Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study
Background Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lip...
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Wiley
2024-08-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.123.032409 |
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| author | Yi Xie Shuai Liu Xinyue Wang Hao Huang Minghuan Wang Wensheng Qu Zhiyuan Yu Wei Wang Xiang Luo |
| author_facet | Yi Xie Shuai Liu Xinyue Wang Hao Huang Minghuan Wang Wensheng Qu Zhiyuan Yu Wei Wang Xiang Luo |
| author_sort | Yi Xie |
| collection | DOAJ |
| description | Background Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid‐lowering interventions on this disease. Methods and Results Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome‐wide association studies. Through 2‐sample Mendelian randomization analyses, it was found that decreased levels of high‐density lipoprotein cholesterol (odds ratio [OR], 0.85, P=0.007) and apolipoprotein A‐I (OR, 0.83, P=0.005), as well as increased level of triglycerides (OR, 1.16, P=0.025) were associated with a higher risk of SVS. A low level of high‐density lipoprotein cholesterol (OR, 0.93, P=0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size‐defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization‐based mediation analysis. For drug‐target Mendelian randomization, the low‐density lipoprotein cholesterol‐reducing genetic variation alleles at HMGCR and NL1CL1 genes and the high‐density lipoprotein cholesterol‐raising genetic variation alleles at the CETP gene were predicted to decrease the risk of SVS. Conclusions The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid‐lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH. |
| format | Article |
| id | doaj-art-b2e9b6c227a54d27a12b60d3a6e26523 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-08-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-b2e9b6c227a54d27a12b60d3a6e265232024-11-28T09:27:29ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-08-01131610.1161/JAHA.123.032409Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization StudyYi Xie0Shuai Liu1Xinyue Wang2Hao Huang3Minghuan Wang4Wensheng Qu5Zhiyuan Yu6Wei Wang7Xiang Luo8Department of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaReproductive Medicine Center, Tongji Hospital, Tongji Medicine College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaDepartment of Neurology, Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan ChinaBackground Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid‐lowering interventions on this disease. Methods and Results Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome‐wide association studies. Through 2‐sample Mendelian randomization analyses, it was found that decreased levels of high‐density lipoprotein cholesterol (odds ratio [OR], 0.85, P=0.007) and apolipoprotein A‐I (OR, 0.83, P=0.005), as well as increased level of triglycerides (OR, 1.16, P=0.025) were associated with a higher risk of SVS. A low level of high‐density lipoprotein cholesterol (OR, 0.93, P=0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size‐defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization‐based mediation analysis. For drug‐target Mendelian randomization, the low‐density lipoprotein cholesterol‐reducing genetic variation alleles at HMGCR and NL1CL1 genes and the high‐density lipoprotein cholesterol‐raising genetic variation alleles at the CETP gene were predicted to decrease the risk of SVS. Conclusions The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid‐lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH.https://www.ahajournals.org/doi/10.1161/JAHA.123.032409cerebral small vessel diseasemediation analysisMendelian randomizationmicrovascular ischemic diseaseserum lipidssmall vessel stroke |
| spellingShingle | Yi Xie Shuai Liu Xinyue Wang Hao Huang Minghuan Wang Wensheng Qu Zhiyuan Yu Wei Wang Xiang Luo Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease cerebral small vessel disease mediation analysis Mendelian randomization microvascular ischemic disease serum lipids small vessel stroke |
| title | Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_full | Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_fullStr | Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_full_unstemmed | Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_short | Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study |
| title_sort | lipids apolipoproteins lipid lowering drugs and the risk of cerebral small vessel disease a mendelian randomization study |
| topic | cerebral small vessel disease mediation analysis Mendelian randomization microvascular ischemic disease serum lipids small vessel stroke |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.032409 |
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