Abstract MP010: A Prospective Study of DNA Methylation Age Acceleration and Incidence of Coronary Heart Disease, Heart Failure, and Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: DNA methylation patterns used to characterize rate of aging (i.e., epigenetic age acceleration) predict all-cause mortality independently of chronological age and traditional risk factors. It remains unclear how epigenetic age acceleration is associated with cardiovascular disease risk and subclinical atherosclerosis. Hypothesis: Higher epigenetic age acceleration is associated prospectively with greater risk of coronary heart disease (CHD), heart failure (HF), and peripheral arterial disease (PAD) and cross-sectionally with higher carotid intima-medial thickness (IMT). Methods: Age acceleration of blood was estimated by two published methods (Horvath and Hannum) using DNA methylation levels (Illumina 450K array) at 353 and 71 CpG sites in African Americans of the Atherosclerosis Risk in Communities study in 1990-95 (baseline). Among those without prevalent disease at baseline, Cox and linear regression models were used to estimate the association of age acceleration with incident cardiovascular events occurring through 2013 and with carotid IMT cross-sectionally at baseline. Results were stratified by follow-up time for HF due to violation of the proportional hazards assumption. Results: Participants [mean baseline age: 57 years (range: 47-72)] were followed prospectively for a mean 17 years. In fully-adjusted models (Figure), a 1 SD increment in Hannum epigenetic age acceleration was associated with 15-31% greater hazard of incident cardiovascular outcomes, except for HF in later follow-up. Associations using Horvath age acceleration were similar, except it was not associated with myocardial infarction. Cross-sectionally, a 1 SD increment in each age acceleration measure was associated with 0.01 higher baseline carotid IMT (both P ≤ 0.01). Conclusion: This study of African Americans provides evidence that epigenetic age acceleration is associated with greater risk of CHD, HF, and PAD events and higher extent of carotid atherosclerosis, independently of traditional risk factors.