How does biological age acceleration mediate the associations of obesity with cardiovascular disease? Evidence from international multi-cohort studies.

IF 8.5 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS
Lin Hu, Jiayuan Li, Zihuan Tang, Peng Gong, Zongqi Chang, Chen Yang, Tianpei Ma, Shuang Jiang, Chunxia Yang, Tao Zhang
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引用次数: 0

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.

生理年龄加速如何介导肥胖与心血管疾病的关联?来自国际多队列研究的证据。
背景:最近的基础生物学研究发现,肥胖加速生物老化,增加心血管疾病(CVD)的风险。然而,仍然缺乏真实世界的人口证据。本研究旨在探讨生物年龄加速在肥胖特征的不同维度与心血管疾病发病率之间的关联中的潜在中介作用。方法:采用中国健康与退休纵向研究(CHARLS)的3波纵向数据,纳入年龄在45岁以上的国际多队列研究。采用中国健康与营养调查(CHNS)建立klemera - double法-生物年龄(KDM-BA),并在UK Biobank (UKB)和Hongguang Elderly Health Examination Cohort (HEHEC)进行验证分析。肥胖指数包括身体质量指数(BMI)、腰围(WC)、腰高比(WtHR)、体型圆度指数(BRI);中国内脏脂肪指数(CVAI),脂肪堆积积(LAP)用于内脏脂肪堆积;使用代谢功能的甘油三酯-葡萄糖指数(TyG)及其衍生物(TyG- bmi、TyG- wc、TyG- wthr)从不同维度测量肥胖。采用经典KDM-BA加速(KDM-BAacc)评价生物年龄加速。因果中介分析评估了生物年龄加速在介导肥胖和心血管疾病发生中的作用。结果:CHARLS中位随访时间为9.00年,基线年龄为58岁(52,65)岁。肥胖、KDM-BAacc、CVD三者之间均存在显著相关性。KDM-BAacc每增加1年,发生中风、心脏病和心血管疾病的风险分别增加68% (OR 1.68, 95% CI 1.35-2.09)、35% (OR 1.35, 95% CI 1.15-1.59)和44% (OR 1.44, 95% CI 1.25-1.65)。KDM-BAacc介导BMI、WC、WtHR、BRI、CVAI、LAP、TyG-BMI、TyG-WC、TyG-WtHR与CVD之间的关联,中介比例为10.03 ~ 25.46%。然而,在45-65岁的中年人中,中介效应最为显著。此外,在中介机制上存在性别差异。在男性中,生物年龄加速对体型指数和心血管疾病的发生有强烈的调节作用,而在女性中,它主要调节内脏脂肪积累和代谢功能维度与心血管疾病的发生。在UKB和HEHEC中发现了类似的主要结果。结论:生物年龄加速在一定程度上介导了肥胖与心血管疾病发生的关系。这一暂时性证据首次验证了基于国际队列的中介途径,强调了在45-65岁人群中解决生物衰老过程的重要性,同时提供了性别特异性肥胖干预策略来预防心血管疾病。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Cardiovascular Diabetology
Cardiovascular Diabetology 医学-内分泌学与代谢
CiteScore
12.30
自引率
15.10%
发文量
240
审稿时长
1 months
期刊介绍: Cardiovascular Diabetology is a journal that welcomes manuscripts exploring various aspects of the relationship between diabetes, cardiovascular health, and the metabolic syndrome. We invite submissions related to clinical studies, genetic investigations, experimental research, pharmacological studies, epidemiological analyses, and molecular biology research in this field.
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