Abstract
Introduction: Atrial fibrillation is associated with increased morbidity and mortality. A genetic risk score (GRS) comprising 12 single nucleotide polymorphisms (SNPs) has been found to be associated with atrial fibrillation in population-based prospective studies of middle aged participants but this association has not been investigated in the elderly. Hypothesis: A pre-specified GRS for atrial fibrillation is associated with incident atrial fibrillation in the elderly. Methods: The Malmö Prevention Project (MPP) is a population-based prospective study of 18,240 participants who were enrolled in the study between 2002 and 2006. After excluding those with prevalent atrial fibrillation or missing clinical information 4,678 participants (median age of 68.2 years (IQR 66.5 to 73.0)) were randomly selected from the cohort for the current analysis. Cox proportional hazards models were used to estimate the association between GRS and incident atrial fibrillation after adjustment for age, sex, body mass index, systolic and diastolic blood pressure, use of antihypertensive medication, smoking, diabetes, coronary events, and heart failure. Results: Among 4,678 participants, 524 had a first atrial fibrillation event during a median 8.2 years follow-up. Participants in the top quintile of the GRS had two-fold greater risk of atrial fibrillation (HR = 2.03; 95%CI 1.54 to 2.67, P=5.0х10 -7 ) compared with those in the bottom quintile. The GRS was also associated in the elderly (those above median age, >68.2 years): HR=1.82 for those in the top quintile compared with those in the bottom quintile (95%CI 1.31 to 2.52, P=0.0003) as well as in those below median age (HR =2.68; 95%CI 1.58 to 4.55, P =0.0003). Conclusion: A pre-specified GRS for atrial fibrillation comprising 12 SNPs was associated with incident atrial fibrillation in the elderly. Patients with high genetic risk for atrial fibrillation may benefit from aggressive monitoring and control of blood pressure.
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