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, functional assessment of coronary vasomotor abnormalities may provide additional pathophysiologic information.


OBJECTIVE
The study was undertaken to evaluate the relationship between endothelial dysfunction and subangiographic atheroma in patients with CPNA undergoing 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 microvascular vasomotor responses to intracoronary vasodilators [acetylcholine (10(-6) M), adenosine (18 micrograms) and nitroglycerin (300 micrograms)] were investigated in the left anterior descending artery using quantitative angiography and Doppler flow measurements. The presence of subangiographic atheroma was assessed by intravascular ultrasound.


RESULTS
Three patients demonstrated proximal and distal epicardial vasoconstriction and a reduction in coronary flow in response to acetylcholine, indicating concordant epicardial and microvascular endothelial dysfunction. These changes were associated with chest pain and ischemic electrocardiographic changes in two patients. None of the remaining patients suffered chest pain in response to intracoronary acetylcholine. Six patients had significant subangiographic disease (intimal thickness > 0.3 mm) on intravascular ultrasound imaging, and multivariate analysis indicated a significant relationship (R2 = 0.89, overall p = 0.001) between the extent of subangiographic disease and both plasma cholesterol concentration and hypertensive history. No significant relationship was demonstrated between endothelial dysfunction and the extent of subangiographic disease.


CONCLUSIONS
Concordant epicardial and microvascular endothelial dysfunction may be pathophysiologically and clinically significant in unstable patients with CPNA but does not appear to be directly related to the extent of subangiographic atheroma.
Cox
I D
ID
Cardiological Sciences Department, St. George's Hospital Medical School, London, U.K.
Clague
J R
JR
Bagger
J P
JP
Ward
D E
DE
Kaski
J C
JC
D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D017566:Microvascular Angina / Q000000981:diagnostic imaging* / Q000209:etiology / Q000503:physiopathology*; D008875:Middle Aged; D011859:Radiography; D012044:Regression Analysis; D012307:Risk Factors; D018084:Ultrasonography, Interventional; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D000241:Adenosine; D000109:Acetylcholine