The Relationship Between Body Mass Index and Peripheral Artery Disease: Insights from the National Health and Nutrition Examination Survey and Mendelian Randomization Analysis.

INTRODUCTION

Body mass index (BMI) has been implicated in various cardiovascular conditions, but its association with peripheral artery disease (PAD) in both real-world and genetic studies have been contentious and debated.

METHODS

This study enrolled 6707 individuals from the National Health and Nutrition Examination Survey database to investigate the association between BMI and the risk of PAD. The weighted logistic regression, restricted cubic spline, and subgroup analysis were performed using real-world data. Mendelian randomization study was conducted using genetic data from the Genome-Wide Association Study. The inverse variance weighted method was used as the primary analysis approach, and a sensitivity analysis was conducted to identify pleiotropy and heterogeneity bias.

RESULTS

Individuals with PAD had higher mean BMI values compared to those without PAD (28.82 ± 5.87 and 28.31 ± 5.42, P = 0.007). For the categorical variable of BMI, individuals in obesity class 2 (odds ratio [OR] = 1.532, 95% CI = 1.082-2.169; P = 0.013) and obesity class 3 (OR = 2.479, 95% CI = 1.515-4.056; P < 0.001) had a higher risk of PAD analyzed by weighted logistic regression. Subgroup analysis revealed that the association between BMI and PAD persisted. Given that a higher BMI is associated with PAD, we selected obesity for Mendelian randomization analysis and observed that obesity had a relationship with PAD (inverse variance weight: OR = 1.194, 95% CI = 1.099-1.296; P < 0.001). The reliable findings were validated by sensitive analysis (all P > 0.05).

CONCLUSIONS

BMI is a robust risk factor for PAD. A higher BMI (especially ≥35 kg/m2) is associated with an increased risk of developing PAD. Meanwhile, there is a causal relationship between obesity and PAD. Interventions are necessary for targeted obesity prevention and management strategies for PAD.