An Empirically Derived Definition of Metabolically Healthy Obesity Based on Risk of Cardiovascular and Total Mortality.
An Empirically Derived Definition of Metabolically Healthy Obesity Based on Risk of Cardiovascular and Total Mortality.
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DOI：
10.1001/jamanetworkopen.2021.8505
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发表时间：
2021-05-03
影响因子：
13.8
通讯作者：
Schulze MB
中科院分区：
文献类型：
--
作者：
Zembic A;Eckel N;Stefan N;Baudry J;Schulze MB
能不能从经验上得出代谢健康的定义，从而对肥胖人群的死亡风险进行分层？在这项研究中，包括来自两个队列的386420个人的数据，建立了代谢健康肥胖的新定义。根据这一定义，表型被定义为代谢不健康的人在心血管疾病死亡率和总死亡率方面的风险比明显更高，与体重指数类别无关，而表型被定义为代谢健康肥胖的人的风险没有增加。本研究确定的代谢健康的新定义可能允许对肥胖人群以及超重和正常体重人群的死亡风险进行分层。被先天定义为代谢健康型肥胖的人，与代谢健康型正常体重的人相比，死亡风险往往更高，这表明这些定义可能是不够的。系统地得出代谢健康（MH）的新定义，并探讨其与心血管疾病（CVD）死亡率和总死亡率的关系。在一项队列研究中，使用了第三次全国健康与营养调查（NHANES-III）的数据，这是一项使用复杂多阶段概率抽样的代表性调查，人体测量因素、生物标志物和血压（BP）与肥胖参与者的总死亡率和心血管疾病死亡率相关，并通过Cox比例风险回归确定。计算受者工作特征下的面积以确定用于定义MH的死亡率预测因素，通过约登指数确定截止水平，并通过与独立的英国生物银行队列（一项基于人群的前瞻性研究）的比较来验证研究结果。纳入数据库中所有年龄在18 - 75岁、无心血管疾病史、体重指数大于或等于18.5、在NHANES-III检查前禁食6小时或更长时间的非怀孕参与者；未进行血液测量的英国生物银行队列参与者被排除在外。该研究于2015年至2020年进行。采用新定义定义了体质指数和MH，并与3种先验定义进行了比较。心血管疾病死亡率和总死亡率。在NHANES-III （n = 12341）队列中，平均（SD）年龄为41.6（29.2）岁，50.7%为女性，平均随访时间为14.5（2.7）年。在UK Biobank （n = 374079）队列中，平均（SD）年龄为56.2（8.1）岁，55.1%为女性，平均随访时间为7.8（1.0）年。使用降压药物（心血管疾病死亡率的危险比[HR]为2.41；95% CI为1.50-3.87；总死亡率为2.05；95% CI为1.47-2.84）、糖尿病和几个连续因素与死亡率相关。在所有显著的连续因素中，收缩压和腰臀比的组合显示接受者工作特征下的面积最大（心血管疾病死亡率：0.775;95% CI, 0.770-0.781；总死亡率：0.696;95% CI, 0.694-0.699）。因此，MH被定义为收缩压小于130毫米汞柱，没有降压药物，腰臀比女性小于0.95，男性小于1.03，没有自我报告的（即普遍存在的）糖尿病。在这两个队列中，与代谢健康的正常体重相比，代谢健康的肥胖与心血管疾病和总死亡率无关。对于NHANES-III，心血管疾病死亡率的风险比为0.68 (95% CI, 0.30-1.54)，总死亡率的风险比为1.03 （95% CI, 0.70-1.51）。对于UK Biobank，心血管疾病死亡率的风险比为1.17 (95% CI, 0.81-1.69)，总死亡率的风险比为0.98 （95% CI, 0.87-1.10）。无论身体质量指数如何，所有代谢不健康的人群都显示出更高的风险。新提出的MH定义可能会确定一个没有增加死亡风险的肥胖亚组，并对超重或正常体重人群的风险进行分层。本队列研究提出了代谢健康肥胖的新定义，并探讨了其在估计心血管疾病死亡率和总死亡率中的应用。
Can a definition of metabolic health be empirically derived that allows to stratify risk of mortality in people with obesity? In this study including data from 386 420 individuals across 2 cohorts, a new definition of metabolically healthy obesity was established. People with a phenotype defined as metabolically unhealthy using this definition had significantly higher hazard ratios for cardiovascular disease mortality and total mortality irrespective of body mass index category, and people with phenotypes defined as having metabolically healthy obesity displayed no increased risk. A new definition of metabolic health identified in this study may allow to stratify risk of mortality not only in people with obesity but also in people with overweight and normal weight. People classified by a priori definitions as having metabolically healthy obesity have frequently been found to be at increased risk of mortality, compared with individuals with metabolically healthy normal weight, suggesting these definitions may be insufficient. To systematically derive a new definition of metabolic health (MH) and investigate its association with cardiovascular disease (CVD) mortality and total mortality. In a cohort study using data from the third National Health and Nutrition Examination Survey (NHANES-III), a representative survey using complex multistage probability sampling, anthropometric factors, biomarkers, and blood pressure (BP) associated with total and CVD mortality among participants with obesity were identified with Cox proportional hazards regression. Area under the receiver operating characteristic was calculated to identify predictive factors for mortality to be used to define MH, cutoff levels were determined by the Youden index, and the findings were validated through comparison with the independent UK Biobank cohort, a population-based prospective study. All nonpregnant participants in the databases aged 18 to 75 years with no history of CVD, body mass index greater than or equal to 18.5, and who fasted 6 or more hours before examination in NHANES-III were included; participants in the UK Biobank cohort who did not have blood measurements were excluded. The study was conducted from 2015 to 2020. Body mass index and MH were defined by the new definition and compared with 3 a priori definitions. Cardiovascular disease mortality and total mortality. Within the NHANES-III (n = 12 341) cohort, mean (SD) age was 41.6 (29.2) years, 50.7% were women, and mean follow-up was 14.5 (2.7) years. Within the UK Biobank (n = 374 079) cohort, mean (SD) age was 56.2 (8.1) years, 55.1% were women, and mean follow-up was 7.8 (1.0) years. Use of blood pressure (BP)-lowering medication (hazard ratio [HR] for CVD mortality, 2.41; 95% CI, 1.50-3.87 and total mortality, 2.05; 95% CI, 1.47-2.84), diabetes, and several continuous factors were associated with mortality. Of all significant continuous factors, the combination of systolic BP and waist-to-hip ratio showed the highest area under the receiver operating characteristic (CVD mortality: 0.775; 95% CI, 0.770-0.781; total mortality: 0.696; 95% CI, 0.694-0.699). Thus, MH was defined as systolic BP less than 130 mm Hg, no BP-lowering medication, waist-to-hip ratio less than 0.95 for women and less than 1.03 for men, and no self-reported (ie, prevalent) diabetes. In both cohorts, metabolically healthy obesity was not associated with CVD and total mortality compared with metabolically healthy normal weight. For NHANES-III, the hazard ratio was 0.68 (95% CI, 0.30-1.54) for CVD mortality and 1.03 (95% CI, 0.70-1.51) for total mortality. For UK Biobank, the hazard ratio was 1.17 (95% CI, 0.81-1.69) for CVD mortality and 0.98 (95% CI, 0.87-1.10) for total mortality. Regardless of body mass index, all metabolically unhealthy groups displayed increased risks. This newly proposed definition of MH may identify a subgroup of people with obesity without increased risk of mortality and stratify risks in people who are overweight or normal weight. This cohort study formulates a new definition of metabolically healthy obesity and examines its use in estimation of cardiovascular disease mortality and total mortality.
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