Coronary Heart Disease Risk Reduction Research Articles

Abstract 4119941: Identification of individuals who benefit from omega-3 fatty acid supplementation to prevent coronary heart disease: A machine-learning analysis of the VITAL

Backgrounds: Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals would benefit the most from the supplementation. We sought to predict the individual treatment effect of omega-3 FA supplementation on CHD prevention and to develop an omega-3 effect score to stratify individuals according to their expected benefit from the supplementation. Methods: Among the 25,871 randomized participants without history of CVD in the VITamin D and OmegA-3 TriaL (VITAL), we applied machine-learning (ML) approaches to predict individual treatment effect of omega-3 FA supplementation on 5-year CHD risk (a composite of myocardial infarction, coronary revascularization, and CHD death) using 11 covariates pre-specified in the VITAL trial protocol. A 10-fold cross-validation was used and held-out test dataset was used for the evaluation. An omega-3 effect score was developed such that each covariate contributed linearly, and utility of the score was further evaluated by transportability analysis using the National Health and Nutrition Examination Survey (NHANES) data as the target population. Results: Omega-3 FA intervention led to absolute 0.48% [SE: 0.20] reduction in CHD in the total population. ML algorithms effectively stratified participants by their expected benefit according to individual factors; decreased CHD risk was observed in those with quintile 1 and 2 of the expected benefit (absolute CHD risk reduction %: 1.30 % [0.55] and 1.32 % [0.51] in quintile 1 and 2, respectively). Race, diabetes, and fish intake most contributed to the omega-3 effect score. CHD incidence rates per 1000 person-year were 5.5 [0.44] if treated and 8.5 [0.55] if not treated (35.3% reduction) in individuals with the score ≥11 (upper 40th percentile), and 3.9% [0.31] if treated and 3.4% [0.55] if not treated (14.7% increase) in those with the score <11, respectively. The transportability of the utility of the score to baseline NHANES data was confirmed. Conclusion: In VITAL, ML approaches identified individuals who experienced greater CHD reduction from the omega-3 FA intervention, and an omega-3 effect score stratified the expected benefit. Although it warrants testing in a new RCT, the omega-3 effect score holds promise for guiding the indication of omega-3 FA supplementation in US primary prevention population.

The influence of module-based coronary heart disease risk factor education on the level of patient knowledge at Hospital of PKU Muhammadiyah Yogyakarta

Background: Coronary heart disease (CHD) is a leading cause of morbidity and mortality worldwide. Effective patient education regarding CHD and its risk factors is essential for prevention and management. Purpose: This study aims to evaluate the effectiveness of a module-based educational intervention on improving patient knowledge of CHD risk factors. Methods: This quasi-experimental study employed a pre-test and post-test control group design. A total of 34 participants were selected via quota sampling, with 17 assigned to the intervention group and 17 to the control group. Participants' knowledge levels were measured using the Heart Disease Facts Questionnaire (HDFQ) before and after receiving education on CHD risk factors through a structured booklet and Counselling Events Units (SAP). Results: Statistical analysis using the Mann-Whitney test revealed a significant increase in the knowledge levels of the intervention group compared to the control group (p = 0.001), indicating the effectiveness of the module-based education. Conclusion: Module-based education on CHD risk factors significantly improves patient knowledge. This approach can be an effective educational tool in clinical settings for enhancing patient understanding and reducing CHD risk.

Blood lipid levels mediating the effects of sex hormone-binding globulin on coronary heart disease: Mendelian randomization and mediation analysis

Observational studies indicate that serum sex hormone-binding globulin (SHBG) levels are inversely correlated with blood lipid levels and coronary heart disease (CHD) risk. Given that dyslipidemia is an established risk factor for CHD, we aim to employ Mendelian randomization (MR) in conjunction with mediation analysis to confirm the mediating role of blood lipid levels in the association between SHBG and CHD. First, we assessed the causality between serum SHBG levels and five cardiovascular diseases using univariable MR. The results revealed causality between SHBG levels and reduced risk of CHD, myocardial infarction, as well as hypertension. Specifically, the most significant reduction was observed in CHD risk, with an odds ratio of 0.73 (95% CI 0.63–0.86) for each one-standard-deviation increase in SHBG. The summary-level data of serum SHBG levels and CHD are derived from a sex-specific genome-wide association study (GWAS) conducted by UK Biobank (sample size = 368,929) and a large-scale GWAS meta-analysis (60,801 cases and 123,504 controls), respectively. Subsequently, we further investigated the mediating role of blood lipid level in the association between SHBG and CHD. Mediation analysis clarified the mediation proportions for four mediators: high cholesterol (48%), very low-density lipoprotein cholesterol (25.1%), low-density lipoprotein cholesterol (18.5%), and triglycerides (44.3%). Summary-level data for each mediator were sourced from the UK Biobank and publicly available GWAS. The above results confirm negative causality between serum SHBG levels and the risk of CHD, myocardial infarction, and hypertension, with the causal effect on reducing CHD risk largely mediated by the improvement of blood lipid profiles.

