Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes: further evidence for the existence of the "vulnerable" patient

Circulation. 2004 Oct 5;110(14):1926-32. doi: 10.1161/01.CIR.0000143378.58099.8C. Epub 2004 Sep 27.


Background: Endothelial vasodilator dysfunction may serve as a marker integrating the vascular risk of an individual; however, whether systemic vasodilator function predicts disease progression and cardiovascular event rates in patients with manifest acute coronary syndromes (ACS) is unknown.

Methods and results: In 198 patients with angiographically documented ACS, forearm blood flow (FBF) responses to acetylcholine (ACH; 10 to 50 microg/min) and sodium nitroprusside (SNP; 2 to 8 microg/min) were measured by venous occlusion plethysmography before hospital discharge within 5 days of an episode of an ACS. Cardiovascular events (cardiovascular death, myocardial infarction, and ischemic stroke) served as outcome variables over a mean follow-up period of 47.7+/-15.1 months. Patients who experienced cardiovascular events during follow-up (n=31) had a significantly reduced vasodilator response to ACH (P<0.05) and SNP (P<0.05). By multivariate analysis, vasodilator response to ACH and elevated troponin T serum levels were the only significant (P<0.05) independent predictors of a poor prognosis, even after adjustment for traditional cardiovascular risk factors, concurrent medication, invasive treatment strategy, and C-reactive protein serum levels. Recovery of endothelium-dependent vasoreactivity as assessed by repeated FBF assessment 8 weeks after the index measurement after the ACS predicted further event-free survival in a subset of 78 patients.

Conclusions: Systemic endothelium-dependent vasoreactivity predicts recurrence of instability and cardiovascular event rates in patients with ACS. Furthermore, the recovery of systemic endothelial function is associated with event-free survival. Assessment of systemic vasoreactivity, measured by a minimally invasive test, provides important prognostic information in addition to that derived from traditional risk factor assessment in patients with ACS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine*
  • Acute Disease
  • Adult
  • Aged
  • Biomarkers
  • Brain Ischemia / epidemiology
  • C-Reactive Protein / analysis
  • Cohort Studies
  • Disease Progression
  • Disease-Free Survival
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / physiopathology*
  • Female
  • Follow-Up Studies
  • Forearm / blood supply
  • Humans
  • Life Tables
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Myocardial Infarction / epidemiology
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / mortality
  • Myocardial Ischemia / physiopathology*
  • Nitroprusside*
  • Plethysmography
  • Predictive Value of Tests
  • Prognosis
  • Risk Factors
  • Troponin T / blood
  • Vasculitis / blood
  • Vasculitis / complications
  • Vasculitis / physiopathology
  • Vasodilation / drug effects*
  • Vasodilator Agents*


  • Biomarkers
  • Troponin T
  • Vasodilator Agents
  • Nitroprusside
  • C-Reactive Protein
  • Acetylcholine