Effect of exercise on coronary endothelial function in patients with coronary artery disease.

Background: Studies of the cardioprotective effects of exercise training in patients with coronary artery disease have yielded contradictory results. Exercise training has been associated with improvement in myocardial perfus ion even in patients who have progression of coronary atherosclerosis. We t herefore conducted a prospective study of the effect of exercise training o n endothelial function in patients with coronary artery disease. Methods: We randomly assigned 19 patients with coronary endothelial dysfunc tion, indicated by abnormal acetylcholine-induced vasoconstriction, to an e xercise-training group (10 patients) or a control group (9 patients). To re duce confounding, patients with coronary risk factors that could be influen ced by exercise training (such as diabetes, hypertension, hypercholesterole mia, and smoking) were excluded. In an initial study and after four weeks, the changes in vascular diameter in response to the intracoronary infusion of increasing doses of acetylcholine (0.072, 0.72, and 7.2 microg per minut e) were assessed. The mean peak flow velocity was measured by Doppler veloc imetry, and the diameter of epicardial coronary vessels was measured by qua ntitative coronary angiography. Results: In the initial study, the two groups had similar vasoconstrictive responses to acetylcholine. After four weeks of exercise training, coronary -artery constriction in response to acetylcholine at a dose of 7.2 microg p er minute was reduced by 54 percent (from a mean [+/-SE] decrease in the lu minal diameter of 0.41+/-0.05 mm in the initial study to a decrease of 0.19 +/-0.07 mm at four weeks; P<0.05 for the comparison with the change in the control group). In the exercise-training group, the increases in mean peak flow velocity in response to 0.072, 0.72, and 7.2 microg of acetylcholine p er minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the i nitial study. After four weeks of exercise, the increases in response to ac etylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comp arison with the control group). Coronary blood-flow reserve (the ratio of t he mean peak flow velocity after adenosine infusion to the resting velocity ) increased by 29 percent after four weeks of exercise (from 2.8+/-0.2 in t he initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison w ith the control group). Conclusions: Exercise training improves endothelium-dependent vasodilatatio n both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease. (N Engl J Med 2000;342:454-60.) (C)2000, Mas sachusetts Medical Society.