Physiological reserve and cardiometabolic burden in relation to functional decline in older adults: a multicohort study

Activities of daily living (ADL) disability is a clinically important manifestation of functional decline in later life. It remains unclear whether peak expiratory flow (PEF), a simple marker of respiratory physiological reserve, and cardiometabolic burden provide complementary information for identifying older adults at higher risk. We examined their separate and joint associations with incident ADL disability across three ageing cohorts. We conducted harmonized prospective analyses of adults aged > 60 years who were free of ADL disability at baseline in CHARLS, HRS, and SHARE. Low PEF was defined using cohort- and sex-specific lowest-quartile thresholds, and high cardiometabolic burden as two or more of hypertension, diabetes, lipid disorder, and obesity. We fitted cohort-specific Cox models and pooled estimates by random-effects meta-analysis. We evaluated multiplicative and additive interaction, between-cohort heterogeneity, multiple imputation, and proportional hazards assumptions. Among 43,285 participants, 11,315 developed incident ADL disability. Higher PEF was associated with a lower risk, whereas greater cardiometabolic burden was associated with a higher risk. Participants with both low PEF and high cardiometabolic burden had the highest relative hazard (pooled HR 1.73, 95% CI 1.54, 1.95). The multiplicative interaction estimate was statistically significant but small in the complete-case analysis (HR 1.09, 95% CI 1.01, 1.19; P = 0.029). It was similar in the multiple-imputation analysis (HR 1.10, 95% CI 1.02, 1.17; P = 0.008) and heterogeneous across cohorts. Pooled additive interaction estimates were close to the null. The combination of low PEF and high cardiometabolic burden identified an older subgroup at elevated risk of incident ADL disability. However, the small and heterogeneous multiplicative interaction and near-null additive interaction estimates did not support a consistent interaction beyond the separate associations. Aim: To examine the separate and joint associations of peak expiratory flow and cardiometabolic burden with incident activities of daily living (ADL) disability among older adults in three harmonized ageing cohorts Findings: Higher peak expiratory flow and greater cardiometabolic burden were associated with lower and higher risks of incident ADL disability, respectively. Participants with both low peak expiratory flow and high cardiometabolic burden had the highest risk, whereas formal interaction analyses showed limited evidence of synergy. Message: Simple measures of physiological reserve and cardiometabolic burden may help characterize older adults at elevated risk of functional decline.