Molavizadeh Danial, Masrouri Soroush, Esmaeili Farzad, Azizi Fereidoun, Hadaegh Farzad
Prevention of Metabolic Disorders Research Center, Research Institute for Metabolic and Obesity Disorders, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences Tehran Iran.
Endocrine Research Center, Research Institute for Endocrine Disorders, Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences Tehran Iran.
J Am Heart Assoc. 2025 Sep 16;14(18):e040930. doi: 10.1161/JAHA.124.040930. Epub 2025 Sep 1.
Less is known regarding the association between metabolic phenotypes of general and abdominal obesity and incident cardio-renal-metabolic (CRM) multimorbidity, defined as coexistence of at least 2 of the following: diabetes, chronic kidney disease, and cardiovascular diseases (hypertension or stroke or coronary heart disease).
Among 6343 participants (3555 women), with a mean age of 37.06 years, metabolically healthy status was defined as absence of any metabolic syndrome components. Participants were classified as metabolically healthy/unhealthy normal weight, overweight, and obese on the basis of body mass index; and metabolically healthy/unhealthy nonabdominal obese and abdominal obese according to waist circumference. Multivariable Cox hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs, adjusted for age, sex, smoking status, education level, marital status, pulse rate, estimated glomerular filtration rate, family history of premature cardiovascular disease, and family history of diabetes.
During a median follow-up of 14.3 years, CRM multimorbidity occurred in 4.8, 13.4, 15.0, 10.8, 17.4, and 29.9% of participants with metabolically healthy normal weight, metabolically healthy overweight, metabolically healthy obese, metabolically unhealthy normal weight, metabolically unhealthy overweight, and metabolically unhealthy obese phenotypes, respectively. In multivariable analyses, compared with the metabolically healthy normal weight, participants with metabolically healthy overweight (HR, 2.08 [95% CI, 1.35-3.20]), metabolically healthy obese (HR, 2.04 [95% CI, 1.11-3.75]), metabolically unhealthy normal weight (HR, 2.29 [95% CI, 1.61-3.27]), metabolically unhealthy overweight (HR, 2.83 [95% CI, 2.01-3.99]), and metabolically unhealthy obese (HR, 5.16 [95% CI, 3.64-7.32]) phenotypes had higher risk of developing CRM multimorbidity. Compared with the metabolically healthy abdominal obese phenotype, participants with metabolically healthy nonabdominal obese (HR, 1.77 [95% CI, 1.19-2.64)], metabolically unhealthy nonabdominal obese (HR, 1.95 [95% CI, 1.48-2.57]), and metabolically unhealthy abdominal obese (HR, 3.26 [95% CI, 2.49-4.28]) exhibited elevated risk. Generally, we found no statistically significant effect modification by sex and age; however, these associations were more pronounced among women and younger individuals.
Our results indicate that there is no benign phenotype of obesity beyond metabolically healthy normal weight regarding the incidence of CRM multimorbidity.
关于一般肥胖和腹型肥胖的代谢表型与心血管-肾脏-代谢（CRM）多重疾病（定义为以下至少两种疾病共存：糖尿病、慢性肾脏病和心血管疾病（高血压或中风或冠心病））之间的关联，人们了解较少。
在6343名参与者（3555名女性）中，平均年龄为37.06岁，代谢健康状态定义为不存在任何代谢综合征成分。参与者根据体重指数分为代谢健康/不健康的正常体重、超重和肥胖；并根据腰围分为代谢健康/不健康的非腹型肥胖和腹型肥胖。使用多变量Cox风险回归模型来估计风险比（HRs）和95%置信区间（CIs），并对年龄、性别、吸烟状况、教育水平、婚姻状况、脉搏率、估计肾小球滤过率、心血管疾病家族史和糖尿病家族史进行了调整。
在中位随访14.3年期间，代谢健康的正常体重、代谢健康的超重、代谢健康的肥胖、代谢不健康的正常体重、代谢不健康的超重和代谢不健康的肥胖表型的参与者中，CRM多重疾病的发生率分别为4.8%、13.4%、15.0%、10.8%、17.4%和29.9%。在多变量分析中，与代谢健康的正常体重相比，代谢健康的超重（HR，2.08 [95% CI，1.35 - 3.20]）、代谢健康的肥胖（HR，2.04 [95% CI，1.11 - 3.75]）、代谢不健康的正常体重（HR，2.29 [95% CI，1.61 - 3.27]）、代谢不健康的超重（HR，2.83 [95% CI，2.01 - 3.99]）和代谢不健康的肥胖（HR，5.16 [95% CI，3.64 - 7.32]）表型的参与者发生CRM多重疾病的风险更高。与代谢健康的腹型肥胖表型相比，代谢健康的非腹型肥胖（HR，1.77 [95% CI，1.19 - 2.64]）、代谢不健康的非腹型肥胖（HR，1.95 [95% CI，1.48 - 2.57]）和代谢不健康的腹型肥胖（HR，3.26 [95% CI，2.49 - 4.28]）的参与者风险升高。一般来说，我们发现性别和年龄没有统计学上显著的效应修正；然而，这些关联在女性和年轻人中更为明显。
我们的结果表明，就CRM多重疾病的发生率而言，除了代谢健康的正常体重外，不存在肥胖的良性表型。
