The relation among the burden of disease, progression of atherosclerosis, and remodeling in angiographically minimally diseased coronary arteries has not been defined. The present analysis included 1,906 patients who participated in 5 prospective clinical trials examining atheroma progression using intravascular ultrasonography. For the present analysis, the patients were stratified according to baseline quantitative coronary angiographic stenosis: <20%, 20% to 35%, and >35%. Patients with a lesser degree of luminal stenosis had less atherosclerosis. However, in the arteries with minimal angiographic stenosis, a large percentage of images contained atheroma, demonstrating the diffuse nature of coronary atherosclerosis. All 3 groups showed evidence of disease progression. The serial changes in vessel dimensions revealed that both the external elastic membrane and lumen volumes decreased in all 3 subgroups, in keeping with vessel and luminal constriction. In conclusion, these findings have demonstrated that patients with at least one luminal stenosis have diffuse atherosclerosis that progressed during 18 to 24 months, making them a target for therapeutic intervention. These minimally diseased arteries demonstrated evidence of vessel and luminal constriction, regardless of the angiographic appearance.
The aim of the present analysis was to characterize the burden and pattern of atherosclerosis and associated arterial remodeling at baseline and follow-up on serial imaging in vessels, stratified according to the degree of angiographic lumen stenosis at baseline. We hypothesized that once obstructive disease was present in one coronary artery, the imaged vessel would also harbor diffuse disease that would subsequently progress during serial evaluation. In these minimally diseased arteries, it was also hypothesized that evidence of vessel wall expansion would be present to compensate for the plaque progression.
Methods
The subjects participated in clinical trials that evaluated the effect of medical therapies on the progression of coronary atherosclerosis, as assessed by serial intravascular ultrasound (IVUS) and quantitative coronary angiographic (QCA) examinations. These studies included Acyl:Cholesterol Acyltransferase Intravascular Atherosclerosis Treatment Evaluation (ACTIVATE), A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID), Comparison of Pioglitazone vs Glimerpiride on Progression of Coronary Atherosclerosis in Patients with Type 2 Diabetes (PERISCOPE), Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL), and Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis (CAMELOT). In each of these studies, the subjects were required to have coronary artery disease, defined as the presence of lumen stenosis >20% in at least one major epicardial coronary artery on visual estimation of the coronary angiogram performed for a clinical indication. All studies were conducted under the academic leadership of the Cleveland Clinic, and the patients provided informed written consent before enrollment at the sites with approval of the respective institutional review board.
The details of acquisition and analysis of arterial imaging have previously been described in detail. In brief, a vessel was selected for IVUS imaging that contained no stenosis >50% and enabled ≥30 mm of imaging between 2 side branches, which served as the anatomic landmarks (fiduciary points) for matching of segments on serial evaluation. A vessel was required to not have undergone revascularization or be considered the culprit vessel for a previous myocardial infarction. After anticoagulation and administration of intracoronary nitroglycerin, the IVUS catheter, containing a high-frequency (30 to 40 MHz) ultrasound transducer, was placed as distally as possible. Continuous ultrasound imaging was acquired while withdrawing the catheter to the aorta, at a constant rate of 0.5 mm/s.
After digitization of the images and definition of the anatomically matched segment, cross-sectional images spaced 1 mm apart were selected for analysis. The leading edge of the lumen and external elastic membrane (EEM) was defined by manual planimetry. The atheroma area in each measured image was defined as the difference between the lumen and EEM. The total atheroma volume (TAV) was calculated as the summation of plaque area in all measured images and normalized by the median number of images analyzed in the entire study cohort, to account for differences in segment length between subjects.
T A V Normalized = Σ ( E E M area − L u m e n area ) Number of Images in Pullback × Median number of images in cohort
The percentage of atheroma volume (PAV) was calculated as the summation of plaque area in each measured image, divided by the total vessel wall dimensions.
P A V = Σ ( E E M area − L u m e n area ) Σ ( E E M area ) × 100
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