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 additio...

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Published in:Clinical cardiology (Mahwah, N.J.) N.J.), 2000-09, Vol.23 (9), p.645-652
Main Authors: Clague, Jonathan R., Bagger, Jens‐Peder, Ward, David E., Cox, Ian D., Kaski, Juan‐Carlos
Format: Article
Language:English
Subjects:
Acetylcholine - pharmacology
Adenosine - pharmacology
Biological and medical sciences
Cardiology. Vascular system
chest pain
Clinical Investigation
Clinical Investigations
Coronary Artery Disease - diagnostic imaging
Coronary Artery Disease - physiopathology
Coronary Circulation - drug effects
Coronary Circulation - physiology
Coronary heart disease
endothelial dysfunction
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiopathology
Female
Heart
Humans
Male
Medical sciences
Microvascular Angina - diagnostic imaging
Microvascular Angina - etiology
Microvascular Angina - physiopathology
Middle Aged
normal coronary arteriogram
Radiography
Regression Analysis
Risk Factors
subangiographic atheroma
Ultrasonography, Interventional
Vasodilator Agents - pharmacology
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Summary: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. Hypothesis: 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 μg) and nitroglycerin (300 μg)] 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 electrocardio‐graphic 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. Conclusion: 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.
ISSN:0160-9289
1932-8737
DOI:10.1002/clc.4960230904