Genetic Evidence for Causal Effects of Circulating Remnant Lipid Profile on Cerebral Hemorrhage and Ischemic Stroke: A Mendelian Randomization Study

Abstract

Background

Mendelian randomization was employed to investigate the impact of circulating lipids, specifically residual lipids, on the risk of susceptibility to cerebral hemorrhage and ischemic stroke.

Methods

According to the previous studies, we chose 19 circulating lipids, comprising 6 regular lipids and 13 residual lipids, to investigate their potential causal relationship with intracranial hemorrhage and ischemic stroke. The effect estimates were computed utilizing the random-effects inverse-variance-weighted methodology.

Results

The findings revealed negative correlations between high-density lipoprotein cholesterol (HDL-C) and cerebral hemorrhage and large artery stroke. HDL-C, apolipoprotein A1 (Apo A1), TG in very small VLDL, and TG in IDL were found to be negatively correlated with any ischemic stroke. apolipoprotein B (Apo B), triglycerides (TG), low-density lipoprotein cholestrol (LDL-C), L.VLDL-TG, TG in medium VLDL, and TG in small VLDL exhibited positive correlations with large artery stroke. TG in very large HDL and TG in IDL were positively correlated with cardioembolic stroke. No significant causal relationship was observed between circulating lipids, with the exception of HDL-C and cerebral hemorrhage. No causal relationship was identified between any circulating lipids and small vessel stroke. Furthermore, the causal relationships were only found between residual lipids and ischemic stroke.

Conclusions

This study provides evidence for the beneficial impact of Apo A1 and HDL-C in reducing the risk of ischemic stroke, as well as the protective effect of HDL-C against cerebral hemorrhage. It highlights the detrimental effects of Apo B, TG, and LDL-C in increasing the risk of ischemic stroke, particularly in cases of large artery stroke. Furthermore, the study underscores the heterogeneity and 2-sided effects of the causal relationship between triglyceride-rich lipoproteins and ischemic stroke, offering a promising avenue for the treatment of ischemic stroke.