atherosclerosis is a systemic disease plaque development and complications occur in a focal patchy pattern. clinical purposes at baseline and at 6 months (all 22 patients were part of the placebo groups of the prospective National Institutes of Health-sponsored studies: the Correlation of Endothelial Function and Early Coronary Artery Disease in Humans trial [NCT00271492] and the Long-Term l-Arginine Supplementation Improves Small-Vessel Coronary Endothelial Function CO-1686 in Humans trial [HL-03180-01]). Coronary artery segments with normal (n = 22) and abnormal (n = 22) endothelial function were analyzed within the same subject and compared with each other after 6 months of follow-up. Endothelium-dependent and -impartial vasoreactivity was assessed as previously described (1 2 After completing the CO-1686 CO-1686 CO-1686 endothelial function studies standard IVUS analysis with automated pullback (0.5 mm/s) of the left anterior descending coronary artery was performed using a 20-MHz 2.9 Eagle Eye catheter (Volcano Corporation Rancho Cordova California). Comparisons between measurements on segments with versus without endothelial dysfunction were conducted using Wilcoxon signed rank assessments because each patient contributed 1 segment of each kind. Similarly comparisons between baseline and 6-month follow-up measures were conducted using Wilcoxon signed rank assessments. All statistical assessments were 2-sided and a p value <0.05 was considered to be statistically significant. Analyses were conducted using SAS version 9.2 (SAS Institute Cary North Carolina) and SPSS version 11.5 (IBM Armonk New Rabbit polyclonal to KIAA0802. York). There was a significant decrease in total and low-density lipoprotein cholesterol as well as C-reactive protein levels at 6-month follow-up without a significant change in statin use. Lifestyle changes that may have contributed to these changes were not assessed in the current study protocol. Intraindividual percent change of normalized total atheroma volume (TAV) and percent change of percent atheroma volume (PAV) of the segments with endothelial dysfunction were higher than of those with normal endothelial function reaching statistical significance only for changes in PAV (Fig. 1). Although there was significant increase in plaque volume in the segments with endothelial dysfunction lumen size did not change significantly. Although the presence of endothelial dysfunction was associated with coronary plaque progression there was no significant correlation between the degree of percent change of epicardial segmental coronary arterial diameter with acetylcholine infusion during follow-up and percent change of normalized TAV (r = ?0.24 p = 0.40). Likewise there was no significant correlation between percent change of coronary blood flow with acetylcholine during follow-up and percent change of normalized TAV (r = ?0.18 p = 0.52). Physique 1 Comparison of Intraindividual % Change of Normalized PAV and TAV Between the Segments With Endothelial Dysfunction and Those With Normal Endothelial Function The current study thus demonstrates for the first time in patients with moderate coronary artery disease using serial volumetric IVUS analysis that within the same coronary artery segments with endothelial dysfunction show accelerated plaque progression compared with segments with normal endothelial function. Our findings expand previous observations and suggest a regional association between coronary endothelial dysfunction and progression of coronary atherosclerosis. We have previously reported that coronary artery segments with endothelial dysfunction have larger necrotic cores and more features of plaque vulnerability including microcalcification as assessed by virtual histology (VH) (3). In addition the most-recent data from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) CO-1686 study in patients with acute coronary syndromes exhibited that nonculprit lesions with 70% plaque burden and IVUS-VH-derived thin-capped fibroatheroma are more likely associated with the progression of atherosclerosis and recurrent coronary events (4). Thus the current study extends these previous observations and demonstrates that coronary artery segments with relatively small plaque burden but evidence of endothelial dysfunction show faster plaque progression over a relatively short period of.