NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis

AbstractBackground:Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis.Methods:We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays.Results:Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels.Conclusions:Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.

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Association between fibrinogen and fibrinogen γ’ and atherosclerotic plaque morphology and composition in symptomatic carotid artery stenosis: Plaque-At-RISK study

Thrombosis Research ◽

10.1016/j.thromres.2019.02.030 ◽

2019 ◽

Vol 177 ◽

pp. 130-135 ◽

Cited By ~ 3

Author(s):

A.C. van Dijk ◽

S.J. Donkel ◽

T. Zadi ◽

M.A.H. Sonneveld ◽

F.H.B.M. Schreuder ◽

...

Keyword(s):

At Risk ◽

Carotid Artery ◽

Atherosclerotic Plaque ◽

Carotid Artery Stenosis ◽

Artery Stenosis ◽

Plaque Morphology ◽

Symptomatic Carotid

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Optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis

Vascular ◽

10.1258/vasc.2011.cm0008 ◽

2011 ◽

Vol 19 (3) ◽

pp. 117-120 ◽

Cited By ~ 15

Author(s):

Kosmas I Paraskevas ◽

Dimitri P Mikhailidis ◽

Wesley S Moore ◽

Frank J Veith

Keyword(s):

Carotid Artery ◽

Carotid Artery Stenosis ◽

Stroke Risk ◽

Artery Stenosis ◽

Asymptomatic Carotid ◽

Symptomatic Carotid ◽

Asymptomatic Patients ◽

Best Medical Treatment ◽

Asymptomatic Carotid Artery Stenosis ◽

Contemporary Management

This commentary addresses the issue of optimal contemporary management of symptomatic and asymptomatic carotid artery stenosis. Based on current data, carotid endarterectomy (CEA) should be performed in the majority of patients with symptomatic carotid artery stenosis. Carotid artery stenting (CAS) should be reserved for a minority of these symptomatic patients, in whom CEA is contraindicated. In asymptomatic patients, all should be placed on best medical treatment (BMT). With the use of one or more of the proposed stroke risk stratification models or some as yet undetermined method, the identification of those asymptomatic individuals may be possible in whom stroke risk is higher than usual with BMT. This asymptomatic subgroup, which may be small and is yet to be determined with certainty, could be offered an invasive carotid procedure (either CAS or CEA).

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Comparison of the Values of MRI in the Differential Diagnosis of Symptomatic Carotid Stenosis and Atherosclerotic Plaque

Proceedings of Anticancer Research ◽

10.26689/par.v4i4.1396 ◽

2020 ◽

Vol 4 (4) ◽

Author(s):

Junying Bi ◽

Yanni Zeng ◽

Jun Meng ◽

Tiantian Zhou ◽

Xiang Gao

Keyword(s):

Differential Diagnosis ◽

Carotid Artery ◽

Carotid Stenosis ◽

Atherosclerotic Plaque ◽

Carotid Artery Stenosis ◽

Gold Standard ◽

Artery Stenosis ◽

Symptomatic Carotid ◽

Carotid Mri ◽

Symptomatic Carotid Stenosis

Objective: To evaluate the values of Carotid Magnetic Resonance Imaging (MRI) in the differential diagnosis of symptomatic carotid stenosis and atherosclerotic plaque. Methods: 56 patients with ischemic cerebrovascular disease admitted in our hospital from October 2018 to October 2019 were selected and treated with Carotid MRI and digital subtraction angiography (DSA) examinations. According to the two examination results recorded and the “gold standard” of DSA examination, values of Carotid MRI in the differential diagnosis of symptomatic carotid stenosis were evaluated. Results: According to the “gold standard” of DSA examination, the sensitivity and specificity of MRI examination for carotid stenosis were: Mild: 92.54% and 97.78%; Moderate: 85.71% and 88.78%; Severe: 100.00% and 97.8%; and complete occlusion: 100.00% and 100.00%; The proportions of intraplaque haemorrhage and ruptured fibrous cap in different degrees of carotid artery stenosis were: Mild: 30.16% and 22.22%; Moderate: 43.48% and 39.13%; And severe: 57.89% and 52.63%. Conclusion: MRI examination can evaluate the degree of symptomatic carotid artery stenosis, and show the characteristics of atherosclerotic plaque at the same time to provide a reference for early clinical differential diagnosis and treatment.

