Blood Lipids and Cardiovascular Disease: A Mendelian Randomization Study

Abstract

Blood lipids have been considered critical risk factors for cardiovascular disease (CVD). The causal relationship between blood lipids (HDL-C, LDL-C and triglycerides) and cardiovascular disease remains uncertain despite negative and positive associations observed in observational studies, which are susceptible to confounding and reverse causation. This study aimed to investigate the potential causal relationship between the three types of blood lipids and CVD using a two-sample Mendelian randomization (TSMR) approach. Instrumental variables (IVs) representing independent genetic variants associated with HDL-C, LDL-C and triglycerides were derived from the UK Biobank consortium, encompassing genetic data from more than 400,000 individuals. Outcome data for CVD events, including heart disease, stroke, atherosclerosis and so on, were obtained from FinnGen consortium. TSMR analyses were conducted using various methods, such as inverse variance weighted (IVW), MR-Egger regression, and weighted median estimator (WME), to explore the causal relationship between HDL-C, LDL-C and triglycerides levels and CVD events. The results from the Mendelian randomization (MR) analyses suggest a potential causal association between elevated HDL-C, LDL-C and triglycerides levels and CVD events, which indicates that increasing the level of HDL-C and restricting the level of LDL-C and triglycerides are possibly effective methods for the prevention of CVD.