The causal relationship between metabolic syndrome and its components and cardiovascular disease: A mendelian randomization study

Aim: To investigate the causal relationship between metabolic syndrome (MetS) and its components and 14 cardiovascular diseases using Mendelian randomization (MR). Methods: We used summary statistics from large-scale genome-wide association studies of MetS, its components, and cardiovascular diseases. We performed a two-sample MR analysis using the inverse-variance weighted method and other sensitivity methods. We also performed multivariate MR to adjust for potential risk factors. Results: Our study found that MetS was causally associated with an increased risk of ischemic stroke, abdominal aortic aneurysm, pulmonary embolism, coronary heart disease, heart failure, and peripheral artery disease. Waist circumference was causally associated with an increased risk of 6 cardiovascular diseases. Type 2 diabetes mellitus, diastolic blood pressure, systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol were all causally associated with coronary heart disease, with varying causal relationships with the remaining 5 cardiovascular diseases. Multivariate MR showed that, except for ischaemic stroke, waist circumference remained causally associated with the remaining five cardiovascular diseases after adjusting for potential confounders. Conclusion: Our study provides evidence that metabolic syndrome is causally associated with 6 cardiovascular diseases. Waist circumference is the most important component of these relationships. These findings have implications for the prevention and management of metabolic syndrome and cardiovascular diseases.