also included all-cause death, unstable angina, and coronary revascularization. RESULTS:Over a median follow-up of 2.7 years, MACE occurred in 216 patients (4.2%), of which 82 (1.5%) were primary events. After adjustment for risk factors, and compared with individuals without any cPB, hazard ratios for MACE were 0.78 (95% confidence interval [CI]: 0.31 to 1.91), 1.45 (95% CI: 0.67 to 3.14), and 2.36 (95% CI: 1.13 to 4.92) with increasing cPB tertile, with similar results for CAC. Net reclassification significantly improved with either cPB (0.23) or CAC (0.25). MACE rates increased simultaneously with higher levels of both cPB and CAC. CONCLUSIONS:Detection of subclinical carotid or coronary atherosclerosis improves risk predictions and reclassification compared with conventional risk factors, with comparable results for either modality. Cost-effective analyses are warranted to define the optimal roles of these complementary techniques. (BioImage Study: A Clinical Study of Burden of Atherosclerotic Disease in an At-Risk Population; NCT00738725).
10.1016/j.jacc.2015.01.017
Correlation between frequency-domain optical coherence tomography and fractional flow reserve in angiographically-intermediate coronary lesions.
Burzotta Francesco,Nerla Roberto,Hill Jonathan,Paraggio Lazzaro,Leone Antonio Maria,Byrne Jonathan,Porto Italo,Niccoli Giampaolo,Aurigemma Cristina,Trani Carlo,MacCarthy Philip,Crea Filippo
International journal of cardiology
BACKGROUND:The decision-making process of patients with angiographically-intermediate coronary lesions (ICL) is clinically challenging and may benefit from adjunctive invasive techniques. Fractional-flow-reserve (FFR) represents the gold standard to evaluate ICL but frequency-domain optical-coherence-tomography (OCT) is a novel, promising, high resolution coronary imaging technique, which allows physiopathologic assessment of coronary plaque. We investigated the possible relation between OCT and FFR in selected ICL patients. METHODS:Stable or unstable patients with ICL who underwent both FFR and OCT assessment at two large tertiary centers were retrospectively enrolled. FFR was performed according to standard methodology. OCT images were (on blind to clinical and FFR results) analyzed to assess minimal lumen area (MLA), percentage area stenosis (AS), thrombus and plaque ulceration. RESULTS:Forty patients were identified (62±10years, 93% symptomatic, 35% acute presentation, 93% left-anterior-descending artery ICL). Percentage diameter stenosis at quantitative coronary angiography was 40±12% and FFR was 0.85±0.07. MLA (p=0.009), AS (p<0.001) and plaque ulceration (p=0.02) were significantly associated with FFR values. An integrated assessment of AS (≥ or <70%), MLA (≥ or <2.5mm) and presence or absence of thrombus and plaque ulceration was found to have the potential to accurately (sensitivity 91%, specificity 93%) predict FFR results. CONCLUSION:In patients with ICL, a combination of different OCT parameters may help predict FFR results. These findings suggest that only a comprehensive assessment of lesion features by OCT can allow an accurate prediction of lesion severity assessed by FFR.
10.1016/j.ijcard.2017.10.011
Chlamydia Pneumoniae and Immunoinflammatory Reactions in an Unstable Atherosclerotic Plaque in Humans.
Pigarevskii P V,Mal'tseva S V,Snegova V A,Davydova N G,Guseva V A
Bulletin of experimental biology and medicine
Comparative study of the walls of the aorta, coronary artery, and a. basilaris detected for the first time intra- and extracellular depositions of Chlamydia pneumoniae in unstable atherosclerotic plaques. No chlamydia were detected in the intima of normal sites of the vascular wall and just negligible levels thereof in stable atherosclerotic plaques. An unstable plaque with intra- and extracellular colonies was characterized by infiltration of the cap and intima adjacent to the atheromatous core with mononuclear cells, primarily T cells. These data suggested that Chlamydia pneumoniae could play an important role in the development of immunoinflammatory processes in the vascular wall and promote destabilization and progressive development of atherosclerotic plaques in humans.
10.1007/s10517-015-2941-6
Aldehyde dehydrogenase 2 inhibits inflammatory response and regulates atherosclerotic plaque.
Pan Chang,Xing Jun-Hui,Zhang Cheng,Zhang Ying-Mei,Zhang Lue-Tao,Wei Shu-Jian,Zhang Ming-Xiang,Wang Xu-Ping,Yuan Qiu-Huan,Xue Li,Wang Jia-Li,Cui Zhao-Qiang,Zhang Yun,Xu Feng,Chen Yu-Guo
Oncotarget
Previous studies demonstrated that aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism, which eliminates ALDH2 activity down to 1%-6%, is a susceptibility gene for coronary disease. Here we investigated the underlying mechanisms based on our prior clinical and experimental studies. Male apoE-/- mice were transfected with GFP, ALDH2-overexpression and ALDH2-RNAi lentivirus respectively (n=20 each) after constrictive collars were placed around the right common carotid arteries. Consequently, ALDH2 gene silencing led to an increased en face plaque area, more unstable plaque with heavier accumulation of lipids, more macrophages, less smooth muscle cells and collagen, which were associated with aggravated inflammation. However, ALDH2 overexpression displayed opposing effects. We also found that ALDH2 activity decreased in atherosclerotic plaques of human and aged apoE-/- mice. Moreover, in vitro experiments with human umbilical vein endothelial cells further illustrated that, inhibition of ALDH2 activity resulted in elevating inflammatory molecules, an increase of nuclear translocation of NF-κB, and enhanced phosphorylation of NF-κB p65, AP-1 c-Jun, Jun-N terminal kinase and p38 MAPK, while ALDH2 activation could trigger contrary effects. These findings suggested that ALDH2 can influence plaque development and vulnerability, and inflammation via MAPK, NF-κB and AP-1 signaling pathways.
10.18632/oncotarget.9384
Prognosis of vulnerable plaque on computed tomographic coronary angiography with normal myocardial perfusion image.
Otsuka Kenichiro,Fukuda Shota,Tanaka Atsushi,Nakanishi Koki,Taguchi Haruyuki,Yoshiyama Minoru,Shimada Kenei,Yoshikawa Junichi
European heart journal cardiovascular Imaging
AIMS:Increasing clinical evidence has emphasized the importance of coronary plaque characteristics, rather than the severity of luminal narrowing on acute coronary syndrome (ACS) outcome. Computed tomographic coronary angiography (CTCA) is a unique, non-invasive approach for assessing plaque characteristics. This study was prospectively designed to investigate the prognostic value of physiologically non-obstructive but a vulnerable coronary plaque on CTCA for predicting future ACS events. METHODS AND RESULTS:This study consisted of 543 patients who had undergone CTCA and had normal findings on exercise-stress myocardial perfusion single-photon emission computed tomography. CTCA analysis included the presence of >50% luminal stenosis and vulnerable features including positive remodelling (PR), low-attenuation plaque, and ring-like sign. The primary endpoint was ACS events including cardiac death, non-fatal myocardial infarction, and unstable angina. The mean follow-up period was 3.4 ± 0.8 years. The 3-year cumulative event rate was 1.2% per year, and 87% of ACS events occurred in plaques with at least one of vulnerable features. In patient-based multivariate analysis, the presence of plaque with vulnerable features on CTCA was a significant predictor for future ACS events (P = 0.001). Patients with vulnerable plaque had worse ACS outcomes compared with those without vulnerable plaques (3-year cumulative event rate; 3.2 per year vs. 0.8%, P < 0.001). CONCLUSION:This study demonstrated that physiologically non-obstructive but vulnerable coronary plaques were associated with future ACS events. We should pay more attention to currently non-obstructive plaque but showing vulnerable morphologies on CTCA.
10.1093/ehjci/jet232
Expression of the NLRP3 Inflammasome in Carotid Atherosclerosis.
Shi Xin,Xie Wen-Li,Kong Wei-Wei,Chen Dong,Qu Peng
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
BACKGROUND:The aim of the present study was to investigate NLRP3 inflammasome expression in human carotid atherosclerotic plaques and its relationship to plaque vulnerability. METHODS:Carotid atherosclerotic plaques collected from 30 patients scheduled for carotid endarterectomy (CEA) were subjected to immunohistochemical, mRNA, and protein expression studies. Ten mesenteric arteries from intestinal cancer patients served as controls for the immunohistochemical studies. Twenty individuals who had no carotid stenosis or coronary artery stenosis served as controls for analyzing atherosclerotic risk factors and for enzyme-linked immunosorbent assay (ELISA) studies. Serum samples were collected from all patients to determine interleukin-1β (IL-1β) and IL-18 levels. RESULTS:The NLRP3 inflammasome signaling pathway components NLRP3, ASC, caspase-1, IL-1β, and IL-18 were strongly expressed in carotid atherosclerotic plaques, but not in healthy mesenteric arteries. Immunohistochemical, mRNA, and protein expression studies revealed higher expression levels of NLRP3, ASC, caspase-1, IL-1β, and IL-18 in unstable compared to stable plaques. The NLRP3 inflammasome was localized in the cytoplasm of macrophages and foam cells and was associated with cholesterol crystal clefts inside and outside of cells. ELISA showed that the serum levels of the cytokines IL-1β and IL-18 were higher in the CEA group compared to controls. CONCLUSIONS:These results demonstrated for the first time the close relationship between the expression of NLRP3 signaling pathway and human carotid atherosclerotic plaques. NLRP3, ASC, caspase-1, IL-1β, and IL-18 were associated with plaque vulnerability and atherogenesis. The serum levels of IL-1β and IL-18 may be useful predictors of atherosclerosis.
10.1016/j.jstrokecerebrovasdis.2015.03.024
White Blood Cell Subtypes and Neutrophil-Lymphocyte Ratio in Prediction of Coronary Thrombus Formation in Non-ST-Segment Elevated Acute Coronary Syndrome.
Yilmaz Mustafa,Tenekecioglu Erhan,Arslan Burhan,Bekler Adem,Ozluk Ozlem Arican,Karaagac Kemal,Agca Fahriye Vatansever,Peker Tezcan,Akgumus Alkame
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
Leukocytes are reported as crucial not only for plaque activation but also in thrombus formation in acute coronary syndromes (ACSs). Among the markers of inflammation, in coronary artery disease neutrophil-lymphocyte ratio (NLR) has been reported to have the greatest predictive power of poor outcomes. Our aim was to evaluate the association of NLR with coronary thrombus in patients with non-ST-segment elevated ACSs (NST-ACSs). A total of 251 patients were hospitalized with a diagnosis of NST-ACS including non-ST-segment elevated myocardial infarction and unstable angina pectoris. Coronary angiographies were performed. In 167 patients, coronary thrombus was detected. Between the patient groups with and without coronary thrombus, neutrophil count, platelet count, and NLR are significantly increased, and lymphocyte count is significantly decreased in the group with coronary thrombus as compared to patient group without coronary thrombus. Leukocyte count and NLR may give an indication about the presence of coronary thrombus. In NST-ACS, blood parameters may give valuable information about the status of the coronary arteries.
10.1177/1076029613507337
Prevalence of Thin-Cap Fibroatheroma in Relation to the Severity of Anatomical and Physiological Stenosis.
Circulation journal : official journal of the Japanese Circulation Society
BACKGROUND:The relationship between the features of morphologically unstable plaque and physiological lesion severity remains elusive. We aimed to investigate this relationship using optical coherence tomography (OCT)-derived high-risk plaque characteristics and fractional flow reserve (FFR) as the degree of anatomical and physiological stenosis severity. METHODS AND RESULTS:We investigated 286 de novo intermediate and severe coronary lesions in 248 patients who underwent OCT and FFR examinations. Lesions were divided into tertiles based on either FFR or quantitative coronary angiographic diameter stenosis (QCA-%DS). The OCT findings were compared among the tertiles of FFR and QCA-%DS. FFR and QCA tertiles were defined as follows: FFR-T1 (FFR <0.74), FFR-T2 (0.74≤FFR≤0.81), and FFR-T3 (FFR >0.81); and QCA-T1 (%DS ≥61%), QCA-T2 (51%≤%DS<61%), and QCA-T3 (%DS <51%). The prevalence of thin-cap fibroatheroma (TCFA) was significantly greater in FFR-T1 (20.0%) than in FFR-T2 and FFR-T3 (7.0%, P=0.03 and 7.7%, P=0.04, respectively), although no significant differences were observed among the QCA tertiles. CONCLUSIONS:Physiological severity of coronary stenosis evaluated by FFR correlated with plaque instability in terms of TCFA. Preferable clinical outcomes for lesions with negative FFR based on the existing clinical evidence might be attributable to less likelihood of TCFA.
10.1253/circj.CJ-17-0122
Obstructive sleep apnea is associated with increased coronary plaque instability: an optical frequency domain imaging study.
Konishi Takao,Kashiwagi Yusuke,Funayama Naohiro,Yamamoto Tadashi,Murakami Hironori,Hotta Daisuke,Tanaka Shinya
Heart and vessels
Obstructive sleep apnea (OSA) is associated with coronary artery disease (CAD) and with an increased risk for myocardial infarction, stroke or death due to cardiovascular disease. Optical frequency-domain imaging (OFDI) is a useful modality for evaluating the characteristics of atherosclerotic plaque. The purpose of the study was to use OFDI to investigate the association of OSA with coronary plaque characteristics in patients undergoing percutaneous coronary intervention (PCI). We retrospectively analyzed OFDI data for coronary artery plaques from 15 patients with OSA and 35 non-OSA patients treated between October 2015 and October 2018. Plaque morphology was evaluated for 70 lesions, including 21 from patients with OSA and 49 from non-OSA patients. Compared with the non-OSA group, patients with OSA had significantly higher prevalences of thinned cap fibroatheroma (TCFA) (67% vs. 35%, P = 0.014) and microchannels (86% vs. 55%, P = 0.014); a significantly higher mean lipid index (1392 ± 982 vs. 817 ± 699, P = 0.021), macrophage grade (8.4 ± 6.4 vs. 4.8 ± 4.5, P = 0.030), and maximum number of microchannels (1.5 ± 1.0 vs. 0.7 ± 0.7, P = 0.001); and a significantly lower mean minimum fibrous cap thickness (69.4 ± 28.7 vs. 96.1 ± 51.8 μm, P = 0.008). This OFDI analysis suggests that OSA is associated with unstable plaque characteristics in patients with CAD. More intensive medical management for stabilization of coronary atherosclerotic plaque is required in patients with OSA.
10.1007/s00380-019-01363-8
Apolipoprotein B correlates with intra-plaque necrotic core volume in stable coronary artery disease.
Ohwada Takayuki,Sakamoto Takayuki,Kanno Yuki,Yokokawa Sayoko,Amami Kazuaki,Nakazato Kazuhiko,Takeishi Yasuchika,Watanabe Kenichi
PloS one
OBJECTIVE:To determine the relationship between plaque composition and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (Apo-B), and Apo-A1 using virtual-histology intravascular ultrasound (VH-IVUS). METHODS:We assessed plaque composition in patients with stable coronary artery disease (SCD) admitted to our hospital for percutaneous coronary intervention (PCI) between November 1, 2012, and March 10, 2015. Before PCI, fibrous (FI), fibrofatty (FF), necrotic core (NC), and dense calcium (DC) regions were evaluated using VH-IVUS, and the contributions of each to the culprit lesion volume were recorded. Plasma LDL-C, HDL-C, Apo-B, and Apo-A1 levels were assessed before PCI. The relationship between the regions on VH-IVUS and plasma lipid levels was assessed. Patients were categorized into low Apo-B (LAB) and high Apo-B (HAB) groups, based on the overall cohort median Apo-B level. RESULTS:We enrolled 115 patients (median Apo-B, 91 mg/dL, male n = 88) with 57 and 58 patients in the LAB (Apo-B ≤ 90 mg/dL) and HAB (Apo-B ≥ 91 mg/dL) groups, respectively. Vessel, plaque, and %NC volumes were significantly greater in the HAB group than in the LAB group. The %FI, %FF, and %DC volumes were similar in both groups. In all 115 patients, the %NC volume correlated with LDL-C (r = 0.2353, P = 0.0114) and Apo-B (r = 0.2487, P = 0.0074) but not with HDL-C and Apo A-1. The high-sensitivity C-reactive protein level tended to be higher in the HAB group than in the LAB group. Multiple regression analysis showed that being male, Apo-A1, and Apo-B were significant predictors of %NC volume extent. CONCLUSIONS:Elevated Apo-B level was related to the %NC in target coronary artery lesions in SCD patients, suggesting a role of Apo-B as a biomarker of unstable plaque in this population.
10.1371/journal.pone.0212539
Pro-opiomelanocortin and its Processing Enzymes Associate with Plaque Stability in Human Atherosclerosis - Tampere Vascular Study.
Rinne Petteri,Lyytikäinen Leo-Pekka,Raitoharju Emma,Kadiri James J,Kholova Ivana,Kähönen Mika,Lehtimäki Terho,Oksala Niku
Scientific reports
α-melanocyte-stimulating hormone (α-MSH) is processed from pro-opiomelanocortin (POMC) and mediates anti-inflammatory actions in leukocytes. α-MSH also promotes macrophage reverse cholesterol transport by inducing ATP-binding cassette transporters ABCA1 and ABCG1. Here we investigated the regulation of POMC and α-MSH expression in atherosclerosis. First, transcript levels of POMC and its processing enzymes were analyzed in human arterial plaques (n = 68) and non-atherosclerotic controls (n = 24) as well as in whole blood samples from coronary artery disease patients (n = 55) and controls (n = 45) by microarray. POMC expression was increased in femoral plaques compared to control samples as well as in unstable advanced plaques. α-MSH-producing enzyme, carboxypeptidase E, was down-regulated, whereas prolylcarboxypeptidase, an enzyme inactivating α-MSH, was up-regulated in unstable plaques compared to stable plaques, suggesting a possible reduction in intraplaque α-MSH levels. Second, immunohistochemical analyses revealed the presence of α-MSH in atherosclerotic plaques and its localization in macrophages and other cell types. Lastly, supporting the role of α-MSH in reverse cholesterol transport, POMC expression correlated with ABCA1 and ABCG1 in human plaque and whole blood samples. In conclusion, α-MSH is expressed in atherosclerotic plaques and its processing enzymes associate with plaque stability, suggesting that measures to enhance the local bioavailability of α-MSH might protect against atherosclerosis.
10.1038/s41598-018-33523-7
Plasma signature of apoptotic microvesicles is associated with endothelial dysfunction and plaque rupture in acute coronary syndromes.
Zacharia Effimia,Antonopoulos Alexios S,Oikonomou Evangelos,Papageorgiou Nikolaos,Pallantza Zoi,Miliou Antigoni,Mystakidi Vasiliki Chara,Simantiris Spyridon,Kriebardis Anastasios,Orologas Nikolaos,Valasiadi Eftychia,Papaioannou Spyridon,Galiatsatos Nikolaos,Antoniades Charalambos,Tousoulis Dimitris
Journal of molecular and cellular cardiology
OBJECTIVE:Circulating microvesicles (MV) are surrogate biomarkers of atherosclerosis. However, their role in acute coronary syndromes (ACS) has not been fully elucidated yet. We sought to examine the association of circulating apoptotic MVs with ACS pathophysiology. APPROACH AND RESULTS:One hundred and fifty-three patients (n = 153) were included in the study; 49 patients with ST-elevation myocardial infarction (STEMI), 35 with non-STEMI (NSTEMI), 38 with unstable angina, 15 with stable coronary artery disease and 16 control individuals. Flow cytometry analysis was used to quantify circulating apoptotic/non-apoptotic (phospatidyloserine/phospatidyloserine) endothelial cell (EMV), red blood cell (RMV) and platelet (PMV) derived MV. Flow-mediated dilatation (FMD) of the brachial artery was assessed by ultrasound to estimate endothelial function. The inflammatory profile was assessed by serum C-reactive protein (hsCRP) levels. Apoptotic only (but not non-apoptotic) MV were increased in patients with ACS (EMV, P = 2.32 × 10; RMV, P = .0019; PMV, P = .01). Hierarchical clustering of the total population of ACS patients (n = 122) by circulating levels of phospatidyloserine EMV, RMV and PMV identified two discreet clusters of patients without any differences in traditional risk factors, but significant differences in brachial FMD (5.2% (2.5) vs. 4.1% (2.3), P < .05) that remained significant after adjustment for co-variates. The prevalence of STEMI, a surrogate for plaque rupture and vessel thrombotic occlusion, was significantly higher in the patient cluster with impaired endothelial function (60% vs 32%, P = .016, adjusted odds ratio for STEMI, 3.041, 95%CI, 1.160 to 7.968, p = .024). CONCLUSION:Our findings indicate that the circulating levels of apoptotic MV are increased in ACS patients and their plasma profiles associate with endothelial dysfunction and thrombotic complications in ACS patients.
10.1016/j.yjmcc.2019.11.153
The clinical significance of echo-attenuated plaque in stable angina pectoris compared with acute coronary syndromes: A combined intravascular ultrasound and optical coherence tomography study.
