Estimated cardiorespiratory fitness and long-term health outcomes: evidence from multiple large-scale cohorts

Cardiorespiratory fitness is a robust predictor of morbidity and mortality; however, its direct measurement is often impractical in large population-based studies. Non-exercise estimated cardiorespiratory fitness (eCRF) provides a feasible alternative, but its association with health outcomes across diverse populations remains unclear. We therefore investigated associations between eCRF and major health outcomes using cohort data from Europe, North America, and Asia. Participants were obtained from three large cohorts: the UK Biobank, the Health and Retirement Study, and the China Health and Retirement Longitudinal Study. Estimated cardiorespiratory fitness was calculated using validated non-exercise equations and then categorized into quartiles. In the UK Biobank, outcomes comprised all-cause mortality, cardiovascular mortality, cancer mortality, incident cardiovascular disease, incident diabetes, and incident cancer, whereas all-cause mortality and incident cardiovascular disease were assessed in the other two cohorts. Multivariable-adjusted hazard ratios and corresponding 95% confidence intervals were estimated using Cox proportional hazards models. Subgroup analyses and restricted cubic spline models were further conducted to examine the consistency of the associations and potential dose-response relationships. More than half a million participants were included. In the UK Biobank and the Health and Retirement Study, higher eCRF levels were consistently associated with lower risks of mortality and major chronic diseases, with a particularly pronounced association observed for incident diabetes. By contrast, eCRF was not significantly associated with either all-cause mortality or incident cardiovascular disease in the China Health and Retirement Longitudinal Study. Subgroup analyses generally supported consistent protective associations in the European and North American cohorts. Restricted cubic spline analyses further suggested nonlinear inverse associations in the UK Biobank and approximately linear patterns in the other cohorts. Higher eCRF was associated with lower risks of multiple adverse health outcomes in European and North American populations, particularly incident diabetes. The weaker associations in the Chinese cohort suggest that current eCRF equations may require population-specific calibration. These findings support the potential utility of eCRF for risk stratification in large population-based settings, while highlighting the need for further validation in Asian populations.