Coronary Artery Disease Events Research Articles

Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease.

This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD. D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves. CAD events were observed in 238 male and 67 female patients. The Kaplan-Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15-1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27-2.37). Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not. UMIN-CTR Clinical Trial Number: UMIN000027504.

Haptoglobin phenotype and intensive glycemic control for coronary artery disease risk reduction in people with type two diabetes: The Veterans Affairs Diabetes Trial

BackgroundIntensive glycemic control reduced the risk of coronary artery disease (CAD) events among White ACCORD study participants with the haptoglobin (Hp)2-2 phenotype, and not among participants without the Hp2-2 phenotype. It is unknown whether these results persist in a population with more severe diabetes. MethodsHaptoglobin phenotype was measured in 1746 (97 %) samples from the Veterans Affairs Diabetes Trial (VADT) randomized controlled trial. Multivariable-adjusted Cox regression models assessed the effect of intensive therapy on CAD risk among participants with and without the Hp2-2 phenotype separately and when stratified within pre-specified race/ethnicity-based subgroups. Time-varying (achieved) HbA1c data (<7.0 % or ≥8.0 % compared to 7.0–7.9, updated every 3 months) were also analyzed in relation to CAD risk within each phenotype. Results567 (32.5 %) participants had the Hp2-2 phenotype. Compared to standard therapy, intensive glycemic control was not associated with risk of CAD among participants with the non-Hp2-2 or the Hp2-2 phenotype or for any race/ethnicity-based group. Compared to HbA1c of 7.0–7.9 %, having HbA1c <7.0 % was not associated with CAD risk for either phenotype or among any race/ethnicity-based group. Having HbA1c ≥8.0 % was associated with an increased risk of CAD among Hispanic participants without the Hp2-2 phenotype (HR= 3.61, 95 % CI: 1.54–8.41, p-interaction=0.53). ConclusionThe effect of intensive glycemic therapy on CAD events was not dependent on Hp phenotype in the VADT study of veterans with severe diabetes who may represent a population where Hp phenotype information would not be useful for personalizing diabetes management. However, further research is needed to determine if these results are conclusive.

Insulin sensitivity estimates and their longitudinal association with coronary artery disease in type 1 diabetes. Does it matter?

BackgroundInsulin resistance and chronic kidney disease are both associated with increased coronary artery disease risk. Many formulae estimating glucose disposal rate in type 1 diabetes infer insulin sensitivity from clinical data. We compare associations and performance relative to traditional risk factors and kidney disease severity between three formulae estimating the glucose disposal rate and coronary artery disease in people with type 1 diabetes.MethodsThe baseline glucose disposal rate was estimated by three (Williams, Duca, and Januszewski) formulae in FinnDiane Study participants and related to subsequent incidence of coronary artery disease, by baseline kidney status.ResultsIn 3517 adults with type 1 diabetes, during median (IQR) 19.3 (14.6, 21.4) years, 539 (15.3%) experienced a coronary artery disease event, with higher rates with worsening baseline kidney status. Correlations between the three formulae estimating the glucose disposal rate were weak, but the lowest quartile of each formula was associated with higher incidence of coronary artery disease. Importantly, only the glucose disposal rate estimation by Williams showed a linear association with coronary artery disease risk in all analyses. Of the three formulae, Williams was the strongest predictor of coronary artery disease. Only age and diabetes duration were stronger predictors. The strength of associations between estimated glucose disposal rate and CAD incidence varied by formula and kidney status.ConclusionsIn type 1 diabetes, estimated glucose disposal rates are associated with subsequent coronary artery disease, modulated by kidney disease severity. Future research is merited regarding the clinical usefulness of estimating the glucose disposal rate as a coronary artery disease risk factor and potential therapeutic target.