Kimura Shigeki,Sugiyama Tomoyo,Hishikari Keiichi,Nakagama Shun,Nakamura Shun,Misawa Toru,Mizusawa Masafumi,Hayasaka Kazuto,Yamakami Yosuke,Sagawa Yuichiro,Kojima Keisuke,Ohtani Hirofumi,Hikita Hiroyuki,Takahashi Atsushi
International journal of cardiology
BACKGROUND:Echo-attenuated plaque (EA) on intravascular ultrasound (IVUS) is related to poor outcomes after percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) patients. However, the clinical significance of EA in stable angina pectoris (SAP) patients compared with that in ACS patients remains unclear. We assessed the relationships between EA and unstable plaque characteristics in patients with ACS and SAP. METHODS:We investigated 609 coronary lesions in 609 patients (234 with ACS; 375 with SAP) undergoing pre-intervention IVUS and optical coherence tomography (OCT). The differences in plaque morphology and post-PCI outcomes were assessed according to the clinical status of ACS or SAP and the presence or absence of EA. RESULTS:EA was more frequent in patients with ACS than in those with SAP (44.0% vs. 25.1%, p < 0.001). SAP-EA lesions showed thicker fibrous cap (157 ± 97 μm vs. 100 ± 58 μm, p < 0.001), smaller lipid arc (208 ± 76° vs. 266 ± 99°, p < 0.001), smaller plaque burden (83.0 ± 6.1% vs. 86.5 ± 4.1%, p < 0.001), and lower frequency of transient slow-reflow phenomenon during PCI (21.3% vs. 51.5%, p < 0.001) than ACS-EA lesions, but similar plaque vulnerability compared with ACS-non-EA lesions. SAP-EA lesions had less frequent OCT-thrombus than ACS-non-EA lesions (20.2% vs. 71.2%, p < 0.001). CONCLUSIONS:SAP-EA lesions had less plaque vulnerability than ACS-EA lesions, but were comparable to ACS-non-EA lesions. Less frequent thrombus formation might differentiate SAP-EA lesions from ACS-non-EA lesions. A combined IVUS and OCT approach might be useful to assess plaque vulnerability in SAP-EA lesions compared with ACS lesions.
10.1016/j.ijcard.2018.05.117
Ultra-rapid progression of coronary artery disease or undiagnosed unstable plaque? A brief review from a case report.
Montenegro Sá Fernando,Ruivo Catarina,Graça Santos Luís,Antunes Alexandre,Campos Soares Francisco,Baptista José,Morais João
Revista portuguesa de cardiologia
Coronary artery disease rarely manifests itself in the first decades of life, which explains why this population is underrepresented in clinical studies. The mechanisms and natural history of the disease seem to differ between this population and older patients. Recent studies suggest a more rapid disease progression in youth, presenting more unstable atherosclerotic plaques, although this correlation has yet to be proven. In this paper, we present the case of a 41-year-old man who presented with a non-ST elevation myocardial infarction, with percutaneous coronary intervention of the culprit lesion (70-90% lesion at bifurcation of the circumflex artery with the first marginal obtuse artery and a sub-occlusive lesion of the ramus intermedius). There was also a non-significant lesion (estimated at 30%) located in the left anterior descending coronary artery. Ten days after discharge, the patient suffered another non-ST elevation myocardial infarction. The coronary angiography revealed a surprising sub-occlusive lesion of the left anterior descending coronary artery. Regarding this case, the authors reviewed the literature on the pathophysiology of rapidly progressive coronary artery disease and the approach for non-significant lesions in patients with acute coronary syndrome, especially in the younger population.
10.1016/j.repc.2017.04.005
High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial.
Puchner Stefan B,Liu Ting,Mayrhofer Thomas,Truong Quynh A,Lee Hang,Fleg Jerome L,Nagurney John T,Udelson James E,Hoffmann Udo,Ferencik Maros
Journal of the American College of Cardiology
BACKGROUND:It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain. OBJECTIVES:The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI). METHODS:We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment. RESULTS:Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis. CONCLUSIONS:In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239).
10.1016/j.jacc.2014.05.039
Abnormal circadian rhythms are associated with plaque instability in acute coronary syndrome patients.
Zhang Zai-Qiang,Ding Jia-Wang,Wang Xin-An,Luo Cai-Yun,Yu Bin,Zheng Xia-Xia,Zhou Tian,Shang Bai-Xue,Tong Xiao-Hong,Zhang Jing
International journal of clinical and experimental pathology
AIM:Acute coronary syndrome (ACS), a leading cause of morbidity and mortality worldwide, is among the most serious cardiovascular diseases. Circadian rhythms are present in almost all organisms. In clinical practice, we have found that ACS is closely related to these circadian rhythms. However, the relationship between circadian rhythms and plaque instability in ACS patients is incompletely understood. The aim of this study is to provide new insights into the relationship between circadian rhythms and plaque instability in ACS patients. METHODS:We enrolled patients with ACS and individuals with normal coronary artery function in this study. The Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), International Physical Activity Questionnaire (IPAQ) and Healthy Diet Score (HDS) were used to evaluate circadian rhythms. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was used to assess the mRNA expression levels of muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 (Bmal1), circadian locomotor output cycles kaput (Clock), Cryptochrome1 (Cry1), Period2 (Per2), nuclear receptor subfamily 1, group D, member 1 (Rev-erbα), and matrix metalloproteinases MMP2 and MMP9. RESULTS:AIS scores and PSQI scores were significantly higher in patients with ST segment elevation myocardial infarction (STEMI), non-ST segment elevation myocardial infarction (NSTEMI), and unstable angina pectoris (UA) than in the normal controls (NCs) (). The IPAQ scores of the NCs and patients with UA were significantly higher than in patients with STEMI and NSTEMI (). Notably higher HDS scores were recorded for the NCs compared to those of patients with UA, NSTEMI, and STEMI (). Consistent with these findings, compared with the NCs, the lowest levels of Bmal1, Clock, Cry1, Per2 and Rev-erbα mRNAs were detected in patients with STEMI, followed by patients with NSTEMI and then patients with UA (). Furthermore, the levels of MMP2 and MMP9 mRNA were significantly higher in the patients with STEMI, NSTEMI, and UA than those in the NCs (). In addition, we found that the levels of MMP mRNA negatively correlated with the levels of clock genes mRNAs (, respectively). CONCLUSIONS:Based on our data, the circadian rhythms and clock genes are correlatively with the occurrence of ACS, and the expression levels of clock genes are negatively correlated with plaque stability in ACS patients.
MicroRNA-24 regulates macrophage behavior and retards atherosclerosis.
Di Gregoli Karina,Jenkins Nicholas,Salter Rebecca,White Stephen,Newby Andrew C,Johnson Jason L
Arteriosclerosis, thrombosis, and vascular biology
OBJECTIVE:Our recent studies have highlighted membrane type-1 matrix metalloproteinase (MMP)-14 as a selective marker for an invasive subset of macrophages potentially related to atherosclerotic plaque progression. Moreover, colony stimulating factors (CSF) may exert divergent effects on macrophage MMP expression, possibly through microRNAs. We, therefore, aim to identify and test the pathophysiological role of microRNAs, which modulate macrophage MMP-14 expression in atherosclerotic plaque progression. APPROACH AND RESULTS:Compared with macrophage CSF-differentiated macrophages, granulocyte/macrophage CSF-matured macrophages exhibited reduced MMP-14 mRNA levels but increased protein expression and activity, which resulted in heightened macrophage invasion. MicroRNA-24, identified to target MMP-14, was accordingly increased in macrophage CSF compared with granulocyte/macrophage CSF macrophages. Silencing microRNA-24 in macrophage CSF macrophages significantly increased MMP-14 expression and enhanced their invasive capacity, mimicking granulocyte/macrophage CSF macrophages, and suggesting that granulocyte/macrophage CSF modulates MMP-14 protein expression and subsequent macrophage invasion in a microRNA-24-dependent manner. In human coronary atherosclerotic plaques, increased MMP-14 protein expression in foam cell macrophages was associated with lesions exhibiting histological characteristics associated with an unstable phenotype. Furthermore, microRNA-24 expression in these atherosclerotic plaques was inversely related to MMP-14 protein expression. Moreover, stable plaques contained higher microRNA-24 levels than unstable plaques, and microRNA-24 colocalized with foam cell macrophages that exhibited low MMP-14 protein expression. Finally, in atherosclerotic mice (apolipoprotein E-deficient), microRNA-24 inhibition increased plaque size and macrophage MMP-14 expression. CONCLUSIONS:Taken together, our data demonstrates that downregulation of microRNA-24 promotes an invasive macrophage subset and plays a novel regulatory role in MMP-14 proteolytic activity and, therefore, plaque stability, highlighting its therapeutic potential.
10.1161/ATVBAHA.114.304088
B Lymphocytes and Macrophages in the Perivascular Adipose Tissue Are Associated With Coronary Atherosclerosis: An Autopsy Study.
Farias-Itao Daniela Souza,Pasqualucci Carlos Augusto,Nishizawa Aline,da Silva Luiz Fernando Ferraz,Campos Fernanda Marinho,Bittencourt Márcio Sommer,da Silva Karen Cristina Souza,Leite Renata Elaine Paraízo,Grinberg Lea Tenenholz,Ferretti-Rebustini Renata Eloah de Lucena,Jacob-Filho Wilson,Suemoto Claudia Kimie
Journal of the American Heart Association
Background Macrophages and T lymphocytes in the perivascular adipose tissue (PvAT) were previously linked to coronary artery disease. However, the role of these cells and B lymphocytes in the human PvAT adjacent to unstable atherosclerotic plaques has not been investigated. Moreover, previous studies were inconclusive on whether PvAT inflammation was restricted to the surroundings of the atheroma plaque. Methods and Results Coronary arteries were freshly dissected with the surrounding PvAT. Atherosclerotic plaques were classified according to the internationally accepted anatomopathological criteria. Immune cells in the PvAT were detected using immunohistochemistry and then quantified. We used linear and logistic regressions with robust standard errors, adjusted for possible confounding factors. In 246 atherosclerotic plaques (205 stable and 41 unstable plaques) from 82 participants (mean age=69.0±14.4 years; 50% men), the percentage of arterial obstruction was positively correlated with the densities of CD68 macrophages (=0.003) and CD20 B lymphocytes (=0.03) in the periplaque PvAT. The number of cells was greater in the periplaque PvAT than in the distal PvAT (macrophages, <0.001; B lymphocytes, =0.04). In addition, the density of macrophages in the periplaque PvAT was greater in the presence of unstable plaques (=0.03) and was also greater near unstable plaques than in the distal PvAT (=0.001). CD3 T lymphocytes were not associated with percentage of obstruction and stable/unstable plaque composition. Conclusions The density of CD20 B lymphocytes and CD68 macrophages in periplaque PvAT was increased with plaque size, and the CD68 macrophages were greater near unstable atherosclerotic plaques than near stable lesions. This inflammation was more intense in the periplaque PvAT than in the PvAT distal to the atherosclerotic plaques.
10.1161/JAHA.119.013793
Effect of Stress, Depression and Type D Personality on Immune System in the Incidence of Coronary Artery Disease.
Masafi Saideh,Saadat Seyed Hassan,Tehranchi Katayoun,Olya Roohollah,Heidari Mostafa,Malihialzackerini Saied,Jafari Mahdi,Rajabi Ehsan
Open access Macedonian journal of medical sciences
BACKGROUND:Psychoneuroimmunology (PNI) is the study of the interaction between psychological processes and the nervous and immune systems of the human body. The impact of psychological factors on the immune system and the role of this system in Coronary Artery Disease (CAD) are confirmed. Coronary Heart Disease (CHD) is arisen due to the failure of blood and oxygen to the heart tissues. AIM:The present study aimed to describe psychoneuroimmunological processes which contribute to CAD and CHD progression. METHOD:Such psychological risk factors like stress, depression and type D personality were investigated here. Psychoneuroimmunological pathways of all three mentioned risk factors were described for CAD. RESULTS:The studies review indicated that stress could be accompanied with myocardial ischemia and help to rupture. The depression involves in the transfer of stable atherosclerotic plaque to unstable, and type D personality is effective in the initial stages of a CAD. CONCLUSION:As more information on cardiovascular immunity becomes available, this will provide a better understanding and thus act as the foundation for the potential development of new treatment strategies for treatment of cardiovascular disorders.
10.3889/oamjms.2018.217
Circulating Microparticles and Coronary Plaque Components Assessed by Virtual Histology Intravascular Ultrasound of the Target Lesion in Patients with Stable Angina.
Min Pil-Ki,Cho Minhee,Hong Sung-Yu,Kim Jong-Youn,Choi Eui-Young,Yoon Young-Won,Lee Byoung Kwon,Hong Bum-Kee,Rim Se-Joong,Kwon Hyuck Moon
PloS one
High levels of microparticles (MPs) circulate in the blood of patients with atherosclerotic diseases where they can serve as potential biomarkers of vascular injury and cardiovascular outcome. We used virtual histology intravascular ultrasound (VH-IVUS) to evaluate the relationship between the levels of circulating MPs and the coronary plaque composition in patients with stable angina. We included 35 patients with stable angina (22 men, age 64 ± 9 years) and a de novo target lesion. Preintervention gray-scale and VH-IVUS analysis was performed across the target lesion. Volumetric analysis was performed over a 10-mm-long segment centered at the minimum luminal site. Blood samples were obtained from the femoral artery before coronary angioplasty. MPs were measured using a solid-phase capture assay from a commercial kit. We divided participants into either a low MPs group or high MPs group based on the median value of MPs. There was no significant difference in baseline characteristics between the groups. The plaque burden and remodeling index were similar between the groups. The presence of VH-IVUS-derived thin-cap fibroatheroma was not different between the groups. The percentage of the necrotic core (NC) was significantly higher in the high MPs group than in the low MPs group, both in planar (17.0 ± 8.8% vs. 24.1 ± 6.9%, p = 0.012) and volumetric analyses (17.0 ± 4.8% vs. 22.1 ± 4.3%, p = 0.002). Circulating MPs were positively correlated with the percentage of the NC area at the minimal luminal site (r = 0.491, p = 0.003) and the percentage of the NC volume (r = 0.496, p = 0.002). Elevated levels of circulating MPs were associated with the amount of NC in the target lesion in those with stable angina, suggesting a potential role of circulating MPs as a biomarker for detecting unstable plaque in patients with stable angina.
10.1371/journal.pone.0148128
Interleukin-5 levels are decreased in the plasma of coronary artery disease patients and inhibit Th1 and Th17 differentiation in vitro.
Ye Di,Wang Zhen,Ye Jing,Wang Menglong,Liu Jianfang,Xu Yao,Jiang Huimin,Chen Jiangbin,Wan Jun
Revista espanola de cardiologia (English ed.)
INTRODUCTION AND OBJECTIVES:Interleukin (IL)-5 is an anti-inflammatory cytokine that has been demonstrated to be involved in cardiovascular diseases, including aortic aneurysm and heart failure. This study aimed to investigate the involvement of IL-5 in coronary artery disease (CAD) and the possible mechanisms. METHODS:We analyzed IL-5 expression in human coronary artery specimens collected from CAD patients and deceased donors. Plasma IL-5, IL-17, and interferon-γ levels in CAD patients were detected using ELISA kits, with samples from chest pain patients (non-CAD) as controls. Mouse CD4T helper (Th) cells were separated, and the effect of IL-5 on Th1, regulatory T cell and Th17 differentiation and mRNA levels of their characteristic cytokines were detected using flow cytometry and reverse transcription-quantitative polymerase chain reaction, respectively. RESULTS:IL-5 was significantly decreased in the coronary plaque of CAD patients compared with the deceased donors group, and IL-5 was mainly derived from macrophages in the coronary artery plaque. Compared with the non-CAD group, plasma IL-5 levels in the CAD groups were significantly lower, and the sequence from high to low was stable angina pectoris, unstable angina pectoris, and acute myocardial infarction. Binary linear regression analysis showed that IL-5 was independently correlated with the occurrence of CAD. Recombinant mouse IL-5 treatment decreased Th1 and Th17 levels and mRNA expression of their characteristic cytokines in oxidized low-density lipoprotein-treated CD4Th cells. CONCLUSION:IL-5 levels were decreased in CAD patients and inhibited oxidized low-density lipoprotein Th1 and Th17 differentiation in vitro.
10.1016/j.rec.2019.07.005
Relation Between Superficial Calcifications and Plaque Rupture: An Optical Coherence Tomography Study.
Zhan Yefei,Zhang Yingying,Hou Jingbo,Lin Guochang,Yu Bo
The Canadian journal of cardiology
BACKGROUND:There are several forms of calcium deposition, which play different roles in the stability of the coronary artery. It remains unknown whether certain calcification morphological characteristics determine rupture of lipid-rich lesions in the same plaque in acute coronary syndrome (ACS). METHODS:We retrospectively analyzed 550 patients with ACS between May 2008 and October 2014, who had undergone preintervention optical coherence tomography (OCT) imaging examination. A total of 78 patients with 78 culprit lipid-rich lesions having superficial calcifications on OCT images were included in this study, among which 45 were ruptured lesions with calcium and 33 were nonruptured lipid-rich lesion with calcium. The smallest depth of calcium (CAL-DEP) was determined, and the morphology of the calcifications and plaques was analyzed during preintervention OCT imaging. RESULTS:The CAL-DEP was significantly thinner in ruptured lesions with calcium than in nonruptured lipid-rich lesion with calcium (median, 50 [interquartile range (IQR), 33-63] μm vs 110 [73-208] μm; P < 0.001) and in myocardial infarction than in unstable angina pectoris patients (median, 57 [IQR, 36-78] μm vs median, 85 [IQR, 43-140] μm; P = 0.045). For lipid-rich calcified plaques, when CAL-DEP was < 63 μm, the lipid-rich lesion was most vulnerable and prone to rupture (sensitivity = 77.8%; specificity = 81.8%; area under the curve: 0.804; P < 0.0001). CONCLUSIONS:Small CAL-DEP in lipid-rich calcified plaques is a morphological characteristic of a vulnerable plaque phenotype. A CAL-DEP ≤ 63 μm is the critical depth of calcification for lipid-rich calcified plaque rupture in patients with ACS.
10.1016/j.cjca.2017.05.003
Non-calcified coronary atherosclerotic plaque characterization by dual energy computed tomography.
Yamak Didem,Panse Prasad,Pavlicek William,Boltz Thomas,Akay Metin
IEEE journal of biomedical and health informatics
Coronary heart disease (CHD) is the most prevalent cause of death worldwide. Atherosclerosis which is the condition of plaque buildup on the inside of the coronary artery wall is the main cause of CHD. Rupture of unstable atherosclerotic coronary plaque is known to be the cause of acute coronary syndrome. Vulnerability of atherosclerotic plaque has been related to a large lipid core covered by a fibrous cap. Non-invasive assessment of plaque characterization is necessary due to prognostic importance of early stage identification. The purpose of this study is to use the additional attenuation data provided by dual energy computed tomography (DECT) for plaque characterization. We propose to train supervised learners on pixel values recorded from DECT monochromatic X-ray and material basis pairs images, for more precise classification of fibrous and lipid plaques. The interaction of the pixel values from different image types is taken into consideration, as single pixel value might not be informative enough to separate fibrous from lipid. Organic phantom plaques scanned in a fabricated beating heart phantom were used as ground truth to train the learners. Our results show that support vector machines, artificial neural networks and random forests provide accurate results both on phantom and patient data.
10.1109/JBHI.2013.2295534
Sex differences in coronary atherosclerosis progression and major adverse cardiac events in patients with suspected coronary artery disease.
Gu Hui,Gao Yang,Wang Haiping,Hou Zhihui,Han Lei,Wang Ximing,Lu Bin
Journal of cardiovascular computed tomography
BACKGROUND:Little is known about the influence of coronary atherosclerosis progression on the risk of major adverse cardiac events (MACE). Similarly, differences between men and women regarding atherosclerosis progression are poorly understood. The purpose of this study was to investigate the progression of coronary atherosclerosis by coronary CT angiography (coronary CTA) in men and women, and to evaluate its prognostic value regarding MACE. METHODS:This study included 1046 patients with suspected coronary artery disease (CAD) who underwent serial coronary CTA because of new or worsening symptoms or because follow-up coronary CTA had been recommended by attending physicians. Coronary atherosclerosis was semi-quantitatively assessed as follows: three-vessel plaque score (TVPS), severe proximal plaque score (SPPS), segment stenosis score (SSS), segment involvement score (SIS), and coronary artery calcium score (CACS). Patients were followed-up regarding the occurrence of MACE, defined as cardiac death, coronary revascularization, nonfatal myocardial infarction and hospitalization due to unstable angina. Follow-up information was gathered by clinical visits or telephone contacts. RESULTS:Follow-up was achieved in 953 (91.1%) patients (63.8% male; mean age, 53.9 ± 9.7 years) with a mean interval of 4.9 ± 1.1 years. MACE occurred in 132 (13.9%) patients. The average interscan time was 2.1 years. Compared with women, men had significantly higher progression of SPPS, SSS and SIS (6.6% vs. 3.5%, 28.0% vs. 18.3%, 26.6% vs. 16.8%, respectively, all P < 0.005). There was a strong association between the progression of SPPS as well as SSS and MACE, both for men (SPPS, HR:2.17, P < 0.001; SSS, HR:1.28, P = 0.023) and women (SPPS, HR:2.75, P < 0.001; SSS, HR:1.19, P = 0.027). CONCLUSIONS:Progression of coronary atherosclerosis as determined by coronary CTA is higher in men than women, it is associated with the risk of future MACE.
