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 1,090,261 AF cases and 2,456,308 LPA 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%, <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.