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Genetically higher Lp(a) raises atrial fibrillation risk in Europeans but not in a Chinese cohort, a Mendelian randomisation meta-analysis of 2.1 million participants (Curr Probl Cardiol 2024)

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

Curr Probl Cardiol · · 8

Singh S, Baars DP, Desai R, Singh D, Pinto-Sietsma SJ

This systematic review and meta-analysis of Mendelian randomisation (MR) studies examined the association between Lp(a) and atrial fibrillation (AF), pooling 275,647 AF cases among 2,100,172 Lp(a) participants. Genetically higher Lp(a) was associated with increased AF risk across MR studies (OR 1.024, 95% CI 1.007-1.042, I2=87.72%, P<0.001), confirmed by leave-one-out sensitivity analysis. In subgroup analysis, the association held in the European cohort (OR 1.023, 95% CI 1.007-1.040, I2=89.05%, P<0.001) but reversed to a low risk in the Chinese population (OR 0.940, 95% CI 0.893-0.990). The findings support a causal, ancestry-dependent role for Lp(a) in AF risk, warranting prospective validation.

Read the paper (DOI)PubMed

Original abstract

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.

ancestryDutch researchgenetics

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.