Association Between Lipoprotein (a) and Risk of Atrial Fibrillation: A Systematic Review and Meta-analysis of Mendelian Randomization Studies

Lipoprotein (a) (Lp[a]) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, data on association of Lp(a) with risk of atrial fibrillation (AF) is still limited. We searched PubMed/Medline, Scopus, and EMBASE for studies evaluating the association of Lp(a) with the occurrence of AF until July 2023. Random effects models and I² statistics were used for pooled odds ratios (OR), and heterogeneity assessments. A subgroup analysis was performed based on the cohort population, and a one-out sensitivity analysis was performed. This meta-analysis comprised 275,647 AF cases and 2,100,172 Lp(a) participants. An increase in Lp(a) was associated with an increased risk of AF in mendelian randomization (MR) studies (OR 1.024, 95% CI: 1.007-1.042, I² = 87.72%, P < 0.001). Leave-one-out sensitivity analysis confirmed equivalent results in MR studies. Subgroup analysis of MR studies revealed a higher risk of AF in the European cohort (OR 1.023, 95% CI: 1.007-1.040, I² = 89.05%, P < 0.001) and a low risk (OR 0.940, 95% CI: 0.893-0.990) in the Chinese population. Meta-analysis of the MR data suggested higher levels of Lp(a) were associated with increased risk of AF. Future robust prospective studies are warranted to validate these findings.