Endothelial dysfunction, subangiographic atheroma, and unstable symptoms in patients with chest pain and normal coronary arteriograms

Background: Patients with chest pain and normal coronary arteriograms (CPNA ) may present with unstable symptoms and other evidence of ischemia during clinical follow-up. Although repeat angiography usually proves negative, fu nctional assessment of coronary vasomotor abnormalities may provide additio nal pathophysiologic information. Hypothesis: The study was undertaken to evaluate the relationship between e ndothelial dysfunction and subangiographic atheroma in patients with CPNA u ndergoing repeat angiography because of unstable symptoms. Methods: We investigated nine patients with CPNA (8 women, mean age 57 +/- 9 years) undergoing repeat angiography because of unstable anginal symptoms . After normal angiography, simultaneous coronary epicardial and microvascu lar vasomotor responses to intracoronary vasodilators l[acetylcholine (10(- 6) M), adenosine (18 mu g) and nitroglycerin (300 mu g)] were investigated in the left anterior descending artery using quantitative angiography and D oppler flow measurements. The presence of subangiographic atheroma was asse ssed by intravascular ultrasound. Results: Three patients demonstrated proximal and distal epicardial vasocon striction and a reduction in response to acetylcholine, indicating concorda nt epicardial and microvascular endothelial dysfunction. These changes were associated with chest pain and ischemic electrocardiographic changes in tw o patients. None of the remaining patients suffered chest pain in response to intracoronary acetylcholine. Six patients had significant subangiographi c disease (intimal thickness >0.3 mm) on intravascular ultrasound imaging, and multivariate analysis indicated a significant relationship (R-2 = 0.89, overall p = 0.001) between the extent of subangiographic disease and both plasma cholesterol concentration and hypertensive history. No significant r elationship was demonstrated between endothelial dysfunction and the extent of subangiographic disease. Conclusion: Concordant epicardial and microvascular endothelial dysfunction may be pathophysiologically and clinically significant in unstable patient s with CPNA but does not appear to be directly related to the extent of sub angiographic atheroma.