High Familial Risk of Atrial Fibrillation/Atrial Flutter in Multiplex Families: A Nationwide Family Study in Sweden

Background-Although the heritability of atrial fibrillation/atrial flutter (AF/AFl) has been determined, the familial risk in multiplex families is unclear. The main aim of this nationwide study was to determine the familial risk of AF/AFl in multiplex families. Methods and Results-We examined the familial risk of AF/AFl in the entire Swedish population. We linked Multigeneration Register data on individuals aged 0 to 76 years with Hospital Discharge Register data for 1987-2008 and Outpatient Register data for 2001-2008 to compare AF/AFl risk among relatives of all 300 586 individuals with AF/AFl with that among relatives of unaffected individuals. We used conditional logistic regression to investigate differences in exposure between cases and controls. Parents (odds ratio [OR] 1.95 [95% CI 1.89 to 2.00]) and siblings (OR=3.08 [3.00 to 3.16]) of cases had higher odds of AF/AFl than did parents and siblings of controls. AF/AFl ORs were increased in both sexes. For 2% of cases, both parents had AF/AFl, compared with only 0.7% of controls (OR= 3.60 [3.30 to 3.92]). Moreover, 3% of cases had >= 2 siblings with AF/AFl, compared with 1% of controls (OR= 5.72 [5.28 to 6.19]). In premature cases (diagnosed at age < 50 years), the ORs were 5.04 (4.36 to 5.82) and 8.51 (6.49 to 11.15) for AF/AFl in both parents and AF/AFl in >= 2 siblings, respectively. The overall spouse OR was 1.16 (1.13 to 1.19). Conclusions-Family history of AF/AFl increases the odds of AF/AFl in first-degree relatives. High familial risks were observed in multiplex families.