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    Inflammasome activation in end-stage heart failure-associated atrial fibrillation. ESC heart failure AIMS:Inflammatory pathways are increasingly recognized as an important factor in the pathophysiology of both heart failure (HF) and atrial fibrillation (AF). However, there is no data about inflammation-related histological and molecular alterations in HF-associated AF. The objective of our study was to investigate inflammatory pathways and fibrosis in end-stage HF-associated AF. METHODS AND RESULTS:Left atrial samples of 24 male patients with end stage ischemic HF undergoing heart transplantation were analysed. Twelve patients suffered from sustained AF while the others had no documented AF. The expression of inflammasome sensors and their downstream signalling were investigated by Western blot. No differences were observed in the expression of inflammasome sensors between the two groups, while cleaved caspase-1 increased tendentiously in the AF group (P = 0.051). Cleaved caspase-1 also showed significant correlation with the expression of interleukin-1β and its cleaved form in the total population and in the AF group (P < 0.05). The presence of myocardial and epicardial macrophages were assessed by ionized calcium-binding adaptor molecule 1 (Iba1) immunostaining. Number of macrophages showed a tendency towards elevation in the left atrial myocardium and epicardium of AF compared with SR group. The amount of total and interstitial fibrosis was determined on Masson's trichrome-stained sections. Histological assessment revealed no difference between AF and SR groups in the amount of either total or interstitial fibrosis. CONCLUSIONS:This is the first study on inflammation-related differences between HF with SR or AF showing elevated inflammasome activity and enhanced macrophage infiltration in left atrial samples of patients with AF. 10.1002/ehf2.13972
    Serum Urate and Heart Failure: A Bidirectional Mendelian Randomisation Study. European journal of preventive cardiology AIMS:Observational studies indicate that serum urate level is associated with heart failure. However, whether this association is causal remains controversial, due to confounding factors and reverse causality. We aim to evaluate the causal relationship of genetically predicted serum urate level with heart failure (HF). METHODS:A bidirectional Mendelian randomisation (MR) study was performed. Instrumental variables were obtained from the largest genome-wide association studies of serum urate (457,690 individuals) to date. We obtained summary statistics of HF from HERMES consortium (47,309 cases; 930,014 controls), the FinnGen study (13,087 cases; 195,091 controls), and the UK Biobank study (1,088 cases; 360,106 controls). Inverse-variance weighted method was applied to obtain MR estimates and other statistical methods were conducted in the sensitivity analyses. The reverse MR analysis was performed to evaluate the effect of HF on serum urate levels. RESULTS:Genetically determined serum urate level was associated with HF (odds ratio (OR), 1.07; 95% CI, 1.03-1.10; p=8.6×10-5). The main results kept robust in the most sensitivity analyses. The association pattern remained for the heart failure in FinnGen (OR, 1.10; 95%CI, 1.03-1.19; p=0.008) and the combined results of three data sources (OR, 1.08; 95%CI, 1.04-1.13; p<0.001). No consistent evidence was found for the causal effect of HF on serum urate levels. CONCLUSIONS:We provide consistent evidence for the causal effect of genetically predicted serum urate level on HF, but not the reverse effect of HF. Urate-lowering therapy may be of cardiovascular benefit in the prevention of HF. 10.1093/eurjpc/zwac100
    Diagnosis of acute heart failure in CT pulmonary angiography: feasibility and accuracy. Vittoria de Martini Ilaria,Kobe Adrian Raoul,Roeren Christian,Manka Robert,Euler André,Keller Dagmar I,Ruschitzka Frank,Alkadhi Hatem,Eberhard Matthias European radiology OBJECTIVES:To evaluate the feasibility and accuracy of diagnosing acute heart failure (HF) with CT pulmonary angiography (CTPA) in emergency department patients. METHODS:In this retrospective single-center study, we evaluated 150 emergency department patients (mean age 65 ± 17 years) undergoing CTPA with a fixed scan (100 kVp) and contrast media protocol (60 mL, 4 mL/s) who had no pulmonary embolism (PE). Patients were subdivided into training cohort (n = 100) and test cohort (n = 50). Three independent, blinded readers measured the attenuation in the right ventricle (RV) and left ventricle (LV) on axial images. The ratio (HU) and difference (HU) between RV and LV attenuation were calculated. Diagnosis of acute HF was made on the basis of clinical, laboratory, and echocardiography data. Optimal thresholds, sensitivity, and specificity were calculated using the area under the curve (AUC) from receiver operating characteristics analysis. RESULTS:Fifty-nine of the 150 patients (40%) were diagnosed with acute HF. Attenuation measurements showed an almost perfect interobserver agreement (intraclass correlation coefficient: 0.986, 95%CI: 0.980-0.991). NT-pro BNP exhibited moderate correlations with HU (r = 0.50, p < 0.001) and HU (r = 0.50, p < 0.001). In the training cohort, HU (AUC: 0.89, 95%CI: 0.82-0.95) and HU (AUC: 0.88, 95%CI: 0.81-0.95) showed a very good performance to diagnose HF. Optimal cutoff values were 1.42 for HU (sensitivity 93%; specificity 75%) and 113 for HU (sensitivity 93%; specificity 73%). Applying these thresholds to the test cohort yielded a sensitivity of 89% and 89% and a specificity of 69% and 63% for HU and HU, respectively. CONCLUSION:In emergency department patients undergoing CTPA and showing no PE, both HU and HU have a high sensitivity for diagnosing acute HF. KEY POINTS:• Heart failure is a common differential diagnosis in patients undergoing CT pulmonary angiography. • In emergency department patients undergoing CT pulmonary angiography and showing no pulmonary embolism, attenuation differences of the left and right ventricle have a high sensitivity for diagnosing acute heart failure. 10.1007/s00330-022-08676-9
    Prediction of Mortality in Coronary Artery Disease: Role of Machine Learning and Maximal Exercise Capacity. Mayo Clinic proceedings OBJECTIVE:To develop a prediction model for survival of patients with coronary artery disease (CAD) using health conditions beyond cardiovascular risk factors, including maximal exercise capacity, through the application of machine learning (ML) techniques. METHODS:Analysis of data from a retrospective cohort linking clinical, administrative, and vital status databases from 1995 to 2016 was performed. Inclusion criteria were age 18 years or older, diagnosis of CAD, referral to a cardiac rehabilitation program, and available baseline exercise test results. Primary outcome was death from any cause. Feature selection was performed using supervised and unsupervised ML techniques. The final prognostic model used the survival tree (ST) algorithm. RESULTS:From the cohort of 13,362 patients (60±11 years; 2400 [18%] women), 1577 died during a median follow-up of 8 years (interquartile range, 4 to 13 years), with an estimated survival of 67% up to 21 years. Feature selection revealed age and peak metabolic equivalents (METs) as the features with the greatest importance for mortality prediction. Using these 2 features, the ST generated a long-term prediction with a C-index of 0.729 by splitting patients in 8 clusters with different survival probabilities (P<.001). The ST root node was split by peak METs of 6.15 or less or more than 6.15, and each patient's subgroup was further split by age or other peak METs cut points. CONCLUSION:Applying ML techniques, age and maximal exercise capacity accurately predict mortality in patients with CAD and outperform variables commonly used for decision-making in clinical practice. A novel and simple prognostic model was established, and maximal exercise capacity was further suggested to be one of the most powerful predictors of mortality in CAD. 10.1016/j.mayocp.2022.01.016
    Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self. Circulation research BACKGROUND:Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation' notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. METHODS:We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. RESULTS:In addition to macrophages, we found a high proportion of αβ T cells in the coronary plaques. Most of these T cells lack high expression of and , indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated αβ T cells (CD4<CD8), exhibiting clonal expansion of specific TCRs. Interestingly, we found that these plaque T cells had TCRs specific for influenza, coronavirus, and other viral epitopes, which share sequence homologies to proteins found on smooth muscle cells and endothelial cells, suggesting potential autoimmune-mediated T-cell activation in the absence of active infection. To better understand the potential function of these activated plaque T cells, we then interrogated their transcriptome at the single-cell level. Of the 3 T-cell phenotypic clusters with the highest expression of the activation marker , 2 clusters expressed a proinflammatory and cytolytic signature characteristic of CD8 cells, while the other expressed AREG (amphiregulin), which promotes smooth muscle cell proliferation and fibrosis, and, thus, contributes to plaque progression. CONCLUSIONS:Taken together, these findings demonstrate that plaque T cells are clonally expanded potentially by antigen engagement, are potentially reactive to self-epitopes, and may interact with smooth muscle cells and macrophages in the plaque microenvironment. 10.1161/CIRCRESAHA.121.320090
    Physical activity attenuates but does not eliminate coronary heart disease risk amongst adults with risk factors: EPIC-CVD case-cohort study. European journal of preventive cardiology AIMS:This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. METHODS AND RESULTS:EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal).Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32-64%] and 21% (95%CI 2-44%), with hypercholesterolaemia were 80% (95%CI 55-108%) and 48% (95%CI 22-81%), with hypertension were 80% (95%CI 65-96%) and 49% (95%CI 28-74%), with diabetes were 142% (95%CI 63-260%), and 100% (95%CI 32-204%), and amongst smokers were 152% (95%CI 122-186%) and 109% (95%CI 74-150%). CONCLUSIONS:In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk. 10.1093/eurjpc/zwac055
    Causal Gene Confusion: The Complicated Locus for Coronary Artery Disease. Arteriosclerosis, thrombosis, and vascular biology 10.1161/ATVBAHA.122.317539
    Long-Term Treatment with the Combination of Rivaroxaban and Aspirin in Patients with Chronic Coronary or Peripheral Artery Disease: Outcomes During the Open Label Extension of the COMPASS trial. Eikelboom John W,Bosch Jacqueline,Connolly Stuart J,Tyrwitt Jessica,Fox Keith A A,Muehlhofer Eva,Neumann Christoph,Tasto Christoph,Bangdiwala Shrikant,Diaz Rafael,Alings Marco,Dagenais Gilles R,Leong Darryl P,Lonn Eva M,Avezum Alvaro,Piegas Leopoldo S,Widimsky Petr,Parkhomenko Alexander N,Bhatt Deepak L,Branch Kelley R H,Probstfield Jeffrey L,Lopez-Jaramillo Patricio,Rydén Lars,Pogosova Nana,Keltai Katalin,Keltai Matyas,Ertl Georg,Stoerk Stefan,Dans Antonio L,Lanas Fernando,Liang Yan,Zhu Jun,Torp-Pedersen Christian,Maggioni Aldo P,Commerford Patrick J,Guzik Tomasz J,Vanassche Thomas,Verhamme Peter,O'Donnell Martin,Tonkin Andrew M,Varigos John D,Vinereanu Dragos,Felix Camillo,Kim Jae-Hyung,Ibrahim Khairul S,Lewis Basil S,Metsarinne Kaj P,Aboyans Victor,Steg Phillippe Gabriel,Hori Masatsugu,Kakkar Ajay,Anand Sonia S,Lamy Andre,Sharma Mukul,Yusuf Salim European heart journal. Cardiovascular pharmacotherapy AIMS:To describe outcomes of patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial who were treated with the combination of rivaroxaban 2.5 mg twice daily and aspirin 100 mg once daily during long term open label extension (LTOLE). METHODS AND RESULTS:Of 27 395 patients enrolled in COMPASS, 12 964 (mean age at baseline 67.2 years) from 455 sites in 32 countries were enrolled in LTOLE and treated with the combination of rivaroxaban and aspirin for a median of 374 additional days (range 1-1 191 days). During LTOLE, the incident events per 100 patient years were: for the primary outcome (cardiovascular [CV] death, stroke, or myocardial infarction [MI]) 2.35 (95% CI 2.11-2.61), mortality 1.87 (1.65-2.10), stroke 0.62 (0.50-0.76) and MI 1.02 (0.86-1.19), with confidence intervals that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major bleeding were 1.01 (0.86-1.19) and for minor bleeding 2.49 (2.24-2.75), compared with 1.67 (1.48-1.87) and 5.11 (95% CI 4.77-5.47), respectively, during the randomized treatment phase with the combination. CONCLUSION:In patients with chronic CAD and/or PAD, extended combination treatment for a median of 1 year and a maximum of 3 years was associated with incidence rates for efficacy and bleeding that were similar to or lower than those seen during the randomized treatment phase, without any new safety signals. 10.1093/ehjcvp/pvac023
    Circadian regulation of innate immunity in animals and humans and implications for human disease. Poole Joanna,Kitchen Gareth B Seminars in immunopathology Circadian rhythms are 24-h oscillating variations in physiology generated by the core circadian clock. There is now a wide body of evidence showing circadian regulation of the immune system. Innate immune cells contain the molecular circadian clock which drives rhythmic responses, from the magnitude of the inflammatory response to the numbers of circulating immune cells varying throughout the day. This leads to rhythmic presentation of disease clinically, for example the classic presentation of nocturnal asthma or the sudden development of pulmonary oedema from acute myocardial infarction first thing in the morning. 10.1007/s00281-022-00921-z
    Osteoblast MR deficiency protects against adverse ventricular remodeling after myocardial infarction. Journal of molecular and cellular cardiology RATIONALE:Mineralocorticoid receptor (MR) antagonists have been clinically used to treat heart failure. However, the underlying cellular and molecular mechanisms remain incompletely understood. METHODS AND RESULTS:Using osteoblast MR knockout (MR) mouse in combination with myocardial infarction (MI) model, we demonstrated that MR deficiency in osteoblasts significantly improved cardiac function, promoted myocardial healing, as well as attenuated cardiac hypertrophy, fibrosis and inflammatory response after MI. Gene expression profiling using RNA sequencing revealed suppressed expression of osteocalcin (OCN) in calvaria from MR mice compared to littermate control (MR) mice with or without MI. Plasma levels of undercarboxylated OCN (ucOCN) were also markedly decreased in MR mice compared to MR mice. Administration of ucOCN abolished the protective effects of osteoblast MR deficiency on infarcted hearts. Mechanistically, ucOCN treatment promoted proliferation and inflammatory cytokine secretion in macrophages. Spironolactone, an MR antagonist, significantly inhibited the expression and secretion of OCN in post-MI mice. More importantly, spironolactone decreased plasma levels of ucOCN and inflammatory cytokines in heart failure patients. CONCLUSIONS:MR deficiency in osteoblasts alleviates pathological ventricular remodeling after MI, likely through its regulation on OCN. Spironolactone may work through osteoblast MR/OCN axis to exert its therapeutic effects on pathological ventricular remodeling and heart failure in mice and human patients. 10.1016/j.yjmcc.2022.03.003
    Hyperglycaemia-associated Caspase-3 predicts diabetes and coronary artery disease events. Sun Jiangming,Singh Pratibha,Österlund Johan,Orho-Melander Marju,Melander Olle,Engström Gunnar,Edsfeldt Andreas Journal of internal medicine BACKGROUND:Apoptosis is central in both diabetes and atherosclerosis, linked to pancreatic beta cell death and plaque progression. Circulating Caspase-3 has also been associated with diabetes and coronary calcium score. Here, we explored if soluble Caspase-3 (sCaspase-3) is associated with cardio-metabolic risk factors and predicts incidence of diabetes and coronary artery disease (CAD). METHODS:Clinical data and plasma from 4637 individuals from the Malmö Diet and Cancer cohort were studied. Plasma sCaspase-3 was measured by a Proximity Extension Assay. National registers were used to identify diabetes and CAD events during follow-up. Type 2 diabetes risk variants and expression quantitative trait loci (eQTL) for sCaspase-3 were retrieved from the DIAGRAM consortium and the Genotype-Tissue Expression project. RESULTS:HbA1c was the factor with the strongest association with sCaspase-3 (r = 0.18, P = 1.3x10 ). During follow-up 666 individuals developed diabetes and 648 individuals suffered from CAD. Increasing sCaspase-3 was associated with a higher risk of developing diabetes (hazard ratio (HR) 1.18 per 1unit; P = 7 × 10 ) and CAD (HR 1.2 per 1 unit, P = 1 × 10 ) during follow-up. A genetic variant rs60780116, located upstream of CASP3, showed strong association with type 2 diabetes (OR 1.06, 95%CI 1.04-1.07, P = 8.4 × 10 ). An eQTL was identified between this variant and gene expression of CASP3, where the allele positively correlated with type 2 diabetes was associated with increased CASP3 expression in blood. CONCLUSIONS:The present study provides evidence for plasma sCaspase-3 as a marker of cardio-metabolic risk factors and as a predictor of future diabetes and CAD in a cohort without cardiovascular disease or diabetes at baseline. 10.1111/joim.13327
    Coronary Artery Disease Events and Carotid Intima-Media Thickness in Type 1 Diabetes in the DCCT/EDIC Cohort. Journal of the American Heart Association Background Carotid artery intima-media thickness (IMT) is associated with the risk of subsequent cardiovascular events in the general population. This association has not been established in type 1 diabetes. Methods and Results We studied if carotid IMT is associated with the risk of a first coronary artery disease event in participants with type 1 diabetes in the EDIC (Epidemiology of Diabetes Interventions and Complications) study, the long-term observational follow-up of the DCCT (Diabetes Control and Complications Trial). Between 1994 and 1996, common carotid artery and internal carotid artery IMT were measured with high-resolution ultrasound in 1309 study participants with a mean age of 35 years and diabetes duration of 13.8 years; 52% were men. Cox proportional hazards models evaluated the association of standardized common carotid artery IMT and internal carotid artery IMT with subsequent cardiovascular events over the next 17 years. Models were adjusted for age, sex, mean hemoglobin A1c levels, and traditional cardiovascular risk factors. Associations of common carotid artery IMT with subsequent CAD were significant after adjustment for imaging device, sex, and age (hazard ratio [HR], 1.23 per 0.09 mm [95% CI, [1.04-1.45]; =0.0141), but did not remain significant after further adjustment for traditional risk factors and hemoglobin A1c (HR, 1.14 per 0.09 mm [95% CI, 0.97-1.33]; =0.1206). No significant associations with subsequent coronary artery disease events were seen for internal carotid artery IMT. Conclusions In the DCCT/EDIC cohort with type 1 diabetes, common carotid artery IMT, but not internal carotid artery IMT, is weakly associated with subsequent coronary artery events, an association eliminated after adjusting for coexistent traditional cardiovascular risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifiers: NCT00360815 and NCT00360893. 10.1161/JAHA.121.022922
    Psychosocial Well-Being and Progression of Coronary Artery Calcification in Midlife Women. Journal of the American Heart Association Background Prevention of cardiovascular disease (CVD) is a public health priority. The combination of physical activity, a healthy diet, and abstaining from tobacco plays an important role in prevention whereas aspects of psychosocial well-being have largely been examined separately with conflicting results. This study evaluated whether the combination of indices of psychosocial well-being was associated with less progression of coronary artery calcium (CAC). Methods and Results Participants were 312 women (mean age 50.8) from the SWAN (Study of Women's Health Across the Nation) ancillary Heart Study, free of clinical CVD at baseline. A composite psychosocial well-being score was created from 6 validated psychosocial questionnaires assessing optimism, vitality, life engagement, life satisfaction, rewarding multiple roles, and positive affect. Subclinical CAC progression was defined as an increase of ≥10 Agatston units over 2.3 years measured using electron beam tomography. Relative risk (RR) regression models examined the effect of well-being on CAC progression, progressively adjusting for sociodemographic factors, depression, healthy lifestyle behaviors, and standard CVD risk factors. At baseline, 42.9% had a CAC score >0, and progression was observed in 17.6%. Well-being was associated with less progression (RR, 0.909; 95% CI, 0.843-0.979; =0.012), which remained significant with adjustment for potential confounders, depression, and health behaviors. Further adjustment for standard CVD risk factors weakened the association for the total sample (RR, 0.943; 95% CI, 0.871-1.020; =0.142) but remained significant for the 134 women with baseline CAC>0 (RR, 0.921; 95% CI, 0.852-0.995; =0.037). Conclusions Optimum early prevention of CVD in women may result from including the mind side of the mind-heart-body continuum. 10.1161/JAHA.121.023937
    Circulating Cystatin C Is an Independent Risk Marker for Cardiovascular Outcomes, Development of Renal Impairment, and Long-Term Mortality in Patients With Stable Coronary Heart Disease: The LIPID Study. Journal of the American Heart Association Background Elevated plasma cystatin C levels reflect reduced renal function and increased cardiovascular risk. Less is known about whether the increased risk persists long-term or is independent of renal function and other important biomarkers. Methods and Results Cystatin C and other biomarkers were measured at baseline (in 7863 patients) and 1 year later (in 6106 patients) in participants in the LIPID (Long-Term Intervention with Pravastatin in Ischemic Disease) study, who had a previous acute coronary syndrome. Outcomes were ascertained during the study (median follow-up, 6 years) and long-term (median follow-up, 16 years). Glomerular filtration rate (GFR) was estimated using Chronic Kidney Disease Epidemiology Collaboration equations (first GFR-creatinine, then GFR-creatinine-cystatin C). Over 6 years, in fully adjusted multivariable time-to-event models, with respect to the primary end point of coronary heart disease mortality or nonfatal myocardial infarction, for comparison of Quartile 4 versus 1 of baseline cystatin C, the hazard ratio was 1.37 (95% CI, 1.07-1.74; =0.01), and for major cardiovascular events was 1.47 (95% CI, 1.19-1.82; <0.001). Over 16 years, the association of baseline cystatin C with coronary heart disease, cardiovascular, and all-cause mortality persisted (each <0.001) and remained significant after adjustment for estimated GFR-creatinine-cystatin C. Cystatin C also predicted the development of chronic kidney disease for 6 years (odds ratio, 6.61; 95% CI, 4.28-10.20) independently of estimated GFR-creatinine and other risk factors. However, this association was no longer significant after adjustment for estimated GFR-creatinine-cystatin C. Conclusions Cystatin C independently predicted major cardiovascular events, development of chronic kidney disease, and cardiovascular and all-cause mortality. Prediction of long-term mortality was independent of improved estimation of GFR. Registration URL: https://anzctr.org.au; Unique identifier: ACTRN12616000535471. 10.1161/JAHA.121.020745
