More About Plaques

Abstracts & Commentary

By Jonathan Abrams, MD, Professor of Medicine, Division of Cardiology, University of New Mexico, Albuquerque. Dr. Abrams serves on the speaker's bureau for Merck, Pfizer, and Parke-Davis.

Synopsis: Although patients with SVG plaque ruptures are older and have more co-morbidities, the clinical presentation and angiographic and IVUS features are remarkably similar to those of native artery plaque ruptures. Also, MDCT "may be used to characterize coronary atherosclerotic plague morphology."

Sources: Pregowski J, et al. Comparison of Ruptured Plaques in Native Coronary Arteries and in Saphenous Vein Grafts: An Intravascular Ultrasound Study. Am J Cardiol. 2006;97:593-597; Carrascosa PM, et al. Characterization of Coronary Atherosclerotic Plaques by Multidetector Computed Tomography. Am J Cardiol. 2006;97:598-602.

A great deal of interest and investigation into the biology of vascular plaque has occurred over the past decade. It is now generally accepted that plaques are common, often throughout the coronary tree, and that many if not all may remain silent. It is also known that plaques can rupture or fissure, producing thrombus, and this may be a silent event, although often leading to the worsening of atherothrombosis. High quality coronary angiography has been the gold standard for identification of plaques, particularly so-called vulnerable or ruptured plaque. We have learned that in the presence of an acute coronary syndrome, presumably related to plaque rupture or erosion, there are often other plaques in the same coronary artery or in other arteries which are active and vulnerable. Importantly, the recognition that a relatively modest or non-obstructive narrowing in a coronary vessel may produce a fatal or non-fatal myocardial infarction has contributed to the great interest in plaque biology.

Two reports in the March 1, 2006, issue of the American Journal of Cardiology contribute to our knowledge of plaques. Pregowski and colleagues investigated the appearance of ruptured plaques in coronary arteries and saphenous vein grafts (SVG) using intravascular ultrasound (IVUS); the goal was to determine if there are significant differences between these sites of plaque formation. They studied 95 plaque ruptures within 76 SVGs in 73 patients, and visually compared the SVG ruptured plaques to a cohort of native coronary artery events matched for mean reference lumen area. While coronary plaque ruptures were located in the proximal or mid segments of the parent artery, SVG ruptures were noted at any site in a saphenous vein. Angiographic features that were tabulated included ulceration, intimal flap formation, lumen irregularity, or aneurysm. Coronary lesions were classified as simple in nature if there were no complex features. A standard IVUS pull-back was performed in both groups. Plaque rupture was defined as a cavity that communicated with lumen, with an overlying fragment of residual fibrous cap. Deposits of calcium and increased or decreased brightness of the plaque (hyperechoic or hypoechoic plaque) were noted. Thrombus was found in the coronary arteries, but not in the SVGs. Eccentricity and remodeling characteristics were identified.

The results indicate that patients who had a ruptured SVG plaque were older and more often had major coronary risk factors. Of note, anginal symptoms were similar in the 2 groups, with 70% of patients presenting with an acute coronary syndrome. The mean SVG graft age was 12 years ± 5 years. Angiographic analysis defined over 90% of all ruptured plaques as complex, with a visible intimal flap far more commonly seen in the ruptured SVG. Otherwise, the features were similar. Grade 3 TIMI flow was present in all imaged SVG and native vessels before percutaneous intervention. The IVUS comparisons between the 2 groups demonstrated longer lesion lengths in the native coronary arteries, but comparable ruptured plaque and plaque cavity length. Minimal lumen area was found at the maximum plaque cavity site in half of the SVG ruptures, but only 30% of the native artery ruptures. In addition, distal lumen areas at the site of maximal plaque cavity were larger in the SVG lesions than in the coronary lesions. More than 70% of both groups demonstrated positive arterial remodeling. Calcium deposition and the frequency of eccentric lesions were similar. The site of initial rupture could be identified in approximately 60% in both groups; the rupture typically appeared at the shoulder of the plaque in 2/3 of all patients. Additional ruptures were noted in 40% of SVG lesions and 20% of native plaque patients; 5 patients had 2 additional native ruptures.

Pregowski et al conclude that the clinical, angiographic, and IVUS data support comparable complex angiographic appearances with similar IVUS features (the latter including positive remodeling, eccentricity, shoulder rupture, etc). Clinical presentations were similar between the 2 groups; most patients presented with an acute coronary syndrome, with the culprit lesion more likely to be located in the SVG rather than a native coronary artery.

