Genetic evidence for lifestyle and cardiometabolic factors on the risk of aortic aneurysms: A comprehensive Mendelian randomization study

IF 4.9 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Atherosclerosis Pub Date : 2024-08-24 DOI:10.1016/j.atherosclerosis.2024.118572
Chenxi Liu , Jia Peng , Yubo Liu , Yi Peng , Qilin Ma
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Abstract

Background and aims

Aortic aneurysm (AAs) is a chronic and severe aortic disease, which is extremely life-threatening due to its delayed diagnosis and a high risk of rupture. In current studies, the association between lifestyle and metabolic factors remains controversial given the complexity of pathogenesis and progression in AAs. Consequently, more reliable and robust evidence should be provided.

Methods

Genome-wide association studies summary statistics were obtained for 25 factors (6 lifestyle factors and 19 cardiometabolic factors) and AAs. Univariable Mendelian randomization (UVMR) and multivariable MR (MVMR) were used to estimate the causal effect of these factors on AAs. Meanwhile, mediation analysis was applied to assess the mediated effect of lifestyle on the association of cardiometabolic factors with AAs.

Results

Several factors were associated with AA risk, among which triglyceride (TG) (OR = 1.32, 95 % CI = [1.18–1.47], p < 0.001) and high-density lipoprotein cholesterol (HDL-C) (OR = 0.70, 95 % CI = [0.61–0.82], p < 0.001) remain consistently associated with AA risk, with an idependent effect on AAs after adjusting for body mass index (BMI). In addition, TG mediated 15.6 % of BMI effects and 3.7 % of smoking effects on AAs, and HDL-C mediated 5.3 % of the effects of cigarette smoking on AAs.

Conclusions

TG and HDL-C may be the most reliable factors in the risk of AAs. More scientific management of lifestyle and regular monitoring for cardiometabolic traits may serve as a new and effective direction for the prevention and control of the occurrence of AAs.

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生活方式和心脏代谢因素对主动脉瘤风险的遗传学证据:孟德尔随机综合研究
背景和目的主动脉瘤(AAs)是一种慢性、严重的主动脉疾病,由于诊断不及时和破裂风险高,极易危及生命。在目前的研究中,生活方式和代谢因素之间的关联仍存在争议,因为 AAs 的发病机制和进展十分复杂。方法对 25 个因素(6 个生活方式因素和 19 个心脏代谢因素)和 AAs 进行了全基因组关联研究,并获得了汇总统计数据。采用单变量孟德尔随机化(UVMR)和多变量 MR(MVMR)来估计这些因素对 AAs 的因果效应。结果几个因素与 AA 风险相关,其中甘油三酯(TG)(OR = 1.32,95 % CI = [1.18-1.47],p <0.001)和高密度脂蛋白胆固醇(HDL-C)(OR = 0.70,95 % CI = [0.61-0.82],p <0.001)仍与 AA 风险持续相关,在调整体重指数(BMI)后,对 AA 的影响与之相同。此外,总胆固醇介导了体重指数对 AAs 15.6% 的影响和吸烟对 AAs 3.7% 的影响,而高密度脂蛋白胆固醇介导了吸烟对 AAs 5.3% 的影响。更科学的生活方式管理和定期监测心血管代谢特征可能是预防和控制 AAs 发生的一个新的有效方向。
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来源期刊
Atherosclerosis
Atherosclerosis 医学-外周血管病
CiteScore
9.80
自引率
3.80%
发文量
1269
审稿时长
36 days
期刊介绍: Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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