Phytosterol intake and risk of coronary artery disease: Results from 3 prospective cohort studies

BackgroundPhytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol, although their impact on coronary artery disease (CAD) risk remains to be elucidated. ObjectivesThis study aimed to prospectively assess the associations between total and individual phytosterol intake and CAD risk in United States health professionals. MethodsThe analysis included 213,992 participants from 3 prospective cohorts—the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study—without cardiovascular disease or cancer at baseline. Diet was assessed using a validated food frequency questionnaire every 2–4 y since baseline. Associations between phytosterol intake and the risk of CAD, such as nonfatal myocardial infarction and fatal CAD, were evaluated using Cox proportional hazards regression models. ResultsMore than 5,517,993 person-years, 8725 cases with CAD were documented. Comparing extreme quintiles, pooled hazard ratios (95% CIs) of CAD were 0.93 (0.86, 1.01; P-trend = 0.16) for total phytosterols, 0.89 (0.82, 0.96; P-trend = 0.05) for campesterol, 0.95 (0.88, 1.02; P-trend = 0.10) for stigmasterol, and 0.92 (0.85, 1.00; P-trend = 0.09) for β-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and β-sitosterol: the risk reduction plateaued at intakes above ∼180, 30, and 130 mg/d, respectively (P-nonlinearity < 0.001). In a subset of participants (N range between 11,983 and 22,039), phytosterol intake was inversely associated with plasma concentrations of total cholesterol, triglycerides, high-density lipoprotein cholesterol, and IL-6 and positively associated with adiponectin, whereas no significant associations were observed for low-density lipoprotein cholesterol or C-reactive protein concentrations. ConclusionsHigher long-term intake of total and major subtypes of phytosterols may be associated with a modest reduction in CAD risk, displaying a nonlinear relationship that plateau at moderate intake levels. The role of phytosterols in preventing CAD warrants further investigation.

Comparing the drug target effects of Cholesteryl ester transfer protein (CETP) on cardiovascular diseases in East Asian and European populations

Abstract Introduction Cholesteryl ester transfer protein (CETP) is a drug target originally evaluated for raising HDL-C, for efficacy against coronary heart disease (CHD). Previous attempts to develop a licensed drug compound inhibiting CETP have heterogeneous CHD effects, which are likely attributable to the developed compound rather than CETP itself. Currently, novel CETP inhibitors are being pursued for the treatment of CHD. Drug target Mendelian randomization studies, leveraging genetic evidence, have shown that on-target CETP inhibition reduces CHD risk in individuals of European ancestries. However, similar MR studies conducted in East Asian ancestries have failed to show a CHD effect, questioning the value of pharmacological inhibition of CETP in this population. Purpose In this study, we compared drug target MR effects of CETP inhibition in Europeans and East Asians, focusing on cardiovascular efficacy outcomes, and relevant safety outcomes. Methods We used ancestry-specific GWAS summary statistics for Europeans (n=1,320,016) and East Asians (n=146,492) from the Global Lipids Genetics Consortium, taking variants from within and around ±50 kbp of the CETP locus. Colocalization was employed to determine potential trans-ancestry signals between CETP variants for HDL-C and LDL-C. Subsequently, drug target MR was used to estimate ancestry-specific effects of on-target CETP inhibition on 11 plasma biomarkers and 15 clinical outcomes between East Asian and European populations. Differences between ancestries were evaluated using interaction tests. Results There was strong support (posterior probability: 99.8%) of a shared causal CETP variant affecting HDL-C in both populations. Given the absence of a LDL-C signal in East Asians, similar colocalization was not observed for LDL-C. Employing drug target MR scaled to a standard deviation increase in HDL-C, we found that lower CETP had more pronounced decreasing effects in Europeans on LDL-C, LP[a], systolic blood pressure and pulse pressure (interaction p-values &amp;gt;1.9×10-3). Nevertheless, lower CETP protected against CHD, angina, intracerebral haemorrhage, and heart failure in both ancestries, for example for CHD (OR, 0.89; 95%CI, 0.84-0.94) in East Asians, compared to Europeans (OR, 0.95; 95%CI, 0.92-0.99, interaction p-value: 0.05). Exploring potential safety outcomes, lower CETP was protective against pneumonia in Europeans and East Asians (interaction p-value=0.53) and had a potential harmful effect on asthma and chronic kidney disease in East Asians (interaction p-value &amp;gt; 1.9×10-3). Conclusion In conclusion, on-target and sufficiently potent CETP inhibition is anticipated to prevent cardiovascular diseases in both European and East Asian populations.

