Joint association of body mass index and lipoprotein(a) with atrial fibrillation prevalence: an observational and mendelian randomization study.

Introduction: Although previous studies have demonstrated that lipoprotein(a) [Lp(a)] and body mass index (BMI) are associated with atrial fibrillation (AF), their joint effect on atrial fibrillation remains poorly understood.

Objectives: Our primary objective was to examine the combined influence of body mass index and lipoprotein(a) on atrial fibrillation.

Patients and methods: The study included 8886 patients, among whom 205 were diagnosed with persistent AF. The joint association between BMI and Lp(a) with AF was evaluated. A mediation Mendelian randomization analysis was also performed.

Results: Compared with people with a higher Lp(a) level (≥30 mg/dL) and a BMI ≥24 kg/m2, those with a lower Lp(a) level and BMI had the lowest prevalence of AF (OR 0.96 [0.95-0.97], P <0.001), which was predominant between 50-69 years, and the lowest risk of stroke (HR 0.28 [0.12-0.68], P = 0.004), heart failure (HR 0.24 [0.08-0.66], P = 0.006) and major adverse cardiovascular events (MACE) (HR 0.35 [0.18-0.66], P = 0.001). Mediation Mendelian randomization analysis highlight the coexposure effects of Lp(a) levels and BMI on AF and that both act independently of AF.

Conclusions: Lower BMI and Lp(a) levels were associated with a reduced prevalence of AF. Mediation analysis showed that neither BMI nor Lp(a) mediates the effect of the other, suggesting that their contributions to AF risk operate through independent pathways.