Epigenetic Aging Clocks and Incident Cardiovascular Outcomes: Results From the MESA

Area of Science:

• Cardiovascular Disease Research
• Epigenetics and Aging
• Biomarker Discovery

Background:

• DNA methylation-based aging clocks assess biological age and may enhance cardiovascular risk prediction.
• Limited data exists on epigenetic clocks, incident cardiovascular outcomes, and their interaction with biomarkers like coronary artery calcium (CAC) in diverse populations.

Purpose of the Study:

• To investigate the association between epigenetic aging clocks (GrimAge, age acceleration) and incident cardiovascular disease outcomes.
• To examine the interplay between epigenetic aging clocks and coronary artery calcium (CAC) in predicting cardiovascular risk.

Main Methods:

• Retrospective cohort study of 1264 Multi-Ethnic Study of Atherosclerosis (MESA) participants.
• Assessed GrimAge and age acceleration from DNA methylation data.
• Utilized Cox proportional hazards models, adjusting for confounders and stratifying by CAC presence, to analyze associations with cardiovascular events.

Main Results:

• GrimAge independently predicted higher risk for composite cardiovascular disease, stroke, and heart failure with mildly reduced ejection fraction.
• Associations with myocardial infarction risk were significant in individuals with CAC > 0, but attenuated in those without baseline CAC.

Conclusions:

• Epigenetic aging clocks may provide cardiovascular risk information beyond traditional factors and interact with subclinical disease markers like CAC.
• Further research in diverse populations is needed to validate these findings and explore potential interventions targeting epigenetic aging or CAC.