AUTHOR=Qin Hao , Yang Fan , Zhao Haitao , Zhao Jinchuan , Lin Siyuan , Shang Yinshuai , Zhang Chaoling , Hao Pengfei , Zhang Xianfeng 

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

JOURNAL=Frontiers in Neurology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1185986

DOI=10.3389/fneur.2023.1185986

ISSN=1664-2295

ABSTRACT=<sec id="sec1"><title>Background</title><p>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.</p></sec><sec id="sec2"><title>Methods</title><p>We used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes.</p></sec><sec id="sec3"><title>Results</title><p>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; <italic>p</italic> = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21–1.77; <italic>p</italic> = 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; <italic>p</italic> = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10–1.51; <italic>p</italic> = 0.001), and LAS (OR, 1.73; 95% CI, 1.15–2.59; <italic>p</italic> = 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; <italic>p</italic> = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03–1.28; <italic>p</italic> = 0.01), AIS (OR, 1.02; 95% CI, 1.14–1.29; <italic>p</italic> = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01–1.61; <italic>p</italic> = 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; <italic>p</italic> = 0.04).</p></sec><sec id="sec4"><title>Conclusion</title><p>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.</p></sec>