Prognostic impact of coronary vasodilator dysfunction on adverse long-termoutcome of coronary heart disease

Background-Endothelial vasodilator dysfunction is a characteristic feature of patients at risk for coronary atherosclerosis. Therefore, we prospective ly investigated whether coronary endothelial dysfunction predicts disease p rogression and cardiovascular event rates. Methods and Results-Coronary vasoreactivity was assessed in 147 patients us ing the endothelium-dependent dilator acetylcholine, sympathetic activation by cold presser testing, dilator responses to increased blood flow, and di lation in response to nitroglycerin. Cardiovascular events (cardiovascular death, unstable angina, myocardial infarction, percutaneous transluminal co ronary angioplasty, coronary bypass grafting, ischemic stroke, or periphera l artery revascularization) served as outcome variables over a median follo w-up period of 7.7 years. Patients suffering from cardiovascular events dur ing follow-up (n=16) had significantly increased vasoconstrictor responses to acetylcholine infusion (P=0.009) and cold presser testing (P=0.002), as well as significantly blunted vasodilator responses to increased blood flow (P<0.001) and the intracoronary injection of nitroglycerin (P=0.001). Impa ired endothelial and endothelium-independent coronary vasoreactivity were a ssociated with a significantly higher incidence of cardiovascular events by Kaplan-Meier analysis. By multivariate analysis, all tests of coronary vas oreactivity were significant, independent predictors of a poor prognosis, e ven after adjustment for traditional cardiovascular risk factors or the pre sence of atherosclerosis itself. Conclusions-Coronary endothelial vasodilator dysfunction predicts long-term atherosclerotic disease progression and cardiovascular event rates. Thus, the assessment of coronary endothelial vasoreactivity can provide pivotal i nformation as both a diagnostic and prognostic tool in patients at risk for coronary heart disease.