Coronary Artery Disease Events Research Articles

Phenotyping coronary plaque by computed tomography in premature coronary artery disease

Abstract Background Premature coronary artery disease (CAD) is an aggressive chronic disease with multiple recurrences mostly related to the progression or complication of new coronary lesions. Purpose To compare coronary plaque characteristics of individuals with premature CAD with those of incidental plaques found in matched individuals free of overt cardiovascular disease, using coronary computed tomography angiography (CCTA). Methods 106 individuals with premature CAD were matched by age, sex, smoking status, family history of CAD, and dyslipidemia with 106 controls free of overt cardiovascular disease. CCTA were standardly analyzed for CAD-RADS score, plaque composition (calcified, partially or non-calcified), and the following four high-risk plaque (HRP) features : spotty calcification, positive remodeling, napkin-ring sign, and low-attenuation plaque. Results At least one coronary plaque was found in 85% of individuals with premature CAD vs. 62% of matched controls. The prevalence of non-calcified plaques was higher among individuals with premature CAD (65.1% vs. 30.2%, p<0,001), as well as spotty calcification (42.5% vs. 17.9%, p<0.001), positive remodeling (41.5% vs. 9.4%, p<0.001), low-attenuation plaques (24.5% vs. 3.8%, p<0.001) and napkin-ring sign (1.9% vs. 0.0%) (Figure 1). Individuals with premature CAD exhibited an average of 2.2 (±2.7) HRP features per person, while the control group displayed 0.4 (±0.8) HRP per person (p<0.001). Within a median follow-up of 24 [16,34] months, 24 ischemic recurrent events occurred in 24 individuals, all in the in premature CAD group. Individuals with premature CAD and recurrent ischemic event had more high-risk plaque features (4.3±3.9) than those without ischemic recurrence (1.5±1.9). They displayed more frequently non-calcified plaques (91.7% vs. 57.3%) with positive remodeling (75.0% vs. 31.7%) and low-attenuation plaques (45.8% vs. 18.3%) as compared to those without ischemic recurrence (Figure 2). Conclusions Coronary atherosclerosis in individuals with premature CAD is characterized by a high and predominant burden of non-calcified plaque and unusual high prevalence of high-risk plaque features, contributing to disease progression with multiple recurrences in this setting.HRP features in study populationHRP according to ischemic recurrence

High mannose correlates with surrogate indexes of insulin resistance and predicts cardiovascular events independently of glycaemic status and traditional risk factors

Abstract Background Plasma mannose, an emerging marker of insulin resistance (IR), is independently associated with coronary artery disease and cardiovascular (CV) events, not only in patients with altered glycaemic status, but also among those with normal glucose tolerance (NGT) [1, 2]. Whether mannose is a predictor of future CV events is not known. Purpose To investigate the association of mannose with surrogate indexes of IR as well as with long-term prognosis in patients with and without dysglycaemia. Methods Fasting plasma mannose was measured by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS-MS) in 696 cases with a first myocardial infarction (MI) and 707 controls matched for age, gender and living area from the PAROKRANK study [3]. Subjects free of known diabetes were further categorized as having either NGT (n=1045) or newly detected dysglycaemia (i.e., impaired glucose tolerance or type 2 diabetes; n=358) according to the results of an oral glucose tolerance test (OGTT). Surrogate indexes of IR and insulin secretion were calculated using glucose, insulin and C-peptide levels measured at 0, 30 and 120 minutes during the OGTT. The relationship between plasma mannose and different indexes was explored by fitting univariate and multivariate linear regression models. Kaplan-Meier functions were used to estimate crude survival across mannose quartiles. Unadjusted and adjusted Cox proportional hazards models were used to investigate the prognostic capacity of mannose, categorized as high (top quartile) vs low (lowest three quartiles), in relation to major adverse cardiac events (MACE) defined as CV death, MI and stroke during 10 years of follow-up. Secondary outcomes were single components of MACE and all-cause mortality. Results Mannose levels were associated with indexes of IR independently of BMI and other covariates in both the NGT and dysglycaemia subgroups. There was no difference in crude MACE-free survival between subjects with high and low mannose (log-rank p=0.10; Figure 1). However, high mannose remained as the only predictor of MACE in the overall population (Hazard ratio (HR): 1.58 (1.10-2.27); p=0.014) after multiple adjustments (Figure 2). This association was independent of the presence of dysglycaemia (interaction p between mannose category and dysglycaemia group=0.94) and IR expressed as HOMA-IR. High mannose also predicted MI, independently of the presence of a first MI (HR: 1.62 (1.00-2.62); p=0.050), while there was no significant association with the other secondary outcomes. Conclusions In a case-control setting of first MI, high mannose was the only significant predictor of future CV events, independently of traditional CV risk factors including a previous MI, glycaemic state and IR. Our findings expand the knowledge indicating that mannose might be used as a clinical tool for CV risk stratification.

