Grand Rounds

Is There Such a Thing as Too Much Cardiorespiratory Fitness When it Comes to Mortality?

BACKGROUND AND PURPOSE:

There is strong evidence that cardiorespiratory fitness is inversely associated with mortality, regardless of age, sex, race/ethnicity and comorbidies
However, there is some literature to suggest that habitual vigorous exercise may not result in lower mortality risk and may even be associated with harms
- ‘Plateau effect’ where there is no longer an inverse association with mortality risk
Mandsager et al. (JAMA Network Open 2018) sought to determine whether cardiorespiratory fitness is associated with all-cause mortality and whether there is an intensity threshold

Retrospective cohort
- Individuals at a tertiary care academic medical center
- Adult patients undergoing a stress test
- Symptom-limited exercise treadmill testing
Cardiorespiratory fitness: Quantified by peak estimated metabolic equivalents on treadmill testing
Performance groups
- Low (<25th percentile)
- Below average (25th-49th percentile)
- Above average (50th-74th percentile)
- High (75th-97.6th percentile)
- Elite (≥97.7th percentile)
Patients stratified by age and sex
Main outcome: All-cause mortality

122,007patients were included
- 40.8% women
- Mean age: 53.4 years
- 1.1 million person-years of observation
Risk-adjusted all-cause mortality was inversely proportional to cardiorespiratory fitness and was lowest in elite performers
- Elite vs low: Adjusted hazard ratio (aHR) 0.20 (95% CI, 0.16-0.24; P < .001)
- Elite vs high: aHR 0.77 (95% CI, 0.63-0.95; P = .02)
Low cardiorespiratory fitness was associated with increased mortality
- Low vs elite: aHR 5.04 (95% CI, 4.10-6.20; P < .001)
- Below average vs above average: aHR 1.41 (95% CI, 1.34-1.49; P < .001)

Subgroup analysis:

Benefit of elite vs high cardiorespiratory fitness was seen in the overall cohort, but when broken out by age, benefit was only seen in older adults ≥70 years
- Elite over high performance: aHR 0.71 (95% CI, 0.52-0.98; P = .04)
Benefit seen in all comorbidity groups and in patients with hypertension there was significant difference
- Elite over high performance: aHR 0.70 (95% CI, 0.50-0.99; P = .05)
Extreme cardiorespiratory fitness (≥2 SDs above the mean for age and sex) was associated with the lowest risk-adjusted all-cause mortality compared with all other performance groups

The increase in all-cause mortality associated with reduced cardiorespiratory fitness was greater than or equal to traditional clinical risk factors such as smoking, diabetes and coronary artery disease
There was no observed upper limit of benefit associated cardiorespiratory fitness
High/extreme levels of fitness in older individuals may reflect long-term habits and have a cumulative effect

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