Exploring the Causal Roles of Circulating Remnant Lipid Profile on Cardiovascular and Cerebrovascular Diseases: Mendelian Randomization Study

Abstract

Background Causal evidence of circulating lipids especially the remnant cholesterol with cardiovascular and cerebrovascular disease (CVD) is lacking. This research aimed to explore the causal roles of extensive lipid traits especially the remnant lipids in CVD. Methods Two-sample Mendelian randomization (TSMR) analysis was performed based on large-scale meta-analysis datasets in European ancestry. The causal effect of 15 circulating lipid profiles including 6 conventional lipids and 9 remnant lipids on coronary heart disease (CHD) and ischemic stroke (IS), as well as the subtypes, was assessed. Results Apo B, TC, LDL-C, and TG were still important risk factors for CHD and MI but not for IS. Apo B is the strongest which increased the CHD and MI risk by 44% and 41%, respectively. The OR(95%CI) of total TG on CHD and MI were 1.25(1.13 to 1.38) and 1.24(1.11 to 1.38), respectively. 1-SD increased M.VLDL.TG, S.VLDL.TG, XS.VLDL.TG, IDL.TG, XL.HDL.TG, and S.HDL.TG particles also robustly increased the risk of CHD and MI by 9%-28% and 9%-27%, respectively. TG in very/extremely large VLDL (XXL.VLDL.TG and XL.VLDL.TG) were insignificant or even negatively associated with CHD (in multivariable MR), and negatively associated with IS as well. Conclusions The remnant lipids presented heterogeneity and two-sided effects for the risk of CHD and IS that may partially rely on the particle size. The findings suggested that the remnant lipids were required to be intervened according to specific components. This research confirms the importance of remnant lipids and provides causal evidence for potential targets for intervention.