10.1016/j.jcct.2017.07.002
Prognostic Value of Coronary CTA in Stable Chest Pain: CAD-RADS, CAC, and Cardiovascular Events in PROMISE.
Bittner Daniel O,Mayrhofer Thomas,Budoff Matt,Szilveszter Balint,Foldyna Borek,Hallett Travis R,Ivanov Alexander,Janjua Sumbal,Meyersohn Nandini M,Staziaki Pedro V,Achenbach Stephan,Ferencik Maros,Douglas Pamela S,Hoffmann Udo,Lu Michael T,
JACC. Cardiovascular imaging
OBJECTIVES:The purpose of this study was to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) to traditional stenosis categories and the coronary artery calcium score (CACS) for predicting cardiovascular events in patients with stable chest pain and suspected coronary artery disease (CAD). BACKGROUND:The 2016 CAD-RADS has been established to standardize the reporting of CAD on coronary CT angiography (CTA). METHODS:PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial participants' CTAs were assessed by a central CT core laboratory for CACS, traditional stenosis-based categories, and modified CAD-RADS grade including high-risk coronary plaque (HRP) features. Traditional stenosis categories and CAD-RADS grade were compared for the prediction of the composite endpoint of death, myocardial infarction, or hospitalization for unstable angina over a median follow-up of 25 months. Incremental prognostic value over traditional risk factors and CACS was assessed. RESULTS:In 3,840 eligible patients (mean age: 60.4 ± 8.2 years; 49% men), 3.0% (115) experienced events. CAD-RADS (concordance statistic [C-statistic] 0.747) had significantly higher discriminatory value than traditional stenosis-based assessments (C-statistic 0.698 to 0.717; all p for comparison ≤0.001). With no plaque (CAD-RADS 0) as the baseline, the hazard ratio (HR) for an event increased from 2.43 (95% confidence interval [CI]: 1.16 to 5.08) for CAD-RADS 1 to 21.84 (95% CI: 8.63 to 55.26) for CAD-RADS 4b and 5. In stepwise nested models, CAD-RADS added incremental prognostic value beyond ASCVD risk score and CACS (C-statistic 0.776 vs. 0.682; p < 0.001), and added incremental value persisted in all CACS strata. CONCLUSIONS:These data from a large representative contemporary cohort of patients undergoing coronary CTA for stable chest pain support the prognostic value of CAD-RADS as a standard reporting system for coronary CTA.
10.1016/j.jcmg.2019.09.012
Lymphocytic myocarditis occurs with myocardial infarction and coincides with increased inflammation, hemorrhage and instability in coronary artery atherosclerotic plaques.
Woudstra Linde,Biesbroek P Stefan,Emmens Reindert W,Heymans Stephane,Juffermans Lynda J,van Rossum Albert C,Niessen Hans W M,Krijnen Paul A J
International journal of cardiology
OBJECTIVE:Although lymphocytic myocarditis (LM) clinically can mimic myocardial infarction (MI), they are regarded as distinct clinical entities. However, we observed a high prevalence (32%) of recent MI in patients diagnosed post-mortem with LM. To investigate if LM changes coronary atherosclerotic plaque, we analyzed in autopsied hearts the inflammatory infiltrate and stability in coronary atherosclerotic lesions in patients with LM and/or MI. METHODS:The three main coronary arteries were isolated at autopsy of patients with LM, with MI of 3-6h old, with LM and MI of 3-6h old (LM+MI) and controls. In tissue sections of atherosclerotic plaque-containing coronary segments inflammatory infiltration, plaque stability, intraplaque hemorrhage and thrombi were determined via (immuno)histological criteria. RESULTS:In tissue sections of those coronary segments the inflammatory infiltrate was found to be significantly increased in patients with LM, LM+MI and MI compared with controls. This inflammatory infiltrate consisted predominantly of macrophages and neutrophils in patients with only LM or MI, of lymphocytes in LM+MI and MI patients and of mast cells in LM+MI patients. Moreover, in LM+MI and MI patients this coincided with an increase of unstable plaques and thrombi. Finally, LM and especially MI and LM+MI patients showed significantly increased intraplaque hemorrhage. CONCLUSIONS:This study demonstrates prevalent co-occurrence of LM with a very recent MI at autopsy. Moreover, LM was associated with remodeling and inflammation of atherosclerotic plaques indicative of plaque destabilization pointing to coronary spasm, suggesting that preexistent LM, or its causes, may facilitate the development of MI.
10.1016/j.ijcard.2017.01.052
Impact of Plaque Composition on Risk of Coronary Artery Diseases in Patients with Carotid Artery Stenosis.
Hamada Saori,Kashiwazaki Daina,Yamamoto Shusuke,Akioka Naoki,Kuwayama Naoya,Kuroda Satoshi
Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association
OBJECT:Recent clinical studies have recently demonstrated a strong association between carotid artery stenosis and coronary artery disease (CAD). However, the clinical impact of carotid plaque composition on CAD remains unclear. This study was aimed to determine the relationship between carotid plaque composition and CAD in patients who underwent carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS:This prospective cohort study included a total of 97 patients who were admitted to our institution between January 2012 and April 2016. Magnetic resonance (MR) imaging was performed to semi-quantitatively analyze the components of carotid plaques by calculating the ratio of plaque intensity to muscle intensity on T1-weighted image. Diagnosis of CAD was based on patient history and clinical examinations during preoperative, postoperative and follow-up periods. Multivariate logistic analysis was performed to determine the risk factors for CAD. The relationship between contralateral plaque composition and CAD was also investigated. RESULTS:Of 97 patients, 33 were diagnosed as having 44 episodes of CAD. Multivariate logistic analysis revealed that ASO (odds ratio [OR], 5.7; 95% confidence interval [CI], 1.8-18.9), contralateral carotid occlusive disease (OR, 6.5; 95%CI, 1.7-22.9), and plaque/muscle ratio (OR, 3.0; 95%CI, 1.4-10.1) were independent factors for predicting CAD. The patients diagnosed as having CAD during the follow-up period had significantly higher plaque/muscle ratio than those with CAD on preoperative evaluations (2.29 ± .21vs. 1.97 ± .33, P < .01). CONCLUSIONS:This study clearly demonstrates that ASO, contralateral carotid artery stenosis, and high-intensity carotid plaque on T1-weighted MRI independently predict CAD. Contralateral carotid plaque composition was also associated with concomitant CAD. Moreover, high-intensity carotid plaque may predict the future development of CAD. Therefore, unstable carotid plaque should be considered as the clinical phenotype of systemic inflammation and a novel, robust marker for future CAD.
10.1016/j.jstrokecerebrovasdis.2018.08.031
Localization of Coronary High-Intensity Signals on T1-Weighted MR Imaging: Relation to Plaque Morphology and Clinical Severity of Angina Pectoris.
Matsumoto Kenji,Ehara Shoichi,Hasegawa Takao,Sakaguchi Mikumo,Otsuka Kenichiro,Yoshikawa Junichi,Shimada Kenei
JACC. Cardiovascular imaging
OBJECTIVES:This study sought to investigate the relationship between localization of high-intensity signals (HISs) on T1-weighted imaging (T1WI) with the noncontrast magnetic resonance technique and plaque morphology detected on optical coherence tomography, and the clinical severity of angina pectoris. BACKGROUND:Since the introduction of the T1WI noncontrast magnetic resonance technique for plaque imaging, some groups have reported that HISs in the coronary artery on T1WI are associated with a vulnerable morphology and future cardiac events. However, the association between the localization of HISs, such as coronary intrawall or intraluminal, and plaque morphology has not been investigated. METHODS:One hundred lesions with either stable or unstable angina were included and divided into 3 groups according to the following criteria using T1WI. First, the plaques with the ratio between the signal intensities of coronary plaque and cardiac muscle ≤1.0 were classified as non-HISs (n = 39). Then, HISs with the ratio between the signal intensities of coronary plaque and cardiac muscle >1.0 were classified into 2 types by using cross-sectional T1WI. Those localized within the coronary wall when the lumen was identified were defined as intrawall HISs (n = 37), whereas those occupying the lumen when the lumen was not, or even if only partly, identified, were defined as intraluminal HISs (n = 24). RESULTS:Multivariate analysis revealed that intrawall HISs were associated with macrophage accumulation and the absence of calcification assessed by using optical coherence tomography. In contrast, thrombus and intimal vasculature were independent factors associated with intraluminal HISs. Furthermore, 50% of patients with intraluminal HISs experienced rest angina, such as Braunwald class II or III. CONCLUSIONS:This study shows that intrawall and intraluminal HISs on T1WI in patients with angina are related to the different types of vulnerable plaque morphology and the clinical severity.
10.1016/j.jcmg.2015.06.013
Prognostic value of computed tomographic coronary angiography and exercise electrocardiography for cardiovascular events.
Kim Kye-Hwan,Jeon Kyung Nyeo,Kang Min Gyu,Ahn Jong Hwa,Koh Jin-Sin,Park Yongwhi,Hwang Seok-Jae,Jeong Young-Hoon,Kwak Choong Hwan,Hwang Jin-Yong,Park Jeong Rang
The Korean journal of internal medicine
BACKGROUND/AIMS:This study is a head-to-head comparison of predictive values for long-term cardiovascular outcomes between exercise electrocardiography (ex-ECG) and computed tomography coronary angiography (CTCA) in patients with chest pain. METHODS:Four hundred and forty-two patients (mean age, 56.1 years; men, 61.3%) who underwent both ex-ECG and CTCA for evaluation of chest pain were included. For ex-ECG parameters, the patients were classified according to negative or positive results, and Duke treadmill score (DTS). Coronary artery calcium score (CACS), presence of plaque, and coronary artery stenosis were evaluated as CTCA parameters. Cardiovascular events for prognostic evaluation were defined as unstable angina, acute myocardial infarction, revascularization, heart failure, and cardiac death. RESULTS:The mean follow-up duration was 2.8 ± 1.1 years. Fifteen patients experienced cardiovascular events. Based on pretest probability, the low- and intermediate-risks of coronary artery disease were 94.6%. Odds ratio of CACS > 40, presence of plaque, coronary stenosis ≥ 50% and DTS ≤ 4 were significant (3.79, p = 0.012; 9.54, p = 0.030; 6.99, p < 0.001; and 4.58, p = 0.008, respectively). In the Cox regression model, coronary stenosis ≥ 50% (hazard ratio, 7.426; 95% confidence interval, 2.685 to 20.525) was only significant. After adding DTS ≤ 4 to coronary stenosis ≥ 50%, the integrated discrimination improvement and net reclassification improvement analyses did not show significant. CONCLUSIONS:CTCA was better than ex-ECG in terms of predicting long-term outcomes in low- to intermediate-risk populations. The predictive value of the combination of CTCA and ex-ECG was not superior to that of CTCA alone.
10.3904/kjim.2015.263
Serum IgE levels in coronary artery disease.
Kounis Nicholas G,Hahalis George
Atherosclerosis
The development and progression of atherosclerosis and its predisposition for unstable angina, myocardial infarction and stroke is associated with traditional risk factors such as family history, cigarette smoking, hypertension, dyslipidemia, diabetes mellitus, obesity, imbalance of the hemostatic/fibrinolytic system and sedentary lifestyle. However, much of the variability in atherosclerosis and its manifestations still remains unexplained. Nowadays, there is increasing evidence that immunologic mechanisms play a major role in etiology, prediction of coronary plaque instability and foreseeing severe reaction leading to an actual coronary event. Cells of the immune system such as macrophages, mast cells and T-lymphocytes are major components of human atheromatous plaque. These cells participate in a vicious immune cycle and activate each others via bidirectional stimuli. For example, mast cells can activate macrophages and may enhance T-cell activation. Inducible macrophage protein 1a may activate mast cells, while CD169+ macrophages activate CD8 T cells. T cells may mediate mast-cell activation and proliferation and regulate macrophage activity. Mediators secreted by these cells, including histamine, neutral proteases, arachidonic acid products, platelet activating factor and a variety of cytokines and chemokines, can induce coronary artery spasm and atheromatous plaque erosion and rupture, culminating in the development of acute coronary syndromes.
10.1016/j.atherosclerosis.2016.05.045
Coronary computed tomography angiography derived risk score in predicting cardiac events.
Uusitalo Valtteri,Kamperidis Vasileios,de Graaf Michiel A,Maaniitty Teemu,Stenström Iida,Broersen Alexander,Dijkstra Jouke,Scholte Arthur J,Saraste Antti,Bax Jeroen J,Knuuti Juhani
Journal of cardiovascular computed tomography
BACKGROUND:We evaluated the prognostic value of an integrated atherosclerosis risk score combining the markers of coronary plaque burden, location and composition as assessed by computed tomography angiography (CTA). METHODS:922 consecutive patients underwent CTA for suspected coronary artery disease (CAD). Patients without atherosclerosis (n = 261) and in whom quantitative CTA analysis was not feasible due to image quality, step-artefacts or technical factors related to image acquisition or data storage (n = 153) were excluded. Thus, final study group consisted of 508 patients aged 63 ± 9 years. Coronary plaque location, severity and composition for each coronary segment were identified using automated CTA quantification software and integrated in a single CTA score (0-42). Adverse events (AE) including death, myocardial infarction (MI) and unstable angina (UA) were obtained from the national healthcare statistics. RESULTS:There were a total of 20 (4%) AE during a median follow-up of 3.6 years (9 deaths, 5 MI and 6 UA). The CTA risk score was divided into tertiles: 0-6.7, 6.8-14.8 and > 14.8, respectively. All MI (n = 5) and most of the other AE occurred in the highest risk score tertile (3 vs. 3 vs. 14, p = 0.002). After correction for age and gender, the CTA risk score remained independently associated with AE. CONCLUSIONS:Comprehensive CTA risk score integrating the location, burden and composition of coronary atherosclerosis predicts future cardiac events in patients with suspected CAD.
10.1016/j.jcct.2017.04.010
Recurrent acute coronary syndrome and mechanisms of plaque instability.
Di Vito Luca,Niccoli Giampaolo,Porto Italo,Vergallo Rocco,Gatto Laura,Prati Francesco,Crea Filippo
International journal of cardiology
Patients with an acute coronary syndrome (ACS) due to plaque rupture had a worse prognosis when compared with those without plaque rupture with a higher rate of target vessel revascularization and readmission for unstable angina, suggesting that both stent failure and disease progression occur more frequently. However, it is not known whether recurrent episodes of coronary instability in the same patient are caused by the same pathogenetic mechanism. Thus, we sought to investigate the mechanisms of coronary instability imaged by optical coherence tomography in patients with recurrent ACS events. The present case series, with 4 patients having recurrent ACS, shows that the same mechanism of coronary instability is present during both first and recurrent instability. This hypothesis-generating finding may support further studies targeted at assessing the mechanisms of coronary instability recurrence and how to tailor preventive measures to the underlying mechanism of instability.
10.1016/j.ijcard.2017.05.121
Perivascular Adipose Tissue Inflammation and Coronary Artery Disease: An Autopsy Study Protocol.
Farias-Itao Daniela Souza,Pasqualucci Carlos Augusto,Nishizawa Aline,Silva Luiz Fernando Ferraz,Campos Fernanda Marinho,Silva Karen Cristina Souza da,Leite Renata Elaine Paraizo,Grinberg Lea Tenenholz,Ferretti-Rebustini Renata Eloah Lucena,Jacob Filho Wilson,Suemoto Claudia Kimie
JMIR research protocols
BACKGROUND:Perivascular adipose tissue (PAT) inflammation may have a role in coronary artery disease (CAD) pathophysiology. However, most evidence has come from samples obtained during surgical procedures that may imply in some limitations. Moreover, the role of B lymphocytes and inflammation in PAT that is adjacent to unstable atheroma plaques has not been investigated in humans using morphometric measurements. OBJECTIVE:The objective of this study is to investigate the inflammation in PAT, subcutaneous, and perirenal adipose tissues (SAT and PrAT) among chronic CAD, acute CAD, and control groups in an autopsy study. METHODS:Heart, SAT, and PrAT samples are collected from autopsied subjects in a general autopsy service, with the written informed consent of the next-of-kin (NOK). Sociodemographic and clinical data are obtained from a semistructure interview with the NOK. Coronary arteries are dissected and PAT are removed. Sections with the greatest arterial obstruction or unstable plaques, and the local with absence of atherosclerosis in all coronary arteries are sampled. PAT are represented adjacent to these fragments. Adipose tissues are fixed in 4% buffered paraformaldehyde solution and analyzed immunohistochemically for macrophages (CD68), macrophage polarization (CD11c for proinflammatory and CD206 for anti-inflammatory), B lymphocytes (CD20), and T lymphocytes (CD3). Slides will be scanned, and inflammatory cells will be quantified in 20 random fields. Participants will be categorized in CAD groups, after morphometric measurement of arterial obstruction and plaque composition analysis in accordance with American Heart Association classification. Three study groups will be investigated: acute CAD (at least one unstable plaque); chronic CAD (≥50% arterial obstruction); and controls (<50% arterial obstruction). Inflammatory cells in PAT, SAT, and PrAT will be counted and compared between groups using multivariate linear regression, adjusted for age, body mass index, hypertension, diabetes, alcohol use, and smoking. RESULTS:We present the methods of our study that was developed from 2 pilots. Currently, data collection and tissue processing are ongoing. Data collection, histology and immunochemistry procedures, and quantification of all inflammatory cells are expected to be concluded within 1 year. CONCLUSIONS:This study will contribute for the understanding of the mechanisms of CAD pathophysiology because it will help to clarify the role of inflammation both in chronic and acute CAD.
10.2196/resprot.6340
Plaque rupture and intact fibrous cap assessed by optical coherence tomography portend different outcomes in patients with acute coronary syndrome.
Niccoli Giampaolo,Montone Rocco A,Di Vito Luca,Gramegna Mario,Refaat Hesham,Scalone Giancarla,Leone Antonio M,Trani Carlo,Burzotta Francesco,Porto Italo,Aurigemma Cristina,Prati Francesco,Crea Filippo
European heart journal
AIMS:Patients presenting with acute coronary syndrome (ACS) may have different plaque morphologies at the culprit lesion. In particular, plaque rupture (PR) has been shown as the more frequent culprit plaque morphology in ACS. However, its prognostic value is still unknown. In this study, we evaluated the prognostic value of PR, compared with intact fibrous cap (IFC), in patients with ACS. METHODS AND RESULTS:We enrolled consecutive patients admitted to our Coronary Care Unit for ACS and undergoing coronary angiography followed by interpretable optical coherence tomography (OCT) imaging. Culprit lesion was classified as PR and IFC by OCT criteria. Prognosis was assessed according to such culprit lesion classification. Major adverse cardiac events (MACEs) were defined as the composite of cardiac death, non-fatal myocardial infarction, unstable angina, and target lesion revascularization (follow-up mean time 31.58 ± 4.69 months). The study comprised 139 consecutive ACS patients (mean age 64.3 ± 12.0 years, male 73.4%, 92 patients with non-ST elevation ACS and 47 with ST-elevation ACS). Plaque rupture was detected in 82/139 (59%) patients. There were no differences in clinical, angiographic, or procedural data between patients with PR when compared with those having IFC. Major adverse cardiac events occurred more frequently in patients with PR when compared with those having IFC (39.0 vs. 14.0%, P = 0.001). Plaque rupture was an independent predictor of outcome at multivariable analysis (odds ratio 3.735, confidence interval 1.358-9.735). CONCLUSION:Patients with ACS presenting with PR as culprit lesion by OCT have a worse prognosis compared with that of patients with IFC. This finding should be taken into account in risk stratification and management of patients with ACS.
10.1093/eurheartj/ehv029
AMPKα inactivation destabilizes atherosclerotic plaque in streptozotocin-induced diabetic mice through AP-2α/miRNA-124 axis.
