作者：钮岳岳1，2 ，艾克热木·艾尔肯1，2 ，李红萍1，2 ，李明昊1，2 ，李琳轩1 ，冯玲1

单位：

1.100053北京市，中国中医科学院广安门医院干保科 2.100029北京市，北京中医药大学研究生院

Units：

1.Cadres Health Protection Department, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China 2.Graduate School of Beijing University of CM, Beijing 100029, China

关键词：

心力衰竭；肌肉减少症；孟德尔随机化分析；因果关系

Keywords：

Heart failure; Sarcopenias; Mendelian randomization analysis; Causality

CLC：

R 541.62 R 746.4

DOI：

10.12114/j.issn.1008-5971.2024.00.003

Funds：

中国中医科学院科技创新工程重大攻关项目（CI2021A03001）

摘要：

目的　采用双样本孟德尔随机化（MR）方法分析肌肉减少症与心力衰竭的因果关系。方法　本研究 采用双样本MR方法，暴露因素为肌肉减少症，结局为心力衰竭。筛选工具变量，主要采用逆方差加权法（IVW）进 行MR，然后采用加权中位数法评估因果关系的可靠性，采用MR-Egger回归识别水平多效性并校正多重效应。最后采 用Cochran Q检验、MR-Egger截距法、留一法进行敏感性分析。结果　本研究共筛选出556个与四肢瘦体重（ALM） 强相关的单核苷酸多态性（SNP）、147个与左手握力强相关的SNP、157个与右手握力强相关的SNP、54个与步行速 度强相关的SNP。IVW分析结果显示，ALM升高与心力衰竭发生风险升高有关〔OR=1.05，95%CI（1.02～1.09）， P=4.95×10-4〕，步行速度增快与心力衰竭发生风险降低有关〔OR=0.33，95%CI（0.26～0.43），P=7.07×10-18〕； 加权中位数法分析结果显示，ALM升高与心力衰竭发生风险升高有关〔OR=1.09，95%CI（1.05～1.14 ）， P = 3.25× 10-5〕，步行速度增快与心力衰竭发生风险升高有关〔OR=0.36，95%CI（0.27～0.48），P=5.13×10 -12〕； MR-Egger 回归分析结果显示，ALM升高与心力衰竭发生风险升高有关〔OR=1.11，95%CI（1.03～1.19），P=3.82×10 -3 〕，但 步行速度增快与心力衰竭发生风险降低无关〔OR=0.92，95%CI（0.34～2.51），P=0.869）。IVW、加权中位数法、 MR-Egger回归分析结果均显示，左侧握力和右侧握力与心力衰竭发生风险无关（P＞0.05）。Cochran Q检验结果显 示，与ALM、左侧握力、右侧握力、步行速度强相关的SNP间有统计学异质性（P＜0.05）；MR-Egger截距法分析结果 显示，与ALM、左侧握力、右侧握力、步行速度强相关的SNP不存在水平多效性。留一法分析结果显示，ALM、左侧 握力、右侧握力、步行速度与心力衰竭的因果关系并非由单个SNP驱动。结论　ALM升高与心力衰竭发生风险增加有 关，步行速度增快与心力衰竭发生风险降低相关，但并未发现握力与心力衰竭发生风险相关。

Abstract：

Objective To analyze the causality between sarcopenia and heart failure by two-sample Mendelian randomization (MR) method. Methods In this study, a two-sample MR method was used. The exposure factor was sarcopenia and the outcome was heart failure. The instrumental variables were screened, and the inverse variance weighting (IVW) was mainly used for MR. Then the weighted median method was used to evaluate the reliability of causality, and the MR-Egger regression was used to identify the horizontal pleiotropy and correct the multiple effects. Finally, Cochran Q test, MR-Egger intercept method and leave-one-out method were used for sensitivity analysis. Results In this study, a total of 556 single nucleotide polymorphisms (SNPs) strongly associated with appendicular lean mass (ALM) , 147 SNPs strongly associated with left hand grip strength, 157 SNPs strongly associated with right hand grip strength, and 54 SNPs strongly associated with walking speed were screened. IVW analysis results showed that increased ALM was associated with increased risk of heart failure [OR=1.05, 95%CI (1.02-1.09) , P=4.95×10-4] , and increased walking speed was associated with decreased risk of heart failure [ OR=0.33, 95%CI (0.26-0.43) , P=7.07×10 -18] . The results of weighted median analysis showed that increased ALM was associated with increased risk of heart failure [OR=1.09, 95%CI (1.05-1.14) , P=3.25×10 -5] , and increased walking speed was associated with decreased risk of heart failure [OR=0.36, 95%CI (0.27-0.48) , P=5.13×10 -12 ] . The results of MR-Egger regression analysis showed that increased ALM was associated with increased risk of heart failure [OR=1.11, 95%CI (1.03-1.19) , P=3.82×10 -3] , while increased walking speed was not associated with decreased risk of heart failure [OR=0.92, 95%CI (0.34-2.51) , P=0.869] . IVW, weighted median method and MR-Egger regression analysis showed that left hand grip strength and right hand grip strength were not related to the risk of heart failure (P > 0.05) . Cochran Q test results showed that there was statistical heterogeneity between SNPs related to ALM, left hand grip strength, right hand grip strength and walking speed (P < 0.05) . The results of MR-Egger intercept method showed that there was no horizontal pleiotropy in the SNPs strongly related to ALM, left hand grip strength, right hand grip strength and walking speed. The results of leave-one-out analysis showed that the causality between ALM, left hand grip strength, right hand grip strength, walking speed and heart failure was not driven by a single SNP. Conclusion Increased ALM is associated with increased risk of heart failure, increased walking speed is associated with decreased risk of heart failure, while hand grip strength is not found to be associated with the risk of heart failure.

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