Background: Prevalence of diastolic dysfunction increases significantly with aging and becomes more prevalent in middle-age to older adulthood. DNA methylation markers of aging have been identified and integrated into an epigenetic age (EA) score, which has been demonstrated to be associated with cardiovascular morbidity and mortality. Epigenetic age acceleration (EAA) is the residual value of EA methylation markers regressed on chronologic age (CA), and is thus independent of CA. Therefore, we sought to examine the association of a previously identified DNA methylation molecular signature in blood (EAA) with cardiac mechanics.
Methods: A subset of participants in the CARDIA cohort (n=1200) randomly selected (balanced on race and sex) underwent genome-wide DNA methylation profiling with the Illumina EPIC array from exam year 15 (2000-01 [age 33-45 years]) for calculation of EA and EAA. Echocardiography was completed at exam year 25 (2010-11 [age 43-55]). We used linear regression to examine the association of EA and EAA with parameters of cardiac mechanics. Models were adjusted for age, race, sex, education, study center, and Y15 cardiovascular risk factors (heart rate, body mass index, hypertension, hyperlipidemia, diabetes, and smoking).
Results: Mean age of participant was 45.4±3.5 years, 52% female, and 41% black. DNA methylation markers of aging (EA and EAA) were associated with tissue Doppler measures of diastolic function, but not with parameters of left ventricular structure and systolic function (Table).
Conclusions: EA and EAA are associated with changes in cardiac structure and function. Abnormalities in cardiac structure and function are an important intermediate phenotype prior to the development of symptomatic heart failure, and additional longitudinal research should examine DNA methylation markers as potential mediator of or novel biomarker for incident heart failure in young to middle-age adults.