Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation
Background—The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown.
Methods—We estimated lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of approximately 1,000 AF-associated single nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk.
Results—Among 4,606 participants without AF at age 55 years, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF after age 55 years was 37.1%, and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at age 55 years, those in low polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval [CI], 15.4%-29.1%), whereas those in high risk tertiles had a risk of 48.2% (95% CI, 41.3%-55.1%). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P value <0.001).
Conclusions—In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible, and together with clinical risk factor burden explains a substantial gradient in long-term AF risk.
- Received August 31, 2017.
- Accepted November 2, 2017.