Liang Wen-Jing,Zhou Sheng-Nan,Shan Mei-Rong,Wang Xue-Qin,Zhang Miao,Chen Yuan,Zhang Yun,Wang Shuang-Xi,Guo Tao
Journal of molecular medicine (Berlin, Germany)
Diabetes mellitus is one of risk factors of cardiovascular diseases including atherosclerosis. Whether and how diabetes promotes the formation of unstable atherosclerotic plaque is not fully understood. Here, we show that streptozotocin-induced type 1 diabetes reduced collagen synthesis, leading to the formation of unstable atherosclerotic plaque induced by collar placement around carotid in apolipoprotein E knockout (Apoe) mice. These detrimental effects of hyperglycemia on plaque stability were reversed by metformin in vivo without altering the levels of blood glucose and lipids. Mechanistically, we found that high glucose reduced the phosphorylated level of AMP-activated protein kinase alpha (AMPKα) and the transcriptional activity of activator protein 2 alpha (AP-2α), increased the expression of miR-124 expression, and downregulated prolyl-4-hydroxylase alpha 1 (P4Hα1) protein expression and collagen biosynthesis in cultured vascular smooth muscle cells. Importantly, these in vitro effects produced by high glucose were abolished by AMPKα pharmacological activation or adenovirus-mediated AMPKα overexpression. Further, adenovirus-mediated AMPKα gain of function remitted the process of diabetes-induced plaque destabilization in Apoe mice injected with streptozotocin. Administration of metformin enhanced pAP-2α level, reduced miR-124 expression, and increased P4Hα1 and collagens in carotid atherosclerotic plaque in diabetic Apoe mice. We conclude that streptozotocin-induced toxic diabetes promotes the formation of unstable atherosclerotic plaques based on the vulnerability index in Apoe mice, which is related to the inactivation of AMPKα/AP-2α/miRNA-124/P4Hα1 axis. Clinically, targeting AMPKα/AP-2α/miRNA-124/P4Hα1 signaling should be considered to increase the plaque stability in patients with atherosclerosis. KEY MESSAGES:Hyperglycemia reduced collagen synthesis, leading to the formation of unstable atherosclerotic plaque induced by collar placement around carotid in apolipoprotein E knockout mice. Hyperglycemia destabilizes atherosclerotic plaque in vivo through an AMPKα/AP-2α/miRNA-124/P4Hα1-dependent collagen synthesis. Metformin functions as a stabilizer of atherosclerotic plaque to reduce acute coronary accent.
10.1007/s00109-018-1627-8
Immunohistochemical Features of Different Types of Unstable Atherosclerotic Plaques of Coronary Arteries.
Murashov I S,Volkov A M,Kazanskaya G M,Kliver E E,Chernyavsky A M,Nikityuk D B,Lushnikova E L
Bulletin of experimental biology and medicine
We performed a complex morphological study of samples of different types of unstable atherosclerotic plaques obtained from 33 men with occlusive coronary atherosclerosis, who underwent coronary artery endarterectomy during coronary artery bypass surgery. In the samples, expression of MMP-2 and MMP-9, collagen IV, CD31, CD34, factor VIII, and actin of smooth muscle cells was evaluated by morphometric and immunohistochemical methods. The maximum expression of MMP-9 was found in unstable plaques of the lipid type, where it 1.4- and 1.24-fold surpassed the corresponding levels in plaques of the inflammatory-erosive and degenerative-necrotic types. Unstable plaques of the degenerative-necrotic type are characterized by the most intensive expression of collagen IV in comparison with plaques of the inflammatory-erosive and lipid types (by 2.8 and 2.2 times, respectively). The maximum neovascularization was detected in inflammatory-erosive plaques, which was confirmed by enhanced expression of CD31 and CD34 markers in comparison with plaques of the lipid (by 7.6 and 18.95 times, respectively) and degenerative-necrotic (by 31.1 and 39.8 times) types.
10.1007/s10517-018-4297-1
Myeloperoxidase is a potential molecular imaging and therapeutic target for the identification and stabilization of high-risk atherosclerotic plaque.
Rashid Imran,Maghzal Ghassan J,Chen Yung-Chih,Cheng David,Talib Jihan,Newington Darren,Ren Minqin,Vajandar Saumitra K,Searle Amy,Maluenda Ana,Lindstedt Eva-Lotte,Jabbour Andrew,Kettle Antony J,Bongers Andre,Power Carl,Michaëlsson Erik,Peter Karlheinz,Stocker Roland
European heart journal
Aims:As the inflammatory enzyme myeloperoxidase (MPO) is abundant in ruptured human atherosclerotic plaques, we aimed to investigate the role of MPO as a potential diagnostic and therapeutic target for high-risk plaque. Methods and results:We employed the tandem stenosis model of atherosclerotic plaque instability in apolipoprotein E gene knockout (Apoe-/-) mice. To test the role of MPO, we used Mpo-/-Apoe-/- mice and the 2-thioxanthine MPO inhibitor AZM198. In vivo MPO activity was assessed by liquid chromatography-tandem mass spectrometry detection of 2-chloroethidium generation from hydroethidine and by bis-5HT-DTPA-Gd (MPO-Gd) molecular magnetic resonance imaging (MRI), while plaque phenotype was verified histologically. Myeloperoxidase activity was two-fold greater in plaque with unstable compared with stable phenotype. Genetic deletion of MPO significantly increased fibrous cap thickness, and decreased plaque fibrin and haemosiderin content in plaque with unstable phenotype. AZM198 inhibited MPO activity and it also increased fibrous cap thickness and decreased fibrin and haemosiderin in plaque with unstable phenotype, without affecting lesion monocytes and red blood cell markers or circulating leukocytes and lipids. MPO-Gd MRI demonstrated sustained enhancement of plaque with unstable phenotype on T1-weighted imaging that was two-fold greater than stable plaque and was significantly attenuated by both AZM198 treatment and deletion of the Mpo gene. Conclusion:Our data implicate MPO in atherosclerotic plaque instability and suggest that non-invasive imaging and pharmacological inhibition of plaque MPO activity hold promise for clinical translation in the management of high-risk coronary artery disease.
10.1093/eurheartj/ehy419
Potential clinical utility of macrophage colony-stimulating factor, monocyte chemotactic protein-1 and myeloperoxidase in predicting atherosclerotic plaque instability.
Viktorinova Alena
Discovery medicine
Coronary artery diseases (CAD) are the most common cause of morbidity and mortality despite significant advances in their treatment. Therefore, current research focuses on identifying at-risk individuals with vulnerable atherosclerotic plaques in coronary arteries prior to its rupture. This requires to determine specific biomarkers that can not only detect active vulnerable plaque, but also monitor the risk of its progression and rupture. Various biomolecules, from the foam cell formation to plaque rupture, are released into the blood plasma and may serve as biomarkers of atherogenesis. This review provides an up-to-date overview of some biomolecules released from activated macrophages with a focus on their potential utility for clinical practice. It is important that these biomarkers can distinguish patients with stable, inactive plaques from those with unstable, active plaques, and also predict an increased risk of acute coronary events. Special attention was focused on the selected myeloid markers of atherosclerosis and plaque instability, including macrophage colony-stimulating factor (M-CSF), monocyte chemotactic protein-1 (MCP-1), and myeloperoxidase (MPO), which are released from activated leukocytes into blood plasma. Changed plasma levels of these biomarkers can indicate an acute phase of plaque destabilization. This makes it possible not only to measure their plasma concentrations using available biochemical laboratory methods, but also to apply them in clinical practice. In addition, the discussed biomarkers could be a potential therapeutic target leading to a reduction in premature morbidity and mortality of CAD.
Molecular Imaging of Inflammation in Ischemic Heart Disease.
Current cardiovascular imaging reports
PURPOSE OF REVIEW:. Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. . This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease. RECENT FINDINGS:A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging. SUMMARY:While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed.
10.1007/s12410-018-9452-6
Multimodality imaging of attenuated plaque using grayscale and virtual histology intravascular ultrasound and optical coherent tomography.
Kang Soo-Jin,Ahn Jung-Min,Han Seungbong,Park Duk-Woo,Lee Seung-Whan,Kim Young-Hak,Lee Cheol Whan,Park Seong-Wook,Mintz Gary S,Park Seung-Jung
Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions
BACKGROUND:Although attenuated plaque is a marker for plaque vulnerability, the quantification and its implication have not been known. METHODS:Multimodality pre-procedural imaging using grayscale intravascular ultrasound (IVUS), virtual histology-IVUS (VH-IVUS), and optical coherence tomography (OCT) were performed in 115 coronary lesions with diameter stenosis (DS) >30% and plaque burden ≥50% and compared the diagnostic accuracies for detecting thin-cap fibroatheromas (TCFA). RESULTS:A maximal arc of attenuation (40 MHz IVUS) ≥29.0° was the cutoff for predicting VH-TCFA (sensitivity 74%, specificity 66%); and OCT-TCFA (sensitivity 89%, specificity 64%), while a maximal arc attenuation ≥29.0° (20MHz IVUS) showed a poor sensitivity for predicting TCFA. Compared to the lesions with an arc of attenuation <30° as a rough cutoff value, the lesions with a maximum arc of attenuation ≥30° (40 MHz) were associated with more severe (smaller angiographic minimum lumen diameter and greater DS, smaller IVUS-MLA and a larger plaque burden) and had more unstable lesion characteristics: (1) larger remodeling index and more plaque ruptures (grayscale IVUS); (2) greater %necrotic core and more VH-TCFAs (VH-IVUS); and (3) more lipid, macrophages, cholesterol crystals, and microchannels; thinner fibrous caps; and more OCT-TCFAs, OCT-detected plaque ruptures, and red and white thrombi (OCT). Among 58 patients treated with stent implantation, postintervention peak CK-MB was higher in patients with the maximal attenuation ≥30° compared to those without (median 2.7 ng/ml [IQR 0.9-18.7 ng/ml] vs. median 0.9 ng/ml [IQR 0.7-2.1 ng/ml], P = 0.012). CONCLUSION:Attenuated plaque with a maximal attenuation ≥30° vs. <30° (40 MHz, but not 20 MHz IVUS) were more likely to be associated with unstable lesion morphology that may contribute to the immediate poststenting CK-MB elevation. © 2016 Wiley Periodicals, Inc.
10.1002/ccd.25786
RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease.
Holvoet Paul,Klocke Bernward,Vanhaverbeke Maarten,Menten Roxane,Sinnaeve Peter,Raitoharju Emma,Lehtimäki Terho,Oksala Niku,Zinser Christian,Janssens Stefan,Sipido Karin,Lyytikainen Leo-Pekka,Cagnin Stefano
PloS one
Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.
10.1371/journal.pone.0225621
Association of target lesion characteristics evaluated by coronary computed tomography angiography and plaque debris distal embolization during percutaneous coronary intervention.
Nishio Mayu,Ueda Yasunori,Matsuo Koshi,Tsujimoto Masahiko,Hao Hiroyuki,Asai Mitsutoshi,Nemoto Takayoshi,Wada Mitsuru,Hirata Akio,Murakami Ayaka,Kashiwase Kazunori,Kodama Kazuhisa
Circulation journal : official journal of the Japanese Circulation Society
BACKGROUND:The slow-flow or no re-flow phenomenon has been associated with distal embolization, especially of plaque debris, and with unfavorable clinical outcomes. Therefore, we examined the association between the coronary computed tomography angiography (CCTA) findings of the target lesion and distal embolization during percutaneous coronary intervention (PCI). METHODS AND RESULTS: Consecutive patients (n=55: 18 unstable angina, 19 stable effort angina, 18 silent ischemia) who underwent PCI with a filter-type distal protection device after evaluation of the target lesion by CCTA were analyzed. CCTA examined low-attenuation plaque (LAP), positive remodeling (PR), and ring-like enhancement of the target lesion. Distal embolization of thrombus and plaque debris was evaluated by pathological examination of material collected in the filter.Any distal embolization and distal embolization of plaque debris were respectively detected in 75% and 0% of patients with LAP or PR alone, in 95% and 17% of patients with both LAP and PR, and in 100% and 27% of patients with all of LAP, PR and ring-like enhancement. The sensitivity and specificity to predict plaque debris embolization by having both findings of LAP and PR was 100% and 46%, respectively. CONCLUSIONS:The CCTA findings of the target lesion were associated with distal embolization and were very sensitive for predicting plaque debris embolization.
Association between serum N-terminal pro-B-type natriuretic peptide levels and characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography.
Gan Lu,Feng Cong,Liu Chunlei,Tian Shuping,Song Xiang,Yang Li
Experimental and therapeutic medicine
The aim of the present study was to explore the association between the levels of serum N-terminal pro-B-type natriuretic peptide (NT-pro BNP) and the characteristics of coronary atherosclerotic plaque detected by coronary computed tomography angiography (CCTA), in patients with unstable angina (UA). A total of 202 patients (age range, 47-82 years) were divided into the following three groups: Non-cardiac disease group (57 patients); stable angina pectoris (SAP) group (62 patients); and UA group (83 patients). There were significant differences between the serum NT-pro BNP levels among the three groups (P=0.007). However, in multivariant diagnoses, NT-pro BNP level was not an independent risk factor for UA. The levels of serum NT-pro BNP were observed to be positively correlated with the number of vessels involved (r=0.462; P<0.001), SIS (r=0.475; P<0.001), segment-stenosis score (r=0.453; P<0.001), coronary calcification score (r=0.412; P=0.001), number of obstructive diseases (r=0.346; P<0.001), and the number of segments with non-calcified plaque (r=0.235; P=0.017), mixed plaque (r=0.234; P=0.017) and calcified plaque (r=0.431; P<0.001). The levels of serum NT-pro BNP were significantly higher in patients with UA and left main-left anterior descending (LM-LAD) disease, compared with UA patients without LM-LAD disease (P<0.001). In addition, serum NT-pro BNP was significantly higher in patients with obstructive disease and UA than in those without obstructive disease (P<0.001). The area under the curve of log(NT-pro BNP) was 0.656 (P=0.006; optimal cut-off value, 1.74; sensitivity, 77.6%; specificity, 51.9%). In conclusion, the levels of serum NT-pro BNP are associated with the burden and severity of coronary artery atherosclerotic disease in patients with UA, and may be helpful in risk stratification of patients with UA.
10.3892/etm.2016.3371
Comparison of quantitative atherosclerotic plaque burden from coronary CT angiography in patients with first acute coronary syndrome and stable coronary artery disease.
Dey Damini,Achenbach Stephan,Schuhbaeck Annika,Pflederer Tobias,Nakazato Ryo,Slomka Piotr J,Berman Daniel S,Marwan Mohamed
Journal of cardiovascular computed tomography
BACKGROUND:Coronary CTA allows characterization of non-calcified and calcified plaque and identification of high-risk plaque features. OBJECTIVE:We aimed to quantitatively characterize and compare coronary plaque burden from CTA in patients with a first acute coronary syndrome (ACS) and controls with stable coronary artery disease. MATERIALS AND METHODS:We retrospectively analyzed consecutive patients with non-ST-segment elevation myocardial infarction (NSTEMI) or unstable angina with a first ACS, who underwent CTA as part of their initial workup before invasive coronary angiography and age- and gender-matched controls with stable chest pain; controls also underwent CTA with subsequent invasive angiography (total n = 28). Culprit arteries were identified in ACS patients. Coronary arteries were analyzed by automated software to quantify calcified plaque (CP), noncalcified plaque (NCP), and low-density NCP (LD-NCP, attenuation <30 Hounsfield units) volumes, and corresponding burden (plaque volume × 100%/vessel volume), stenosis, remodeling index, contrast density difference (maximum percent difference in attenuation/cross-sectional area from proximal cross-section), and plaque length. RESULTS:ACS patients had fewer lesions (median, 1), with higher total NCP and LD-NCP burdens (NCP: 57.4% vs 41.5%; LD-NCP: 12.5% vs 8%; P ≤ .04), higher maximal stenoses (85.6% vs 53.0%; P = .003) and contrast density differences (46.1 vs 16.3%; P < .006). Per-patient CP burden was not different between ACS and controls. NCP and LD-NCP plaque burden was higher in culprit vs nonculprit arteries (NCP: 57.8% vs 9.5%; LD-NCP: 8.4% vs 0.6%; P ≤ .0003); CP was not significantly different. Culprit arteries had increased plaque lengths, remodeling indices, stenoses, and contrast density differences (46.1% vs 10.9%; P ≤ .001). CONCLUSION:Noninvasive quantitative coronary artery analysis identified several differences for ACS, both on per-patient and per-vessel basis, including increased NCP, LD-NCP burden, and contrast density difference.
10.1016/j.jcct.2014.07.007
Netrin-1 and the Grade of Atherosclerosis Are Inversely Correlated in Humans.
Bruikman Caroline S,Vreeken Dianne,Hoogeveen Renate M,Bom Michiel J,Danad Ibrahim,Pinto-Sietsma Sara-Joan,van Zonneveld Anton Jan,Knaapen Paul,Hovingh G Kees,Stroes Erik S G,van Gils Janine M
Arteriosclerosis, thrombosis, and vascular biology
OBJECTIVE:Netrin-1 has been shown to play a role in the initiation of atherosclerosis in mice models. However, little is known about the role of Netrin-1 in humans. We set out to study whether Netrin-1 is associated with different stages of atherosclerosis. Approach and Results: Plasma Netrin-1 levels were measured in different patient cohorts: (1) 22 patients with high cardiovascular risk who underwent arterial wall inflammation assessment using positron-emission tomography / computed tomography, (2) 168 patients with a positive family history of premature atherosclerosis in whom coronary artery calcium scores were obtained, and (3) 104 patients with chest pain who underwent coronary computed tomography angiography imaging to evaluate plaque vulnerability and burden. Netrin-1 plasma levels were negatively correlated with arterial wall inflammation (β, -0.01 [95% CI, 0.02 to -0.01] , 0.61; <0.0001), and concentrations of Netrin-1 were significantly lower when atherosclerosis was present compared with individuals without atherosclerosis (28.01 versus 10.51 ng/mL, <0.001). There was no difference in Netrin-1 plasma concentrations between patients with stable versus unstable plaques (11.17 versus 11.74 ng/mL, =0.511). However, Netrin-1 plasma levels were negatively correlated to total plaque volume (β, -0.09 [95% CI, -0.11 to -0.08] , 0.57, <0.0001), calcified plaque volumes (β, -0.10 [95% CI, -0.12 to -0.08] , 0.53; <0.0001), and noncalcified plaque volumes (β, -0.08 [95% CI, -0.10 to -0.06] , 0.41; <0.0001). Treatment of inflammatory stimulated endothelial cells with plasma with high Netrin-1 level resulted in reduced endothelial inflammation and consequently, less monocyte adhesion. CONCLUSIONS:Netrin-1 plasma levels are lower in patients with subclinical atherosclerosis and in patients with arterial wall inflammation. Netrin-1 is not associated with plaque vulnerability; however, it is negatively correlated to plaque burden, suggesting that Netrin-1 is involved in some, but not all, stages of atherosclerosis.
10.1161/ATVBAHA.119.313624
Mast cells are increased in the media of coronary lesions in patients with myocardial infarction and may favor atherosclerotic plaque instability.
Kupreishvili Koba,Fuijkschot Wessel W,Vonk Alexander B A,Smulders Yvo M,Stooker Wim,Van Hinsbergh Victor W M,Niessen Hans W M,Krijnen Paul A J
Journal of cardiology
OBJECTIVES:Mast cells (MCs) may play an important role in plaque destabilization and atherosclerotic coronary complications. Here, we have studied the presence of MCs in the intima and media of unstable and stable coronary lesions at different time points after myocardial infarction (MI). METHODS:Coronary arteries were obtained at autopsy from patients with acute MI (up to 5 days old; n=27) and with chronic MI (5-14 days old; n=18), as well as sections from controls without cardiac disease (n=10). Herein, tryptase-positive MCs were quantified in the intima and media of both unstable and stable atherosclerotic plaques in infarct-related and non-infarct-related coronary arteries. RESULTS:In the media of both acute and chronic MI patients, the number of MCs was significantly higher than in controls. This was also found when evaluating unstable and stable plaques separately. In patients with chronic MI, the number of MCs in unstable lesions was significantly higher than in stable lesions. This coincided with a significant increase in the relative number of unstable plaques in patients with chronic MI compared with control and acute MI. No differences in MC density were found between infarct-related and non-infarct-related coronary arteries in patients with MI. CONCLUSION:The presence of MCs in the media of both stable and unstable atherosclerotic coronary lesions after MI suggests that MCs may be involved in the onset of MI and, on the other hand, that MI triggers intra-plaque infiltration of MCs especially in unstable plaques, possibly increasing the risk of re-infarction.
10.1016/j.jjcc.2016.04.018
Circulating CD36 and fractalkine levels are associated with vulnerable plaque progression in patients with unstable angina pectoris.
Li Rui Jian,Yang Ming,Li Ji Fu,Xue Li,Chen Yu Guo,Chen Wen Qiang
Clinical and experimental pharmacology & physiology
The chemokine, fractalkine, independently enhances the vulnerability of coronary atherosclerotic plaques. The present study investigated the combined effects of CD36 and fractalkine on coronary plaque progression in patients with unstable angina pectoris. In the present study, 120 unstable angina pectoris patients undergoing coronary angiography and intravascular ultrasound were divided into two groups: an intermediate lesion group (lumen diameter stenosis 50-70%, 80 patients) and a severe lesion group (at least one lesion with lumen diameter stenosis > 70%, 40 patients). The control group consisted of 40 healthy age- and sex-matched subjects. Concentrations of CD36 and fractalkine were measured by enzyme-linked immunosorbent assay. Major adverse cardiovascular events were monitored over a 2-year follow up. Intravascular ultrasound showed that patients with severe lesions had more calcified and mixed plaques, and a larger plaque area and plaque burden than patients with intermediate lesions (P < 0.05-0.01). More patients with severe lesions underwent stent deployment (P < 0.05) than those with intermediate lesions. CD36 and fractalkine concentrations were significantly higher in the severe lesion patients (P < 0.05), and both had significant positive correlations (P < 0.05) with the plaque burden of atherosclerotic lesions. Using the matched nested case-control study, we found that CD36 and fractalkine levels were higher in patients with recurrent major adverse cardiovascular events than controls (P < 0.05). In conclusion, CD36 and fractalkine both promote, and might synergistically enhance, the progression of coronary atherosclerotic plaques.
