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CLINICAL RESEARCH: EXERCISE TESTING

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

Esther S.H. Kim, MD, MPH^_*, Hemant Ishwaran, PhD, Eugene Blackstone, MD, FACC^, and Michael S. Lauer, MD, FACC, FAHA^_*,,,_*

^_* Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio
Department of Cardiothoracic Surgery, Cleveland Clinic, Cleveland, Ohio
Division of Prevention and Population Science, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Manuscript received May 18, 2007; revised manuscript received July 19, 2007, accepted August 6, 2007.

^_* Reprint requests and correspondence: Dr. Michael S. Lauer, 6701 Rockledge Drive, Room 10122, Bethesda, Maryland 20892. (Email: lauerm{at}nhlbi.nih.gov).

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 x 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 x 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.

Abbreviations and Acronyms   AIC = Akaike Information Criterion   EC = exercise capacity   MET = metabolic equivalent   VA = Veterans Affairs