肥胖作为主动脉瓣狭窄的病因危险因素。

Obesity as a Causal Risk Factor for Aortic Valve Stenosis.

机构信息

Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

J Am Coll Cardiol. 2020 Jan 21;75(2):163-176. doi: 10.1016/j.jacc.2019.10.050.

DOI:10.1016/j.jacc.2019.10.050

PMID:31948645

Abstract

BACKGROUND

Causal risk factors for aortic valve stenosis are poorly understood, limiting the possibility of preventing the most common heart valve disease.

OBJECTIVES

The hypothesis was tested that genetically based obesity measured by body mass index is causally associated with risk of aortic valve stenosis and replacement.

METHODS

The authors included 108,211 individuals from the Copenhagen General Population Study. Participants had measurements of body mass index, waist-hip ratio, and waist circumference, and information on 5 genetic variants associated with obesity. A Mendelian randomization design was used to investigate genetic and observational associations of obesity with incident aortic valve stenosis (n = 1,215) and replacement (n = 467) for a median follow-up time of 8.7 years.

RESULTS

Genetically increased body mass index was causally associated with increased risk of aortic valve stenosis. Compared with an unweighted allele score of 0 to 3, individuals with an allele score 7 to 10 had a mean increase in body mass index of 0.87 kg/m, and the age and sex-adjusted hazard ratio for aortic valve stenosis was 1.3 (95% confidence interval [CI]: 1.0 to 1.7) for allele score 4, 1.4 (95% CI: 1.1 to 1.8) for allele score 5 to 6, and 1.6 (95% CI: 1.3 to 2.1) for allele score 7 to 10 (p for trend: 9 × 10). A 1-kg/m increase in body mass index was associated with causal risk ratios for aortic valve stenosis and replacement, respectively, of 1.52 (95% CI: 1.23 to 1.87) and 1.49 (95% CI: 1.07 to 2.08) genetically, and with corresponding hazard ratios of 1.06 (95% CI: 1.05 to 1.08) and 1.06 (95% CI: 1.03 to 1.08) observationally.

CONCLUSIONS

Obesity from human genetics was causally associated with higher risk of aortic valve stenosis and replacement.

摘要

背景

主动脉瓣狭窄的因果风险因素尚未被充分认识，这限制了预防最常见的心脏瓣膜疾病的可能性。

目的

作者假设，通过体重指数测量的遗传肥胖与主动脉瓣狭窄和置换的风险具有因果关系，并对此假设进行了检验。

方法

作者纳入了来自哥本哈根普通人群研究的 108211 名参与者。参与者的体重指数、腰臀比和腰围均经过测量，同时还收集了与肥胖相关的 5 种遗传变异信息。采用孟德尔随机化设计，分析了肥胖的遗传和观察性关联与主动脉瓣狭窄（n=1215）和置换（n=467）的发病风险之间的关系，中位随访时间为 8.7 年。

结果

遗传上体重指数的增加与主动脉瓣狭窄风险的增加具有因果关系。与未加权的等位基因评分 0 至 3 相比，等位基因评分 7 至 10 的个体体重指数平均增加 0.87kg/m，年龄和性别校正后的主动脉瓣狭窄风险比为 1.3（95%置信区间[CI]：1.0 至 1.7），评分 4 为 1.4（95%CI：1.1 至 1.8），评分 5 至 6 为 1.4（95%CI：1.1 至 1.8），评分 7 至 10 为 1.6（95%CI：1.3 至 2.1）（趋势检验 p 值：9×10）。体重指数每增加 1kg/m，主动脉瓣狭窄和置换的因果风险比分别为 1.52（95%CI：1.23 至 1.87）和 1.49（95%CI：1.07 至 2.08），相应的危险比分别为 1.06（95%CI：1.05 至 1.08）和 1.06（95%CI：1.03 至 1.08）。