Published Online
on September 27, 2004

A more recent version of this article appeared on October 5, 2004

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Submitted on February 1, 2004
Revised on May 14, 2004
Accepted on June 29, 2004

Prognostic Value of Systemic Endothelial Dysfunction in Patients With Acute Coronary Syndromes. Further Evidence for the Existence of the "Vulnerable" Patient

Stephan Fichtlscherer MD^*, Susanne Breuer MD, and Andreas M. Zeiher MD

From the Department of Internal Medicine IV, Division of Cardiology, Johann W. Goethe University, Frankfurt, Germany.

^* To whom correspondence should be addressed. E-mail: fichtlscherer{at}em.uni-frankfurt.de.

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 µg/min) and sodium nitroprusside (SNP; 2 to 8 µg/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.

Key words: acute coronary syndromes • prognosis • inflammation • endothelium • nitric oxide

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