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Abstract 327: Diabetes Influences Carotid Artery Endarterectomy Plaque Lipidomics

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.36.suppl_1.327 ◽

2016 ◽

Vol 36 (suppl_1) ◽

Author(s):

Mohamed A Zayed ◽

Fong-Fu Hsu ◽

Bruce W Patterson ◽

Yan Yan ◽

Uzma Naim ◽

...

Keyword(s):

Arachidonic Acid ◽

Carotid Artery ◽

Carotid Endarterectomy ◽

Carotid Artery Stenosis ◽

Artery Stenosis ◽

Differentially Expressed ◽

Diabetic Patients ◽

Symptomatic Carotid ◽

Asymptomatic Patients ◽

Increased Risk

Nearly 20% of all ischemic strokes result from an atherosclerotic embolic source at the carotid arterial bifurcation. Patients with diabetes (DM) are at significantly increased risk of developing carotid artery stenosis, which predisposes to disabling strokes. Initial evidence suggests that carotid artery phospholipids are differentially expressed in patients with advanced atherosclerotic disease. However, it is unknown whether patients with DM and/or symptomatic carotid artery stenosis have unique carotid artery lipidomic profiles. To test this hypothesis, we performed a comprehensive analysis of phospholipid expression in carotid endarterectomy tissue harvested from a cohort of 18 patients (11 DM; 7 non-DM). Diabetic patients had a higher BMI (P=0.02), and increased use of b-blockers (P<0.01), but there was no difference in age, hyperlipidemia status, statin use, smoking incidence, severity of carotid stenosis, or carotid symptoms. Maximally (MAX) diseased carotid endarterectomy plaque segments at the carotid bifurcation were analyzed relative to correspondingly minimally (MIN) diseased distal internal carotid artery segments. Mass spectrometry-derived phospholipid absolute quantity profiles between MAX and MIN diseased carotid endarterectomy segments demonstrated significantly lower phosphatidylserine (PS; P<0.01), phosphatidylinositol (PI; P=0.03), and plasminogen phosphatidylethanolamine (pPE; P<0.01) phospholipids in MAX diseased segments. Paired analyses of MAX and MIN diseased segments revealed higher pPE in diabetic patients (P<0.01), and higher PI in non-diabetic and asymptomatic patients (P=0.03 and 0.05, respectively). The arachidonic acid-containing 1-(1Z-octadecenyl)-2-arachidonoyl- sn -glycero-3-phosphoethanolamine (pPE38:4) and 1-(1Z,9Z-octadecedienyl)-2-arachidonoyl- sn -glycero-3-phosphoethanolamine (pPE38:5) were the most highly (>109% increase) and differentially expressed phospholipids in the plaque segments of DM patients (P<0.01). These findings suggest that these pre-arachidonic acid phospholipids that affect plaque inflammation are more abundant in diseased carotid arteries of DM patients, which may influence disease progression and plaque vulnerability.

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Atherosclerotic plaque rupture in symptomatic carotid artery stenosis

Journal of Vascular Surgery ◽

10.1016/s0741-5214(96)70237-9 ◽

1996 ◽

Vol 23 (5) ◽

pp. 755-766 ◽

Cited By ~ 328

Author(s):

Sandra Carr ◽

Andrew Farb ◽

William H. Pearce ◽

Renu Virmani ◽

James S.T. Yao

Keyword(s):

Carotid Artery ◽

Atherosclerotic Plaque ◽

Carotid Artery Stenosis ◽

Plaque Rupture ◽

Artery Stenosis ◽

Symptomatic Carotid ◽

Atherosclerotic Plaque Rupture

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Carotid artery stenosis – Current evidence and treatment recommendations

Clinical and Translational Neuroscience ◽

10.1177/2514183x211001654 ◽

2021 ◽

Vol 5 (1) ◽

pp. 2514183X2110016

Author(s):

Mandy D Müller ◽

Leo H Bonati

Keyword(s):

