Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.
The New England journal of medicine
BACKGROUND:Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS:We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS:A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS:Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).
10.1056/NEJMoa2400969
Comparative analysis of hospitalization risk for incident heart failure in non-Hispanic Black versus non-Hispanic White individuals with type 2 diabetes on empagliflozin (Empa-AA): Insights from real-world data.
Diabetes, obesity & metabolism
AIM:There are limited data to evaluate hospitalization for heart failure (hHF) in non-Hispanic Black (hereafter Black) or non-Hispanic White (hereafter White) individuals without previous hHF. Our goal was to evaluate the risk of hHF among Black versus White patients with type 2 diabetes (T2DM) who were initially prescribed empagliflozin using real-world data. METHODS:This multicentre retrospective cohort study included participants aged ≥18 years who had T2DM, were either Black or White, had no previous hHF, and were prescribed empagliflozin between August 2014 and December 2019. Our primary outcome was time to first hHF after the initial prescription of empagliflozin. A propensity-score (PS)-weighted analysis was performed to balance characteristics by race. The inverse probability treatment weighting method based on PS was used to make treatment comparisons. To compare Black with White, a PS-weighted Cox's cause-specific hazards model was used. RESULTS:In total, 8789 participants were eligible for inclusion (Black = 3216 vs. White = 5573). The Black cohort was significantly younger, had a higher proportion of females, and had a higher prevalence of chronic kidney disease, hypertension and diabetic retinopathy, while the White cohort had a higher prevalence of coronary artery disease. After adjustment for confounding factors such as age, gender, coronary artery disease, hypertension and diabetic retinopathy, the hazard ratio for first-time hHF was not significantly different between the two racial groups [hazard ratio (95% confidence interval) = 1.09 (0.84-1.42), p = .52]. CONCLUSION:This study showed no significant difference in incident hHF among Black versus White individuals with T2DM following a prescription for empagliflozin.
10.1111/dom.15499
Plasma lipidomic markers of diet quality are associated with incident coronary heart disease in American Indian adults: the Strong Heart Family Study.
The American journal of clinical nutrition
BACKGROUND:Identifying lipidomic markers of diet quality is needed to inform the development of biomarkers of diet, and to understand the mechanisms driving the diet- coronary heart disease (CHD) association. OBJECTIVES:This study aimed to identify lipidomic markers of diet quality and examine whether these lipids are associated with incident CHD. METHODS:Using liquid chromatography-mass spectrometry, we measured 1542 lipid species from 1694 American Indian adults (aged 18-75 years, 62% female) in the Strong Heart Family Study. Participants were followed up for development of CHD through 2020. Information on the past year diet was collected using the Block Food Frequency Questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index-2010 (AHEI). Mixed-effects linear regression was used to identify individual lipids cross-sectionally associated with AHEI. In prospective analysis, Cox frailty model was used to estimate the hazard ratio (HR) of each AHEI-related lipid for incident CHD. All models were adjusted for age, sex, center, education, body mass index, smoking, alcohol drinking, level of physical activity, energy intake, diabetes, hypertension, and use of lipid-lowering drugs. Multiple testing was controlled at a false discovery rate of <0.05. RESULTS:Among 1542 lipid species measured, 71 lipid species (23 known), including acylcarnitine, cholesterol esters, glycerophospholipids, sphingomyelins and triacylglycerols, were associated with AHEI. Most of the identified lipids were associated with consumption of ω-3 (n-3) fatty acids. In total, 147 participants developed CHD during a mean follow-up of 17.8 years. Among the diet-related lipids, 10 lipids [5 known: cholesterol ester (CE)(22:5)B, phosphatidylcholine (PC)(p-14:0/22:1)/PC(o-14:0/22:1), PC(p-38:3)/PC(o-38:4)B, phosphatidylethanolamine (PE)(p-18:0/20:4)/PE(o-18:0/20:4), and sphingomyelin (d36:2)A] were associated with incident CHD. On average, each standard deviation increase in the baseline level of these 5 lipids was associated with 17%-23% increased risk of CHD (from HR: 1.17; 95% CI: 1, 1.36; to HR: 1.23; 95% CI: 1.05, 1.43). CONCLUSIONS:In this study, lipidomic markers of diet quality in American Indian adults are found. Some diet-related lipids are associated with risk of CHD beyond established risk factors.
10.1016/j.ajcnut.2023.12.024
Interplay Between Plasma Glycine and Branched-Chain Amino Acids Contributes to the Development of Hypertension and Coronary Heart Disease.
Hypertension (Dallas, Tex. : 1979)
BACKGROUND:Higher levels of plasma glycine are linked to a reduced risk, while increased levels of total branched-chain amino acids (tBCAAs) are associated with a higher risk of essential hypertension (HTN) and coronary heart disease (CHD). As these metabolic components are interconnected, analyzing the tBCAAs/glycine ratio may help to understand their interplay in the pathogenesis of cardiovascular disease. METHODS:The Cox regression approach was combined with the development of novel genetic tools for assessments of associations between plasma metabolomic data (glycine, tBCAAs, and tBCAAs/glycine ratio) from the UK Biobank and the development of hypertension and CHD. Genome-wide association study was performed on 186 523 White UK Biobank participants to identify new independent genetic instruments for the 2-sample Mendelian randomization analyses. -gain statistic >10 identified instruments associated with tBCAAs/glycine ratio significantly stronger compared with individual amino acids. Outcomes of genome-wide association study on hypertension and CHD were derived from the UK Biobank (nonoverlapping sample), FinnGen, and CARDIoGRAMplusC4D. RESULTS:The tBCAAs/glycine ratio was prospectively associated with a higher risk of developing hypertension and CHD (hazard ratio quintile, Q5 versus Q1, 1.196 [95% CI, 1.109-1.289] and 1.1226 [95% CI, 1.160-1.1296], respectively). Mendelian randomization analysis demonstrated that tBCAAs/glycine ratio (-gain >10) was a risk factor for hypertension (meta-analyzed inverse-variance weighted causal estimate 0.45 log odds ratio/SD (95% CI, 0.26-0.64) and CHD (0.48 [95% CI, 0.29-0.67]) with an absolute effect significantly larger compared with the effect of glycine (-0.06 [95% CI, -0.1 to -0.03] and -0.08 [95% CI, -0.11 to -0.05], respectively) or tBCAAs (0.22 95% CI, 0.09-0.34] and 0.12 [95% CI, 0.01-0.24], respectively). CONCLUSIONS:The total BCAAs/glycine ratio is a key element of the metabolic signature contributing to hypertension and CHD, which may reflect biological pathways shared by glycine and tBCAAs.
