Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study
BackgroundStroke 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.MethodsWe used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on...
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Neurology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fneur.2023.1185986/full |
| _version_ | 1797778061213564928 |
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| author | Hao Qin Fan Yang Haitao Zhao Jinchuan Zhao Siyuan Lin Yinshuai Shang Chaoling Zhang Pengfei Hao Xianfeng Zhang |
| author_facet | Hao Qin Fan Yang Haitao Zhao Jinchuan Zhao Siyuan Lin Yinshuai Shang Chaoling Zhang Pengfei Hao Xianfeng Zhang |
| author_sort | Hao Qin |
| collection | DOAJ |
| description | BackgroundStroke 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.MethodsWe used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes.ResultsThe inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17–1.83; p = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21–1.77; p = 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; p = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10–1.51; p = 0.001), and LAS (OR, 1.73; 95% CI, 1.15–2.59; p = 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; p = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03–1.28; p = 0.01), AIS (OR, 1.02; 95% CI, 1.14–1.29; p = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01–1.61; p = 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; p = 0.04).ConclusionWe 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. |
| first_indexed | 2024-03-12T23:11:55Z |
| format | Article |
| id | doaj.art-cb6687dc365542fd9bc20ca6411c1794 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-03-12T23:11:55Z |
| publishDate | 2023-07-01 |
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| series | Frontiers in Neurology |
| spelling | doaj.art-cb6687dc365542fd9bc20ca6411c17942023-07-18T01:00:57ZengFrontiers Media S.A.Frontiers in Neurology1664-22952023-07-011410.3389/fneur.2023.11859861185986Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization studyHao Qin0Fan Yang1Haitao Zhao2Jinchuan Zhao3Siyuan Lin4Yinshuai Shang5Chaoling Zhang6Pengfei Hao7Xianfeng Zhang8Department of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Anesthesiology, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaDepartment of Neurosurgery, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, ChinaDepartment of Neurosurgery, The First Hospital of Jilin University, Changchun, ChinaBackgroundStroke 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.MethodsWe used two-sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid-lowering drugs on stroke and its subtypes.ResultsThe inverse variance weighted Mendelian randomization (IVW-MR) revealed the low-density lipoprotein cholesterol (LDL-C) (OR, 1.46; 95% CI, 1.17–1.83; p = 0.0008) and apolipoprotein B (apoB) (OR, 1.46; 95% CI, 1.21–1.77; p = 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; p = 0.0003), any ischemic stroke (AIS) (OR, 1.29; 95% CI, 1.10–1.51; p = 0.001), and LAS (OR, 1.73; 95% CI, 1.15–2.59; p = 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; p = 0.0008). The SMR revealed that expression of PCSK9 was associated with risk of AS (OR, 1.15; 95% CI, 1.03–1.28; p = 0.01), AIS (OR, 1.02; 95% CI, 1.14–1.29; p = 0.03), cardioembolic stroke (CES) (OR, 1.28; 95% CI, 1.01–1.61; p = 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; p = 0.04).ConclusionWe 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.https://www.frontiersin.org/articles/10.3389/fneur.2023.1185986/fulllipidslipid-lowering drugsstrokecausalityMendelian randomization |
| spellingShingle | Hao Qin Fan Yang Haitao Zhao Jinchuan Zhao Siyuan Lin Yinshuai Shang Chaoling Zhang Pengfei Hao Xianfeng Zhang Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study Frontiers in Neurology lipids lipid-lowering drugs stroke causality Mendelian randomization |
| title | Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study |
| title_full | Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study |
| title_fullStr | Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study |
| title_full_unstemmed | Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study |
| title_short | Associations of lipids and lipid-lowering drugs with risk of stroke: a Mendelian randomization study |
| title_sort | associations of lipids and lipid lowering drugs with risk of stroke a mendelian randomization study |
| topic | lipids lipid-lowering drugs stroke causality Mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fneur.2023.1185986/full |
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