The data are consistent with other studies indicating that both native arteries and SVGs often undergo plaque rupture or erosion with subsequent thrombus formation in SVGs, as well as native vessels. Other reports using angioscopy and coronary angiography have also suggested a similarity between ulcerated plaques in native arteries and SVGs. In the present study, comparable features of atherosclerotic plaque and similar degrees of positive remodeling, eccentricity, and calcium deposition, suggest "that the mechanisms of plaque ruptures in native arteries and SVGs may also be similar." The SVGs tended to have larger reference plaque area, suggesting that "the atherosclerotic process is more diffuse in vein grafts than native arteries."

Another investigation of coronary plaque is a report of multi-detector computer tomography (MDCT) in the characterization of coronary plaque (Carrascosa, et al.). In this study, 40 patients were subjected both to MDCT and IVUS studies. All had documented coronary disease with > 50% lesion severity and were stable. Phillips 4 row multi-detector computed tomography was utilized, as well as IVUS, which was performed within 3 days of the CT evaluation. Multiple cross-sectional images were generated at 10 mm increments from the coronary ostia to the most distal segment. Digital coronary angiographic studies were performed using interventional techniques. IVUS pull-back was used in all subjects. The data sets of cross-sectional images from the MDCT and IVUS were matched according to the distance from the coronary ostia to be certain the same segments in plaques were evaluated.

A separate analysis of the MDCT and IVUS images were made by 2 independent investigators for the determination of obstructive coronary atherosclerosis. Percent luminal diameter was calculated for both techniques. Plaques were classified as soft, fibrous, or calcified. Percent decreases in luminal area for each segment were independently determined by both IVUS and MDCT; IVUS was considered to be the gold-standard. Overall, 194 segments were reviewed in 71 vessels. Obstructive coronary disease was found in 50 segments by IVUS, and in 57 by MDCT. Sensitivity for MDCT was 86% and specificity was 90%. Correlation between the methods was 0.78 to 0.87 for observer 1, P < 0.0001, and 0.83 to 0.92 for the second investigator, P < 0.0001. Inter-observer agreement for detection of obstructive coronary disease was good.

Overall, 276 plaques were observed by both techniques. The large majority were soft plaques with a relatively small percentage of fibrous and calcified plaques. MDCT showed excellent discrimination between calcified and non-calcified plaques, as well as "significant discrimination between fibrous and soft plaques." Pregowski et al conclude that their results are similar to other MDCT reports using coronary angiography as a comparator. They conclude that MDCT "may be used to characterize coronary atherosclerotic plaque morphology." They also stress that this technique can "in most cases" further differentiate soft from fibrous plaque. They conclude that "MDCT may provide unique, non-invasive, valuable information…to predict patients at risk for developing acute coronary syndrome." They suggest that MRI and contrast ultrasound may be useful, but have "limited spatial resolution for smaller vessels, such as coronary arteries." Finally, they predict that newer generation multi-detector computer tomography (> 16 slices) will result in improved image quality and a greater ability to identify soft from fibrous plaques.

Commentary

There are no surprises in these 2 articles, both of which contribute to our knowledge of coronary plaque behavior, and stress the importance of being able to differentiate plaque characteristics in stable, as well as unstable individuals. The SVG study is of particular interest in that it documents the morphology and behavior of plaque rupture within venous grafts, which appear to be very similar to that which occurs in coronary arteries. This certainly suggests that preventive approaches, particularly extremely aggressive lipid lowering, should be beneficial in maintaining the health of SVGs. The Coronary Bypass Graft lovastatin trial of many years ago suggested that those individuals who achieved the lowest LDL levels had the least amount of graft disease. Little data are available regarding the role of newer statins in SVGs; the current publication strongly suggests that plaque behavior is comparable between diseased coronary arteries and diseased bypass grafts, with plaque rupture features being very similar. Thus, individuals who have had previous bypass grafting with saphenous veins should be treated to the same LDL targets as individuals who have acute coronary syndrome. I suggest that this target should be as low as 70 mg/dL. It would be of considerable interest to see an analysis of long-term results of bypass grafting with respect to lipid levels, comparing individuals who have not been well controlled to those who have had excellent lipid profiles for over a period of 10 or more years.

The MDCT study is already outdated with respect to the advances in the field of imaging. Nevertheless, the ability of MDCT to characterize plaques as soft or fibrous, as well as being able to potentially identify vulnerable vs stable plaques certainly contributes to the Holy Grail today. Cardiologists are increasingly learning about the new imaging and, although many problems remain (see the April 2006 issue of Clinical Cardiology Alert), it is seems that non-invasive imaging of the coronary arteries has become big business. It remains unclear as to the clinical implications of MDCT being able to identify soft, fibrous, or calcified plaque. It will be important in future studies to see whether there are clinical outcomes differences with the different kinds of plaque identified by CT or other techniques, such that different therapies might be employed. The goal of this particular study was not to compare techniques with respect to the degree of coronary obstruction, but rather to characterize the nature of coronary plaque. This is an important and active area of current research; more to come!