Superficial and multiple calcifications and ulceration associate with intraplaque hemorrhage in the carotid atherosclerotic plaque

Abstract

ObjectiveIntraplaque hemorrhage (IPH) and ulceration of carotid atherosclerotic plaques have been associated with vulnerability while calcification has been conventionally thought protective. However, studies suggested calcification size and location may increase plaque vulnerability. This study explored the association between calcium configurations and ulceration with IPH.MethodsOne hundred thirty-seven consecutive symptomatic patients scheduled for carotid endarterectomy were recruited. CTA and CTP were performed prior to surgery. Plaque samples were collected for histology. According to the location, calcifications were categorized into superficial, deep and mixed types; according to the size and number, calcifications were classified as thick and thin, multiple and single.ResultsSeventy-one plaques had IPH (51.8%) and 83 had ulceration (60.6%). The appearance of IPH and ulceration was correlated (r = 0.49; p < 0.001). The incidence of multiple, superficial and thin calcifications was significantly higher in lesions with IPH and ulceration compared with those without. After adjusting factors including age, stenosis and ulceration, the presence of calcification [OR (95% CI), 3.0 (1.1-8.2), p = 0.035], multiple calcification [3.9 (1.4-10.9), p = 0.009] and superficial calcification [3.4 (1.1-10.8), p = 0.001] were all associated with IPH. ROC analysis showed that the AUC of superficial and multiple calcifications in detecting IPH was 0.63 and 0.66, respectively (p < 0.05). When the ulceration was combined, AUC increased significantly to 0.82 and 0.83, respectively. Results also showed that patients with lesions of both ulceration and IPH have significantly reduced brain perfusion in the area ipsilateral to the infarction.ConclusionsSuperficial and multiple calcifications and ulceration were associated with carotid IPH, and they may be a surrogate for higher risk lesions.Key Points • CTA-defined superficial and multiple calcifications in carotid atherosclerotic plaques are independently associated with the presence of intraplaque hemorrhage. • The combination of superficial and multiple calcifications and ulceration is highly predictive of carotid intraplaque hemorrhage. • Patients with lesions of both ulceration and intraplaque hemorrhage have significantly reduced brain perfusion in the area ipsilateral to the infarction.

Calcification in Atherosclerotic Plaque Vulnerability: Friend or Foe?

“…Two high-resolution MRI studies classified plaques into single or multiple calcifications. Multiple calcifications have been observed more often in plaques with IPH and ulceration than in those with neither IPH nor ulceration (Yang et al, 2018). Of 142 carotid plaques in 117 patients with cerebrovascular symptoms, plaques with IPH showed a greater prevalence of calcification.…”

“…Two recent studies on carotid atherosclerotic plaque employed this definition to examine the association of calcification location and IPH. One study used carotid CTA source images to illustrate superficial calcifications as calcified nodules located at the intimal-luminal interface or close to the lumen (Yang et al, 2018). The other defined surface calcifications as calcified nodules within or very close to the fibrous cap but without complete coverage of fibrous tissue by means of MRI (Lin et al, 2017).…”

“…Although the definition of superficial calcification varies, the association between superficial calcification and plaque vulnerability has been demonstrated (Xu et al, 2010;Lin et al, 2017;Zhan et al, 2017;Yang et al, 2018). During the complex physiological and biomechanical processes of IPH and plaque rupture, superficial calcifications could increase the local stress and stretch concentration (Zhongzhao et al, 2014).…”

“…The patchy type was calcification, which occupied >50% of the plaque. Another MR study found that thin calcification (the maximum thickness < 2 mm) was associated with IPH (Yang et al, 2018). Due to the limited resolution of imaging techniques, more detailed shape features of calcifications have not been analyzed in vivo.…”

Superficial Calcification With Rotund Shape Is Associated With Carotid Plaque Rupture: An Optical Coherence Tomography Study

“…Two recent studies on carotid atherosclerotic plaque employed this definition to examine the association of calcification location and intraplaque hemorrhage. One used carotid CT angiography source images to illustrate superficial calcifications (28). The other defined surface calcifications as calcified nodule within or very close to the fibrous cap but without fibrous tissue completely covering by means of MRI (9).…”