Combined sodium-glucose-transporters inhibitors and glucagon-like-peptide receptor agonist compared with monotherapy improves long-term survival: A Real-World Registry

BackgroundThe benefits of new glucose-lowering agents on cardiovascular disease have been demonstrated in randomized clinical trials. However, more evidence is required to assess the additive value of a combined therapy based on sodium-glucose transporter inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1ra) in a real-world population. MethodsA non-concurrent prospective study was conducted using integrated electronic medical records from primary care and hospitals obtained through 'Big data' technologies in a healthy area in Galicia. The study involved patients who were given SGLT2i, GLP1ra, or both treatments between January 2018 and June 2022 and were categorized as either mono or combined therapy (SGLT2i, GLP1ra, or both). The cumulative risk for different events: hospitalization and/or mortality for a) coronary artery disease, b) heart failure, c) cerebrovascular accident, and all-cause mortality were represented by Kaplan Meier curves and multivariate Cox regression analysis to obtain the hazard rate (HR) and (95% confidence interval (CI)). Validation was performed in a subpopulation with a propensity score matching. ResultsThe patients (15,549) who were included were 68 (12) years old, with 41% of them being females and 46% experiencing obesity. The median (interquartile range) of follow-up was 19 (8-33) months. The Kaplan-Meier analysis determined that the cumulative risk for coronary artery disease and cerebrovascular accident events was similar among the 3 different therapy groups. However, the combined therapy vs. SGLT2i reduced the risk of, heart failure events (HR: 0.69 [95% CI; 0.56-0.87]) or all-cause mortality (HR: 0.68 [95% CI;0.54-0.86]). Multivariate Cox regression analysis, after matching with a propensity score, confirmed the benefits of combined therapy regarding SGLT2i or GLP1ra monotherapy. ConclusionCompared to SGLT2i or GLP1ra alone, combined therapy SGLT2i + GLP1ra reduces heart failure risk and all-cause mortality in a real-world population.

Deep learning approach for cardiovascular disease risk stratification and survival analysis on a Canadian cohort.

The quantification of carotid plaque has been routinely used to predict cardiovascular risk in cardiovascular disease (CVD) and coronary artery disease (CAD). To determine how well carotid plaque features predict the likelihood of CAD and cardiovascular (CV) events using deep learning (DL) and compare against the machine learning (ML) paradigm. The participants in this study consisted of 459 individuals who had undergone coronary angiography, contrast-enhanced ultrasonography, and focused carotid B-mode ultrasound. Each patient was tracked for thirty days. The measurements on these patients consisted of maximum plaque height (MPH), total plaque area (TPA), carotid intima-media thickness (cIMT), and intraplaque neovascularization (IPN). CAD risk and CV event stratification were performed by applying eight types of DL-based models. Univariate and multivariate analysis was also conducted to predict the most significant risk predictors. The DL's model effectiveness was evaluated by the area-under-the-curve measurement while the CV event prediction was evaluated using the Cox proportional hazard model (CPHM) and compared against the DL-based concordance index (c-index). IPN showed a substantial ability to predict CV events (p < 0.0001). The best DL system improved by 21% (0.929 vs. 0.762) over the best ML system. DL-based CV event prediction showed a ~ 17% increase in DL-based c-index compared to the CPHM (0.86 vs. 0.73). CAD and CV incidents were linked to IPN and carotid imaging characteristics. For survival analysis and CAD prediction, the DL-based system performs superior to ML-based models.

Association of triglyceride-glucose index with adverse cardiovascular events in patients with established coronary artery disease according to different inflammatory status

Background and aimsThis study aimed to investigate the association of the triglyceride-glucose (TyG) index, a simple-but-reliable indicator of insulin resistance, with risk of cardiovascular (CV) events in coronary artery disease (CAD) patients with different inflammation status. Methods and resultsWe consecutively recruited 20,518 patients with angiograph-proven-CAD from 2017 to 2018 at Fuwai Hospital. Patients were categorized according to baseline TyG index tertiles (T) (tertile 1: ≤8.624; T2: 8.624–9.902 and T3: >9.902) and further assigned into 6 groups by high-sensitivity C-reactive protein (hsCRP) medians. The primary endpoint was CV events including CV death, nonfatal myocardial infarction and nonfatal stroke. During the 3.1-year-follow-up, 618 (3.0%) CV events were recorded. Overall, patients with high TyG index levels (T2 or T3) showed significantly increased risk of CV events (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.01–1.53; HR: 1.33; 95%CI: 1.05–1.68, respectively) compared with those with lowest Tyg index (T1) after adjusting for confounding factors. Upon stratification by hsCRP levels, elevated TyG index was associated with increased risk of CV events only in patients with hsCRP levels > median (per-1-unit-increase HR: 1.39; 95%CI: 1.11–1.74), rather than in those with hsCRP levels ≤ median. Furthermore, adding the TyG index to the predicting model led to a significant improvement in patients with hsCRP > median rather than in those with hsCRP ≤ median. ConclusionsWe firstly found that elevated TyG index levels were associated with increased risk of CV events in CAD patients, especially in those with increased inflammatory status, suggesting that it could help in risk stratification and prognosis in this population.

