Longitudinal changes of cardiorespiratory fitness are associated with cardiovascular disease and mortality: evidence from the UK Biobank

AIMS: Cardiorespiratory fitness (CRF) is a strong predictor of cardiovascular disease (CVD) and mortality. However, whether longitudinal changes in CRF independently predict cardiovascular outcomes beyond baseline CRF remains unclear. METHODS AND RESULTS: We analysed 11 530 UK Biobank participants (aged 40-73 years) who completed two CRF assessments via submaximal cycle ergometry. Annualized change in estimated VO₂max (mL·kg-1·min-1·year-1) was calculated as the difference between assessments divided by the time between the two measurements. After excluding participants with prior CVD or events within 2 years of follow-up, we identified incident CVD and CVD mortality through clinical records and self-reports. Cox models were adjusted for baseline CRF, sociodemographic and lifestyle behaviours, genetic predisposition to CVD, BMI change, and physical activity. Over a median follow-up of 14.0 years (interquartile range 13.0-14.6), 921 incident CVD events and 119 CVD-related fatalities occurred. Annual improvements in VO₂max were associated with a lower risk of incident CVD [hazard ratio (HR) per +1 mL·kg-1·min-1·year-1 = 0.85; 95% confidence interval (CI) 0.75-0.96] and CVD-related mortality (HR = 0.66, 95% CI 0.51-0.87). Conversely, declines in VO₂max were associated with increased CVD risk. Analyses demonstrated an approximately linear dose-response pattern, with progressively lower risk across the spectrum of positive VO₂max change and higher risk with negative change, without evidence of threshold effects. CONCLUSION: An annual improvement as little as 1 mL/kg/min may be enough to lower CVD risk, independent of baseline CRF. Longitudinal assessment of CRF may enhance cardiovascular risk stratification and inform prevention strategies.