New research hopes to predict future unstable coronary lesions

February 10, 2008 By Benjamin A. Olenchock, M.D. Ph.D. [mailto:bolenchock@partners.org]

The paradox of coronary artery disease is that the most angiographically impressive, flow-limiting coronary lesions are not the most dangerous. These lesions grow slowly over years, allowing time for collateral blood flow to develop and supply the chronically hypoxic myocardium. Consequently, blockages at these lesions result in smaller, frequently non ST-elevation myocardial infarcts. The more dangerous coronary lesions have small fibrin caps and high lipid content. These lesions are usually not flow-limiting, so collateralization is less common. Rupture of these plaques results in large, usually ST-elevation myocardial infarctions. The difficulty is that flow-limiting lesions can be easily identified, while it is currently impossible to predict where in the coronary tree high risk lesions will develop. New research published in the journal Circulation hopes to use intravascular ultrasound (IVUS) to predict where these high risk vulnerable plaques will develop.

The investigators studies pigs which had been rendered diabetic and hyperlipidemic in order to promote atherogenesis. Pigs underwent coronary angiography and IVUS at either 4 and 8 weeks or at 23 and 30 weeks. Endothelial shear stress (ESS) was calculated along coronary subsegments of interest. Subsegments were included in the analysis if they had uniform intra-medial thickness which was less than 0.5 mm at baseline. The most severe-appearing subsegments at follow-up were chosen for analysis, and subsegments adjacent to or involving side branches were not included in the analysis. Coronary arteries were harvest at 30 weeks, subsegments were located, and lesions were classified as either minimal, intermediate, or fibroatheromas. Additionally, the quality of arterial remodeling was assessed as change in plaque area by IVUS compared to the remodeling response of the entire reconstructed artery.

Overall, there were 32 coronary arteries from 11 pigs profiled in the early group (4 and 8 weeks) and 31 arteries from the late group (23 and 30 weeks). The atherosclerotic burden was minimal at weeks 4 and 8, and was greatly increased by week 23 and even more so by week 30. The researchers focused on 142 subsegments that were free from atherosclerosis at week 23. Based on the histological appearance of the lesions within these segments at week 30, lesions were classified as minimal, intermediate or fibroatheroma. Lesions classified as fibroatheromas had much higher lipid and inflammatory cell content with thin fibrous caps. Comparing ESS with lesion classification, they found that intermediate and fibroatheroma lesions developed in sections with lower ESS at baseline and follow-up. The segments with lowest baseline ESS (<0.50 Pa) developed lesions with the higheset intima-to-media ratio, lipid content, and inflammation. The relationship between baseline ESS and high risk lesion characteristics was almost linear, meaning that the lower the baseline ESS the higher the risk characteristics of the lesion. Similarly, low baseline ESS predicted low internal elastic lamina thickness, meaning higher risk plaques.

Corresponding author Peter Stone explained to wikidoc the importance of the work: “The value of this study is that it underscores that the development and progression of coronary artery disease occurs in predictable regions and for predictable reasons, and perhaps most importantly, that we now have in-vivo tools to enable us to know where high-risk vulnerable plaque will develop in man. The ultimate goal of these studies is to perform vascular profiling methods in vivo to assess local endothelial shear stress throughout the entire coronary artery tree in man to be able to risk-stratify individual coronary lesions and to identify just where a new adverse cardiac event will occur. This insight will enable us to consider pre-emptive strategies to avert major cardiac events in hundreds of thousands of cardiac patients around the world. A large scale trial is currently underway in Japan, the PREDICTION Trial, to investigate this hypothesis in man.”