Lower BMI combined with lower Lp(a) tracks with the least atrial fibrillation, and Mendelian randomization shows the two act independently (Pol Arch Intern Med 2025)

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 AF remains poorly understood.

Objectives: Our primary objective was to examine the combined influence of BMI and Lp(a) on AF occurrence.

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

Results: In comparison with the individuals with a higher Lp(a) level (≥30 mg/dl) and BMI equal to or above 24 kg/m2, those with a lower Lp(a) level and BMI had the lowest prevalence of AF (odds ratio, 0.96; 95% CI, 0.95-0.97; P <0.001), especially at the age of 50-69 years, and the lowest risk of stroke (hazard ratio [HR], 0.28; 95% CI, 0.12-0.68; P = 0.004), heart failure (HF; HR, 0.24; 95% CI, 0.08-0.66; P = 0.006), and major adverse cardiovascular events (MACE; HR, 0.35; 95% CI, 0.18-0.66; P = 0.001). Mediation MR analysis highlighted the coexposure effects of Lp(a) levels and BMI on AF and their independent influence on AF development.

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