Physiological age a better predictor of survival than chronological age

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PhysiologicalPhysiological age is a better predictor of survival than chronological age, even after adjusting for sex, smoking, body mass index, statin use, diabetes, hypertension, coronary artery disease, and end-stage kidney disease, according to a large 15-year US study.

“Age is one of the most reliable risk factors for death: the older you are, the greater your risk of dying,” said study author Dr Serge Harb, cardiologist at the Cleveland Clinic in the US. “But we found that physiological health is an even better predictor. If you want to live longer then exercise more. It should improve your health and your length of life.”

Based on exercise stress testing performance, the researchers developed a formula to calculate how well people exercise – their “physiological age” – which they call A-BEST (Age Based on Exercise Stress Testing). The equation uses exercise capacity, how the heart responds to exercise (chronotropic competence), and how the heart rate recovers after exercise.

“Knowing your physiological age is good motivation to increase your exercise performance, which could translate into improved survival,” said Harb. “Telling a 45-year-old that their physiological age is 55 should be a wake-up call that they are losing years of life by being unfit. On the other hand, a 65-year-old with an A-BEST of 50 is likely to live longer than their peers.”

The study included 126,356 patients referred to the Cleveland Clinic between 1991 and 2015 for their first exercise stress test, a common examination for diagnosing heart problems. It involves walking on a treadmill, which gets progressively more difficult. During the test, exercise capacity, heart rate response to exercise, and heart rate recovery are all routinely measured. The data were used to calculate A-BEST, taking into account gender and use of medications that affect heart rate.

The average age of study participants was 53.5 years and 59% were men. More than half of patients aged 50-60 years – 55% of men and 57% of women – were physiologically younger according to A-BEST. After an average follow-up of 8.7 years, 9,929 (8%) participants had died. As expected, the individual components of A-BEST were each associated with mortality.

Patients who died were 10 years older than those who survived. But A-BEST was a significantly better predictor of survival than chronological age, even after adjusting for sex, smoking, body mass index, statin use, diabetes, hypertension, coronary artery disease, and end-stage kidney disease. This was true for the overall cohort and for both men and women when they were analysed separately.

Harb said doctors could use A-BEST to report results of exercise testing to patients “Telling patients their estimated age based on exercise performance is a powerful estimate of longevity and easier to understand than providing results for the individual components of the examination.”

Harb noted that this type of approach has shown merit in specific disease areas. For example, ESC guidelines advocate using “cardiovascular risk age” – based on risk factors including smoking, blood cholesterol and blood pressure – to communicate with patients.

Aims: We sought to estimate patients’ age based on their stress testing exercise performance (A-BEST), and evaluate whether A-BEST would be a better predictor of mortality when compared to chronological age.
Methods: We included 126,356 consecutive patients referred for exercise (electrocardiography, echocardiography or myocardial perfusion imaging) stress testing at our institution from January 1st, 1991 to February 27th, 2015. Estimated age was computed based on exercise capacity (number of peak estimated metabolic equivalents of task), chronotropic reserve index and heart rate recovery, taking into account patient’s gender and medications that affect heart rate. Uni and multivariable Cox models were used to determine the association of A-BEST with mortality. Improvement in predicting mortality using A-BEST compared to chronological age was evaluated with the use of net reclassification improvement and C statistic.
Results: Mean age was 53.5 ± 12.6 years and 59% were men. At follow-up (mean duration was 8.7 years), 9929 (8%) died. After adjustment for clinical comorbidities, higher metabolic equivalents of task (adjusted hazard ratio (HR) for mortality 0.71, 95% confidence interval (CI) 0.70–0.72, P < 0.001) and higher chronotropic reserve index (adjusted HR for mortality 0.97, 95% CI 0.96–0.99, P = 0.0135) were associated with improved survival, whereas abnormal heart rate recovery (adjusted HR for mortality 1.53, 95% CI 1.46–1.61, P < 0.001) and higher A-BEST (adjusted HR for mortality 1.05, 95% CI 1.04–1.05, P < 0.001) were associated with higher mortality. When comparing prediction models using A-BEST versus chronological age, a significant increase in the area under the curve was demonstrated if A-BEST was used (0.82 vs. 0.79, P < 0.001). The overall net reclassification improvement was 0.30 (P < 0.001).
Conclusion: Estimated age based on exercise stress testing performance is a better predictor of mortality when compared to chronological age.

Serge C Harb, Paul C Cremer, Yuping Wu, Bo Xu, Leslie Cho, Venu Menon, Wael A Jaber

European Society of Cardiology material
European Journal of Preventative Cardiology abstract

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