Abstract P1013: Ideal cardiovascular health is associated with reduced epigenetic aging: cross-sectional findings from the INSPIRE-T cohort

Abstract

Introduction: Chronological age is the main non-modifiable risk factor for morbidity, but it cannot be the only factor responsible for these age-related changes. Several teams have taken an interest in the biological mechanisms underlying ageing and have developed biological clocks, in particular epigenetic clocks such as DNAm GrimAge. These clocks could help to identify factors protecting against accelerated ageing and associated diseases. In this context, our aim was to assess the association between ideal cardiovascular health and reduced epigenetic ageing. Method Our cross-sectional analysis included participants from the INSPIRE-T human translational cohort. Cardiovascular health (CVH) was assessed using the Life’s Essential 8 composite score (0 to 100 points, higher means better) and calculated as the average of 8 component metric scores (healthy diet, physical activity, avoidance of nicotine, healthy sleep, healthy weight, and healthy levels of blood lipids, glucose and blood pressure). Overall CVH scores of 80-100 points were considered high CVH, 50-79, moderate CVH; 0 to 49, low CVH. Epigenetic aging was derived from the residuals of a linear regression of epigenetic age calculated using the GrimAge epigenetic clock and chronological age. Linear regression models were used in the analyses. Results We included 937 subjects (age range 20-100, mean age 60 years, 67% men). On average, the subjects had an LE8 score of 68 points (± 9.7) and 11.7% had a high CVH. After adjustment for chronological age and sex, compared to those with low to moderate CVH, subjects with high CVH had reduced epigenetic aging (β = -1.1 ± 0.4, p =0.002). Among LE8 components and per 1-unit increase in scoring (0 to 100) physical activity (β = -0.9 ± 0.4, p =0.02), BMI (β = -1.3 ± 0.2, p <0.001), diabetic status (β = -0.4 ± 0.1, p =0.001), smoking status (β = -3.6 ± 0.3, p <0.001) and blood pressure level (β = -0.9 ± 0.3, p =0.004) were significantly associated with a reduction in epigenetic ageing. This association was not found for dietary score, lipid levels or sleep. Discussion Our study reported an association between ideal global CVH and optimal levels of multiple health behaviors and health factors with reduced epigenetic aging after adjustment for chronological age and sex. This suggests that epigenetic aging is potentially modifiable by healthy lifestyle and control of cardiovascular risk factors although a potential underlying causal relationship remains to be established.