10.1161/HYPERTENSIONAHA.123.22649
Plasma Biomarker Profiles for Premature and Nonpremature Coronary Heart Disease in Women.
Clinical chemistry
BACKGROUND:Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years. METHODS:In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors. RESULTS:Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)]. CONCLUSIONS:In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.
10.1093/clinchem/hvae007
Genome-Wide Search Links Senescence-Associated Secretory Proteins With Susceptibility for Coronary Artery Disease in Mouse and Human.
The journals of gerontology. Series A, Biological sciences and medical sciences
Advanced age is an independent risk factor for coronary artery disease (CAD), the leading global cause of mortality. Senescent vascular cells in the atherosclerotic plaques exhibit senescence-associated secretory phenotype (SASP). How SASP contributes to atherosclerosis and CAD, however, remains unclear. Here, we integrated RNA-array datasets of senescent human coronary arterial endothelial cells (HCAECs) and aortic smooth muscle cells (HASMCs) as well as genome-wide association data for CAD. We identified 26 genes from HCAECs and 6 genes from HASMCs related to SASP and CAD in both in-house and published datasets. Of which, Cystatin C (CST3), a CAD susceptibility gene, was found to be expressed in both HCAECs and HASMCs, thus, it was prioritized for further investigation. We demonstrated it was significantly elevated in senescent vascular cells, aged arteries, and early atherosclerosis. In vitro experiments showed that CST3 enhances the monocyte-endothelial cell adhesion. Additionally, ligand-receptor pairing analyses revealed two important pathways, COL4A1-ITGA1 and LPL-LRP1 pathways, linked to the critical processes in the development of atherosclerosis, including cell adhesion, inflammation response, extracellular matrix organization, and lipid metabolism. We further demonstrated a reduced monocyte-endothelial cell adhesion following the knockdown of COL4A1 or ITGA1 and a significantly increased expression of COL4A1, ITGA1, and LPL in arterial intima of aged mice and ApoE-/- mice. Our findings demonstrate that vascular cell-derived SASP proteins increase the CAD susceptibility and identify CST3 functionally contributing to atherosclerosis.
10.1093/gerona/glae070
Neuroprotective effects of the salidroside derivative SHPL-49 via the BDNF/TrkB/Gap43 pathway in rats with cerebral ischemia.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.
10.1016/j.biopha.2024.116460
Lipoprotein(a), Oxidized Phospholipids, and Coronary Artery Disease Severity and Outcomes.
Journal of the American College of Cardiology
BACKGROUND:Lipoprotein(a) (Lp[a]) and oxidized phospholipids (OxPLs) are each independent risk factors for atherosclerotic cardiovascular disease. The extent to which Lp(a) and OxPLs predict coronary artery disease (CAD) severity and outcomes in a contemporary, statin-treated cohort is not well established. OBJECTIVES:This study sought to evaluate the relationships between Lp(a) particle concentration and OxPLs associated with apolipoprotein B (OxPL-apoB) or apolipoprotein(a) (OxPL-apo[a]) with angiographic CAD and cardiovascular outcomes. METHODS:Among 1,098 participants referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study, Lp(a), OxPL-apoB, and OxPL-apo(a) were measured. Logistic regression estimated the risk of multivessel coronary stenoses by Lp(a)-related biomarker level. Cox proportional hazards regression estimated the risk of major adverse cardiovascular events (MACEs) (coronary revascularization, nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death) in follow-up. RESULTS:Median Lp(a) was 26.45 nmol/L (IQR: 11.39-89.49 nmol/L). Lp(a), OxPL-apoB, and OxPL-apo(a) were highly correlated (Spearman R ≥0.91 for all pairwise combinations). Lp(a) and OxPL-apoB were associated with multivessel CAD. Odds of multivessel CAD per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.10 (95% CI: 1.03-1.18; P = 0.006), 1.18 (95% CI: 1.03-1.34; P = 0.01), and 1.07 (95% CI: 0.99-1.16; P = 0.07), respectively. All biomarkers were associated with cardiovascular events. HRs for MACE per doubling of Lp(a), OxPL-apoB, and OxPL-apo(a) were 1.08 (95% CI: 1.03-1.14; P = 0.001), 1.15 (95% CI: 1.05-1.26; P = 0.004), and 1.07 (95% CI: 1.01-1.14; P = 0.02), respectively. CONCLUSIONS:In patients undergoing coronary angiography, Lp(a) and OxPL-apoB are associated with multivessel CAD. Lp(a), OxPL-apoB, and OxPL-apo(a) are associated with incident cardiovascular events. (Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868).
10.1016/j.jacc.2023.02.050
Association between non-alcoholic fatty liver disease and coronary artery disease outcomes: A systematic review and meta-analysis.
