Metabolic disorders and risk of cardiovascular diseases: a two-sample mendelian randomization study

BACKGROUND: Metabolic disorders are increasing worldwide and are characterized by various risk factors such as abdominal obesity, insulin resistance, impaired glucose metabolism, and dyslipidemia. Observational studies suggested a bidirectional association between cardiovascular diseases and metabolic disorders and its components. However, the causal associations between them remained unclear. This study aims to investigate the causal relationship between metabolic disorders and cardiovascular disease through Mendelian randomization (MR) analysis. METHODS: A two-sample MR analysis based on publicly available genome-wide association studies were used to infer the causality. The single-nucleotide polymorphisms with potential pleiotropy were excluded by MR-PRESSO. The effect estimates were constructed using the random-effects inverse-variance-weighted method as the primary estimate. Furthermore, MR-Egger and weighted median were also performed to detect heterogeneity and pleiotropy. RESULTS: Genetically predicted metabolic disorders increased the risk for coronary heart disease (OR = 1.77, 95% CI: 1.55-2.03, p < 0.001), myocardial infarction (OR = 1.75, 95% CI: 1.52-2.03, p < 0.001), heart failure (OR = 1.26, 95% CI: 1.14-1.39, p < 0.001), hypertension (OR = 1.01, 95% CI: 1.00-1.02, p = 0.002), and stroke (OR = 1.19, 95% CI: 1.08-1.32, p < 0.001). The concordance of the results of various complementary sensitivity MR methods reinforces the causal relationship further. CONCLUSION: This study provides evidence of a causal relationship between metabolic disorders and increased risk of coronary heart disease, myocardial infarction, heart failure, hypertension, and stroke. Special attention should be paid to improving metabolic disorders to reduce the development of cardiovascular diseases.