Familial clustering and subsequent incidence of atrial fibrillation among first-degree relatives in Denmark

Abstract

Aims: Atrial fibrillation (AF) is associated with increased morbidity and mortality. Determination and quantification of familial risk may help identify high-risk patients.

Methods and results: Using Danish nationwide registry data (1978-2012), we identified all first-time AF patients (probands) in Denmark. Relatives to these probands were grouped according to proband-relation: offspring from either maternal or paternal proband, and siblings to proband. Age-specific incidence of AF for these three groups of relatives and for the general Danish population was estimated. Using the general population as reference, we calculated adjusted rate ratios (RRs) of AF in the three groups of relatives. We identified 67 310, 103 822, and 11 800 AF probands who were mothers (median age 74 years, IQR 66-81), fathers (70 years, IQR 62-78), and siblings (46 years, IQR 38-52), respectively. Among those, 133 516, 221 774, and 21 448 offspring from a maternal proband, offspring from a paternal proband, and siblings, respectively, were screened for incident AF. This was recorded in 2536 (1.9%), 2906 (1.3%), and 292 (1.4%) relatives, respectively. Compared with the general Danish population, the adjusted RRs for incident AF were 3.37 [95% confidence interval (CI) 3.21-3.53] for offspring from maternal probands, 2.81 (95% CI 2.69-2.93) for offspring from paternal probands, and 5.20 (95% CI 4.61-5.85) for siblings to sibling probands. Subgroup analyses showed increased RRs with younger aged probands.

Conclusion: Familial AF was associated with an increased RR of AF in first-degree relatives compared with the general Danish population. This suggests that familial AF is a major risk factor for developing AF in relatives.

Keywords: Arrhythmia; Atrial fibrillation; Genetics.