Published Online
on May 10, 2004

A more recent version of this article appeared on June 1, 2004

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Submitted on December 5, 2004
Revised on February 19, 2004
Accepted on February 25, 2004

Endothelial Function Predicts Future Development of Coronary Artery Disease. A Study of Women With Chest Pain and Normal Coronary Angiograms

Raffaele Bugiardini MD^*, Olivia Manfrini MD, Carmine Pizzi MD, Fiorella Fontana MD, and Gianluigi Morgagni MD

From the University of Bologna, Bologna, (R.B., O.M., C.P., F.F.) and Macerata Hospital, Macerata (G.M.), Italy.

^* To whom correspondence should be addressed. E-mail: raffaele.bugiardini{at}unibo.it.

Background--The prognosis for women with chest pain and angiographically normal coronary arteries is believed to be totally benign. Previous studies, however, did not account for the delay of a decade or so in the development of coronary artery disease that women may experience.

Methods and Results--This study assessed long-term follow-up of 42 women with de novo angina, evidence of reversible myocardial perfusion defects on SPECT, and normal coronary angiograms. At recruitment, all women underwent endothelial function testing (intracoronary acetylcholine) during catheterization. Patients were followed up for >10 years. Angiography was repeated at the end of the follow-up in 37 patients. At recruitment, 22 patients developed diffuse vasoconstriction during acetylcholine in the absence of identifiable focal coronary spasm (acetylcholine-positive group). The remaining 20 patients showed vasodilation (acetylcholine-negative group). At the end of follow-up, in the acetylcholine-positive group, 1 patient developed cardiac death, 13 still complained of chest pain, and 8 had remission of symptoms. In the acetylcholine-negative group, all patients showed complete resolution of chest pain beginning 6 to 36 months after baseline assessment. Angiography showed development of coronary artery disease in the 13 symptomatic patients in the acetylcholine-positive group.

Conclusions--In women with angiographically normal-appearing coronary arteries, persistence of chest pain over the years often relates to development of coronary artery disease. Endothelial dysfunction in a setting of normal coronary arteries is a sign of future development of atherosclerosis.

Key words: acetylcholine • angina • endothelium • prognosis • women

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