Exercise Capacity and Risk of Death Across the Age Spectrum in 750,302 Male and Female US Veterans

Background: Most studies that have evaluated the association between exercise capacity and the risk of all-cause mortality have focused on middle-aged Caucasian populations. We assessed the risk associated with fitness in male and female participants 30-95 years of age and of different ethnicities.  Methods:In this retrospective cohort study, we included male and female US Veterans who completed an exercise treadmill test (ETT) between 1999-2020. We assigned participants to one of ten age-specific fitness categories (deciles) based on peak metabolic equivalents (METs) achieved during the ETT. The primary endpoint was all-cause mortality assessed from Veterans Affairs medical records up to Dec 31, 2020. We compared fitness categories with Cox proportional hazard model adjusted for age, body-mass index, ethnic origin, sex, cardiovascular disease, cardiovascular risk factors and medications. Findings: We assessed 750,302 US male and female US Veterans nationwide, ages 30-95 years (mean age 61.3 years, SD 9.8 years).  During a median follow-up of 9.8 years (IQR 5.6-14.0), 164,288 died with an average yearly mortality rate of 22 deaths per1,000 person-years. The association between cardiorespiratory fitness (CRF) and mortality risk was independent, inverse, and graded for all ages, ethnicities, and gender. Compared to the least fit group within each age category, mortality risk was 50% lower at peak exercise capacities of approximately 10.0 METs for those 30-49 years, 8.0 METs for septuagenarians, and 7.0 METs for octogenarians. The lowest mortality risk was observed at approximately 14.0 METs with no additional decline or increase in risk beyond this level. Being unfit, defined having exercise capacity below the median ( 2 times higher mortality risk compared to being fit (≥8.5 METs), and was higher than the risk of the traditional cardiac risk factors examined. Interpretation: Higher CRF is independently associated with lower mortality risk for all ages, ethnicities, and gender. Exercise capacity <8.5 METs carried a greater risk than that of the traditional cardiac risk factors. Approximately 50% lower risk was noted in all age categories, commensurate to an exercise capacity achievable by most individuals within a given age category. Funding: None to declare. Declaration of Interest: None to declare. Ethical Approval: This paper was approved by The Veterans Affairs Medical Center, Washington, DC, USA