    Long-Term Outcomes are Similar Despite Sex Disparities in High-Intensity Statin Use in Patients With Nonobstructive Coronary Artery Disease Diagnosed Via Invasive Coronary Angiography. Journal of the American Heart Association 10.1161/JAHA.121.022202
    Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk. Mehta Anurag,Vasquez Nestor,Ayers Colby R,Patel Jaideep,Hooda Ananya,Khera Amit,Blumenthal Roger S,Shapiro Michael D,Rodriguez Carlos J,Tsai Michael Y,Sperling Laurence S,Virani Salim S,Blaha Michael J,Joshi Parag H Journal of the American College of Cardiology BACKGROUND:Elevated lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) score are individually associated with increased atherosclerotic cardiovascular disease (ASCVD) risk but have not been studied in combination. OBJECTIVES:This study sought to investigate the independent and joint association of Lp(a) and CAC with ASCVD risk. METHODS:Plasma Lp(a) and CAC were measured at enrollment among asymptomatic participants of the MESA (Multi-Ethnic Study of Atherosclerosis) (n = 4,512) and DHS (Dallas Heart Study) (n = 2,078) cohorts. Elevated Lp(a) was defined as the highest race-specific quintile, and 3 CAC score categories were studied (0, 1-99, and ≥100). Associations of Lp(a) and CAC with ASCVD risk were evaluated using risk factor-adjusted Cox regression models. RESULTS:Among MESA participants (61.9 years of age, 52.5% women, 36.8% White, 29.3% Black, 22.2% Hispanic, and 11.7% Chinese), 476 incident ASCVD events were observed during 13.2 years of follow-up. Elevated Lp(a) and CAC score (1-99 and ≥100) were independently associated with ASCVD risk (HR: 1.29; 95% CI: 1.04-1.61; HR: 1.68; 95% CI: 1.30-2.16; and HR: 2.66; 95% CI: 2.07-3.43, respectively), and Lp(a)-by-CAC interaction was not noted. Compared with participants with nonelevated Lp(a) and CAC = 0, those with elevated Lp(a) and CAC ≥100 were at the highest risk (HR: 4.71; 95% CI: 3.01-7.40), and those with elevated Lp(a) and CAC = 0 were at a similar risk (HR: 1.31; 95% CI: 0.73-2.35). Similar findings were observed when guideline-recommended Lp(a) and CAC thresholds were considered, and findings were replicated in the DHS. CONCLUSIONS:Lp(a) and CAC are independently associated with ASCVD risk and may be useful concurrently for guiding primary prevention therapy decisions. 10.1016/j.jacc.2021.11.058
    Correlation Between Smoking Paradox and Heart Rhythm Outcomes in Patients With Coronary Artery Disease Receiving Percutaneous Coronary Intervention. Frontiers in cardiovascular medicine BACKGROUND:The effect of smoking on short-term outcomes among patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) is controversial. However, little is known about the impact of smoking on long-term outcomes in patients with stable coronary artery disease (CAD) who receive PCI. METHODS:A total of 2,044 patients with stable CAD undergoing PCI were evaluated. They were divided into two groups according to smoking status (current smokers vs. non-smokers). Baseline characteristics, exposed risk factors, angiographic findings, and interventional strategies were assessed to compare the long-term clinical outcomes between groups. Predictors for myocardial infarction (MI), all-cause death, cardiovascular (CV) death, and repeated PCI procedures were also analyzed. RESULTS:Compared with non-smokers, current smokers were younger and mostly male (both < 0.01). They also had a lower prevalence of chronic kidney disease (CKD) and diabetes (both < 0.01). Drugs including a P2Y12 receptor inhibitor of platelets (P2Y12 inhibitor), beta-blockers (BB), and statins were used more frequently in current smokers ( < 0.01, < 0.01, = 0.04, respectively). Freedom from all-cause death and CV death was lower in the non-smoker group ( < 0.001, = 0.003, respectively). After adjustment, logistic regression revealed smoking was a major predictor for all-cause death and repeated PCI procedure [hazard ratio(HR): 1.71 and 1.46, respectively]. CONCLUSIONS:Smoker's paradox extends to long-term outcome in patients with stable CAD undergoing PCI, which is partially explained by differences in baseline characteristics. However, smoking strongly predicted all-cause mortality and repeated PCI procedures in patients with stable CAD undergoing PCI. 10.3389/fcvm.2022.803650
    Immune response to a conserved enteroviral epitope of the major capsid VP1 protein is associated with lower risk of cardiovascular disease. Pupina Nadežda,Avarlaid Annela,Sadam Helle,Pihlak Arno,Jaago Mariliis,Tuvikene Jürgen,Rähni Annika,Planken Anu,Planken Margus,Kalso Eija,Tienari Pentti J,Nieminen Janne K,Seppänen Mikko R J,Vaheri Antti,Lindholm Dan,Sinisalo Juha,Pussinen Pirkko,Timmusk Tõnis,Palm Kaia EBioMedicine BACKGROUND:Major cardiac events including myocardial infarction (MI) are associated with viral infections. However, how specific infections contribute to the cardiovascular insults has remained largely unclear. METHODS:We employed next generation phage display mimotope-variation analysis (MVA) to explore the link between antibody-based immune response and severe cardiovascular conditions. Here, we used a case-control design, including the first-stage discovery cohort (n = 100), along with cohorts for second-stage discovery (n = 329) and validation (n = 466). FINDINGS:We observed strong antibody response to the peptide antigens with Gly-Ile-X-Asp (G-I-X-D) core structure in healthy individuals but not in patients with MI. Analysis of the origin of this epitope linked it with the N-terminus of the VP1 protein of poliovirus 3 (PV3), but also other species of picornaviruses. Consistently, we found low levels of antibody response to the G-I-X-D epitope in individuals with severe cardiac disease complications. INTERPRETATION:Our findings imply that antibody response to the G-I-X-D epitope is associated with polio vaccinations and that high antibody levels to this epitope could discriminate healthy individuals from prospective MI patients as a blood-derived biomarker. Together, these findings highlight the importance of epitope-specific antibody response and suggest that protective immunity against the polio- and non-polio enteroviral infections support improved cardiovascular health. FUNDING:Estonian Ministry of Education (5.1-4/20/170), Estonian Research Council (PRG573, PRG805), H2020-MSCA-RISE-2016 (EU734791), H2020 PANBioRA (EU760921), European Union through the European Regional Development Fund (Project no. 2014-2020.4.01.15-0012), Helsinki University Hospital grants, Mary and Georg C. Ehrnrooth Foundation, Finnish Eye Foundation, Finska Läkaresällskapet, The Finnish Society of Sciences and Letters, Magnus Ehrnrooth Foundation and Sigrid Jusélius Foundation. 10.1016/j.ebiom.2022.103835
    Role of Coronary Artery Calcium Testing for Risk Assessment in Primary Prevention of Atherosclerotic Cardiovascular Disease: A Review. Greenland Philip,Lloyd-Jones Donald M JAMA cardiology Importance:Current guidelines recommend a few different approaches to the use of coronary artery calcium (CAC) testing as a tool for risk assessment and decision-making regarding drug therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD). Observations:Coronary artery calcium testing is not recommended for universal screening, particularly in patients at very low or high predicted risk for ASCVD, where its yield and utility for altering clinical decisions are limited. Use of CAC testing appears to be optimal when used in selected patients who are at intermediate or borderline risk of ASCVD as a sequential decision aid after initial quantitative risk assessment and consideration of individual patient risk-enhancing factors (eg, strong family history of premature ASCVD, chronic kidney disease). Although convincing clinical trials have not been completed, observational studies strongly suggest that, in those at intermediate risk, CAC testing can meaningfully reclassify risk and can support improved targeting of drug therapy to patients most likely to benefit. Conclusions and Relevance:This narrative review summarizes the evidence available about the appropriate role of CAC testing for ASCVD risk assessment. Coronary artery calcium testing should be used selectively in patients who are at intermediate risk of ASCVD, when there is persistent uncertainty after performing standard risk assessment using traditional risk factors in a risk score, and after consideration of additional individual risk-enhancing factors. In these situations, the result of the CAC test can be helpful to clarify whether the patient's true risk is high enough to justify initiation of primary prevention medications, such as statins or aspirin. 10.1001/jamacardio.2021.3948
    Thrombosis and Major Bleeding Risk After Primary PCI Among Patients With Multivessel Coronary Artery Disease. Frontiers in cardiovascular medicine BACKGROUND AND AIM:This study aimed to develop and validate separate risk prediction models for thrombosis events (TEs) and major bleeding (MB) in patients with multivessel coronary artery lesions who had undergone primary percutaneous coronary intervention (PCI). METHODS AND RESULTS:Thrombosis events (TEs) were defined as the composite of myocardial infarction recurrence or ischemic cerebrovascular events, whereas MB was defined as the occurrence of bleeding academic research consortium (BARC) three or five bleeding. The derivation and validation cohorts comprised 2,976 patients who underwent primary PCI between January 2010 and June 2017. At a median follow-up of 3.07 years (1,122 days), TEs and MB occurred in 167 and 98 patients, respectively. Independent predictors of TEs were older age, prior PCI, non-ST elevated MI (NSTEMI), and stent thrombosis (ST). Independent predictors of MB were triple therapy at discharge, coronary artery bifurcation lesions, lesion restenosis, target lesion of the left main coronary artery, stent thrombosis, non-use of IABP during primary PCI, type A/B according to the American College of Cardiology classification of the coronary lesion, and PTCA. In the derivation and validation cohorts, the areas under the curve were 0.817 and 0.82 for thrombosis and 0.886 and 0.976 for bleeding, respectively. In the derivation cohort, high thrombotic risk ( = 755) was associated with higher 3-year incidence of TEs, major adverse cardiovascular events (MACEs), and all-cause death compared to low risk ( = 1,275) ( = 0.0022, 0.019, and 0.012, respectively). High bleeding risk ( = 1,675) was associated with higher incidence of bleeding, MACEs, and cardiac death compared to low risk ( = 355) ( < 0.0001). CONCLUSION:Simple risk scores can be useful in predicting risks of ischemic and bleeding events after primary PCI, thereby stratifying thrombotic or MB risks and facilitating clinical decisions. 10.3389/fcvm.2021.729432
    Kynurenine Pathway Metabolites as Potential Clinical Biomarkers in Coronary Artery Disease. Frontiers in immunology Coronary artery disease (CAD) is one of the leading cause of mortality worldwide. Several risk factors including unhealthy lifestyle, genetic background, obesity, diabetes, hypercholesterolemia, hypertension, smoking, age, etc. contribute to the development of coronary atherosclerosis and subsequent coronary artery disease. Inflammation plays an important role in coronary artery disease development and progression. Pro-inflammatory signals promote the degradation of tryptophan the kynurenine pathway resulting in the formation of several immunomodulatory metabolites. An unbalanced kynurenic pathway has been implicated in the pathomechanisms of various diseases including CAD. Significant improvements in detection methods in the last decades may allow simultaneous measurement of multiple metabolites of the kynurenine pathway and such a thorough analysis of the kynurenine pathway may be a valuable tool for risk stratification and determination of CAD prognosis. Nevertheless, imbalance in the activities of different branches of the kynurenine pathway may require careful interpretation. In this review, we aim to summarize clinical evidence supporting a possible use of kynurenine pathway metabolites as clinical biomarkers in various manifestations of CAD. 10.3389/fimmu.2021.768560
    Bypass Grafting and Native Coronary Artery Disease Activity. JACC. Cardiovascular imaging OBJECTIVES:The aim of this study was to describe the potential of F-sodium fluoride (F-NaF) positron emission tomography (PET) to identify graft vasculopathy and to investigate the influence of coronary artery bypass graft (CABG) surgery on native coronary artery disease activity and progression. BACKGROUND:As well as developing graft vasculopathy, CABGs have been proposed to accelerate native coronary atherosclerosis. METHODS:Patients with established coronary artery disease underwent baseline F-NaF PET, coronary artery calcium scoring, coronary computed tomographic angiography, and 1-year repeat coronary artery calcium scoring. Whole-vessel coronary microcalcification activity (CMA) on F-NaF PET and change in calcium scores were quantified in patients with and without CABG surgery. RESULTS:Among 293 participants (mean age 65 ± 9 years, 84% men), 48 (16%) underwent CABG surgery 2.7 years [IQR: 1.4-10.4 years] previously. Although all arterial and the majority (120 of 128 [94%]) of vein grafts showed no F-NaF uptake, 8 saphenous vein grafts in 7 subjects had detectable CMA. Bypassed native coronary arteries had 3 times higher CMA values (2.1 [IQR: 0.4-7.5] vs 0.6 [IQR: 0-2.7]; P < 0.001) and greater progression of 1-year calcium scores (118 Agatston unit [IQR: 48-194 Agatston unit] vs 69 [IQR: 21-142 Agatston unit]; P = 0.01) compared with patients who had not undergone CABG, an effect confined largely to native coronary plaques proximal to the graft anastomosis. In sensitivity analysis, bypassed native coronary arteries had higher CMA (2.0 [IQR: 0.4-7.5] vs 0.8 [IQR: 0.3-3.2]; P < 0.001) and faster disease progression (24% [IQR: 16%-43%] vs 8% [IQR: 0%-24%]; P = 0.002) than matched patients (n = 48) with comparable burdens of coronary artery disease and cardiovascular comorbidities in the absence of bypass grafting. CONCLUSIONS:Native coronary arteries that have been bypassed demonstrate increased disease activity and more rapid disease progression than nonbypassed arteries, an observation that appears independent of baseline atherosclerotic plaque burden. Microcalcification activity is not a dominant feature of graft vasculopathy. 10.1016/j.jcmg.2021.11.030
    Predicting Left Main Coronary Artery Stenosis Without Imaging: Are We There Yet? Kayani Waleed T,Khalid Umair,Alam Mahboob Journal of the American College of Cardiology 10.1016/j.jacc.2021.11.054
    Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial. Senior Roxy,Reynolds Harmony R,Min James K,Berman Daniel S,Picard Michael H,Chaitman Bernard R,Shaw Leslee J,Page Courtney B,Govindan Sajeev C,Lopez-Sendon Jose,Peteiro Jesus,Wander Gurpreet S,Drozdz Jaroslaw,Marin-Neto Jose,Selvanayagam Joseph B,Newman Jonathan D,Thuaire Christophe,Christopher Johann,Jang James J,Kwong Raymond Y,Bangalore Sripal,Stone Gregg W,O'Brien Sean M,Boden William E,Maron David J,Hochman Judith S, Journal of the American College of Cardiology BACKGROUND:Detection of ≥50% diameter stenosis left main coronary artery disease (LMD) has prognostic and therapeutic implications. Noninvasive stress imaging or an exercise tolerance test (ETT) are the most common methods to detect obstructive coronary artery disease, though stress test markers of LMD remain ill-defined. OBJECTIVES:The authors sought to identify markers of LMD as detected on coronary computed tomography angiography (CTA), using clinical and stress testing parameters. METHODS:This was a post hoc analysis of ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches), including randomized and nonrandomized participants who had locally determined moderate or severe ischemia on nonimaging ETT, stress nuclear myocardial perfusion imaging, or stress echocardiography followed by CTA to exclude LMD. Stress tests were read by core laboratories. Prior coronary artery bypass grafting was an exclusion. In a stepped multivariate model, the authors identified predictors of LMD, first without and then with stress testing parameters. RESULTS:Among 5,146 participants (mean age 63 years, 74% male), 414 (8%) had LMD. Predictors of LMD were older age (P < 0.001), male sex (P < 0.01), absence of prior myocardial infarction (P < 0.009), transient ischemic dilation of the left ventricle on stress echocardiography (P = 0.05), magnitude of ST-segment depression on ETT (P = 0.004), and peak metabolic equivalents achieved on ETT (P = 0.001). The models were weakly predictive of LMD (C-index 0.643 and 0.684). CONCLUSIONS:In patients with moderate or severe ischemia, clinical and stress testing parameters were weakly predictive of LMD on CTA. For most patients with moderate or severe ischemia, anatomical imaging is needed to rule out LMD. (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches [ISCHEMIA]; NCT01471522). 10.1016/j.jacc.2021.11.052
    Percutaneous coronary intervention vs. coronary artery bypass graft for left main coronary artery disease: a never-ending debate. European heart journal 10.1093/eurheartj/ehac081
    Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease. Taron Jana,Foldyna Borek,Mayrhofer Thomas,Osborne Michael T,Meyersohn Nandini,Bittner Daniel O,Puchner Stefan B,Emami Hamed,Lu Michael T,Ferencik Maros,Pagidipati Neha J,Douglas Pamela S,Hoffmann Udo JACC. Cardiovascular imaging OBJECTIVES:The purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD. BACKGROUND:Among stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed. METHODS:In PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD. RESULTS:Of 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007). CONCLUSIONS:Advanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events. 10.1016/j.jcmg.2021.03.019
    Prognostic Value of Stress Cardiac Magnetic Resonance in Patients With Known Coronary Artery Disease. Antiochos Panagiotis,Ge Yin,Heydari Bobak,Steel Kevin,Bingham Scott,Abdullah Shuaib M,Mikolich J Ronald,Arai Andrew E,Bandettini W Patricia,Patel Amit R,Farzaneh-Far Afshin,Heitner John F,Shenoy Chetan,Leung Steve W,Gonzalez Jorge A,Shah Dipan J,Raman Subha V,Ferrari Victor A,Schulz-Menger Jeanette,Stuber Matthias,Simonetti Orlando P,Kwong Raymond Y JACC. Cardiovascular imaging OBJECTIVES:This study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States. BACKGROUND:Despite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing. METHODS:From the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined. RESULTS:Out of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P < 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P < 0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P < 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively. CONCLUSIONS:In a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a <2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891). 10.1016/j.jcmg.2021.06.025
    Segmental Tissue Speckle Tracking Predicts the Stenosis Severity in Patients With Coronary Artery Disease. Frontiers in cardiovascular medicine OBJECTIVE:Two-dimensional speckle tracking echocardiography (2D-STE) has been used as a diagnostic tool for coronary artery disease (CAD). However, whether vessel supplied myocardial strain and strain rate (SR) predict the severity of coronary artery stenosis in patients with CAD is unknown. This study aimed to investigate correlation of cardiac mechanical parameters in tissue speckle tracking measurements with coronary artery stenosis diagnosed by cardiac catheterization in patients with clinically diagnosed CAD. METHODS AND RESULTS:Among 59 patients analyzed, 170 vessels were evaluated by coronary angiography and the corresponding echocardiography to quantify left ventricular myocardial strain and SR. The average longitudinal strain and SR of the segmental myocardium supplied by each coronary artery were calculated to achieve vessel myocardium strain (VMS) and strain rate (VMSR). The VMS and VMSR at each of four severity levels of stenosis showed significant differences among groups ( = 0.016, and < 0.001, respectively). The strain and SR in vessels with very severe stenosis (≥75%, group IV; = 29), 13.9 ± 4.3, and 0.9 ± 0.3, respectively, were significantly smaller than those of vessels with mild stenosis ≤ 25%, group I; = 88, 16.9 ± 4.9, = 0.023, and 1.2 ± 0.3, = 0.001, respectively. The SR in vessels with moderate stenosis (26-49%, group II; = 37), 1.0 ± 0.2, was significantly smaller than that in vessels with mild stenosis vessels ( = 0.021). The lower VMS and VMSR, the higher possibility of severe coronary stenosis is. The VMS and VMSR lower than 13.9 ± 4.3 and 0.9 ± 0.3, respectively predicted the severe coronary stenosis. The VMS and VMSR higher than 16.9 ± 4.9 and 1.2 ± 0.3, respectively predicted mild or no coronary artery stenosis. CONCLUSIONS:The actual stenosis rate in catheterization demonstrates that this technique was able to assess coronary artery condition. Thus, the application of a non-invasive method of 2D-STE to evaluate and simplify diagnosis of CAD is feasible. 10.3389/fcvm.2021.832096
    Coronary Calcium to Rule Out Obstructive Coronary Artery Disease in Patients With Acute Chest Pain. Grandhi Gowtham R,Mszar Reed,Cainzos-Achirica Miguel,Rajan Tanuja,Latif Muhammad A,Bittencourt Marcio S,Shaw Leslee J,Batlle Juan C,Blankstein Ron,Blaha Michael J,Cury Ricardo C,Nasir Khurram JACC. Cardiovascular imaging OBJECTIVES:This study aimed to evaluate the ability of coronary artery calcium (CAC) as an initial diagnostic tool to rule out obstructive coronary artery disease (CAD) in a very large registry of patients presenting to the emergency department (ED) with acute chest pain (CP) who were at low to intermediate risk for acute coronary syndrome (ACS). BACKGROUND:It is not yet well established whether CAC can be used to rule out obstructive CAD in the ED setting. METHODS:We included patients from the Baptist Health South Florida Chest Pain Registry presenting to the ED with CP at low to intermediate risk for ACS (Thrombolysis In Myocardial Infarction risk score ≤2, normal/nondiagnostic electrocardiography, and troponin levels) who underwent CAC and coronary computed tomography angiography (CCTA) procedures for evaluation of ACS. To assess the diagnostic accuracy of CAC testing to diagnose obstructive CAD and identify the need for coronary revascularization during hospitalization, we estimated sensitivity, specificity, positive predictive values (PPV), and negative predictive values (NPV). RESULTS:Our study included 5,192 patients (mean age: 53.5 ± 10.8 years; 46% male; 62% Hispanic). Overall, 2,902 patients (56%) had CAC = 0, of which 135 (4.6%) had CAD (114 [3.9%] nonobstructive and 21 [0.7%] obstructive). Among those with CAC >0, 23% had obstructive CAD. Sensitivity, specificity, PPV, and NPV of CAC testing to diagnose obstructive CAD were 96.2%, 62.4%, 22.4%, and 99.3%, respectively. The NPV for identifying those who needed revascularization was 99.6%. Among patients with CAC = 0, 11 patients (0.4%) underwent revascularization, and the number needed to test with CCTA to detect 1 patient who required revascularization was 264. CONCLUSIONS:In a large population presenting to ED with CP at low to intermediate risk, CAC = 0 was common. CAC = 0 ruled out obstructive CAD and revascularization in more than 99% of the patients, and <5% with CAC = 0 had any CAD. Integrating CAC testing very early in CP evaluation may be effective in appropriate triage of patients by identifying individuals who can safely defer additional testing and more invasive procedures. 10.1016/j.jcmg.2021.06.027
