Metabolic Phenotypes of Overweight/Obesity and Risk of Cardiovascular Diseases in Postmenopausal Women: Findings from the China PEACE Million Persons Project

BACKGROUND Obesity and metabolic abnormalities were associated with increased risk of cardiovascular diseases (CVD). However, much remains unknown about which metabolic weight phenotypes and how relate to CVD, especially in postmenopausal women. METHODS AND RESULTS We included 15,575 postmenopausal women aged 35 to 75 years (median age, 60.6 [IQR: 55.0-65.7]) free of CVD at baseline from a subcohort of the China Patient-centered Evaluative Assessment of Cardiac Events Million Persons Project between 1 January 2016 and 31 December 2020 in Guangdong Province at 8 sites. Cox regression models were used to investigate the associations of metabolic and overweight/obese status with the risk of developing CVD. Over a median follow-up period of 3.32 years, a total of 1354 CVD events occurred. Overall, 30.3% were metabolically heathy among the 9404 overweight/obese participants, while 49.2% were metabolically unhealthy among the 6171 normal weight subjects. Compared with the metabolically healthy normal weight group, the remaining three groups of participants were all at higher risk of combined CVD, with multivariate-adjusted hazard ratios and 95% confidence intervals of 1.41 (1.16–1.71) for metabolically unhealthy normal weight, 1.42 (1.16–1.73) for metabolically healthy overweight/obesity, and 1.75 (1.47–2.07) for metabolically unhealthy overweight/obesity. When subdividing overweight/obesity separately into overweight and obesity, combined CVD risk was only greater in metabolically unhealthy individuals across different weight categories. CONCLUSIONS Postmenopausal women with metabolically healthy overweight/obesity and metabolically unhealthy normal weight had a higher risk of cardiovascular disease than those with metabolically healthy normal weight, and the association of metabolically unhealthy overweight/obesity was greatest among four categories, suggesting that metabolic abnormalities and overweight/obesity should be monitored and controlled. CLINICAL PERSPECTIVE What Is New? Postmenopausal women with metabolic abnormalities combined with overweight/obesity and even normal weight had a higher risk of cardiovascular disease (CVD) than those with metabolically healthy normal weight. Metabolically healthy overweight/obesity were associated with greater risk of CVD, indicating that overweight/obesity alone may contribute to CVD risk in postmenopausal women. What Are the Clinical Implications? Individuals who are metabolically unhealthy and overweight/obese warrant close clinical supervision, while those of normal weight should not be ignored.