Stress-Related Methylation Risk Scores Predict Coronary Heart Disease

Intergenerational and life-course links between a cardiovascular health-related methylation score and early vascular changes

An LE8-derived DNAm score was associated with lower cIMT across the life course and, to a lesser extent, across generations, suggesting that blood DNAm reflects cumulative cardiovascular health and vascular burden and may complement conventional cardiovascular risk assessment.

Sex-specific effects of depression on the incidence and risk factors for coronary heart disease: insights from multi-omics approaches.

AIMS Depression and coronary heart disease (CHD) exhibit notable sex disparities; however, the sex-specific effect of depression on the development of CHD remains unexplored. We explored these effects using multi-omics approaches. METHODS AND RESULTS In the UK Biobank cohort, we conducted sex-stratified survival analyses and multi-omics investigations, including sex-specific two-sample and one-sample Mendelian randomisation (MR) analyses, reproductive factor assessments, Life's Essential 8 factor evaluations, and plasma proteomics analysis. Depression was associated with a higher risk of CHD in females (adjusted hazard ratio [aHR]: 1.30; 95% confidence interval [CI]: 1.24-1.37) than in males (aHR: 1.14; 95% CI: 1.09-1.19; P-interaction < 0.001), compared with individuals without depression. Sex-specific two-sample and one-sample MR analyses showed that genetically predicted depression in females was causally related to CHD, but no causal effect was observed in males. Some key reproductive factors in females with depression were associated with a high risk of CHD. Among the Life's Essential 8 factors, poor control of nicotine exposure, blood pressure, body mass index, and blood glucose had an additional effect on CHD risk in females with depression compared with that in males (all P-interaction < 0.05). Analysis of the UKB-PPP cohort revealed 26 proteins with sex-specific associations, predominantly significant in females. CONCLUSIONS Our findings highlight significant sex differences in the effect of depression on CHD risk, which could inform sex-specific preventive strategies for reducing the cardiovascular burden in individuals with depression.

Longitudinal associations between positive psychological factors and cardiovascular health

Background The health promoting effects of positive psychological factors in cardiovascular disease (CVD) are gaining increasing attention. Key factors such as optimism, mindfulness, positive affect, and life satisfaction have been linked to a lower incidence of CVD. While these effects are often explained by favorable health behaviors, potential biological mechanisms are insufficiently explored. Objectives We aimed to to investigate independent associations between positive psychological factors and prospective changes in intermediate biological coronary heart disease (CHD) risk factors in CHD-patients, hypertensives (HT), and normotensive controls (NT). Methods At baseline, 200 men (CHD=86,HT = 61,NT = 53) completed questionnaires on positive psychological factors and had blood samples collected. As CHD-risk factors lipid profiles (TC/HDL-ratio), blood glucose (HbA1c), coagulation (fibrinogen, D-dimer), and inflammation markers (CRP, IL-6, TNF-α) were measured. At 3-year follow-up, blood sample were collected from 126 men (NT = 34,HT = 37,CHD=55). Results At baseline, the groups differed in positive affect only [F(2,197) = 3.63, p = .028], with highest levels in NT and lowest levels in CHD. Prospectively, higher baseline positive affect (p = .026) and life satisfaction (p = .026) were associated with lower CHD-risk over time. Specifically, higher baseline positive affect predicted lower increase in coagulation markers (p = .010), particularly fibrinogen (ß=-0.37, p = .003), while higher baseline life satisfaction predicted lower increase in inflammation markers, especially IL-6 (ß=-.38, p = .005). Neither optimism nor mindfulness were linked to change in CHD-risk factors over time. Conclusion Positive affect and life-satisfaction may benefit cardiovascular health by favorably affecting coagulation and inflammation, with potential implications for CHD prevention and intervention strategies.

