Angina pectoris caused by coronary microvascular spasm

Lancet. 1998 Apr 18;351(9110):1165-9. doi: 10.1016/S0140-6736(97)07329-7.


Background: Microvascular angina can occur during exercise and at rest. Reduced vasodilator capacity of the coronary microvessels is implicated as a cause of angina during exercise, but the mechanism of angina at rest is not known. Our aim was to test the hypothesis that primary hyperconstriction (spasm) of coronary microvessels causes myocardial ischaemia at rest.

Methods: Acetylcholine induces coronary artery spasm in patients with variant angina. We tested the effects of intracoronary acetylcholine at graded doses in 117 consecutive patients with chest pain (at rest, during exertion, or both) and no flow-limiting (>50%) organic stenosis in the large epicardial coronary arteries. We also assessed the metabolism of myocardial lactate during acetylcholine administration in 36 of the patients by measurement of lactate in paired blood samples from the coronary artery and coronary sinus vein.

Findings: Of the 117 patients, 63 (54%) had large-artery spasm, 29 (25%) had microvascular spasm, and 25 (21%) had atypical chest pain. The 29 patients with microvascular spasm developed angina-like chest pain, ischaemic electrocardiogram (ECG) changes, or both spontaneously (two patients) or after administration of acetylcholine (27 patients) without spasm of the large epicardial coronary arteries. Testing of paired samples of arterial and coronary sinus venous blood showed that lactate was produced during angina attack in nine of 11 patients with microvascular spasm. There was more women (p<0.01) and fewer coronary risk factors (p<0.01) in patients with microvascular spasm than in those with large-artery spasm.

Interpretation: Coronary microvascular spasm and resultant myocardial ischaemia may be the cause of chest pain in a subgroup of patients with microvascular angina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine
  • Aged
  • Angina, Unstable / diagnostic imaging
  • Angina, Unstable / physiopathology
  • Coronary Angiography*
  • Coronary Artery Disease / diagnostic imaging
  • Coronary Artery Disease / physiopathology
  • Coronary Circulation / physiology
  • Coronary Vasospasm / diagnostic imaging
  • Coronary Vasospasm / physiopathology
  • Diagnosis, Differential
  • Dose-Response Relationship, Drug
  • Electrocardiography / drug effects
  • Female
  • Humans
  • Lactic Acid / blood
  • Male
  • Microcirculation / physiopathology
  • Microvascular Angina / diagnostic imaging*
  • Microvascular Angina / physiopathology
  • Middle Aged
  • Myocardial Ischemia / diagnostic imaging
  • Myocardial Ischemia / physiopathology
  • Risk Factors


  • Lactic Acid
  • Acetylcholine