Familial atrial fibrillation was associated with an increased risk of new-onset atrial fibrillation compared to those without familial AF (HR 1.40; 95% CI 1.13-1.74).
Cohort (n=4,421)
Does familial AF predict new-onset AF beyond established risk factors in adults free of AF at baseline?
Familial AF, particularly premature familial AF, is an independent risk factor for new-onset AF and provides a very slight increase in predictive accuracy over traditional risk factors.
Effect estimate: HR 1.40 (95% CI 1.13-1.74)
Absolute Event Rate: 5.8% vs 3.1%
CONTEXT: Although the heritability of atrial fibrillation (AF) is established, the contribution of familial AF to predicting new-onset AF remains unknown. OBJECTIVE: To determine whether familial occurrence of AF is associated with new-onset AF beyond established risk factors. DESIGN, SETTING, AND PARTICIPANTS: The Framingham Heart Study, a prospective community-based cohort study started in 1948. Original and Offspring Cohort participants were aged at least 30 years, were free of AF at the baseline examination, and had at least 1 parent or sibling enrolled in the study. The 4421 participants in this analysis (mean age, 54 SD, 13 years; 54% women) were followed up through December 31, 2007. MAIN OUTCOME MEASURES: Incremental predictive value of incorporating different features of familial AF (any familial AF, premature familial AF onset ≤65 years old, number of affected relatives, and youngest age of onset in a relative) into a risk model for new-onset AF. RESULTS: Across 11,971 examinations during the period 1968-2007, 440 participants developed AF. Familial AF occurred among 1185 participants (26.8%) and premature familial AF occurred among 351 participants (7.9%). Atrial fibrillation occurred more frequently among participants with familial AF than without familial AF (unadjusted absolute event rates of 5.8% and 3.1%, respectively). The association was not attenuated by adjustment for AF risk factors (multivariable-adjusted hazard ratio, 1.40; 95% confidence interval CI, 1.13-1.74) or reported AF-related genetic variants. Among the different features of familial AF examined, premature familial AF was associated with improved discrimination beyond traditional risk factors to the greatest extent (traditional risk factors, C statistic, 0.842 95% CI, 0.826-0.858; premature familial AF, C statistic, 0.846 95% CI, 0.831-0.862; P = .004). Modest changes in integrated discrimination improvement were observed with premature familial AF (2.1%). Net reclassification improvement (assessed using 8-year risk thresholds of 10%) did not change significantly with premature familial AF (index statistic, 0.011; 95% CI, -0.021 to 0.042; P = .51), although categoryless net reclassification was improved (index statistic, 0.127; 95% CI, 0.064-0.189; P = .009). CONCLUSIONS: In this cohort, familial AF was associated with an increased risk of AF that was not attenuated by adjustment for AF risk factors including genetic variants. Assessment of premature familial AF was associated with a very slight increase in predictive accuracy compared with traditional risk factors.
Lubitz et al. (2010) conducted a cohort in Atrial fibrillation (n=4,421). Familial atrial fibrillation vs. No familial atrial fibrillation was evaluated on New-onset atrial fibrillation (HR 1.40, 95% CI 1.13-1.74). Familial atrial fibrillation was associated with an increased risk of new-onset atrial fibrillation compared to those without familial AF (HR 1.40; 95% CI 1.13-1.74).