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The exercise response of the ratio of systolic blood pressure to end-systolic volume was studied in 243 patients with chest pain and coronary artery disease who underwent supine rest and exercise equilibrium radionuclide angiography. There was a wide variation in both rest and exercise variables in this group. The exercise response of the systolic pressure/volume ratio also varied greatly, ranging from a decrease of 59% to an increase of 136%. Twenty-one clinical, catheterization and radionuclide angiographic variables were examined to determine their relation to the exercise response of the systolic pressure/volume ratio; nine variables were individually correlated with this ratio. Multiple regression analysis identified the change in end-diastolic volume index with exercise, rest systolic blood pressure, coronary artery Gensini score and peak work load as significant independent predictors of the exercise response of the systolic pressure/volume ratio; the latter correlated significantly with the change in ejection fraction with exercise (r = 0.73, p less than 0.0001). Its sensitivity for the detection of coronary artery disease in the study group (84%) and its "normalcy rate" in a group of 120 patients with a low likelihood of coronary artery disease (81%) were similar to those of the peak exercise ejection fraction (75 and 82%, respectively). These results demonstrate that the exercise response of the systolic pressure/end-systolic volume ratio is a complex response that is influenced by several pathophysiologic variables in the presence of coronary artery disease. It does not offer any advantage over ejection fraction measurements for the detection of exercise-induced ischemia.