The association of clinical indication for exercise stress testing with all-cause mortality: the FIT Project

Introduction: We hypothesized that the indication for stress testing provided by the referring physician would be an independent predictor of all-cause mortality. Material and methods: We studied 48,914 patients from The Henry Ford Exercise Testing Project (The FIT Project) without known congestive heart failure who were referred for a clinical treadmill stress test and followed for 11 +/- 4.7 years. The reason for stress test referral was abstracted from the clinical test order, and should be considered the primary concerning symptom or indication as stated by the ordering clinician. Hierarchical multivariable Cox proportional hazards regression was performed, after controlling for potential confounders including demographics, risk factors, and medication use as well as additional adjustment for exercise capacity in the final model. Results: A total of 67% of the patients were referred for chest pain, 12% for shortness of breath (SOB), 4% for palpitations, 3% for pre-operative evaluation, 6% for abnormal prior testing, and 7% for risk factors only. There were 6,211 total deaths during follow-up. Compared to chest pain, those referred for palpitations (HR = 0.72, 95% CI: 0.60-0.86) and risk factors only (HR = 0.72, 95% CI: 0.63-0.82) had a lower risk of all-cause mortality, whereas those referred for SOB (HR = 1.15, 95% CI: 1.07-1.23) and pre-operative evaluation (HR = 2.11, 95% CI: 1.94-2.30) had an increased risk. In subgroup analysis, referral for palpitations was protective only in those without coronary artery disease (CAD) (HR = 0.75, 95% CI: 0.62-0.90), while SOB increased mortality risk only in those with established CAD (HR = 1.25, 95% CI: 1.10-1.44). Conclusions: The indication for stress testing is an independent predictor of mortality, showing an interaction with CAD status. Importantly, SOB may be associated with higher mortality risk than chest pain, particularly in patients with CAD.