10.1111/1440-1681.12302
Targeting therapy to the fibrin-mediated pathophysiology of acute coronary syndrome.
White Harvey
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
Acute coronary syndrome (ACS) encompasses a spectrum of diseases, ranging from ST-elevation myocardial infarction to non-ST-elevation myocardial infarction and unstable angina. A key initiating event in the pathology of ACS is atheromatous plaque disruption, in which the exposure of thrombogenic material triggers simultaneous activation of primary and secondary hemostatic pathways. Targeting platelet-mediated thrombus formation with dual antiplatelet therapy comprising acetylsalicylic acid and a P2Y12 antagonist is the current mainstay for management of ACS. However, a significant proportion of patients remain at risk of cardiovascular events. Fibrin is an important contributor to thrombogenesis and may account for the residual event rates. This review examines evidence for the role of the coagulation cascade in thrombus formation in ACS, which provides a rationale for the use of anticoagulation therapy. The current status of research with novel oral anticoagulants in combination with dual antiplatelet therapy for the secondary prevention of ACS is also discussed.
10.1177/1076029612472551
AG1296 enhances plaque stability via inhibiting inflammatory responses and decreasing MMP-2 and MMP-9 expression in ApoE-/- mice.
Dong Min,Zhou Changping,Ji Liang,Pan Bing,Zheng Lemin
Biochemical and biophysical research communications
BACKGROUND:Atherosclerosis is a chronic process that progresses to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, thrombosis and stroke. AG1296 is a potent tyrosine kinase inhibitor which is able to block PDGF-PDGFR signaling pathway. This study aims to assess the effect of AG1296 on plaque stability and explore the potential mechanisms. METHODS:Atherosclerotic plaques were induced in carotid arteries in ApoE-/- mice by perivascular collar placement. All mice were randomly divided into PBS and AG1296 groups. 3 weeks after the surgery, the carotid arteries were harvested for histological analysis. RESULTS:In AG1296 group, plaque area decreased by 41.5% (p = 0.0041) and the contents of macrophages and lipids decreased by 43.5% (p = 0.0003) and 35.6% (p = 0.0032) respectively. The contents of smooth muscle cells increased by 22.3% (p = 0.0214) in AG1296 group. Vulnerable index decreased by 48.3% (p = 0.0002). The inflammation factors IL-6 and TNF- alpha decreased by 49.0% (p = 0.0008) and 51.8% (p < 0.0001) and matrix metalloproteinases MMP-2 and MMP-9 decreased by 54.1% (p = 0.0004) and 37.1% (p < 0.0001) in AG1296 group. M1 macrophage markers (MCP-1) were downregulated by 30.3% (p = 0.0007) and M2 macrophage markers (ARG-1) were increased by 55.2% (p = 0.0009) in AG1296 group. CONCLUSION:AG1296 inhibited the atherosclerotic plaque progression and enhanced plaque stability by inhibiting inflammatory responses, reducing the expression of matrix metalloproteinases and promoting macrophages from proinflammatory phenotype to anti-inflammatory phenotype.
10.1016/j.bbrc.2017.05.159
Therapeutic Role of Innovative Anti-Inflammatory Medications in the Prevention of Acute Coronary Syndrome.
Pashun Raymond Anthony,Frishman William H
Cardiology in review
An improved understanding of the pathogenesis of acute coronary syndromes and its relationship to atherosclerotic plaque rupture and thrombosis has contributed to the investigation of novel therapies for prevention and treatment. New data ascribe an increasingly important role of active inflammation in contributing to thinning of the atherosclerotic fibrous cap and plaque instability. Despite this understanding, there are currently no therapeutic approaches to specifically target the unstable plaque. Multiple randomized trials investigating treatment strategies have recently been completed or are currently being conducted, using anti-inflammatory medications, such as methotrexate, colchicine, darapladib, varespladib, losmapimod, and canakinumab, to reduce the incidence of cardiovascular events including acute coronary syndromes. These anti-inflammatory medications differ in their mechanism of action from having widespread targets (as is the case for methotrexate and colchicine) to having specific targets (as is the case for darapladib, varespladib, losmapimod, and canakinumab). The trials investigating the efficacy of darapladib in reducing cardiovascular events revealed no significant benefit when compared with the current standard of care. The varespladib studies were terminated early because of adverse outcomes. However, the outcomes of the remaining drug studies may still contribute to novel therapeutic approaches in the treatment of patients with unstable coronary artery disease.
10.1097/CRD.0000000000000062
Coronary plaque rupture with subsequent thrombosis typifies the culprit lesion of non-ST-segment-elevation myocardial infarction, not unstable angina: non-ST-segment-elevation acute coronary syndrome study.
Sakaguchi Mikumo,Ehara Shoichi,Hasegawa Takao,Matsumoto Kenji,Nishimura Satoshi,Yoshikawa Junichi,Shimada Kenei
Heart and vessels
Recently, unstable angina pectoris (UAP) and non-ST-segment-elevation myocardial infarction (NSTEMI) have been considered together because they exhibit indistinguishable clinical and electrocardiogram features, and constitute non-ST-segment-elevation acute coronary syndrome (NSTE-ACS). However, no optical coherence tomography (OCT) studies have reported the association between vulnerable plaque morphology and clinical characteristics in NSTE-ACS patients based on assessment of clinical symptoms and myocardial necrosis. The aim of this study was to investigate the differences in clinical characteristics and plaque morphology assessed by OCT between patients with UAP and NSTEMI. Preinterventional OCT images of 84 NSTE-ACS patients were studied, 19 with NSTEMI and 65 with UAP, according to levels of high-sensitivity troponin T. The frequency of plaque rupture and thrombus in patients with NSTEMI was higher than in UAP patients with either class I or II + III (rupture: NSTEMI, 68 %; UAP classes II + III, 30 %; UAP class I, 19 %, thrombus: NSTEMI, 73 %; UAP classes II + III, 22 %; UAP class I, 14 %). In NSTEMI patients, the frequency of occurrence of both thrombus and rupture was the highest. Conversely, patients with UAP class I or those with UAP classes II + III most frequently had no thrombus and rupture, and the frequencies of the presence of thrombus were only 14 and 22 %, respectively. Multivariate analysis revealed that thrombus and plaque rupture were independently associated with NSTEMI. This study demonstrates that the morphological features of culprit lesions could be related to clinical severity in NSTE-ACS patients.
10.1007/s00380-016-0862-6
Coronary atheroma regression and adverse cardiac events: A systematic review and meta-regression analysis.
Bhindi Rahul,Guan Meijiao,Zhao Yinshan,Humphries Karin H,Mancini G B John
Atherosclerosis
BACKGROUND AND AIMS:The relationship between plaque regression induced by dyslipidemia therapies and occurrence of major adverse cardiovascular events (MACE) is controversial. We performed a systematic review and meta-regression of dyslipidemia therapy studies reporting MACE and intravascular ultrasound (IVUS) measures of change in coronary atheroma. METHODS:Prospective studies of dyslipidemia therapies reporting percent atheroma volume (PAV) measured by IVUS and reporting death, myocardial infarction, stroke, unstable angina or transient ischemic attack (MACE) were included. The association between mean change in PAV and MACE was examined using meta-regression via mixed-effects binomial logistic regression models, unadjusted and adjusted for mean age, baseline PAV, baseline low density lipoprotein-cholesterol and study duration. RESULTS:The study included 17 prospective studies published between 2001 and 2018 totaling 6333 patients. Study duration varied from 11 to 104 weeks. Mean change in PAV, across the study arms, ranged from -5.6% to 3.1%. MACE ranged from 0 to 72 events per study arm: 13 study arms (38%) reported no events, 8 (24%) reported 1-2 events and 13 (38%) reported 3 or more events. Meta-regression demonstrated a decline in the odds of MACE associated with reduction in mean PAV: unadjusted odds ratio (OR): 0.78, 95% Confidence Interval (CI): [0.63, 0.96], p = 0.018; adjusted OR: 0.82, 95% CI: [0.70, 0.95], p = 0.011, per 1% decrease in mean PAV. CONCLUSIONS:A 1% reduction in mean PAV as induced by dyslipidemia therapies was associated with a 20% reduction in the odds of MACE.
10.1016/j.atherosclerosis.2019.03.005
Structure of Atherosclerotic Plaques in Different Vascular Territories: Clinical Relevance.
Poredos Pavel,Poredos Peter,Jezovnik Mateja Kaja
Current vascular pharmacology
BACKGROUND:Atherosclerosis is a systemic disease with different faces. Despite similar, or even identical, risk factors and pathogenesis, atherosclerotic lesions and their clinical manifestations vary in different parts of the vasculature. Peripheral arterial disease (PAD) in the superficial femoral artery (SFA) represents a frequent clinical manifestation of atherosclerotic disease. The pathohistological characteristics of plaques in PAD differ from lesions in the coronary arteries. Plaques in the SFA have more fibrotic elements with less lipid and degenerative tissue elements; this makes them more stable and less prone to rupture. The density of vasa vasorum, an important determinant of structure and stability of atherosclerotic lesions, is significantly lower in PAD than in coronary arteries. Further, haemodynamic forces and shear stress vary in different segments of the arterial tree and influence the development of atherosclerotic lesions and their stability. It follows that the clinical consequences differ depending on the vascular territory involved. In the coronary arteries, acute thrombotic occlusion with clinical manifestation of myocardial infarction is one of the most frequent manifestations due to unstable atherosclerotic lesions. Atherosclerotic lesions in SFA progress slowly and are more stable; therefore, clinical manifestations develop more gradually. CONCLUSION:The atherosclerotic process in SFA is frequently asymptomatic or presents as stable intermittent claudication, and in a relatively low percentage, progresses to critical limb ischaemia. Also, remodelling of the arterial wall in peripheral arteries compensates for the reduction of arterial lumen and provides blood flow in spite of relatively large atherosclerotic lesions. However, arterial restenosis after recanalization procedures in SFA reduces the long-term success of recanalization.
10.2174/1570161115666170227103125
Coronary plaque redistribution after stent implantation is determined by lipid composition: A NIRS-IVUS analysis.
Roleder Tomasz,Dobrolinska Magdalena,Pociask Elzbieta,Wanha Wojciech,Smolka Grzegorz,Walkowicz Wojciech,Parma Radoslaw,Lebek Mariusz,Bochenek Tomasz,Pietraszewski Przemysław,Kedhi Elvin,Ochala Andrzej,Gasior Zbigniew,Ali Ziad A,Wojakowski Wojciech
Cardiology journal
BACKGROUND:The composition of plaque impacts the results of stenting. The following study evaluated plaque redistribution related to stent implantation using combined near-infrared spectroscopy and intravascular ultrasound (NIRS-IVUS) imaging. METHODS:The present study included 49 patients (mean age 66 ± 11 years, 75% males) presenting with non-ST elevation myocardial infarction (8%), unstable angina (49%) and stable coronary artery disease (43%). The following parameters were analyzed: mean plaque volume (MPV, mm3), plaque burden (PB, %), remodeling index (RI), and maximal lipid core burden index in a 4 mm segment (maxLCBI4mm). High-lipid burden lesions (HLB) were defined as by maxLCBI4mm > 265 with positive RI. Otherwise plaques were defined as low-lipid burden lesions (LLB). Measurements were done in the target lesion and in 4 mm edges of the stent before and after stent implantation. RESULTS:MPV and maxLCBI4mm decreased in both HLB (MPV 144.70 [80.47, 274.25] vs. 97.60 [56.82, 223.45]; maxLCBI4mm: 564.11 ± 166.82 vs. 258.11 ± 234.24, p = 0.004) and LLB (MPV: 124.50 [68.00, 186.20] vs. 101.10 [67.87, 165.95]; maxLCBI4mm: 339.07 ± 268.22 vs. 124.60 ± 160.96, p < 0.001), but MPV decrease was greater in HLB (28.00 [22.60, 57.10] vs. 13.50 [1.50, 28.84], p = 0.019). Only at the proximal stent edge of LLB, maxLCBI4mm decreased (34 [0, 207] vs. 0 [0, 45], p = 0.049) and plaque burden increased (45.48 [40.34, 51.55] vs. 51.75 [47.48, 55.76], p = 0.030). CONCLUSIONS:NIRS-IVUS defined HLB characterized more significant decreases in plaque volume by stenting. Plaque redistribution to the proximal edge of the implanted stent occurred only in LLB.
10.5603/CJ.a2018.0111
Carotid thickness and atherosclerotic plaque stability, serum inflammation, serum MMP-2 and MMP-9 were associated with acute cerebral infarction.
Chen Lilin,Yang Qihua,Ding Rui,Liu Dan,Chen Zhijun
Experimental and therapeutic medicine
Correlations of carotid intima-media thickness (IMT), atherosclerotic plaque stability, serum inflammatory factors and serum matrix metalloproteinase (MMP)-2 and MMP-9 levels with the condition of disease in patients with acute cerebral infarction were analyzed to explore the predictive value of these risk factors. A total of 56 patients diagnosed with acute cerebral infarction in Jingmen First People's Hospital from February 2016 to January 2017 were selected and divided into the plaque stability group (n=25) and plaque instability group (n=31). Our results showed that the level of total cholesterol (TC) in the plaque instability group was significantly higher than that in the plaque stability group (P<0.05). IMT and National Institutes of Health Stroke Scale (NIHSS) score in the plaque instability group were significantly higher than those in the plaque stability group, but eccentricity index (EI) and Barthel index were significantly lower than those in the plaque stability group (P<0.05). The serum C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in the plaque instability group were significantly higher than those in the plaque stability group (P<0.05). The levels of serum MMP-2 and MMP-9 in the plaque instability group were significantly higher than those in the plaque stability group (P<0.05). Barthel index was correlated with IMT (r=-0.693, P<0.01), MMP-2 (r=-0.605, P<0.01), CRP (r=-0.765, P<0.01) and EI (r=0.811, P<0.01), respectively. Hemoglobin A1c (HbA1c), TC, systolic blood pressure, coronary heart disease, diabetes mellitus, IMT, EI, CRP, TNF-α, IL-6, MMP-2 and MMP-9 had independent predictive values for acute cerebral infarction (P<0.05). Carotid IMT, stability of the atherosclerotic plaque, serum inflammation, serum MMP-2 and MMP-9 levels have close correlations with acute cerebral infarction. The larger the carotid IMT is, the more unstable the plaque is and the higher the levels of serum inflammatory factors, MMP-2 and MMP-9 are, the greater the risk of acute cerebral infarction will be.
10.3892/etm.2018.6868
Assessment of vulnerable and unstable carotid atherosclerotic plaques on endarterectomy specimens.
Butcovan Doina,Mocanu Veronica,Baran Dana,Ciurescu Diana,Tinica Grigore
Experimental and therapeutic medicine
The types of lesion instability responsible for the majority of acute coronary events frequently include plaque disruption and plaque erosion with superimposed thrombosis. The term 'vulnerable plaque is used to describe atherosclerotic (ATS) plaques that are particularly prone to rupture and susceptible to thrombus formation, such as the thin-cap fibroatheroma (TCFA). The aim of the present study was to assess the morphological and histological differences between plaques that are unstable and those that are vulnerable to instability. Carotid artery endarterectomy specimens were obtained from 26 patients with carotid artery stenosis, consisting of 20 men and 6 women (age range, 35-80 years). Histological and morphometric methods were used to visualize and characterize the ATS plaques. Among the 26 carotid ATS plaques, 23% were stable, 23% were unstable and 54% were vulnerable. With regard to morphometric characteristics, the following mean values were obtained for the TCFA and unstable plaques, respectively: Fibrous cap thickness, 21.91 and 11.66 µM; proportion of necrotic core area in the total plaque area, 25.90 and 22.03%; and the proportion of inflammatory area in the total plaque area, 8.41 and 3.04%. No plaque calcification was observed in any of them. Since ATS coronary artery disease is considerably widespread and fatal, it is crucial to further study ATS lesions to obtain an improved understanding of the nature of vulnerable and unstable plaques. The methods used to detect plaque size, necrotic core area and fibrous cap thickness are considered to be particularly useful for identifying vulnerable and unstable plaques.
10.3892/etm.2016.3096
Molecular Imaging of Vulnerable Coronary Plaque: A Pathophysiologic Perspective.
Krishnan Sandeep,Otaki Yuka,Doris Mhairi,Slipczuk Leandro,Arnson Yoav,Rubeaux Mathieu,Dey Damini,Slomka Piotr,Berman Daniel S,Tamarappoo Balaji
Journal of nuclear medicine : official publication, Society of Nuclear Medicine
Atherothrombotic events in coronary arteries are most often due to rupture of unstable plaque resulting in myocardial infarction. Radiolabeled molecular imaging tracers directed toward cellular targets that are unique to unstable plaque can serve as a powerful tool for identifying high-risk patients and for assessing the potential of new therapeutic approaches. Two commonly available radiopharmaceuticals-F-FDG and F-NaF-have been used in clinical research for imaging coronary artery plaque, and ongoing clinical studies are testing whether there is an association between F-NaF uptake and future atherothrombotic events. Other, less available, tracers that target macrophages, endothelial cells, and apoptotic cells have also been tested in small groups of patients. Adoption of molecular imaging of coronary plaque into clinical practice will depend on overcoming major hurdles, ultimately including evidence that the detection of unstable plaque can change patient management and improve outcomes.
10.2967/jnumed.116.187906
Role of cardiac multidetector computed tomography beyond coronary angiography.
Sato Akira,Aonuma Kazutaka
Circulation journal : official journal of the Japanese Circulation Society
Cardiac multidetector computed tomography (MDCT) has become a useful noninvasive modality for anatomical imaging of coronary artery disease (CAD). Currently, the main clinical advantage of coronary computed tomography angiography (CCTA) appears to be related to its high negative predictive value at low or intermediate pretest probability for CAD. With the development of technical aspects of MDCT, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology, myocardial perfusion, and patient outcomes. The presence of positive vessel remodeling, low-attenuation plaques, napkin-ring sign, or spotty calcification on CCTA could be useful information on high-risk vulnerable plaques. The napkin-ring sign, especially, showed higher accuracy for the detection of thin-cap fibroatheroma. Recently, it was reported that cardiac 3D single-photon emission tomography/CT fusion imaging, noninvasive fractional flow reserve computed from CT, and integrated CCTA and CT myocardial perfusion were associated with improved diagnostic accuracy for the detection of hemodynamically significant CAD. Furthermore, several randomized, large clinical trials have evaluated the clinical value of CCTA for chest pain triage in the emergency department or long-term reduction in death, myocardial infarction, or hospitalization for unstable angina. In this review we discuss the role of cardiac MDCT beyond coronary angiography, including a comparison with other currently available imaging modalities used to examine atherosclerotic plaque and myocardial perfusion.
10.1253/circj.CJ-15-0102
Markers of preclinical atherosclerosis and their clinical relevance.
Poredoš Pavel,Ježovnik Mateja Kaja
VASA. Zeitschrift fur Gefasskrankheiten
The estimation of risk for atherosclerotic and cardiovascular events based only on the presence of classical risk factors is often insufficient. Therefore, efforts have been made to find markers that indicate the presence of preclinical disease in individual subjects: blood markers of atherosclerosis and preclinical deterioration of the arterial wall. Elevated levels of several inflammatory mediators have been found in subjects with atherosclerosis. Increased basal levels of cytokines, the cell adhesion molecules, selectins and acute-phase reactants such as high sensitive C-reactive protein (hsCRP), fibrinogen, and serum amyloid A are related to an increased risk of cardiovascular events. For clinical purposes, the most promising inflammatory biomarker appears to be hsCRP. In the last decade, markers of plaque stability and unstable coronary artery disease have been sought. Further, markers of endothelial dysfunction, like circulating molecules as well as indicators of functional deterioration of the arterial wall were identified. It was shown that endothelial dysfunction is closely related to different risk factors of atherosclerosis, and to their intensity and duration. Intima-media thickness measurement has emerged as one of the methods of choice for determining the anatomic extent of preclinical atherosclerosis and for assessing cardiovascular risk.Determination of markers of preclinical atherosclerosis improve individual risk determination and could influence the decision of a clinician to intervene with medication and to use more aggressive treatment of risk factors in high risk subjects and in patients with atherosclerotic disease.
10.1024/0301-1526/a000439
Role of Platelet Activation and Oxidative Stress in the Evolution of Myocardial Infarction.
