How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies
Abstract Background Recent basic biological research found that obesity accelerates biological aging and increases cardiovascular disease (CVD) risk. However, there is still a lack of real-world population evidence. This study aimed to explore the potential mediation roles of biological age accelera...
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BMC
2025-05-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02770-0 |
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| author | Lin Hu Jiayuan Li Zihuan Tang Peng Gong Zongqi Chang Chen Yang Tianpei Ma Shuang Jiang Chunxia Yang Tao Zhang |
| author_facet | Lin Hu Jiayuan Li Zihuan Tang Peng Gong Zongqi Chang Chen Yang Tianpei Ma Shuang Jiang Chunxia Yang Tao Zhang |
| author_sort | Lin Hu |
| collection | DOAJ |
| description | Abstract Background Recent basic biological research found that obesity accelerates biological aging and increases cardiovascular disease (CVD) risk. However, there is still a lack of real-world population evidence. This study aimed to explore the potential mediation roles of biological age acceleration in the associations between different dimensions of obesity characterization and incident CVD. Methods This international multi-cohort study included participants aged over 45 years with 3 waves longitudinal data from China Health and Retirement Longitudinal Study (CHARLS). China Health and Nutrition Survey (CHNS) was used to develop Klemera-Doubal method-biological age (KDM-BA), and the validation analysis was performed in UK Biobank (UKB) and Hongguang Elderly Health Examination Cohort (HEHEC). Obesity indices including body mass index (BMI), waist circumference (WC), waist height ratio (WtHR), body roundness index (BRI) for body shape; Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) for visceral fat accumulation; triglyceride-glucose index (TyG) and its derivatives (TyG-BMI, TyG-WC, TyG-WtHR) for metabolic function were used to measure obesity across different dimensions. Biological age acceleration was evaluated by the classic KDM-BA acceleration (KDM-BAacc). Causal mediation analyses assessed the role of biological age acceleration in mediating obesity and incident CVD. Results In CHARLS, the median follow-up period was 9.00 years, with a baseline age of 58 (52, 65) years. Obesity, KDM-BAacc, and CVD were all significantly associated with each other. For each 1-year increase in KDM-BAacc, the risk of incident stroke, heart disease and CVD increased by 68% (OR 1.68, 95% CI 1.35–2.09), 35% (OR 1.35, 95% CI 1.15–1.59), and 44% (OR 1.44, 95% CI 1.25–1.65), respectively. KDM-BAacc mediated the associations between BMI, WC, WtHR, BRI, CVAI, LAP, TyG-BMI, TyG-WC, TyG-WtHR, with CVD, with the mediation proportions ranging from 10.03 to 25.46%. However, the mediating effect was significant mostly in middle-aged individuals aged 45–65 years. Furthermore, sex differences existed in the mediation mechanisms. Biological age acceleration strongly mediated body shape indices and incident CVD in males, whereas in females, it predominantly mediated visceral fat accumulation and metabolic function dimensions with incident CVD. Similar main results were found in UKB and HEHEC. Conclusions Biological age acceleration partially mediates the relationship between obesity and incident CVD. This temporal evidence firstly validated the mediation pathway based on international cohorts, emphasizing the importance of addressing biological aging processes in population aged 45–65 years while providing sex-specific obesity intervention strategies to prevent CVD. Graphical abstract |
| format | Article |
| id | doaj-art-ace30440292c43e1b71f2f24769db722 |
| institution | DOAJ |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-05-01 |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-ace30440292c43e1b71f2f24769db7222025-08-20T03:10:16ZengBMCCardiovascular Diabetology1475-28402025-05-0124111410.1186/s12933-025-02770-0How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studiesLin Hu0Jiayuan Li1Zihuan Tang2Peng Gong3Zongqi Chang4Chen Yang5Tianpei Ma6Shuang Jiang7Chunxia Yang8Tao Zhang9Department of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityDepartment of Epidemiology and Health Statistics, West China School of Public Health and West China Fourth Hospital, Sichuan UniversityAbstract Background Recent basic biological research found that obesity accelerates biological aging and increases cardiovascular disease (CVD) risk. However, there is still a lack of real-world population evidence. This study aimed to explore the potential mediation roles of biological age acceleration in the associations between different dimensions of obesity characterization and incident CVD. Methods This international multi-cohort study included participants aged over 45 years with 3 waves longitudinal data from China Health and Retirement Longitudinal Study (CHARLS). China Health and Nutrition Survey (CHNS) was used to develop Klemera-Doubal method-biological age (KDM-BA), and the validation analysis was performed in UK Biobank (UKB) and Hongguang Elderly Health Examination Cohort (HEHEC). Obesity indices including body mass index (BMI), waist circumference (WC), waist height ratio (WtHR), body roundness index (BRI) for body shape; Chinese visceral adiposity index (CVAI), lipid accumulation product (LAP) for visceral fat accumulation; triglyceride-glucose index (TyG) and its derivatives (TyG-BMI, TyG-WC, TyG-WtHR) for metabolic function were used to measure obesity across different dimensions. Biological age acceleration was evaluated by the classic KDM-BA acceleration (KDM-BAacc). Causal mediation analyses assessed the role of biological age acceleration in mediating obesity and incident CVD. Results In CHARLS, the median follow-up period was 9.00 years, with a baseline age of 58 (52, 65) years. Obesity, KDM-BAacc, and CVD were all significantly associated with each other. For each 1-year increase in KDM-BAacc, the risk of incident stroke, heart disease and CVD increased by 68% (OR 1.68, 95% CI 1.35–2.09), 35% (OR 1.35, 95% CI 1.15–1.59), and 44% (OR 1.44, 95% CI 1.25–1.65), respectively. KDM-BAacc mediated the associations between BMI, WC, WtHR, BRI, CVAI, LAP, TyG-BMI, TyG-WC, TyG-WtHR, with CVD, with the mediation proportions ranging from 10.03 to 25.46%. However, the mediating effect was significant mostly in middle-aged individuals aged 45–65 years. Furthermore, sex differences existed in the mediation mechanisms. Biological age acceleration strongly mediated body shape indices and incident CVD in males, whereas in females, it predominantly mediated visceral fat accumulation and metabolic function dimensions with incident CVD. Similar main results were found in UKB and HEHEC. Conclusions Biological age acceleration partially mediates the relationship between obesity and incident CVD. This temporal evidence firstly validated the mediation pathway based on international cohorts, emphasizing the importance of addressing biological aging processes in population aged 45–65 years while providing sex-specific obesity intervention strategies to prevent CVD. Graphical abstracthttps://doi.org/10.1186/s12933-025-02770-0Biological age accelerationObesityCardiovascular diseaseCohort |
| spellingShingle | Lin Hu Jiayuan Li Zihuan Tang Peng Gong Zongqi Chang Chen Yang Tianpei Ma Shuang Jiang Chunxia Yang Tao Zhang How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies Cardiovascular Diabetology Biological age acceleration Obesity Cardiovascular disease Cohort |
| title | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies |
| title_full | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies |
| title_fullStr | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies |
| title_full_unstemmed | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies |
| title_short | How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies |
| title_sort | how does biological age acceleration mediate the associations of obesity with cardiovascular disease evidence from international multi cohort studies |
| topic | Biological age acceleration Obesity Cardiovascular disease Cohort |
| url | https://doi.org/10.1186/s12933-025-02770-0 |
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