The paradox of the association between epicardial adipose tissue, infarct size and left ventricular remodelling after ST-segment elevation myocardial infarction: a CMR study

Abstract Background Epicardial adipose tissue (EAT) is a biologically active fat deposit contained below the visceral pericardium. In latest years, EAT has emerged as a predictor of atherosclerosis, coronary artery disease and adverse cardiovascular events. Nevertheless, EAT significance after ST-segment elevation myocardial infarction (STEMI) in acute phase and its association with left ventricular remodelling is unknown. Purpose We aimed to assess the association of cardiac magnetic resonance (CMR)-derived EAT with the extent of infarct size (IS), microvascular obstruction (MVO) and left ventricular remodelling in a homogeneous cohort of STEMI patients. Methods We prospectively included 255 patients discharged after a first reperfused, anterior STEMI. An early CMR (1-week after STEMI) was performed in all patients. EAT volume (mL/m2), left ventricular (LV) end-diastolic and end-systolic indexed volumes (LVEDiV and LVESiV, mL/m2), left ventricular ejection fraction (LVEF, %), infarct size (IS, % of LV mass) and microvascular obstruction (MVO, % of LV mass) were quantified. A subgroup of 195 patients underwent a follow-up (6-month) CMR. Patients were categorized as extensive EAT (>35 mL/m2) or non-extensive EAT (≤35 mL/m2) according to the upper tertile of this parameter. A specific analysis was performed in patients with extensive IS (>30% of LV mass). Results Patients with extensive EAT were older (62±12 vs. 57±13 years, p=0.004), had an increased prevalence of diabetes mellitus (31% vs. 16%, p=0.007) and depicted a worse baseline risk profile (GRACE risk score 138±37 vs. 126±36 points, p=0.02). At 1-week CMR, patients with extensive EAT displayed larger IS (31±17% vs 24±16%, p=0.001), more MVO (1.4 [0-6.2]% vs 0 [0-2.5]% of LV mass, p=0.022) and more myocardial oedema (39±16% vs 32±17% of LV mass, p=0.003). After adjustment for baseline characteristics, EAT was independently associated with IS (standardized beta coefficient=0.30, p<0.001). However, patients with extensive EAT did not show neither larger LV volumes nor more depressed LVEF (p>0.1 for all comparisons). In the extensive IS subgroup (n=69, 27%), patients with extensive EAT depicted less dilated ventricular volumes (LVEDiV 90±26 vs 111±40 mL/m2, p=0.011; LVESiV 51±26 vs 72±36 mL/m2, p=0.009) and higher LVEF (46±13 vs. 38±10%, p=0.007) at 6-month CMR. At 6-month CMR, in a propensity score-matched population (n=170, 85 with extensive EAT and 85 without extensive EAT), EAT was independently associated with more preserved LVEF, and less dilated LVEDiV and LVESiV only in the subgroup of patients with extensive IS (p<0.05 for all comparisons) (Figure 1). Conclusions EAT seems to exert a bimodal effect in patients with anterior STEMI. More extensive EAT is associated with more extensive infarct size in acute phase but, in patients with large IS, those with extensive EAT display less adverse remodelling during follow-up. This "paradox" of EAT after STEMI merits further investigation.Figure 1.