    Performance of the GRACE 2.0 score in patients with type 1 and type 2 myocardial infarction. Hung John,Roos Andreas,Kadesjö Erik,McAllister David A,Kimenai Dorien M,Shah Anoop S V,Anand Atul,Strachan Fiona E,Fox Keith A A,Mills Nicholas L,Chapman Andrew R,Holzmann Martin J European heart journal AIMS:The Global Registry of Acute Coronary Events (GRACE) score was developed to evaluate risk in patients with myocardial infarction. However, its performance in type 2 myocardial infarction is uncertain. METHODS AND RESULTS:In two cohorts of consecutive patients with suspected acute coronary syndrome from 10 hospitals in Scotland (n = 48 282) and a tertiary care hospital in Sweden (n = 22 589), we calculated the GRACE 2.0 score to estimate death at 1 year. Discrimination was evaluated by the area under the receiver operating curve (AUC), and compared for those with an adjudicated diagnosis of type 1 and type 2 myocardial infarction using DeLong's test. Type 1 myocardial infarction was diagnosed in 4981 (10%) and 1080 (5%) patients in Scotland and Sweden, respectively. At 1 year, 720 (15%) and 112 (10%) patients died with an AUC for the GRACE 2.0 score of 0.83 [95% confidence interval (CI) 0.82-0.85] and 0.85 (95% CI 0.81-0.89). Type 2 myocardial infarction occurred in 1121 (2%) and 247 (1%) patients in Scotland and Sweden, respectively, with 258 (23%) and 57 (23%) deaths at 1 year. The AUC was 0.73 (95% CI 0.70-0.77) and 0.73 (95% CI 0.66-0.81) in type 2 myocardial infarction, which was lower than for type 1 myocardial infarction in both cohorts (P < 0.001 and P = 0.008, respectively). CONCLUSION:The GRACE 2.0 score provided good discrimination for all-cause death at 1 year in patients with type 1 myocardial infarction, and moderate discrimination for those with type 2 myocardial infarction. TRIAL REGISTRATION:ClinicalTrials.gov number, NCT01852123. 10.1093/eurheartj/ehaa375
    Rural-Urban Disparities in Outcomes of Myocardial Infarction, Heart Failure, and Stroke in the United States. Loccoh Eméfah C,Joynt Maddox Karen E,Wang Yun,Kazi Dhruv S,Yeh Robert W,Wadhera Rishi K Journal of the American College of Cardiology BACKGROUND:U.S. policy efforts have focused on reducing rural-urban health inequities. However, it is unclear whether gaps in care and outcomes remain among older adults with acute cardiovascular conditions. OBJECTIVES:This study aims to evaluate rural-urban differences in procedural care and mortality for acute myocardial infarction (AMI), heart failure (HF), and ischemic stroke. METHODS:This is a retrospective cross-sectional study of Medicare fee-for-service beneficiaries aged ≥65 years with acute cardiovascular conditions from 2016 to 2018. Cox proportional hazards models with random hospital intercepts were fit to examine the association of presenting to a rural (vs urban) hospital and 30- and 90-day patient-level mortality. RESULTS:There were 2,182,903 Medicare patients hospitalized with AMI, HF, or ischemic stroke from 2016 to 2018. Patients with AMI were less likely to undergo cardiac catherization (49.7% vs 63.6%, P < 0.001), percutaneous coronary intervention (42.1% vs 45.7%, P < 0.001) or coronary artery bypass graft (9.0% vs 10.2%, P < 0.001) within 30 days at rural versus urban hospitals. Thrombolysis rates (3.1% vs 10.1%, P < 0.001) and endovascular therapy (1.8% vs 3.6%, P < 0.001) for ischemic stroke were lower at rural hospitals. After adjustment for demographics and clinical comorbidities, the 30-day mortality HR was significantly higher among patients presenting to rural hospitals for AMI (HR: 1.10, 95% CI: 1.08 to 1.12), HF (HR: 1.15; 95% CI: 1.13 to 1.16), and ischemic stroke (HR: 1.20; 95% CI: 1.18 to 1.22), with similar patterns at 90 days. These differences were most pronounced for the subset of critical access hospitals that serve remote, rural areas. CONCLUSIONS:Clinical, public health, and policy efforts are needed to improve rural-urban gaps in care and outcomes for acute cardiovascular conditions. 10.1016/j.jacc.2021.10.045
    Conservative, surgical, and percutaneous treatment for mitral regurgitation shortly after acute myocardial infarction. European heart journal AIMS:Severe mitral regurgitation (MR) following acute myocardial infarction (MI) is associated with high mortality rates and has inconclusive recommendations in clinical guidelines. We aimed to report the international experience of patients with secondary MR following acute MI and compare the outcomes of those treated conservatively, surgically, and percutaneously. METHODS AND RESULTS:Retrospective international registry of consecutive patients with at least moderate-to-severe MR following MI treated in 21 centres in North America, Europe, and the Middle East. The registry included patients treated conservatively and those having surgical mitral valve repair or replacement (SMVR) or percutaneous mitral valve repair (PMVR) using edge-to-edge repair. The primary endpoint was in-hospital mortality. A total of 471 patients were included (43% female, age 73 ± 11 years): 205 underwent interventions, of whom 106 were SMVR and 99 PMVR. Patients who underwent mitral valve intervention were in a worse clinical state (Killip class ≥3 in 60% vs. 43%, P < 0.01), but yet had lower in-hospital and 1-year mortality compared with those treated conservatively [11% vs. 27%, P < 0.01 and 16% vs. 35%, P < 0.01; adjusted hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.18-0.46, P < 0.01]. Surgical mitral valve repair or replacement was performed earlier than PMVR [median of 12 days from MI date (interquartile range 5-19) vs. 19 days (10-40), P < 0.01]. The immediate procedural success did not differ between SMVR and PMVR (92% vs. 93%, P = 0.53). However, in-hospital and 1-year mortality rates were significantly higher in SMVR than in PMVR (16% vs. 6%, P = 0.03 and 31% vs. 17%, P = 0.04; adjusted HR 3.75, 95% CI 1.55-9.07, P < 0.01). CONCLUSIONS:Early intervention may mitigate the poor prognosis associated with conservative therapy in patients with post-MI MR. Percutaneous mitral valve repair can serve as an alternative for surgery in reducing MR for high-risk patients. 10.1093/eurheartj/ehab496
    Identifying the cardioprotective mechanism of Danyu Tongmai Granules against myocardial infarction by targeted metabolomics combined with network pharmacology. Cui Jing,Shi Yangyang,Xu Xueli,Zhao Fei,Zhang Ji,Wei Bo Phytomedicine : international journal of phytotherapy and phytopharmacology BACKGROUND:Danyu Tongmai Granules (DY), the commercial Chinese medicine, was well-accepted cardiovascular protective actions in clinic. However, the mechanisms underlying the beneficial effects of DY on cardiovascular disease still need largely to be clarified. PURPOSE:Therefore, this study was designed to explore potential mechanisms of DY in myocardial infarction (MI) by integrated strategy of metabolomics and network pharmacology. METHODS:Cardiomyocytes were subjected to HO induced myocardial injury and rats were induced MI via isoproterenol (ISO) injection. The entire metabolic alterations in serum and heart tissues of experimental rats were profiled by UPLC-MS/MS. Based on the identified differential metabolites, the pathway analysis results were obtained and further validated using the network pharmacology approach. RESULTS:We found that DY exerted significant cardioprotective effects in vitro and in vivo, and ameliorated inflammatory cell infiltration and cardiomyocyte apoptosis induced by ISO. The metabolomics data suggested that DY mainly affected the amino acid metabolism (i.e., valine, leucine and isoleucine biosynthesis, arginine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, glycine, serine, as well as the alanine metabolism, aspartate and glutamate metabolism, etc.). Simultaneously, DY participated in the regulation of the biosynthesis of bile acids and biosynthesis of unsaturated fatty acids. Notably, DY significantly reduced the biosynthesis of valine, leucine and isoleucine to regulating the metabolism of branched chain amino acids (BCAAs) in infarcted myocardium, thus blocking the inflammation via inhibiting the expression of NLRP3 inflammasome in ISO-induced rats. The anti-inflammatory system of DY was further validated with the results of network pharmacology. CONCLUSION:Our study, for the first time, confirmed that DY inhibited inflammation and further exerted significant anti-myocardial infarction effect. Additionally, our work further demonstrated that the myocardial protective effect of DY was contributed to the inhibition of the NLRP3 inflammasome activation by regulating BCAAs in infarcted myocardium using the comprehensive metabolomics, molecular biology and network analysis. Overall, our study gained new insights into the role of the relationship between the metabolic regulation of BCAAs and the NLRP3 inflammasome against MI. 10.1016/j.phymed.2021.153829
    Multifunctional elastomer cardiac patches for preventing left ventricle remodeling after myocardial infarction in vivo. Biomaterials Myocardial infarction (MI) is still a major cause of mortality and morbidity worldwide. Elastomer cardiac patches have shown great potential in preventing left ventricle (LV) remodeling post-MI by providing mechanical support to the infarcted myocardium. Improved therapeutic outcomes are expected by mediating pathological processes in the necrosis phase, inflammation phase, and fibrosis phase, through orchestrated biological and mechanical treatments. In this study, a mechanically robust multifunctional cardiac patch integrating reactive oxygen species (ROS)-scavenging, anti-inflammatory, and pro-angiogenic capabilities was developed to realize the integrative strategy. An elastomeric polyurethane (PFTU) containing ROS-sensitive poly (thioketal) (PTK) and unsaturated poly (propylene fumarate) (PPF) segments was synthesized, which was further clicked with pro-angiogenic Arg-Glu-Asp-Val (REDV) peptides to obtain PFTU-g-REDV (PR), and was formulated into a macroporous patch containing rosuvastatin (PRR). The mechanical support and multifunctional effects of the patch were confirmed in a rat MI model in vivo compared to the patches with only mechanical support, leading to reduced cell apoptosis, suppressed local inflammatory response, alleviated fibrosis, and induced angiogenesis. The cardiac functions and LV morphology were also well maintained. These results demonstrate the advantages of the integrated and orchestrated treatment strategy in MI therapy. 10.1016/j.biomaterials.2022.121382
    High on-treatment platelet reactivity to aspirin in patients after myocardial infarction. Stolarek Wioleta,Kasprzak Michał,Sikora Joanna,Siemińska Emilia,Grześk Grzegorz Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie Aspirin (ASA) is widely used as an antiplatelet therapeutic drug in secondary prevention. Last years brought many reports on ASA resistance or high on-treatment platelet reactivity (HTPR) to aspirin.This study is a post-hoc prospective analysis with 30 patients evaluated during follow up on average of 6.3 years after hospitalization from myocardial infarction. The examined population was divided into two subgroups according to the response to ASA. In order to estimate the function of blood platelets and their responsiveness to acetylsalicylic acid therapy, ASPI-test was used. The measurements were performed by the method of whole blood impedance aggregometry. During long-term follow up significantly higher percentage of high platelet reactivity was observed, compared with previous visits (p = 0.00001). Considering clinical endpoints of the research that were connected with coronary disease, no differences were obtained.The frequency of HTPR to aspirin in this study was higher than data reported in literature among subjects with CV diseases. In long-term observation the highest percentage of ASA non-responders was reported (58.6%). HTPR to aspirin did not affect the presence of the clinical endpoints for the study. 10.1016/j.biopha.2022.112618
    DNA-Templated ultrasmall bismuth sulfide nanoparticles for photoacoustic imaging of myocardial infarction. Zhao Peng,Li Bing,Li Yingxu,Chen Leshan,Wang Hao,Ye Ling Journal of colloid and interface science Photoacoustic imaging (PAI) has shown great clinical potential in diagnosing various diseases due to its noninvasive, cost-effective, and real-time imaging properties but is limited by the lack of contrast agents with high sensitivity for deep tissue imaging. Here, DNA-templated ultrasmall bismuth sulfide (BiS) nanoparticles (NPs) were reported as a photoacoustic (PA) probe for imaging myocardial infarction. We present a simple synthesis strategy of ultrasmall NPs via self-assembly of single-stranded DNA (ssDNA)/metal ion complexes. The in vivo imaging results showed a dramatically enhanced PA signal in the region of myocardial infarction after intravenous injection of DNA-BiS NPs in the myocardial ischaemia/reperfusion (I/R) mouse model. Further near infrared fluorescence imaging indicated that BiS NPs mainly accumulated in the infarcted area, leading to enhancement of PA signals. Moreover, such hybrid NPs possess a well-defined nanostructure, superior photobleaching resistance, excellent water dispersibility and negligible acute toxicity. These results not only demonstrate that ultrasmall DNA-BiS NPs are a potent PA probe for imaging the infarcted region but also provide a new avenue for preparing ultrasmall-sized PA probes by using ssDNA as a template. 10.1016/j.jcis.2022.01.194
    Nanoengineered Sprayable Therapy for Treating Myocardial Infarction. ACS nano We report the development, as well as the and testing, of a sprayable nanotherapeutic that uses surface engineered custom-designed multiarmed peptide grafted nanogold for on-the-spot coating of an infarcted myocardial surface. When applied to mouse hearts, 1 week after infarction, the spray-on treatment resulted in an increase in cardiac function (2.4-fold), muscle contractility, and myocardial electrical conductivity. The applied nanogold remained at the treatment site 28 days postapplication with no off-target organ infiltration. Further, the infarct size in the mice that received treatment was found to be <10% of the total left ventricle area, while the number of blood vessels, prohealing macrophages, and cardiomyocytes increased to levels comparable to that of a healthy animal. Our cumulative data suggest that the therapeutic action of our spray-on nanotherapeutic is highly effective, and in practice, its application is simpler than other regenerative approaches for treating an infarcted heart. 10.1021/acsnano.1c08890
    Innate Lymphoid Cells and Myocardial Infarction. Yang Wenling,Lin Jibin,Zhou Jin,Zheng Yuqi,Jiang Shijiu,He Shaolin,Li Dazhu Frontiers in immunology Myocardial infarction results from obstruction of a coronary artery that causes insufficient blood supply to the myocardium and leads to ischemic necrosis. It is one of the most common diseases threatening human health and is characterized by high morbidity and mortality. Atherosclerosis is the pathological basis of myocardial infarction, and its pathogenesis has not been fully elucidated. Innate lymphoid cells (ILCs) are an important part of the human immune system and participate in many processes, including inflammation, metabolism and tissue remodeling, and play an important role in atherosclerosis. However, their specific roles in myocardial infarction are unclear. This review describes the current understanding of the relationship between innate lymphoid cells and myocardial infarction during the acute phase of myocardial infarction, myocardial ischemia-reperfusion injury, and heart repair and regeneration following myocardial infarction. We suggest that this review may provide new potential intervention targets and ideas for treatment and prevention of myocardial infarction. 10.3389/fimmu.2021.758272
    CD36 is Associated With the Development of Coronary Artery Lesions in Patients With Kawasaki Disease. Guo Mindy Ming-Huey,Huang Ying-Hsien,Wang Feng-Sheng,Chang Ling-Sai,Chen Kuang-Den,Kuo Ho-Chang Frontiers in immunology Kawasaki disease (KD) is an autoimmune-like vasculitis of childhood involving the coronary arteries. Macrophages require scavenger receptors such as CD36 to effectively clear cellular debris and induce self-tolerance. In this study, we hypothesized that CD36 plays an important role in the immunopathogenesis of KD, by aiding in the clearance of plasma mitochondrial DNA, and by amplifying the immune response by activating the inflammasome pathway AIM2. Fifty-two healthy controls, 52 febrile controls, and 102 KD patients were recruited for RT-PCR of target mRNA expression and plasma mitochondrial DNA. Blood samples were obtained 24 hours prior and 21 days after the administration of intravenous immunoglobulin (IVIG) therapy. Patients with acute KD had higher plasma levels of cell-free mitochondrial DNA (ND1, ND4, and COX1), and higher mRNA expressions of CD36 and AIM2 when compared to both healthy and febrile controls. A greater decrease in both CD36 and AIM2 mRNA expression after IVIG therapy was associated with the development of coronary artery lesions. Coronary artery lesions were associated with a larger decrease of CD36 expression following IVIG therapy, which may indicate that prolonged expression of the scavenger receptor may have a protective effect against the development of coronary artery lesions in KD. 10.3389/fimmu.2022.790095
    The Emerging Role of Irisin in Cardiovascular Diseases. Fu Jinjuan,Li Fangtang,Tang Yuanjuan,Cai Lin,Zeng Chunyu,Yang Yongjian,Yang Jian Journal of the American Heart Association Irisin, a novel hormone like polypeptide, is cleaved and secreted by an unknown protease from a membrane-spanning protein, FNDC5 (fibronectin type III domain-containing protein 5). The current knowledge on the biological functions of irisin includes browning white adipose tissue, regulating insulin use, and anti-inflammatory and antioxidative properties. Dysfunction of irisin has shown to be involved in cardiovascular diseases such as hypertension, coronary artery disease, myocardial infarction, and myocardial ischemia-reperfusion injury. Moreover, irisin gene variants are also associated with cardiovascular diseases. In this review, we discuss the current knowledge on irisin-mediated regulatory mechanisms and their roles in the pathogenesis of cardiovascular diseases. 10.1161/JAHA.121.022453
    Mendelian Randomization Analyses Suggest Childhood Body Size Indirectly Influences End Points From Across the Cardiovascular Disease Spectrum Through Adult Body Size. Power Grace M,Tyrrell Jessica,Frayling Timothy M,Davey Smith George,Richardson Tom G Journal of the American Heart Association Background Obesity is associated with long-term health consequences including cardiovascular disease. Separating the independent effects of childhood and adulthood obesity on cardiovascular disease risk is challenging as children with obesity typically remain overweight throughout the lifecourse. Methods and Results This study used 2-sample univariable and multivariable Mendelian randomization to estimate the effect of childhood body size both independently and after accounting for adult body size on 12 endpoints across the cardiovascular disease disease spectrum. Univariable analyses identified strong evidence of a total effect between genetically predicted childhood body size and increased risk of atherosclerosis, atrial fibrillation, coronary artery disease, heart failure, hypertension, myocardial infarction, peripheral artery disease, and varicose veins. However, evidence of a direct effect was weak after accounting for adult body size using multivariable Mendelian randomization, suggesting that childhood body size indirectly increases risk of these 8 disease outcomes via the pathway involving adult body size. Conclusions These findings suggest that the effect of genetically predicted childhood body size on the cardiovascular disease outcomes analyzed in this study are a result of larger body size persisting into adulthood. Further research is necessary to ascertain the critical timepoints where, if ever, the detrimental impact of obesity initiated in early life begins to become immutable. 10.1161/JAHA.121.021503
    Gastrin exerts a protective effect against myocardial infarction via promoting angiogenesis. Fu Jinjuan,Tang Yuanjuan,Zhang Zhen,Tong Lin,Yue Rongchuan,Cai Lin Molecular medicine (Cambridge, Mass.) BACKGROUND:It is known that increased gastrin concentration is negatively correlated with cardiovascular mortality, and plasma gastrin levels are increased in patients after myocardial infarction (MI). However, whether gastrin can play a protective role in MI remains unknown. METHODS:Adult C57BL/6 mice were subjected to ligation of the left anterior descending coronary artery (LAD) and subcutaneous infusion of gastrin (120 μg/Kg body weight/day, 100 μL in the pump) for 28 days after MI. Plasma gastrin concentrations were measured through an ELISA detection kit. Mice were analyzed by echocardiography after surgery. CD31 and VEGF expression were quantified using immunofluorescence staining or/and western blot to assess the angiogenesis in peri-infarct myocardium. Capillary-like tube formation and cell migration assays were performed to detect gastrin-induced angiogenesis. RESULTS:We found that gastrin administration significantly ameliorated MI-induced cardiac dysfunction and reduced fibrosis at 28 days in post-MI hearts. Additionally, gastrin treatment significantly decreased cardiomyocyte apoptosis and increased angiogenesis in the infarct border zone without influencing cardiomyocyte proliferation. In vitro results revealed that gastrin up-regulated the PI3K/Akt/vascular endothelial growth factor (VEGF) signaling pathway and promoted migration and tube formation of human coronary artery endothelial cells (HCAECs). Cholecystokinin 2 receptor (CCKR) mediated the protective effect of gastrin since the CCKR blocker CI988 attenuated the gastrin-mediated angiogenesis and cardiac function protection. CONCLUSION:Our data revealed that gastrin promoted angiogenesis and improved cardiac function in post-MI mice, highlighting its potential as a therapeutic target candidate. 10.1186/s10020-021-00352-w
