Elevated EMMPRIN serum levels indicate plaque vulnerability in patients with asymptomatic high grade carotid stenosis

Open AccessPublished:December 16, 2022DOI:
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      Carotid atherosclerosis, is an important cause of cerebral ischemic stroke. Sonographic plaques characteristics are inappropriate for exact prediction of possible future ischemic events. Additional markers are needed to forecast clinical outcome in high grade carotid stenosis. The aim of our study was to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to the involvement in plaque formation/destabilization, as a potential marker of high-risk vulnerable plaques.


      EMMPRIN was analyzed in preoperative blood serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by specific ELISA. Preoperative duplex sonography classified the atherosclerotic plaque due to echogenicity. Histopathological analysis of vulnerable and non-vulnerable plaques was based on the American Heart Association (AHA) classification.


      265 patients undergoing carotid endarterectomy were included: 90 (m/f = 69/21) patients with symptomatic and 175 (m/f = 118/57) with asymptomatic disease. Analysis of circulating EMMPRIN revealed significantly higher levels in patients with echolucent plaques (4480 (IQR: 3745 - 6144) pg/ml) compared to echogenic plaques (4159 (IQR: 3418 - 5402) pg/ml, p = .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4875 (IQR: 3850 - 7016) pg/ml) compared with non-vulnerable plaques (4109 (IQR: 3433 - 5402) pg/ml, p < .001). In logistic regression analysis, duplex sonography combined with age, sex and clinical risk factors predicted vulnerable plaques in asymptomatic patients with an AUC of 0.71 (95% CI 0.61 – 0.80). EMMPRIN significantly improved the area under the curve in asymptomatic patients (AUC of 0.79 (95% CI 0.71 – 0.87, p = .014).


      Patients with high-risk plaques according to ultrasound and histopathological characteristics demonstrated increased serum EMMPRIN levels. EMMPRIN on top of clinical risk factors including age and gender as well as duplex sonography may be used for preoperative risk stratification in asymptomatic patients.



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