Exercise Stress Test Performance Beats Age in Predicting Longevity

The old cliché that you’re only as old as you feel just got an evidentiary boost from findings of the largest cohort of exercise stress test participants reported to date.

The cohort study, published by Cleveland Clinic researchers in the European Journal of Preventive Cardiology (2019 Feb 13 [Epub ahead of print]), shows that physiological age, based on exercise stress test performance, is a better predictor of survival than chronological age.

The study evaluates a formula that the researchers developed for calculating exercise performance, which they dub A-BEST (Age Based on Exercise Stress Testing), or physiological age. It is sex-specific and consists of three components, taking into account the use of negative chronotropic medications:

• Exercise capacity (number of peak estimated metabolic equivalents of task [METs])
• Chronotropic reserve index (heart rate response to exercise)
• Heart rate recovery

“The three exercise parameters included in our A-BEST prediction model are readily available in stress test reports,” explains lead author and Cleveland Clinic cardiologist Serge Harb, MD. “Our goal was to develop a mortality risk estimate that is more practical and easy to understand for both patients and clinicians. The A-BEST measure can be used as a surrogate for ‘physiological age,’ as it incorporates factors associated with diminishing treadmill exercise performance.”

He notes that this concept has been proposed in other clinical realms, such as calculating arterial age on the basis of coronary calcium score or vascular age based on carotid intimal medial thickness.

Study essentials

To test the A-BEST formula, the researchers applied it to 126,356 consecutive patients who underwent exercise stress testing (electrocardiography, echocardiography or myocardial perfusion imaging) at Cleveland Clinic from January 1991 to February 2015. Univariable and multivariable regression analysis was used to determine the association of A-BEST with all-cause mortality throughout the duration of available follow-up.

Mean (± SD) patient age was 53.5 ± 12.6 years. Fifty-nine percent of patients were men. During mean follow-up of 8.7 years across the cohort, a total of 9,929 patients (7.9 percent) died.

Following adjustment for clinical comorbidities, each of the three components of the A-BEST formula was significantly associated with mortality, as follows:

• Greater exercise capacity (higher METs) was associated with lower mortality, with an adjusted hazard ratio (HR) of 0.71 (95% CI, 0.70-0.72); P < 0.001.
• Higher chronotropic reserve index was associated with lower mortality, with an adjusted HR of 0.97 (95% CI, 0.96-0.99); P = 0.0135.
• Abnormal heart rate recovery was associated with higher mortality, with an adjusted HR of 1.53 (95% CI, 1.46-1.61); P < 0.001.

In keeping with the above results, the A-BEST measure itself was also significantly associated with mortality, with a higher A-BEST correlating with higher mortality (adjusted HR = 1.05 [95% CI, 1.04-1.05]; P < 0.001).

Moreover, the researchers found that A-BEST was significantly more predictive of death than was a patient’s chronological age (net reclassification improvement = 0.30, P < 0.001; area under the curve = 0.82 with A-BEST vs. 0.79 with chronological age, P < 0.001).

The above findings applied to both the overall cohort and to men and women when analyzed separately.

Helping patients better understand their risk

“These findings show that estimated ‘physiological’ age based on readily available exercise stress testing parameters performs better than chronological age in predicting patients’ all-cause mortality,” Dr. Harb observes.

“The primary advantage of using A-BEST is that it reliably and conveniently translates exercise variables to a risk estimate that’s more easily appreciated by both patients and their providers,” adds senior author Wael Jaber, MD. “The hope is that this can help motivate patients to exercise more.”

The simple formulas for calculating A-BEST for both men and women are presented in the “Results” section of the researchers’ European Journal of Preventive Cardiology paper. “Physicians are free to use these tools to refine their prognostic estimates for patients,” Dr. Jaber notes. “The results can also be used as a carrot or stick to encourage improved exercise tolerance and fitness through exercise.”