Causal association of modifiable factors with cardiometabolic multimorbidity: an exposome-wide Mendelian randomization investigation.

IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Dun Li, Jing Lin, Hongxi Yang, Lihui Zhou, Yujian Li, Zhe Xu, Li Sun, Xinyu Zhang, Weili Xu, Yaogang Wang
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引用次数: 0

Abstract

Background: Cardiometabolic multimorbidity (CMM), characterized by the co-existence of two or more cardiometabolic diseases (CMDs) including type 2 diabetes (T2D), coronary artery disease (CAD), and stroke, persists as a global health challenge. However, the causal associations of modifiable factors with CMDs and CMM remains to be systematically investigated.

Methods: In this study, a three-stage design Mendelian randomization (MR) investigation was conducted, using two-sample MR with potential sample overlap correction and multiple testing, multivariable MR analysis, and multi-response MR, with modifiable factors covering domains of socioeconomic factors, behavioral factors, biochemical factors, and physical measures as exposures, and CMM and CMDs as outcomes. Updated large-scale genome-wide association study (GWAS) data based on systematic collection from GWAS Catalog were applied.

Results: Our major findings suggested that, 13 of 23 modifiable factors across four domains, including educational attainment (odds ratio: 0.858, 95% confidence interval: 0.834-0.883), household income (0.794, 0.720-0.875), lifetime smoking behavior (1.201, 1.145-1.260), leisure screen time (1.255, 1.186-1.327), low-density lipoprotein cholesterol levels (1.062, 1.046-1.079), total cholesterol levels (1.045, 1.029-1.062), Apolipoprotein B (1.035, 1.019-1.051), fasting glucose (1.096, 1.038-1.157), glycated hemoglobin (HbA1c) (1.062, 1.037-1.089), systolic blood pressure (1.125, 1.104-1.146), diastolic blood pressure (1.104, 1.083-1.126), forced expiratory volume in 1 s (FEV1) (0.953, 0.931-0.975), and body mass index (BMI) (1.243, 1.210-1.277) were evaluated with relatively robust effects on CMM. Furthermore, household income, lifetime smoking behavior, HbA1c, systolic blood pressure, and FEV1 with CMM were detected as independent associations within a single domain. Similar results were observed in each CMD. Moreover, the multi-response MR provided reinforcing evidence for the associations of educational attainment, serum urate, and BMI with CMM, and lifetime smoking behavior, moderate to vigorous intensity physical activity, and leisure screen time with diverse CMDs.

Conclusions: Promoting educational attainment, maintaining favorable serum urate, and controlling obesity are specifically prioritized for CMM prevention. Furthermore, avoiding smoking and sedentary behavior, and strengthening physical activity held prominent protective impacts on CMDs. Additionally, improving dyslipidemia and dysglycemia, maintaining favorable blood pressure, and enhancing lung function, would contribute to the co-management of CMDs and preventing the long-term CMM condition. Our investigation provided causality-oriented evidence to establish the risk profile of CMM.

可改变因素与心脏代谢多病的因果关系:一项暴露范围内的孟德尔随机化调查。
背景:心脏代谢多病(CMM)以两种或两种以上的心脏代谢疾病(cmd)共存为特征,包括2型糖尿病(T2D)、冠状动脉疾病(CAD)和中风,一直是全球健康面临的挑战。然而,可改变因素与CMDs和CMM的因果关系仍有待系统研究。方法:本研究采用三阶段设计的孟德尔随机化(Mendelian randomization, MR)调查方法,采用具有潜在样本重叠校正和多重检验的双样本MR、多变量MR分析和多反应MR,以社会经济因素、行为因素、生化因素和物理测量等可修改因素为暴露因素,以CMM和CMDs为结果。应用基于GWAS目录系统收集的最新大规模全基因组关联研究(GWAS)数据。结果:我们的主要研究结果表明,23个可改变因素中的13个在四个领域,包括教育程度(优势比:0.858,95%置信区间:家庭收入(0.794,0.720-0.875),终生吸烟行为(1.201,1.145-1.260),休闲屏幕时间(1.255,1.186-1.327),低密度脂蛋白胆固醇水平(1.062,1.046-1.079),总胆固醇水平(1.045,1.029-1.062),载脂蛋白B(1.035, 1.019-1.051),空腹血糖(1.096,1.038-1.157),糖化血红蛋白(HbA1c)(1.062, 1.037-1.089),收缩压(1.125,1.104-1.146),舒张压(1.104,1.083-1.126),1 s用力呼气量(FEV1)(0.953, 0.931-0.975)和体重指数(BMI)(1.243, 1.210-1.277)对CMM的影响相对较强。此外,家庭收入、终生吸烟行为、HbA1c、收缩压和FEV1与CMM在单一域内被检测为独立的关联。在每个CMD中观察到相似的结果。此外,多反应MR为受教育程度、血清尿酸和BMI与CMM以及终生吸烟行为、中高强度身体活动和休闲屏幕时间与不同CMDs之间的关系提供了强化证据。结论:提高受教育程度、维持良好的血清尿酸水平和控制肥胖是预防慢性粒细胞白血病的重点。此外,避免吸烟和久坐行为以及加强体育活动对慢性阻塞性肺病有显著的保护作用。此外,改善血脂异常和血糖异常,维持良好的血压,增强肺功能,将有助于共同管理CMDs和预防长期CMM病情。我们的调查提供了以因果关系为导向的证据,以建立CMM的风险概况。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cardiovascular Diabetology
Cardiovascular Diabetology 医学-内分泌学与代谢
CiteScore
12.30
自引率
15.10%
发文量
240
审稿时长
1 months
期刊介绍: Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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