Atherosclerosis in angiographically "normal" coronary artery reference segments: an intravascular ultrasound study with clinical correlations.

Objectives: This study evaluated the magnitude, patterns and clinical correlates of atherosclerosis in angiographically "normal" reference segments in patients undergoing transcatheter therapy for symptomatic coronary artery disease.

Background: Pathologic studies indicate that the extent of coronary atherosclerosis is underestimated by visual analysis of angiographically normal coronary artery segments. Intravascular ultrasound allows detailed, high quality cross-sectional imaging of the coronary arteries in vivo.

Methods: Intravascular ultrasound was used to study angiographically normal coronary artery reference segments in 884 patients evaluated for transcatheter therapy for symptomatic native coronary artery disease. The reference segment was the most visually normal intravascular ultrasound cross section within 10 mm proximal to the target lesion but distal to any major side branch. Results are presented as mean value +/- 1 SD.

Results: Only 60 (6.8%) of 884 angiographically normal reference segments were normal by intravascular ultrasound. Reference segment percent cross-sectional narrowing measured 51 +/- 13% and correlated poorly with the target lesion percent cross-sectional narrowing (r = 0.166, p < 0.0001). Reference segments contained less calcific and dense fibrotic plaque and proportionately more soft plaque elements. Independent predictors of reference segment percent cross-sectional narrowing were male gender, patient age, diabetes mellitus, hypercholesterolemia and presence of multivessel disease. Independent predictors of reference segment calcification were patient age and serum creatinine levels. Reference segment percent cross-sectional narrowing in 723 patients undergoing transcatheter therapy was similar to that in patients studied for diagnostic purposes; however, reference segment arc of calcium was greater in treated patients (43 +/- 81 vs. 25 +/- 57, p = 0.015). Reference segment disease was not an independent predictor of subsequent angiographic restenosis or clinical events within 12 months of follow-up.

Conclusions: Atherosclerosis is ubiquitous in angiographically normal coronary artery reference segments. Reference segment disease parallels the severity of target lesion disease and is associated with many of the conventional risk factors for coronary artery disease. Because of its sensitivity in detecting atherosclerosis in angiographically normal reference segments, intravascular ultrasound should enhance the study of risk factors for atherosclerosis and the results of therapies to control disease progression.