Ye Chaojie, Liu Dong, Kong Lijie, Wang Yiying, Dou Chun, Xu Min, Zheng Jie, Zheng Ruizhi, Li Mian, Zhao Zhiyun, Lu Jieli, Chen Yuhong, Wang Weiqing, Bi Yufang, Xu Yu, Wang Tiange, Ning Guang
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, Shanghai Key Laboratory for Endocrine Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mayo Clin Proc. 2024 Oct;99(10):1589-1605. doi: 10.1016/j.mayocp.2024.02.019. Epub 2024 Jul 10.
To investigate the causal effect of protein intake on hypertension and the related mediating pathways.
Using genome-wide association study summary statistics of European ancestry, we applied univariable and multivariable Mendelian randomization to estimate the bidirectional associations of relative protein intake and related metabolomic signatures with hypertension (FinnGen: Ncase=42,857/Ncontrol=162,837; UK Biobank: Ncase=77,723/Ncontrol=330,366) and blood pressure (International Consortium of Blood Pressure: N=757,601) and two-step Mendelian randomization to assess the mediating roles of 40 cardiometabolic factors therein. Mendelian randomization estimates of hypertension from FinnGen and UK Biobank were meta-analyzed without heterogeneity. We performed the study from May 15, 2023, to September 15, 2023.
Each 1-SD higher relative protein intake was causally associated with 69% (odds ratio, 0.31; 95% CI, 0.11 to 0.89) lower hypertension risk independent of the effects of other macronutrients, and was the only macronutrient associated with 2.21 (95% CI, 0.52 to 3.91) mm Hg lower pulse pressure, in a unidirectional manner. Higher plant protein-related metabolomic signature (glycine) was associated with lower hypertension risk and pulse pressure, whereas higher animal protein-related metabolomic signatures (leucine, isoleucine, valine, and isovalerylcarnitine [only systolic blood pressure]) were associated with higher hypertension risk, pulse pressure, and systolic blood pressure. The effect of relative protein intake on hypertension was causally mediated by frailty index (mediation proportion, 40.28%), monounsaturated fatty acids (13.81%), saturated fatty acids (11.39%), grip strength (5.34%), standing height (3.99%), and sitting height (3.61%).
Higher relative protein intake causally reduces the risk of hypertension, partly mediated by physical fitness and circulating fatty acids.
研究蛋白质摄入量对高血压的因果效应及相关中介途径。
利用欧洲血统人群的全基因组关联研究汇总统计数据，我们应用单变量和多变量孟德尔随机化方法来估计相对蛋白质摄入量及相关代谢组学特征与高血压（芬兰基因库：病例数 = 42,857/对照数 = 162,837；英国生物银行：病例数 = 77,723/对照数 = 330,366）和血压（国际血压联盟：N = 757,601）之间的双向关联，并采用两步孟德尔随机化方法评估40种心血管代谢因素在其中的中介作用。对来自芬兰基因库和英国生物银行的高血压孟德尔随机化估计值进行了无异质性的荟萃分析。我们于2023年5月15日至2023年9月15日开展了该研究。
相对蛋白质摄入量每增加1个标准差，在不考虑其他常量营养素影响的情况下，与高血压风险降低69%（比值比，0.31；95%置信区间，0.11至0.89）存在因果关联，并且是唯一与脉压降低2.21（95%置信区间，0.52至3.91）mmHg存在单向关联的常量营养素。较高的植物蛋白相关代谢组学特征（甘氨酸）与较低高血压风险和脉压相关，而较高的动物蛋白相关代谢组学特征（亮氨酸、异亮氨酸、缬氨酸和异戊酰肉碱[仅收缩压]）与较高高血压风险、脉压和收缩压相关。相对蛋白质摄入量对高血压的影响通过衰弱指数（中介比例，40.28%）、单不饱和脂肪酸（13.81%）、饱和脂肪酸（11.39%）、握力（5.34%）、身高（3.99%）和坐高（3.61%）产生因果中介作用。
较高的相对蛋白质摄入量可因果性降低高血压风险，部分由身体健康状况和循环脂肪酸介导。
