肥胖增加心力衰竭发病率和死亡率：观察性和孟德尔随机化研究总计超过 100 万人。

Obesity increases heart failure incidence and mortality: observational and Mendelian randomization studies totalling over 1 million individuals.

机构信息

Department of Clinical Biochemistry, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.

Department of Clinical Biochemistry, The Copenhagen General Population Study, Copenhagen University Hospital-Herlev and Gentofte Hospital, Herlev, Denmark.

出版信息

Cardiovasc Res. 2023 Feb 3;118(18):3576-3585. doi: 10.1093/cvr/cvab368.

DOI:10.1093/cvr/cvab368

PMID:34954789

Abstract

AIMS

Whether high body mass index (BMI) causally influences development and prognosis of heart failure has implications for clinical practice. We tested the hypotheses that high BMI causally influences heart failure incidence and mortality.

METHODS AND RESULTS

Using observational and Mendelian randomization causal, genetic analyses, we studied 106 121 individuals from the Copenhagen General Population Study, 18 407 from the Copenhagen City Heart Study, and 977 323 from publicly available databases. In observational analyses in the Copenhagen studies with 10 years of median follow-up, multivariable adjusted hazard ratios per 1 kg/m2 increment of BMI were 1.06 (95% confidence interval: 1.05-1.07; P < 0.001; n = 124 528; events = 6589) for heart failure incidence, 1.04 (1.03-1.06; P < 0.001; n = 124 528; events = 1237) for heart failure mortality, and 1.01 (1.00-1.01; P < 0.001; n = 124 528; events = 24 144) for all-cause mortality. In genetic analyses in the Copenhagen studies, the age and sex adjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.19 (1.05-1.36; P = 0.008; n = 118 200; events = 6541) for heart failure incidence, 1.27 (0.82-1.98; P = 0.28; n = 118 200; events = 889) for heart failure mortality, and 1.11 (1.02-1.22; P = 0.022; n = 118 200; events = 16 814) for all-cause mortality. Finally, combining genetic data from the Copenhagen studies, the Genetic Investigation of ANthropometric Traits, the Heart Failure Molecular Epidemiology for Therapeutic Targets, and the UK Biobank, the unadjusted causal risk ratios per 1 kg/m2 increment of BMI were 1.39 (1.27-1.52; P < 0.001; n = 1 095 523; events = 53 850) for heart failure incidence, 1.18 (1.00-1.38; P = 0.05; n = 576 853; events = 2373) for heart failure mortality, and 1.02 (1.00-1.04; P = 0.03; n = 576 853; events = 44 734) for all-cause mortality.

CONCLUSION

High BMI causally increases the risk of both heart failure incidence and mortality.

摘要

目的

高身体质量指数（BMI）是否会对心力衰竭的发生和预后产生因果影响，这对临床实践具有重要意义。我们检验了以下假设，即高 BMI 会对心力衰竭的发病率和死亡率产生因果影响。

方法和结果

我们使用观察性和孟德尔随机化因果遗传分析方法，研究了来自哥本哈根普通人群研究的 106121 人、来自哥本哈根城市心脏研究的 18407 人和来自公开数据库的 977323 人。在哥本哈根研究的观察性分析中，中位随访时间为 10 年，BMI 每增加 1kg/m2，多变量调整后的风险比为 1.06（95%置信区间：1.05-1.07；P<0.001；n=124528；事件=6589），用于心力衰竭的发病率；1.04（1.03-1.06；P<0.001；n=124528；事件=1237），用于心力衰竭死亡率；1.01（1.00-1.01；P<0.001；n=124528；事件=24144），用于全因死亡率。在哥本哈根研究的遗传分析中，BMI 每增加 1kg/m2，年龄和性别调整后的因果风险比为 1.19（1.05-1.36；P=0.008；n=118200；事件=6541），用于心力衰竭的发病率；1.27（0.82-1.98；P=0.28；n=118200；事件=889），用于心力衰竭死亡率；1.11（1.02-1.22；P=0.022；n=118200；事件=16814），用于全因死亡率。最后，结合哥本哈根研究、遗传研究所的人体测量性状的遗传研究、心力衰竭分子流行病学治疗靶点和英国生物银行的遗传数据，BMI 每增加 1kg/m2，未调整的因果风险比为 1.39（1.27-1.52；P<0.001；n=1095523；事件=53850），用于心力衰竭的发病率；1.18（1.00-1.38；P=0.05；n=576853；事件=2373），用于心力衰竭死亡率；1.02（1.00-1.04；P=0.03；n=576853；事件=44734），用于全因死亡率。