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

N Engl J Med. 2000 Feb 17;342(7):454-60. doi: 10.1056/NEJM200002173420702.


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 perfusion even in patients who have progression of coronary atherosclerosis. We therefore conducted a prospective study of the effect of exercise training on endothelial function in patients with coronary artery disease.

Methods: We randomly assigned 19 patients with coronary endothelial dysfunction, indicated by abnormal acetylcholine-induced vasoconstriction, to an exercise-training group (10 patients) or a control group (9 patients). To reduce confounding, patients with coronary risk factors that could be influenced by exercise training (such as diabetes, hypertension, hypercholesterolemia, 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 minute) were assessed. The mean peak flow velocity was measured by Doppler velocimetry, and the diameter of epicardial coronary vessels was measured by quantitative 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 per minute was reduced by 54 percent (from a mean [+/-SE] decrease in the luminal 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 per minute were 12+/-7, 36+/-11, and 78+/-16 percent, respectively, in the initial study. After four weeks of exercise, the increases in response to acetylcholine were 27+/-7, 73+/-19, and 142+/-28 percent (P<0.01 for the comparison with the control group). Coronary blood-flow reserve (the ratio of the 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 the initial study to 3.6+/-0.2 after four weeks; P<0.01 for the comparison with the control group).

Conclusions: Exercise training improves endothelium-dependent vasodilatation both in epicardial coronary vessels and in resistance vessels in patients with coronary artery disease.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Acetylcholine / pharmacology
  • Blood Flow Velocity / drug effects
  • Coronary Disease / physiopathology*
  • Coronary Disease / therapy
  • Coronary Vessels / drug effects
  • Coronary Vessels / physiopathology*
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Exercise / physiology*
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Vasodilation / drug effects
  • Vasodilation / physiology
  • Vasodilator Agents / pharmacology


  • Vasodilator Agents
  • Acetylcholine