Abstract P037: Epigenetic Markers of Cardiovascular Health Trajectories and Coronary Artery Calcification in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Abstract

Background: Trajectory of AHA’s cardiovascular health (CVH) through young adulthood are associated with subclinical CVD. The human epigenome is modifiable by lifestyle and environmental factors and may be an important mechanism of CVH outcomes. We sought to determine associations of epigenetic markers with CVH trajectories and with coronary artery calcification (CAC) through young adulthood.

Methods: Among CARDIA ppts, we performed methylome analysis at follow up year (Y) 15 and Y20 using Illumina Methylation EPIC array (~850K CpG loci). We compared methylome between those with optimal CVH at baseline and remained stable (optimal-stable, n=645) and individuals with baseline optimal but declining CVH during follow up (n=100) to identify methylomic biomarkers of CVH trajectories. Differentially methylated CpGs were further examined in association with incident CAC risk at Y25 (n=745), and for their potential mediating role in CVH-associated CAC risk.

Results: In 1,087 CARDIA ppts (mean age=25 at baseline), we identified 25 hypermethylated CpGs (18 at Y15, 13 at Y20, including 6 seen at both Y15 and Y20) significantly associated with optimal-stable CVH trajectories. The 6 common CpGs were stable (mean ICC = 0.66) whereas the remaining 19 CpGs were dynamic (mean ICC = 0.39) over a 5-year interval. Hypermethylation of 6 stable CpGs was associated with a decreased risk of having future CAC incidence (Table 1). Hypermethylation of 10 (out of 19) dynamic CpGs at Y20 was associated with a decreased risk for incident CAC while the associations was less pronounced at Y15. Mediation analyses showed that hypermethylation of these 16 CpGs at Y15 and Y20 contributed 15% and 23% reduction in the CVH-associated relative risks (RRs) of CAC incidence at Y25.

Conclusion: We observed distinct methylomic patterns in young adulthood with stable optimal CVH trajectories relative to those with declining CVH. CVH associated methylomic marks may predict CAC incidence and potentially mediate the associations of CVH trajectories with incident CAC risk.