Abstract P1045: Replacement Of Wearable-device-measured Sedentary Time By Physical Activity, Genetic Susceptibility, And Risk Of Coronary Heart Disease

Backgrounds: Excess sedentary time (ST) is recognized as an important modifiable risk factor for coronary heart disease (CHD). However, whether the associations of genetic susceptibility with CHD incidence can be modified by replacing wearable-device-measured ST with physical activity (PA) is unknown. This study aims to examine the combined associations of genetic susceptibility to CHD, and wearable-device-measured ST replaced by moderate-to-vigorous PA (MVPA) or light PA in relation to incident CHD. Methods and Findings: This study included 75,545 white British (57% female) with valid wrist-worn accelerometer data and without prevalent CHD/stroke from UK Biobank. Genetic susceptibility to CHD was quantified through weighted polygenic risk scores for CHD based on 300 single-nucleotide polymorphisms. Wrist-worn accelerometer data were used to derive ST, light PA and MVPA. The hazard ratio of CHD was 1.36 (95% CI: 1.03-1.80) for every-30-minute/day-increase in ST relative to other movement behaviors, after adjusting for genetic risk and confounders. Reallocation of any amount of ST (as little as 1 minute/day) into the same MVPA time (but not light PA) was associated with lower CHD hazards overall and within strata of genetic risk: no evidence of interaction between genetic risk and ST (p-value: 0.739). However, differences in absolute risk of CHD for ST replaced by MVPA were greater at high genetic risk versus low genetic risk. Limitations of our study include no causal evidence derived, limited generalizability to individuals of other ethnic groups or with sub-clinical symptoms, and potential residual confounding. Conclusions: Replacing any amount of ST with an equal amount of MVPA time is associated with a lower relative risk of developing CHD at all levels of genetic susceptibility to CHD. Potential reductions in absolute risk of CHD through replacement of ST by MVPA in equivalent amounts may be greater in individuals at high genetic risk of CHD.

Genetic Association and Potential Mediators between Sarcopenia and Coronary Heart Disease: A Bidirectional Two-Sample, Two-Step Mendelian Randomization Study.

To elucidate the bidirectional correlation of sarcopenia with coronary heart disease (CHD), as well as to investigate the mediating role of cardiometabolic factors and inflammatory biomarkers, a bidirectional two-sample, two-step Mendelian randomization (MR) study was conducted. Summary statistics were obtained from genome-wide association studies (GWAS). In our bidirectional two-sample MR, genetic variants associated with sarcopenia-related traits and CHD were instrumented for the estimation of bidirectional correlations. Besides, genetic variants associated with thirteen cardiometabolic factors and six inflammatory biomarkers were selected for further mediation analyses. To confirm the consistency of the results, several sensitivity analyses were carried out. Genetically predicted higher appendicular lean mass (OR = 0.835, 95% CI: 0.790-0.882), left hand grip strength (OR = 0.703, 95% CI: 0.569-0.869), right hand grip strength (OR = 0.685, 95% CI: 0.555-0.844), and walking pace (OR = 0.321, 95% CI: 0.191-0.539) reduced CHD risk, while genetic predisposition to CHD did not affect any of the sarcopenia-related traits. Seven mediators were identified for the effects of appendicular lean mass on CHD, including waist-to-hip ratio, hip circumference, systolic blood pressure, low-density lipoprotein cholesterol, total cholesterol, triglycerides, and fasting insulin. The mediation proportion ranged from 10.23% for triglycerides to 35.08% for hip circumference. Hip circumference was found to mediate the relationships between both left (mediation proportion: 24.61%) and right-hand grip strength (24.14%) and CHD, and the link between walking pace and CHD was partially mediated by waist-to-hip ratio (31.15%) and body mass index (26.66%). Our results showed that higher appendicular lean mass, hand grip strength, and walking pace reduced CHD risk, but the causal relationship was not bidirectional. Several mediators were found to mediate the causal pathways between sarcopenia-related traits and CHD, and intervention of these factors may be helpful in terms of CHD prevention in sarcopenia patients.

