Prognostic value of systemic endothelial dysfunction in patients with acute coronary syndromes - Further evidence for the existence of the vulnerable patient

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