Contribution of Lipoprotein(a) to polygenic risk of coronary artery disease: A prospective UK Biobank analysis

Abstract Background Lipoprotein(a) (Lp[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Purpose Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD. Methods 372,385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using LDpred2. Over the median follow-up of 12.6 years, 13,538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting or coronary angioplasty). Results The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (6.5%). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C-statistic 0.751 versus 0.746, difference = 0.005 (95% CI, 0.004-0.006). Compared to participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L (CAD event rate 6.6%), the hazard ratio for incident CAD in participants in the bottom CAD-PRS quintile with Lp(a) levels <25 nmol/L was 0.18 (95% CI, 0.17-0.20, p=6.41e-241, CAD event rate 2.0%). Conclusions Compared to individuals with a high genetic risk of CAD (high CAD-PRS and high Lp(a) levels), those with a low genetic risk had an 82% lower CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD should consider blood levels of Lp(a).

Abstract 11735: The Effect of Different NLRP3 Inflammasome Inhibitors on High-Sensitivity C-reactive Protein in Patients After Percutaneous Coronary Intervention

Background: Colchicine treatment inhibits the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome assembly and reduces atherothrombotic cardiovascular events in coronary artery disease (CAD). However, the effects of other inhibitors targeting NLRP3 inflammasome needs further verification in CAD. Aims: This study aimed to investigate whether inhibitors targeting NLRP3 inflammasome besides colchicine are effective in patients after percutaneous coronary interventions (PCI). Methods: The study included 132 patients aged 18-80 years who completed the planned PCI and were treated with aggressive secondary prevention strategies for four weeks. The subjects were randomly assigned to one of the following treatment groups for four weeks: (1) control: no additional intervention; (2) colchicine: 0.5 mg once a day; (3) tranilast: 0.1 g thrice a day; or (4) oridonin: 0.5 g thrice a day. The primary outcome was the percentage change in hsCRP levels at the end of four weeks. Results: In total, 109 patients completed the study. The mean age was 58.33 years, 81 (74.31%) were male and 28 (25.69%) were female. The percentage changes in hsCRP after four weeks of treatment were -11.62%, -48.28%, -21.60%, and -7.81%, in the control, colchicine, tranilast, and the oridonin groups respectively. Compared with the control group, the colchicine group showed significantly greater reduction in hsCRP levels (P=0.022). The tranilast and oridonin groups did not show obvious changes. In targeted proteomic analysis, proteins associated with neutrophil activation (azurocidin,myeloperoxidase, myeloblastin), platelet aggregation (glycoprotein VI) and endothelial damage (galectin-3) were reduced with colchicine therapy. Conclusions: Colchicine could reduce hsCRP in patients after PCI, which is likely to act on neutrophils. Colchicine may still be the important choice for anti-inflammatory treatment of CAD.

Definition and reporting of composite outcomes are often inadequate in randomized clinical trials on pharmacological interventions for coronary artery disease

ObjectivesTo estimate the frequency and critically appraise the use and reporting of composite outcomes in randomized clinical trials on pharmacological interventions for coronary artery disease. Study Design and SettingA metaresearch study. A search strategy was developed to retrieve references from MEDLINE. We considered articles, published from 1st January 2020, to December 31, 2021, reporting results of clinical primary outcomes from randomized clinical trials which assessed pharmacological interventions, used alone or in combination, for the treatment or secondary prevention (previous coronary event) of coronary artery disease. ResultsFrom the 34 included studies, 28 (82.35%) had a primary composite outcome. Thirteen unique composite primary outcomes were used with the most frequent being "cardiovascular death, myocardial infarction, stroke" (12/28, 42.86%). The term major adverse cardiac events was used for five distinct composite primary outcomes. A combination of 12 different components resulted in the 28 primary composite outcomes, with stroke being the most frequent component present in 96.43% (27/28) of the primary composite outcomes. From the included studies, 60.71% (17/28) reported the estimates for each individual component and the direction of the effect was consistent between all components and the composite outcomes in 58.82% (10/17) of them. Additionally, no included study discussed potential limitations and/or related advantages of the composite outcomes. ConclusionIn randomized clinical trials on pharmacological interventions for coronary artery disease, composite outcomes are frequently used, but the definition of their components is very heterogeneous. The estimate for individual components within the composite outcome is often not fully reported, which prevents a complete analysis of their adequacy for clinical practice. The term major adverse cardiac events was used inconsistently and to refer to different set of components, which can also be misleading and confusing.