    Association of Culprit Lesion Location With Outcomes of Culprit-Lesion-Only vs Immediate Multivessel Percutaneous Coronary Intervention in Cardiogenic Shock: A Post Hoc Analysis of a Randomized Clinical Trial. Farhan Serdar,Vogel Birgit,Montalescot Gilles,Barthelemy Olivier,Zeymer Uwe,Desch Steffen,de Waha-Thiele Suzanne,Maier Lars S,Sandri Marcus,Akin Ibrahim,Fuernau Georg,Ouarrak Taoufik,Hauguel-Moreau Marie,Schneider Steffen,Thiele Holger,Huber Kurt JAMA cardiology Importance:Myocardial infarction with a culprit lesion located in the left main or proximal left anterior descending artery compared with other coronary segments is associated with more myocardium at risk and worse clinical outcomes. Objective:To evaluate the association of culprit lesion location with outcomes of culprit-lesion-only percutaneous coronary intervention with optional staged revascularization vs immediate multivessel percutaneous coronary intervention in patients with multivessel disease, myocardial infarction, and cardiogenic shock. Design, Setting, and Participants:Post hoc analysis of the Culprit Lesion Only Coronary Intervention vs Multivessel Coronary Intervention in Cardiogenic Shock (CULPRIT-SHOCK), an investigator-initiated randomized, open-label clinical trial. Patients with multivessel disease, acute myocardial infarction, and cardiogenic shock were enrolled at 83 European centers from April 2013 through April 2017. Interventions:Patients were randomized to culprit-lesion-only percutaneous coronary intervention with optional staged revascularization or immediate multivessel percutaneous coronary intervention (1:1). For this analysis, patients were stratified by culprit lesion location in the left main or proximal left anterior descending artery group and other-culprit-lesion location group. Main Outcomes and Measures:End points included a composite of death or kidney replacement therapy at 30 days and death at 1 year. Results:The median age of the study population was 70 (interquartile range, 60-78 years) and 524 of the study participants were men (76.4%). Of the 685 patients, 33.4% constituted the left main or proximal left anterior descending artery group and 66.6% the other-culprit-lesion location group. The left main or proximal left anterior descending artery group had worse outcomes compared with the other-culprit-lesion location group (56.8% vs 47.5%; P = .02 for the composite end point at 30 days and 59.8% vs 50.1%; P = .02 for death at 1 year). In both groups, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a reduced risk of the composite end point at 30 days (49.1% vs 64.3% and 44.1% vs 50.9%; P for interaction = .27). At 1 year, culprit-lesion-only vs immediate multivessel percutaneous coronary intervention was associated with a significantly reduced risk of death in the left main or proximal left anterior descending artery but not the other-culprit-lesion location group (50.0% vs 69.6%; P = .003 and 49.8% vs 50.4%; P = .89; P for interaction = 0.02). Conclusions and Relevance:In patients with multivessel disease with myocardial infarction and cardiogenic shock, a culprit lesion located in the left main or proximal left anterior descending artery vs other coronary segments was associated with worse outcomes. These patients may especially benefit from culprit-lesion-only percutaneous coronary intervention with optional staged revascularization, although further investigation is needed to confirm this finding. Trial Registration:ClinicalTrials.gov Identifier: NCT01927549. 10.1001/jamacardio.2020.3377
    Genetic testing in ambulatory cardiology clinics reveals high rate of findings with clinical management implications. Murdock David R,Venner Eric,Muzny Donna M,Metcalf Ginger A,Murugan Mullai,Hadley Trevor D,Chander Varuna,de Vries Paul S,Jia Xiaoming,Hussain Aliza,Agha Ali M,Sabo Aniko,Li Shoudong,Meng Qingchang,Hu Jianhong,Tian Xia,Cohen Michelle,Yi Victoria,Kovar Christie L,Gingras Marie-Claude,Korchina Viktoriya,Howard Chad,Riconda Daniel L,Pereira Stacey,Smith Hadley S,Huda Zohra A,Buentello Alexandria,Marino Patricia R,Leiber Lee,Balasubramanyam Ashok,Amos Christopher I,Civitello Andrew B,Chelu Mihail G,Maag Ronald,McGuire Amy L,Boerwinkle Eric,Wehrens Xander H T,Ballantyne Christie M,Gibbs Richard A Genetics in medicine : official journal of the American College of Medical Genetics PURPOSE:Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted. METHODS:We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record. RESULTS:Notably, 32% of patients had a genetic finding with clinical management implications, even after excluding PGx results, including 9% who were molecularly diagnosed with a Mendelian condition. Among surveyed physicians, 84% reported medical management changes based on these results, including specialist referrals, cardiac tests, and medication changes. LPA polymorphisms and high polygenic risk of CAD were found in 20% and 9% of patients, respectively, leading to diet, lifestyle, and other changes. Warfarin and simvastatin pharmacogenetic variants were present in roughly half of the cohort. CONCLUSION:Our results support the use of genetic information in routine cardiovascular health management and provide a roadmap for accompanying research. 10.1038/s41436-021-01294-8
    Nrf2 for protection against oxidant generation and mitochondrial damage in cardiac injury. Chen Qin M Free radical biology & medicine Myocardial infarction is the most common form of acute coronary syndrome. Blockage of a coronary artery due to blood clotting leads to ischemia and subsequent cell death in the form of necrosis, apoptosis, necroptosis and ferroptosis. Revascularization by coronary artery bypass graft surgery or non-surgical percutaneous coronary intervention combined with pharmacotherapy is effective in relieving symptoms and decreasing mortality. However, reactive oxygen species (ROS) are generated from damaged mitochondria, NADPH oxidases, xanthine oxidase, and inflammation. Impairment of mitochondria is shown as decreased metabolic activity, increased ROS production, membrane permeability transition, and release of mitochondrial proteins into the cytoplasm. Oxidative stress activates Nrf2 transcription factor, which in turn mediates the expression of mitofusin 2 (Mfn 2) and proteasomal genes. Increased expression of Mfn2 and inhibition of mitochondrial fission due to decreased Drp1 protein by proteasomal degradation contribute to mitochondrial hyperfusion. Damaged mitochondria can be removed by mitophagy via Parkin or p62 mediated ubiquitination. Mitochondrial biogenesis compensates for the loss of mitochondria, but requires mitochondrial DNA replication and initiation of transcription or translation of mitochondrial genes. Experimental evidence supports a role of Nrf2 in mitophagy, via up-regulation of PINK1 or p62 gene expression; and in mitochondrial biogenesis, by influencing the expression of PGC-1α, NResF1, NResF2, TFAM and mitochondrial genes. Oxidative stress causes Nrf2 activation via Keap1 dissociation, de novo protein translation, and nuclear translocation related to inactivation of GSK3β. The mechanism of Keap 1 mediated Nrf2 activation has been hijacked for Nrf2 activation by small molecules derived from natural products, some of which have been shown capable of mitochondrial protection. Multiple lines of evidence support the importance of Nrf2 in protecting mitochondria and preserving or renewing energy metabolism following tissue injury. 10.1016/j.freeradbiomed.2021.12.001
    Vitamin D Deficiency as a Predictor of a High Prevalence of Coronary Artery Disease in Pancreas Transplant Candidates With Type 1 Diabetes. Buksińska-Lisik Małgorzata,Kwasiborski Przemysław J,Ryczek Robert,Lisik Wojciech,Mamcarz Artur Frontiers in endocrinology Introduction:Pancreas transplantation is a high-risk procedure in terms of cardiovascular complications. Therefore, identification of all cardiovascular risk factors is crucial to prevent cardiovascular complications after pancreas transplantation. Vitamin D deficiency (VDD) appears to be a potential risk factor for coronary artery disease. Objective:To determine the prevalence of VDD in pancreas transplant candidates, and further to examine the relationship between vitamin D and the prevalence of coronary artery disease and lipid profile parameters. Materials and Methods:This is a prospective cross-sectional study. We enrolled consecutive patients with type 1 diabetes eligible for simultaneous pancreas-kidney transplantation or pancreas transplant alone. The laboratory tests included HbA1c, lipid profile, creatinine, and total 25-hydroxyvitamin D (25(OH)D). The diagnosis of coronary artery disease was based on coronary angiography. Results:The study population included 48 patients. VDD was revealed in 48% of patients and coronary artery disease in 35% of patients. The mean concentration of vitamin D in the entire cohort was 21.3 ± 9.48 ng/ml. The median value of 25(OH)D in patients with coronary artery disease was significantly lower than in patients without coronary artery disease (18.5 (11.6-21.5) . 24.8 (18.4-31.8) ng/ml, p = 0.018). There was a significant relationship between VDD and coronary artery disease (OR = 4.36; 95% confidence interval (CI): 1.22-15.64, p = 0.034). A patient's odds of having coronary artery disease while having a sufficient level of vitamin D was 4.36 times lower than if the patient had VDD. There was a significant relationship between VDD and hypertension (OR = 5.91; 95% CI: 1.12-31.20, p = 0.039) and hemodialysis (OR = 4.25; 95% CI: 1.25-14.5, p = 0.023). There was no significant correlation between 25(OH)D and lipid profile. Conclusions:VDD is highly prevalent in pancreas transplant candidates with type 1 diabetes. There is a significant relationship between VDD and increased prevalence of coronary disease. The lack of any significant association between serum vitamin D and lipid profile suggests that the relationship between vitamin D and coronary artery disease results from other causes. 10.3389/fendo.2021.714728
    Supervised exercise therapy for patients with peripheral artery disease: Clinical update and pathways forward. Progress in cardiovascular diseases Peripheral artery disease (PAD) is an atherosclerotic vascular disease resulting in pervasive morbidity and mortality, particularly among older adults. One first-line therapy to improve symptoms, function, and clinical outcomes in PAD is supervised exercise therapy (SET), which is based primarily on a structured, start-and-stop walking protocol and is often implemented in cardiac rehabilitation programs. SET is supported by a Class IA guideline for patients with symptomatic PAD; however, despite the effectiveness of SET and the 2017 CMS decision to cover SET for PAD, challenges of awareness, access, and implementation of SET persist. Recent efforts to address these challenges include digital health and hybrid approaches to SET that may minimize barriers to care by delivering SET in more innovative, flexible formats. Further study is needed to understand barriers, improve awareness, and implement SET in more equitable and accessible ways. 10.1016/j.pcad.2022.01.006
    Saving time by replacing the standardised two-hour oral glucose tolerance test with a one-hour test: Validation of a new screening algorithm in patients with coronary artery disease from the ESC-EORP EUROASPIRE V registry. Ferrannini Giulia,De Bacquer Dirk,Gyberg Viveca,De Backer Guy,Kotseva Kornelia,Mellbin Linda G,Risebrink Rebecca,Tuomilehto Jaakko,Wood David,Rydén Lars Diabetes research and clinical practice AIMS:An oral glucose tolerance test (OGTT) combining fasting (FPG) and 2-hour plasma glucose (2hPG) is the most sensitive method for detecting type 2 diabetes (T2DM). Since it is considered time-consuming, we aim at validating a previously proposed screening algorithm based on a 1-hour plasma glucose (1hPG) with a 12 mmol/L threshold. METHODS:Nine-hundred-eighteen patients with coronary artery disease (CAD) without known T2DM from the EUROASPIRE V cross-sectional survey underwent an OGTT. The reference for T2DM was 2hPG ≥ 11.1 mmol/L. T2DM diagnosis by HbA1c ≥ 6.5%(48 mmol/mol), FPG ≥ 7.0 mmol/L, and 1hPG ≥ 12 mmol/L were compared with the outcome of 2hPG. RESULTS:Mean FPG, HbA1c and 2hPG were 6.1 mmol/L, 5.6%(38 mmol/mol) and 7.8 mmol/L respectively. Ninety-six patients (10%) were diagnosed with T2DM according to 2hPG. Using this definition, in the group with FPG < 6.5 mmol/L and 1hPG < 12 only 5 (1%) were misdiagnosed as false negatives. All patients with a FPG > 8.0 mmol/L and 1hPG > 15.0 mmol/L were identified as having T2DM. According to the algorithm, in 79% of patients T2DM could be excluded by combining FPG < 6.5 mmol/L and 1hPG < 12 mmol/L. CONCLUSIONS:T2DM Screening by means of an algorithm combining FPG and 1hPG limits the demand of a 2hOGTT in 79% of CAD patients without known T2DM. HbA1c did not add to the information derived from this algorithm. 10.1016/j.diabres.2021.109156
    Current management and screening of peripheral and coronary artery disease in people with diabetes mellitus in Europe. The PADDIA/CADDIA survey. Mahe Guillaume,Brodmann Marianne,Capodanno Davide,Ceriello Antonio,Cuisset Thomas,Delgado Victoria,Espinola-Klein Christine,Johnson Thomas W,Sprynger Muriel,Sattar Naveed,Schnell Oliver,Valensi Paul Diabetes research and clinical practice AIMS:This survey aimed to evaluate the current management and screening of coronary artery disease and peripheral artery disease in people with type 2 diabetes mellitus (T2DM) in Europe, utilizing the 2013 ESC/EASD (European Society of Cardiology/European Association for the Study of Diabetes) guidelines as a benchmark. METHODS:The PADDIA/CADDIA survey is a European medical research collaboration targeting cardiologists, vascular physicians, diabetologists and general practitioners from Austria, Belgium, France, Germany, Italy, Netherlands and United Kingdom. RESULTS:The questionnaire was completed by sixty-three physicians, of whom 75% declared assessing the cardiovascular risk of people with T2DM mostly without using a risk score (59%). More than 90% of the panel, check HbA1c, blood pressure and low-density lipoprotein cholesterol targets in their patients with T2DM and coronary or peripheral artery disease. For 94% the presence of T2DM influence their patients' management, by optimizing blood glucose, blood pressure and low-density lipoprotein cholesterol control. Only 37% considered screening for lower extremity peripheral artery disease among their T2DM patients and 35% among those with cardiovascular disease. CONCLUSIONS:Physicians mostly follow the ESC/EASD 2013 guidelines, but when it comes to screening for additional conditions including coronary artery disease or peripheral artery disease, or intensifying the antithrombotic regimen there is need for better guidance. 10.1016/j.diabres.2022.109214
    Physical activity, sedentary behavior and risk of coronary artery disease, myocardial infarction and ischemic stroke: a two-sample Mendelian randomization study. Bahls Martin,Leitzmann Michael F,Karch André,Teumer Alexander,Dörr Marcus,Felix Stephan B,Meisinger Christa,Baumeister Sebastian E,Baurecht Hansjörg Clinical research in cardiology : official journal of the German Cardiac Society AIMS:Observational evidence suggests that physical activity (PA) is inversely and sedentarism positively related with cardiovascular disease risk. We performed a two-sample Mendelian randomization (MR) analysis to examine whether genetically predicted PA and sedentary behavior are related to coronary artery disease, myocardial infarction, and ischemic stroke. METHODS AND RESULTS:We used single nucleotide polymorphisms (SNPs) associated with self-reported moderate to vigorous PA (n = 17), accelerometer based PA (n = 7) and accelerometer fraction of accelerations > 425 milli-gravities (n = 7) as well as sedentary behavior (n = 6) in the UK Biobank as instrumental variables in a two sample MR approach to assess whether these exposures are related to coronary artery disease and myocardial infarction in the CARDIoGRAMplusC4D genome-wide association study (GWAS) or ischemic stroke in the MEGASTROKE GWAS. The study population included 42,096 cases of coronary artery disease (99,121 controls), 27,509 cases of myocardial infarction (99,121 controls), and 34,217 cases of ischemic stroke (404,630 controls). We found no associations between genetically predicted self-reported moderate to vigorous PA, accelerometer-based PA or accelerometer fraction of accelerations > 425 milli-gravities as well as sedentary behavior with coronary artery disease, myocardial infarction, and ischemic stroke. CONCLUSIONS:These results do not support a causal relationship between PA and sedentary behavior with risk of coronary artery disease, myocardial infarction, and ischemic stroke. Hence, previous observational studies may have been biased. 10.1007/s00392-021-01846-7
    Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis. Vähätalo Juha H,Holmström Lauri T A,Pylkäs Katri,Skarp Sini,Porvari Katja,Pakanen Lasse,Kaikkonen Kari S,Perkiömäki Juha S,Kerkelä Risto,Huikuri Heikki V,Myerburg Robert J,Junttila M Juhani Frontiers in cardiovascular medicine Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD. The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 ( = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy. A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias. Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease. 10.3389/fcvm.2021.755062
    Long-Term (7-Year) Clinical Implications of Newly Unveiled Asymptomatic Abnormal Ankle-Brachial Index in Patients With Coronary Artery Disease. Lee Jong-Young,Lee Seung-Jae,Lee Seung-Whan,Kim Tae Oh,Yang Yujin,Jeong Yeong Jin,Park Hanbit,Lee Junghoon,Hyun Junho,Kim Ju Hyeon,Lee Pil Hyung,Kang Soo-Jin,Kim Young-Hak,Lee Cheol Whan,Park Seong-Wook Journal of the American Heart Association Background The long-term impact of newly discovered, asymptomatic abnormal ankle-brachial index (ABI) in patients with significant coronary artery disease is limited. Methods and Results Between January 2006 and December 2009, ABI was evaluated in 2424 consecutive patients with no history of claudication or peripheral artery disease who had significant coronary artery disease. We previously reported a 3-year result; therefore, the follow-up period was extended. The primary end point was a composite of all-cause death, myocardial infarction (MI), and stroke over 7 years. Of the 2424 patients with significant coronary artery disease, 385 had an abnormal ABI (ABI ≤0.9 or ≥1.4). During the follow-up period, the rate of the primary outcome was significantly higher in the abnormal ABI group than in the normal ABI group (<0.001). The abnormal ABI group had a significantly higher risk of composite of all-cause death/MI/stroke than the normal ABI group, after adjustment with multivariable Cox proportional hazards regression analysis (hazard ratio [HR], 2.07; 95% CI, 1.67-2.57; <0.001) and propensity score-matched analysis (HR, 1.97; 95% CI, 1.49-2.60; <0.001). In addition, an abnormal ABI was associated with a higher risk of all-cause death, MI, and stroke, but not repeat revascularization. Conclusions Among patients with significant coronary artery disease, asymptomatic abnormal ABI was associated with sustained and increased incidence of composite of all-cause death/MI/stroke, all-cause death, MI, and stroke during extended follow-up over 7 years. 10.1161/JAHA.121.021587
    Retrospective analysis of renal prognosis in elderly coronary artery disease patients complicated with renal insufficiency. Li Jun,Liu Fa-Hu,Guo Jing,Yu Ya-Fen,Li Chun-Qing Aging OBJECTIVE AND METHODS:The aim of this study was to retrospectively analyze the renal prognosis of elderly coronary artery disease (CAD) patients complicated with renal insufficiency. RESULTS:A total of 307 patients were included. The mean follow-up period was 25±11months. The average age was 79±7 years. In the worsening renal function group, there were higher occurrence rate of heart failure and severe coronary artery stenosis, lower rate of percutaneous coronary intervention, lower medication rate of renin-angiotensin blocker, lower plasma albumin, magnesium and hemoglobulin level. There was no significant difference in the rate of worsening renal function or gastrointestinal bleeding between patients who took anti-platelet agents/statins and those without. Patients with reduced left ventricular ejective fraction had higher rate of worsening renal function, yet lower medication rate of renin-angiotensin blockers, lower plasma albumin and hemoglobulin level. Anemia, malnutrition and worsening cardiac function were risk factors of renal function deterioration and mortality. CONCLUSIONS:In the elderly coronary artery disease patients who had renal insufficiency, antiplatelet agents and statin have non-adverse effects on renal function; lower medication rate of renin-angiotensin blocker were found in patients with either worsening renal function or heart failure. Anemia, malnutrition and worsening cardiac function are risk factors of renal function deterioration and mortality. 10.18632/aging.203579
    Mendelian randomization study on the causal effects of tumor necrosis factor inhibition on coronary artery disease and ischemic stroke among the general population. Kang Xiaoying,Jiao Tong,Wang Haiyang,Pernow John,Wirdefeldt Karin EBioMedicine BACKGROUND:Tumor necrosis factor (TNF) is a potent inflammatory cytokine that has been causally associated with coronary artery disease (CAD) and ischemic stroke (IS), implying opportunities for disease prevention by anti-TNF therapeutics. METHODS:Leveraging summary statistics of several genome-wide association studies (GWAS), we assessed the repurposing potential of TNF inhibitors for CAD and IS using drug-target Mendelian randomization (MR) design. Pharmacologic blockade of the pro-inflammatory TNF signalling mediated by TNF receptor 1 (TNFR1) was instrumented by four validated variants. Causal effects of TNF/TNFR1 blockade on CAD (N upto 122,733/424,528) and IS (N upto 60,341/454,450) were then estimated via various MR estimators using circulating C-reactive protein (CRP; N=204,402) as downstream biomarker to reflect treatment effect. Associations of a functional variant, rs1800693, with CRP, CAD and IS were also examined. FINDINGS:No protective effect of TNF/TNFR1 inhibition on CAD or IS was observed. For every 10% decrease of circulating CRP achieved by TNF/TNFR1 blockade, odds ratio was 0.98 (95% confidence interval [CI]: 0.60-1.60) for CAD and 0.77 (95% CI: 0.36-1.63) for IS. Findings remained null in all supplement analyses. INTERPRETATION:Our findings do not support TNFR1 as a promising target for CAD or IS prevention among the general population. Future research is warranted to investigate whether the detrimental effect of circulating TNF on CAD and IS might be counteracted by modulating other relevant drug targets. FUNDING:No. 10.1016/j.ebiom.2022.103824
    Diabetes and Risk of Sudden Death in Coronary Artery Disease Patients Without Severe Systolic Dysfunction. Venkateswaran Ramkumar V,Moorthy M V,Chatterjee Neal A,Pester Julie,Kadish Alan H,Lee Daniel C,Cook Nancy R,Albert Christine M JACC. Clinical electrophysiology OBJECTIVES:This study sought to determine the absolute and relative associations of diabetes mellitus (DM) and hemoglobin A (HbA) with sudden and/or arrhythmic death (SAD) versus other modes of death in patients with coronary artery disease (CAD) who do not qualify for implantable cardioverter-defibrillators. BACKGROUND:Patients with CAD and DM are at elevated risk for SAD; however, it is unclear whether these patients would benefit from implantable cardioverter-defibrillators given competing causes of death and/or whether HbA might augment SAD risk stratification. METHODS:In the PRE-DETERMINE study of 5,764 patients with CAD with left ventricular ejection fraction (LVEF) of >30% to 35%, competing risk analyses were used to compare the absolute and relative risks of SAD versus non-SAD by DM status and HbA level and to identify risk factors for SAD among 1,782 patients with DM. RESULTS:Over a median follow-up of 6.8 years, DM and HbA were significantly associated with SAD and non-SAD (P < 0.05 for all comparisons); however, the cumulative incidence of non-SAD (19.2%; 95% CI: 17.3%-21.2%) was almost 4 times higher than SAD (4.8%; 95% CI: 3.8%-5.9%) in DM patients. A similar pattern of absolute risk was observed across categories of HbA. In analyses limited to patients with DM, HbA was not associated with SAD, whereas low LVEF, atrial fibrillation, and electrocardiogram measurements were associated with higher SAD risk. CONCLUSIONS:In patients with CAD and LVEF of >30% to 35%, patients with DM and/or elevated HbA are at much higher absolute risk of dying from non-SAD than SAD. Clinical risk markers, and not HbA, were associated with SAD risk in patients with DM. (PRE-DETERMINE: Biologic Markers and MRI SCD Cohort Study; NCT01114269). 10.1016/j.jacep.2021.05.014
    NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease. Aukrust Sverre Grøver,Holte Kristine Bech,Opstad Trine B,Seljeflot Ingebjørg,Berg Tore Julsrud,Helseth Ragnhild Frontiers in immunology Background:Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD. Material and Methods:102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes. Results:Circulating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001). Conclusions:In this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation. 10.3389/fimmu.2021.799539
