Supplementary Material for: Coexistence of Calcification, Intraplaque Hemorrhage and Lipid Core within the Asymptomatic Atherosclerotic Carotid Plaque: The Rotterdam Study

<b><i>Background:</i></b> There is a growing amount of evidence suggesting that the composition of carotid atherosclerotic plaques may be of clinical relevance. Yet, little is known on the coexistence of potentially vulnerable and stabilizing components within asymptomatic plaques. Therefore, in this study we set out to investigate the coexistence of intraplaque calcification, hemorrhage and lipid core within the carotid artery using a multi-modality imaging approach. <b><i>Methods:</i></b> In 329 subjects from the population-based Rotterdam Study, all with ultrasound-confirmed carotid wall thickening, we performed a multi-detector CT and a high-resolution MRI of the carotid artery bifurcation at both sides. On the CT examinations, we quantified the volume of intraplaque calcification, and using the MRI examinations we rated the presence of intraplaque hemorrhage and of lipid core. In total, we investigated 611 carotid arteries with plaques. With logistic regression models we investigated the relationship of calcification volume - as a potential stabilizing component - with the presence of potential vulnerable components (intraplaque hemorrhage and lipid core) within each carotid plaque. We adjusted all analyses for age, sex and maximal plaque thickness. Next, we stratified on degree of stenosis (≤ or >30%) to evaluate effect modification by atherosclerotic burden. <b><i>Results:</i></b> We found that a larger calcification volume was associated with a higher prevalence of intraplaque hemorrhage, and a lower prevalence of lipid core (fully-adjusted odds ratio (OR) per standard deviation (SD) increase in calcification volume: 2.04 (95% confidence intervals (CI): 1.49; 2.78) and 0.72 (95% CI: 0.58; 0.90), respectively). Stratification on the degree of stenosis showed no difference in the association between calcification volume and hemorrhage over strata, while the relationship between a larger calcification volume and a lower prevalence of lipid seemed more pronounced in persons with a high degree of stenosis. <b><i>Conclusions:</i></b> In this population-based setting, we found that there is a complex relationship between calcification, intraplaque hemorrhage and lipid core within the carotid atherosclerotic plaque. Plaques with a higher load of calcification contain more often hemorrhagic components, but less often lipid core. Our results suggest that both in small and large plaques, intraplaque calcification may not be a stabilizing factor per se. These findings create an urge for conducting prospective studies investigating the interrelation of these different plaque components with regard to future cerebrovascular events.