Abstract 13692: Incidence, Recurrence, and Ethnicity Specific Risk Factors for Premature Coronary Artery Disease in South Asians and Europeans

Introduction: Premature coronary artery disease (CAD) incidence is increasing globally. South Asians (SA) have a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD). However, the effect of SA ethnicity on the risk of recurrent events in patients with premature CAD has not been prospectively evaluated. Methods: Patients in the SAVEBC and UK biobank (UKB) registries were enrolled and stratified by ethnicity and presence of premature CAD. The co-primary outcomes were to compare proportion of premature CAD and the incidence of recurrent ASVCD events. Secondary exploratory outcomes included describing demographic, physical, biochemical variables between cohorts. Results: 11,136 patients were included, 1,129 (143 SA; 21%) were from SAVEBC and 10,007 (400 SA; 4.0%) from UKB. There was a higher proportion of premature CAD in SA compared to Caucasians in UKB (5.2% vs. 2.0%, p < 0.001). Similarly, SA were overrepresented in SAVEBC (21% of cohort vs. 7.9% of British Columbia population). SA compared to Caucasians with premature CAD had increased prevalence of diabetes (SAVEBC: 20.1% vs 13.8%, p=0.08; UKB: 37.5% vs 18.0%, p<0.001), and lower mean HDL cholesterol (SAVEBC: 1.4±0.4 vs 1.5±0.4, p=0.21; UKB: 1.1±0.3 vs 1.2±0.3, p<0.001). SA had more diffuse disease reflected by more coronary segments affected (4.9±3.0 vs. 4.1±2.6, p=0.05), and a trend towards more affected coronary vessels compared to Caucasians (1.31±1.4 vs. 0.61±0.91, p=0.14). SA had greater incidence of recurrent ASCVD vs. Caucasians (4.19 vs. 3.08 events per 100 P-Y; incidence rate ratio p-value < 0.001). SA had higher risk of recurrent ASCVD events (HR 1.35, 95% CI 1.13,1.61, p<0.001). SA ethnicity remained a predictor of recurrent events on adjusted COX regression (HR 1.24, 95% CI 1.03,1.48, p=0.02). Conclusion: Using two prospective registries, SA had a higher proportion of premature CAD and recurrent cardiovascular events with shorter time to recurrent events. Some risk may be explained by adverse cardiometabolic profiles, however significant risk mechanisms are yet to be elucidated. Understanding the unique mechanisms of cardiovascular risk in SA is critical to appropriately identify high-risk individuals and initiate contemporary preventative therapies.

Abstract 14928: Coronary Artery Disease Impacts Cardiac Remodeling in Patients Treated for Severe Aortic Stenosis in the PARTNER Trials

Introduction: Coronary artery disease (CAD) is common in patients with severe aortic stenosis (AS), but the impact on cardiac remodeling and outcomes after AS treatment is unknown. Hypothesis: We hypothesize that greater CAD burden will be associated with less beneficial remodeling and increased adverse events. Methods: Patients with severe AS in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2 or 3 trials, with baseline and 1 year echoes, were categorized as: 1. Obstructive CAD (coronary stenosis ≥50% on invasive angiography, prior myocardial infarction (MI) or previous revascularization); or 2. Non-obstructive or no CAD (all stenosis <50% and no prior MI or revasc). Clinical and imaging characteristics were compared and changes in cardiac structure and function were assessed at 1 year. Associations between CAD, cardiac remodeling and cardiovascular (CV) events at 2 years were examined. Results: Among 5552 patients with severe AS, 1598 (28.8%) had non-obstructive or no CAD and were more likely to be female (67.1%), have fewer CAD risk factors, and receive SAVR (28% vs. 19%) compared to those with obstructive CAD (all p<0.0001). Despite lower LV mass index (LVMi), patients with non-obstructive or no CAD had higher aortic valve velocities, gradients, ejection fraction (EF) and stroke volume index compared to those with obstructive CAD. After 1 year, the decrease in LVMi was similar between groups (p=0.91), but patients with obstructive CAD were more likely to increase EF by ≥5% (p=0.006), reduce LV dimensions (p=0.04), or decrease mitral regurgitation (p=0.01). After adjustment for baseline factors and AS treatment, CV death or heart failure (HF) hospitalization was higher among patients with obstructive CAD (HR 1.16, 95% CI: 1.03-1.30, p=0.01). When LV remodeling at 1 year was also adjusted for, the point estimate was similar but there was no significant difference in the landmarked rate of CV death or HF hospitalization between year 1 and 2 (HR 1.22, 95% CI: 0.95-1.56, p=0.12). Conclusions: Nearly a third of patients with severe AS did not have obstructive CAD and had a better prognosis after treatment for AS. However, patients with obstructive CAD and LV remodeling were not at greater risk for CV events compared to those with non-obstructive or no CAD.

