Association of cardiorespiratory fitness with the incidence and progression trajectory of cardiometabolic multimorbidity

Objectives This study examined the relationship of cardiorespiratory fitness (CRF) in the transition from healthy status to first cardiometabolic disease, subsequent cardiometabolic multimorbidity and further to death. Methods We used data from the UK Biobank of 47 484 participants without cardiometabolic diseases at baseline. CRF was assessed via a 6 min incremental ramp cycle ergometer test and expressed in metabolic equivalent of tasks (METs, 1 MET=3.5 mL/kg/min). Cardiometabolic multimorbidity was defined as at least two diseases among diabetes, hypertension, coronary heart disease and stroke. Results Over 12.5 years median follow-up, 8123 participants developed first cardiometabolic disease, 1958 developed cardiometabolic multimorbidity and 2177 died. CRF was associated with different transition stages in cardiometabolic multimorbidity development. The HRs (95% CIs) per MET increase in CRF were 0.94 (0.93 to 0.95) and 0.97 (0.96 to 0.99) for transitions from healthy baseline to first cardiometabolic disease and subsequent cardiometabolic multimorbidity. Per MET increase in CRF was associated with reduced risk of transition from healthy baseline to death (HR: 0.97, 95% CI 0.95 to 0.99), but not for the transition from first cardiometabolic disease and cardiometabolic multimorbidity to death. When first cardiometabolic disease was divided into specific cardiometabolic diseases, there were comparable trends of CRF on the disease-specific transitions from healthy baseline to first cardiometabolic disease and subsequent cardiometabolic multimorbidity. Conclusion Higher CRF was associated with a lower risk of progression from a healthy state to first cardiometabolic disease and subsequently to cardiometabolic multimorbidity. These findings suggest that improving CRF is a potential strategy for preventing cardiometabolic multimorbidity development. Data are available upon reasonable request. The data that support the findings of this study are available from UK Biobank (), but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of UK Biobank.