Association of Cardiorespiratory Fitness With Long-term Mortality Among Adults Undergoing Exercise Treadmill Testing.
Level 3 - non-randomized controlled study
Non-randomized retrospective cohort study of clinically referred patients.
PubMed 30646252 · doi:10.1001/jamanetworkopen.2018.3605
What was done
This retrospective cohort study evaluated 122,007 consecutive adult patients (mean age 53.4 years; 59.2% male) undergoing symptom-limited exercise treadmill testing at a tertiary academic medical center between 1991 and 2014 (median follow-up 8.4 years; 1.1 million person-years). Cardiorespiratory fitness was quantified by peak estimated metabolic equivalents (METs) and categorized into age- and sex-matched performance tiers: low (<25th percentile), below average (25th–49th percentile), above average (50th–74th percentile), high (75th–97.6th percentile), and elite (≥97.7th percentile, ≥2 SD above mean). The primary outcome was all-cause mortality.
What was found
During follow-up, 13,637 deaths occurred. Risk-adjusted all-cause mortality was inversely associated with cardiorespiratory fitness across all performance groups, with elite performers having the lowest mortality risk. Compared with low fitness, elite performers had an adjusted hazard ratio (aHR) of 0.20 (95% CI, 0.16–0.24; P < .001), while low fitness versus elite showed an aHR of 5.04 (95% CI, 4.10–6.20; P < .001). Elite performers also had lower mortality compared to high performers (aHR 0.77; 95% CI, 0.63–0.95; P = .02). The excess mortality associated with low fitness exceeded or matched traditional risk factors including coronary artery disease (aHR 1.29; 95% CI, 1.24–1.35), smoking (aHR 1.41; 95% CI, 1.36–1.46), and diabetes (aHR 1.40; 95% CI, 1.34–1.46). In subgroup analyses, elite performance maintained a survival advantage over high performance in patients aged 70 years or older (aHR 0.71; 95% CI, 0.52–0.98; P = .04) and patients with hypertension (aHR 0.70; 95% CI, 0.50–0.99; P = .05).
Why it matters
This study demonstrates an incremental survival benefit across the entire spectrum of aerobic fitness without an observed upper threshold, indicating that extreme cardiorespiratory fitness remains protective rather than harmful.
Limits
The cohort was drawn from a single tertiary academic medical center among patients clinically referred for exercise treadmill testing, which may introduce referral bias and limit generalizability to healthy unreferred populations. Cardiorespiratory fitness was estimated via treadmill workload rather than direct gas exchange measurement, and fitness was assessed only at baseline without tracking changes over time. Residual confounding from unmeasured lifestyle and clinical characteristics cannot be excluded.
Cited by
- supports Having low cardiorespiratory fitness in the absence of other chronic diseases is as strong or stronger a predictor of all-cause mortality than cardiovascular disease, hypertension, or smoking.
- supports VO2 max is a primary metric used to determine or predict human life expectancy and longevity.