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

作者：Tingting Lin, Ximin Fan, Liangtang Zeng, Qiang Li, Feilong Wang, Hao Lu · 发表于：The journal of nutrition health & aging · 年份：2025 · DOI：10.1016/j.jnha.2025.100562 · 被引用次数：6 · 研究领域：Genetic Associations and Epidemiology、Atrial Fibrillation Management and Outcomes、BRCA gene mutations in cancer

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....