Abstract
Atrial fibrillation (AF) has been associated with numerous diseases. However, whether AF is a cause or consequence of these diseases is uncertain. To clarify, we assessed the causal role of AF on ischemic heart disease (IHD), stroke, other cardiovascular disease (CVD) subtypes, type 2 diabetes mellitus (T2DM), and late-onset AD using bi-directional two-sample Mendelian randomization (MR) among people primarily of European descent. Genetically predicted log odds of AF was associated with any stroke (odds ratio (OR) 1.22, 95% CI 1.18 to 1.27), particularly cardioembolic stroke and possibly subdural hemorrhage, with sensitivity analyses showing similar positive findings. Genetically predicted AF was also associated with arterial thromboembolism (1.32, 1.13 to 1.53), and heart failure (1.26, 1.21 to 1.30). No association of genetically predicted AF with IHD, T2DM, cognitive function, or late-onset AD was found. Conversely, genetically predicted IHD, heart failure and possibly ischemic stroke, particularly cardioembolic stroke, were positively associated with AF. Atrial fibrillation plays a role in any stroke, arterial thromboembolism, and heart failure, corroborating current clinical guidelines on the importance of preventing these complications by effective AF management. In addition, patients with IHD, heart failure or possibly ischemic stroke might be predisposed to developing AF, with implications for management.
Highlights
Atrial fibrillation (AF) has been associated with numerous diseases
We assessed the causal role of AF using bi-directional two-sample Mendelian randomization (MR) i.e., we assessed whether genetically higher risk of AF was associated with ischemic heart disease (IHD), stroke, other cardiovascular disease (CVD) subtypes, type 2 diabetes mellitus (T2DM), cognitive function, and late-onset Alzheimer’s disease (AD); we assessed whether genetically higher risk of IHD, stroke, other CVD subtypes, T2DM, cognitive function, and late-onset AD were associated with AF
Genetically predicted AF was positively associated with cardioembolic stroke at Bonferroni-corrected significance and subdural hemorrhage at nominal significance, and perhaps intracerebral hemorrhage
Summary
Atrial fibrillation (AF) has been associated with numerous diseases. whether AF is a cause or consequence of these diseases is uncertain. We assessed the causal role of AF on ischemic heart disease (IHD), stroke, other cardiovascular disease (CVD) subtypes, type 2 diabetes mellitus (T2DM), and late-onset AD using bi-directional two-sample Mendelian randomization (MR) among people primarily of European descent. Previous MR studies have suggested ischemic stroke may have a bi-directional relationship with AF23 whereas T2DM unlikely affects AF24, with the genetic variants identified from relatively small samples (ischemic stroke: n = 10,307 cases and 19,326 controls; T2DM: n = 26,676 cases and 132,532 controls) and without consideration of ischemic stroke subtypes and associations in the other direction[25] Another MR study did not find AF affected late-onset AD26, but whether the association is in the other direction and how AF relates to cognitive function has not been examined yet.
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