EVIDENCE THAT SELECTIVE ENDOTHELIAL DYSFUNCTION MAY OCCUR IN THE ABSENCE OF ANGIOGRAPHIC OR ULTRASOUND ATHEROSCLEROSIS IN PATIENTS WITH RISK-FACTORS FOR ATHEROSCLEROSIS

Objectives. The purpose of this study was to test the hypothesis that endothelial dysfunction occurs in humans before the development of str uctural coronary atherosclerosis when risk factors for this disease ar e present. Background, Animal studies have demonstrated that known ris k factors for coronary atherosclerosis (hyperlipidemia, hypertension, diabetes) result in impaired endothelium dependent vascular reactivity before the development of structural atherosclerosis. Previous studie s in patients have been unable to distinguish early structural atheros clerotic disease from dysfunctional endothelium. Methods. Twenty six p atients with angiographically normal coronary arteries were studied at cardiac catheterization. The epicardial arteries were imaged using hi gh resolution intravascular ultrasound to detect early structural chan ges and to determine changes in lumen size during pharmacologic provoc ation. A selective intracoronary Doppler velocity catheter was subsequ ently used to determine coronary blood flow velocity changes in respon se to the same pharmacologic provocation, Group I (9 patients) had no risk factors for atherosclerosis. Group II (17 patients) had one or mo re risk factors present. Results. Although both Groups I and II had a normal microvascular vasodilator response to adenosine or papaverine i nfusion (estimated coronary flow increase 396 +/- 200% vs. 326 +/- 161 % [mean +/- SD], respectively, p = 0.103), only Group I patients had a n intact response to acetylcholine infusion (378 +/- 203% vs. 75 +/- 9 3% in Group II, p = 0.001). Group II patients had an abnormal epicardi al artery cross-sectional area vasoconstriction response to acetylchol ine infusion (-16.6 +/- 12.4% [13 patients] vs, 1.3 +/- 11.5% in Group I, p = 0.0007). An additional four Group II patients had severe spasm during acetylcholine infusion. Epicardial vasodilator response to nit roglycerin infusion, however, was preserved in Group II (14.6 +/- 4.3% vs. 9.6 +/- 3.5% in Group I, p = 0.212). All Group I patients had nor mal vessels by intravascular ultrasound. Of the 17 patients in Group I I, 7 had minimal disease on ultrasound (intimal thickening or small ec centric plaque) in the study vessel. These patients did not respond di fferently from the 10 Group II patients without demonstrable disease o n ultrasound. Conclusions. Patients with risk factors for coronary art ery disease, normal coronary angiograms and no measurable disease by i ntracoronary ultrasound exhibit selective endothelial dysfunction at b oth the epicardial and microvascular levels. These find ings may have implications for the treatment of ''preclinical'' coronary atheroscler osis.