. 2025 Jul 15;25(1):2464.

doi: 10.1186/s12889-025-23628-w.

Association of obesity phenotypes with risk of cardiovascular disease mortality: a prospective cohort study

Ruixue Song^#^{1

2

3

4

5}, Yanfeng Jiang^#^{6

7}, Jiaojiao Pang^#^{1

2

3

4

5}, Shuo Wu¹, Jingjing Ma^{1

2

3

4

5}, Ping Li^{1

2

3

4

5}, Xiaohui Wu^{1

2

3

4

5}, Feng Xu^{1

2

3

4

5}, Jiali Wang^{8

9

10

11

12}, Xingdong Chen^{13

14}, Yuguo Chen^{15

16

17

18

19}

Affiliations

¹ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China.
² Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China.
³ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
⁴ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China.
⁵ The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China.
⁶ State Key Laboratory of Genetics and Development of Complex Phenotypes, Research and Innovation Center, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
⁷ Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
⁸ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China. wangjiali_2000@126.com.
⁹ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹⁰ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹¹ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹² The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹³ State Key Laboratory of Genetics and Development of Complex Phenotypes, Research and Innovation Center, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University, Shanghai, China. xingdongchen@fudan.edu.cn.
¹⁴ Fudan University Taizhou Institute of Health Sciences, Taizhou, China. xingdongchen@fudan.edu.cn.
¹⁵ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China. chen919085@sdu.edu.cn.
¹⁶ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁷ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁸ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁹ The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.

^# Contributed equally.

PMID: 40665287
PMCID: PMC12261586
DOI: 10.1186/s12889-025-23628-w

Association of obesity phenotypes with risk of cardiovascular disease mortality: a prospective cohort study

Ruixue Song et al. BMC Public Health. 2025.

. 2025 Jul 15;25(1):2464.

doi: 10.1186/s12889-025-23628-w.

Authors

Affiliations

¹ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China.
² Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China.
³ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China.
⁴ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China.
⁵ The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China.
⁶ State Key Laboratory of Genetics and Development of Complex Phenotypes, Research and Innovation Center, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
⁷ Fudan University Taizhou Institute of Health Sciences, Taizhou, China.
⁸ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China. wangjiali_2000@126.com.
⁹ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹⁰ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹¹ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹² The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. wangjiali_2000@126.com.
¹³ State Key Laboratory of Genetics and Development of Complex Phenotypes, Research and Innovation Center, Zhangjiang Fudan International Innovation Center, and National Clinical Research Center for Aging and Medicine, Human Phenome Institute, Shanghai Pudong Hospital, Fudan University, Shanghai, China. xingdongchen@fudan.edu.cn.
¹⁴ Fudan University Taizhou Institute of Health Sciences, Taizhou, China. xingdongchen@fudan.edu.cn.
¹⁵ Department of Emergency Medicine, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, China. chen919085@sdu.edu.cn.
¹⁶ Shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine, Chest Pain Center, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁷ Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Shandong Provincial Engineering Laboratory for Emergency and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁸ NMPA Key Laboratory for Clinical Research and Evaluation of Innovative Drug, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.
¹⁹ The Key Laboratory of Cardiovascular Remodeling and Function Research, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, China. chen919085@sdu.edu.cn.

^# Contributed equally.

PMID: 40665287
PMCID: PMC12261586
DOI: 10.1186/s12889-025-23628-w

Abstract

Background: Prospective longitudinal studies have shown inconsistent effects of obesity phenotypes on the risk of cardiovascular disease (CVD) mortality. Also, longitudinal evidence from Chinese populations remained scarce. We aimed to investigate the association of obesity phenotypes assessed by body mass index (BMI) and metabolic syndrome (MetS) with risk of CVD mortality, leveraging the unique adiposity patterns and metabolic vulnerability of Asian populations.

Methods: A subset of 26,884 participants (aged 49.30 ± 10.37 years, 39.23% men) from Taizhou longitudinal study were followed up to 8 years. Obesity phenotypes were categorized into 4 groups including metabolically healthy non-obese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy non-obese (MUNO) and metabolically unhealthy obese (MUO), using BMI categories from Chinese criteria (obesity: ≥28.0 kg/m²) and MetS defined by International Diabetes Federation (IDF) consensus. The death caused by CVD were identified based on international classification of diseases-10th Revision (ICD-10). Data were analyzed using the Cox regression models and Laplace regression models.

Results: Of 26,884 participants, 15,462 (57.5%), 1,702 (6.3%), 3,656 (13.6%) and 2,064 (7.7%) subjects were classified into the MHNO, MHO, MUNO and MUO group, respectively. At the end of the follow-up, 113 (0.39%) participants died because of CVD. Compared with the MHNO group, the hazards ratios (HRs) and 95% confidence intervals (CIs) of CVD mortality were 1.73 (1.03–2.91) and 1.97 (1.11–3.52) respectively in MUNO and MUO group. The multi-adjusted 50th percentile differences (50th PDs) (95% CIs) of time at incident CVD mortality in MUNO and MUO group were 0.97 (0.00-1.93) and 1.35 (0.31–2.39) years earlier respectively than those in MHNO group. MHO group showed no significant risk elevation (HR = 1.21, 0.68–2.17) despite the earlier 50th percentile differences of CVD mortality years (50th PD = 0.94, 95%CI: 0.38–2.25).

Conclusions: Metabolic abnormalities increased the risk of CVD mortality especially in participants with obesity.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12889-025-23628-w.

Keywords: CVD mortality; Metabolic syndrome; Metabolically unhealthy non-obese; Metabolically unhealthy obese; Obesity phenotypes.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: This study was approved by the ethics committee of the Taizhou Institute of Health Sciences, Fudan University. All the participants provided written informed consent before data collection. This research conformed to the principles of the Helsinki Declaration. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

**Fig. 1**
Flowchart of the study population

**Fig. 2**
Forest plot for the association of obesity phenotypes with cardiovascular disease (CVD) mortality Adjusted for age, sex, education, smoking, alcohol consumption, physical activity and family history of heart diseaseAbbreviations: MHNO= Metabolically healthy non-obese, MHO= Metabolically healthy obese, MUNO= Metabolically unhealthy non-obese, MUO= Metabolically unhealthy obese

See this image and copyright information in PMC

References

1. WHO, Obesity. and Overweight. 2025. Available from: https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight.
1. Collaborators GBDAB. Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. Lancet. 2025;405:813–38. 10.1016/S0140-6736(25)00355-1. - PMC - PubMed
1. Pan XF, Wang L, Pan A. Epidemiology and determinants of obesity in China. Lancet Diabetes Endocrinol. 2021;9:373–92. 10.1016/S2213-8587(21)00045-0. - PubMed
1. Tian Y, Jiang C, Wang M, Cai R, Zhang Y, He Z, et al. BMI, leisure-time physical activity, and physical fitness in adults in china: results from a series of National surveys, 2000-14. Lancet Diabetes Endocrinol. 2016;4:487–97. 10.1016/S2213-8587(16)00081-4. - PubMed
1. Schienkiewitz A, Schulze MB, Hoffmann K, Kroke A, Boeing H. Body mass index history and risk of type 2 diabetes: results from the European prospective investigation into Cancer and nutrition (EPIC)-Potsdam study. Am J Clin Nutr. 2006;84:427–33. 10.1093/ajcn/84.1.427. - PubMed

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Association of obesity phenotypes with risk of cardiovascular disease mortality: a prospective cohort study

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Association of obesity phenotypes with risk of cardiovascular disease mortality: a prospective cohort study

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