The relationship between polycystic ovary syndrome and coronary heart disease: a bibliometric analysis.

Polycystic ovary syndrome (PCOS) is one of the most common gynecological endocrine diseases for women of puberty and reproductive age. PCOS can affect women's health for the rest of their lives since the incidence of coronary heart disease (CHD) may increase in the perimenopausal and senile periods among PCOS women compared with non-PCOS women. A literature retrieval based on the Science Citation Index Expanded (SCI-E) database. All obtained records results were downloaded in plain text format for subsequent analysis. VOSviewer v1.6.10, Citespace and Microsoft Excel 2010 software were utilized for analyzing the following terms: countries, institutions, authors, journals, references and keywords. There were 312 articles retrieved from January 1, 2000 to February 8, 2023, and the frequency of citations was 23,587. The United States, England, and Italy contributed the majority of the records. Harvard University, the University of Athens, and Monash University were the top 3 most productive institutions with publications on the relationship between PCOS and CHD. Journal of clinical endocrinology & metabolism ranked first with the highest publications (24 records), followed by Fertility and sterility (18 records). The keywords were divided into six clusters in the overlay keywords network: (1) the correlation between CHD risk factors and PCOS women; (2) the relationship between cardiovascular disease and female reproductive system hormone secretion; (3) the interaction between CHD and metabolic syndrome; (4) the relationship between c-reactive protein and endothelial function and oxidative stress in PCOS patients; (5) the potential positive effect of metformin on reducing CHD risk factors in PCOS patients; (6) the study of serum cholesterol and body-fat distribution in patients with CHD in PCOS. Oxidative stress, genome-wide association, obesity, primary prevention, and sex difference were main hotspots in this field in recent five years according to the keyword citation burst analysis. The article obtained the hotspots and trends and provided a reference for subsequent research on the association between PCOS and CHD. Moreover, it is hypothesized that oxidative stress and genome-wide association were frontier hotspots in studies that explore the relationship between PCOS and CHD, and prevention research may be valued in the future.

Abstract P595: Low Serum Cholesterol and Coronary Heart Disease Mortality in Veterans

Background: The lipid hypothesis postulates that lower blood cholesterol is associated with reduced coronary heart disease (CHD) risk, which has been challenged by recent studies that observed a U-shaped relation between cholesterol and mortality. The effect of low cholesterol and CHD risk among Veterans is unclear. Methods: This prospective cohort study included Veterans greater than 18 years of age with baseline outpatient visits from 2002 to 2007 and follow-up to December 30, 2018 in the Veterans Health Administration electronic health record system. Veterans were followed to assess CHD mortality risk in relation to outpatient blood cholesterol levels. We used Cox proportional hazard regression to estimate the hazard ratio (HR) and 95% confidence interval (CI) of CHD mortality associated with total cholesterol (TC). Results: Among 4,467,942 Veterans, 381,871 CHD deaths were recorded. We observed a V-shaped relation between TC and age-, sex, race and smoking-adjusted risk of CHD mortality. The association became U-shaped after adjustment for statin use, body mass index, hypertension, and diabetes. When further adjusted for high-density lipoprotein level, 11 baseline diseases, and applying a 2-year lag analysis, the relation to CHD mortality was J-shaped--flat for TC&lt;180 mg/dL and greater risk was present at higher cholesterol levels. Compared to Veterans with TC between 180-199 mg/dL, risk for CHD mortality (HR (95%CI)) was 1.03 (1.02-1.04), 1.07 (1.06-1.09), 1.15 (1.13-1.18), 1.25 (1.22-1.28) and 1.45 (1.42-1.49) times greater among Veterans with TC (mg/dL) of 200-219, 220-239, 140-259, 260-279 and ≥280, respectively. Transition of the TC- CHD mortality patterns were J-J-J, V-U-J and L-U-J among young, middle, and older veterans (P for interaction between TC and age group &lt; 0.001). Similar J-shaped but weaker relations were observed in statin users at baseline. Conclusions: Based on prospective data for almost 4.5 million adult Veterans, CHD mortality risk steadily increased for TC ≥200mg/dL after adjustment for a range of health conditions. Our results support the lipid hypothesis that lower blood cholesterol is associated with reduced CHD risk and lower prevalence of multimorbidity, mental health disorders, nutritional deficits, and other risk factors for CHD. Furthermore, the hypothesis remained true when TC was low due to use of statins or other lipid-lowering medication. The changes in risk for CHD mortality by TC groups observed in our study (L- to U- to J-shape) highlights the importance of fully adjusting for the presence of multimorbidity and HDL-C to avoid misleading conclusions.

