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 the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 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 mellitus, 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 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (
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.
|Year of Publication||
2018 03 06
|PubMed Central ID||
R01 HL139731 / HL / NHLBI NIH HHS / United States
K24 HL105780 / HL / NHLBI NIH HHS / United States
HHSN268201500001C / HL / NHLBI NIH HHS / United States
R01 HL104156 / HL / NHLBI NIH HHS / United States
R01 HL092577 / HL / NHLBI NIH HHS / United States
RC1 HL101056 / HL / NHLBI NIH HHS / United States
R01 HL128914 / HL / NHLBI NIH HHS / United States
R01 HL102214 / HL / NHLBI NIH HHS / United States
HHSN268201500001I / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
2014105 / Doris Duke Charitable Foundation / United States
K23 HL114724 / HL / NHLBI NIH HHS / United States