Metabolic Obesity Phenotypes and Incident Cardiovascular Outcomes in Middle-Aged and Older Korean Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study.

Background: This study investigated the association of four metabolic obesity phenotypes with incident coronary artery disease and stroke in a large-scale, community population-based, prospective Korean cohort observed for over 10 years. Methods: The study participants included 7374 adults aged 40-69 years, drawn from the Korean Genome and Epidemiology Study. Participants with different metabolic obesity phenotypes were categorized according to body weight and metabolic health status into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Combined cardiovascular events were defined as coronary artery disease and stroke. We used multivariate Cox proportional hazards regression models to prospectively assess hazard ratios (HRs) with 95% confidence intervals (CIs) for incident coronary artery disease or stroke over 10 years after the baseline survey. Results: During the follow-up period, newly developed coronary artery disease, stroke, and combined cardiovascular events were diagnosed in 151 (2.0%), 137 (1.9%), and 283 (3.8%) participants, respectively. After adjusting for confounding variables, the HRs (95% CIs) for incident combined cardiovascular events were 1.81 (1.34-2.46) in the MUHO group, 1.29 (0.92-1.81) in the MUHNO group, and 1.21 (0.81-1.79) in the MHO group compared with those in the MHNO group. Conclusions: This study revealed distinct risks associated with four metabolic obesity phenotypes concerning incident coronary artery disease and stroke. After adjusting for potential confounding variables, the results indicated that MUHO, but not MUHNO or MHO, showed a higher risk of developing coronary artery disease and stroke than MHNO.

Footsteps to Wellness: A Systematic Review and Meta-Analysis of Walking Pace and Coronary Artery Disease Event.

Coronary artery disease (CAD) poses a global health challenge, necessitating effective preventive strategies. Despite the pivotal role of physical activity in cardiovascular health, many fall short of recommended guidelines for daily physical activity. Simple and accessible, walking presents an opportunity, with increased pace emerging as a potential strategy for reducing the risk of cardiovascular diseases. Thus, we aimed to elucidate the potential association between walking pace and the risk of CAD events in adults without a prior history of CAD through a systematic review. We searched PubMed, Scopus, Web of Science, and ScienceDirect without publication date restrictions to identify prospective cohorts that analyzed walking pace and adult CAD events. The literature search conducted from April 02, 2023, to August 21, 2023, identified a total of four studies (six cohorts) for meta-analysis using random-effects models. The Newcastle-Ottawa Scale was used to assess study quality, and data extraction involved two independent reviewers. The analysis calculated overall relative risks (RRs) and 95% confidence intervals (CIs) for those with the quickest walking paces compared to those with the slowest walking paces. A funnel plot analysis for publication bias and subgroup analysis were also conducted. Results from the meta-analysis involving 160,519 participants and 3,351 CAD events demonstrated a 46% decreased risk for those walking at the quickest pace (pooled RR = 0.54, 95% CI = 0.45-0.66). No significant heterogeneity was observed. In conclusion, walking pace emerges as a significant risk factor for CAD events in adults without a prior history of CAD. It serves as a potential screening tool to identify individuals at higher risk. Promoting a faster walking pace as a daily activity may effectively mitigate the burden of CAD.