Diabetes & metabolic syndrome
OBJECTIVES:To evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular outcomes, including angina, coronary artery disease (CAD), coronary artery calcification (CAC), myocardial infarction (MI), and calcified coronary plaques. METHODS:A comprehensive search of databases, including PubMed, EMBASE, and Cochrane Library, was conducted up to January 2023. Studies were included investigating the relationship between NAFLD and cardiovascular outcomes in adult populations. Exclusion criteria were studies on animals, pediatric populations, and those not published in English. Two reviewers assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS:The meta-analysis included 32 studies with a total of 5,610,990 participants. NAFLD demonstrated significant associations with increased risks of angina (Relative Risk (RR): 1.45, 95% CI: 1.17, 1.79), CAD (RR: 1.21, 95% CI: 1.07, 1.38), CAC >0 (RR: 1.39, 95% CI: 1.15, 1.69), and calcified coronary plaques (RR: 1.55, 95% CI: 1.05, 2.27). However, no significant association was found between NAFLD and CAC >100 (RR: 1.16, 95% CI: 0.97, 1.38) or MI (RR: 1.70, 95% CI: 0.16, 18.32). CONCLUSION:The meta-analysis demonstrated a significant association between NAFLD and cardiovascular outcomes independent of conventional cardiovascular disease (CVD) risk factors. These findings emphasize the importance of prevention, early detection, and proper management of NAFLD.
10.1016/j.dsx.2023.102938
Results beyond 5-years of surgery or percutaneous approach in severe coronary disease. Reconstructed time-to-event meta-analysis of randomized trials.
Revista espanola de cardiologia (English ed.)
INTRODUCTION AND OBJECTIVES:There is controversy about the optimal revascularization strategy in severe coronary artery disease (CAD), including left main disease and/or multivessel disease. Several meta-analyses have analyzed the results at 5-year follow-up but there are no results after the fifth year. We conducted a systematic review and meta-analysis of randomized clinical trials, comparing results after the fifth year, between coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) using drug-eluting stents in patients with severe CAD. METHODS:We analyzed all clinical trials between January 2010 and January 2023. The primary endpoint was all-cause mortality. The databases of the original articles were reconstructed from Kaplan-Meier curves, simulating an individual-level meta-analysis. Comparisons were made at certain cutoff points (5 and 10 years). The 10-year restricted median survival time difference between CABG and PCI was calculated. The random effects model and the DerSimonian-Laird method were applied. RESULTS:The meta-analysis included 5180 patients. During the 10-year follow-up, PCI showed a higher overall incidence of all-cause mortality (HR, 1.19; 95%CI, 1.04-1.32; P=.008)]. PCI showed an increased risk of all-cause mortality within 5 years (HR, 1.2; 95%CI, 1.06-1.53; P=.008), while no differences in the 5-10-year period were revealed (HR, 1.03; 95%CI, 0.84-1.26; P=.76). Life expectancy of CABG patients was slightly higher than that of PCI patients (2.4 months more). CONCLUSIONS:In patients with severe CAD, including left main disease and/or multivessel disease, there was higher a incidence of all-cause mortality after PCI compared with CABG at 10 years of follow-up. Specifically, PCI has higher mortality during the first 5 years and comparable risk beyond 5 years.
10.1016/j.rec.2023.09.007
Potential mechanisms linking high-volume exercise with coronary artery calcification.
Heart (British Cardiac Society)
Recent studies have found an association between high volumes of physical activity and increased levels of coronary artery calcification (CAC) among older male endurance athletes, yet the underlying mechanisms have remained largely elusive. Potential mechanisms include greater exposure to inflammatory cytokines, reactive oxygen species and oxidised low-density lipoproteins, as acute strenuous physical activity has been found to enhance their systemic release. Other possibilities include post-exercise elevations in circulating parathyroid hormone, which can modify the amount and morphology of calcific plaque, and long-term exposure to non-laminar blood flow within the coronary arteries during vigorous physical activity, particularly in individuals with pre-existing atherosclerosis. Further, although the association has only been identified in men, the role of testosterone in this process remains unclear. This brief review discusses the association between high-volume endurance exercise and CAC in older men, elaborates on the potential mechanisms underlying the increased calcification, and provides clinical implications and recommendations for those at risk.
10.1136/heartjnl-2022-321986
The lead and cadmium content in rice and risk to human health in China: A systematic review and meta-analysis.
PloS one
Numerous studies have investigated concentrations of lead (Pb) and cadmium (Cd) in rice in China, but have come to divergent conclusions. Therefore we systematically reviewed and meta-analyzed the available evidence on levels of Pb and Cd in rice in different regions of China in order to assess the potential risk to human health. The meta-analysis included 24 studies of Pb levels and 29 studies of Cd levels, published in 2011-2021. The pooled Pb concentration in rice was 0.10 mg per kg dry weight (95% CI 0.08-0.11), while the pooled Cd concentration was 0.16 mg per kg dry weight (95% CI 0.14-0.18). These levels are within the limits specified by national food safety standards. However, the total target hazard quotient for both metals exceeded 1.0 for adults and children, suggesting that rice consumption poses a health risk.
10.1371/journal.pone.0278686
Procedural Outcomes After Percutaneous Coronary Interventions in Focal and Diffuse Coronary Artery Disease.
Journal of the American Heart Association
Background Coronary artery disease (CAD) patterns play an essential role in the decision-making process about revascularization. The pullback pressure gradient (PPG) quantifies CAD patterns as either focal or diffuse based on fractional flow reserve (FFR) pullbacks. The objective of this study was to evaluate the impact of CAD patterns on acute percutaneous coronary intervention (PCI) results considered surrogates of clinical outcomes. Methods and Results This was a prospective, multicenter study of patients with hemodynamically significant CAD undergoing PCI. Motorized FFR pullbacks and optical coherence tomography (OCT) were performed before and after PCI. Post-PCI FFR >0.90 was considered an optimal result. Focal disease was defined as PPG >0.73 (highest PPG tertile). Overall, 113 patients (116 vessels) were included. Patients with focal disease were younger than those with diffuse CAD (61.4±9.9 versus 65.1±8.7 years, =0.042). PCI in vessels with high PPG (focal CAD) resulted in higher post-PCI FFR (0.91±0.07 in the focal group versus 0.86±0.05 in the diffuse group, <0.001) and larger minimal stent area (6.3±2.3 mm in focal versus 5.3±1.8 mm in diffuse CAD, =0.015) compared withvessels with low PPG (diffuse CAD). The PPG was associated with the change in FFR after PCI (=0.51, <0.001). The PPG significantly improved the capacity to predict optimal PCI results compared with an angiographic assessment of CAD patterns (area under the curve 0.81 [95% CI, 0.73-0.88] versus area under the curve 0.51 [95% CI, 0.42-0.60]; <0.001). Conclusions PCI in vessels with focal disease defined by the PPG resulted in greater improvement in epicardial conductance and larger minimal stent area compared with diffuse disease. PPG, but not angiographically defined CAD patterns, distinguished patients attaining superior procedural outcomes. Registration URL: https://clinicaltrials.gov/ct2/show/NCT03782688.