Fuentes Eduardo,Moore-Carrasco Rodrigo,de Andrade Paes Antonio Marcus,Trostchansky Andres
Journal of cardiovascular pharmacology and therapeutics
Myocardial infarction, commonly known as heart attack, evolves from the rupture of unstable atherosclerotic plaques to coronary thrombosis and myocardial ischemia-reperfusion injury. A body of evidence supports a close relationship between the alterations following an ischemia-reperfusion injury-induced oxidative stress and platelet activity. Through their critical role in thrombogenesis and inflammatory responses, platelets are fully (totally) implicated from atherothrombotic plaque formation to myocardial infarction onset and expansion. However, mere platelet aggregation prevention does not offer full protection, suggesting that other antiplatelet therapy mechanisms may also be involved. Thus, the present review discusses the integrative role of platelets, oxidative stress, and antiplatelet therapy in triggering myocardial infarction pathophysiology.
10.1177/1074248419861437
Deciphering acute coronary syndrome biomarkers: High-resolution proteomics in platelets, thrombi and microparticles.
Navas-Carrillo Diana,Marín Francisco,Valdés Mariano,Orenes-Piñero Esteban
Critical reviews in clinical laboratory sciences
Acute coronary syndromes (ACS) encompass unstable angina, non-ST segment elevation myocardial infarction, ST-segment elevation myocardial infarction and sudden cardiac death. They are commonly associated with the presence of vulnerable plaques in the coronary arteries and occur when a thrombus formed from a ruptured atheromatous plaque causes a prolonged occlusion of a coronary artery. The erosion of the vulnerable plaques results in the formation of luminal thrombi secondary to platelet activation and the release of thrombogenic elements within the atherosclerotic lesions. Proteomic approaches offer an unbiased platform for the comprehensive analysis of the whole proteome in a certain physiological time. Although mRNA expression is widely considered to be indicative of protein expression, protein levels are the result of protein synthesis and degradation, and RNA levels are not informative of protein degradation. In contrast, the proteomic technology investigates protein expression directly. This is particularly important in the context of atherosclerosis in which protein degradation is as decisive as protein synthesis. Moreover, proteomics reveals post-translational modifications known to be determinant for many human diseases. Clinically, there is increasing evidence for the role of proteomic technology in biomarker discovery that will provide novel information on the molecular events associated with ACS, and potentially lead to the identification of novel drug targets. In this review, we describe in detail the importance of proteomic approaches to identify new biomarkers associated with ACS from three perspectives: biomarkers associated with platelet metabolism; the study of proteomics of intravascular thrombi; and proteome analysis of membrane microparticles released from activated cells, mostly by platelets.
10.1080/10408363.2016.1241214
Impact of Pre-Diabetes on Coronary Plaque Composition and Clinical Outcome in Patients With Acute Coronary Syndromes: An Analysis From the PROSPECT Study.
Farhan Serdar,Redfors Björn,Maehara Akiko,McAndrew Thomas,Ben-Yehuda Ori,De Bruyne Bernard,Mehran Roxana,Giustino Gennaro,Kirtane Ajay J,Serruys Patrick W,Mintz Gary S,Stone Gregg W
JACC. Cardiovascular imaging
OBJECTIVES:The aim of this study was to investigate the impact of pre-diabetes (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients with acute coronary syndromes (ACS). BACKGROUND:Pre-DM (i.e., the early stages of glucometabolic disturbance) is common among patients with ACS, but the extent to which pre-DM influences coronary plaque characteristics and the risk for adverse ischemic events is unclear. METHODS:In the PROSPECT (Providing Regional Observations to Study Predictors of Events in Coronary Tree) study, patients with ACS underwent quantitative coronary angiography, grayscale intravascular ultrasound, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention. Patients were divided into 3 groups according to their glucometabolic status, as defined by the American Diabetes Association: normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups were compared with regard to coronary plaque characteristics and the risk for major adverse cardiac events (MACEs) (defined as cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina). RESULTS:Among 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183 (33.4%) had DM. There were no significant differences between the groups with regard to intravascular ultrasound findings indicative of vulnerable plaques. Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20; 95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio: 1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with increased risk for MACEs. CONCLUSIONS:Impaired glucose metabolism is common among patients presenting with ACS. DM but not pre-DM is associated with an increased risk for MACEs. Thus, preventing patients from progressing from pre-DM to DM is important. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466).
10.1016/j.jcmg.2017.06.023
Therapeutic modulation of the natural history of coronary atherosclerosis: lessons learned from serial imaging studies.
Andrews Jordan,Puri Rishi,Kataoka Yu,Nicholls Stephen J,Psaltis Peter J
Cardiovascular diagnosis and therapy
Despite advances in risk prediction, preventive and therapeutic strategies, atherosclerotic cardiovascular disease remains a major public health challenge worldwide, carrying considerable morbidity, mortality and health economic burden. There continues to be a need to better understand the natural history of this disease to guide the development of more effective treatment, integral to which is the rapidly evolving field of coronary artery imaging. Various imaging modalities have been refined to enable detailed visualization of the pathological substrate of atherosclerosis, providing accurate and reproducible measures of coronary plaque burden and composition, including the presence of high-risk characteristics. The serial application of such techniques, including coronary computed tomography angiography (CTA), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) have uncovered important insights into the progression of coronary plaque over time in patients with stable and unstable coronary artery disease (CAD), and its responsiveness to therapeutic interventions. Here we review the use of different imaging modalities for the surveillance of coronary atherosclerosis and the lessons they have provided about the modulation of CAD by both traditional and experimental therapies.
10.21037/cdt.2015.10.02
New insights into the vulnerable plaque from imaging studies.
Fenning Robert S,Wilensky Robert L
Current atherosclerosis reports
The concept of the vulnerable atherosclerotic plaque first developed through histological evaluation of post-mortem coronary arteries has been significantly advanced in recent years by new imaging modalities. Imaging has: 1) verified histological findings, 2) identified features that are associated with unstable plaque, 3) followed plaques over time to study the dynamic nature of vulnerable plaque, 4) predicted clinical events based on imaging features, 5) tested the impact of medical interventions on plaque morphology. This review will summarize the major findings of imaging studies with a focus on how the knowledge base of vulnerable plaque has been advanced.
10.1007/s11883-014-0397-1
Prevalence and Predictors of Multiple Coronary Plaque Ruptures: In Vivo 3-Vessel Optical Coherence Tomography Imaging Study.
Vergallo Rocco,Uemura Shiro,Soeda Tsunenari,Minami Yoshiyasu,Cho Jin-Man,Ong Daniel S,Aguirre Aaron D,Gao Lei,Biasucci Luigi M,Crea Filippo,Yu Bo,Lee Hang,Kim Chong-Jin,Jang Ik-Kyung
Arteriosclerosis, thrombosis, and vascular biology
OBJECTIVE:Plaque rupture may be the local expression of a widespread coronary instability. This study aimed to investigate: (1) the prevalence and characteristics of nonculprit plaque rupture; (2) the pancoronary atherosclerotic phenotype in patients with and without nonculprit plaque rupture; and (3) the prevalence and predictors of multiple plaque ruptures. APPROACH AND RESULTS:Six hundred and seventy-five nonculprit plaques from 261 patients (34 acute myocardial infarction, 73 unstable angina pectoris, and 154 stable angina pectoris) were analyzed by 3-vessel optical coherence tomography. Nonculprit plaque ruptures were identified in 51 patients (20%). Patients with nonculprit plaque ruptures had higher prevalence of thin-cap fibroatheroma (51% versus 13%; P<0.001) in the 3 major epicardial coronary vessels. Multiple plaque ruptures were observed in 20% of patients (38% acute myocardial infarction versus 10% unstable angina pectoris versus 19% stable angina pectoris; P=0.042). Thin-cap fibroatheroma, intimal vasculature, and macrophages were independent morphological predictors of multiple plaque ruptures, whereas acute myocardial infarction and chronic kidney disease were independent clinical predictors. Patients with nonculprit plaque ruptures showed higher 1-year rates of nontarget lesion revascularization (11.8% versus 4.4%; P=0.039). CONCLUSIONS:Nonculprit plaque ruptures were observed in 20% of patients with coronary artery disease and were associated with pancoronary vulnerability and higher 1-year revascularization rate.
10.1161/ATVBAHA.116.307891
Profiling and functional characterization of circulation LncRNAs that are associated with coronary atherosclerotic plaque stability.
Pan Zhicheng,Fan Zixu,Ma Jianwei,Liu Hua,Shen Linghong,He Ben,Zhang Min
American journal of translational research
BACKGROUND:Accumulating studies have demonstrated that some long non-coding RNAs (lncRNAs) play critical roles in the pathogenesis of atherosclerosis. We aimed to identify circulation lncRNAs that are potential biomarkers to evaluate coronary atherosclerotic plaque stability. METHODS AND RESULTS:The transcriptomes of blood samples of three patients with stable plaque and three patients with unstable plaque were sequenced by RNA-sequencing. A total of 62 lncRNAs were found to be differentially expressed in patients with unstable plaques. The expressions of four candidate lncRNAs (ANP32A-005, TULP4-005, PDCD4-010, and SNHG7-003) were quantified using blood samples from 15 patients with stable plaques and 15 patients with unstable plaques, subsequently. In addition, the expression levels of these four lncRNAs in LPS (lipopolysaccharide)-activated THP-1 monocytes and THP-1-derived macrophages were measured. LncRNA-SNHG7-003 was validated to be significantly down-regulated in blood samples of patients with unstable plaques and LPS-stimulated monocytes and macrophages. Moreover, plasmid-transfection mediated over-expression of SNHG7-003 markedly inhibited the activation of NF-κB pathway, and reduced the secretion of inflammatory mediators (TNF-α, IL-1β, MCP-1 and MMP-9) in LPS-activated THP-1 monocytes and macrophages. CONCLUSION:LncRNA-SNHG7-003 inhibits NF-κB activation and regulates inflammatory responses in human monocytes and macrophages. Blood lncRNA-SNHG7-003 is a potential biomarker for evaluating plaque stability in patients with coronary artery diseases.
Immune-Inflammatory Activation in Acute Coronary Syndromes: A Look into the Heart of Unstable Coronary Plaque.
Cimmino Giovanni,Loffredo Francesco S,Morello Alberto,D'Elia Saverio,De Palma Raffaele,Cirillo Plinio,Golino Paolo
Current cardiology reviews
In the last twenty years, our comprehension of the molecular mechanisms involved in the formation, progression and complication of atherosclerotic plaque has advanced significantly and the main role of inflammation and immunity in this phenomenon is now largely accepted. Accumulating evidence highlight the crucial role of different inflammatory and immune cells, such as monocytes and T-lymphocytes, in the pathophysiology of atherosclerotic lesion, particularly in contributing to its complications, such as rupture or ulceration. According to the new terminology, "vulnerable plaque" identifies an inflamed atherosclerotic lesion that is particularly prone to rupture. Once disrupted, prothrombotic material is exposed to the flowing blood, thus activating coagulation cascade and platelet aggregation, ultimately leading to acute thrombus formation within the coronary vessel. To date this is the key event underlying the clinical manifestations of acute coronary syndromes (ACS). The degree of vessel occlusion (complete vs. incomplete) and the time of blood flow cessation will define the severity of clinical picture. This phenomenon seems to be the final effect of a complex interaction between different local and systemic factors, involving the degree of inflammation, type of cells infiltration and the rheological characteristics of blood flow at the site of plaque rupture, thrombogenic substrates within the atherosclerotic lesion and different soluble mediators, already present or acutely released in the circulating blood. This article will review currently available data on the pathophysiology of ACS, emphasizing the immunological and inflammatory aspects of vulnerable plaque. We may postulate that intraplaque antigens and local microenvironment will define the immune-inflammatory response and cells phenotype, thus determining the severity of clinical manifestations.
10.2174/1573403X12666161014093812
Simultaneous evaluation of plaque stability and ischemic potential of coronary lesions in a fluid-structure interaction analysis.
Wu Xinlei,von Birgelen Clemens,Zhang Su,Ding Daixin,Huang Jiayue,Tu Shengxian
The international journal of cardiovascular imaging
The measurement of fractional flow reserve (FFR) and superficial wall stress (SWS) identifies inducible myocardial ischemia and plaque vulnerability, respectively. A simultaneous evaluation of both FFR and SWS is still lacking, while it may have a major impact on therapy. A new computational model of one-way fluid-structure interaction (FSI) was implemented and used to perform a total of 54 analyses in virtual coronary lesion models, based on plaque compositions, arterial remodeling patterns, and stenosis morphologies under physiological conditions. Due to a greater lumen dilation and more induced strain, FFR in the lipid-rich lesions (0.81 ± 0.15) was higher than that in fibrous lesions (0.79 ± 0.16, P = 0.001) and calcified lesions (0.79 ± 0.16, P = 0.001). Four types of lesions were further defined, based on the combination of cutoff values for FFR (0.80) and maximum relative SWS (30 kPa): The level of risk increased from (1) plaques with mild-to-moderate stenosis but negative remodeling for lipid-rich (Type A: non-ischemic, stable) to (2) lipid-rich plaques with mild-to-moderate stenosis and without-to-positive remodeling (Type B: non-ischemic, unstable) or plaques with severe stenosis but negative remodeling for lipid-rich (Type C: ischemic, stable) to (3) lipid-rich plaques with severe stenosis and without-to-positive remodeling (Type D: ischemic, unstable). The analysis of FSI to simultaneously evaluate inducible myocardial ischemia and plaque stability may be useful to identify coronary lesions at a high risk and to ultimately optimize treatment. Further research is warranted to assess whether a more aggressive treatment may improve the prognosis of patients with non-ischemic, intermediate, and unstable lesions.
10.1007/s10554-019-01611-y
How do we prevent the vulnerable atherosclerotic plaque from rupturing? Insights from in vivo assessments of plaque, vascular remodeling, and local endothelial shear stress.
Andreou Ioannis,Antoniadis Antonios P,Shishido Koki,Papafaklis Michail I,Koskinas Konstantinos C,Chatzizisis Yiannis S,Coskun Ahmet U,Edelman Elazer R,Feldman Charles L,Stone Peter H
Journal of cardiovascular pharmacology and therapeutics
Coronary atherosclerosis progresses both as slow, gradual enlargement of focal plaque and also as a more dynamic process with periodic abrupt changes in plaque geometry, size, and morphology. Systemic vasculoprotective therapies such as statins, angiotensin-converting enzyme inhibitors, and antiplatelet agents are the cornerstone of prevention of plaque rupture and new adverse clinical outcomes, but such systemic therapies are insufficient to prevent the majority of new cardiac events. Invasive imaging methods have been able to identify both the anatomic features of high-risk plaque and the ongoing pathobiological stimuli responsible for progressive plaque inflammation and instability and may provide sufficient information to formulate preventive local mechanical strategies (eg, preemptive percutaneous coronary interventions) to avert cardiac events. Local endothelial shear stress (ESS) triggers vascular phenomena that synergistically exacerbate atherosclerosis toward an unstable phenotype. Specifically, low ESS augments lipid uptake and catabolism, induces plaque inflammation and oxidation, downregulates the production, upregulates the degradation of extracellular matrix, and increases cellular apoptosis ultimately leading to thin-cap fibroatheromas and/or endothelial erosions. Increases in blood thrombogenicity that result from either high or low ESS also contribute to plaque destabilization. An understanding of the actively evolving vascular phenomena, as well as the development of in vivo imaging methodologies to identify the presence and severity of the different processes, may enable early identification of a coronary plaque destined to acquire a high-risk state and allow for highly selective, focal preventive interventions to avert the adverse natural history of that particular plaque. In this review, we focus on the role of ESS in the pathobiologic processes responsible for plaque destabilization, leading either to accelerated plaque growth or to acute coronary events, and emphasize the potential to utilize in vivo risk stratification of individual coronary plaques to optimize prevention strategies to preclude new cardiac events.
10.1177/1074248414555005
Coronary Atherosclerotic Phenotype and Plaque Healing in Patients With Recurrent Acute Coronary Syndromes Compared With Patients With Long-term Clinical Stability: An In Vivo Optical Coherence Tomography Study.
Vergallo Rocco,Porto Italo,D'Amario Domenico,Annibali Gianmarco,Galli Mattia,Benenati Stefano,Bendandi Francesco,Migliaro Stefano,Fracassi Francesco,Aurigemma Cristina,Leone Antonio Maria,Buffon Antonino,Burzotta Francesco,Trani Carlo,Niccoli Giampaolo,Liuzzo Giovanna,Prati Francesco,Fuster Valentin,Jang Ik-Kyung,Crea Filippo
JAMA cardiology
Importance:At one end of the coronary artery disease (CAD) spectrum, there are patients with multiple recurrent acute coronary syndromes (rACS), and at the other end there are those with long-standing clinical stability. Predicting the natural history of these patients is challenging because unstable plaques often heal without resulting in ACS. Objective:To assess in vivo the coronary atherosclerotic phenotype as well as the prevalence and characteristics of healed coronary plaques by optical coherence tomography (OCT) imaging in patients at the extremes of the CAD spectrum. Design, Setting, and Participants:This is an observational, single-center cohort study with prospective clinical follow-up. From a total of 823 consecutive patients enrolled in OCT Registry of the Fondazione Policlinico A. Gemelli-IRCCS, Rome, Italy, from March 2009 to February 2016, 105 patients were included in the following groups: (1) patients with rACS, defined as history of at least 3 acute myocardial infarctions (AMIs) or at least 4 ACS with at least 1 AMI; (2) patients with long-standing stable angina pectoris (ls-SAP), defined as a minimum 3-year history of stable angina; and (3) patients with a single unheralded AMI followed by a minimum 3-year period of clinical stability (sAMI). Data were analyzed from January to August 2018. Exposures:Intracoronary OCT imaging of nonculprit coronary segments. Main Outcomes and Measures:Coronary plaque features and the prevalence of healed coronary plaques in nonculprit segments as assessed by intracoronary OCT imaging. Results:Of 105 patients, 85 were men (81.0%); the median (interquartile range) age was 68 (63-75) years. Median (interquartile range) time of clinical stability was 9 (5.0-15.0) years in the ls-SAP group and 8 (4.5-14.5) years in the sAMI group. Patients in the rACS and sAMI groups showed similar prevalence of lipid-rich plaque and thin-cap fibroatheroma, which was significantly higher than in those with ls-SAP (lipid-rich plaque 80.0% [n = 24 of 30] vs 76.3% [n = 29 of 38] vs 37.8% [n = 14 of 37], respectively; P < .001; thin-cap fibroatheroma 40.0% [n = 12 of 30] vs 34.2% [n = 13 of 38] vs 8.1% [n = 3 of 37], respectively; P = .006). Spotty calcifications were more frequently observed in patients with rACS than in those with ls-SAP and sAMI (70.0% [n = 21 of 30] vs 40.5% [n = 15 of 37] vs 44.7% [n = 17 of 38], respectively; P = .04). Healed coronary plaques were rarely observed in patients with rACS, whereas their prevalence was significantly higher in patients with ls-SAP and sAMI (3.3% [n = 1 of 30] vs 29.7% [n = 11 of 37] vs 28.9% [n = 11 of 38], respectively; P = .01). Conclusions and Relevance:Patients with rACS have a distinct atherosclerotic phenotype compared with those with ls-SAP, including higher prevalence of thin-cap fibroatheroma and lower prevalence of healed coronary plaques, suggesting that atherosclerotic profile and plaque healing may play a role in leading the natural history of patients with CAD.
10.1001/jamacardio.2019.0275
Acute management of unstable angina and non-ST segment elevation myocardial infarction.
Silva Fernando Morita Fernandes,Pesaro Antonio Eduardo Pereira,Franken Marcelo,Wajngarten Mauricio
Einstein (Sao Paulo, Brazil)
Non-ST segment elevation coronary syndrome usually results from instability of an atherosclerotic plaque, with subsequent activation of platelets and several coagulation factors. Its treatment aims to reduce the ischemic pain, limiting myocardial damage and decreasing mortality. Several antiplatelet and anticoagulation agents have been proven useful, and new drugs have been added to the therapeutic armamentarium in the search for higher anti-ischemic efficacy and lower bleeding rates. Despite the advances, the mortality, infarction and readmission rates remain high.
10.1590/S1679-45082015RW3172
Molecular magnetic resonance imaging of atherosclerotic vessel wall disease.
Nörenberg Dominik,Ebersberger Hans U,Diederichs Gerd,Hamm Bernd,Botnar René M,Makowski Marcus R
European radiology
UNLABELLED:Molecular imaging aims to improve the identification and characterization of pathological processes in vivo by visualizing the underlying biological mechanisms. Molecular imaging techniques are increasingly used to assess vascular inflammation, remodeling, cell migration, angioneogenesis and apoptosis. In cardiovascular diseases, molecular magnetic resonance imaging (MRI) offers new insights into the in vivo biology of pathological vessel wall processes of the coronary and carotid arteries and the aorta. This includes detection of early vascular changes preceding plaque development, visualization of unstable plaques and assessment of response to therapy. The current review focuses on recent developments in the field of molecular MRI to characterise different stages of atherosclerotic vessel wall disease. A variety of molecular MR-probes have been developed to improve the non-invasive detection and characterization of atherosclerotic plaques. Specifically targeted molecular probes allow for the visualization of key biological steps in the cascade leading to the development of arterial vessel wall lesions. Early detection of processes which lead to the development of atherosclerosis and the identification of vulnerable atherosclerotic plaques may enable the early assessment of response to therapy, improve therapy planning, foster the prevention of cardiovascular events and may open the door for the development of patient-specific treatment strategies. KEY POINTS:Targeted MR-probes allow the characterization of atherosclerosis on a molecular level. Molecular MRI can identify in vivo markers for the differentiation of stable and unstable plaques. Visualization of early molecular changes has the potential to improve patient-individualized risk-assessment.