Abstract MP34: Association of Biological Age Acceleration With Incident Type 2 Diabetes and Coronary Artery Disease

Introduction: Biological age (BA), compared to chronological age, offers a more accurate reflection of aging status and prediction of cardiometabolic disease mortality. Genetics play an important role in the pathogenesis of type 2 diabetes (T2D) and coronary artery disease (CAD). However, the associations of BA acceleration with incident T2D and CAD as well as how the interactions between genetic risk and BA acceleration implicate in the development of these two diseases remain unclear. Hypothesis: We hypothesized that BA acceleration was significantly associated with incident T2D and CAD. We further hypothesized that there were significant interactions between BA acceleration and genetic risk in relation to risk of T2D and CAD. Methods: This prospective cohort study utilized data from the UK Biobank. BA was quantified by KDM-BA and PhenoAge, two composite measures derived from blood chemistry and physical examination data. T2D and CAD were diagnosed using self-reported medical history, medication, and hospital inpatient records. Multivariable Cox proportional hazard models were employed to estimate the associations of BA acceleration with incident T2D and CAD. A polygenic risk score (PRS) for T2D or CAD divided into tertiles was used to assess the interactions between BA acceleration (divided into quartiles) and genetic risk with regards to the development of T2D and CAD. Derived estimates were hazard ratios (HRs) and their 95% confidence intervals (CIs) per one standard deviation increment in each of the two BA measures. Results: This study analyzed 271,855 participants without T2D and 267,293 participants without CAD at baseline. Over a median follow-up time of 14.6 and 14.5 years, 9,562 incident T2D events and 18,509 incident CAD events occurred, respectively. Individuals with greater BA acceleration were at increased risk of T2D (HR for KDM-BA: 1.42, [95% CI: 1.39-1.46]; HR for PhenoAge: 1.23, [95% CI: 1.20-1.25]). Similarly, BA acceleration was significantly associated with a higher risk of CAD (HR for KDM-BA: 1.22, [95% CI: 1.20-1.25]; HR for PhenoAge: 1.12, [95% CI: 1.10-1.14]). People with greater genetic risk and BA acceleration had higher risks of T2D and CAD (P for interaction &lt; 0.002). Compared with participants with the lowest level of PRS and BA acceleration, those with the highest level of PRS and BA acceleration had a higher risk of developing T2D (HR for KDM-BA: 7.03, [95% CI: 6.16-8.02]; HR for PhenoAge: 6.39, [95% CI: 5.38-7.58]) and CAD (HR for KDM-BA: 2.83, [95% CI: 2.62-3.06]; HR for PhenoAge: 2.27, [95% CI: 2.09-2.46]). Conclusions: BA acceleration was significantly associated higher risks of T2D and CAD, especially among individuals with a high genetic predisposition to T2D and CAD.

Haptoglobin Phenotype and Intensive Glycemic Control for Coronary Artery Disease Risk Reduction in People With Type 2 Diabetes: The ADVANCE Study.

Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among participants with (n = 1,327) and without (n = 2,077) the Hp2-2 phenotype separately and within prespecified stratifications by sex, race, previous cardiovascular disease (CVD), diabetes duration, and HDL-cholesterol. While the hazard ratios (HRs) were in the hypothesized differing directions, compared with standard therapy, intensive glycemic control was not significantly associated with risk of CAD events among participants without (1.04, 95% CI 0.82-1.32) or with (0.84, 0.63-1.14, Pinteraction = 0.27) the Hp2-2 phenotype overall. Intensive therapy was associated with lower CAD risk among participants with the Hp2-2 phenotype who had no previous CVD (0.47, 0.29-0.76, Pinteraction = 0.01). Our findings suggest that intensive glycemic control contributes to the prevention of major CAD events among ADVANCE participants with the Hp2-2 phenotype and no previous CVD and are in alignment with our hypothesis that intensive glycemic control may be beneficial in a subset of people with the Hp2-2 phenotype.

An update on cardiovascular disorders in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a complex multifactorial etiology that develops as a result of autoimmune processes, leading to widespread inflammation and malfunction of multiple tissues and organs, and, as a consequence, triggers arterial hypertension, conduction disorders, valvular heart disease, pulmonary hypertension (PH), and venous thromboembolism events (VTE), contributing to increased mortality. Moreover, autoimmune abnormalities can accelerate atherogenesis and lead to many SLE manifestations, including coronary artery disease (CAD) and cerebrovascular events. The current review aimed to systematize existing data from the latest works and summarize published guidelines and recommendations. In particular, the prevalence of cardiovascular disorders in SLE patients, advances in diagnostics (including imaging methods and biomarker laboratory testing), the possible future direction of therapy, and the latest European Alliance of Associations for Rheumatology (EULAR) guidelines for optimal management of cardiovascular risk in SLE were overviewed.