10.1161/JAHA.122.026960
Relationship between NAFLD and coronary artery disease: A Mendelian randomization study.
Hepatology (Baltimore, Md.)
BACKGROUND AND AIMS:There is an ongoing debate on whether NAFLD is an active contributor or an innocent bystander in the pathogenesis of coronary artery disease (CAD). The aim of the present study was to assess the causal relationship between NAFLD and CAD. APPROACH AND RESULTS:We performed two-sample Mendelian randomization (MR) analyses using summary-level data to assess the association between genetically predicted NAFLD (i.e., chronically elevated serum alanine aminotransferase levels [cALT], imaging-based and biopsy-confirmed NAFLD) and risk of CAD. Analyses were repeated after exclusion of NAFLD susceptibility genes that are associated with impaired VLDL secretion.Inverse-variance weighted MR analyses showed a statistically significant association between genetically predicted cALT and risk of CAD (OR: 1.116, 95% CI: 1.039, 1.199), but not for the other NAFLD-related traits (OR: 1.046, 95% CI: 0.764, 1.433 and OR: 1.014, 95% CI: 0.968, 1.062 for imaging-based and biopsy-confirmed NAFLD, respectively). MR-Egger regression revealed a statistically significant intercept, indicative of directional pleiotropy, for all traits. Repeat analyses after exclusion of genes associated with impaired VLDL secretion showed consistent associations between genetically predicted NAFLD and CAD for all traits (i.e., cALT [OR: 1.203, 95% CI: 1.113, 1.300]), imaging-based (OR: 2.149, 95% CI: 1.276, 3.620) and biopsy-confirmed NAFLD (OR: 1.113, 95% CI: 1.041, 1.189), which persisted when more stringent biopsy-confirmed NAFLD criteria were used (OR: 1.154, 95% CI: 1.043, 1.278) or when more stringent MR methods were applied. MR-Egger regression did not show a statistically significant intercept. CONCLUSION:The two-sample MR analyses showed a robust association between genetically predicted NAFLD and CAD after exclusion of genetic variants that are implicated in impaired VLDL secretion.
10.1002/hep.32534
The Gene at the 15q26 Coronary-Artery-Disease Locus Inhibits Atherosclerosis.
Circulation research
BACKGROUND:Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. METHODS AND RESULTS:Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed . There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. CONCLUSIONS:We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.
10.1161/CIRCRESAHA.122.321146
Acute myocardial infarction in sickle cell disease: a systematic review.
Pannu Rajmony,Zhang Jun,Andraws Richard,Armani Annemarie,Patel Praful,Mancusi-Ungaro Peter
Critical pathways in cardiology
Myocardial infarction in young adults is, in practice, a diagnosis of exclusion. Given the fact that most of the patients with sickle cell disease are young and have predisposition to painful crisis, they are often overlooked for myocardial infarction. These patients often have few or no traditional risk factors for coronary artery disease, and risk stratification tools such as the Thrombolysis in Myocardial Infarction (TIMI) and Global Registry of Acute Coronary Events (GRACE) models place these patients at low risk. Nonspecific changes on electrocardiogram are of little diagnostic value. Myocardial infarction is very often a missed diagnosis in patients with sickle cell disease. Diagnostic criteria, potential mechanisms, and management for acute myocardial infarction in patients with sickle cell disease are discussed.
10.1097/HPC.0b013e3181668ac3
Myocardial infarction in young patients.
Choudhury L,Marsh J D
The American journal of medicine
Myocardial infarction in persons under the age of 45 years accounts for 6% to 10% of all myocardial infarctions in the United States. In this age group, it is predominantly a disease of men. Important risk factors include a family history of myocardial infarction before age 55 years, hyperlipidemia, smoking, and obesity. Unlike older patients, approximately half of young patients have single-vessel coronary disease, and in up to 20%, the cause is not related to atherosclerosis. Coronary angiography may be warranted in young patients with myocardial infarction to define the anatomy of the disease and to permit optimal management.
10.1016/s0002-9343(99)00218-1
[Myocardial infarction with non-obstructive coronary arteries (MINOCA): diagnosis, pathogenesis, therapy and prognosis].
Buono Andrea,Pedrotti Patrizia,Soriano Francesco,Veas Nicolas,Oliva Fabrizio,Oreglia Jacopo,Ammirati Enrico
Giornale italiano di cardiologia (2006)
The term MINOCA (myocardial infarction with non-obstructive coronary arteries) defines acute myocardial infarction with angiographic evidence of no significant coronary artery stenosis. Heterogeneous diseases are labelled as MINOCA. Incidence and epidemiological aspects differ on the basis of etiological causes. MINOCA include plaque (causing <50% stenosis) rupture or erosion, coronary embolism and dissection, and coronary artery spasm. Diagnosis may require multiple diagnostic tools, including cardiac imaging or provocative tests, in addition to standard coronary angiography, according to clinical suspicion. Cardiac magnetic resonance plays a key role in confirming the diagnosis and excluding other diseases with similar clinical presentation. Prognosis is not as benign as previously thought, on the opposite it is characterized by morbidity and mortality rates similar to other forms of myocardial infarction. Once the causative mechanism has been identified, appropriate therapy can be delivered.