10.1007/s00330-015-3881-2
Inflammation, oxidative stress and renin angiotensin system in atherosclerosis.
Husain Kazim,Hernandez Wilfredo,Ansari Rais A,Ferder Leon
World journal of biological chemistry
Atherosclerosis is a chronic inflammatory disease associated with cardiovascular dysfunction including myocardial infarction, unstable angina, sudden cardiac death, stroke and peripheral thromboses. It has been predicted that atherosclerosis will be the primary cause of death in the world by 2020. Atherogenesis is initiated by endothelial injury due to oxidative stress associated with cardiovascular risk factors including diabetes mellitus, hypertension, cigarette smoking, dyslipidemia, obesity, and metabolic syndrome. The impairment of the endothelium associated with cardiovascular risk factors creates an imbalance between vasodilating and vasoconstricting factors, in particular, an increase in angiotensin II (Ang II) and a decrease in nitric oxide. The renin-angiotensin system (RAS), and its primary mediator Ang II, also have a direct influence on the progression of the atherosclerotic process via effects on endothelial function, inflammation, fibrinolytic balance, and plaque stability. Anti-inflammatory agents [statins, secretory phospholipase A2 inhibitor, lipoprotein-associated phospholipase A2 inhibitor, 5-lipoxygenase activating protein, chemokine motif ligand-2, C-C chemokine motif receptor 2 pathway inhibitors, methotrexate, IL-1 pathway inhibitor and RAS inhibitors (angiotensin-converting enzyme inhibitors)], Ang II receptor blockers and ranin inhibitors may slow inflammatory processes and disease progression. Several studies in human using anti-inflammatory agents and RAS inhibitors revealed vascular benefits and reduced progression of coronary atherosclerosis in patients with stable angina pectoris; decreased vascular inflammatory markers, improved common carotid intima-media thickness and plaque volume in patients with diagnosed atherosclerosis. Recent preclinical studies have demonstrated therapeutic efficacy of vitamin D analogs paricalcitol in ApoE-deficient atherosclerotic mice.
10.4331/wjbc.v6.i3.209
Feasibility of diagnosing unstable plaque in patients with acute coronary syndrome using iMap-IVUS.
Liu Jian,Wang Zhao,Wang Wei-min,Li Qi,Ma Yu-liang,Liu Chuan-fen,Lu Ming-yu,Zhao Hong
Journal of Zhejiang University. Science. B
OBJECTIVE:To compare the plaque composition between stable and unstable plaques, characterize unstable plaque by using iMap-intravascular ultrasound (IVUS), and quantify the diagnostic criteria for unstable plaque. METHODS:Thirty-three acute coronary syndrome (ACS) patients who had undergone coronary angiography and IVUS from February 19, 2014 to December 19, 2014 at Peking University People's Hospital were enrolled in the study. Baseline data were collected. The patients were divided into two groups according to their gray-scale IVUS imaging, stable plaque and unstable plaque. A difference-in-difference evaluation was performed using the baseline data and off-line iMap imaging results between the two groups. A receiver operating characteristic (ROC) curve was constructed to obtain the optimal cut-off value to diagnose unstable plaque. RESULTS:Percentages of fibrotic and necrotic tissues, absolute values of lipidic, necrotic, and calcified tissues, and plaque burden were independent predictors for unstable plaque. Absolute necrotic area was the best predictor and exhibited the highest diagnostic value for plaque vulnerability (area under the curve (AUC)=0.806, P=0.000, 95% CI (0.718, 0.894)). The cut-off score for predicting unstable plaque was 4.0 mm(2). CONCLUSIONS:This study attempted to propose a cut-off value based on absolute necrotic area using iMap-IVUS to predict plaque vulnerability in patients with ACS. This score might provide a valuable reference for diagnosing unstable plaque.
10.1631/jzus.B1500206
Nonatherosclerotic causes of acute coronary syndrome: recognition and management.
Bastante Teresa,Rivero Fernando,Cuesta Javier,Benedicto Amparo,Restrepo Jorge,Alfonso Fernando
Current cardiology reports
Acute coronary syndromes (ACS) frequently result from the rupture or erosion of a vulnerable coronary plaque, with associated intracoronary thrombosis. ACS also may occur in patients with angiographically normal coronary arteries. Some of these patients, however, still have angiographically silent underlying coronary artery disease. In this setting, subtle atherosclerotic changes frequently associated with unstable morphologic features or residual intracoronary thrombus may be detected with intracoronary imaging techniques. Nevertheless, other patients develop ACS as a result of nonatherosclerotic coronary artery disease (NA-CAD). ACS in patients with NA-CAD may be the consequence of coronary spasm or transient coronary embolic phenomena. In these patients, after the initial ischemic insult, late coronary angiography usually reveals normal epicardial coronary vessels. Kounis syndrome is a type of ACS generated by allergic reactions. Takotsubo cardiomyopathy is characterized by normal coronary arteries with a distinct pattern of transient left ventricular wall motion abnormalities. ACS also may occur in young patients following illicit drug use. Finally, spontaneous coronary artery dissection and intramural hematoma represent other etiologies of NA-CAD. In this review, we discuss current evidence regarding diagnostic and treatment strategies in patients presenting with ACS as a result of NA-CAD.
10.1007/s11886-014-0543-y
Assessment of coronary atherosclerosis using optical coherence tomography.
Kubo Takashi,Tanaka Atsushi,Ino Yasushi,Kitabata Hironori,Shiono Yasutsugu,Akasaka Takashi
Journal of atherosclerosis and thrombosis
Optical coherence tomography (OCT) is a catheter-based imaging system that uses near-infrared light to produce cross-sectional images of the coronary arteries. With its extraordinarily high resolution (10-20 μm), OCT allows clinicians to observe various morphological features of coronary atherosclerosis in vivo. For example, intimal thickening presents as homogeneous, signal-rich regions on OCT, while fibroatheroma with a lipid-rich necrotic core is characterized by the presence of signal-poor regions with a diffuse border. Furthermore, plaque rupture is detected in 50〜70% of culprit lesions of acute coronary syndrome (ACS), and plaque erosion develops over areas of intimal thickening and/or thick-cap fibroatheroma. Meanwhile, calcified nodules are common in older patients with hypertension and chronic renal disease. Platelet-rich thrombi are visualized as low backscattering structures and often detected in patients with unstable angina, whereas red blood cell-rich thrombi exhibit a high backscattering structure with signal-free shadowing and are frequently noted in patients with acute myocardial infarction. Moreover, OCT-derived thin cap fibroatheroma has been shown to be a predictor of subsequent plaque progression and acute coronary events, while vasa vasorum and the macrophage density are associated with a thin fibrous cap and large necrotic core as well as increased serum levels of inflammatory biomarkers. One current challenge of OCT examinations is to detect morphologic characteristics capable of discriminating vulnerable from stable plaques. The ability to detect vulnerable plaques in vivo would allow physicians to identify patients at high risk for adverse coronary events, thus significantly helping to prevent ACS.
10.5551/jat.25452
Non-ST Elevation Acute Coronary Syndromes: A Comprehensive Review.
Bob-Manuel Tamunoinemi,Ifedili Ikechuckwu,Reed Guy,Ibebuogu Uzoma N,Khouzam Rami N
Current problems in cardiology
Non-ST elevation-acute coronary syndrome (NSTE-ACS) includes NSTE myocardial infarction and unstable angina. This patient population forms approximately two-thirds of all hospital admissions for ACS in the United States each year and is associated with an in-hospital mortality of 5%. NSTE-ACS is primarily due to an acute change in the supply and demand balance of coronary perfusion and myocardial oxygen consumption, because of the significant coronary artery obstruction presenting as plaque rupture or erosion. Nevertheless, nonobstructive causes may lead to that same phenomenon by excessive myocardial oxygen demand or reduced coronary supply from hypotension, anemia, or sepsis, including transient coronary vasospasm and endocardial dysfunction. The recent clinical application of high-sensitivity troponin biomarker assays and computer tomography angiography shows promise for improving the diagnosis and the risk stratification of patients with angina symptoms. Implementation of recent updates to the American College of Cardiology/American Heart Association (ACC/AHA) guidelines on NSTE-ACS, especially regarding the selection and duration of antiplatelet therapy, have led to improvement in management and outcomes of this disease. Additionally, new adjunctive therapies and approaches to diagnosis and treatment are discussed. Despite the progress made in recent years in the diagnosis and management of NSTE-ACS, morbidity remains high and mortality is significant. Such a fact suggests that future research targeting prevention, early diagnosis, and intervention in these patients is warranted. This article provides a detailed overview of the most recent information on the pathophysiology, diagnosis, treatment, and prognosis of NSTE-ACS.
10.1016/j.cpcardiol.2017.04.006
Transcoronary gradients of vascular miRNAs and coronary atherosclerotic plaque characteristics.
Leistner David M,Boeckel Jes-Niels,Reis Sophia M,Thome Claudia E,De Rosa Roberta,Keller Till,Palapies Lars,Fichtlscherer Stephan,Dimmeler Stefanie,Zeiher Andreas M
European heart journal
AIMS:Circulating microRNAs (miRs) may reflect pathophysiologically relevant processes in the atherosclerotically diseased coronary arterial wall. Given the unmet medical need to identify patients with an unstable plaque phenotype, we determined the relation of circulating atherosclerosis-regulatory miRs with plaque phenotypes. METHODS AND RESULTS:We assessed coronary atherosclerotic plaque burden and phenotype by optical coherence tomography in 52 patients and measured the levels of circulating miRs across the transcoronary gradient. The overall plaque load was significantly correlated with transcoronary concentration gradients of miR-126-3p (P = 0.04), miR-145-5p (P = 0.01), miR-155-5p (P < 0.01), and miR-29b-3p (P = 0.02), but not with other miRs such as miR-92a-3p. In patients with a high extent of vulnerable plaques as assessed by the presence of thin-cap fibroatheromas (TCFAs), significantly higher transcoronary gradients were observed, particularly for miR-126-3p, miR-126-5p, and miR-145-5p (all P < 0.02). Transcoronary gradients of miR-126-3p (P < 0.01), miR-126-5p (P < 0.01), miR-145-5p (P = 0.01), miR-29b-3p (P = 0.03), and miR-155-5p (P = 0.02) demonstrated a significant discriminatory power to predict the presence of TCFAs (AUC > 0.7 for all). Moreover, aortic and venous coronary sinus levels of miR-29b-3p were inversely correlated with plaque fibrosis, a finding that is consistent with the anti-fibrotic activity of miR-29b-3p. CONCLUSION:The overall plaque burden and plaque phenotypes are associated with changes in the kinetics of miR-concentrations across the transcoronary passage. Transcoronary gradients of the anti-atherosclerotic miR-126-3p and miR-145-5p correlated with the extent of TCFAs, suggesting that instable plaques may affect the local uptake or degradation of these miRs.
10.1093/eurheartj/ehw047
Has our understanding of calcification in human coronary atherosclerosis progressed?
Otsuka Fumiyuki,Sakakura Kenichi,Yahagi Kazuyuki,Joner Michael,Virmani Renu
Arteriosclerosis, thrombosis, and vascular biology
Coronary artery calcification is a well-established predictor of future cardiac events; however, it is not a predictor of unstable plaque. The intimal calcification of the atherosclerotic plaques may begin with smooth muscle cell apoptosis and release of matrix vesicles and is almost always seen microscopically in pathological intimal thickening, which appears as microcalcification (≥0.5 μm, typically <15 μm in diameter). Calcification increases with macrophage infiltration into the lipid pool in early fibroatheroma where they undergo apoptosis and release matrix vesicles. The confluence of calcified areas involves extracellular matrix and the necrotic core, which can be identified by radiography as speckled (≤2 mm) or fragmented (>2, <5 mm) calcification. The calcification in thin-cap fibroatheromas and plaque rupture is generally less than what is observed in stable plaques and is usually speckled or fragmented. Fragmented calcification spreads into the surrounding collagen-rich matrix forming calcified sheets, the hallmarks of fibrocalcific plaques. The calcified sheets may break into nodules with fibrin deposition, and when accompanied by luminal protrusion, it is associated with thrombosis. Calcification is highest in fibrocalcific plaques followed by healed plaque rupture and is the least in erosion and pathological intimal thickening. The extent of calcification is greater in men than in women especially in the premenopausal period and is also greater in whites compared with blacks. The mechanisms of intimal calcification remain poorly understood in humans. Calcification often occurs in the presence of apoptosis of smooth muscle cells and macrophages with matrix vesicles accompanied by expression of osteogenic markers within the vessel wall.
10.1161/ATVBAHA.113.302642
Utility of mass spectrometry for the diagnosis of the unstable coronary plaque.
Jacob Shana S,Hassan Mohamed,Yacoub Magdi H
Global cardiology science & practice
Mass spectrometry is a powerful technique that is used to identify unknown compounds, to quantify known materials, and to elucidate the structure and chemical properties of molecules. Recent advances in the accuracy and speed of the technology have allowed data acquisition for the global analysis of lipids from complex samples such as blood plasma or serum. Here, mass spectrometry as a tool is described, its limitations explained and its application to biomarker discovery in coronary artery disease is considered. In particular an application of mass spectrometry for the discovery of lipid biomarkers that may indicate plaque morphology that could lead to myocardial infarction is elucidated.
10.5339/gcsp.2015.25
The diagnosis of coronary plaque stability by multi-slice computed tomography coronary angiography.
Song Feng-Xiang,Zhou Jun,Zhou Jian-Jun,Shi Yu-Xin,Zeng Meng-Su,Zhang Zhi-Yong,Lv Peng,Sheng Ruo-Fan
Journal of thoracic disease
BACKGROUND:Coronary computed tomographic angiography is a robust non-invasive method to assess coronary artery disease (CAD) and analyze coronary plaque stability, especially for the non-calcified plaques. The aim of this study was to investigate the differential characteristics between the unstable coronary plaques and the stable coronary plaques using multi-slice computed tomography (MSCT). METHODS:Sixty patients with coronary heart disease (37 unstable plaques and 31 stable plaques) were included. The napkin ring thickness, napkin-ring sign, plaque CT attenuation and degree of lumen stenosis were retrospectively analyzed. The diagnostic performances of MSCT were determined to predict the unstable plaques. The difference was statistically significant if P<0.05. RESULTS:The napkin ring thickness of the unstable plaques was thinner than that of the stable plaques (P<0.05). The napkin-ring sign was more frequently observed in the unstable group (89.2%) than the stable group (22.6%, P<0.05). The average CT value of the unstable plaques (26.8±17.8 HU) was lower than that of the stable plaques (68.5±25.5 HU, P<0.05). The unstable plaques had more severe lumen stenosis or occlusion (70.3%) than the stable plaques (41.9%, P<0.05). The measurable napkin ring thickness of the plaques with a cutoff value of 0.8 mm and an accuracy of 89.5% was one independent factor to predict unstable plaques. The optimal combined threshold of the napkin-ring sign and/or the plaque CT value of 53 HU with an accuracy of 80.9% was to predict unstable plaques. CONCLUSIONS:The optimal combined threshold of the napkin-ring sign and/or the plaque CT value ≤53 HU may be a good indicator to predict the unstable plaques in patients with CAD. The subgroup of measurable napkin ring thickness of the non-calcified plaques may also be an independent factor to predict the unstable plaques in patients with CAD.
10.21037/jtd.2018.04.43
Ultrasound tissue characterization of vulnerable atherosclerotic plaque.
Picano Eugenio,Paterni Marco
International journal of molecular sciences
A thrombotic occlusion of the vessel fed by ruptured coronary atherosclerotic plaque may result in unstable angina, myocardial infarction or death, whereas embolization from a plaque in carotid arteries may result in transient ischemic attack or stroke. The atherosclerotic plaque prone to such clinical events is termed high-risk or vulnerable plaque, and its identification in humans before it becomes symptomatic has been elusive to date. Ultrasonic tissue characterization of the atherosclerotic plaque is possible with different techniques--such as vascular, transesophageal, and intravascular ultrasound--on a variety of arterial segments, including carotid, aorta, and coronary districts. The image analysis can be based on visual, video-densitometric or radiofrequency methods and identifies three distinct textural patterns: hypo-echoic (corresponding to lipid- and hemorrhage-rich plaque), iso- or moderately hyper-echoic (fibrotic or fibro-fatty plaque), and markedly hyperechoic with shadowing (calcific plaque). Hypoechoic or dishomogeneous plaques, with spotty microcalcification and large plaque burden, with plaque neovascularization and surface irregularities by contrast-enhanced ultrasound, are more prone to clinical complications than hyperechoic, extensively calcified, homogeneous plaques with limited plaque burden, smooth luminal plaque surface and absence of neovascularization. Plaque ultrasound morphology is important, along with plaque geometry, in determining the atherosclerotic prognostic burden in the individual patient. New quantitative methods beyond backscatter (to include speed of sound, attenuation, strain, temperature, and high order statistics) are under development to evaluate vascular tissues. Although not yet ready for widespread clinical use, tissue characterization is listed by the American Society of Echocardiography roadmap to 2020 as one of the most promising fields of application in cardiovascular ultrasound imaging, offering unique opportunities for the early detection and treatment of atherosclerotic disease.
10.3390/ijms160510121
Intravascular imaging of coronary calcification and its clinical implications.
Mintz Gary S
JACC. Cardiovascular imaging
Calcium impacts the natural history and treatment of coronary artery disease in many ways. Intravascular imaging studies, mostly intravascular ultrasound, but more recently studies using optical coherence tomography, have been instrumental in increasing our understanding of the relationship between calcium and coronary atherosclerosis, the predictors, the natural history of this relationship, and the impact on treatment. On one hand, stable coronary lesions are associated with more calcium than unstable lesions; and the amount of calcium may affect the success of percutaneous coronary intervention. On the other hand, calcium correlates with plaque burden; unstable lesions are associated with focal calcium deposits; and calcific nodules are one of the morphologies of vulnerable plaque. This review focuses on more than 20 years of intravascular imaging studies of the relationship between calcium and coronary atherosclerosis.
10.1016/j.jcmg.2015.02.003
Prevalence and predictors of culprit plaque rupture at OCT in patients with coronary artery disease: a meta-analysis.
Iannaccone Mario,Quadri Giorgio,Taha Salma,D'Ascenzo Fabrizio,Montefusco Antonio,Omede' Pierluigi,Jang Ik-Kyung,Niccoli Giampaolo,Souteyrand Geraud,Yundai Chen,Toutouzas Konstantinos,Benedetto Sara,Barbero Umberto,Annone Umberto,Lonni Enrica,Imori Yoichi,Biondi-Zoccai Giuseppe,Templin Christian,Moretti Claudio,Luscher Thomas F,Gaita Fiorenzo
European heart journal cardiovascular Imaging
AIMS:The prevalence of plaque rupture at the culprit lesion identified by optical coherence tomography (OCT) in different clinical subset of patients undergoing coronary angiography and its clinical predictors remain to be defined. METHODS:All studies including patients with OCT evaluation of the culprit coronary plaque were included. The prevalence of culprit plaque rupture (CPR) and thin-cap fibro-atheroma (TCFA) were the primary endpoints. The factors associated with these findings were studied in a subset of patients with different clinical presentations [ST-elevation myocardial (STEMI) vs. nonST-elevation myocardial infarction (NSTEMI) vs. unstable angina (UA) vs. stable angina pectoris (SAP)]. RESULTS:One hundred and fifty citations were initially appraised at the abstract level and 23 full-text studies were assessed. The mean prevalence of CPR and TCFA was 48.1% (40.5-55.8) and 48.7% (37.4-60.1), respectively. The prevalence of CPR and TCFA were higher in STEMI (70.4 and 76.6%) than in NSTEMI (55.6 and 56.3%) and UA (39.1 and 52.9%) or SAP (6.2 and 22.8%). In the overall population at meta-regression analysis, TCFA and current smoking were the only predictors of CPR (B 3.6:2.0-5.1, P < 0.001 and 0.06:0.02-0.1, P = 0.002, respectively). The factors associated with CPR were different depending on clinical presentation. Hypertension was the only clinical predictor for STEMI (B 3.3: 1.2.-5.3 P = 0.001), while advanced age (B 0.12: 0.02-0.22, P = 0.021), diabetes mellitus (B 0.04: 0.01-0.08, P = 0.012), and hyperlipidaemia (B 0.07:0.02-0.11, P = 0.005) were the predictors in NSTEMI and UA. No clinical predictor was found in SA. CONCLUSIONS:Our analysis showed high rates of CPR and TCFA detected by OCT in CAD patients, especially in those with ACS, although their prevalence is not negligible in stable patients. TCFA seems to be a strong predictor of CPR in all the ACS scenarios.
10.1093/ehjci/jev283
CT Imaging of the Vulnerable Plaque.