Does fear of activity predict exercise capacity in patients with coronary artery disease in both sexes? A cross-sectional multicenter study.

This study aimed to identify whether fear of activity predicts exercise capacity in patients with coronary artery disease (CAD) and whether there is a difference between sexes regarding this relationship. One hundred ninety-seven patients (145 males, 52 females; mean age: 56.3±10.8 years; range, 22 to 80 years) with a diagnosis of CAD or cardiac event in the previous one to 60 months were enrolled in this cross-sectional multicenter study between November 2015 and February 2017. Demographic and clinical features were recorded. Fear of activity was assessed by the fear of activity scale in patients with CAD (FactCAD). A 6-min walk test was used to assess exercise capacity. Female participants were older, less educated, and less employed (p=0.045, p=0.048, and p<0.001, respectively) than males. Prevalence of myocardial infarction was higher in males. Comorbidities were higher in females. Multiple linear regression predicted 6-min walk distance (6MWD) based on FactCAD, sex, and education level with an r-squared of 0.321 (p<0.001). Fear of activity had an effect on walking distance in males (each additional score of FactCAD predicts a decrease of 1.3 m in 6MWD), together with disease duration, presence of chronic pulmonary disease, and low back pain, whereas fear of activity was not a predicting factor on walking distance in females. Age, education, and presence of angina predicted 6MWD in females. This study emphasizes that fear of activity is one of the predictors of 6MWD in males with CAD, and its assessment is recommended as a possible barrier to rehabilitation.

The Correlation between Region-specific Epicardial Adipose Tissue and Myocardial Ischemia Defined by CT-FFR in Type 2 Diabetes Mellitus Patients.

Epicardial Adipose Tissue (EAT) accumulation is closely associated with the presence and severity of coronary artery disease (CAD), myocardial ischemia, plaque vulnerability, and major adverse cardiovascular events. The aim of this study was to investigate the correlation between myocardial ischemia defined by computed tomography-derived fractional flow reserve (CT-FFR) and region-specific EAT in patients with type 2 diabetes mellitus (T2DM). Between January 2022 and May 2023, 200 T2DM patients were randomly selected from the Department of Endocrinology in The Central Hospital of Wuhan. These patients were divided into two groups based on myocardial ischemia defined by CT-FFR: myocardial ischemia group (152 cases) and control group (48 cases). Both groups of patients used a post-treatment workstation to measure the thickness of region-specific EAT. Receiver operating characteristic (ROC) curve analysis and binary logistic regression were used to evaluate the correlation between various parameters and myocardial ischemia. Patients in the myocardial ischemia group had significantly higher values of age, male gender, systolic blood pressure, total cholesterol, triglycerides, LDL, HDL, fasting blood glucose, fasting insulin, HOMA-IR, EAT thickness in right ventricular wall, left atrioventricular groove, and superior and inferior interventricular groove. ROC curve analysis results showed that EAT thickness in the left atrioventricular groove had the largest area under the ROC curve for diagnosing myocardial ischemia (0.837 [95% CI 0.766-0.865]; P < 0.001). Binary logistic regression analysis showed that EAT thickness in the left atrioventricular groove was an independent risk factor for myocardial ischemia in patients with T2DM (P < 0.05). The EAT thickness in the left atrioventricular groove is an independent risk factor for myocardial ischemia in patients with T2DM. Adipose tissue in the left atrioventricular groove region plays a major role in EAT-mediated CAD.

Fixed combination of rivaroxaban and Aspirin: Tablet formulation and analytical method validation

Rivaroxaban and aspirin are commonly used antithrombotic agents in combination to prevent coronary artery disease (CAD) and atherothrombotic events in adult patients after acute coronary syndrome (ACS) with elevated cardiac biomarkers, or with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) in high-risk patients. The recommended dosage is 2.5 mg rivaroxaban twice daily in combination with 75–100 mg aspirin once daily. This study aimed to develop a fixed-dose combination tablet of rivaroxaban (2.5 mg) and aspirin (50 mg) to enhance medication adherence and decrease pill burden.Compatibility studies were conducted on the active ingredients to develop the product formula. The formula and the manufacturing procedure were chosen based on the risk assessment for each active substance, wet granulation with both actives intragranular was found to have faster dissolution than direct mix formulae. Furthermore, a validated reverse-phase HPLC stability indicator method was developed to detect APIs and their possible degradants.