The association between meat intake and the risk of coronary heart disease in Korean men using the Framingham risk score: A prospective cohort study

Background and aimsResearch suggests that meat intake may increase the risk of coronary heart disease (CHD), but most studies take place in Western countries, where the types and amount of meat products consumed differ from those in Asian countries. We aimed to identify the association between meat intake and CHD risk in Korean male adults, using the Framingham risk score. Methods and resultsWe used data from the Korean Genome and Epidemiology Study (KoGES) Health Examinees (HEXA) study, including 13,293 Korean male adults. We estimated the association of meat intake with ≥20% 10-year CHD risk using Cox proportional hazards regression models to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Subjects with the highest total meat intake had a 53% (model 4: HR 1.53, 95% CI 1.05–2.21) increased 10-year CHD risk compared to those with the lowest intake. Those with the highest red meat intake had a 55% (model 3: HR 1.55, 95% CI 1.16–2.06) increased 10-year CHD risk compared to those with the lowest intake. No association was observed between poultry or processed meat intake and 10-year CHD risk. ConclusionsConsumption of total meat and red meat was associated with a higher risk of CHD in Korean male adults. Further studies are needed to provide criteria for the appropriate meat intake by meat type to reduce CHD risk.

Apolipoprotein Proteomics for Residual Lipid-Related Risk in Coronary Heart Disease.

Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls). The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a). Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM. Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.

Replacing Sedentary Behavior Time With Physical Activities, Recommended Physical Activity, and Incident Coronary Heart Disease

ObjectiveTo prospectively analyze the associations with coronary heart disease (CHD) risk of reallocating time from sedentary behavior to various physical activities using the isotemporal substitution model, particularly according to whether the participants meet the recommended physical activity level. MethodsWe included 455,298 UK Biobank participants free of CHD at baseline (March 13, 2006, to October 10, 2010). Sedentary behavior time was quantified by summing up the time spent on television watching, computer (not at work), and driving. Physical activities were categorized as daily-life activities (walking for pleasure, light do-it-yourself, and heavy do-it-yourself) and structured exercise (strenuous sports and other exercise). ResultsDuring a median follow-up of 11 years, 20,162 incident CHD cases were documented. Sedentary behavior time was significantly associated with a higher risk of CHD, independent of physical activity. Replacing 30 min/d of sedentary behavior with an equal time of various physical activities was associated with a 3% to 12% risk reduction of CHD. Replacing 1 h/d of sedentary behavior with different types of physical activities was associated with a 6% to 23% risk reduction of CHD. Sedentary behavior to strenuous sports reallocations showed the largest benefit. Reallocations of sedentary behavior to various physical activities showed particularly greater benefits among those who did not meet the physical activity recommendations. ConclusionsReplacing sedentary behavior time with various daily-life activities or structured exercise is associated with significant reductions in CHD risk.

Abstract 13262: Phytosterol Intake and Risk of Coronary Heart Disease in U.S. Men and Women

