Background— Previous studies suggest that erythrocyte membranes from intraplaque hemorrhage into the necrotic core are a source of free cholesterol and may become a driving force in the progression of atherosclerosis. We have shown that MRI can accurately identify carotid intraplaque hemorrhage and precisely measure plaque volume. We tested the hypothesis that hemorrhage into carotid atheroma stimulates plaque progression.

Methods and Results— Twenty-nine subjects (14 cases with intraplaque hemorrhage and 15 controls with comparably sized plaques without intraplaque hemorrhage at baseline) underwent serial carotid MRI examination with a multicontrast weighted protocol (T1, T2, proton density, and 3D time of flight) over a period of 18 months. The volumes of wall, lumen, lipid-rich necrotic core, calcification, and intraplaque hemorrhage were measured with a custom-designed image analysis tool. The percent change in wall volume (6.8% versus −0.15%; P=0.009) and lipid-rich necrotic core volume (28.4% versus −5.2%; P=0.001) was significantly higher in the hemorrhage group than in controls over the course of the study. Furthermore, those with intraplaque hemorrhage at baseline were much more likely to have new plaque hemorrhages at 18 months compared with controls (43% versus 0%; P=0.006).

Conclusions— Hemorrhage into the carotid atherosclerotic plaque accelerated plaque progression in an 18-month period. Repeated bleeding into the plaque may produce a stimulus for the progression of atherosclerosis by increasing lipid core and plaque volume and creating new destabilizing factors.