Rationale: Epigenetic aging is a novel measure of biological age, reflecting exposures and disease risks independent of chronological age. It may serve as a useful biomarker of cardiovascular health (CVH) or cardiovascular disease risk for early detection or prevention. Objective: To examine associations between GrimAge acceleration (GrimAA), a measure of epigenetic aging calculated from the residuals of GrimAge regressed on chronological age, and 2 repeated CVH measures: a full score for the AHA Life’s Simple 7 (diet, smoking, physical activity, body mass index, blood pressure, total cholesterol, and glucose) and a clinical CVH score (body mass index, blood pressure, cholesterol, and glucose). Methods and Results: We used Illumina array DNA methylation data from 2 prospective cohort studies, the CARDIA study (Coronary Artery Risk Development in Young Adults) and FHS (Framingham Heart Study), to calculate GrimAA and model associations with CVH. CARDIA randomly selected 1118 participants for assays at Y15 (2000–2001; mean age, 40 years) and Y20 (2005–2006); in FHS, 2106 Offspring participants had DNA methylation measured at exam 8 (2005–2008; mean age, 66 years). We examined multiple cross-sectional and longitudinal models of GrimAA and each CVH score measured at CARDIA Y0 to Y20 and FHS exams 7 to 8. In CARDIA, clinical CVH score from Y0 to Y20 was associated with Y15 and Y20 GrimAA (β range, −0.41 to −0.21 years per 1-point increase in CVH; P range, <0.01–0.01), as was full score (β range, −0.65 to −0.67 years; P <0.01 for all). These findings were validated in FHS (clinical score β range, −0.51 to −0.54 years; full score β range, −0.76 to −0.83 years; P <0.01 for all). Conclusions: Our data demonstrate that faster GrimAA is associated with the loss of CVH from young age. Epigenetic age may be a useful biomarker of cardiovascular disease risk and provides biological insight into the role of epigenetic mechanisms linking age-related CVH loss and cardiovascular disease.

Objectives. We evaluated the cross-sectional association between race and hysterectomy prevalence in a population-based cohort of US women and investigated participant characteristics associated with racial differences. Methods. The cohort consisted of 1863 Black and White women in the Coronary Artery Risk Development in Young Adults (CARDIA) study from 2000 to 2002 (years 15 and 16 after baseline). We used logistic regression to examine unadjusted and multivariable adjusted odds ratios. Results. Black women demonstrated greater odds of hysterectomy compared with White women (odds ratio [OR] = 3.52; 95% confidence interval [CI] = 2.52, 4.90). Adjustment for age, educational attainment, perceived barriers to accessing medical care, body mass index, polycystic ovarian syndrome, tubal ligation, depressive symptoms, age at menarche, and geographic location minimally altered the association (OR = 3.70; 95% CI = 2.44, 5.61). In a subset of the study population, those with directly imaged fibroids, the association was minimally attenuated (OR = 3.47; 95% CI = 2.23, 5.40). Conclusions. In both unadjusted and multivariable adjusted models, Black women, compared with White women, had increased odds of hysterectomy that persisted despite adjustment for participant characteristics. The increased odds are possibly related to decisions to undergo hysterectomy.

Background: Residential segregation, a geospatial manifestation of structural racism, is a fundamental driver of racial and ethnic health inequities, and longitudinal studies examining segregation’s influence on cardiovascular health are limited. This study investigates the impact of segregation on hypertension in a multiracial and multiethnic cohort and explores whether neighborhood environment modifies this association. Methods and Results: Leveraging data from a diverse cohort of adults recruited from 6 sites in the United States with 2 decades of follow‐up, we used race‐ and ethnicity‐stratified Cox models to examine the association between time‐varying segregation with incident hypertension in 1937 adults free of hypertension at baseline. Participants were categorized as residing in segregated and nonsegregated neighborhoods using a spatial‐weighted measure. We used a robust covariance matrix estimator to account for clustering within neighborhoods and assessed effect measure modification by neighborhood social or physical environment. Over an average follow‐up of 7.35 years, 65.5% non‐Hispanic Black, 48.1% Chinese, and 53.7% Hispanic participants developed hypertension. Net of confounders, Black and Hispanic residents in segregated neighborhoods were more likely to develop hypertension relative to residents in nonsegregated neighborhoods (Black residents: hazard ratio [HR], 1.33; 95% CI, 1.09–1.62; Hispanic residents: HR, 1.33; 95% CI, 1.04–1.70). Results were similar but not significant among Chinese residents (HR, 1.20; 95% CI, 0.83–1.73). Among Black residents, neighborhood social environment significantly modified this association such that better social environment was associated with less pronounced impact of segregation on hypertension. Conclusions: This study underscores the importance of continued investigations of groups affected by the health consequences of racial residential segregation while taking contextual neighborhood factors, such as social environment, into account.

Background: Cardiovascular health (CVH) from young adulthood is strongly associated with an individual’s future risk of cardiovascular disease (CVD) and total mortality. Defining epigenomic biomarkers of lifelong CVH exposure and understanding their roles in CVD development may help develop preventive and therapeutic strategies for CVD. Methods: In 1085 CARDIA study (Coronary Artery Risk Development in Young Adults) participants, we defined a clinical cumulative CVH score that combines body mass index, blood pressure, total cholesterol, and fasting glucose measured longitudinally from young adulthood through middle age over 20 years (mean age, 25–45). Blood DNA methylation at >840 000 methylation markers was measured twice over 5 years (mean age, 40 and 45). Epigenome-wide association analyses on the cumulative CVH score were performed in CARDIA and compared in the FHS (Framingham Heart Study). We used penalized regression to build a methylation-based risk score to evaluate the risk of incident coronary artery calcification and clinical CVD events. Results: We identified 45 methylation markers associated with cumulative CVH at false discovery rate <0.01 ( P =4.7E-7–5.8E-17) in CARDIA and replicated in FHS. These associations were more pronounced with methylation measured at an older age. CPT1A , ABCG1 , and SREBF1 appeared as the most prominent genes. The 45 methylation markers were mostly located in transcriptionally active chromatin and involved lipid metabolism, insulin secretion, and cytokine production pathways. Three methylation markers located in genes SARS1 , SOCS3 , and LINC-PINT statistically mediated 20.4% of the total effect between CVH and risk of incident coronary artery calcification. The methylation risk score added information and significantly ( P =0.004) improved the discrimination capacity of coronary artery calcification status versus CVH score alone and showed association with risk of incident coronary artery calcification 5 to 10 years later independent of cumulative CVH score (odds ratio, 1.87; P =9.66E-09). The methylation risk score was also associated with incident clinical CVD in FHS (hazard ratio, 1.28; P =1.22E-05). Conclusions: Cumulative CVH from young adulthood contributes to midlife epigenetic programming over time. Our findings demonstrate the role of epigenetic markers in response to CVH changes and highlight the potential of epigenomic markers for precision CVD prevention, and earlier detection of subclinical CVD, as well.