Abstract 16844: Identifying Splenic Radiomics Features Associated With Risk of Coronary Artery Disease

Introduction: Inflammation is a validated mechanism for residual coronary artery disease (CAD) risk via clinical trials and analysis of germline and somatic genetic variation in blood cells. While the spleen plays an important role in regulating inflammation, the role it plays in CAD is unclear. Hypothesis: We aim to test the hypothesis that radiographic splenic biomarkers may offer novel insights for CAD. Methods: We used deep learning to segment spleens from the abdominal MRIs of 38,474 patients in the UK Biobank. CAD was defined as history of coronary artery bypass grafting, myocardial infarction (MI), coronary artery angioplasty, or billing codes (OPCS-4: K40, K41, K45, K49, K50.2, K75). We extracted image features using the pyradiomics package. To identify image features associated with CAD, we used L1-regularized logistic regression models with the splenic features and clinical features used in the Pooled Cohort Equations (PCE) for outcomes of CAD and cardiovascular disease (CVD) events (defined as a composite of CAD, MI, and stroke outcomes). We computed the area under the receiver operating characteristic (AUROC) on a held-out 30% of the patient population and determined 95% confidence intervals using 1,000 Monte-Carlo resampled bootstraps. Results: Study participants had mean (SD) age 55.1 (7.5) years, 19,921 (51.8%) were women, 1,412 (3.7%) had CAD, and 2,473 (6.4%) had CVD events. The model to predict CAD using the splenic and PCE features had an AUROC of 0.84 (95% CI, 0.84-0.85), and 3 out of 10 significant covariates were splenic features. 1-SD increases in sphericity, minor axis length, and entropy in neighboring voxel gray levels were associated with 5.4% (95% CI, 5.1-5.7) higher, 13.3% (95% CI, 13.0-13.6) lower, and 10.5% (95% CI, 10.2-10.8) higher odds of CAD after adjustment. Results were consistent in the model to predict CVD events, and decreased minor axis length and increased texture variation were associated with increased risk. Model performance was lower for older age groups, who had higher incidences of CAD. Conclusions: This study leverages deep-learning methods across a population based cohort to highlight splenic features correlated with CAD and offers new opportunities to understand the role of the hematopoietic system in CAD.

Abstract 16466: Sex-Specific Risks of Air Pollution on Coronary Artery Disease and Adverse Events: Insights From the PROMISE Trial

Introduction: Sex-specific differences in coronary artery disease (CAD) have significant implications, yet the potential sex-specific impact of air pollution on CAD and adverse outcomes remains unexplored. Hypothesis: The association between air pollution and CT-derived CAD phenotype or cardiovascular (CV) events varies by sex. Methods: We assessed annual average exposure to particulate matter (PM 2.5 & PM 10 ) and ozone by home zip codes in the CT arm of the PROMISE trial. Pollutant exposure was related to CAD measures on CT (any plaque, obstructive CAD (stenosis ≥50%), high-risk plaque (HRP)) and composite endpoint (death, myocardial infarction, unstable angina), adjusting for age, obesity, ASCVD risk, and Socioeconomic Determinants of Health, using sex-stratified regression analyses. Results: We analyzed 2,252 (52%) women and 2,091 (48%) men (62±8 vs. 59±8 years, p<0.001) with intermediate ASCVD risk (12% vs. 17%, p<0.001). Women were less frequently exposed to PM 2.5 ≥9.5 μm/m 3 (45.1% vs. 48.8%, p=0.011) but more frequently to ozone >45 ppb (40.5% vs. 36.8%, p=0.011) compared to men. Exposure to PM 2.5 ≥9.5 μm/m 3 related to 42% higher odds of obstructive CAD (aOR 1.42, 95%CI: 1.02-1.97, p=0.040) in women but not in men. High PM 10 and ozone exposures did not relate to stenosis or HRP in either sex (p>0.14) (Figure 1a) . Exposure to ozone >45 ppb was related to a higher hazard of events in men (aHR 2.20, 95%CI: 1.36-3.55, p=0.001) but not in women (aHR 1.05, 95%CI: 0.58-1.90, p=0.88). Exposure to high PM 2.5 and PM 10 levels was not associated with events in sex-stratified analysis (Figure 1b) . Conclusions: Sex significantly influences pollutant impact on CAD. High PM 2.5 exposure increases obstructive CAD risk exclusively in women, while high ozone exposure raises CV event risk in men. Findings stress the need for sex-specific strategies in combating pollution's cardiovascular effects.

