While obesity increases the risk of developing cardiometabolic diseases (CMDs), these associations seem to attenuate with increasing age, albeit studied poorly. The present study aimed to investigate the associations between adiposity and CMDs in sex-specific groups of chronological age and leukocyte telomere length (LTL) as a measure of biological age. We investigated the associations between BMI, a body shape index, waist-to-hip ratio (adjusted for BMI) and total body fat, and incident coronary artery disease (CAD), type 2 diabetes (T2D) and ischemic stroke (IS) in 413,017 European-ancestry participants of the UK Biobank without CMD at baseline. We assessed the change in the associations between adiposity and CMD over strata of increasing chronological age or decreasing LTL. Participants (56% women) had a median (IQR) age of 57.0 (50.0–63.0) years. The median follow-up time was 12 years. People with higher BMI had a higher risk of incident CAD (HR 1.14 (95% confidence interval [CI] 1.13, 1.16)), T2D (HR 1.70 (95% CI 1.68, 1.72)) and IS (HR 1.09 (95% CI 1.06, 1.12)). In groups based on chronological age and LTL, adiposity measures were associated with higher risk of CAD and T2D in both men and women, but these associations attenuated with increasing chronological age (P_interactions < 0.001), but not with decreasing LTL (P_interaction men = 0.85; P_interaction women = 0.27). Increased (abdominal) adiposity was associated with higher risk of incident CMDs, which attenuated with increasing chronological age but not with decreasing LTL. Future research may validate these findings using different measures of biological age.

虽然肥胖会增加患心脏代谢疾病 (CMD) 的风险，但这些关联似乎随着年龄的增长而减弱，尽管研究很少。本研究旨在调查按实际年龄和白细胞端粒长度 (LTL) 作为生物学年龄衡量指标的特定性别群体中肥胖与 CMD 之间的关联。我们研究了 BMI、体型指数、腰臀比（根据 BMI 调整）和全身脂肪与冠状动脉疾病 (CAD)、2 型糖尿病 (T2D) 和缺血性中风 (IS) 之间的关联。英国生物银行的 413,017 名欧洲血统参与者在基线时没有 CMD。我们评估了随着实际年龄的增加或 LTL 的减少，肥胖与 CMD 之间关联的变化。参与者（56% 为女性）的中位 (IQR) 年龄为 57.0 (50.0–63.0) 岁。中位随访时间为 12 年。BMI 较高的人发生 CAD (HR 1.14 (95% CI 1.13, 1.16))、T2D (HR 1.70 (95% CI 1.68, 1.72)) 和 IS (HR 1.09 (95% CI)) 的风险较高1.06、1.12））。在基于实际年龄和 LTL 的群体中，肥胖指标与男性和女性患 CAD 和 T2D 的较高风险相关，但这些关联随着实际年龄的增加而减弱（ P 相互作用 < 0.001），但与 LTL 的降低_无关 （P_相互作用男性= 0.85；P_相互作用女性 = 0.27）。（腹部）肥胖的增加与 CMD 事件的较高风险相关，这种风险随着实际年龄的增加而减弱，但不会随着 LTL 的减少而减弱。未来的研究可能会使用不同的生物年龄测量方法来验证这些发现。