Genetics
Lp(a) is not clinically linked to atrial fibrillation, meta-analysis of 16 observational and 7 Mendelian randomisation studies (J Clin Lipidol 2026)
Original title: Lipoprotein(a) and atrial fibrillation: Meta-analysis of observational and mendelian randomization studies shows no clinically meaningful association
Meta-analysis pooling 16 observational studies and 7 Mendelian randomisation (MR) studies to test whether lipoprotein(a) is associated with atrial fibrillation (AF). Observational studies showed no association (odds ratio 0.980, 95% CI 0.901-1.070; hazard ratio 1.058, 95% CI 0.998-1.110), consistent across European and East Asian subgroups. MR analyses accounting for sample overlap likewise showed no association (odds ratio 0.976, 95% CI 0.940-1.013); pooling all MR studies with substantial sample overlap produced a statistically significant but very small positive effect (odds ratio 1.023, 95% CI 1.002-1.044). The authors conclude Lp(a) is not associated with AF in either observational or independent MR analysis, and that any true causal effect is too small to be clinically meaningful.
Original abstract
Background: Elevated lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerotic cardiovascular disease, but its relationship with atrial fibrillation (AF) remains uncertain. We conducted a meta-analysis of observational studies and Mendelian randomization (MR) analyses to clarify whether Lp(a) is associated with AF.
Objective: To clarify the relationship between Lp(a) and AF.
Methods: We systematically pooled 16 observational studies analyzing odds ratios (ORs) and hazard ratios (HRs) for AF across higher vs lower Lp(a) exposure, as defined within each study, in 2 separate random-effects models. In parallel, we pooled 7 MR studies that used genetic instruments for Lp(a) to estimate the causal effect on AF. Subgroup analyses were performed by ancestry (European and East Asian).
Results: Observational studies showed no association between Lp(a) and AF (OR 0.980 [0.901, 1.070], P = .581; HR 1.058 [0.998, 1.110], P = .057). Stratification by ancestry showed no association either (European, OR 1.079 [0.759, 1.533], P = .673; East Asian, OR 0.978 [0.896, 1.068], P = .621). In MR studies accounting for sample overlap, we observed no association between Lp(a) and AF (OR 0.976 [0.940, 1.013], P = .208). All MR studies pooled with substantial sample overlap showed statistically significant but very small positive effects (OR 1.023 [1.002, 1.044], P < .001).
Conclusion: Lp(a) is not associated with AF in observational or MR meta-analysis. MR analyses do not demonstrate a significant association when restricted to independent datasets, indicating that any true causal relationship is unlikely to be clinically meaningful.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.