Leukocyte DNA methylation-based signatures for atherosclerotic cardiovascular disease risk prediction in the Million Veteran Program

Socioeconomic Status, lifestyle factors, and lipid profiles: a comprehensive analysis of cardiovascular risk factors in the UK biobank

Background Cardiovascular disease (CVD) remains a leading cause of mortality worldwide and is influenced by a complex interplay of modifiable and non-modifiable risk factors. Methods We analyzed data from 502,112 UK Biobank participants (mean age 56.53 years, 45.6% male) with complete lipid and sociodemographic information. Multiple regression analysis was employed to assess the relationships between cholesterol levels and various risk factors, while Cox proportional hazards models were used to explore associations with cardiovascular events. Results Increasing age was positively associated with cholesterol levels (β=0.0079, P < 0.001), whereas higher socioeconomic deprivation (Townsend deprivation index, TDI) correlated with lower cholesterol levels (β=−0.0151, P < 0.001). Compared to daily alcohol consumers, abstainers had significantly lower total cholesterol (β=−0.407, P < 0.001), with a dose-response pattern observed across alcohol intake categories. Male sex was strongly associated with higher cardiovascular risk (HR = 1.72, 95% CI: 1.14–2.6, P = 0.011). Moderate alcohol intake showed protective effects compared to daily consumption. Cholesterol levels alone were not significantly associated with cardiovascular events (HR = 0.94, 95% CI: 0.83–1.1, P = 0.316). Higher socioeconomic deprivation was inversely associated with both total cholesterol levels and cardiovascular events, contrary to some previous reports. Conclusions Our findings elucidate the complex relationships between social determinants, lifestyle factors, and cardiovascular risk. The results highlight the importance of considering socioeconomic context and lifestyle in CVD risk assessment, with potential implications for public health policy and personalized prevention strategies.

Proteomic signature of healthy dietary patterns and risk of cardiovascular disease in the framingham heart study.

BACKGROUND & AIMS Healthy dietary patterns are associated with a lower risk of cardiovascular disease (CVD). Proteomic correlates of healthy dietary patterns are understudied and may provide mechanistic insight and suggest putative markers between diet and CVD risk. We investigated the prospective association of a dietary proteomic score with cardiometabolic risk factors and CVD in a multi-generational cohort of middle-aged adults. METHODS We examined participants from the Framingham Heart Study Generation 2 (n = 1611, mean age 55 ± 10, 55.4% women) and Generation 3 (n = 862, mean age 46 ± 8, 56.6% women) who had complete dietary, proteomic, and covariate data, and were free from prevalent CVD. We analyzed plasma proteins using DNA aptamer-based technology, and three dietary pattern indices were derived from a semiquantitative food frequency questionnaire. With elastic net regression, we identified 11 diet-related proteins and created a weighted DPS, which had the strongest correlation with the DASH diet score (r = 00.30, p < 0.0001). RESULTS Over a median of 25 and 13 years we observed 533 CVD events. A 1-standard deviation (SD) increase in dietary proteomic score was associated with a 54% lower prevalence of Metabolic Syndrome (P ≤ 0.001) in multivariable-adjusted logistic regression models. Using multivariable Cox regression models adjusted for adjusting for lifestyle factors and the Dietary Approaches to Stop Hypertension (DASH) diet score, a 1-SD increase in the dietary proteomic score was associated with a 20% lower risk of CVD (HR [95% CI], 0.80 [0.73, 0.88]) and those in the highest tertile of the dietary proteomic score, compared to the lowest, had a 38% reduced risk of CVD (0.62 [0.49, 0.78]). However, these associations were attenuated after further adjustment for known cardiometabolic risk factors (1-SD: HR 0.94, [0.85, 1.04]; T3 vs T1: 0.81 [0.63, 1.03]). CONCLUSION A dietary proteomic score of three healthy dietary pattern indices was strongly associated with prevalent metabolic health cross-sectionally and incident CVD prospectively. These findings provide insight into the mechanisms linking diet quality and cardiometabolic health, and suggest future dietary proteomic studies in independent populations, as well as incorporating proteomics into dietary intervention trials.