Bone mineral loss and risk of atrial fibrillation: a multicohort study

Abstract Aims Existing evidence has supported a correlation between osteoporosis and vascular damage conditions, yet studies investigating heart rhythm dysfunction are scarce. This study aimed to explore the link between osteoporosis and atrial fibrillation (AF), with a particular focus on the potential role of genetic predisposition, sex, and circulating proteins. Methods and results This population-based study included 495 549 participants from three independent cohorts. Cox proportional hazard models were conducted separately for each cohort and combined in a random-effect meta-analysis to determine the association between osteoporosis and AF. The role of genetic susceptibility, sex, and circulating proteins was further assessed in osteoporosis-related AF by integrating phenotype, gene, and protein data. The predictive performance was assessed via receiver operating characteristic curves. Compared with individuals without osteoporosis, individuals with osteoporosis experienced an elevated risk of AF (HR 1.38, 95% CI: 1.01–1.89), independent of AF-related genetic susceptibility. Moreover, an obvious sex disparity was present in the osteoporosis-AF relationship in the primary cohort, with a higher risk of AF for osteoporosis males (HR 1.30, 95% CI: 1.11–1.51 for males; HR 1.16, 95% CI: 1.04–1.28 for females). 19 proteins were indicated to contribute to the relationship between osteoporosis and increased AF risk, with LMNB2 improving the predictive accuracy for the incidence of AF. Conclusion This research revealed an increased risk of AF in individuals with osteoporosis, especially in males. These findings highlight the need for regular heart rhythm monitoring in osteoporosis individuals, with LMNB2 potentially being a candidate marker for predicting AF incidence.