Rationale:
Atrial Fibrillation (AF) and Heart Failure (HF) are major global health burdens. While genetics influence susceptibility, it remains unclear to what extent modifiable lifestyle factors can offset high genetic risk. Additionally, the intermediate cardiac structural changes (detectable via CMR) linking genetics to clinical phenotypes are not fully understood.
Research Questions:
Can adherence to a healthy lifestyle (optimal BMI, non-smoking, activity, diet) attenuate AF/HF risk across different genetic strata?
Do synergistic interactions exist between high genetic risk and unhealthy lifestyles?
Do cardiac imaging phenotypes mediate the association between risk factors and disease onset?
Objectives:
Construct Polygenic Risk Scores (PRS) for AF and HF using the latest GWAS data.
Derive a composite Healthy Lifestyle Score and evaluate its association with disease incidence using Cox proportional hazards models.
Quantify additive and multiplicative interactions between PRS and lifestyle factors.
Analyze associations between risk factors and cardiac remodeling markers in the imaging sub-cohort.
Impact:
Findings will inform personalized prevention strategies, emphasizing the potential of lifestyle interventions to mitigate genetic risks for cardiovascular diseases.
