Epigenetic age acceleration is associated with cardiometabolic risk factors and clinical cardiovascular disease risk scores in African Americans

Clinical Epigenetics

Xiang Zhou¹  Sharon L. R. Kardia²  Farah Ammous²  Patricia A. Peyser²  Scott M. Ratliff²  Wei Zhao²  Lawrence F. Bielak²  Jennifer A. Smith³  Thomas H. Mosley⁴ 

[1] Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA;Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA;Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA;Survey Research Center, Institute for Social Research, University of Michigan, Ann Arbor, MI, USA;Memory Impairment and Neurodegenerative Dementia (MIND) Center, University of Mississippi Medical Center, Jackson, MS, USA;

关键词: Age acceleration;    DNA methylation;    Epigenetic age;    Cardiovascular disease;    Clinical risk scores;    Cardiometabolic risk factors;   

DOI  :  10.1186/s13148-021-01035-3

来源: Springer

【 摘 要 】

BackgroundCardiovascular disease (CVD) is the leading cause of mortality among US adults. African Americans have higher burden of CVD morbidity and mortality compared to any other racial group. Identifying biomarkers for clinical risk prediction of CVD offers an opportunity for precision prevention and earlier intervention.ResultsUsing linear mixed models, we investigated the cross-sectional association between four measures of epigenetic age acceleration (intrinsic (IEAA), extrinsic (EEAA), PhenoAge (PhenoAA), and GrimAge (GrimAA)) and ten cardiometabolic markers of hypertension, insulin resistance, and dyslipidemia in 1,100 primarily hypertensive African Americans from sibships in the Genetic Epidemiology Network of Arteriopathy (GENOA). We then assessed the association between epigenetic age acceleration and time to self-reported incident CVD using frailty hazard models and investigated CVD risk prediction improvement compared to models with clinical risk scores (Framingham risk score (FRS) and the atherosclerotic cardiovascular disease (ASCVD) risk equation). After adjusting for sex and chronological age, increased epigenetic age acceleration was associated with higher systolic blood pressure (IEAA), higher pulse pressure (EEAA and GrimAA), higher fasting glucose (PhenoAA and GrimAA), higher fasting insulin (EEAA), lower low density cholesterol (GrimAA), and higher triglycerides (GrimAA). A five-year increase in GrimAA was associated with CVD incidence with a hazard ratio of 1.54 (95% CI 1.22–2.01) and remained significant after adjusting for CVD risk factors. The addition of GrimAA to risk score models improved model fit using likelihood ratio tests (P = 0.013 for FRS and P = 0.008 for ASCVD), but did not improve C statistics (P > 0.05). Net reclassification index (NRI) showed small but significant improvement in reassignment of risk categories with the addition of GrimAA to FRS (NRI: 0.055, 95% CI 0.040–0.071) and the ASCVD equation (NRI: 0.029, 95% CI 0.006–0.064).ConclusionsEpigenetic age acceleration measures are associated with traditional CVD risk factors in an African-American cohort with a high prevalence of hypertension. GrimAA was associated with CVD incidence and slightly improved prediction of CVD events over clinical risk scores.

【 授权许可】

CC BY