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Elevated EMMPRIN Serum Levels Indicate Plaque Vulnerability in Patients With Asymptomatic High Grade Carotid Stenosis
Stephanie Kampf1, Alexander Micko2, Stefan Stojkovic3
1Department of Surgery, Division of Vascular Surgery, Medical University of Vienna, Vienna, Austria.
Insights
Elevated extracellular matrix metalloproteinase inducer (EMMPRIN) levels indicate high-risk carotid plaques. EMMPRIN aids in predicting stroke risk for asymptomatic patients when combined with clinical factors and sonography.
Area of Science:
- Cardiovascular Medicine
- Neurology
- Biochemistry
Background:
- Carotid atherosclerosis is a major cause of ischemic stroke.
- Current sonographic plaque characteristics are insufficient for predicting future ischemic events.
- Novel biomarkers are needed for risk stratification in high-grade carotid stenosis.
Purpose of the Study:
- To evaluate extracellular matrix metalloproteinase inducer (EMMPRIN) as a potential marker for high-risk vulnerable carotid plaques.
- To assess the role of EMMPRIN in plaque formation and destabilization.
- To determine if EMMPRIN can improve risk prediction in patients with carotid stenosis.
Main Methods:
- EMMPRIN levels were measured in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis using ELISA.
- Duplex sonography classified atherosclerotic plaques by echogenicity.
- Histopathological analysis of plaques followed the American Heart Association classification.
Main Results:
- Significantly higher EMMPRIN levels were found in patients with echolucent plaques compared to echogenic plaques (p = .025).
- Asymptomatic patients with vulnerable plaques showed significantly higher EMMPRIN levels than those with non-vulnerable plaques (p < .001).
- EMMPRIN improved the predictive accuracy (AUC) for vulnerable plaques in asymptomatic patients when added to clinical factors and sonography (0.79 vs 0.71).
Conclusions:
- Increased serum EMMPRIN levels are associated with high-risk carotid plaques.
- EMMPRIN, along with clinical risk factors and duplex sonography, can enhance pre-operative risk stratification for asymptomatic patients.
- EMMPRIN shows promise as a biomarker for identifying vulnerable carotid plaques and predicting stroke risk.
Objective:
Carotid atherosclerosis is an important cause of cerebral ischaemic stroke. Sonographic plaque characteristics are inappropriate for exact prediction of possible future ischaemic events. Additional markers are needed to predict the clinical outcome in high grade carotid stenosis. This study aimed to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to its involvement in plaque formation and destabilisation, as a potential marker of high risk vulnerable plaques.
Methods:
EMMPRIN was analysed in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by a specific ELISA. Pre-operative 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.
Results:
The study included 265 patients undergoing carotid endarterectomy: 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 (4 480; IQR 3 745, 6 144 pg/mL) compared with echogenic plaques (4 159; IQR 3 418, 5 402 pg/mL; p = .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4 875; IQR 3 850, 7 016 pg/mL) compared with non-vulnerable plaques (4 109; IQR 3 433, 5 402 pg/mL; p < .001). In logistic regression analysis, duplex sonography combined with age, gender, 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 AUC in asymptomatic patients (AUC 0.79; 95% CI 0.71 - 0.87; p = .014).
Conclusion:
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, gender, and duplex sonography may be used for pre-operative risk stratification in asymptomatic patients.
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