Contribution of Lipoprotein(a) to Polygenic Risk Prediction of Coronary Artery Disease: A Prospective UK Biobank Analysis.

Lp(a) (lipoprotein[a]) is a highly atherogenic lipoprotein subfraction that may contribute to polygenic risk of coronary artery disease (CAD), but the extent of this contribution is unknown. Our objective was to estimate the contribution of Lp(a) to polygenic risk of CAD and to evaluate the respective contributions of Lp(a) and a CAD polygenic risk score (PRS) to CAD. A total of 372 385 UK Biobank participants of European ancestry free of CAD at baseline were included. Plasma Lp(a) levels were measured and a CAD-PRS was calculated using the LDpred2 algorithm. Over the median follow-up of 12.6 years, 13 538 participants had incident CAD (myocardial infarction, coronary artery bypass grafting, or coronary angioplasty). The LPA region contribution to the CAD-PRS-mediated CAD risk was modest (7.2% [95% CI, 6.1-8.3]). Lp(a) levels significantly increased the predictive performance of a CAD-PRS including age and sex in Cox regression (C statistic 0.751 versus 0.746, difference, 0.005 [95% CI, 0.004-0.006]). Compared with participants in the bottom CAD-PRS quintile with Lp(a) levels <25 nmol/L (CAD event rate, 1.4%), the hazard ratio for incident CAD in participants in the top CAD-PRS quintile with Lp(a) levels ≥125 nmol/L was 5.45 (95% CI, 4.93-6.03; P=9.35×10-242, CAD event rate 6.6%). Compared with individuals with a low genetic risk of CAD (low CAD-PRS and low Lp[a] levels), those with a high genetic risk (high CAD-PRS and high Lp[a] levels) had a 5-fold higher CAD risk. These results highlight a substantial contribution of genetic risk factors to CAD and that accurate estimation of genetic risk of CAD may need to consider blood levels of Lp(a).

Platelets and the Atherosclerotic Process: An Overview of New Markers of Platelet Activation and Reactivity, and Their Implications in Primary and Secondary Prevention.

The key role played by platelets in the atherosclerosis physiopathology, especially in the acute setting, is ascertained: they are the main actors during thrombus formation and, thus, one of the major investigated elements related to atherothrombotic process involving coronary arteries. Platelets have been studied from different points of view, according with the technology advances and the improvement in the hemostasis knowledge achieved in the last years. Morphology and reactivity constitute the first aspects investigated related to platelets with a significant body of evidence published linking a number of their values and markers to coronary artery disease and cardiovascular events. Recently, the impact of genetics on platelet activation has been explored with promising findings as additional instrument for patient risk stratification; however, this deserves further confirmations. Moreover, the interplay between immune system and platelets has been partially elucidated in the last years, providing intriguing elements that will be basic components for future research to better understand platelet regulation and improve cardiovascular outcome of patients.

Reticulated Platelets Predict Cardiovascular Death and Adverse Events in Coronary Artery Disease: A Systematic Review and Meta-analysis.

