External Prognostic Validations and Comparisons of Age- and Gender-Adjusted Exercise Capacity Predictions

Objectives: The purpose of this study was to externally validate the prognostic value of age- and gender-based nomograms and categorical definitions of impaired exercise capacity (EC). Background: Exercise capacity predicts death, but its use in routine clinical practice is hampered by its close correlation with age and gender. Methods: For a median of 5 years, we followed 22,275 patients without known heart disease who underwent symptom-limited stress testing. Models for predicted or impaired EC were identified by literature search. Gender-specific multivariable proportional hazards models were constructed. Four methods were used to assess validity: Akaike Information Criterion (AIC), right-censored c-index in 100 out-of-bootstrap samples, the Nagelkerke Index R², and calculation of calibration error in 100 bootstrap samples. Results: There were 646 and 430 deaths in 13,098 men and 9,177 women, respectively. Of the 7 models tested in men, a model based on a Veterans Affairs cohort (predicted metabolic equivalents [METs] = 18 - [0.15 × age]) had the highest AIC and R². In women, a model based on the St. James Take Heart Project (predicted METs = 14.7 - [0.13 × age]) performed best. Categorical definitions of fitness performed less well. Even after accounting for age and gender, there was still an important interaction with age, whereby predicted EC was a weaker predictor in older subjects (p for interaction <0.001 in men and 0.003 in women). Conclusions: Several methods describe EC accounting for age and gender-related differences, but their ability to predict mortality differ. Simple cutoff values fail to fully describe EC's strong predictive value.