Prognostic value of heart rate adjustment of exercise-induced ST segment depression in the multiple risk factor intervention trial

OBJECTIVES: We sought to assess the effect of heart rate adjustment of ST segment depression on risk stratification for the prediction of death from coronary artery disease. BACKGROUND: Standard analysis of the ST segment response to exercise based on a fixed magnitude of horizontal or downsloping ST segment depression has demonstrated only limited diagnostic sensitivity for the detection of coronary artery disease and has variable test performance in predicting coronary artery disease mortality. Heart rate adjustment of the magnitude of ST segment depression has been proposed as an alternative approach to increase the diagnostic and prognostic accuracy of the exercise electrocardiogram (ECG). METHODS: Exercise ECGs were performed in 5,940 men from the Usual Care Group of the Multiple Risk Factor Intervention Trial at entry into the study. An abnormal ST segment response to exercise was defined according to standard criteria as > or = 100 micro V of additional horizontal or downsloping ST segment depression at peak exercise. The ST segment/heart rate index was calculated by dividing the change in ST segment depression from rest to peak exercise by the exercise-induced change in heart rate. An abnormal ST segment/heart rate index was defined as >1.60 micro V/beats per min. RESULTS: After a mean follow-up of 7 years there were 109 coronary artery disease deaths. Using a Cox proportional hazards model, a positive exercise ECG by standard criteria was not predictive of coronary mortality (age-adjusted relative risk [RR] 1.5, 95% confidence interval [CI] 0.6 to 3.6, p = 0.39). In contrast, an abnormal ST segment/heart rate index significantly increased the risk of death from coronary artery disease (age-adjusted RR 4.1, 95% CI 2.7 to 6.0, p < 0.0001). Excess risk of death was confined to the highest quintile of ST segment/heart rate index values, and within this quintile, risk was directly related to the magnitude of test abnormality. After multivariate adjustment for age, diastolic blood pressure, serum cholesterol and cigarettes smoked per day, the ST segment/heart rate index remained a significant independent predictor of coronary death (RR 3.6, 95% CI 2.4 to 5.4, p < 0.001). CONCLUSIONS: Simple heart rate adjustment of the magnitude of ST segment depression improves the prediction of death from coronary artery disease in relatively high risk, asymptomatic men. These findings strongly support the use of heart rate-adjusted indexes of ST segment depression to improve the predictive value of the exercise ECG.