No Ceiling to Mortality Benefits of Cardiorespiratory Fitness in Patients Undergoing Stress Testing

Cardiorespiratory fitness is associated with long-term mortality benefits in a dose-response manner that shows no upper limit, according to a large retrospective cohort study in adults undergoing exercise treadmill testing. Cleveland Clinic researchers published the findings in JAMA Network Open on Oct. 19, 2018.

“We found that extremely high aerobic fitness was associated with the greatest survival and that this benefit extended to individuals aged 70 or older and to people with hypertension,” says Cleveland Clinic cardiologist Wael Jaber, MD, the paper’s senior author. “These results underscore the importance of aerobic fitness to overall health, including its importance relative to traditional clinical risk factors.”

Does extreme fitness have a downside?

The authors note that while the cardiovascular and noncardiovascular benefits of cardiorespiratory fitness are well documented, some recent studies have yielded evidence of adverse cardiovascular effects of habitual vigorous exercise. Many such studies have been limited by reliance on self-reported data.

“In our analysis, we were interested particularly in the relationship between extremely high fitness and mortality,” says the study’s first author, Kyle Mandsager, MD, an electrophysiology fellow at Cleveland Clinic. “This relationship had never been looked at using an objective fitness measure like treadmill test results, and it had never been studied at such a large scale.”

Study design and results

The scale he refers to is a cohort of 122,007 consecutive adults (mean age, 53.4 years) referred for symptom-limited exercise treadmill testing at Cleveland Clinic from 1991 through 2014. Median follow-up was 8.4 years, yielding 1.1 million person-years of observation.

Based on their treadmill test results, patients were stratified by age- and sex-matched cardiorespiratory fitness levels into five performance groups:

• Low (< 25th percentile)
• Below average (25th-49th percentile)
• Above average (50th-74th percentile)
• High (75th-97.6th percentile)
• Elite (≥ 97.7th percentile)

Risk-adjusted all-cause mortality — the primary outcome measure — was found to be inversely proportional to cardiorespiratory fitness, with statistically significant differences between each increment in fitness level.

Among other notable findings:

• The increase in all-cause mortality associated with each increment of reduced fitness (e.g., below average vs. above average) was comparable to or greater than that of traditional clinical risk factors such as coronary artery disease, smoking and diabetes.
• The dose-related mortality benefit from fitness was observed in both sexes, in all age groups, and regardless of history of coronary artery disease or other risk factors.
• The magnitude of benefit was striking, as elite fitness was associated with an 80 percent reduction in mortality risk relative to low fitness.

An empowering message for patients

“These findings illustrate the importance of aerobic fitness as a powerful, modifiable indicator of long-term mortality,” says Dr. Jaber. “Overall, increases in fitness were associated with reductions in all-cause mortality at any level, with no evidence of a plateau effect.”

“Achieving very high levels of aerobic fitness may be especially valuable in patients aged 70 or older and in those with hypertension, as elite fitness conferred significant benefits over even a high level of fitness in these subgroups,” adds Dr. Mandsager.

While acknowledging the limitations of this study’s retrospective nature, the investigators note that their findings are bolstered by its objective testing measure. “This is, to our knowledge, the largest cohort study of long-term mortality among patients undergoing exercise treadmill testing,” Dr. Mandsager observes.

Together with concordant results from previous studies, these findings can help patients feel empowered, says Leslie Cho, MD, Cleveland Clinic’s Section Head of Preventive Cardiology and Rehabilitation. “In consultation with their physician, individuals should aim to maintain the highest exercise performance they can regardless of age, sex or prior history of heart disease,” she concludes.