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

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Aortic Atherosclerosis Determines Increased Retrograde Blood Flow as a Potential Mechanism of Retrograde Embolic Stroke

“…However, as all examinations were performed by the same echocardiographers, we believe that this has not introduced any systematic error, especially because VTI ratio is a relative parameter and not strongly affected by angulation of the TEE probe. Moreover, TEE has only limited capabilities in evaluation of the internal structure of plaques, which is relevant for differentiating between stable and potentially vulnerable plaques [18,19]. In this context, MRI [20] and CT imaging [21] or dedicated ultrasound techniques [22,23] may provide additional information; however, those techniques are mostly designed for carotid plaque imaging and not suitable for the aorta.…”

Carotid Plaque Morphology Is Significantly Associated With Sex, Age, and History of Neurological Symptoms

“…Plaque hemorrhage has already been considered an important vulnerable plaque component that was shown to be associated with increased risk of stroke in clinical studies. [26][27][28] In addition, intraplaque hemorrhage noninvasively detected on magnetic resonance imaging was demonstrated to be a strong predictor for cerebrovascular events and might therefore be used for noninvasive risk stratification. [29][30][31] However, contradictory results have also been published showing that there is no association between plaque hemorrhage and microembolic signals 32 or the risk of stroke on a histopathologic analysis.…”

“…Although Davaine et al 34 showed that vascular calcification is associated with plaque stability, other studies revealed ambiguous results. 26,33,35 Howard et al 33 did not find any relationships between calcification, intraplaque hemorrhage, or lymphocyte infiltration and stroke occurrence. In accordance with the latter findings, our study confirmed the assumption that increased calcification or higher amounts of inflammatory infiltration were also not associated with a history of neurological symptoms.…”

Prediction of Carotid Intraplaque Hemorrhage Using Adventitial Calcification and Plaque Thickness on CTA

“…16 An additional study of patients with symptomatic plaques (recent TIA, stroke, or amaurosis fugax) versus asymptomatic patients with critical stenosis found that the percentage of plaque calcification area was 2-fold greater in asymptomatic-versus-symptomatic plaques, and there was an inverse relationship between calcification and macrophage infiltration. 17 A different study investigating 611 carotid plaques by CT and MR imaging found that larger calcification volume was associated with higher IPH prevalence and a lower lipid core prevalence, suggesting that calcification may not be a stabilizing factor. 18 However, these studies evaluated total calcification volume or its binary presence or absence, and adventitial calcification coupled with soft plaque has not yet been addressed, to our knowledge.…”