J Clin Lipidol. 2026 Jul 10:S1933-2874(26)00439-3. doi: 10.1016/j.jacl.2026.07.006. Online ahead of print.
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.
PMID:42509093 | DOI:10.1016/j.jacl.2026.07.006