Introduction: Phytosterols are structurally similar to cholesterol and partially inhibit intestinal absorption of cholesterol. Evidence regarding dietary phytosterols in relation to coronary heart disease (CHD) risk remains limited. We aimed to prospectively assess the associations between total and individual phytosterol intake and CHD risk in U.S. men and women. Methods: A total of 214,108 men and women from the Nurses’ Health Study (NHS), NHSII, and Health Professionals Follow-Up Study without cardiovascular disease or cancer at baseline were included in the analyses. Diet was assessed using a validated food frequency questionnaire every 2-4 years since baseline. Cox proportional hazards regression models were used to evaluate associations between phytosterol intake and CHD risk. Results: During 5,516,455 person-years of follow-up, 10,152 CHD cases were documented. Comparing extreme quintiles, pooled hazard ratios (HRs) (95% CIs) of CHD were 0.91 (0.85-0.98; P -trend=0.08) for total phytosterols, 0.88 (0.82-0.95; P -trend=0.02) for campesterol, 0.96 (0.90-1.02; P -trend=0.22) for stigmasterol, and 0.91 (0.84-0.98; P -trend=0.03) for beta-sitosterol. Nonlinear associations were observed for total phytosterols, campesterol, and beta-sitosterol: the risk reduction plateaued at intakes above ~180 mg/day, 30 mg/day, and 130 mg/day, respectively ( P -nonlinearity&lt;0.001). Among 23,543 participants with existing CHD risk markers, phytosterol intake was inversely associated with plasma levels of total cholesterol, triglycerides, C-reactive protein, and interleukin-6, and was positively associated with adiponectin. Phytosterol intake was not associated with LDL or HDL cholesterol levels. Conclusions: Higher long-term intake of total and major subtypes of phytosterols was associated with modest CHD risk reduction, which may plateau at moderate intake levels. The role of phytosterols in preventing CHD needs further investigation.

Does Cardiovascular Disease Risk Decrease after Smoking Cessation in Occupational Risk Groups?

Smoking cessation is very important for workers due to the possibility of exposure to additional environmental risks in the workplace environment. This study was performed to determine the changes in the Framingham Risk Score (FRS) and 10-year risk of cardiovascular disease (CVD) of employees before smoking cessation and after 6 months. Five hundred and sixty-two employees who want to quit smoking were included in the study. In this prospective study, the baseline and 6-month FRS, and 10-year risk of CVD of workers were calculated. Furthermore, the Hospital Anxiety and Depression Scale was used for assessments of employees' anxiety and depression symptoms. After 6 months, 37% of the participants quit smoking. It was determined that 11.9% of employees have a high CVD risk and 10.6% moderate CVD risk. After 6 months, there was a statistically significant reduction in FRS who quit smoking (P < 0.001). In addition, within the 6 months after smoking cessation, 10-year coronary heart disease risk reduction was higher in quitters than those who cannot quit smoking (47.6% decrease in quitters and 14.9% in nonquitters, P < 0.001). Significant decreases in fasting blood glucose levels were determined after smoking cessation (P = 0.003). The FRS and CVD risk of smoker employees were decreased 6 months after smoking cessation. In 6 months, CVD risk is reduced in almost half of those who quit smoking. Even in the short term, it is possible to reduce the CVD risk of a worker who quits smoking.

Development of a diet pattern assessment tool for coronary heart disease risk reduction

ObjectiveExisting diet indices have gaps including neglect of the patterns of intake known to affect the final metabolic impact and use of measurement units prone to reporting error, and have applicability that is limited to specific populations. This study sought to develop a tool for diet-pattern assessment (Prudent Approach to Cardiovascular Epidemic, for Indians – Diet Quality Index (iPACE-DQI)) to reduce diet-related coronary-heart-disease (CHD) risk. Study designThe iPACE-DQI was developed on a 0–100 points scale (higher numeric value healthier). A proof-of-concept analysis was done to examine its construct validity and relation with risk-markers. MethodsDevelopment of iPACE-DQI was partly guided by ‘prudent diet’ principles, with assessment focus on quality, quantity, and the pattern of intake. In the second part of the study, construct validity was evaluated by association of iPACE-DQI score with nutrients. Further, relationship of the score with risk-markers high-sensitivity C-reactive protein(hs-CRP), body-mass-index(BMI) and body-fat-percent was examined at single-point-in-time (baseline), and predictive ability of score change on hs-CRP change was evaluated in a proof-of-concept 12-weeks pre-post intervention, among free-living Indians (25–44years,n = 55) in an urban setting. ResultsThe iPACE-DQI consists of eight main components. Associations of iPACE-DQI score with mean daily intake of key nutrients were robust and in expected direction [total-dietary-fiber (r = 0.5, p < 0.001), crude-fiber (r = 0.6, p < 0.001), protein (r = 0.5, p < 0.001), total-fat (r = −0.4, p = 0.002), vitamin-C (r = 0.5, p < 0.001), total-carbohydrate (r = 0.3, p = 0.017)]. Trends of hs-CRP, BMI and body-fat-percent across increasing diet-pattern score showed highest degree of abnormality in lowest tertile (≤35). Logistic regression model indicated higher likelihood for hs-CRP reduction (OR: 1.6, 95% CI 0.5–4.9) among those with ≥20% increase in iPACE-DQI score as compared with <20% increase or no-increase over 12-weeks ConclusionThe iPACE-DQI is a 100-point scale that assesses diet-pattern with respect to CHD-risk. The proposed tool could be useful for researchers/health practitioners to track diet-pattern change and concomitant CHD-risk reduction.