10.1714/3207.31839
On the Natural History of Coronary Artery Disease: A Longitudinal Nationwide Serial Angiography Study.
Journal of the American Heart Association
Background The long-term course of coronary atherosclerosis has not been studied in large nationwide cohorts. Understanding the natural history of coronary atherosclerosis could help identify patients at risk for future coronary events. Methods and Results All coronary artery segments with <50% luminal stenosis in patients with a first-time coronary angiogram between 1989 and 2017 were identified (n=2 661 245 coronary artery segments in 248 736 patients) and followed until a clinically indicated angiography within 15 years was performed or until death or end of follow-up (April 2018) using SCAAR (Swedish Coronary Angiography and Angioplasty Registry). The stenosis progression and incidence rates were 2.6% and 1.45 (95% CI, 1.43-1.46) per 1000 segment-years, respectively. The greatest progression rate occurred in the proximal and middle segments of the left anterior descending artery. Male sex and diabetes were associated with a 2-fold increase in risk, and nearly 70% of new stenoses occurred in patients with baseline single-vessel disease (hazard ratio, 3.86 [95% CI, 3.69-4.04]). Coronary artery segments in patients with no baseline risk factors had a progression rate of 0.6% and incidence rate of 0.36 (95% CI, 0.34-0.39), increasing to 8.1% and 4.01 (95% CI, 3.89-4.14) per 1000 segment-years, respectively, in patients with ≥4 risk factors. The prognostic impact of risk factors on stenosis progression was greatest in younger patients and women. Conclusions Coronary atherosclerosis progressed slowly but more frequently in the left coronary artery in men and in the presence of traditional risk factors. Coronary artery segments in patients without risk factors had little or no risk of stenosis progression, and the relative impact of risk factors appears to be of greater importance in younger patients and women. These findings help in the understanding the long-term course of coronary atherosclerosis.
10.1161/JAHA.122.026396
Single-nucleus chromatin accessibility profiling highlights regulatory mechanisms of coronary artery disease risk.
Nature genetics
Coronary artery disease (CAD) is a complex inflammatory disease involving genetic influences across cell types. Genome-wide association studies have identified over 200 loci associated with CAD, where the majority of risk variants reside in noncoding DNA sequences impacting cis-regulatory elements. Here, we applied single-nucleus assay for transposase-accessible chromatin with sequencing to profile 28,316 nuclei across coronary artery segments from 41 patients with varying stages of CAD, which revealed 14 distinct cellular clusters. We mapped ~320,000 accessible sites across all cells, identified cell-type-specific elements and transcription factors, and prioritized functional CAD risk variants. We identified elements in smooth muscle cell transition states (for example, fibromyocytes) and functional variants predicted to alter smooth muscle cell- and macrophage-specific regulation of MRAS (3q22) and LIPA (10q23), respectively. We further nominated key driver transcription factors such as PRDM16 and TBX2. Together, this single-nucleus atlas provides a critical step towards interpreting regulatory mechanisms across the continuum of CAD risk.
10.1038/s41588-022-01069-0
Deep learning artificial intelligence framework for multiclass coronary artery disease prediction using combination of conventional risk factors, carotid ultrasound, and intraplaque neovascularization.
Computers in biology and medicine
OBJECTIVE:Cardiovascular disease (CVD) is a major healthcare challenge and therefore early risk assessment is vital. Previous assessment techniques use either "conventional CVD risk calculators (CCVRC)" or machine learning (ML) paradigms. These techniques are ad-hoc, unreliable, not fully automated, and have variabilities. We, therefore, introduce AtheroEdge-MCDL (AE3.0) windows-based platform using multiclass Deep Learning (DL) system. METHODS:Data was collected on 500 patients having both carotid ultrasound and corresponding coronary angiography scores (CAS), measured as stenosis in coronary arteries and considered as the gold standard. A total of 39 covariates were used, clubbed into three clusters, namely (i) Office-based: age, gender, body mass index, smoker, hypertension, systolic blood pressure, and diastolic blood pressure; (ii) Laboratory-based: Hyperlipidemia, hemoglobin A1c, and estimated glomerular filtration rate; and (iii) Carotid ultrasound image phenotypes: maximum plaque height, total plaque area, and intra-plaque neovascularization. Baseline characteristics for four classes (target labels) having significant (p < 0.0001) values were calculated using Chi-square and ANOVA. For handling the cohort's imbalance in the risk classes, AE3.0 used the synthetic minority over-sampling technique (SMOTE). AE3.0 used Recurrent Neural Network (RNN) and Long Short-Term Memory (LSTM) DL models and the performance (accuracy and area-under-the-curve) was computed using 10-fold cross-validation (90% training, 10% testing) frameworks. AE3.0 was validated and benchmarked. RESULTS:The AE3.0 using RNN and LSTM showed an accuracy and AUC (p < 0.0001) pairs as (95.00% and 0.98), and (95.34% and 0.99), respectively, and showed an improvement of 32.93% and 9.94% against CCVRC and ML, respectively. AE3.0 runs in <1 s. CONCLUSION:DL algorithms are a powerful paradigm for coronary artery disease (CAD) risk prediction and CVD risk stratification.
10.1016/j.compbiomed.2022.106018
Coronary artery disease risk factors affected by RNA modification-related genetic variants.
