Estimating the causal effect of BMI on mortality risk in people with heart disease, diabetes and cancer using Mendelian randomization
Estimating the causal effect of BMI on mortality risk in people with heart disease, diabetes and cancer using Mendelian randomization
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DOI：
10.1016/j.ijcard.2021.02.027
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发表时间：
2021-03-19
影响因子：
3.5
通讯作者：
Rutter, Martin K.
中科院分区：
文献类型：
--
作者：
Jenkins, David A.;Wade, Kaitlin H.;Rutter, Martin K.
背景资料：观察数据表明，与正常体重相比，超重或肥胖与死亡风险相关-“肥胖悖论”。我们使用孟德尔随机化（MR）来估计体重指数（BMI）对冠心病（CHD）、2型糖尿病（T2 DM）或恶性肿瘤患者死亡风险的因果影响，这些患者中经常报告这种矛盾。我们研究了457，746名白色英国生物样本库参与者，包括3个T2 DM亚组（n = 19，737），CHD（n = 21，925）或癌症（n = 42，612），并使用多变量调整的考克斯模型和MR方法来描述BMI和死亡风险之间的关系。观察性考克斯模型显示BMI和死亡风险之间的J形关系，包括在与最小死亡风险相关的BMI值在超重/肥胖范围内的疾病亚组内（26.5- 32.5kg/m2）。在所有参与者中，MR分析显示BMI对死亡风险的正线性因果效应（每单位BMI升高的死亡率HR：1.05; 95% CI：1.03-1.08），在CHD患者中也很明显（HR：1.08; 95% CI：1.01-1.14）。点估计的风险比在所有的BMI值与T2 DM和癌症的参与者是一致的整体积极的线性效应，但置信区间包括null.Conclusion：这些数据支持的想法，人口努力促进有意减肥对正常的BMI范围将减少，而不是提高，死亡风险在一般人群中，包括，重要的是，个人与冠心病。(C)2021由爱思唯尔公司出版
Background: Observational data have reported that being overweight or obese, compared to being normal weight, is associated with a tower risk for death - the "obesity paradox". We used Mendelian randomization (MR) to estimate causal effects of body mass index (BMI) on mortality risks in people with coronary heart disease (CHD), type 2 diabetes mellitus (T2DM) or malignancy in whom this paradox has been often reported.Methods: We studied 457,746 White British UK Biobank participants including three subgroups with T2DM (n = 19,737), CHD (n = 21,925) or cancer (n = 42,612) at baseline and used multivariable-adjusted Cox models and MR approaches to describe relationships between BMI and mortality risk.Results: Observational Cox models showed J-shaped relationships between BMI and mortality risk including within disease subgroups in which the BMI values associated with minimum mortality risk were within overweight/obese ranges (26.5-32.5 kg/m(2)). In all participants, MR analyses showed a positive linear causal effect of BMI on mortality risk (HR for mortality per unit higher BMI: 1.05; 95% CI: 1.03-1.08), also evident in people with CHD (HR: 1.08; 95% CI: 1.01-1.14). Point estimates for hazard ratios across all BMI values in participants with T2DM and cancer were consistent with overall positive linear effects but confidence intervals included the null.Conclusion: These data support the idea that population efforts to promote intentional weight loss towards the normal BMI range would reduce, not enhance, mortality risk in the general population including, importantly, individuals with CHD. (C) 2021 Published by Elsevier B.V.