    Clusters of the Risk Markers and the Pattern of Premature Coronary Heart Disease: An Application of the Latent Class Analysis. Jahangiry Leila,Abbasalizad Farhangi Mahdieh,Najafi Mahdi,Sarbakhsh Parvin Frontiers in cardiovascular medicine Coronary heart disease (CHD) is the major cause of mortality in the world with a significant impact on the younger population. The aim of this study was to identify prematurity among patients with coronary artery bypass graft surgery (CABG) based on the clustering of CHD risk factors. Patients were recruited from an existing cohort of candidates for CABG surgery named Tehran Heart Center Coronary Outcome Measurement (THC-COM). A latent class analysis (LCA) model was formed using 11 potential risk factors as binary variables: cigarette smoking, obesity, diabetes, family history of CHD, alcohol use, opium addiction, hypertension, history of stroke, history of myocardial infarction (MI), peripheral vascular disease (PVD), and hyperlipidemia (HLP). We analyzed our data to figure out how the patients are going to be clustered based on their risk factors. For 566 patients who were studied, the mean age (SD) and BMI of patients were 59.1 (8.9) and 27.3 (4.1), respectively. The LCA model fit with two latent classes was statistically significant ( = 824.87, = 21, < 0.0001). The mean (SD) age of patients for Class I and Class II was 55.66 (8.55) and 60.87 (8.66), respectively. Class I (premature) was characterized by a high probability of smoking, alcohol consumption, opium addiction, and a history of MI ( < 0.05), and class II by a high probability of obesity, diabetes, and hypertension. Latent class analysis calculated two groups of severe CHD with distinct risk markers. The younger group, which is characterized by smoking, addiction, and the history of MI, can be regarded as representative of premature CHD. 10.3389/fcvm.2021.707070
    Cardiovascular computed tomography imaging for coronary artery disease risk: plaque, flow and fat. Channon Keith M,Newby David E,Nicol Edward D,Deanfield John Heart (British Cardiac Society) Cardiac imaging is central to the diagnosis and risk stratification of coronary artery disease, beyond symptoms and clinical risk factors, by providing objective evidence of myocardial ischaemia and characterisation of coronary artery plaque. CT coronary angiography can detect coronary plaque with high resolution, estimate the degree of functional stenosis and characterise plaque features. However, coronary artery disease risk is also driven by biological processes, such as inflammation, that are not fully reflected by severity of stenosis, myocardial ischaemia or by coronary plaque features. New cardiac CT techniques can assess coronary artery inflammation by imaging perivascular fat, and this may represent an important step forward in identifying the 'residual risk' that is not detected by plaque or ischaemia imaging. Coronary artery disease risk assessment that incorporates clinical factors, plaque characteristics and perivascular inflammation offers a more comprehensive individualised approach to quantify and stratify coronary artery disease risk, with potential healthcare benefits for prevention, diagnosis and treatment recommendations. Furthermore, identifying new biomarkers of cardiovascular risk has the potential to refine early-life prevention strategies, before atherosclerosis becomes established. 10.1136/heartjnl-2021-320265
    Coronary Artery Calcium Versus Pooled Cohort Equations Score for Primary Prevention Guidance: Randomized Feasibility Trial. JACC. Cardiovascular imaging OBJECTIVES:This study sought to determine the feasibility of performing an extensive randomized outcomes trial comparing a coronary artery calcium (CAC)- versus a pooled cohort equations (PCE) risk score-based strategy for initiating statin therapy for primary atherosclerotic cardiovascular disease (ASCVD) prevention. BACKGROUND:Statin therapy is standard for the primary prevention of ASCVD in subjects at increased risk. National guidelines recommend using the American College of Cardiology/American Heart Association PCE risk score to guide a statin recommendation. Whether guidance by a CAC score is equivalent or superior is unknown. METHODS:CorCal (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events) was a randomized trial consenting 601 patients without known ASCVD, diabetes, or prior statin therapy recruited from primary care clinics and randomized to CAC- (n = 302) or PCE guidance (n = 299) of statin initiation for primary prevention. Enrolled subjects and their physicians made final treatment decisions. Primary outcomes compared the proportion of statin recommendations received and subject adherence over 1 year between CAC- and PCE-arm subjects. Modeled medical costs, adverse effects, and low-density lipoprotein-cholesterol (LDL-C) were additional measures of interest. RESULTS:Subjects were well matched, and 540 (89.9%) completed entry testing and received a protocol-based recommendation. A statin was recommended in 101 (35.9%) CAC-arm and 124 (47.9%) PCE-arm subjects (P = 0.005). Compared to PCE-based recommendations, CAC-arm subjects were reclassified from statin to no statin in 36.0% and from no statin to statin in 5.6% of cases, resulting in a total reclassification of 20.6%. Physicians accepted the study-dictated recommendation to start a statin in 88.1% of CAC-arm vs 75.0% of PCE-arm subjects (P = 0.01). Patient-reported adherence to this recommendation at 3 months was 62.2% vs 42.2%, respectively (P = 0.009). At 1 year, statin adherence remained superior, LDL-C levels were lower, estimated costs were similar or reduced in CAC subjects, and few events occurred. CONCLUSIONS:CAC guidance may be a more efficient, personalized, cost-effective, and motivating approach to statin initiation and maintenance in primary prevention. This feasibility phase of CorCal should be regarded as hypothesis-generating with respect to cardiovascular outcomes, which is being addressed in a large, longer-term outcomes trial. (Effectiveness of a Proactive Cardiovascular Primary Prevention Strategy, With or Without the Use of Coronary Calcium Screening, in Preventing Future Major Adverse Cardiac Events [CorCal]; NCT03439267). 10.1016/j.jcmg.2021.11.006
    A Meta-Analysis Evaluating the Colchicine Therapy in Patients With Coronary Artery Disease. Grajek Stefan,Michalak Michał,Urbanowicz Tomasz,Olasińska-Wiśniewska Anna Frontiers in cardiovascular medicine Evidence from recent studies has shown the benefits of colchicine for patients with coronary artery disease. The aim was to assess the effect of colchicine treatment on cardiovascular events, with an estimation of the risk of discontinuation and net clinical benefit. Fourteen trials with a total of 13,186 patients were selected through a systematic search. Colchicine therapy significantly reduced the relative risk of primary endpoint by about 30% [RR 0.70 (95%CI:0.56-0.88)]. Compared with placebo, colchicine significantly reduced the risk of ischemia-driven revascularization [RR 0.57 (95%CI 0.41-0.80)], ischemia-driven revascularization and resuscitation [RR 0.50 (95%CI 0.34-0.73)], myocardial infarction [RR 0.73 (95%CI 0.57-0.95)], and stroke [RR 0.49 (95%CI 0.30-0.7)]. Patients treated with colchicine in comparison with placebo have a significant increase in the risk of treatment cessation (RR 1.60 95%CI 1.06-2.42). However, in the analysis which excluded studies without placebo, the relative risk of discontinuation was smaller (RR 1.34 95%CI 0.97-1.84) and in the three largest studies, the risk of discontinuation was lower and insignificant [RR 1.26 (95%CI 0.87-1.83)]. The net clinical benefit was 17.8/1,000 patients ( < 0.001). In coronary artery disease, low-dose colchicine significantly reduces the risk of the primary composite endpoint by about 30%. The drug should be considered as part of the preventive treatment in patients with good tolerance. 10.3389/fcvm.2021.740896
    Temporal Changes and Institutional Variation in Use of Percutaneous Coronary Intervention for ST-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease in the United States: An NCDR Research to Practice Project. Secemsky Eric A,Butala Neel,Raja Aishwarya,Khera Rohan,Wang Yongfei,Curtis Jeptha P,Maddox Thomas M,Virani Salim S,Armstrong Ehrin J,Shunk Kendrick A,Brindis Ralph G,Bhatt Deepak,Yeh Robert W JAMA cardiology Importance:After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI). Objective:To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice. Design, Setting, and Participants:This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a PCI to a nonculprit lesion within 45 days of the index procedure. Exposures:Multivessel PCI, defined as placement of coronary stents in 2 or more major epicardial vessels or the staged placement of 1 or more coronary stents in a major epicardial vessel distinct from the index culprit vessel, within 45 days of the index PCI. Main Outcomes and Measures:Outcomes included the proportional use of MV PCI among STEMI admissions with MV disease, and the timing of MV PCI (an index procedure, a staged procedure during index hospitalization, or a postdischarge procedure within 45 days). Results:Among 359 879 admissions with STEMI and MV disease, MV PCI was performed in 38.5% (n = 138 380; mean [SD] age of patients, 62.3 [12.3] years; 102 266 men [73.9%]) within 45 days. Of those receiving MV PCIs, 30.8% (n = 42 629) had a procedure performed during the index procedure, 31.6% (n = 43 696) as a staged procedure during the index hospitalization, and 37.6% (n = 52 055) within 45 days of discharge. Complete revascularization of all diseased arteries was performed in 76.2% (n = 105 389). From the third quarter of 2009 to the second quarter of 2013, MV PCI use declined by 10%, from 42.7% (3230 of 7572 cases) to a nadir of 32.7% (3386 of 10 342 cases), followed by an increase to 44.0% (5062 of 11 497 cases) by the fourth quarter of 2017. During this time, there was a 13.6% decline in use of postdischarge staged MV PCI (from 23.4% of STEMI cases [1772 of 7572 cases] in the third quarter of 2009 to 9.9% [1094 of 11 171 cases] in the fourth quarter of 2014) and an 12.5% increase in MV PCI performed during the index admission (from 19.3% [1458 of 7572 cases] in the third quarter of 2009 to 31.8% [3557 of 11 171 cases] in the first quarter of 2018). Multivessel PCI use varied substantially across institutions, with a median use of 37.9% (interquartile range, 30.0%-46.5%). Conclusions and Relevance:In this large, nationwide analysis, MV PCI use for patients with STEMI has been increasing through early 2018 but was used in the minority of patients and with wide variability across US institutions. The adoption of new trial results into guidelines and practice may further promote the growth of MV PCI. 10.1001/jamacardio.2020.5354
    Clinical Characteristics, Management Strategies, and Outcomes of Non-ST-Segment-Elevation Myocardial Infarction Patients With and Without Prior Coronary Artery Bypass Grafting. Shoaib Ahmad,Rashid Muhammad,Berry Colin,Curzen Nick,Kontopantelis Evangelos,Timmis Adam,Ahmad Ayesha,Kinnaird Tim,Mamas Mamas A Journal of the American Heart Association Background There are limited data on the management strategies, temporal trends and clinical outcomes of patients who present with non-ST-segment-elevation myocardial infarction and have a prior history of CABG. Methods and Results We identified 287 658 patients with non-ST-segment-elevation myocardial infarction between 2010 and 2017 in the United Kingdom Myocardial Infarction National Audit Project database. Clinical and outcome data were analyzed by dividing into 2 groups by prior history of coronary artery bypass grafting (CABG): group 1, no prior CABG (n=262 362); and group 2, prior CABG (n=25 296). Patients in group 2 were older, had higher GRACE (Global Registry of Acute Coronary Events) risk scores and burden of comorbid illnesses. More patients underwent coronary angiography (69% versus 63%) and revascularization (53% versus 40%) in group 1 compared with group 2. Adjusted odds of receiving inpatient coronary angiogram (odds ratio [OR], 0.91; 95% CI, 0.88-0.95; <0.001) and revascularization (OR, 0.73; 95% CI, 0.70-0.76; <0.001) were lower in group 2 compared with group 1. Following multivariable logistic regression analyses, the OR of in-hospital major adverse cardiovascular events (composite of inpatient death and reinfarction; OR, 0.97; 95% CI, 0.90-1.04; =0.44), all-cause mortality (OR, 0.96; 95% CI, 0.88-1.04; =0.31), reinfarction (OR, 1.02; 95% CI, 0.89-1.17; =0.78), and major bleeding (OR, 1.01; 95% CI, 0.90-1.11; =0.98) were similar across groups. Lower adjusted risk of inpatient mortality (OR, 0.67; 95% CI, 0.46-0.98; =0.04) but similar risk of bleeding (OR,1.07; CI, 0.79-1.44; =0.68) and reinfarction (OR, 1.13; 95% CI, 0.81-1.57; =0.47) were observed in group 2 patients who underwent percutaneous coronary intervention compared with those managed medically. Conclusions In this national cohort, patients with non-ST-segment-elevation myocardial infarction with prior CABG had a higher risk profile, but similar risk-adjusted in-hospital adverse outcomes compared with patients without prior CABG. Patients with prior CABG who received percutaneous coronary intervention had lower in-hospital mortality compared with those who received medical management. 10.1161/JAHA.120.018823
    Predictors of Coronary Artery Calcium and Long-Term Risks of Death, Myocardial Infarction, and Stroke in Young Adults. Javaid Aamir,Mitchell Joshua D,Villines Todd C Journal of the American Heart Association Background Coronary artery calcium (CAC) is well-validated for cardiovascular disease risk stratification in middle to older-aged adults; however, the 2019 American College of Cardiology/American Heart Association guidelines state that more data are needed regarding the performance of CAC in low-risk younger adults. Methods and Results We measured CAC in 13 397 patients aged 30 to 49 years without known cardiovascular disease or malignancy between 1997 and 2009. Outcomes of myocardial infarction (MI), stroke, major adverse cardiovascular events (MACE; MI, stroke, or cardiovascular death), and all-cause mortality were assessed using Cox proportional hazard models, controlling for baseline risk factors (including atrial fibrillation for stroke and MACE) and the competing risk of death or noncardiac death as appropriate. The cohort (74% men, mean age 44 years, and 76% with ≤1 cardiovascular disease risk factor) had a 20.6% prevalence of any CAC. CAC was independently predicted by age, male sex, White race, and cardiovascular disease risk factors. Over a mean of 11 years of follow-up, the relative adjusted subhazard ratio of CAC >0 was 2.9 for MI and 1.6 for MACE. CAC >100 was associated with significantly increased hazards of MI (adjusted subhazard ratio, 5.2), MACE (adjusted subhazard ratio, 3.1), stroke (adjusted subhazard ratio, 1.7), and all-cause mortality (hazard ratio, 2.1). CAC significantly improved the prognostic accuracy of risk factors for MACE, MI, and all-cause mortality by the likelihood ratio test (<0.05). Conclusions CAC was prevalent in a large sample of low-risk young adults. Those with any CAC had significantly higher long-term hazards of MACE and MI, while severe CAC increased hazards for all outcomes including death. CAC may have utility for clinical decision-making among select young adults. 10.1161/JAHA.121.022513
    Surgical Techniques for the Treatment of Anomalous Origin of Right Coronary Artery From the Left Sinus: A Comparative Review. Gharibeh Lara,Rahmouni Kenza,Hong Seok Joon,Crean Andrew M,Grau Juan B Journal of the American Heart Association The anomalous aortic origin of the right coronary artery (AAORCA) from the left sinus is a congenital anomaly affecting both the origin and course of the right coronary artery. AAORCA is nowadays easily and increasingly recognized by several cardiac imaging modalities. In most cases, patients remain asymptomatic; however, in some, and especially in young athletes, symptoms start to appear following exertion. A literature review was conducted on the surgical management of AAORCA by searching the Pubmed and Google Scholar databases. The inclusion criteria included manuscripts reporting surgical outcomes of AAORCA for ≥1 of the 3 techniques of interest (unroofing, reimplantation, and coronary artery bypass grafting) and manuscripts written in English and that were published between 2010 and 2020. The surgical management of AAORCA can be done through several techniques, most commonly the unroofing of the intramural segment of the AAORCA, the reimplantation of the native right coronary artery onto the right sinus of the aortic root, and coronary artery bypass grafting with either arterial or venous graft conduits with or without ligation of the proximal right coronary artery. Superiority of one surgical technique has not yet been formally proven because of the rare nature of this condition and the lack of any prospective randomized controlled trial or robust prospective observational studies. 10.1161/JAHA.121.022377
    Anatomical and clinical risk stratification tool for mortality risk assessment following revascularization for multivessel coronary artery disease. Ram Eilon,Kassif Tohar,Peled Yael,Kassif Yigal,Koren Roni Postan,Sternik Leonid,Raanani Ehud The Journal of thoracic and cardiovascular surgery OBJECTIVE:This study aimed to assess the prognostic ability of SYNTAX score II in left main and/or 3-vessel disease patients undergoing revascularization either by coronary artery bypass grafting or percutaneous coronary intervention in a national registry. METHODS:This prospective registry included consecutive patients with multivessel disease enrolled between January and April 2013 from all 22 hospitals in Israel that perform coronary angiography. Of the 1112 study patients, 368 patients (33%) had a low (<25), 372 (33%) had an intermediate (25-35) and 372 patients (33%) a high (≥35) SYNTAX score II. RESULTS:Patients with a high SYNTAX score II had higher 30-day mortality compared with those with an intermediate or low SYNTAX score II (2.8% vs 0.6% vs 0% respectively, P = .001). Each 1-unit increment in SYNTAX score II increased the odds for death at 30 days by 11% (95% CI, 1.02-1.22; P = .026). Six-year mortality was higher among patients with a high compared with an intermediate or low SYNTAX score II (34.9% vs 11% vs 3.8%; log-rank P < .001). By adding a SYNTAX score II to standard prognostic factors, we showed a significant improvement of 40.1% (P < .001) for predicting 6-year mortality. The area under the curve of the SYNTAX score II (continuous) yielded 0.79 (95% CI, 0.75-0.82) in predicting 6-year mortality. CONCLUSIONS:Our findings show that the admission SYNTAX score II is a powerful marker of short- and long-term mortality, and therefore may be used as a risk stratification tool in patients with multivessel coronary artery disease who are candidates for revascularization. 10.1016/j.jtcvs.2021.11.090
    Influence of /MicroRNA-223-3p/P2Y12 Axis on Clopidogrel Response in Coronary Artery Disease. Liu Yan-Ling,Hu Xiao-Lei,Song Pei-Yuan,Li He,Li Mu-Peng,Du Yin-Xiao,Li Mo-Yun,Ma Qi-Lin,Peng Li-Ming,Song Ming-Yu,Chen Xiao-Ping Journal of the American Heart Association Background Dual antiplatelet therapy based on aspirin and P2Y12 receptor antagonists such as clopidogrel is currently the primary treatment for coronary artery disease (CAD). However, a percentage of patients exhibit clopidogrel resistance, in which genetic factors play vital roles. This study aimed to investigate the roles of GAS5 (growth arrest-specific 5) and its rs55829688 polymorphism in clopidogrel response in patients with CAD. Methods and Results A total of 444 patients with CAD receiving dual antiplatelet therapy from 2017 to 2018 were enrolled to evaluate the effect of single nucleotide polymorphism rs55829688 on platelet reactivity index. Platelets from 37 patients of these patients were purified with microbeads to detect GAS5 and microRNA-223-3p (miR-223-3p) expression. Platelet-rich plasma was isolated from another 17 healthy volunteers and 46 newly diagnosed patients with CAD to detect GAS5 and miR-223-3p expression. A dual-luciferase reporter assay was performed to explore the interaction between miR-223-3p and or 3'-UTR in (human embryonic kidney 293 cell line that expresses a mutant version of the SV40 large T antigen) HEK 293T and (megakaryoblastic cell line derived in 1983 from the bone marrow of a chronic myeloid leukemia patient with megakaryoblastic crisis) MEG-01 cells. Loss-of-function and gain-of-function experiments were performed to reveal the regulation of GAS5 toward P2Y12 via miR-223-3p in MEG-01 cells. We observed that rs55829688 CC homozygotes showed significantly decreased platelet reactivity index than TT homozygotes in poor metabolizers. Platelet GAS5 expression correlated positively with both platelet reactivity index and mRNA expressions, whereas platelet miR-223-3p expression negatively correlated with platelet reactivity index. Meanwhile, a negative correlation between GAS5 and miR-223-3p expressions was observed in platelets. MiR-223-3p mimic reduced while the miR-223-3p inhibitor increased the expression of GAS5 and P2Y12 in MEG-01 cells. Knockdown of GAS5 by siRNA increased miR-223-3p expression and decreased P2Y12 expression, which could be reversed by the miR-223-3p inhibitor. Meanwhile, overexpression of GAS5 reduced miR-223-3p expression and increased P2Y12 expression, which could be reversed by miR-223-3p mimic. Conclusions rs55829688 polymorphism might affect clopidogrel response in patients with CAD with the poor metabolizer genotypes, and GAS5 regulates P2Y12 expression and clopidogrel response by acting as a competitive endogenous RNA for miR-223-3p. 10.1161/JAHA.121.021129
    Anxiety Disorders Are Associated With Coronary Endothelial Dysfunction in Women With Chest Pain and Nonobstructive Coronary Artery Disease. Sara Jaskanwal D S,Ahmad Ali,Toya Takumi,Suarez Pardo Laura,Lerman Lilach O,Lerman Amir Journal of the American Heart Association Background Anxiety disorders are the most prevalent mental disorders and are an emerging risk factor for coronary artery disease and its complications. We determine the relationship between having a clinical diagnosis of an anxiety disorder and coronary endothelial dysfunction (CED) using invasive coronary reactivity testing across both sexes. Methods and Results Patients presenting with chest pain and nonobstructive coronary artery disease (stenosis <40%) at coronary angiography underwent an invasive assessment of CED. Patients were categorized as having a clinical diagnosis of an anxiety disorder at the time of coronary angiography by chart review. The frequency of CED was compared between patients with versus without an anxiety disorder and after stratifying patients by sex. Between 1992 and 2020, 1974 patients (mean age, 51.3 years; 66.2% women) underwent invasive coronary reactivity testing, of which 550 (27.9%) had a documented anxiety disorder at the time of angiography. There was a significantly higher proportion of patients with any type of CED in those with an anxiety disorder in all patients (343 [62.7%] versus 790 [56.4%]; =0.011) that persisted in women but not in men. After adjusting for covariables, anxiety was significantly associated with any CED among all patients (odds ratio [95% CI], 1.36 [1.10-1.68]; =0.004), and after stratifying by sex in women but not in men. Conclusions Anxiety disorders are significantly associated with CED in women presenting with chest pain and nonobstructive coronary artery disease. Thus, CED may represent a mechanism underpinning the association between anxiety disorders and coronary artery disease and its complications, highlighting the role of anxiety as a potential therapeutic target to prevent cardiovascular events. 10.1161/JAHA.121.021722