Frontiers in cardiovascular medicine
Background:Single nucleotide polymorphisms that affect RNA modification (RNAm-SNPs) may have functional roles in coronary artery disease (CAD). The aim of this study was to identify RNAm-SNPs in CAD susceptibility loci and highlight potential risk factors. Methods:CAD-associated RNAm-SNPs were identified in the CARDIoGRAMplusC4D and UK Biobank genome-wide association studies. Gene expression and circulating protein levels affected by the RNAm-SNPs were identified by QTL analyses. Cell experiments and Mendelian randomization (MR) methods were applied to test whether the gene expression levels were associated with CAD. Results:We identified 81 RNAm-SNPs that were associated with CAD or acute myocardial infarction (AMI), including mA-, mA-, mC-, A-to-I- and mG-related SNPs. The mA-SNPs rs3739998 in , rs148172130 in and rs12190287 in and the mG-SNP rs186643756 in were genome-wide significant. The RNAm-SNPs were associated with gene expression (e.g., and ), and the expression levels were associated with CAD. Differential mA methylation and differential expression in FTO-overexpressing human aorta smooth muscle cells and peripheral blood mononuclear cells of CAD patients and controls were detected. The RNAm-SNPs were associated with circulating levels of proteins with specific biological functions, such as blood coagulation, and the proteins (e.g., cardiotrophin-1) were confirmed to be associated with CAD and AMI in MR analyses. Conclusion:The present study identified RNAm-SNPs in CAD susceptibility genes, gene expression and circulating proteins as risk factors for CAD and suggested that RNA modification may play a role in the pathogenesis of CAD.
10.3389/fcvm.2022.985121
Rivaroxaban and aspirin vs. aspirin alone in Asian compared with non-Asian patients with chronic coronary artery disease or peripheral arterial disease: the COMPASS trial.
European heart journal
AIMS:It is unknown whether Asian and non-Asian patients with atherosclerotic vascular disease derive similar benefits from long-term antithrombotic therapy. METHODS AND RESULTS:In patients with chronic coronary artery disease (CAD) and/or peripheral artery disease (PAD) enrolled in The Cardiovascular Outcomes for People Using Anticoagulation Strategies trial, the effects of rivaroxaban 2.5 mg b.i.d. plus aspirin 100 mg o.d. were compared with those of aspirin 100 mg o.d. in Asian vs. non-Asian patients (race was self-identified). Asians (n = 4269) vs. non-Asians (n = 23 126) had similar rates of major adverse cardiovascular events (MACEs) (4.85% vs. 4.83%, P = 0.30) and modified International Society on Thrombosis and Haemostasis (ISTH) major bleeding (2.72% vs. 2.58%, P = 0.22), but higher rates of intracranial haemorrhage (ICH) (0.63% vs. 0.29%, P = 0.01) and minor bleeding (13.61% vs. 6.49%, P < 0.001). In Asians vs. non-Asians, the combination of rivaroxaban and aspirin compared with aspirin alone produced consistent reductions in MACE [Asians: hazard ratio (HR): 0.64, 95% confidence interval (CI): 0.45-0.90; non-Asians: HR: 0.78, 95% CI: 0.67-0.90; P(heterogeneity) = 0.29], increases in modified ISTH major bleeding (Asians: HR 2.24, 95% CI: 1.40-3.58; non-Asians: HR: 1.60, 95% CI: 1.30-1.97; P = 0.20), and net clinical outcome (Asians: HR: 0.77, 95% CI: 0.56-1.05; non-Asians: HR: 0.81, 95% CI: 0.70-0.93, P = 0.78), but borderline higher rates of ICH (Asians: HR: 3.50, 95% CI: 0.98-12.56; non-Asians: HR: 0.81, 95% CI: 0.43, 1.53; P = 0.04). CONCLUSION:Asian compared with non-Asian patients with chronic CAD and/or PAD have higher rates of ICH and minor bleeding. The combination of rivaroxaban and aspirin vs. aspirin alone produces similar effects for MACE, modified ISTH major bleeding, and net clinical outcome but may be associated with higher rates of ICH in Asian patients.
10.1093/eurheartj/ehac309
Effects of traditional mind-body movement therapy on chronic cardiopulmonary dyspnoea: a systematic review and meta-analysis.
Thorax
PURPOSE:To evaluate whether traditional mind-body movement therapy (TMBM) can be used as a complementary or alternative therapy for exercise-based cardiopulmonary rehabilitation (EBCR) on chronic cardiopulmonary dyspnoea. METHODS:PubMed, Embase, Scopus, Web of Science and China National Knowledge Infrastructure were searched from their inception to 2 July 2021. Randomised clinical trials evaluating the effectiveness of TMBM versus EBCR, and TMBM +EBCR versus TMBM in the treatment of chronic cardiopulmonary dyspnoea were selected. The outcomes were exercise capacity (6 min walk distance, 6MWD) and quality of life (QoL). RESULTS:Thirty-four randomised clinical trials with 2456 patients were included. For TMBM vs EBCR alone, statistically significant improvements in the 6MWD favoured the TMBM for chronic obstructive pulmonary disease (COPD) (mean difference(MD)=12.22 m; 95% CI 5.94 to 18.50; I=56%) and heart failure (HF) patients (MD=43.65 m; 95% CI 7.91 to 79.38; I=0%). Statistically significant improvements in QoL also favoured TMBM over EBCR for patients with HF(MD=-9.19; 95% CI -11.05 to -7.32; I=0%) but non-significant trend for COPD (standardised mean difference (SMD)=-0.31; 95% CI -0.62 to 0.01; I=78%). Comparisons of TMBM +EBCR versus EBCR alone revealed significant improvements in the QoL for COPD (SMD=-0.52; 95% CI -0.94 to -0.10; I=86%) and patients with HF (MD=-2.82; 95% CI -4.99 to -0.64; I=0%). The 6MWD results favoured the TMBM +EBCR for patients with COPD (MD=16.76 m; 95% CI 10.24 to 23.29; I=0%), but only showed a slight trend towards additional benefits of TMBM +EBCR in the HF studies (MD=13.77 m; 95% CI -1.01 to 28.54; I2=65%) . CONCLUSIONS:TMBM has positive effects on patients' 6MWD and QoL, with similar or even better effects than EBCR. It may be beneficial to use TMBM as a supplementary or alternative strategy for EBCR in treatment plans. PROSPERO REGISTRATION NUMBER:CRD42021241181.
