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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621501/ https://www.ncbi.nlm.nih.gov/pubmed/34834523 http://dx.doi.org/10.3390/jpm11111171 |
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author | Chen, Yanghui Huang, Man Xuan, Yunling Li, Ke Xu, Xin Wang, Linlin Sun, Yang Xiao, Lei Xu, Ping Kong, Wei Wang, Dao Wen |
author_facet | Chen, Yanghui Huang, Man Xuan, Yunling Li, Ke Xu, Xin Wang, Linlin Sun, Yang Xiao, Lei Xu, Ping Kong, Wei Wang, Dao Wen |
author_sort | Chen, Yanghui |
collection | PubMed |
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- (HMGCR, NPC1L1, PCSK9, CETP, and LDLR) and TG-lowering targets (ANGPTL3 and LPL) 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 (ANGPTL3, 0.51, 0.29–0.89) and abdominal aortic aneurysms (LPL, 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 | Online Article Text |
id | pubmed-8621501 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86215012021-11-27 Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study Chen, Yanghui Huang, Man Xuan, Yunling Li, Ke Xu, Xin Wang, Linlin Sun, Yang Xiao, Lei Xu, Ping Kong, Wei Wang, Dao Wen J Pers Med Article 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- (HMGCR, NPC1L1, PCSK9, CETP, and LDLR) and TG-lowering targets (ANGPTL3 and LPL) 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 (ANGPTL3, 0.51, 0.29–0.89) and abdominal aortic aneurysms (LPL, 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. MDPI 2021-11-10 /pmc/articles/PMC8621501/ /pubmed/34834523 http://dx.doi.org/10.3390/jpm11111171 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Yanghui Huang, Man Xuan, Yunling Li, Ke Xu, Xin Wang, Linlin Sun, Yang Xiao, Lei Xu, Ping Kong, Wei Wang, Dao Wen Association between Lipid Levels and Risk for Different Types of Aneurysms: A Mendelian Randomization Study |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621501/ https://www.ncbi.nlm.nih.gov/pubmed/34834523 http://dx.doi.org/10.3390/jpm11111171 |
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