[Bidirectional causal relationship between glucose-lipid metabolism, obesity indicators, and myocardial infarction: a bidirectional Mendelian randomization analysis study].

Objective: To explore the causal association of glucose-lipid metabolism and obesity indicators with myocardial infarction by a two-sample Mendelian randomization analysis. Methods: Single nucleotide polymorphisms (SNPs) related to phenotypes were obtained from genome-wide association study databases. The body mass index (BMI) and glycated hemoglobin dataset includes 99 998 samples and 8 126 035 SNPs; the waist-to-hip ratio dataset includes 224 459 samples and 2 562 516 SNPs; the waist circumference and hip circumference dataset includes 462 166 samples and 9 851 867 SNPs; the fasting glucose dataset includes approximately 12 million SNPs; the low-density lipoprotein cholesterol (LDL-C) dataset includes 201 678 samples and 12 321 875 SNPs; the high-density lipoprotein cholesterol (HDL-C), and triglycerides dataset includes 156 109 samples and 15 784 414 SNPs; and the body fat percentage, whole-body fat mass, trunk fat percentage, and trunk fat mass dataset includes 454 588 samples and 9 851 867 SNPs. This study primarily used inverse-variance weighted method to analyze the associations between various exposure factors and outcomes. Heterogeneity among SNPs was assessed using Cochran's Q test, and horizontal pleiotropy of SNPs was examined using the MR-Egger method. Additionally, a multivariable MR approach was used to adjust for BMI, further validating associations between exposure factors and the risk of myocardial infarction. Results: Higher BMI ( OR= 1.070, 95% CI : 1.041-1.100), waist-to-hip ratio ( OR =1.366, 95% CI : 1.113-1.677), LDL-C ( OR =1.638, 95% CI : 1.488-1.803), triglycerides ( OR =1.445, 95% CI : 1.300-1.606), waist circumference ( OR =1.841, 95% CI : 1.650-2.055), hip circumference ( OR =1.247, 95% CI : 1.132-1.372), body fat percentage ( OR =1.795, 95% CI : 1.568-2.055), whole-body fat mass ( OR =1.519, 95% CI: 1.381-1.670), trunk fat percentage ( OR =1.538, 95% CI : 1.374-1.723), and trunk fat mass ( OR =1.421, 95% CI : 1.294-1.561), as well as lower HDL-C ( OR =0.799, 95% CI : 0.729-0.875), have causal effects on myocardial infarction (all P <0.05). After adjusting for BMI, hip circumference, trunk fat percentage, and trunk fat mass were no longer associated with myocardial infarction. However, waist-to-hip ratio ( OR =1.457, 95% CI : 1.132-1.877), fasting glucose ( OR =1.191, 95% CI : 1.024-1.383), glycated hemoglobin ( OR =1.129, 95% CI : 1.034-1.233), LDL-C ( OR =1.592, 95% CI : 1.314-1.929), triglycerides ( OR =1.410, 95% CI : 1.279-1.553), waist circumference ( OR =1.922, 95% CI : 1.448-2.551), body fat percentage ( OR =1.421, 95% CI : 1.072-1.884), and whole-body fat mass ( OR =1.295, 95% CI : 1.031-1.626) remained positively associated with myocardial infarction, while HDL-C ( OR =0.809, 95% CI : 0.729-0.897) remained negatively associated. Conclusions: Abdominal obesity and dysregulation of glucose-lipid metabolism are risk factors for myocardial infarction. Screening for glucose-lipid metabolism (fasting glucose, HDL-C, LDL-C, triglycerides) and obesity-related indicators (waist circumference, waist-to-hip ratio, body fat percentage, and whole-body fat mass) is of great importance for the primary prevention of myocardial infarction.