Missense Variant rs28362680 in BTNL2 Reduces Risk of Coronary Heart Disease.

BackgroundThe pathological basis of coronary heart disease (CHD) is atherosclerosis. BTNL2 can inhibit the activation of T cells. We aimed to explore the association between BTNL2 genetic variants and CHD risk in the southern Chinese Han population.MethodsWe recruited 1419 participants to perform an association analysis between missense variants in BTNL2 and CHD risk through SNPStats online software. Genotyping of all candidate SNPs were completed by the Agena MassARRAY. In addition, we used false-positive report probability analysis to detect whether the positive findings were noteworthy observations. We also used Haploview 4.2 software and SNPStats online software to conduct the haplotype analysis and analysis of linkage disequilibrium (LD). Finally, the interaction of SNP-SNP in CHD risk was evaluated by multi-factor dimensionality reduction (MDR).ResultsThe results showed that BTNL2-rs35624343, -rs117896888, -rs41441651, -rs41417449, -rs28362680 and -rs2076523 were significantly associated with the CHD susceptibility. Especially for BTNL2-rs28362680, the allele A (OR = 0.68, p < 0.0001), genotype AA (OR = 0.40, p = 0.001) or GA (OR = 0.68, p < 0.0001) were associated with the reducing CHD risk. And -rs28362680 significantly reduced the CHD risk under all genetic models (dominant: OR = 0.64, p < 0.0001; recessive: OR = 0.47, p = 0.003; overdominant: OR = 0.73, p = 0.004; log-additive: OR = 0.66, p < 0.0001). And -rs28362680 was also closely associated with CHD risk reduction in all stratified analyses (age, gender, smoking, drinking, hypertension and diabetes). In addition, haplotype analysis showed that the “Crs117896888Crs41441651Trs41417449Ars28362680” (OR = 0.65, p < 0.0001) and “Grs117896888Trs41441651Crs41417449Ars28362680” (OR = 0.68, p = 0.013) may reduce CHD risk.ConclusionMissense variants (rs35624343, rs117896888, rs41441651, rs41417449, rs28362680, rs2076523) may be protective factors for the CHD risk. In particular, there were sufficient evidences that BTNL2-rs28362680 can protective CHD risk.

What characterizes event-free elderly FH patients? A comprehensive lipoprotein profiling

Background and aimsFamilial hypercholesterolemia (FH) is a genetic disorder characterized by lifelong elevated low-density lipoprotein cholesterol (LDL-C) and increased risk of premature coronary heart disease (CHD). Cholesterol-lowering therapy (statins) reduces CHD risk, but have been available only in the last 25 years, thus, elderly FH patients have been exposed to elevated LDL-C levels most of their life. Surprisingly, some of these have never experienced any CHD event, raising the question whether they present CHD resistant characteristics.Identifying possible cardioprotective biomarkers could contribute to future CHD preventive treatment, therefore, we aimed to identify metabolic markers in event-free elderly FH subjects. Methods and resultsWe used a high-throughput nuclear magnetic resonance (NMR) spectroscopy platform to quantify a large number of metabolites in serum samples from 83 FH patients ≥65 years, and analyze differences between subjects with (n = 39) and without (n = 44) CHD.Mean age was 70 years in both groups (57% and 38% female in the event-free group and CHD group, respectively). The event-free group had significantly higher levels of large and extra-large high-density lipoprotein (HDL) particles, and higher concentration of Apolipoprotein A1 (ApoA1) and cholesterol in HDL and HDL2 particles, compared to the CHD group (p ≤ 0.05 for all). ConclusionCHD resistant elderly FH patients have higher levels of large HDL particles. The mechanisms behind the event-free survival among these patients remain unclear; hence, a deeper understanding of the metabolic profile in event-free elderly FH subjects may lead to development of novel preventive therapies.