Intensive lifestyle intervention in type 2 diabetes and risk of incident coronary artery disease for the common haptoglobin phenotypes: the Look AHEAD study

BackgroundIntensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Disease Risk in Diabetes (ACCORD) participants with the haptoglobin (Hp) 2-2 phenotype only. It remains unknown whether Hp phenotype modifies the effect of an intensive lifestyle intervention (ILI) on CAD in type 2 diabetes.MethodsHaptoglobin phenotype was measured in 4542 samples from the Action for Health in Diabetes (Look AHEAD) study. Cox regression models assessed the effect of ILI (focused on weight loss from caloric restriction and physical activity) versus diabetes support and education (DSE) on CAD events in each phenotype group, and within pre-specified subgroups including race/ethnicity, sex, history of cardiovascular disease, diabetes medication use, and diabetes duration.Results1590 (35%) participants had the Hp2-2 phenotype. The ILI did not lower glycated hemoglobin (%HbA1c) to < 6.5% in either phenotype, with a peak significant difference between treatment arms of 0.5% [non-Hp2-2] and 0.6% [Hp2-2]. The cumulative CAD incidence was 13.4% and 13.8% in the DSE arm and 12.2% and 13.6% in the ILI arm for non-Hp2-2 and Hp2-2 groups, respectively. Compared to DSE, the ILI was not associated with CAD among participants without (HR = 0.95, 95% CI 0.78–1.17) or with (0.89, 0.68–1.19) the Hp2-2 phenotype (p-interaction between Hp phenotype and ILI = 0.58). After Bonferroni correction, there were no significant results among any subgroups.ConclusionsHp phenotype did not modify the effect of the weight loss ILI on risk of CAD in Look AHEAD, potentially because it did not substantially impact glycemic control among participants with or without the Hp2-2 phenotype. Further research is needed to determine if these results are conclusive.

Coronary artery disease incidence, risk factors, awareness, and medication utilization in a 10-year cohort study

BackgroundThere is a substantial disparity in coronary artery disease (CAD) burden between Iran and other nations that place a strong emphasis on the assessment of CAD risk factors and individuals’ awareness and ability to control them.MethodsTwo thousand participants of a community-based Iranian population aged 20–74 years were investigated with a mean follow-up of 9.9 years (range: 7.6 to 12.2). An analysis of Cox regression was conducted to determine the association between CAD development and classic risk factors such as age, sex, smoking, physical activity, education, obesity, dyslipidemia, hypertension, and diabetes mellitus. Furthermore, we computed the population attributable fraction for these risk factors.ResultsAfter a follow-up period of nearly 10 years, 225 CAD events were reported, constituting 14.5% of the overall incidence. Nighty three percent of participants had more than one risk factor. Age was the most predictive risk factor, with a hazard ratio (HR) and confidence interval (CI) of 5.56 (3.87–7.97, p < 0.001) in men older than 45 and females older than 55 compared to lower ages. In comparison to females, males had an HR of 1.45 (CI: 1.11–1.90, p value = 0.006) for developing CAD. Nearly 80% of the patients had dyslipidemia, with a hazard ratio of 2.19 (CI: 1.40–3.44, p = 0.01). Among the participants, 28.9% had hypertension, and 52% had prehypertension, which had HRs of 4.1 (2.4–7.2, p < 0.001) and 2.4 (1.4–4.2, p < 0.001), respectively. Diabetes, with a prevalence of 17%, had an HR of 2.63 (CI: 2 -3.47, p < 0.001), but prediabetes was not significantly associated with CAD. Awareness of diabetes, dyslipidemia, and hypertension was 81%, 27.9%, and 48.1%, respectively. Regarding medication usage, the corresponding percentages were 51% for diabetes, 13.2% for dyslipidemia, and 41% for hypertension.ConclusionsCompared to previous studies in Iran and neighboring countries, the current study found a higher incidence of CAD, more prevalent risk factors, and a lower awareness and ability to control these risk factors. Thus, an effective preventive strategy is needed to reduce the CAD burden in Iran.

