Determinants of plaque instability in atherosclerotic vascular disease

Background: Despite numerous advances in the understanding of the pathogenesis of atherosclerosis, the factors that determine atheromatous plaque instability remain unclear. The prediction of the vulnerability of a plaque to rupture and subsequent thrombosis would be useful in guiding development of diagnostic and therapeutic approaches. Methods: Aortas with areas of gross atherosclerosis were obtained from seven autopsy cases. These were then serially sectioned at 3-mm intervals, analyzed histologically, and scored as to plaque size, calcification, lipid content, intraplaque hemorrhage, inflammation, plaque disruption, and plaque thrombosis. Bivariate correlations and binary multivariate regression analyses were performed using SPSS software. Results: Plaque instability was highly correlated with intraplaque hemorrhage, lipid content, and plaque size. Weaker but statistically significant correlations were found with inflammation and calcification. However, in multivariate regression analyses, only plaque size, intraplaque hemorrhage, and lipid content, independent predictors of plaque instability, were significant. Conclusions: Atheromatous plaques may be rendered unstable by increases in size, increased intra- and extracellular lipid accumulation, and intraplaque hemorrhage. Based on these results, diagnostic modalities that detect plaque size, plaque hemorrhage, and/or lipid content are most likely to be useful in predicting unstable plaques.