Familial atrial fibrillation predicts increased risk of mortality: a study in Danish twins.

BACKGROUND Atrial fibrillation (AF) is a common arrhythmia. Several studies have shown association of genetic variants with AF and that familial AF increases the risk of AF. We have previously shown a substantial heritability of AF in a twin study. The objective of this study was to determine whether having a co-twin with AF influences mortality. METHODS AND RESULTS We identified all Danish twins with AF born during and after 1912 in the Danish Twin Registry, the National Patient Registry, and the Central Office of Civil Registration. For each twin, we randomly identified 4 twins without AF, matched on sex, zygosity, and age. We compared survival among the co-twins of the affected twins (co-cases, n=2164) and the co-twins of the unaffected twins (co-controls, n=8626). The co-cases showed increased death rates compared with the co-controls (hazard ratio, 1.20; 95% confidence interval, 1.11-1.30; P<0.0001), and this effect was more pronounced in monozygotic twins (hazard ratio, 1.30; 95% confidence interval, 1.09-1.55; P=0.003), compared with dizygotic same sex (hazard ratio, 1.16; 95% confidence interval, 1.04-1.29; P=0.006) and opposite sex twins (hazard ratio, 1.20; 95% confidence interval, 0.97-1.47; P=0.093). CONCLUSIONS The mortality rate was 20% higher in twins who had a co-twin with AF than in twins without familial AF. This effect was almost doubled in monozygotic twins compared with dizygotic twins, suggesting the influence of genetic factors.