10.1136/thoraxjnl-2021-218030
Dietary Habits of Patients with Coronary Artery Disease: A Case-Control Study from Pakistan.
International journal of environmental research and public health
BACKGROUND:Adults in South Asian countries have high chances of developing coronary artery disease (CAD) as compared to the developed nations. CAD is among the primary non-communicable causes of death in this region. Dyslipidemia, obesity, smoking hypertension, diabetes are considered as important risk factors for CVD. METHODS:A case-control study was conducted, with data was collected from the Punjab Institute of Cardiology in Lahore and the University of Lahore Teaching Hospital. A total of 500 subjects were selected, of which 250 were coronary artery disease patients and 250 were healthy controls. The CAD patients were selected from the outpatient department (OPD) and emergency unit of the Punjab Institute of Cardiology and the University of Lahore Teaching Hospital. RESULTS:The mean age of CAD patients was 57.83 ± 7.51 years and that of the controls was 55.32 ± 6.40 years. There was a significant difference in the mean values of biochemical parameters among cases and controls except for fasting blood sugar levels while there was a significant difference (-value: 0.000) in the mean values of systolic blood pressure among cases and controls. Similarly, the values of diastolic blood pressure were also significantly different (-value: 0.000) among cases and controls. The values of total blood cholesterol, LDL, triglycerides and HDL were also significantly different among cases and controls. There was a significant relationship between consumption of chicken, eggs, beef, yogurt, junk food, fresh vegetables, and fruits, and incidence of CAD. Consuming milk every day, and consuming fish weekly and consuming ghee had no significant association with the risk of coronary artery disease. On the other hand, from the findings of the unadjusted model, there was a significant association between CAD risk and intake of chicken, beef, egg, yogurt, junk food, fish, vegetables, and fruits. CONCLUSIONS:Diet is a risk factor for coronary artery disease and can be adjusted to reduce the risk of CAD. A key finding is that consumption of chicken, beef, eggs and junk food are associated with a high risk of CAD whereas consumption of ghee is not associated with the risk of CAD.
10.3390/ijerph19148635
Sex-specific differences and long-term outcome of patients with coronary artery disease and chronic kidney disease: the Coronary Artery Disease and Renal Failure (CAD-REF) Registry.
Clinical research in cardiology : official journal of the German Cardiac Society
BACKGROUND:Cardiovascular morbidity and mortality are closely linked to chronic kidney disease (CKD). Sex-specific long-term outcome data of patients with coronary artery disease (CAD) and CKD are scarce. METHODS:In the prospective observational multicenter Coronary Artery Disease and REnal Failure (CAD-REF) Registry, 773 (23.1%) women and 2,579 (76.9%) men with angiographically documented CAD and different stages of CKD were consecutively enrolled and followed for up to 8 years. Long-term outcome was evaluated using survival analysis and multivariable Cox-regression models. RESULTS:At enrollment, women were significantly older than men, and suffered from more comorbidities like CKD, hypertension, diabetes mellitus, and multivessel coronary disease. Regarding long-term mortality, no sex-specific differences were observed (Kaplan-Meier survival estimates: 69% in women vs. 69% in men, p = 0.7). Survival rates decreased from 89% for patients without CKD at enrollment to 72% for patients with CKD stages 1-2 at enrollment and 49% for patients with CKD stages 3-5 at enrollment (p < 0.001). Cox-regression analysis revealed that sex or multivessel coronary disease were no independent predictors of long-term mortality, while age, CKD stages 3-5, albumin/creatinine ratio, diabetes, valvular heart disease, peripheral artery disease, and left-ventricular ejection fraction were predictors of long-term mortality. CONCLUSIONS:Sex differences in CAD patients mainly exist in the cardiovascular risk profile and the extent of CAD. Long-term mortality was not depended on sex or multivessel disease. More attention should be given to treatment of comorbidities such as CKD and peripheral artery disease being independent predictors of death. Clinical Trail Registration ClinicalTrials.gov Identifier: NCT00679419.
10.1007/s00392-021-01864-5
A comprehensive review of coronary artery disease in patients with end-stage liver disease.
Transplantation reviews (Orlando, Fla.)
The prevalence of coronary artery disease has increased in patients with end stage liver disease. In the near future, non-alcoholic steatohepatitis is expected to be the leading cause of end stage liver disease and shares common risk factors with coronary artery disease such as hypertension, hyperlipidemia, obesity and diabetes mellitus. At present, liver transplantation is the only definitive treatment for end stage liver disease, with post-operative mortality associated with the presence of coronary artery disease. Given the high prevalence of cardiovascular disease and the unique balance of pro-thrombotic and antithrombotic factors in patients with end stage liver disease, we sought to discuss the non-invasive and invasive diagnosis, medical and procedural management considerations and pre-transplant evaluation of coronary artery disease in patients with end stage liver disease.
10.1016/j.trre.2022.100709
Prevalence of Coronary Microvascular Disease and Coronary Vasospasm in Patients With Nonobstructive Coronary Artery Disease: Systematic Review and Meta-Analysis.
Journal of the American Heart Association
Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.
10.1161/JAHA.121.023207
Insulin Response to Oral Glucose and Cardiometabolic Disease: A Mendelian Randomization Study to Assess Potential Causality.
