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Coronary artery disease is the leading cause of morbidity and mortality around the world. Autonomic nervous system abnormalities are associated with coronary artery disease and its complications. Exercise stress tests are routinely used for the detection of the presence of coronary artery disease. In this study, we observed the association between heart rate profile during exercise and the severity of coronary artery disease.One hundred and sixty patients with abnormal exercise treadmill test (≥1 mm horizontal or downsloping ST-segment depression; 119 men, 41 women; mean age = 57 ± 9 years) were included in the study. Use of any drug affecting heart rate was not permitted. Resting heart rate before exercise, maximum heart rate during exercise, and resting heart rate after exercise (5 min later) were measured and two parameters were calculated: heart rate increment (maximum heart rate – resting heart rate before exercise) and heart rate decrement (maximum heart rate – resting heart rate after exercise). All patients underwent selective coronary angiography and subclassified into two groups according to stenotic lesion severity. Group 1 had at least 50% of stenotic lesion and group 2 had less than 50%. Patients in the first group had increased resting heart rate, decreased maximum heart rate, decreased heart rate increment, and decreased heart rate decrement compared with second group. All patients were classified into tertiles of resting heart rate, heart rate increment, and heart rate decrement level to evaluate whether these parameters were associated with severity of coronary artery stenosis in the study. The multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 21.888 (95% confidence interval 6.983–68.606) for the highest tertile of resting heart rate level compared with the lowest tertile. In addition, the multiple-adjusted odds ratio of the risk of severe coronary atherosclerosis was 20.987 (95% confidence interval 6.635–66.387) for the lowest tertile of heart rate increment level compared with the highest tertile and 2.360 (95% confidence interval 1.004–5.544) for the lowest tertile of heart rate decrement level compared with the highest tertile.Altered autonomic nervous system regulation affects heart rate profile, increased resting heart rate, decreased heart rate increment, and decreased heart rate decrement, during exercise and this effect is strongly and independently associated with the severity of coronary artery disease.