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 (P<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.
['Weng|Lu-Chen|LC|', 'Preis|Sarah R|SR|', 'Hulme|Olivia L|OL|', 'Larson|Martin G|MG|', 'Choi|Seung Hoan|SH|', 'Wang|Biqi|B|', 'Trinquart|Ludovic|L|', 'McManus|David D|DD|', 'Staerk|Laila|L|', 'Lin|Honghuang|H|', 'Lunetta|Kathryn L|KL|', 'Ellinor|Patrick T|PT|', 'Benjamin|Emelia J|EJ|', 'Lubitz|Steven A|SA|']
D000328:Adult D000959:Antihypertensive Agents D001281:Atrial Fibrillation D015331:Cohort Studies D055812:Community-Based Participatory Research D005260:Female D005500:Follow-Up Studies D020022:Genetic Predisposition to Disease D006801:Humans D006973:Hypertension D008137:Longitudinal Studies D008297:Male D008875:Middle Aged D009203:Myocardial Infarction D020641:Polymorphism, Single Nucleotide D012307:Risk Factors D014481:United States
genetics risk factor lifetime risk atrial fibrillation polygenic risk epidemiology risk stratification