Diabetes
Mendelian randomization (MR) suggests that postprandial hyperinsulinemia (unadjusted for plasma glucose) increases BMI, but its impact on cardiometabolic disease, a leading cause for mortality and morbidity in people with obesity, is not established. Fat distribution i.e., increased centripetal and/or reduced femoro-gluteal adiposity, is causally associated with and better predicts cardiometabolic disease than BMI. We therefore undertook bidirectional MR to assess the effect of corrected insulin response (CIR) (insulin 30 min after a glucose challenge adjusted for plasma glucose) on BMI, waist-to-hip ratio (WHR), leg fat, type 2 diabetes (T2D), triglyceride (TG), HDL, liver fat, hypertension (HTN), and coronary artery disease (CAD) in people of European descent. Inverse variance-weighted MR suggests a potential causal association between increased CIR and increased BMI (b = 0.048 ± 0.02, P = 0.03), increased leg fat (b = 0.029 ± 0.012, P = 0.01), reduced T2D (b = -0.73 ± 0.15, P = 6 × 10-7, odds ratio [OR] 0.48 [95% CI 0.36-0.64]), reduced TG (b = -0.07 ± 0.02, P = 0.003), and increased HDL (b = 0.04 ± 0.01, P = 0.006) with some evidence of horizontal pleiotropy. CIR had neutral effects on WHR (b = 0.009 ± 0.02, P = 0.69), liver fat (b = -0.08 ± 0.04, P = 0.06), HTN (b = -0.001 ± 0.004, P = 0.7, OR 1.00 [95% CI 0.99-1.01]), and CAD (b = -0.002 ± 0.002, P = 0.48, OR 0.99 [95% CI 0.81-1.21]). T2D decreased CIR (b -0.22 ± 0.04, P = 1.3 × 10-7), with no evidence that BMI, TG, HDL, liver fat, HTN, and CAD modulate CIR. In conclusion, we did not find evidence that increased CIR increases cardiometabolic disease. It might increase BMI with favorable fat distribution, reduce T2D, and improve lipids.
10.2337/db22-0138
The HDAC9-associated risk locus promotes coronary artery disease by governing TWIST1.
PLoS genetics
Genome wide association studies (GWAS) have identified thousands of single nucleotide polymorphisms (SNPs) associated with the risk of common disorders. However, since the large majority of these risk SNPs reside outside gene-coding regions, GWAS generally provide no information about causal mechanisms regarding the specific gene(s) that are affected or the tissue(s) in which these candidate gene(s) exert their effect. The 'gold standard' method for understanding causal genes and their mechanisms of action are laborious basic science studies often involving sophisticated knockin or knockout mouse lines, however, these types of studies are impractical as a high-throughput means to understand the many risk variants that cause complex diseases like coronary artery disease (CAD). As a solution, we developed a streamlined, data-driven informatics pipeline to gain mechanistic insights on complex genetic loci. The pipeline begins by understanding the SNPs in a given locus in terms of their relative location and linkage disequilibrium relationships, and then identifies nearby expression quantitative trait loci (eQTLs) to determine their relative independence and the likely tissues that mediate their disease-causal effects. The pipeline then seeks to understand associations with other disease-relevant genes, disease sub-phenotypes, potential causality (Mendelian randomization), and the regulatory and functional involvement of these genes in gene regulatory co-expression networks (GRNs). Here, we applied this pipeline to understand a cluster of SNPs associated with CAD within and immediately adjacent to the gene encoding HDAC9. Our pipeline demonstrated, and validated, that this locus is causal for CAD by modulation of TWIST1 expression levels in the arterial wall, and by also governing a GRN related to metabolic function in skeletal muscle. Our results reconciled numerous prior studies, and also provided clear evidence that this locus does not govern HDAC9 expression, structure or function. This pipeline should be considered as a powerful and efficient way to understand GWAS risk loci in a manner that better reflects the highly complex nature of genetic risk associated with common disorders.
10.1371/journal.pgen.1010261
Anti-inflammatory diet and incident peripheral artery disease: Two prospective cohort studies.
Clinical nutrition (Edinburgh, Scotland)
BACKGROUND & AIMS:Systemic inflammation plays a role in peripheral artery disease (PAD), and therefore, an anti-inflammatory diet may reduce PAD risk. We examined the association between the anti-inflammatory diet and PAD risk by smoking status, a trigger of systemic inflammation. METHODS:The study was based on two cohorts of 82 295 Swedish adults aged 45-83 years (38 823 women from Swedish Mammography Cohort and 45 472 men from Cohort of Swedish Men). An anti-inflammatory diet index (AIDI; 0-17 scores) was used to estimate the anti-inflammatory potential of diet. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS:Over a median 22-year (interquartile range 7.5 years) follow-up period, 3413 PAD cases were ascertained. Compared with individuals in the lowest quartile of the AIDI (score ≤4), the HR of PAD for those in the highest quartile (score ≥8) was 0.84 (95% CI, 0.74-0.94). The inverse association was observed in current and past smokers but not in never smokers. The HR of PAD comparing extreme quartiles of the AIDI was 0.67 (95% CI, 0.53-0.86) in current smoker, 0.78 (95% CI, 0.63-0.97) in past smoker, and 1.00 (95% CI, 0.82-1.23) in never smokers. Among foods included in AIDI, high consumption of breakfast cereals, chocolate, red wine, and olive/canola oil, and low consumption of processed red meat and organ meats were associated with low PAD risk. CONCLUSIONS:The study suggests that adherence to a diet with high anti-inflammatory potential may lower PAD risk, especially in smokers.
10.1016/j.clnu.2022.04.002
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 randomization study.
European journal of preventive cardiology
AIMS:Observational studies indicate that serum urate level is associated with heart failure (HF). 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 HF. METHODS AND RESULTS:A bidirectional Mendelian randomization (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 (1088 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. Genetically determined serum urate level was associated with HF [odds ratio (OR), 1.07; 95% confidence interval (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 HF 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. CONCLUSION: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.
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
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.
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 the 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 1-1191 days). During LTOLE, the incident events per 100 patient years were as follows: for the primary outcome [cardiovascular death, stroke, or myocardial infarction (MI)] 2.35 [95% confidence interval (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 CIs that overlapped those seen during the randomized treatment phase with the combination of rivaroxaban and aspirin. The incidence rates for major and minor bleeding were 1.01 (0.86-1.19) and 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.
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
Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk.
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
Predictors of Left Main Coronary Artery Disease in the ISCHEMIA Trial.
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
Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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
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.
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
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.
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.
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
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.
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.
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.
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
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.
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.
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.
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