Dietary protein sources, genetics, and cardiovascular disease incidence

BackgroundTo explore the potential correlation between the amount and source of dietary protein and cardiovascular disease (CVD), as well as the potential impact of genetic susceptibility on these connections. MethodsWe performed a prospective analysis of 98,224 participants from the UK. We measured dietary protein intake using two 24-hour dietary recall interviews. To analyze the data, we used multivariable-adjusted Cox regression models and restricted cubic spline models. Additionally, we calculated weighted genetic risk scores. ResultsA total of 8818 new cases of CVD were documented, which included 4076 cases of coronary artery disease (CAD) and 1126 cases of stroke. The study found a J-shaped association (p nonlinearity = 0.005) between CVD risk and the percentage of energy obtained from consuming plant protein. Higher intake of plant protein and whole protein was associated with a decreased risk of CVD. On the other hand, larger intakes of animal protein was linked to a higher occurrence of CAD. Additionally, increased intake of plant protein was also linked to a lower incidence of stroke. Replacing 5 % of animal protein-based energy intake with plant protein-based energy intake resulted in a 5 % decrease in CVD risk. LimitationsThere remains an effect of residual confounders. ConclusionThe consumption of larger amounts of plant protein, whole protein, and nut protein was found to be associated with a lower risk of CVD events. Conversely, higher intakes of animal protein was associated with an increased risk of CAD events. Furthermore, replacing 5 % of energy intake from animal protein with energy intake from plant protein was found to reduce the risk of CVD by 5 %.

Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular toxicity from androgen deprivation therapy in men with prostate cancer.

312 Background: Androgen deprivation therapy (ADT) with agonists of the gonadotropin releasing hormone (GnRH) receptor (e.g. leuprolide) is associated with coronary artery disease and major adverse cardiovascular (CV) events. CHIP, an age-related expanded somatic blood cell clone without other hematologic abnormalities, is associated with inflammation and accelerated atherosclerosis. Whether CHIP is associated with adverse CV outcomes in patients receiving ADT is unknown. Methods: Twenty-five men with localized prostate cancer pursuing radiotherapy plus ≥ 6 months of leuprolide were enrolled on a prospective biorepository. Using pre-treatment blood samples, whole exome sequencing libraries were generated; identified variants were filtered to retain &lt;1% MAF variants found amongst the three most common CHIP genes ( DNMT3A, TET2, ASXL1). Pre-treatment and 6-month blood samples from each patient subsequently were analyzed using a commercially available, validated 4-protein risk score that is predictive of 4-year major adverse CV events (Prevencio Inc HART CVE, Seattle WA). Multivariable logistic regression measured the association of CHIP with increased CV risk after initiation of leuprolide, defined as a clinically significant rise in 4-protein risk score at six months compared with baseline. Results: Median age was 70 years (IQR 65-76), 10 men (40%) were Black, and 4 men (16%) had a history of myocardial infarction. CHIP gene variants were found in 7 men (28%). Amongst the men with CHIP variants, 6 (85.7%) were Black. Amongst the entire cohort, 11/25 (44%) men had a clinically significant rise in CV risk score after six months of ADT. These men, compared with those who did not experience a rise in CV risk, were more often Black (72.7% versus 14.3%), on anti-hypertensive medication (72.7% versus 14.3%), and had higher baseline LDL cholesterol level (median 98 versus 81 mg/dL). On univariate analysis, harboring ≥1 CHIP variant was associated with a significantly increased odds of having an elevated CV risk score after 6 months of ADT. On multivariable analysis, after adjusting for race, anti-hypertensive medication use, and baseline LDL cholesterol, harboring ≥1 CHIP variant was associated with increased odds of having an elevated CV risk score after 6 months of ADT (adjusted OR 1.44, 95% CI 0.88-1.83), which did not meet statistical significance but limited by small sample size. Conclusions: Six months of GnRH-agonist leuprolide resulted in a rise in CV risk score in 44% of this cohort. CHIP variants, identified in 28% of this cohort, was associated with increased odds of experiencing a rise in CV risk score. Notably, Black men were more likely to harbor CHIP and experience increased CV risk after 6 months of leuprolide, respectively. Larger studies are underway to determine if CHIP variants may serve as a biomarker of ADT-induced CV risk, especially in older Black men.

