Association of Lactate with Risk of Cardiovascular Diseases: A Two-Sample Mendelian Randomization Study

Xindi Chang,* Wang Zheng,* Yingli Zhao, Wangkang Niku, Bing Deng, Ping Liu, Yiru Wang Department of Cardiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru Wang, Email [email protected]: Studies consistently show abnormally high levels of lactate acid in cardiovascular disease patients, suggested that targeting lactate production may serve as potential strategies for the treatment in the future. However, observational results may be subject to residual confounding and bias.Methods: This study used the dataset from GWAS database to examine confounding in epidemiologic associations between lactate and cardiovascular diseases. A genome-wide genetic association study using Mendelian randomization (MR) was performed from December 02, 2023 to January 15, 2024 to reduce confounding and enhance causal inference. Primary analysis was conducted using inverse-variance-weighted MR. All studies included patients predominantly of European ancestry.Results: The association between lactate and cardiovascular diseases, including 60801 cases from coronary heart disease, 7018 cases from myocardial infarction, 14334 cases from coronary atherosclerosis, 60620 cases from atrial fibrillation, 54358 cases from hypertension, 71 cases from hypertrophic cardiomyopathy, 47309 cases from heart failure, 7055 cases from stroke, 7193 cases from cardioembolic ischemic stroke, 4373 cases from ischemic stroke caused by large vascular atherosclerosis, 2118 cases from pulmonary embolism, 1230 cases from peripheral artery disease, and 4620 cases from venous thromboembolism. Genetically predicted coronary atherosclerosis was associated with a higher risk of lactate level (OR = 1.950; 95% CI (0.087, 1.249); P = 0.024); this association was also evident for peripheral artery disease (OR = 1.003; 95% CI (0.000, 0.005); P = 0.021). No genetically predicted associations were noted for the other cardiovascular diseases.Conclusion: The findings of this study provide genetic evidence supporting a higher risk of lactate level only in coronary atherosclerosis and peripheral artery disease. However, no genetic association between lactate level and the other cardiovascular diseases.Keywords: Mendelian randomization, atherosclerosis, peripheral artery disease, GWAS, single nucleotide polymorphisms