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可改变风险因素与虚弱之间的关联:一项孟德尔随机化研究。

Associations between modifiable risk factors and frailty: a Mendelian randomisation study.

机构信息

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China.

Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin 300211, China

出版信息

J Epidemiol Community Health. 2023 Dec;77(12):782-790. doi: 10.1136/jech-2023-220882. Epub 2023 Aug 21.

Abstract

BACKGROUND

Early identification of modifiable risk factors is essential for the prevention of frailty. This study aimed to explore the causal relationships between a spectrum of genetically predicted risk factors and frailty.

METHODS

Univariable and multivariable Mendelian randomisation (MR) analyses were performed to explore the relationships between 22 potential risk factors and frailty, using summary genome-wide association statistics. Frailty was accessed by the frailty index.

RESULTS

Genetic liability to coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), ischaemic stroke, atrial fibrillation and regular smoking history, as well as genetically predicted 1-SD increase in body mass index, systolic blood pressure, diastolic blood pressure, low-density lipoprotein cholesterol, triglycerides, alcohol intake frequency and sleeplessness were significantly associated with increased risk of frailty (all p<0.001). In addition, there was a significant inverse association between genetically predicted college or university degree with risk of frailty (beta -0.474; 95% CI (-0.561 to -0.388); p<0.001), and a suggestive inverse association between high-density lipoprotein cholesterol level with risk of frailty (beta -0.032; 95% CI (-0.055 to -0.010); p=0.004). However, no significant causal associations were observed between coffee consumption, tea consumption, serum level of total testosterone, oestradiol, 25-hydroxyvitamin D, C reactive protein or moderate to vigorous physical activity level with frailty (all p>0.05). Results of the reverse directional MR suggested bidirectional causal associations between T2DM and CAD with frailty.

CONCLUSIONS

This study provided genetic evidence for the causal associations between several modifiable risk factors with lifetime frailty risk. A multidimensional approach targeting these factors may hold a promising prospect for prevention frailty.

摘要

背景

早期识别可改变的风险因素对于预防虚弱至关重要。本研究旨在探索一系列遗传预测风险因素与虚弱之间的因果关系。

方法

使用汇总全基因组关联统计数据,进行单变量和多变量孟德尔随机化(MR)分析,以探讨 22 种潜在风险因素与虚弱之间的关系。使用虚弱指数评估虚弱。

结果

冠心病(CAD)、2 型糖尿病(T2DM)、缺血性中风、心房颤动和有规律的吸烟史、体重指数、收缩压、舒张压、低密度脂蛋白胆固醇、甘油三酯、饮酒频率和失眠的遗传易感性以及遗传预测的 1-SD 增加与虚弱风险增加显著相关(均 p<0.001)。此外,遗传预测的大学或大学学位与虚弱风险呈显著负相关(β-0.474;95%CI(-0.561 至-0.388);p<0.001),而高密度脂蛋白胆固醇水平与虚弱风险呈显著负相关(β-0.032;95%CI(-0.055 至-0.010);p=0.004)。然而,咖啡消费、茶消费、总睾酮、雌二醇、25-羟维生素 D、C 反应蛋白或中等至剧烈体力活动水平与虚弱之间没有观察到显著的因果关系(均 p>0.05)。反向 MR 的结果表明 T2DM 和 CAD 与虚弱之间存在双向因果关系。

结论

本研究提供了遗传证据,证明了一些可改变的风险因素与终生虚弱风险之间存在因果关系。针对这些因素的多维方法可能为预防虚弱提供有希望的前景。

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