Association of phenotypic aging, lifestyle, and genetic risk with incidence of atrial fibrillation: A large prospective cohort study in the UK Biobank

IF 4 3区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of Nutrition Health & Aging Pub Date : 2025-05-06 DOI:10.1016/j.jnha.2025.100562

Tingting Lin , Ximin Fan , Liangtang Zeng , Qiang Li , Feilong Wang , Hao Lu

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引用次数: 0

Abstract

Objectives

Our study aimed to investigate the association of phenotypic aging, lifestyle, and genetic risk with the risk of incident atrial fibrillation (AF).

Design

A large prospective cohort study.

Setting and participants

This study included 327,122 participants from the UK Biobank.

Methods

PhenoAge acceleration (PhenoAgeAccel) was calculated by regressing phenotypic age (PhenoAge) on chronological age. Two key stratification tools were derived from previous research: the Healthy Lifestyle Score (HLS) based on smoking, body mass index (BMI), physical activity, and diet, to assess participants' lifestyles; and the polygenic risk score (PRS) based on 104 AF-associated SNPs and their effect sizes identified in a GWAS to evaluate genetic risk. Cox proportional hazards models were employed to assess both independent and combined effects of PhenoAgeAccel, HLS, and PRS with AF risk.

Results

At a median follow-up of 10.84 (10.08–11.56) years, 15,997 cases of AF were identified. Each standard deviation (SD) increase in PhenoAgeAccel was associated with a 30% higher AF risk (HR 1.30, 95% CI 1.28–1.31). Participants biologically older (PhenoAgeAccel>0) had a significantly higher risk of AF (HR 1.47, 95% CI 1.42−1.51) compared to those biologically younger (PhenoAgeAccel≤0), whereas ideal HLS was significantly associated with a lower risk of AF (HR 0.52, 95% CI 0.49−0.56 vs. poor HLS), and high genetic risk was significantly associated with a higher risk of AF (HR 2.30, 95% CI 2.21−2.39 vs. low genetic risk). Joint effects and multiplicative/additive interactions were noted between PhenoAgeAccel and HLS (or genetic risk). When combined PhenoAgeAccel and genetic risk, participants biologically older and in high genetic risk had the highest AF risk (HR 3.52, 95% CI 3.31–3.74). When combined PhenoAgeAccel and HLS, participants who were biologically older and had a poor lifestyle had the highest AF risk (HR 2.42, 95% CI 2.23–2.62). Further analysis categorized PhenoAgeAccel into quartiles based on its population distribution, and the associations remained consistent.

Conclusions

Increased PhenoAgeAccel is significantly associated with increased risk of AF. When combined with a poor lifestyle or high genetic risk, the risk is further increased. These findings highlight the importance of integrating phenotypic aging, genetic risk, and lifestyle factors into AF prevention strategies.

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表型衰老、生活方式和遗传风险与房颤发病率的关联：英国生物银行的一项大型前瞻性队列研究

目的本研究旨在探讨表型衰老、生活方式和遗传风险与房颤（AF）发生风险的关系。设计一项大型前瞻性队列研究。环境和参与者本研究包括来自英国生物银行的327122名参与者。方法将表型年龄（PhenoAge）与实足年龄进行回归，计算表型年龄加速（PhenoAgeAccel）。从先前的研究中衍生出两个关键的分层工具：健康生活方式评分（HLS）基于吸烟，体重指数（BMI），身体活动和饮食，以评估参与者的生活方式；以及基于104个af相关snp及其效应量的多基因风险评分（PRS）来评估遗传风险。采用Cox比例风险模型评估PhenoAgeAccel、HLS和PRS对房颤风险的独立和联合影响。结果中位随访10.84（10.08-11.56）年，共发现AF 15997例。PhenoAgeAccel每增加一个标准差（SD）与房颤风险增加30%相关（HR 1.30, 95% CI 1.28-1.31）。与生物学上较年轻的受试者（PhenoAgeAccel≤0）相比，生物学上较年长的受试者（PhenoAgeAccel≤0）患房颤的风险显著较高（HR 1.47, 95% CI 1.42 - 1.51），而理想的HLS与较低的房颤风险显著相关（HR 0.52, 95% CI 0.49 - 0.56，较差的HLS），高遗传风险与较高的房颤风险显著相关（HR 2.30, 95% CI 2.21 - 2.39，较低遗传风险）。phenageaccel和HLS（或遗传风险）之间存在联合效应和倍增/加性相互作用。当将PhenoAgeAccel和遗传风险结合使用时，生物学年龄较大且遗传风险高的参与者AF风险最高（HR 3.52, 95% CI 3.31-3.74）。当phenageaccel和HLS联合使用时，生理年龄较大且生活方式不良的参与者患房颤的风险最高（HR 2.42, 95% CI 2.23-2.62）。进一步的分析将PhenoAgeAccel根据其种群分布分为四分位数，并且相关性保持一致。结论：增加的PhenoAgeAccel与房颤风险增加显著相关，当结合不良的生活方式或高遗传风险时，风险进一步增加。这些发现强调了将表型衰老、遗传风险和生活方式因素整合到房颤预防策略中的重要性。

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

Journal of Nutrition Health & Aging 医学-老年医学

CiteScore

7.80

自引率

3.40%

发文量

136

审稿时长

4-8 weeks

期刊介绍： There is increasing scientific and clinical interest in the interactions of nutrition and health as part of the aging process. This interest is due to the important role that nutrition plays throughout the life span. This role affects the growth and development of the body during childhood, affects the risk of acute and chronic diseases, the maintenance of physiological processes and the biological process of aging. A major aim of "The Journal of Nutrition, Health & Aging" is to contribute to the improvement of knowledge regarding the relationships between nutrition and the aging process from birth to old age.