The pro-thrombotic immature or reticulated platelets (RPs) are known to be elevated in high-risk patients and in different pathological settings. It has been shown that RPs correlate with an insufficient antiplatelet response to antiplatelet agents. RPs are emerging novel predictors of adverse cardiovascular events in cardiovascular disease. This study, using the totality of existing evidence, evaluated the prognostic role of RPs in patients with coronary artery disease. We performed a systematic review and meta-analysis including trials of acute and chronic coronary syndrome reporting clinical outcomes according to RPs levels in the peripheral blood. We compared patients with elevated RPs (RPshigh) to patients without elevated RPs (RPslow). Odds ratios (ORs) and 95% CIs were used as metric of choice for treatment effects with random-effects models. The primary endpoint was major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints were cardiovascular death, myocardial infarction, ischemic stroke, urgent coronary revascularization and bleedings. A total of 7 studies, including 2213 patients, were included. The risk for MACCE was significantly higher in RPshigh compared to RPslow patients (OR 2.67 [1.87; 3.81], I2 = 43.8%). RPshigh were associated with cardiovascular death (OR 2.09 [1.36; 3.22], I2 = 40.4%). No associations for RPshigh were detected with the other singular components of MACCE: myocardial infarction (OR 1.73 [0.89; 3.38] I2 = 60.5%) and stroke (OR 1.72 [0.59; 4.96] I2 = 21%). The risk of bleeding did not differ between groups(OR 0.58 [0.15; 2.22] I2 = 86.1%). Elevated RPs are significantly associated with increased risk of cardiovascular events and cardiovascular death.

Plasma type I collagen α1 chain in relation to coronary artery disease: findings from a prospective population-based cohort and an acute myocardial infarction prospective cohort in Sweden

ObjectivesTo investigate the association between type I collagen α1 chain (COL1α1) levels and coronary artery disease (CAD) by using absolute quantification in plasma. Also, to investigate the correlates of COL1α1...

Genetic Predisposition, Sedentary Behavior and Incident Coronary Artery Disease: A Prospective Chinese Cohort Study.

Whether the association of sedentary behaviors with coronary artery disease (CAD) can be influenced by genetic susceptibility remains unclear. We aimed to investigate the joint and interplay effects between genetic risk and sedentary time (ST), and further explore the extent to which the risk for CAD can be counteracted by reducing ST in different genetic groups. This prospective cohort study included 39,164 Chinese adults without CAD history. Genetic susceptibility was quantified by a predefined polygenic risk score (PRS) with 540 genetic variants, and daily ST was assessed by questionnaire. We analyzed the modification effect of genetic risk on the association of ST with CAD using the Cox proportional hazards models. During a median follow-up of 11.60 years, 1156 CAD events were documented.Higher ST and PRS were separately related to elevated CAD risk. Significant additive interaction was also observed (relative excess risk due to interaction: 0.77; 95%CI: 0.27-1.28). Compared with participants with low genetic risk and low ST (<6 h/day), those with high genetic risk and high ST (≥10 h/day) had the highest CAD risk, with the hazard ratio (HR) and 95% confidence interval (95%CI) of 4.22 (2.65-6.71). When stratified by genetic risks, participants with high ST had gradient increment of CAD risks across low, intermediate, and high genetic risk groups, with the HR (95%CI) of 1.21 (0.61-2.40), 1.57 (1.14-2.16), and 2.15 (1.40-3.31), respectively. For the absolute risk reduction, individuals with high genetic risk achieved the greatest benefit from low ST (Ptrend = 0.024). Genetic susceptibility may synergistically interact with ST to increase CAD risk. Reducing ST could attenuate the CAD risk, especially among individuals with high genetic risk.

The Relationship Between Time-Varying Achieved HbA1c and Risk of Coronary Events Depends on Haptoglobin Phenotype Among White and Black ACCORD Participants.

Intensive glycemic therapy reduced coronary artery disease (CAD) events among White participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study with the haptoglobin (Hp)2-2 phenotype, while participants without the Hp2-2 phenotype had no CAD benefit. The association between achieved glycated hemoglobin (HbA1c) and CAD for each Hp phenotype remains unknown. Achieved HbA1c was similar in each phenotype throughout the study. Prospectively collected HbA1c data (categorized as <6.0%, 6.0-6.5%, 6.6-6.9%, or ≥8.0% compared with 7.0-7.9%) from the ACCORD study, updated every 4 months over a median of 4.7 years, were analyzed in relation to CAD in the Hp2-2 (n = 3,322) and non-Hp2-2 (n = 5,949) phenotypes separately overall, and within White (63%, 37% Hp2-2) and Black (19%, 26% Hp2-2) participants using Cox proportional hazards regression with time-varying covariables. Compared with HbA1c of 7.0-7.9%, having HbA1c ≥8.0% was associated with CAD risk among White (adjusted HR [aHR] 1.43, 95% CI 1.03-1.98) and Black (2.86, 1.09-7.51) participants with the Hp2-2 phenotype, but not when all Hp2-2 participants were combined overall (1.30, 0.99-1.70), and not among participants without the Hp2-2 phenotype. HbA1c <7.0% was not associated with a lower risk of CAD for any Hp phenotype. Achieving HbA1c >8.0% compared with 7.0-7.9% was consistently associated with incident CAD risk among White and Black ACCORD participants with the Hp2-2 phenotype, while no association was observed among participants without the Hp2-2 phenotype. We found no evidence that HbA1c concentration <7.0% prevents CAD in either Hp phenotype group.