Abstract MP26: Replacing Sedentary Behavior Time With Various Daily-life Physical Activities And Structured Exercises, Recommended Physical Activity, And Incident Coronary Heart Disease

Introduction: While excessive sedentary behavior time has been associated with cardiovascular diseases, it is largely unknown to what extend substituting sedentary behaviors with various physical activities may offset the risk of coronary heart disease (CHD). Hypothesis: We hypothesize that reallocating time from sedentary behavior to various daily-life physical activities and structured exercises might be associated with lower risk of CHD. We particularly examined such reallocations according to whether or not the participants meet the recommended physical activity level. Method: A total of 468,960 UK Biobank participants free of CHD were included. Sedentary behavior time was quantified by summing up the time spent on television watching, computer use (not at work), and driving. Physical activities were categorized as daily-life activities (walking for pleasure, light DIY, and heavy DIY) and structured exercise (strenuous sports and other exercises). We used iso-temporal substitution model to estimate the effect of replacing sedentary behavior with each type of physical activity for the same amount of time. Results: During a median follow-up of 11 years, 7,982 incident CHD cases were documented. Sedentary behavior time was significantly associated with a higher risk of CHD, independent of physical activity. In comparison of the extreme categories (≥6 vs. &lt;2 h/d), the HR for CHD was 1.31 (95% CI: 1.18-1.46). Replacing 30 minutes of sedentary behavior per day with an equal time of various physical activities was significantly associated with a 3%-12% risk reduction of CHD. Replacing 1 hour of sedentary behaviors with different types of physical activities was associated with a 6%-23% risk reduction of CHD. Sedentary behavior-to-strenuous sports reallocations showed the largest reduction in CHD risk when replacing sedentary behavior. Moreover, reallocations of sedentary behavior to various physical activities showed particularly greater benefits among those who did not meet the physical activity recommendations. Conclusion: Our study indicates that replacing sedentary behavior time with various daily-life activities or structured exercise was associated with significant reductions in CHD risk.

Trajectories of body mass index and risk for coronary heart disease: A 38-year follow-up study.

ObjectiveObesity is a well-known risk factor for coronary heart disease (CHD), but there is little evidence on the effect of long-term trajectories of body mass index (BMI) over the life course. By using repeated assessments, the aim was to study the risk of CHD in adults during 38 years in different trajectories of BMI.MethodsA sample of 2129 men and women, aged 20–59 years at baseline, took part in four repeated interviews between 1980 and 2005. Data on BMI, medical history, lifestyle and socioeconomy were collected. Based on the World Health Organization categories of BMI, life course trajectories of stable normal weight, stable overweight, stable obesity, increasing BMI and fluctuating BMI were created. The individuals were followed through national registers for first hospitalization of CHD (389 events) until the end of 2017, and Hazard Ratios (HRs) were calculated, adjusted for age, sex, socioeconomic factors, lifestyle factors and metabolic comorbidities.ResultsStable normal weight in all assessments was the reference group. Those who had an increase in BMI from normal weight in the first assessment to overweight or obesity in later assessments had no increased risk of CHD, HR 1.04 (95% CI: 0.70–1.53). The HR for individuals with fluctuating BMI was 1.25 (0.97–1.61), for stable overweight 1.43 (1.03–1.98), for stable obesity 1.50 (0.92–2.55), and for stable overweight or obesity 1.45 (1.07–1.97), after full adjustments.ConclusionHaving a stable overweight or obesity throughout adult life was associated with increased CHD risk but changing from normal weight at baseline to overweight or obesity was not associated with increased CHD risk. Prevention of obesity early in life may be particularly important to reduce CHD risk.

Invention of MK-8262, a Cholesteryl Ester Transfer Protein (CETP) Inhibitor Backup to Anacetrapib with Best-in-Class Properties.

Cholesteryl ester transfer protein (CETP) represents one of the key regulators of the homeostasis of lipid particles, including high-density lipoprotein (HDL) and low-density lipoprotein (LDL) particles. Epidemiological evidence correlates increased HDL and decreased LDL to coronary heart disease (CHD) risk reduction. This relationship is consistent with a clinical outcomes trial of a CETP inhibitor (anacetrapib) combined with standard of care (statin), which led to a 9% additional risk reduction compared to standard of care alone. We discuss here the discovery of MK-8262, a CETP inhibitor with the potential for being the best-in-class molecule. Novel in vitro and in vivo paradigms were integrated to drug discovery to guide optimization informed by a critical understanding of key clinical adverse effect profiles. We present preclinical and clinical evidence of MK-8262 safety and efficacy by means of HDL increase and LDL reduction as biomarkers for reduced CHD risk.