Causal Relationship between Obesity-related Indicators and Major Peripheral Vascular Diseases: Two-sample and...

Epidemiologic studies have shown that obesity is strongly associated with the development of peripheral vascular diseases. However, the causal relationship between obesity and peripheral vascular diseases has not been fully established. Moreover, the basal metabolic rate, a determinant of obesity, has been understudied in peripheral vascular diseases. Therefore, we aimed to assess the causal relationships between obesity-related indicators (waist‒hip ratio, body fat percentage, waist circumference, and basal metabolic rate) and major peripheral vascular diseases.

We first selected GWAS data for obesity-related indicators (waist‒hip ratio, body fat percentage, waist circumference, and basal metabolic rate) and major peripheral vascular diseases (aortic dissection, abdominal aortic aneurysm, thoracic aortic aneurysm, peripheral artery disease, deep vein thrombosis, and varicose veins) from the IEU Open GWAS project and FinnGen databases. Two-sample Mendelian randomization analysis was first used to assess the causal relationships between the obesity-related indicators and major peripheral vascular diseases. Multivariate Mendelian randomization was subsequently used to adjust for total cholesterol, hypertension, and diabetes, thereby assessing the direct effects of obesity-related indicators on peripheral vascular diseases. Finally, a two-sample Mendelian randomization analysis was again used to revalidate the positive results from the multivariate Mendelian randomization analysis using validated GWAS data.

Body fat percentage, waist circumference, and basal metabolic rate were identified as risk factors for major PVDs. Conversely, the waist-to-hip ratio demonstrated a protective effect against varicose veins (OR = 0.79, p = 5.057e-6).

The results of our Mendelian randomization analysis revealed causal relationships between obesity-related indicators and major peripheral vascular diseases, providing valuable guidance for the individualized prevention and treatment of peripheral vascular diseases in clinical practice.

Mendelian randomization establishes that obesity-related indicators (body fat percentage, waist circumference, basal metabolic rate) are causal risk factors for major peripheral vascular diseases. Conversely, waist‒hip ratio demonstrates a protective effect against varicose veins, highlighting distinct roles of adiposity measures in disease etiology and prevention strategies.