    Reduced nitric oxide bioavailability impairs myocardial oxygen balance during exercise in swine with multiple risk factors. van de Wouw Jens,Sorop Oana,van Drie Ruben W A,Joles Jaap A,Danser A H Jan,Verhaar Marianne C,Merkus Daphne,Duncker Dirk J Basic research in cardiology In the present study, we tested the hypothesis that multiple risk factors, including diabetes mellitus (DM), dyslipidaemia and chronic kidney disease (CKD) result in a loss of nitric oxide (NO) signalling, thereby contributing to coronary microvascular dysfunction. Risk factors were induced in 12 female swine by intravenous streptozotocin injections (DM), a high fat diet (HFD) and renal artery embolization (CKD). Female healthy swine (n = 13) on normal diet served as controls (Normal). After 5 months, swine were chronically instrumented and studied at rest and during exercise. DM + HFD + CKD swine demonstrated significant hyperglycaemia, dyslipidaemia and impaired kidney function compared to Normal swine. These risk factors were accompanied by coronary microvascular endothelial dysfunction both in vivo and in isolated small arteries, due to a reduced NO bioavailability, associated with perturbations in myocardial oxygen balance at rest and during exercise. NO synthase inhibition caused coronary microvascular constriction in exercising Normal swine, but had no effect in DM + HFD + CKD animals, while inhibition of phosphodiesterase 5 produced similar vasodilator responses in both groups, indicating that loss of NO bioavailability was principally responsible for the observed coronary microvascular dysfunction. This was associated with an increase in myocardial 8-isoprostane levels and a decrease in antioxidant capacity, while antioxidants restored the vasodilation to bradykinin in isolated coronary small arteries, suggesting that oxidative stress was principally responsible for the reduced NO bioavailability. In conclusion, five months of combined exposure to DM + HFD + CKD produces coronary endothelial dysfunction due to impaired NO bioavailability, resulting in impaired myocardial perfusion at rest and during exercise. 10.1007/s00395-021-00890-8
    Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery. The New England journal of medicine BACKGROUND:Patients with three-vessel coronary artery disease have been found to have better outcomes with coronary-artery bypass grafting (CABG) than with percutaneous coronary intervention (PCI), but studies in which PCI is guided by measurement of fractional flow reserve (FFR) have been lacking. METHODS:In this multicenter, international, noninferiority trial, patients with three-vessel coronary artery disease were randomly assigned to undergo CABG or FFR-guided PCI with current-generation zotarolimus-eluting stents. The primary end point was the occurrence within 1 year of a major adverse cardiac or cerebrovascular event, defined as death from any cause, myocardial infarction, stroke, or repeat revascularization. Noninferiority of FFR-guided PCI to CABG was prespecified as an upper boundary of less than 1.65 for the 95% confidence interval of the hazard ratio. Secondary end points included a composite of death, myocardial infarction, or stroke; safety was also assessed. RESULTS:A total of 1500 patients underwent randomization at 48 centers. Patients assigned to undergo PCI received a mean (±SD) of 3.7±1.9 stents, and those assigned to undergo CABG received 3.4±1.0 distal anastomoses. The 1-year incidence of the composite primary end point was 10.6% among patients randomly assigned to undergo FFR-guided PCI and 6.9% among those assigned to undergo CABG (hazard ratio, 1.5; 95% confidence interval [CI], 1.1 to 2.2), findings that were not consistent with noninferiority of FFR-guided PCI (P = 0.35 for noninferiority). The incidence of death, myocardial infarction, or stroke was 7.3% in the FFR-guided PCI group and 5.2% in the CABG group (hazard ratio, 1.4; 95% CI, 0.9 to 2.1). The incidences of major bleeding, arrhythmia, and acute kidney injury were higher in the CABG group than in the FFR-guided PCI group. CONCLUSIONS:In patients with three-vessel coronary artery disease, FFR-guided PCI was not found to be noninferior to CABG with respect to the incidence of a composite of death, myocardial infarction, stroke, or repeat revascularization at 1 year. (Funded by Medtronic and Abbott Vascular; FAME 3 ClinicalTrials.gov number, NCT02100722.). 10.1056/NEJMoa2112299
    A Dose Response Association Between Body Mass Index and Mortality in Patients with Peripheral Artery Disease: A Meta-analysis Including 5 729 272 Individuals. Lin Donna S-H,Lo Hao-Yun,Yu An-Li,Lee Jen-Kuang,Yang Wei-Shiung,Hwang Juey-Jen European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery OBJECTIVE:Obesity is a significant risk factor for atherosclerotic cardiovascular disease; however, the "obesity paradox", in which obese patients enjoy superior survival, has been observed in various cardiovascular conditions. Whether this phenomenon exists for peripheral artery disease (PAD) remains uncertain. The goal of this study was to evaluate the relationship between body mass index (BMI) and mortality in patients with PAD. METHODS:A comprehensive literature search identified seven eligible cohort studies that reported the association between BMI and all cause mortality in patients with PAD. A dose response meta-analysis was done for all cause mortality, short term (30 day or in hospital) mortality and long term mortality. The dose response association between BMI and mortality was also assessed in patients who received endovascular therapy (EVT). RESULTS:The non-linear dose response analysis showed that higher BMI values were associated with a lower mortality risk from the range between 15 kg/m to approximately 33 - 34 kg/m. The risk of mortality increased slightly thereafter. This relationship was consistent with that of long term mortality but was not apparent in short term mortality. A U shaped relationship was also observed between BMI and mortality in patients who received EVT with the lowest mortality observed at around 30 kg/m. CONCLUSION:The obesity paradox was evident in the analysis of long term survival among patients with PAD, with the lowest mortality rates observed in obese patients. However, this association was not observed for short term or in hospital mortality. 10.1016/j.ejvs.2021.11.016
    Comprehensive Assessment of High-Risk Plaques by Dual-Modal Imaging Catheter in Coronary Artery. Kim Sunwon,Nam Hyeong Soo,Lee Min Woo,Kim Hyun Jung,Kang Woo Jae,Song Joon Woo,Han Jeongmoo,Kang Dong Oh,Oh Wang-Yuhl,Yoo Hongki,Kim Jin Won JACC. Basic to translational science Coronary plaque destabilization involves alterations in microstructure and biochemical composition; however, no imaging approach allows such comprehensive characterization. Herein, the authors demonstrated a simultaneous microstructural and biochemical assessment of high-risk plaques in the coronary arteries in a beating heart using a fully integrated optical coherence tomography and fluorescence lifetime imaging (FLIm). It was found that plaque components such as lipids, macrophages, lipids+macrophages, and fibrotic tissues had unique fluorescence lifetime signatures that were distinguishable using multispectral FLIm. Because FLIm yielded massive biochemical readouts, the authors incorporated machine learning framework into FLIm, and ultimately, their approach enabled an automated, quantitative imaging of multiple key components relevant for plaque destabilization. 10.1016/j.jacbts.2021.10.005
    Galectin-3 is linked to peripheral artery disease severity, and urinary excretion is associated with long-term mortality. Ursli Martin,Zierfuss Bernhard,Grigassy Thomas,Pesau Gerfried,Koppensteiner Renate,Schernthaner Gerit-Holger,Höbaus Clemens Atherosclerosis BACKGROUND AND AIMS:Galectin-3 (Gal-3) is a biomarker involved in fibrosis and vascular inflammation. Gal-3 has been linked to chronic kidney disease (CKD) and patients with peripheral artery disease (PAD). Conflicting reports exist about the relevance of Gal-3 in PAD. The study aims to elucidate a possible link between serum and urinary Gal-3 and long-term survival in PAD patients without critical limb ischemia and mild to moderate CKD. METHODS:Galectin-3 (Gal-3) was measured in serum (n = 311) and urine (n = 266) of PAD patients (age 69 (62-77) years) by bead-based multiplex assay. Urinary Gal-3 concentration was normalized to urine creatinine (cr) levels. Mortality data were retrieved from the Austrian central death registry after a median observation period of 9.2 years. Survival analyses were performed by the Kaplan-Meier method and Cox-regression. RESULTS:Serum Gal-3 was higher in patients with claudication symptoms (p = 0.001) and correlated inversely with the patients' ankle-brachial index (R = -0.168, p = 0.009). Serum Gal-3 and urinary Gal-3 (uGal-3/cr) were associated with the estimated glomerular filtration rate (R = -0.359, p < 0.001; R = -0.285, p < 0.001). Serum Gal-3 was not linked to all-cause mortality [HR 1.17 (CI 0.96-1.42)] over 9.2 years. However, uGal-3/cr was associated with all-cause mortality [HR 1.60 (CI 1.31-1.95)]. This association sustained multivariable adjustment for cardiovascular risk factors and renal function [HR 1.71 (CI 1.35-2.17)]. CONCLUSIONS:This study is the first to show an association of uGal-3/cr and long-term mortality in patients with PAD. Gal-3 was not predictive of long-term mortality but seems to be a marker of PAD severity in patients without critical limb ischemia. 10.1016/j.atherosclerosis.2021.11.016
    Adverse cardiac mechanics and incident coronary heart disease in the Cardiovascular Health Study. Heart (British Cardiac Society) OBJECTIVES:Speckle-tracking echocardiography enables detection of abnormalities in cardiac mechanics with higher sensitivity than conventional measures of left ventricular (LV) dysfunction and may provide insight into the pathogenesis of coronary heart disease (CHD). We investigated the relationship of LV longitudinal strain, LV early diastolic strain rate (SR) and left atrial (LA) reservoir strain with long-term CHD incidence in community-dwelling older adults. METHODS:The association of all three strain measures with incidence of non-fatal and fatal CHD (primary outcome of revascularisation, non-fatal and fatal myocardial infarction) was examined in the population-based Cardiovascular Health Study using multivariable Cox proportional hazards models. Follow-up was truncated at 10 years. RESULTS:We included 3313 participants (mean (SD) age 72.6 (5.5) years). During a median follow-up of 10.0 (25th-75th percentile 7.7-10.0) years, 439 CHD events occurred. LV longitudinal strain (HR=1.25 per SD decrement, 95% CI 1.09 to 1.43) and LV early diastolic SR (HR=1.31 per SD decrement, 95% CI 1.14 to 1.50) were associated with a significantly greater risk of incident CHD after adjustment for potential confounders. By contrast, LA reservoir strain was not associated with incident CHD (HR=1.06 per SD decrement, 95% CI 0.94 to 1.19). Additional adjustment for biochemical and echocardiographic measures of myocardial stress, dysfunction and remodelling did not meaningfully alter these associations. CONCLUSION:We found an association between echocardiographic measures of subclinically altered LV mechanics and incident CHD. These findings inform the underlying biology of subclinical LV dysfunction and CHD. Early detection of asymptomatic myocardial dysfunction may offer an opportunity for prevention and early intervention. 10.1136/heartjnl-2021-319296
    Evaluation of Stress Cardiac Magnetic Resonance Imaging in Risk Reclassification of Patients With Suspected Coronary Artery Disease. Antiochos Panagiotis,Ge Yin,Steel Kevin,Chen Yi-Yun,Bingham Scott,Abdullah Shuaib,Mikolich J Ronald,Arai Andrew E,Bandettini W Patricia,Patel Amit R,Farzaneh-Far Afshin,Heitner John F,Shenoy Chetan,Leung Steve W,Gonzalez Jorge A,Shah Dipan J,Raman Subha V,Ferrari Victor A,Schulz-Menger Jeanette,Stuber Matthias,Simonetti Orlando P,Murthy Venkatesh L,Kwong Raymond Y JAMA cardiology Importance:The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline-recommended categories has not been established. Objective:To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia. Design, Setting, and Participants:A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020. Main Outcomes and Measures:Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery. Results:Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (<1% per year), intermediate (1%-3% per year), and high (>3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk). Conclusions and Relevance:In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI. 10.1001/jamacardio.2020.2834
    Patient-Friendly Summary of the ACR Appropriateness Criteria Asymptomatic Patient at Risk for Coronary Artery Disease. Hahn Emily,Jhala Khushboo Journal of the American College of Radiology : JACR 10.1016/j.jacr.2021.09.031
    Myocardial Infarction and Coronary Artery Disease in Menopausal Women With Type 2 Diabetes Mellitus Negatively Correlate With Total Serum Bile Acids. Feng Xunxun,Zhai Guangyao,Yang Jiaqi,Liu Yang,Zhou Yujie,Guo Qianyun Frontiers in endocrinology Background:As metabolic molecules, bile acids (BAs) not only promote the absorption of fat-soluble nutrients, but they also regulate many metabolic processes, including the homeostasis of glucose and lipids. Although total serum BA (TBA) measurement is a readily available clinical test related to coronary artery disease (CAD), myocardial infarction (MI), and type 2 diabetes mellitus (T2DM), the relationship between TBA and these pathological conditions remain unclear, and research on this topic is inconclusive. Methods:This study enrolled 20,255 menopausal women aged over 50 years, including 6,421 T2DM patients. The study population was divided into different groups according to the median TBA level in order to explore the clinical characteristics of menopausal women with different TBA levels. Spline analyses, generalized additive model (GAM) model and regression analyses based on TBA level were used to explore the relationship between TBA and different diseases independently, including CAD and MI, or in combination with T2DM. Results:Both in the general population and in the T2DM subgroup, the TBA level was significantly lower in CAD patients than in non-CAD patients. Spline analyses indicated that within normal clinical range of TBA concentration (0-10 µmol/L), the presence of CAD and MI showed similar trends in total and T2DM population. Similarly, the GAM model indicated that within the 0-10 μmol/L clinical range, the predicted probability for CAD and MI alone and in combination with T2DM was negatively correlated with TBA concentration. Multivariate regression analysis suggested that low TBA level was positively associated with the occurrence of CAD combined with T2DM (OR: 1.451; 95%CI: 1.141-1.847). Conclusions:In menopausal women, TBA may represent a valuable clinical serum marker with negative correlation for CAD and MI in patients with T2DM. 10.3389/fendo.2021.754006
    Association of Coronary Artery Disease and Metabolic Syndrome: Usefulness of Serum Metabolomics Approach. Jing Ziwei,Liu Liwei,Shi Yingying,Du Qiuzheng,Zhang Dingding,Zuo Lihua,Du Shuzhang,Sun Zhi,Zhang Xiaojian Frontiers in endocrinology Introduction:Individuals with metabolic syndrome (MetS) are at increasing risk of coronary artery disease (CAD). We investigated the common metabolic perturbations of CAD and MetS serum metabolomics to provide insight into potential associations. Methods:Non-targeted serum metabolomics analyses were performed using ultra high-performance liquid chromatography coupled with Q Exactive hybrid quadrupole-orbitrap high-resolution accurate mass spectrometry (UHPLC-Q-Orbitrap HRMS) in samples from 492 participants (272 CAD 121 healthy controls (HCs) as cohort 1, 55 MetS 44 HCs as cohort 2). Cross-sectional data were obtained when the participants were recruited from the First Affiliated Hospital of Zhengzhou University. Multivariate statistics and Student's t test were applied to obtain the significant metabolites [with variable importance in the projection (VIP) values >1.0 and p values <0.05] for CAD and MetS. Logistic regression was performed to investigate the association of identified metabolites with clinical cardiac risk factors, and the association of significant metabolic perturbations between CAD and MetS was visualized by Cytoscape software 3.6.1. Finally, the receiver operating characteristic (ROC) analysis was evaluated for the risk prediction values of common changed metabolites. Results:Thirty metabolites were identified for CAD, mainly including amino acids, lipid, fatty acids, pseudouridine, niacinamide; 26 metabolites were identified for MetS, mainly including amino acids, lipid, fatty acids, steroid hormone, and paraxanthine. The logistic regression results showed that all of the 30 metabolites for CAD, and 15 metabolites for MetS remained significant after adjustments of clinical risk factors. In the common metabolic signature association analysis between CAD and MetS, 11 serum metabolites were significant and common to CAD and MetS outcomes. Out of this, nine followed similar trends while two had differing directionalities. The nine common metabolites exhibiting same change trend improved risk prediction for CAD (86.4%) and MetS (90.9%) using the ROC analysis. Conclusion:Serum metabolomics analysis might provide a new insight into the potential mechanisms underlying the common metabolic perturbations of CAD and MetS. 10.3389/fendo.2021.692893
    Coronary Disease Association With ADAMTS7 Is Due to Protease Activity. Mizoguchi Taiji,MacDonald Bryan T,Bhandary Bidur,Popp Nicholas R,Laprise Dylan,Arduini Alessandro,Lai Daniel,Zhu Qiuyu Martin,Xing Yi,Kaushik Virendar K,Kathiresan Sekar,Ellinor Patrick T Circulation research [Figure: see text]. 10.1161/CIRCRESAHA.121.319163
    Neutrophil Extracellular Traps in the Infarct-Related Coronary Artery-A Marker or Mediator of Adverse Outcome? Gorog Diana Adrienne,Massberg Steffen Thrombosis and haemostasis 10.1055/a-1733-9217
    Radiogenomics and Artificial Intelligence Approaches Applied to Cardiac Computed Tomography Angiography and Cardiac Magnetic Resonance for Precision Medicine in Coronary Heart Disease: A Systematic Review. Infante Teresa,Cavaliere Carlo,Punzo Bruna,Grimaldi Vincenzo,Salvatore Marco,Napoli Claudio Circulation. Cardiovascular imaging The risk of coronary heart disease (CHD) clinical manifestations and patient management is estimated according to risk scores accounting multifactorial risk factors, thus failing to cover the individual cardiovascular risk. Technological improvements in the field of medical imaging, in particular, in cardiac computed tomography angiography and cardiac magnetic resonance protocols, laid the development of radiogenomics. Radiogenomics aims to integrate a huge number of imaging features and molecular profiles to identify optimal radiomic/biomarker signatures. In addition, supervised and unsupervised artificial intelligence algorithms have the potential to combine different layers of data (imaging parameters and features, clinical variables and biomarkers) and elaborate complex and specific CHD risk models allowing more accurate diagnosis and reliable prognosis prediction. Literature from the past 5 years was systematically collected from PubMed and Scopus databases, and 60 studies were selected. We speculated the applicability of radiogenomics and artificial intelligence through the application of machine learning algorithms to identify CHD and characterize atherosclerotic lesions and myocardial abnormalities. Radiomic features extracted by cardiac computed tomography angiography and cardiac magnetic resonance showed good diagnostic accuracy for the identification of coronary plaques and myocardium structure; on the other hand, few studies exploited radiogenomics integration, thus suggesting further research efforts in this field. Cardiac computed tomography angiography resulted the most used noninvasive imaging modality for artificial intelligence applications. Several studies provided high performance for CHD diagnosis, classification, and prognostic assessment even though several efforts are still needed to validate and standardize algorithms for CHD patient routine according to good medical practice. 10.1161/CIRCIMAGING.121.013025
    Additional survival benefit of bilateral in situ internal thoracic artery grafting with composite radial artery graft in total arterial off-pump coronary artery bypass grafting. Shimahara Yusuke,Fukushima Satsuki,Kawamoto Naonori,Tadokoro Naoki,Nakai Michikazu,Kobayashi Junjiro,Fujita Tomoyuki The Journal of thoracic and cardiovascular surgery OBJECTIVE:This study aimed to elucidate whether the use of bilateral internal thoracic arteries (BITAs) confers additional survival benefits compared with a single internal thoracic artery (SITA) in total arterial grafting with the radial artery. METHODS:Between 2002 and 2016, 617 patients underwent a bilateral in situ internal thoracic artery grafting with the radial artery as a composite I-graft (BITA-I group) and 516 patients underwent single in situ internal thoracic artery grafting with the radial artery as a composite Y-graft (SITA-Y group). All anastomoses were performed without cardiopulmonary bypass and aortic manipulation. Propensity score matching was performed to adjust covariates and compared the outcomes between the 2 groups. Subanalysis was also performed to evaluate the effects of the BITA-I group on survival according to the covariates using Cox proportional hazards regression analysis. RESULTS:Propensity score matching yielded 348 well-matched pairs. Early postoperative outcomes were similar in the 2 groups. The BITA-I group showed significantly better survival than the SITA-Y group (79.3% vs 70.2% at 10 years, P = .015). The subanalysis revealed a significantly better survival in the BITA-I group among overall patients (hazard ratio, 0.68; 95% confidence interval, 0.49-0.93). There was a significant positive effect on survival in the BITA-I group among patients without comorbidities or those aged <77 years. CONCLUSIONS:BITA grafting with the radial artery provides better long-term survival than SITA grafting with the radial artery, which is enhanced among patients aged <77 years with minimum comorbidities. 10.1016/j.jtcvs.2021.11.083
    Myocardial ischemia and previous infarction contribute to left ventricular dyssynchrony in patients with coronary artery disease. Hämäläinen Hanna,Corovai Alisa,Laitinen Jussi,Laitinen Tiina M,Hedman Marja,Hedman Antti,Kivelä Antti,Laitinen Tomi P Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology AIMS:The aim of this study was to characterize determinants of left ventricular mechanical dyssynchrony (LVMD) in patients with coronary artery disease (CAD). METHODS:Medical records and results of myocardial perfusion SPECT/CT studies were evaluated in 326 patients with previously diagnosed CAD. LVMD was assessed with the phase analysis of ECG-gated myocardial SPECT. Dyssynchrony was described with phase histogram bandwidth (PHBW), standard deviation (PHSD) or entropy (PHE) values above limit of the highest normal. RESULTS:Prevalence of LVMD was 29% in CAD patients. Size of the infarction scar and ischemia extent correlated significantly with PHBW, PHSD and PHE (P < 0.001 for all). Independent predictors of LVMD were myocardial infarction scar (P = 0.004), ischemia extent (P = 0.003), and QRS duration (P = 0.003). Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. CONCLUSIONS:Almost one-third of CAD patients had significant LVMD. Dyssynchrony was associated with earlier myocardial infarction and presence of myocardial ischemia. Previous percutaneous coronary intervention and coronary artery bypass grafting did not independently predict dyssynchrony. 10.1007/s12350-020-02316-9
