The UK Biobank submaximal cycle ergometer test for assessment of cardiorespiratory fitness: Validity, reliability, and association with disease outcomes

Abstract Background Cardiorespiratory fitness (CRF) was assessed in UK Biobank (UKB) using heart rate response to a submaximal ramped cycle ergometer test that was individualised for participant characteristics including cardiovascular disease risk. Studies have since explored health associations with CRF by estimating maximal oxygen consumption (VO 2 max) from UKB test data using interpretation methods that have not accounted for this individualisation procedure. Thus, dose-response relationships reported in these studies may be inaccurate. We developed and validated a novel VO 2 max estimation approach that accounts for the UKB test individualisation procedure and compared dose-response relationships with health outcomes between the novel and previous methods. Methods In a cross-over study (n=189), participants completed several UKB tests and VO 2 max was measured. A multilevel modelling framework was developed that combines heart rate response features from the UKB test to estimate VO 2 max. Estimates were compared within participants across UKB test protocols, and with directly measured VO 2 max. Short-term test-retest reliability was assessed in a subsample of participants (n=87). In UKB, we examined associations between estimated CRF and disease endpoints (n=80,259) and compared associations obtained with an unvalidated method. Long-term test-retest reliability was examined (n = 2877). Results Estimated and directly measured VO 2 max were strongly correlated (Pearson’s r range: 0.68 to 0.74) with no mean bias (women bias: −0.8 to 0.4; men bias range: −0.3 to 0.3), outperforming a previous approach for interpreting UKB test data. Agreement between estimated VO 2 max across different test protocols was strong (Pearson’s r range: 0.94 to 0.99). Short- and long-term reliability was also high (lambda=0.91 and 0.80, respectively). All-cause mortality was 7% (95%CI 4-10%, 2686 deaths) lower and CVD mortality 9% (95%CI 3-14%, 858 deaths) lower for every 1-MET difference in fitness, associations twice as strong as determined by previous methods. Conclusions We present a valid and reliable method for estimating CRF in UKB and demonstrate its utility in characterising dose-response relationships with health outcomes. Accounting for the individualisation procedure strengthens observed relationships between CRF and disease and enhances the case for promoting improved fitness in the general population.