Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study

Background: Although the associations between serum lipid levels and aneurysms have been investigated in epidemiological studies, causality remains unknown. Thus, this study aimed to investigate the causal relationships of serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein c...

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Autores principales:	Yanghui Chen, Man Huang, Yunling Xuan, Ke Li, Xin Xu, Linlin Wang, Yang Sun, Lei Xiao, Ping Xu, Wei Kong, Dao Wen Wang
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	aneurysm lipid traits lipid-lowering drugs mendelian randomization analyses Medicine R
Acceso en línea:	https://doaj.org/article/101a9f0b8721404eb36d2ff52d78397d
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spelling	oai:doaj.org-article:101a9f0b8721404eb36d2ff52d78397d2021-11-25T18:07:46ZAssociation between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study10.3390/jpm111111712075-4426https://doaj.org/article/101a9f0b8721404eb36d2ff52d78397d2021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4426/11/11/1171https://doaj.org/toc/2075-4426Background: Although the associations between serum lipid levels and aneurysms have been investigated in epidemiological studies, causality remains unknown. Thus, this study aimed to investigate the causal relationships of serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels on five types of aneurysms, using genetic variants associated with four lipid traits as instrumental variables in a Mendelian randomization (MR) analysis. Methods: We performed two-sample Mendelian randomization (MR) analyses to evaluate the associations of HDL-C, LDL-C, TC, and TG levels with risks for five types of aneurysms and those of LDL-C- (<i>HMGCR</i>, <i>NPC1L1</i>, <i>PCSK9</i>, <i>CETP</i>, and <i>LDLR</i>) and TG-lowering targets (<i>ANGPTL3</i> and <i>LPL</i>) with aneurysms. Results: The sample sizes of the included studies ranged from nearly 80,000 to 410,000. We found inverse associations between genetically predicted HDL-C levels and aortic (OR = 0.74, 95% CI = 0.65–0.85) and abdominal aortic aneurysms (0.58, 0.45–0.75). A 1-SD increase in LDL-C and TC levels was associated with increased risks for aortic (1.41, 1.26–1.58 and 1.36, 1.18–1.56, respectively) and abdominal aortic aneurysms (1.82, 1.48–2.22 and 1.55, 1.25–1.93, respectively). TG levels were significantly associated with aortic (1.36, 1.18–1.56) and lower extremity artery aneurysms (2.76, 1.48–5.14), but limited to cerebral aneurysm (1.23, 1.06–1.42). Secondary analyses revealed a relationship between genetically proxied LDL-C-lowering targets and all types of aneurysms; however, the drug targets remained heterogeneous. We found a weak association between TG-lowering therapies and aortic (<i>ANGPTL3</i>, 0.51, 0.29–0.89) and abdominal aortic aneurysms (<i>LPL</i>, 0.64, 0.44–0.94). Conclusion: According to genetic evidence, lipid dysfunction is a causal risk factor for aneurysms. Lipid-lowering drugs may be a potential effective strategy in preventing and managing aneurysms.Yanghui ChenMan HuangYunling XuanKe LiXin XuLinlin WangYang SunLei XiaoPing XuWei KongDao Wen WangMDPI AGarticleaneurysmlipid traitslipid-lowering drugsmendelian randomization analysesMedicineRENJournal of Personalized Medicine, Vol 11, Iss 1171, p 1171 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	aneurysm lipid traits lipid-lowering drugs mendelian randomization analyses Medicine R
spellingShingle	aneurysm lipid traits lipid-lowering drugs mendelian randomization analyses Medicine R Yanghui Chen Man Huang Yunling Xuan Ke Li Xin Xu Linlin Wang Yang Sun Lei Xiao Ping Xu Wei Kong Dao Wen Wang Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
description	Background: Although the associations between serum lipid levels and aneurysms have been investigated in epidemiological studies, causality remains unknown. Thus, this study aimed to investigate the causal relationships of serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels on five types of aneurysms, using genetic variants associated with four lipid traits as instrumental variables in a Mendelian randomization (MR) analysis. Methods: We performed two-sample Mendelian randomization (MR) analyses to evaluate the associations of HDL-C, LDL-C, TC, and TG levels with risks for five types of aneurysms and those of LDL-C- (<i>HMGCR</i>, <i>NPC1L1</i>, <i>PCSK9</i>, <i>CETP</i>, and <i>LDLR</i>) and TG-lowering targets (<i>ANGPTL3</i> and <i>LPL</i>) with aneurysms. Results: The sample sizes of the included studies ranged from nearly 80,000 to 410,000. We found inverse associations between genetically predicted HDL-C levels and aortic (OR = 0.74, 95% CI = 0.65–0.85) and abdominal aortic aneurysms (0.58, 0.45–0.75). A 1-SD increase in LDL-C and TC levels was associated with increased risks for aortic (1.41, 1.26–1.58 and 1.36, 1.18–1.56, respectively) and abdominal aortic aneurysms (1.82, 1.48–2.22 and 1.55, 1.25–1.93, respectively). TG levels were significantly associated with aortic (1.36, 1.18–1.56) and lower extremity artery aneurysms (2.76, 1.48–5.14), but limited to cerebral aneurysm (1.23, 1.06–1.42). Secondary analyses revealed a relationship between genetically proxied LDL-C-lowering targets and all types of aneurysms; however, the drug targets remained heterogeneous. We found a weak association between TG-lowering therapies and aortic (<i>ANGPTL3</i>, 0.51, 0.29–0.89) and abdominal aortic aneurysms (<i>LPL</i>, 0.64, 0.44–0.94). Conclusion: According to genetic evidence, lipid dysfunction is a causal risk factor for aneurysms. Lipid-lowering drugs may be a potential effective strategy in preventing and managing aneurysms.
format	article
author	Yanghui Chen Man Huang Yunling Xuan Ke Li Xin Xu Linlin Wang Yang Sun Lei Xiao Ping Xu Wei Kong Dao Wen Wang
author_facet	Yanghui Chen Man Huang Yunling Xuan Ke Li Xin Xu Linlin Wang Yang Sun Lei Xiao Ping Xu Wei Kong Dao Wen Wang
author_sort	Yanghui Chen
title	Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
title_short	Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
title_full	Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
title_fullStr	Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
title_full_unstemmed	Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study
title_sort	association between lipid levels and risk for different types of aneurysms: a mendelian randomization study
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/101a9f0b8721404eb36d2ff52d78397d
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Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study

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