Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study

• Published in: Frontiers in neurology 2023-07, Vol.14, p.1185986-1185986
• Main Authors: Qin, Hao, Yang, Fan, Zhao, Haitao, Zhao, Jinchuan, Lin, Siyuan, Shang, Yinshuai, Zhang, Chaoling, Hao, Pengfei, Zhang, Xianfeng
• Format: Article
• Language: English
• Subjects: causality; lipid-lowering drugs; lipids; Mendelian randomization; Neurology; stroke
• ISSN: 1664-2295; 1664-2295
• DOI: 10.3389/fneur.2023.1185986

Stroke is a leading cause of death worldwide, but it is unclear whether circulating lipids and lipid-lowering drugs are causally associated with stroke and its subtypes. We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes. The inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17-1.83;  = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21-1.77;  = 0.0001) was positively correlated with large artery stroke (LAS). However, no causal effect was found in LDL-C and apoB on LAS risk when we conducted mvMR. The IVW-MR also found a suggestive evidence that decreased LDL-C levels mediated by the PCSK9 (proprotein convertase subtilisin-kexin type 9) gene were associated with a reduced risk of any stroke (AS) (OR, 1.31; 95% CI, 1.13-1.52;  = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10-1.51;  = 0.001), and LAS (OR, 1.73; 95% CI, 1.15-2.59;  = 0.008), while NPC1L1 (Niemann-Pick C1-like protein)-mediated LDL-C levels were associated with a higher risk of small vessel stroke (SVS) (OR, 6.10; 95% CI, 2.13-17.43;  = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03-1.28;  = 0.01), AIS (OR, 1.02; 95% CI, 1.14-1.29;  = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01-1.61;  = 0.04). And, a significant association was found between the expression of NPC1L1 and the risk of SVS (OR, 1.15; 95% CI, 1.00-1.32;  = 0.04). We cautiously find that LDL-C and apoB was positively correlated with LAS. These findings suggest that the reducing LDL-C levels could be an effective prevention strategy for reducing the risk of stroke.