Endothelial dysfunction in patients with angina and non-obstructed coronary arteries is associated with an increased risk of mayor cardiovascular events. Results of the Spanish ENDOCOR registry

Int J Cardiol. 2023 Jan 1:370:18-25. doi: 10.1016/j.ijcard.2022.10.169. Epub 2022 Nov 1.


Background: Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in patients without obstructive coronary stenoses (INOCA).

Objective: To evaluate the prevalence of endothelial dysfunction and the clinical profile of patients with INOCA in Spain, as well as to identify the predictors and the prognostic impact of endothelial dysfunction in this scenario.

Methods: A total of 438 consecutive patients with INOCA in whom the acetylcholine test was performed were prospectively enrolled. Patients were followed up at 1 and 2 years.

Results: Mean age was 62 ± 11 years with 60% female. Clinical presentation comprised 52.6% angina at rest, 61.2% exertional angina, and 31.7% dyspnea. There were no major complications of the acetylcholine test. Endothelial dysfunction was observed in 198 (45%) of patients, with severe vasoconstriction (defined as over 70% constriction), being observed in 101 (23%). Multivariable regression analysis showed that endothelial dysfunction was predicted by the presence of exertional angina (OR 2.2; CI95%1.01-2.55; p = 0.02), prior coronary disease (OR 2.46; CI95% 1.57-3.89; p < 0.01), and coronary intramyocardial bridging (2.35; CI95% 1.02-5.60; p = 0.04). Patients with endothelial dysfunction presented with worsening angina compared to those without endothelial dysfunction (25.6% vs. 12.8%) and also presented with increased levels of minimal effort angina (40% vs. 26,7%, p = 0.03) more frequently during the follow up than those without endothelial dysfunction. Endothelial dysfunction was also an independent predictor of the occurrence of myocardial infarction or unstable angina at one year (OR 2.85, CI 95% 1.01-9.25; p = 0.03).

Conclusions: Endothelial dysfunction is present in almost half of patients with INOCA and is associated with worsening symptoms, as well as with a higher rate of adverse events.

Keywords: Acetylcholine test; Endothelial dysfunction; INOCA; Prognosis.

MeSH terms

  • Acetylcholine*
  • Aged
  • Angina Pectoris / complications
  • Angina Pectoris / diagnosis
  • Angina Pectoris / epidemiology
  • Angina, Unstable / complications
  • Coronary Artery Disease*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Vasoconstriction


  • Acetylcholine