    Association of Non-High-Density Lipoprotein Cholesterol Measured in Adolescence, Young Adulthood, and Mid-Adulthood With Coronary Artery Calcification Measured in Mid-Adulthood. Armstrong Matthew K,Fraser Brooklyn J,Hartiala Olli,Buscot Marie-Jeanne,Juonala Markus,Wu Feitong,Koskinen Juha,Hutri-Kähönen Nina,Kähönen Mika,Laitinen Tomi P,Lehtimäki Terho,Viikari Jorma S A,Raitakari Olli T,Magnussen Costan G JAMA cardiology Importance:Elevated non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the presence of coronary artery calcification (CAC), a marker of heart disease in adulthood. However, the relative importance of non-HDL-C levels at specific life stages for CAC remains unclear. Objective:To identify the relative association of non-HDL-C measured at distinct life stages (adolescence, young adulthood, mid-adulthood) with the presence of CAC measured in mid-adulthood. Design, Setting, and Participants:The Cardiovascular Risk in Young Finns Study is a population-based prospective cohort study that started in 1980 with follow-up over 28 years. Participants from 3 population centers (Kuopio, Tampere, and Turku in Finland) represent a convenience sample drawn from the 3 oldest cohorts at baseline (aged 12-18 years in 1980). Data were collected from September 1980 to August 2008. Analysis began February 2020. Exposures:Non-HDL-C levels were measured at 3 life stages including adolescence (aged 12-18 years), young adulthood (aged 21-30 years), and mid-adulthood (aged 33-45 years). Main Outcomes and Measures:In 2008, CAC was determined from computed tomography and dichotomized as 0 (no CAC, Agatston score = 0) and 1 (presence of CAC, Agatston score ≥1) for analysis. Using a bayesian relevant life course exposure model, the relative association was determined between non-HDL-C at each life stage and the presence of CAC in mid-adulthood. Results:Of 589 participants, 327 (56%) were female. In a model adjusted for year of birth, sex, body mass index, systolic blood pressure, blood glucose level, smoking status, lipid-lowering and antihypertensive medication use, and family history of heart disease, cumulative exposure to non-HDL-C across all life stages was associated with CAC (odds ratio [OR], 1.50; 95% credible interval [CrI], 1.14-1.92). At each life stage, non-HDL-C was associated with CAC and exposure to non-HDL-C during adolescence had the strongest association (adolescence: OR, 1.16; 95% CrI, 1.01-1.46; young adulthood: OR, 1.14; 95% CrI, 1.01-1.43; mid-adulthood: OR, 1.12; 95% CrI, 1.01-1.34). Conclusions and Relevance:These data suggest that elevated non-HDL-C levels at all life stages are associated with coronary atherosclerosis in mid-adulthood. However, adolescent non-HDL-C levels showed the strongest association with the presence of CAC in mid-adulthood, and greater awareness of the importance of elevated non-HDL-C in adolescence is needed. 10.1001/jamacardio.2020.7238
    Comparison of Midterm Outcomes Associated With Aspirin and Ticagrelor vs Aspirin Monotherapy After Coronary Artery Bypass Grafting for Acute Coronary Syndrome. Björklund Erik,Malm Carl Johan,Nielsen Susanne J,Hansson Emma C,Tygesen Hans,Romlin Birgitta S,Martinsson Andreas,Omerovic Elmir,Pivodic Aldina,Jeppsson Anders JAMA network open Importance:Guidelines recommend dual antiplatelet therapy after coronary artery bypass grafting (CABG) for patients with acute coronary syndrome (ACS). However, the evidence for these recommendations is weak. Objective:To compare midterm outcomes after CABG in patients with ACS treated postoperatively with acetylsalicylic acid (ASA) and ticagrelor or with ASA monotherapy. Design, Setting, and Participants:This cohort study used merged data from several national registries of Swedish patients who were diagnosed with ACS and subsequently underwent CABG. All included patients underwent isolated CABG in Sweden between 2012 and 2017 with an ACS diagnosis less than 6 weeks before the procedure, survived 14 days after discharge from hospital, and were treated postoperatively with ASA plus ticagrelor or ASA monotherapy. A multivariable Cox regression model was used for the main analysis, and propensity score-matched models were performed as sensitivity analysis. Data were analyzed between May and September 2020. Exposures:Postoperative antiplatelet treatment, defined as filled prescriptions, with either ASA and ticagrelor or ASA only. Main Outcomes and Measures:Major adverse cardiovascular events (MACE), defined as all-cause mortality, myocardial infarction, and stroke, and major bleeding, at 12 months and at the end of follow-up. Results:A total of 6558 patients (5281 [80.5%] men; mean [SD] age at surgery, 67.6 [9.3] years) were included; 1813 (27.6%) were treated with ASA plus ticagrelor and 4745 (72.4%) were treated with ASA monotherapy. Crude MACE rate was 3.0 per 100 person years (95% CI, 2.5-3.6 per 100 person years) in the ASA plus ticagrelor group and 3.8 per 100 person years (95% CI, 3.5-4.1 per 100 person years) in the ASA group. After adjustment, there was no significant difference in MACE risk between ASA plus ticagrelor vs ASA only, neither during the first 12 months (adjusted hazard ratio [aHR], 0.84; 95% CI, 0.58-1.21; P = .34) or during total follow-up (aHR, 0.89; 95% CI, 0.71-1.11; P = .29). The use of ASA plus ticagrelor was associated with a significantly increased risk for major bleeding during the first 12 months (aHR, 1.90; 95% CI, 1.16-3.13; P = .011). Sensitivity analyses confirmed the results. Conclusions and Relevance:In patients with ACS who survived 2 weeks after CABG, no significant difference in the risk of death or ischemic events could be demonstrated between ASA plus ticagrelor and patients treated with ASA only, while the risk for major bleeding was higher in patients treated with ASA plus ticagrelor. Sufficiently powered prospective randomized trials comparing different antiplatelet therapy strategies after CABG are warranted. 10.1001/jamanetworkopen.2021.22597
    Spontaneous Coronary Artery Dissection. Ufuk Furkan,Kilic Ismail Dogu Radiology 10.1148/radiol.2021211385
    Assessment of the CHADS-VASc Score for the Prediction of Death in Elderly Patients With Coronary Artery Disease and Atrial Fibrillation. Wu Yangxun,Wang Guanyun,Dong Lisha,Qin Liu'an,Li Jian,Yan Hengming,Guo Wenjie,Feng Xiaodong,Zou Yuting,Wang Ziqian,Du Rina,Zhang Yuxiao,Ma Jing,Yin Tong Frontiers in cardiovascular medicine Coronary artery disease (CAD) and atrial fibrillation (AF) often coexist and lead to a much higher risk of mortality in the elderly population. The aim of this study was to investigate whether the CHADS-VASc score could predict the risk of death in elderly patients with CAD and AF. Hospitalized patients aged ≥65 years with a diagnosis of CAD and AF were recruited consecutively. Patients were divided into 5 groups according to the CHADS-VASc score (≤2, =3, =4, =5, and ≥6). At least a 1-year follow-up was carried out for the assessment of all-cause death. A total of 1,579 eligible patients were recruited, with 582 all-cause deaths (6.86 per 100 patient-years) occurring during a follow-up of at least 1 year. With the increase in the CHADS-VASc score, the 1-year and 5-year survival rate decreased (96.4% vs. 95.7% vs. 94.0% vs. 86.5% vs. 85.7%, respectively, < 0.001; 78.4% vs. 68.9% vs. 64.6% vs. 55.5% vs. 50.0%, respectively, < 0.001). Compared with the patients with CHADS-VASc score <5, for patients with CHADS-VASc score ≥5, the adjusted hazard ratio for death was 1.78 (95% CI: 1.45-2.18, < 0.001). The predictive values of the CHADS-VASc score ≥5 for in-hospital (C-index = 0.66, 95% CI: 0.62-0.69, < 0.001), 1-year (C-index = 0.65, 95% CI: 0.63-0.67, < 0.001) and 5-year (C-index = 0.60, 95% CI: 0.59-0.61, < 0.001) death were in comparable. In elderly patients with concomitant CAD and AF, the CHADS-VASc score can be used to predict death with moderate accuracy. 10.3389/fcvm.2021.805234
    Polygenic Risk Score for Coronary Artery Disease Improves the Prediction of Early-Onset Myocardial Infarction and Mortality in Men. Manikpurage Hasanga D,Eslami Aida,Perrot Nicolas,Li Zhonglin,Couture Christian,Mathieu Patrick,Bossé Yohan,Arsenault Benoit J,Thériault Sébastien Circulation. Genomic and precision medicine BACKGROUND:Several risk factors for coronary artery disease (CAD) have been described, some of which are genetically determined. The use of a polygenic risk score (PRS) could improve CAD risk assessment, but predictive accuracy according to age and sex is not well established. METHODS:A PRS including the weighted effects of >1.14 million single nucleotide polymorphisms associated with CAD was calculated in UK Biobank (n=408 422), using LDpred. Cox regressions were performed, stratified by age quartiles and sex, for incident myocardial infarction (MI) and mortality, with a median follow-up of 11.0 years. Improvement in risk prediction of MI was assessed by comparing PRS to the pooled cohort equation with categorical net reclassification index using a 2% threshold (NRI) and continuous NRI (NRI). RESULTS:From 7746 incident MI cases and 393 725 controls, hazard ratio for MI reached 1.53 (95% CI, 1.49-1.56; =2.69×10) per SD increase of PRS. PRS was significantly associated with MI in both sexes, with a stronger association in men (interaction =0.002), particularly in those aged between 40 and 51 years (hazard ratio, 2.00 [95% CI, 1.86-2.16], =1.93×10). This group showed the highest reclassification improvement, mainly driven by the up-classification of cases (NRI, 0.199 [95% CI, 0.157-0.248] and NRI, 0.602 [95% CI, 0.525-0.683]). From 23 982 deaths, hazard ratio for mortality was 1.08 (95% CI, 1.06-1.09; =5.46×10) per SD increase of PRS, with a stronger association in men (interaction =1.60×10). CONCLUSIONS:Our PRS predicts MI incidence and all-cause mortality, especially in men aged between 40 and 51 years. PRS could optimize the identification and management of individuals at risk for CAD. 10.1161/CIRCGEN.121.003452
    Psychological and pharmacological interventions for depression in patients with coronary artery disease. The Cochrane database of systematic reviews BACKGROUND:Depression occurs frequently in individuals with coronary artery disease (CAD) and is associated with a poor prognosis. OBJECTIVES:To determine the effects of psychological and pharmacological interventions for depression in CAD patients with comorbid depression. SEARCH METHODS:We searched the CENTRAL, MEDLINE, Embase, PsycINFO, and CINAHL databases up to August 2020. We also searched three clinical trials registers in September 2021. We examined reference lists of included randomised controlled trials (RCTs) and contacted primary authors. We applied no language restrictions. SELECTION CRITERIA:We included RCTs investigating psychological and pharmacological interventions for depression in adults with CAD and comorbid depression. Our primary outcomes included depression, mortality, and cardiac events. Secondary outcomes were healthcare costs and utilisation, health-related quality of life, cardiovascular vital signs, biomarkers of platelet activation, electrocardiogram wave parameters, non-cardiac adverse events, and pharmacological side effects. DATA COLLECTION AND ANALYSIS:Two review authors independently examined the identified papers for inclusion and extracted data from the included studies. We performed random-effects model meta-analyses to compute overall estimates of treatment outcomes. MAIN RESULTS:Thirty-seven trials fulfilled our inclusion criteria. Psychological interventions may result in a reduction in end-of-treatment depression symptoms compared to controls (standardised mean difference (SMD) -0.55, 95% confidence interval (CI) -0.92 to -0.19, I = 88%; low certainty evidence; 10 trials; n = 1226). No effect was evident on medium-term depression symptoms one to six months after the end of treatment (SMD -0.20, 95% CI -0.42 to 0.01, I = 69%; 7 trials; n = 2654). The evidence for long-term depression symptoms and depression response was sparse for this comparison. There is low certainty evidence that psychological interventions may result in little to no difference in end-of-treatment depression remission (odds ratio (OR) 2.02, 95% CI 0.78 to 5.19, I = 87%; low certainty evidence; 3 trials; n = 862). Based on one to two trials per outcome, no beneficial effects on mortality and cardiac events of psychological interventions versus control were consistently found. The evidence was very uncertain for end-of-treatment effects on all-cause mortality, and data were not reported for end-of-treatment cardiovascular mortality and occurrence of myocardial infarction for this comparison. In the trials examining a head-to-head comparison of varying psychological interventions or clinical management, the evidence regarding the effect on end-of-treatment depression symptoms is very uncertain for: cognitive behavioural therapy compared to supportive stress management; behaviour therapy compared to person-centred therapy; cognitive behavioural therapy and well-being therapy compared to clinical management. There is low certainty evidence from one trial that cognitive behavioural therapy may result in little to no difference in end-of-treatment depression remission compared to supportive stress management (OR 1.81, 95% CI 0.73 to 4.50; low certainty evidence; n = 83). Based on one to two trials per outcome, no beneficial effects on depression remission, depression response, mortality rates, and cardiac events were consistently found in head-to-head comparisons between psychological interventions or clinical management. The review suggests that pharmacological intervention may have a large effect on end-of-treatment depression symptoms (SMD -0.83, 95% CI -1.33 to -0.32, I = 90%; low certainty evidence; 8 trials; n = 750). Pharmacological interventions probably result in a moderate to large increase in depression remission (OR 2.06, 95% CI 1.47 to 2.89, I = 0%; moderate certainty evidence; 4 trials; n = 646). We found an effect favouring pharmacological intervention versus placebo on depression response at the end of treatment, though strength of evidence was not rated (OR 2.73, 95% CI 1.65 to 4.54, I = 62%; 5 trials; n = 891). Based on one to four trials per outcome, no beneficial effects regarding mortality and cardiac events were consistently found for pharmacological versus placebo trials, and the evidence was very uncertain for end-of-treatment effects on all-cause mortality and myocardial infarction. In the trials examining a head-to-head comparison of varying pharmacological agents, the evidence was very uncertain for end-of-treatment effects on depression symptoms. The evidence regarding the effects of different pharmacological agents on depression symptoms at end of treatment is very uncertain for: simvastatin versus atorvastatin; paroxetine versus fluoxetine; and escitalopram versus Bu Xin Qi. No trials were eligible for the comparison of a psychological intervention with a pharmacological intervention. AUTHORS' CONCLUSIONS:In individuals with CAD and depression, there is low certainty evidence that psychological intervention may result in a reduction in depression symptoms at the end of treatment. There was also low certainty evidence that pharmacological interventions may result in a large reduction of depression symptoms at the end of treatment. Moderate certainty evidence suggests that pharmacological intervention probably results in a moderate to large increase in depression remission at the end of treatment. Evidence on maintenance effects and the durability of these short-term findings is still missing. The evidence for our primary and secondary outcomes, apart from depression symptoms at end of treatment, is still sparse due to the low number of trials per outcome and the heterogeneity of examined populations and interventions. As psychological and pharmacological interventions can seemingly have a large to only a small or no effect on depression, there is a need for research focusing on extracting those approaches able to substantially improve depression in individuals with CAD and depression. 10.1002/14651858.CD008012.pub4
    Elevated levels of apolipoprotein D predict poor outcome in patients with suspected or established coronary artery disease. Annema Wijtske,Gawinecka Joanna,Muendlein Axel,Saely Christoph H,Drexel Heinz,von Eckardstein Arnold Atherosclerosis BACKGROUND AND AIMS:Apolipoprotein D (apoD) is a lipocalin exerting neuroprotective effects. However, the relevance of apoD in respect to cardiovascular risk is largely unexplored. Therefore, this study aimed to evaluate the ability of apoD to predict future all-cause mortality, cardiovascular mortality, and cardiovascular events. METHODS:Serum apoD levels were measured in a cohort of 531 Caucasian individuals who underwent coronary angiography (356 males, 175 females; mean age 65 ± 10 years). Fatal and non-fatal events were recorded over a median follow-up period of 5.8 years. RESULTS:ApoD concentrations at baseline correlated significantly with age, presence of the metabolic syndrome, body mass index, lipoprotein levels, fasting glucose, and estimated glomerular filtration rate. Kaplan-Meier curve analyses by gender-stratified quartiles of apoD revealed that the cumulative incidence rates of mortality and cardiovascular events become higher with increasing apoD levels. The adjusted hazard ratios for participants in the highest quartile of apoD compared to those in the lowest quartile were 4.00 (95% confidence interval [CI] 1.49-10.74) for overall mortality, 5.47 (95% CI 1.20-25.00) for cardiovascular mortality, and 2.52 (95% CI 1.28-5.00) for cardiovascular events. CONCLUSIONS:High circulating levels of apoD are an indicator of poor prognosis in patients with suspected or established coronary artery disease. 10.1016/j.atherosclerosis.2021.12.011
    Evidence-based cardiovascular magnetic resonance cost-effectiveness calculator for the detection of significant coronary artery disease. Pandya Ankur,Yu Yuan-Jui,Ge Yin,Nagel Eike,Kwong Raymond Y,Bakar Rafidah Abu,Grizzard John D,Merkler Alexander E,Ntusi Ntobeko,Petersen Steffen E,Rashedi Nina,Schwitter Juerg,Selvanayagam Joseph B,White James A,Carr James,Raman Subha V,Simonetti Orlando P,Bucciarelli-Ducci Chiara,Sierra-Galan Lilia M,Ferrari Victor A,Bhatia Mona,Kelle Sebastian Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance BACKGROUND:Although prior reports have evaluated the clinical and cost impacts of cardiovascular magnetic resonance (CMR) for low-to-intermediate-risk patients with suspected significant coronary artery disease (CAD), the cost-effectiveness of CMR compared to relevant comparators remains poorly understood. We aimed to summarize the cost-effectiveness literature on CMR for CAD and create a cost-effectiveness calculator, useable worldwide, to approximate the cost-per-quality-adjusted-life-year (QALY) of CMR and relevant comparators with context-specific patient-level and system-level inputs. METHODS:We searched the Tufts Cost-Effectiveness Analysis Registry and PubMed for cost-per-QALY or cost-per-life-year-saved studies of CMR to detect significant CAD. We also developed a linear regression meta-model (CMR Cost-Effectiveness Calculator) based on a larger CMR cost-effectiveness simulation model that can approximate CMR lifetime discount cost, QALY, and cost effectiveness compared to relevant comparators [such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA)] or invasive coronary angiography. RESULTS:CMR was cost-effective for evaluation of significant CAD (either health-improving and cost saving or having a cost-per-QALY or cost-per-life-year result lower than the cost-effectiveness threshold) versus its relevant comparator in 10 out of 15 studies, with 3 studies reporting uncertain cost effectiveness, and 2 studies showing CCTA was optimal. Our cost-effectiveness calculator showed that CCTA was not cost-effective in the US compared to CMR when the most recent publications on imaging performance were included in the model. CONCLUSIONS:Based on current world-wide evidence in the literature, CMR usually represents a cost-effective option compared to relevant comparators to assess for significant CAD. 10.1186/s12968-021-00833-1
    Clinical Outcomes of Acute Myocardial Infarction Hospitalizations With Systemic Lupus Erythematosus: An Analysis of Nationwide Readmissions Database. Sagheer Shazib,Deka Pallav,Pathak Dola,Khan Umair,Zaidi Syeda Humna,Akhlaq Anum,Blankenship James,Annis Ann Current problems in cardiology Hospital readmissions post-acute myocardial infarctions (AMIs) are associated with adverse cardiovascular outcomes and also incur huge healthcare costs. Patients with systemic lupus erythematosus (SLE) are at an increased risk of AMI likely due to multifactorial mechanisms including higher levels of inflammation and accelerated atherosclerosis. We investigated if patients with SLE are at higher risk of hospital readmissions post-AMI compared to the patients without SLE. Furthermore, we sought to assess if inpatient outcomes of AMI in SLE patients are different than AMI without SLE. We conducted a retrospective analysis of adult hospital discharges with the principal diagnosis of AMI using the Nationwide Readmissions Database in 2018. We used the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) to identify comorbid conditions. The primary outcome was all-cause 30-day readmission. Secondary outcomes were cardiac procedures at index hospitalization (percutaneous coronary intervention [PCI] and coronary artery bypass grafting [CABG]), and adverse events at index hospitalization, including inpatient mortality, cardiac arrest, cardiogenic shock, cardiac assist device, coronary artery dissection, acute kidney injury, gastrointestinal bleeding, stroke, post-procedural hemorrhage, sepsis, and hospital costs. Complex samples multivariable logistic regression models were used to determine the association of SLE with outcomes. The patients with AMI and SLE had a higher 30-day readmission rate (15.5% vs 12.5%, aOR = 1.33, CI 1.12-1.57, P = 0.001), and inpatient mortality (aOR = 1.40 CI 1.1-1.79, P = 0.006) compared to the AMI without SLE cohort. The rates of acute kidney injury (aOR = 1.41 CI 1.21-1.64, P < 0.0001) and sepsis (aOR = 1.61 CI 1.16-2.23, P = 0.004) were higher among AMI with SLE group as compared to AMI without SLE group. Within the AMI with SLE cohort, the independent predictors of readmission were diabetes mellitus (aOR = 1.38 CI 0.99-1.91, P = 0.054), peripheral vascular disease (aOR = 2.10 CI 1.22-3.62, P = 0.007), anemia (aOR = 1.50 CI 1.07-2.11, P = 0.019), end-stage renal disease (aOR = 1.91 CI 1.10-3.31, P = 0.021), and congestive heart failure (aOR = 1.55 CI 1.12-2.16, P = 0.009). The length of stay in days during index hospitalization (5.10 vs 4.67) was similar in both cohorts. In the multivariable-adjusted regression model, no statistically significant differences were noted between the AMI with SLE and AMI without SLE cohorts for most inpatient adverse events during the index hospitalization. Patients with AMI and SLE had higher inpatient mortality during the index hospitalization and higher 30-day hospital readmissions compared to AMI patients without SLE. There were no significant differences in most of the other major inpatient outcomes between the 2 cohorts. 10.1016/j.cpcardiol.2021.101086