The Use of Coronary Imaging for Predicting Future Cardiovascular Events.

Despite advancements in coronary artery disease (CAD) treatment with drug-eluting stent, its morbidity and mortality remain high. In context, intravascular imaging-guided percutaneous coronary intervention (PCI) is increasingly recommended for better clinical outcomes in patient with CAD. Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS), as one of the intravascular imaging methods, is effective in detecting lipid-rich plaques, which is crucial for identifying high-risk or vulnerable plaques employing near-infrared light. High lipid core burden, as identified by NIRS-IVUS, correlates with an increased risk of adverse cardiac events and shows varying degrees of efficacy in plaque management and event prevention. This article addresses about how NIRS-IVUS can be used to predict event of CAD. The study highlights the crucial role of NIRS-IVUS in predicting future cardiovascular events. Findings indicate that the presence of high lipid core burden is related to increased risks of periprocedural myocardial infarction and reduced coronary flow during PCI. The study also outlines the predictive value of NIRS-IVUS in non-culprit lesions, where plaques with high lipid core burden significantly increase the occurrence of major adverse cardiac events as demonstrated in the PROSPECT II trial. In terms of therapeutic strategies, the study reviews the effectiveness of high-intensity lipid-lowering strategies in stabilizing vulnerable plaques, as evidenced in trials such as the YELLOW and PACMAN AMI trials. NIRS-IVUS emerges as a valuable diagnostic tool in treating CAD. It effectively identifies vulnerable plaques and aids in predicting and preventing future adverse cardiac events. However, to enhance its practicality and promote widespread adoption in clinical settings, further long-term outcome research of NIRS-IVUS-guided PCI is necessary. These efforts can potentially make NIRS-IVUS a more accessible and indispensable tool in cardiovascular disease management.

C-Reactive Protein, Interleukin-6, and Vascular Recurrence According to Stroke Subtype: An Individual Participant Data Meta-Analysis

Anti-inflammatory therapies reduce major adverse cardiovascular events (MACE) in coronary artery disease but remain unproven after stroke. Establishing the subtype-specific association between inflammatory markers and recurrence risk is essential for optimal selection of patients in randomized trials (RCTs) of anti-inflammatory therapies for secondary stroke prevention. Using individual participant data (IPD) identified from a systematic review, we analyzed the association between high-sensitivity C-reactive protein, interleukin-6 (IL-6), and vascular recurrence after ischemic stroke or transient ischemic attack. The prespecified coprimary end points were (1) any recurrent MACE (first major coronary event, recurrent stroke, or vascular death) and (2) any recurrent stroke (ischemic, hemorrhagic, or unspecified) after sample measurement. Analyses were performed stratified by stroke mechanism, per quarter and per biomarker unit increase after loge transformation. We then did study-level meta-analysis with comparable published studies not providing IPD. Preferred Reporting Items for Systematic Review and Meta-Analyses IPD guidelines were followed. IPD was obtained from 10 studies (8,420 patients). After adjustment for vascular risk factors and statins/antithrombotic therapy, IL-6 was associated with recurrent MACE in stroke caused by large artery atherosclerosis (LAA) (risk ratio [RR] 2.30, 95% CI 1.21-4.36, p = 0.01), stroke of undetermined cause (UND) (RR 1.78, 1.19-2.66, p = 0.005), and small vessel occlusion (SVO) (RR 1.71, 0.99-2.96, p = 0.053) (quarter 4 [Q4] vs quarter 1 [Q1]). No association was observed for stroke due to cardioembolism or other determined cause. Similar results were seen for recurrent stroke and when analyzed per loge unit increase for MACE (LAA, RR 1.26 [1.06-1.50], p = 0.009; SVO, RR 1.22 [1.01-1.47], p = 0.04; UND, RR 1.18 [1.04-1.34], p = 0.01). High-sensitivity CRP was associated with recurrent MACE in UND stroke only (Q4 vs Q1 RR 1.45 [1.04-2.03], p = 0.03). Findings were consistent on study-level meta-analysis of the IPD results with 2 other comparable studies (20,136 patients). Our data provide new evidence for the selection of patients in future RCTs of anti-inflammatory therapy in stroke due to large artery atherosclerosis, small vessel occlusion, and undetermined etiology according to inflammatory marker profile.