Exercise electrocardiography for pre-test assessment of the likelihood of coronary artery disease

ObjectivesTo develop a tool including exercise electrocardiography (ExECG) for patient-specific clinical likelihood estimation of patients with suspected obstructive coronary artery disease (CAD).MethodsAn ExECG-weighted clinical likelihood (ExECG-CL) model was developed in...

Understanding the Link Between Adult Asthma and Coronary Artery Disease: A Narrative Review.

Asthma is a common pathology worldwide that occurs due to chronic inflammation of the respiratory airways. Persistent pulmonary inflammation leads to low-grade systemic inflammation, influencing blood vessels and triggering coronary artery disease (CAD) events. This review's objectives include discussing the susceptible population for CAD, the mechanism underlying CAD creation in asthma patients, the characteristics of asthma, and the influence of anti-asthmatic medications on CAD development. Adult-onset asthma is strongly linked to CAD and stroke. Future research may shed light on these disparities. Atherosclerosis and asthma are linked through both intrinsic and extrinsic pathways, with inflammation being the intrinsic pathway and hypoxia and tachyarrhythmia being the extrinsic pathways. The most probable mechanisms for increased coronary vasospastic angina (CVsA) incidence in asthmatic patients are vascular smooth muscle cell hypercontraction and endothelial dysfunction. Studies have shown a dose-response relationship between asthma control and myocardial infarction (MI) risk, with uncontrolled asthma at the highest risk. Impairment of ventilatory function is a distinct risk factor for lethal MI and cardiovascular death (CVD). The use of beta-2-agonists and chronic oral glucocorticoid therapy in severe asthmatics has been linked to increasing the risk for CAD. However, some studies have shown that the risk of MI among patients with active asthma is not related to the use of asthma medications. Further research is needed to determine the involvement of adult asthma features and their treatments in the development of CAD.

Chronic kidney disease, type 2 diabetes and the risk of major cardiovascular events in coronary artery disease versus peripheral artery disease patients

Chronic kidney disease, type 2 diabetes and the risk of major cardiovascular events in coronary artery disease versus peripheral artery disease patients

Opportunistic screening at chest computed tomography: literature review of cardiovascular significance of incidental findings.

Several incidental cardiovascular findings are present in a routine chest computed tomography (CT) scan, many of which do not make it to the final radiology report. However, these findings have important clinical implications, particularly providing prognosis and risk-stratification for future cardiovascular events. The purpose of this article is to review the literature on these incidental cardiovascular findings in a routine chest CT and inform the radiologist on their clinical relevance. A time unlimited review of PubMed and Web of Science was performed by using relevant keywords. Articles in English that involved adults were included. Coronary artery calcification (CAC) is the most common incidental cardiac finding detected in a routine chest CT and is a significant predictor of cardiovascular events. Noncoronary vascular calcifications in chest CT include aortic valve, mitral annulus, and thoracic aortic calcifications (TAC). Among these, aortic valve calcification (AVC) has the strongest association with coronary artery disease and cardiovascular events. Additional cardiac findings such as myocardial scar and left ventricular size and noncardiac findings such as thoracic fat, bone density, hepatic steatosis, and breast artery calcifications can also help in risk stratification and patient management. The radiologist interpreting a routine chest CT should be cognizant of the incidental cardiovascular findings, which helps in the diagnosis and risk-stratification of cardiovascular disease. This will guide appropriate referral and management.