    Additive Effects of Genetic Interleukin-6 Signaling Downregulation and Low-Density Lipoprotein Cholesterol Lowering on Cardiovascular Disease: A 2×2 Factorial Mendelian Randomization Analysis. Journal of the American Heart Association Background Although trials suggest that anti-inflammatory approaches targeting interleukin (IL)-6 signaling can reduce cardiovascular risk, it remains unknown whether targeting IL-6 signaling could reduce risk additively to low-density lipoprotein cholesterol (LDL-C) lowering. Here, we assess interactions in associations of genetic downregulation of IL-6 signaling and LDL-C lowering with lifetime cardiovascular disease risk. Methods and Results Genetic scores for IL-6 signaling downregulation and LDL-C lowering were used to divide 408 225 White British individuals in UK Biobank into groups of lifelong exposure to downregulated IL-6 signaling, lower LDL-C, or both. Associations with risk of cardiovascular disease (coronary artery disease, ischemic stroke, peripheral artery disease, aortic aneurysm, vascular death) were explored in factorial Mendelian randomization. Compared with individuals with genetic IL-6 and LDL-C scores above the median, individuals with LDL-C scores lower than the median but IL-6 scores above the median had an odds ratio (OR) of 0.96 (95% CI, 0.93-0.98) for cardiovascular disease. A similar OR (0.96; 95% CI, 0.93-0.98) was estimated for individuals with genetic IL-6 scores below the median but LDL-C scores above the median. Individuals with both genetic scores lower than the median were at lower odds of cardiovascular disease (OR, 0.92; 95% CI, 0.90-0.95). There was no interaction between the 2 scores (relative excess risk attributed to interaction index, 0; synergy index, 1; for multiplicative interaction=0.51). Genetic IL-6 score below the median was associated with lower cardiovascular disease risk across measured LDL-C strata (<100 or ≥100 mg/dL). Conclusions Genetically downregulated IL-6 signaling and genetically lowered LDL-C are associated with additively lower lifetime risk of cardiovascular disease. Future trials should explore combined IL-6 inhibition and LDL-C lowering treatments for cardiovascular prevention. 10.1161/JAHA.121.023277
    Sexual Differences in Genetic Predisposition of Coronary Artery Disease. Huang Yunfeng,Hui Qin,Gwinn Marta,Hu Yi-Juan,Quyyumi Arshed A,Vaccarino Viola,Sun Yan V Circulation. Genomic and precision medicine BACKGROUND:The genomic structure that contributes to the risk of coronary artery disease (CAD) can be evaluated as a risk score of multiple variants. However, sex differences have not been fully examined in applications of genetic risk score (GRS) of CAD. METHODS:Using data from the UK Biobank, we constructed a CAD-GRS based on all known loci, 3 mediating trait-based (blood pressure, lipids, and body mass index) subscores, and a genome-wide polygenic risk score based on 1.1 million variants. The differences in genetic associations with prevalent and incident CAD between men and women were investigated among 317 509 unrelated individuals of the European ancestry. We also assessed interactions with sex for 161 individual loci included in the comprehensive GRS. RESULTS:For both prevalent and incident CAD, the associations of comprehensive and genome-wide GRSs were stronger among men than women. Using a score of 161 loci, we observed a 2.4× higher risk for incident CAD comparing men with high genetic risk to men with low genetic risk but an 80% greater risk comparing women with high genetic risk to women with low genetic risk (interaction =0.002). Of the 3 subscores, the blood pressure-associated subscore exhibited sex differences (interaction =0.0004 per SD increase in subscore). Analysis of individual variants identified a novel gene-sex interaction at locus . CONCLUSIONS:Sexual differences in genetic predisposition should be considered in future studies of CAD, and GRSs should not be assumed to perform equally well in men and women. 10.1161/CIRCGEN.120.003147
    PCI versus CABG for left main coronary artery disease: is the jury still out? Belley-Côté Emilie P,Devereaux P J Lancet (London, England) 10.1016/S0140-6736(21)02491-0
    Sex differences in outcomes after coronary artery bypass grafting: a pooled analysis of individual patient data. Gaudino Mario,Di Franco Antonino,Alexander John H,Bakaeen Faisal,Egorova Natalia,Kurlansky Paul,Boening Andreas,Chikwe Joanna,Demetres Michelle,Devereaux Philip J,Diegeler Anno,Dimagli Arnaldo,Flather Marcus,Hameed Irbaz,Lamy Andre,Lawton Jennifer S,Reents Wilko,Robinson N Bryce,Audisio Katia,Rahouma Mohamed,Serruys Patrick W,Hara Hironori,Taggart David P,Girardi Leonard N,Fremes Stephen E,Benedetto Umberto European heart journal AIMS:Data suggest that women have worse outcomes than men after coronary artery bypass grafting (CABG), but results have been inconsistent across studies. Due to the large differences in baseline characteristics between sexes, suboptimal risk adjustment due to low-quality data may be the reason for the observed differences. To overcome this limitation, we undertook a systematic review and pooled analysis of high-quality individual patient data from large CABG trials to compare the adjusted outcomes of women and men. METHODS AND RESULTS:The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and repeat revascularization (major adverse cardiac and cerebrovascular events, MACCE). The secondary outcome was all-cause mortality. Multivariable mixed-effect Cox regression was used. Four trials involving 13 193 patients (10 479 males; 2714 females) were included. Over 5 years of follow-up, women had a significantly higher risk of MACCE [adjusted hazard ratio (HR) 1.12, 95% confidence interval (CI) 1.04-1.21; P = 0.004] but similar mortality (adjusted HR 1.03, 95% CI 0.94-1.14; P = 0.51) compared to men. Women had higher incidence of MI (adjusted HR 1.30, 95% CI 1.11-1.52) and repeat revascularization (adjusted HR 1.22, 95% CI 1.04-1.43) but not stroke (adjusted HR 1.17, 95% CI 0.90-1.52). The difference in MACCE between sexes was not significant in patients 75 years and older. The use of off-pump surgery and multiple arterial grafting did not modify the difference between sexes. CONCLUSIONS:Women have worse outcomes than men in the first 5 years after CABG. This difference is not significant in patients aged over 75 years and is not affected by the surgical technique. 10.1093/eurheartj/ehab504
    Exercise-based cardiac rehabilitation for coronary heart disease. Dibben Grace,Faulkner James,Oldridge Neil,Rees Karen,Thompson David R,Zwisler Ann-Dorthe,Taylor Rod S The Cochrane database of systematic reviews BACKGROUND:Coronary heart disease (CHD) is the most common cause of death globally. However, with falling CHD mortality rates, an increasing number of people living with CHD may need support to manage their symptoms and prognosis. Exercise-based cardiac rehabilitation (CR) aims to improve the health and outcomes of people with CHD. This is an update of a Cochrane Review previously published in 2016. OBJECTIVES:To assess the clinical effectiveness and cost-effectiveness of exercise-based CR (exercise training alone or in combination with psychosocial or educational interventions) compared with 'no exercise' control, on mortality, morbidity and health-related quality of life (HRQoL) in people with CHD. SEARCH METHODS:We updated searches from the previous Cochrane Review, by searching CENTRAL, MEDLINE, Embase, and two other databases in September 2020. We also searched two clinical trials registers in June 2021. SELECTION CRITERIA:We included randomised controlled trials (RCTs) of exercise-based interventions with at least six months' follow-up, compared with 'no exercise' control. The study population comprised adult men and women who have had a myocardial infarction (MI), coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI), or have angina pectoris, or coronary artery disease. DATA COLLECTION AND ANALYSIS:We screened all identified references, extracted data and assessed risk of bias according to Cochrane methods. We stratified meta-analysis by duration of follow-up: short-term (6 to 12 months); medium-term (> 12 to 36 months); and long-term ( > 3 years), and used meta-regression to explore potential treatment effect modifiers. We used GRADE for primary outcomes at 6 to 12 months (the most common follow-up time point).  MAIN RESULTS: This review included 85 trials which randomised 23,430 people with CHD. This latest update identified 22 new trials (7795 participants). The population included predominantly post-MI and post-revascularisation patients, with a mean age ranging from 47 to 77 years. In the last decade, the median percentage of women with CHD has increased from 11% to 17%, but females still account for a similarly small percentage of participants recruited overall ( < 15%). Twenty-one of the included trials were performed in low- and middle-income countries (LMICs). Overall trial reporting was poor, although there was evidence of an improvement in quality over the last decade. The median longest follow-up time was 12 months (range 6 months to 19 years). At short-term follow-up (6 to 12 months), exercise-based CR likely results in a slight reduction in all-cause mortality (risk ratio (RR) 0.87, 95% confidence interval (CI) 0.73 to 1.04; 25 trials; moderate certainty evidence), a large reduction in MI (RR 0.72, 95% CI 0.55 to 0.93; 22 trials; number needed to treat for an additional beneficial outcome (NNTB) 75, 95% CI 47 to 298; high certainty evidence), and a large reduction in all-cause hospitalisation (RR 0.58, 95% CI 0.43 to 0.77; 14 trials;  NNTB 12, 95% CI 9 to 21; moderate certainty evidence). Exercise-based CR likely results in little to no difference in risk of cardiovascular mortality (RR 0.88, 95% CI 0.68 to 1.14; 15 trials; moderate certainty evidence), CABG (RR 0.99, 95% CI 0.78 to 1.27; 20 trials; high certainty evidence), and PCI (RR 0.86, 95% CI 0.63 to 1.19; 13 trials; moderate certainty evidence) up to 12 months' follow-up. We are uncertain about the effects of exercise-based CR on cardiovascular hospitalisation, with a wide confidence interval including considerable benefit as well as harm (RR 0.80, 95% CI 0.41 to 1.59; low certainty evidence). There was evidence of substantial heterogeneity across trials for cardiovascular hospitalisations (I = 53%), and of small study bias for all-cause hospitalisation, but not for all other outcomes. At medium-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.90, 95% CI 0.80 to 1.02; 15 trials), MI (RR 1.07, 95% CI 0.91 to 1.27; 12 trials), PCI (RR 0.96, 95% CI 0.69 to 1.35; 6 trials), CABG (RR 0.97, 95% CI 0.77 to 1.23; 9 trials), and all-cause hospitalisation (RR 0.92, 95% CI 0.82 to 1.03; 9 trials), a large reduction in cardiovascular mortality was found (RR 0.77, 95% CI 0.63 to 0.93; 5 trials). Evidence is uncertain for difference in risk of cardiovascular hospitalisation (RR 0.92, 95% CI 0.76 to 1.12; 3 trials). At long-term follow-up, although there may be little to no difference in all-cause mortality (RR 0.91, 95% CI 0.75 to 1.10), exercise-based CR may result in a large reduction in cardiovascular mortality (RR 0.58, 95% CI 0.43 to 0.78; 8 trials) and MI (RR 0.67, 95% CI 0.50 to 0.90; 10 trials). Evidence is uncertain for CABG (RR 0.66, 95% CI 0.34 to 1.27; 4 trials), and PCI (RR 0.76, 95% CI 0.48 to 1.20; 3 trials). Meta-regression showed benefits in outcomes were independent of CHD case mix, type of CR, exercise dose, follow-up length, publication year, CR setting, study location, sample size or risk of bias. There was evidence that exercise-based CR may slightly increase HRQoL across several subscales (SF-36 mental component, physical functioning, physical performance, general health, vitality, social functioning and mental health scores) up to 12 months' follow-up; however, these may not be clinically important differences. The eight trial-based economic evaluation studies showed exercise-based CR to be a potentially cost-effective use of resources in terms of gain in quality-adjusted life years (QALYs). AUTHORS' CONCLUSIONS:This updated Cochrane Review supports the conclusions of the previous version, that exercise-based CR provides important benefits to people with CHD, including reduced risk of MI, a likely small reduction in all-cause mortality, and a large reduction in all-cause hospitalisation, along with associated healthcare costs, and improved HRQoL up to 12 months' follow-up. Over longer-term follow-up, benefits may include reductions in cardiovascular mortality and MI. In the last decade, trials were more likely to include females, and be undertaken in LMICs, increasing the generalisability of findings. Well-designed, adequately-reported RCTs of CR in people with CHD more representative of usual clinical practice are still needed. Trials should explicitly report clinical outcomes, including mortality and hospital admissions, and include validated HRQoL outcome measures, especially over longer-term follow-up, and assess costs and cost-effectiveness. 10.1002/14651858.CD001800.pub4
    Oxidative Stress and Inflammation Are Associated with Coexistent Severe Multivessel Coronary Artery Stenosis and Right Carotid Artery Severe Stenosis in Elderly Patients. Li Xia,Guo Dianxuan,Hu Youdong,Chen Ying Oxidative medicine and cellular longevity Oxidative stress and inflammatory response are the main pathogenic pathways in atherosclerosis stenosis. This study is aimed at evaluating the roles of oxidative stress and inflammatory response in coexistent right carotid artery severe stenosis and severe multivessel coronary artery stenosis in elderly patients. Circulating levels of total oxidant status (TOS), lipid hydroperoxide (LHP), 8-isoprostane (8-IP), malondialdehyde (MDA), monocyte chemotactic protein-4 (MCP-4), amyloid A (AA), high-sensitivity C-reactive protein (hs-CRP), and tumor necrosis factor- (TNF-) were measured by standardised laboratory test methods. Markers of oxidative stress and inflammatory response: levels of TOS, LHP, 8-IP, MDA, MCP-4, AA, hs-CRP, and TNF-, were increased ( < 0.001) in elderly patient. These results suggested that oxidative stress and inflammatory response may be involved in carotid artery severe stenosis and severe multivessel coronary artery stenosis and measuring oxidative stress and inflammation biomarkers may also be a promising step in the development of an effective method for monitoring the severity of right carotid artery stenosis and multivessel coronary artery stenosis in elderly patients. 10.1155/2021/2976447
    Atherogenic Index of Plasma and Coronary Artery Disease in the Adult Population: A Meta-Analysis. Wu Jing,Zhou Qiang,Wei Zhouxia,Wei Jinying,Cui Meizi Frontiers in cardiovascular medicine The atherogenic index of plasma (AIP), which is the logarithm of the ratio between the triglyceride and high-density lipoprotein cholesterol (TG/HDL-C) concentrations in molar units, is correlated with the burden of atherosclerosis. This study aimed to evaluate the association between the AIP and coronary artery disease (CAD) in the adult population by performing a meta-analysis. Observational studies relevant for this meta-analysis were identified by searching the PubMed, Embase, and Web of Science databases. Only studies using multivariate analysis were considered. A random-effects model, which incorporates potential intra-study heterogeneity, was applied to combine the results. Ten observational studies were included. In studies with the AIP analyzed as a continuous variable, a higher AIP was associated with a higher odds of CAD (adjusted risk ratio [RR] per 1-standard deviation [SD] increment of AIP: 2.10, 95% confidence interval [CI]: 1.51-2.93, < 0.001, I = 90%). Further analysis of studies with the AIP analyzed as a categorical variable showed a higher odds of CAD (adjusted RR: 2.35, 95% CI: 1.88-2.93, < 0.001, I = 37%) in the participants with the highest versus the lowest AIP value. Subgroup analyses demonstrated consistent results in asymptomatic and symptomatic populations as well as in male and female participants (all between-group values > 0.05). Current evidence, mostly from cross-sectional studies, suggests that a higher AIP value may be independently associated with CAD in the adult population. 10.3389/fcvm.2021.817441
    Ten-year all-cause death after percutaneous or surgical revascularization in diabetic patients with complex coronary artery disease. Wang Rutao,Serruys Patrick W,Gao Chao,Hara Hironori,Takahashi Kuniaki,Ono Masafumi,Kawashima Hideyuki,O'leary Neil,Holmes David R,Witkowski Adam,Curzen Nick,Burzotta Francesco,James Stefan,van Geuns Robert-Jan,Kappetein Arie Pieter,Morel Marie-Angele,Head Stuart J,Thuijs Daniel J F M,Davierwala Piroze M,O'Brien Timothy,Fuster Valentin,Garg Scot,Onuma Yoshinobu European heart journal AIMS:The aim of this article was to compare rates of all-cause death at 10 years following coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) in patients with or without diabetes. METHODS AND RESULTS:The SYNTAXES study evaluated up to 10-year survival of 1800 patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) randomized to receive either PCI or CABG in the SYNTAX trial. Ten-year all-cause death according to diabetic status and revascularization strategy was examined. In diabetics (n = 452), the risk of mortality was numerically higher with PCI compared with CABG at 5 years [19.6% vs. 13.3%, hazard ratio (HR): 1.53, 95% confidence interval (CI): 0.96, 2.43, P = 0.075], with the opposite seen between 5 and 10 years (PCI vs. CABG: 20.8% vs. 24.4%, HR: 0.82, 95% CI: 0.52, 1.27, P = 0.366). Irrespective of diabetic status, there was no significant difference in all-cause death at 10 years between patients receiving PCI or CABG, the absolute treatment difference was 1.9% in diabetics (PCI vs. CABG: 36.4% vs. 34.5%, difference: 1.9%, 95% CI: -7.6%, 11.1%, P = 0.551). Among insulin-treated patients (n = 182), all-cause death at 10 years was numerically higher with PCI (47.9% vs. 39.6%, difference: 8.2%, 95% CI: -6.5%, 22.5%, P = 0.227). CONCLUSIONS:The treatment effects of PCI vs. CABG on all-cause death at 10 years in patients with 3VD and/or LMCAD were similar irrespective of the presence of diabetes. There may, however, be a survival benefit with CABG in patients with insulin-treated diabetes. The association between revascularization strategy and very long-term ischaemic and safety outcomes for patients with diabetes needs further investigation in dedicated trials. TRIAL REGISTRATION:SYNTAX: ClinicalTrials.gov reference: NCT00114972 and SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050. 10.1093/eurheartj/ehab441
    Metabolic Impairment in Coronary Artery Disease: Elevated Serum Acylcarnitines Under the Spotlights. Gander Joséphine,Carrard Justin,Gallart-Ayala Hector,Borreggine Rébecca,Teav Tony,Infanger Denis,Colledge Flora,Streese Lukas,Wagner Jonathan,Klenk Christopher,Nève Gilles,Knaier Raphael,Hanssen Henner,Schmidt-Trucksäss Arno,Ivanisevic Julijana Frontiers in cardiovascular medicine Coronary artery disease (CAD) remains the leading cause of death worldwide. Expanding patients' metabolic phenotyping beyond clinical chemistry investigations could lead to earlier recognition of disease onset and better prevention strategies. Additionally, metabolic phenotyping, at the molecular species level, contributes to unravel the roles of metabolites in disease development. In this cross-sectional study, we investigated clinically healthy individuals ( = 116, 65% male, 70.8 ± 8.7 years) and patients with CAD ( = 54, 91% male, 67.0 ± 11.5 years) of the COmPLETE study. We applied a high-coverage quantitative liquid chromatography-mass spectrometry approach to acquire a comprehensive profile of serum acylcarnitines, free carnitine and branched-chain amino acids (BCAAs), as markers of mitochondrial health and energy homeostasis. Multivariable linear regression analyses, adjusted for confounders, were conducted to assess associations between metabolites and CAD phenotype. In total, 20 short-, medium- and long-chain acylcarnitine species, along with L-carnitine, valine and isoleucine were found to be significantly (adjusted ≤ 0.05) and positively associated with CAD. For 17 acylcarnitine species, associations became stronger as the number of affected coronary arteries increased. This implies that circulating acylcarnitine levels reflect CAD severity and might play a role in future patients' stratification strategies. Altogether, CAD is characterized by elevated serum acylcarnitine and BCAA levels, which indicates mitochondrial imbalance between fatty acid and glucose oxidation. 10.3389/fcvm.2021.792350
    One-Stop Hybrid Coronary Revascularization Versus Off-Pump Coronary Artery Bypass Grafting in Patients With Multivessel Coronary Artery Disease. Li Dongjie,Guo Yulin,Gao Yingdi,An Xiangguang,Liu Yan,Gu Song,Zhang Xitao,Zhong Jiuchang,Gao Jie,Su Pixiong Frontiers in cardiovascular medicine Data on one-stop hybrid coronary revascularization (HCR) are limited. This study aimed to compare the early and midterm outcomes of one-stop HCR with off-pump coronary artery bypass grafting (OPCAB) in patients with multivessel coronary artery disease. From April 2018 to May 2021, 752 patients with multivessel coronary artery disease who underwent isolated one-stop HCR or OPCAB were retrospectively included in this analysis. After exclusion and propensity score matching, 151 patients who underwent HCR were matched with 151 patients who underwent OPCAB. The primary endpoints were midterm major adverse cardiovascular and cerebrovascular events (MACCE) after the procedure. The secondary endpoints were in-hospital complications and outcomes. The preprocedural characteristics were well balanced between the two groups after matching. The HCR group was associated with a lower rate of perioperative transfusion (23.8 vs. 53.0%, < 0.001) and new-onset atrial fibrillation (AF) (5.3 vs. 15.2%, = 0.004), shorter time of mechanical ventilation (h) [15 (16, 17) vs. 17 (16, 20), < 0.001], and shorter length of stay (LOS) in the hospital (days) [19 (16, 24) vs. 22 (18, 27), = 0.001]. Cumulated MACCE rates were similar between the two groups (15.9 vs. 14.0%, = 0.59) during a median follow-up of 20 months. One-stop HCR is safe and efficacious with less invasiveness and faster postoperative recovery in selected patients with multivessel coronary artery disease. Randomized controlled trials with larger sample sizes and long-term follow-up are warranted to confirm these findings. 10.3389/fcvm.2021.755797
    Functional rare variant in a binding site in gene increases the risk of coronary artery disease. Wang Pengyun,Wang Yifan,Peng Huixin,Wang Jingjing,Zheng Qian,Wang Pengxia,Wang Jing,Zhang Hongfu,Huang Yufeng,Xiong Liang,Zhang Rongfeng,Xia Yunlong,Wang Qing K,Xu Chengqi Aging OBJECTIVE: regulates activation of vascular endothelial cells, and genome-wide association studies showed that variants in confer risk to stroke. However, whether variants in are associated with coronary artery disease (CAD) is unknown. METHODS:We genotyped rs34166160 in in two independent Chinese GeneID populations which included 2,794 CAD cases and 4,131 controls, and performed genetics association studies. Functional studies were also performed to reveal the mechanisms. RESULTS:Allele rs34166160 significantly confers risk to CAD in the GeneID Hubei population which contained 1,440 CAD cases and 2,660 CAD-free controls (observed = 6.39 × 10 with an odds ratio (OR) was 3.39, adjusted = 8.12 × 10 with an OR of 3.10). The association was replicated in another population, GeneID Shandong population contained 1,354 CAD cases and 1,471 controls ( = 3.33 × 10 with an OR of 3.14, = 0.01 with an OR of 2.74). After combining the two populations, the association was more significant ( = 1.57 × 10 with an OR of 3.58, = 3.41 × 10 with an OR of 2.80). In addition, we found that rs34166160 was associated with the mRNA expression level of and the flanking region of rs34166160 can directly bind with transcriptional factor CCAAT-box/enhancer-binding protein beta, and the risk A allele has more transcription activity than non-risk C allele with or without LPS in HUVEC cells. CONCLUSIONS:Our study demonstrates that the functional rare variant rs34166160 in confers risk to CAD for the first time, and these findings further expand the range of the pathology of CAD and atherosclerosis. 10.18632/aging.203755