Small Gary R,Chow Benjamin J W
Current treatment options in cardiovascular medicine
OPINION STATEMENT:Acute coronary syndromes are most often the result of vulnerable atherosclerotic plaque events. Plaques events occur when intimal fibroatheroma in the coronary artery wall becomes vulnerable to erosion or rupture. Such vulnerable plaques can be distinguished from quiescent atheroma by features that have been defined through histopathology and invasive imaging. A challenge for coronary CT angiography has been to identify vulnerable plaques non-invasively. Were this possible, CT angiography could offer comprehensive vessel assessment including stenosis severity and plaque characteristics with the hope of reducing acute coronary events through timely intervention. Over the past decade, advances in invasive imaging techniques have enabled unstable coronary plaques to be accessed more readily. In this fashion it has been possible to correlate invasive appearances to CT angiographic findings in an unprecedented manner. Several CT defined plaque characteristic have now been described to reliably identify unstable plaques. Retrospective studies have demonstrated the utility of these plaque features to predict future acute coronary events. If these can be confirmed in prospective studies, the intrinsic benefits of non-invasive imaging will position coronary CT angiography firmly in our armamentarium to image coronary arteries and help prevent acute coronary events.
10.1007/s11936-017-0592-9
[Coronary atherosclerosis and progression to unstable plaques : Histomorphological and molecular aspects].
Wohlschlaeger Jeremias,Bertram S,Theegarten D,Hager T,Baba H A
Herz
Atherosclerosis causes clinical symptoms through luminal narrowing by stenosis or by precipitating thrombi that obstruct blood flow to the myocardium (coronary artery disease), central nervous system (ischemic stroke) or lower extremities (peripheral vascular disease). The most common of these manifestations of atherosclerosis is coronary artery disease, clinically presenting as either stable angina or acute coronary syndromes. Atherosclerosis is a mainly lipoprotein-driven disease, which is associated with the formation of atherosclerotic plaques at specific sites of the vascular system through inflammation, necrosis, fibrosis and calcification. In most cases, plaque rupture of a so-called thin-cap fibroatheroma leads to contact of the necrotic core material of the underlying atherosclerotic plaque with blood, resulting in the formation of a thrombus with acute occlusion of the affected (coronary) artery. The atherosclerotic lesions that can cause acute coronary syndromes by formation of a thrombotic occlusion encompass (1) thin-cap fibroatheroma, (2) plaque erosion and (3) so-called calcified nodules in calcified and tortuous arteries of aged individuals. The underlying pathomechanisms remain incompletely understood so far. In this review, the mechanisms of atherosclerotic plaque initiation and progression are discussed.
10.1007/s00059-015-4341-0
Noninvasive Imaging to Assess Atherosclerotic Plaque Composition and Disease Activity: Coronary and Carotid Applications.
JACC. Cardiovascular imaging
Cardiovascular disease is one of the leading causes of mortality and morbidity worldwide. Atherosclerosis imaging has traditionally focused on detection of obstructive luminal stenoses or measurements of plaque burden. However, with advances in imaging technology it has now become possible to noninvasively interrogate plaque composition and disease activity, thereby differentiating stable from unstable patterns of disease and potentially improving risk stratification. This manuscript reviews multimodality imaging in this field, focusing on carotid and coronary atherosclerosis and how these novel techniques have the potential to complement current imaging assessments and improve clinical decision making.
10.1016/j.jcmg.2019.03.033
Inflammation as a Therapeutic Target in Atherosclerosis.
Nguyen Mau T,Fernando Sanuja,Schwarz Nisha,Tan Joanne Tm,Bursill Christina A,Psaltis Peter J
Journal of clinical medicine
Atherosclerotic coronary artery disease (CAD) results from build-up of cholesterol-rich plaques in the walls of the coronary arteries and is a leading cause of death. Inflammation is central to atherosclerosis. Uncontrolled inflammation makes coronary plaques "unstable" and vulnerable to rupture or erosion, leading to thrombosis and myocardial infarction (MI). As multiple inflamed plaques often co-exist in the coronary system, patients are at risk of repeated atherothrombotic cardiovascular events after MI, with rates of 10-12% at one year and 18-20% at three years. This is largely because current therapies for CAD, such as lipid-lowering statins, do not adequately control plaque inflammation. New anti-atherosclerotic agents are therefore needed, especially those that better target inflammation. The recent positive results for the anti-interleukin-1-beta (IL-1β) monoclonal antibody, Canakinumab, in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) clinical trial has provided a major stimulant to the field. It highlights that not only is inflammation important from a pathogenic and risk prediction perspective in CAD, but that reducing inflammation can be beneficial. The challenge is now to find the best strategies to achieve this in real-world practice. This review outlines the role that inflammation plays in atherosclerosis and provides an update on anti-inflammatory therapies currently being investigated to target atherosclerosis.
10.3390/jcm8081109
Contribution of neovascularization and intraplaque haemorrhage to atherosclerotic plaque progression and instability.
Chistiakov D A,Orekhov A N,Bobryshev Y V
Acta physiologica (Oxford, England)
Atherosclerosis is a continuous pathological process that starts early in life and progresses frequently to unstable plaques. Plaque rupture leads to deleterious consequences such as acute coronary syndrome, stroke and atherothrombosis. The vulnerable lesion has several structural and functional hallmarks that distinguish it from the stable plaque. The unstable plaque has large necrotic core (over 40% plaque volume) composed of cholesterol crystals, cholesterol esters, oxidized lipids, fibrin, erythrocytes and their remnants (haeme, iron, haemoglobin), and dying macrophages. The fibrous cap is thin, depleted of smooth muscle cells and collagen, and is infiltrated with proinflammatory cells. In unstable lesion, formation of neomicrovessels is increased. These neovessels have weak integrity and leak thereby leading to recurrent haemorrhages. Haemorrhages deliver erythrocytes to the necrotic core where they degrade promoting inflammation and oxidative stress. Inflammatory cells mostly presented by monocytes/macrophages, neutrophils and mast cells extravagate from bleeding neovessels and infiltrate adventitia where they support chronic inflammation. Plaque destabilization is an evolutionary process that could start at early atherosclerotic stages and whose progression is influenced by many factors including neovascularization, intraplaque haemorrhages, formation of cholesterol crystals, inflammation, oxidative stress and intraplaque protease activity.
10.1111/apha.12438
New methods to image unstable atherosclerotic plaques.
Atherosclerosis
Atherosclerotic plaque rupture is the primary mechanism responsible for myocardial infarction and stroke, the top two killers worldwide. Despite being potentially fatal, the ubiquitous prevalence of atherosclerosis amongst the middle aged and elderly renders individual events relatively rare. This makes the accurate prediction of MI and stroke challenging. Advances in imaging techniques now allow detailed assessments of plaque morphology and disease activity. Both CT and MR can identify certain unstable plaque characteristics thought to be associated with an increased risk of rupture and events. PET imaging allows the activity of distinct pathological processes associated with atherosclerosis to be measured, differentiating patients with inactive and active disease states. Hybrid integration of PET with CT or MR now allows for an accurate assessment of not only plaque burden and morphology but plaque biology too. In this review, we discuss how these advanced imaging techniques hold promise in redefining our understanding of stable and unstable coronary artery disease beyond symptomatic status, and how they may refine patient risk-prediction and the rationing of expensive novel therapies.
10.1016/j.atherosclerosis.2018.03.021
Different Plaque Composition and Progression in Patients with Stable and Unstable Coronary Syndromes Evaluated by Cardiac CT.
Dalager Maiken Glud,Bøttcher Morten,Thygesen Jesper,Andersen Gratien,Bøtker Hans Erik
BioMed research international
OBJECTIVE:To compare the quantity, subtype, and progression of atherosclerosis by cardiac computed tomography (CT) and intravascular ultrasound (IVUS) in patients with stable (SAP) and unstable angina pectoris or non-ST-elevation myocardial infarction (UAP/n-STEMI). METHODS:Forty patients with SAP and 20 with UAP/n-STEMI underwent cardiac CT and angiography with IVUS at baseline and after one year. Atherosclerotic segments were divided into calcified, mixed, or noncalcified subtypes, and significant stenoses were registered. RESULTS:Thirty-two SAP and 15 UAP/n-STEMI patients completed the CT follow-up. At baseline, the number of atherosclerotic segments was higher in UAP/n-STEMI than in SAP (P = 0.039). UAP/n-STEMI patients had more segments with noncalcified plaques (P = 0.0005) whereas SAP patients had more segments with calcified plaques (P = 0.013). The number of segments with significant stenosis did not differ between the groups, but noncalcified plaques more frequently caused significant stenoses in UAP/n-STEMI than in SAP patients (P = 0.0002). After one year the number of segments with atherosclerosis increased in SAP patients (P = 0.0001). The number of atherosclerotic segments remained unchanged in UAP/n-STEMI patients. However, composition was altered as the number of segments with noncalcified plaques decreased (P = 0.018). IVUS data confirmed the CT findings. CONCLUSION:Quantity, subtype, and progression of atherosclerosis differ between SAP and UAP/n-STEMI patients.
10.1155/2015/401357
Advances in mechanisms, imaging and management of the unstable plaque.
Niccoli Giampaolo,Liuzzo Giovanna,Montone Rocco A,Crea Filippo
Atherosclerosis
Post-mortem observations demonstrated that plaque fissure was the final event leading to coronary thrombosis and occlusion in about two-thirds of cases of sudden coronary death. Plaques prone to fissure have, therefore, been defined "vulnerable plaques" and are identified by specific anatomic features including thin inflamed fibrous cap, large lipidic core and positive remodeling. Accordingly, elegant imaging modalities have been developed in order to identify this "holy grail". However, the results of prognostic studies based on the identification of vulnerable plaques have not been encouraging because of the low positive predictive value for major cardiovascular events. This observation is not surprising as the pathogenesis of acute coronary syndromes is complex and multifactorial. In this review we propose a pathogenetic classification of acute coronary syndromes in the attempt to identify homogeneous groups of patients with a common mechanism of coronary instability which can be identified by using specific biomarkers and imaging techniques, and become a specific therapeutic target.
10.1016/j.atherosclerosis.2014.01.036
Cardiac Computed Tomography: Assessment of Coronary Inflammation and Other Plaque Features.
Oikonomou Evangelos K,West Henry W,Antoniades Charalambos
Arteriosclerosis, thrombosis, and vascular biology
Unstable coronary plaques that are prone to erosion and rupture are the major cause of acute coronary syndromes. Our expanding understanding of the biological mechanisms of coronary atherosclerosis and rapid technological advances in the field of medical imaging has established cardiac computed tomography as a first-line diagnostic test in the assessment of suspected coronary artery disease, and as a powerful method of detecting the vulnerable plaque and patient. Cardiac computed tomography can provide a noninvasive, yet comprehensive, qualitative and quantitative assessment of coronary plaque burden, detect distinct high-risk morphological plaque features, assess the hemodynamic significance of coronary lesions and quantify the coronary inflammatory burden by tracking the effects of arterial inflammation on the composition of the adjacent perivascular fat. Furthermore, advances in machine learning, computational fluid dynamic modeling, and the development of targeted contrast agents continue to expand the capabilities of cardiac computed tomography imaging. In our Review, we discuss the current role of cardiac computed tomography in the assessment of coronary atherosclerosis, highlighting its dual function as a clinical and research tool that provides a wealth of structural and functional information, with far-reaching diagnostic and prognostic implications.
10.1161/ATVBAHA.119.312899
Coronary plaque morphology on multi-modality imagining and periprocedural myocardial infarction after percutaneous coronary intervention.
Sato Akira,Aonuma Kazutaka
International journal of cardiology. Heart & vasculature
Percutaneous coronary intervention (PCI) may be complicated by periprocedural myocardial infarction (PMI) as manifested by elevated cardiac biomarkers such as creatine kinase (CK)-MB or troponin T. The occurrence of PMI has been shown to be associated with worse short- and long-term clinical outcome. However, recent studies suggest that PMI defined by biomarker levels alone is a marker of atherosclerosis burden and procedural complexity but in most cases does not have independent prognostic significance. Diagnostic multi-modality imaging such as intravascular ultrasound, optical coherence tomography, coronary angioscopy, near-infrared spectroscopy, multidetector computed tomography, and magnetic resonance imaging can be used to closely investigate the atherosclerotic lesion in order to detect morphological markers of unstable and vulnerable plaques in the patients undergoing PCI. With the improvement of technical aspects of multimodality coronary imaging, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology and patients outcomes. There were numerous published data regarding the relationship between pre-PCI lesion subsets on multi-modality imaging and post-PCI biomarker levels. In this review, we discuss the relationship between coronary plaque morphology estimated by invasive or noninvasive coronary imaging and the occurrence of PMI. Furthermore, this review underlies that the value of the multimodality coronary imaging approach will become the gold standard for invasive or noninvasive prediction of PMI in clinical practice.
10.1016/j.ijcha.2016.03.009
Unstable coronary plaque characteristics are associated with high-sensitivity cardiac troponin T and N-terminal Pro-Brain Natriuretic Peptide.
Altintas Sibel,Cardinaels Eline P M,Versteylen Mathijs O,Joosen Ivo A,Seifert Milan,Wildberger Joachim E,Crijns Harry J,Nelemans Patricia J,Van Dieijen-Visser Marja P,Mingels Alma M A,Das Marco,Kietselaer Bas L
Journal of cardiovascular computed tomography
BACKGROUND:Unstable plaque characteristics on coronary CT angiography (CTA), serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal Pro-Brain Natriuretic Peptide (NT-proBNP) concentrations are associated with cardiovascular events. OBJECTIVE:To investigate the association between coronary CTA defined quantifiable plaque characteristics, hs-cTnT and NT-proBNP. METHODS:81 consecutive stable chest pain patients with an intermediate-to-high risk were analyzed. Coronary CTA was performed using a 64-slice multidetector-row CT-scanner. Total coronary plaque volume, calcified volume, non-calcified volume, plaque burden, remodeling index (RI) and number of plaques were measured using dedicated software. A total plaque score ("Sum plaque score") incorporating total plaque volume, RI, plaque burden and number of plaques was defined. Hs-cTnT and NT-proBNP concentrations were measured in serum samples before coronary CTA. RESULTS:Univariate regression analysis demonstrated significant associations of hs-cTnT and NT-proBNP with total plaque volume (r hs-cTnT = .256; r NT-proBNP = .270), calcified volume (r hs-cTnT = .344; r NT-proBNP = .344), RI (r hs-cTnT = .335; r NT-proBNP = .342) and number of plaques (r hs-cTnT = .355; r NT-proBNP = .301) (all P values ≤ .021). Non-calcified plaque volume showed no association with hs-cTnT and NT-proBNP (r hs-cTnT = .050; r NT-proBNP = .087; P value = .660 and P value = .442). The "Sum plaque score" showed the highest correlation compared to other plaque parameters (r hs-cTnT = .362; r NT-proBNP = .409; P value = .001 and P value ≤ .001). CONCLUSION:Our data suggest that coronary plaque morphology parameters, derived by dedicated software, are associated with serum hs-cTnT and NT-proBNP concentrations.
10.1016/j.jcct.2015.10.001
Use of High-Risk Coronary Atherosclerotic Plaque Detection for Risk Stratification of Patients With Stable Chest Pain: A Secondary Analysis of the PROMISE Randomized Clinical Trial.
Ferencik Maros,Mayrhofer Thomas,Bittner Daniel O,Emami Hamed,Puchner Stefan B,Lu Michael T,Meyersohn Nandini M,Ivanov Alexander V,Adami Elizabeth C,Patel Manesh R,Mark Daniel B,Udelson James E,Lee Kerry L,Douglas Pamela S,Hoffmann Udo
JAMA cardiology
Importance:Coronary computed tomographic angiography (coronary CTA) can characterize coronary artery disease, including high-risk plaque. A noninvasive method of identifying high-risk plaque before major adverse cardiovascular events (MACE) could provide practice-changing optimizations in coronary artery disease care. Objective:To determine whether high-risk plaque detected by coronary CTA was associated with incident MACE independently of significant stenosis (SS) and cardiovascular risk factors. Design, Setting, and Participants:This prespecified nested observational cohort study was part of the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. All stable, symptomatic outpatients in this trial who required noninvasive cardiovascular testing and received coronary CTA were included and followed up for a median of 25 months. Exposures:Core laboratory assessment of coronary CTA for SS and high-risk plaque (eg, positive remodeling, low computed tomographic attenuation, or napkin-ring sign). Main Outcomes and Measures:The primary end point was an adjudicated composite of MACE (defined as death, myocardial infarction, or unstable angina). Results:The study included 4415 patients, of whom 2296 (52%) were women, with a mean age of 60.5 years, a median atherosclerotic cardiovascular disease (ASCVD) risk score of 11, and a MACE rate of 3% (131 events). A total of 676 patients (15.3%) had high-risk plaques, and 276 (6.3%) had SS. The presence of high-risk plaque was associated with a higher MACE rate (6.4% vs 2.4%; hazard ratio, 2.73; 95% CI, 1.89-3.93). This association persisted after adjustment for ASCVD risk score and SS (adjusted hazard ratio [aHR], 1.72; 95% CI, 1.13-2.62). Adding high-risk plaque to the ASCVD risk score and SS assessment led to a significant continuous net reclassification improvement (0.34; 95% CI, 0.02-0.51). Presence of high-risk plaque increased MACE risk among patients with nonobstructive coronary artery disease relative to patients without high-risk plaque (aHR, 4.31 vs 2.64; 95% CI, 2.25-8.26 vs 1.49-4.69). There were no significant differences in MACE in patients with SS and high-risk plaque as opposed to those with SS but not high-risk plaque (aHR, 8.68 vs. 9.31; 95% CI, 4.25-17.73 vs 4.21-20.61). High-risk plaque was a stronger predictor of MACE in women (aHR, 2.41; 95% CI, 1.25-4.64) vs men (aHR, 1.40; 95% CI, 0.81-2.39) and younger patients (aHR, 2.33; 95% CI, 1.20-4.51) vs older ones (aHR, 1.36; 95% CI, 0.77-2.39). Conclusions and Relevance:High-risk plaque found by coronary CTA was associated with a future MACE in a large US population of outpatients with stable chest pain. High-risk plaque may be an additional risk stratification tool, especially in patients with nonobstructive coronary artery disease, younger patients, and women. The importance of findings is limited by low absolute MACE rates and low positive predictive value of high-risk plaque. Trial Registration:clinicaltrials.gov Indentifier: NCT01174550.
10.1001/jamacardio.2017.4973
Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease.
Circulation
BACKGROUND:DNA methylation is implicated in coronary heart disease (CHD), but current evidence is based on small, cross-sectional studies. We examined blood DNA methylation in relation to incident CHD across multiple prospective cohorts. METHODS:Nine population-based cohorts from the United States and Europe profiled epigenome-wide blood leukocyte DNA methylation using the Illumina Infinium 450k microarray, and prospectively ascertained CHD events including coronary insufficiency/unstable angina, recognized myocardial infarction, coronary revascularization, and coronary death. Cohorts conducted race-specific analyses adjusted for age, sex, smoking, education, body mass index, blood cell type proportions, and technical variables. We conducted fixed-effect meta-analyses across cohorts. RESULTS:Among 11 461 individuals (mean age 64 years, 67% women, 35% African American) free of CHD at baseline, 1895 developed CHD during a mean follow-up of 11.2 years. Methylation levels at 52 CpG (cytosine-phosphate-guanine) sites were associated with incident CHD or myocardial infarction (false discovery rate<0.05). These CpGs map to genes with key roles in calcium regulation (ATP2B2, CASR, GUCA1B, HPCAL1), and genes identified in genome- and epigenome-wide studies of serum calcium (CASR), serum calcium-related risk of CHD (CASR), coronary artery calcified plaque (PTPRN2), and kidney function (CDH23, HPCAL1), among others. Mendelian randomization analyses supported a causal effect of DNA methylation on incident CHD; these CpGs map to active regulatory regions proximal to long non-coding RNA transcripts. CONCLUSION:Methylation of blood-derived DNA is associated with risk of future CHD across diverse populations and may serve as an informative tool for gaining further insight on the development of CHD.
10.1161/CIRCULATIONAHA.118.039357
Coronary Artery Calcification and its Progression: What Does it Really Mean?
Mori Hiroyoshi,Torii Sho,Kutyna Matthew,Sakamoto Atsushi,Finn Aloke V,Virmani Renu
JACC. Cardiovascular imaging
Coronary artery calcification is concomitant with the development of advanced atherosclerosis. Coronary artery calcification pathologically begins as microcalcifications (0.5 to 15.0 μm) and grows into larger calcium fragments, which eventually result in sheet-like deposits (>3 mm). This evolution is observed to occur concurrently with the progression of plaque. These fragments and sheets of calcification can be easily identified by radiography as well as by computed tomography and intravascular imaging. Many imaging modalities have proposed spotty calcification to be a predictor of unstable plaque and have suggested more extensive calcification to be associated with stable plaques and perhaps the use of statin therapy. We will review the pathology of coronary calcification in humans with a focus on risk factors, relationship with plaque progression, correlation with plaque (in)stability, and effect of pharmacologic interventions.
10.1016/j.jcmg.2017.10.012