Lone atrial fibrillation: Influence of familial disease on gender predilection

Gender and Lone AF. Introduction: Epidemiological studies report a male predominance in lone atrial fibrillation (LAF). Phenotypic differences between sporadic and familial LAF could aid in deciding which cases should undergo family screening. We sought to determine gender distribution in sporadic and familial LAF, gender-based differences, and phenotypic differences between sporadic and familial LAF. Methods: Since November 2000, 192 unrelated LAF probands were recruited. Sporadic LAF was defined as the absence of a family history of LAF. Familial LAF was classified as possible if one first- or second-degree relative had LAF, or confirmed if ≥ 2 relatives had LAF. Affected relatives (n = 87) of 34 confirmed familial probands were also evaluated. For unrelated LAF probands, differences in proportions and means were tested using χ² and ANOVA, respectively. Difference in gender ratio among the family history groups was tested using mixed models. Results: Male proportion was greater among sporadic (82%) and possible familial probands (84%) than confirmed familial probands (62%), and affected relatives (54%), P < 0.001. Sporadic LAF was more common in men (62%) than women (51%), P = 0.03. More women were affected by palpitation and nocturnal symptoms than men. More patients had permanent AF in the confirmed familial group (27%), compared with the possible familial (7%) and the sporadic LAF group (8%), P = 0.05, but no other phenotypic discriminators were identified. Conclusions: Male predilection for LAF is attenuated as the likelihood of dominant Mendelian inheritance increases. Increased frequency of "sporadic" LAF among men could be partially due to X-linked recessive inheritance. Finally, sporadic and familial LAF are clinically indistinguishable.