Carotid Artery ◽

Carotid Stenosis ◽

Carotid Artery Stenosis ◽

Artery Stenosis ◽

Current Evidence ◽

Asymptomatic Carotid Stenosis ◽

Asymptomatic Carotid ◽

Risk Of Death ◽

Asymptomatic Patients

Background: Carotid artery stenosis is an important cause for stroke. Carotid endarterectomy (CEA) reduces the risk of stroke in patients with symptomatic carotid stenosis and to some extent in patients with asymptomatic carotid stenosis. More than 20 years ago, carotid artery stenting (CAS) emerged as an endovascular treatment alternative to CEA. Objective and Methods: This review summarises the available evidence from randomised clinical trials in patients with symptomatic as well as in patients with asymptomatic carotid stenosis. Results: CAS is associated with a higher risk of death or any stroke between randomisation and 30 days after treatment than CEA (odds ratio (OR) = 1.74, 95% CI 1.3 to 2.33, p < 0.0001). In a pre-defined subgroup analysis, the OR for stroke or death within 30 days after treatment was 1.11 (95% CI 0.74 to 1.64) in patients <70 years old and 2.23 (95% CI 1.61 to 3.08) in patients ≥70 years old, resulting in a significant interaction between patient age and treatment modality (interaction p = 0.007). The combination of death or any stroke up to 30 days after treatment or ipsilateral stroke during follow-up also favoured CEA (OR = 1.51, 95% CI 1.24 to 1.85, p < 0.0001). In asymptomatic patients, there is a non-significant increase in death or stroke occurring within 30 days of treatment with CAS compared to CEA (OR = 1.72, 95% CI 1.00 to 2.97, p = 0.05). The risk of peri-procedural death or stroke or ipsilateral stroke during follow-up did not differ significantly between treatments (OR = 1.27, 95% CI 0.87 to 1.84, p = 0.22). Discussion and Conclusion: In symptomatic patients, randomised evidence has consistently shown CAS to be associated with a higher risk of stroke or death within 30 days of treatment than CEA. This extra risk is mostly attributed to an increase in strokes occurring on the day of the procedure in patients ≥70 years. In asymptomatic patients, there may be a small increase in the risk of stroke or death within 30 days of treatment with CAS compared to CEA, but the currently available evidence is insufficient and further data from ongoing randomised trials are needed.

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A case of severe carotid artery stenosis with jellyfish sign performed endovascular therapy after statin treatment

Journal of Neuroendovascular Therapy ◽

10.5797/jnet.cr.2014-0040 ◽

2015 ◽

Vol 9 (5) ◽

pp. 289-296 ◽

Cited By ~ 1

Author(s):

Yoshiaki KAKEHI ◽

Fumitaka YAMANE ◽

Nahoko UEMIYA ◽

Eisuke TSUKAGOSHI ◽

Jun NIIMI ◽

...

Keyword(s):

Carotid Artery ◽

Endovascular Therapy ◽

Carotid Artery Stenosis ◽

Statin Treatment ◽

Artery Stenosis

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A study on prevalence of carotid artery stenosis in acute ischaemic stroke patients in Amalapuram, Andhra Pradesh, India

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20192489 ◽

2019 ◽

Vol 7 (6) ◽

pp. 2146

Author(s):

Bonthu Mamatha Bharathi ◽

Raveena Gullapalli

Keyword(s):

Risk Factor ◽

Carotid Artery ◽

Ischaemic Stroke ◽

Carotid Stenosis ◽

Carotid Artery Stenosis ◽

Acute Onset ◽

Artery Stenosis ◽

Doppler Study ◽

Diastolic Velocity ◽

Asymptomatic Patients

Background: Extra cranial carotid disease due to arteriosclerosis is usually associated with hypercholesterolemia and hyperlipidemia. Extra cranial carotid stenosis has been found to be less prevalent in black American and in Egyptians while intracranial disease is far more common Various methods includes transcranial doppler (TCD) ultrasonography, cerebral angiography, computed tomography angiography (CTA) and magnetic resonance angiography (MRA).Methods: All patients with ischaemic stroke of acute onset admitted in the medical wards of Konaseema institute of medical sciences between June 2018 and January 2019 were included in the study. All patients were subjected to CT scan brain study and colour Doppler study of extra cranial carotid arteries and vertebral arteries. Systolic and diastolic velocity of blood flow, carotid intimal medial thickness, presence of athermanous plaque and thrombus was looked for and then the percentage of stenosis of the affected arteries was calculated.Results: In the present study 0ut of 23 patients with carotid stenosis 9 patients had mild carotid stenosis, 8 patients had moderate stenosis and 6 patients had severe stenosis. Out of 23 patients with carotid stenosis the 11 patients have stenosis in the right carotid and 12 patients had stenosis in the left side. The site of stenosis is ICA in 17 patients and CCA in 6 patients.Conclusions: In present study every patient with carotid artery stenosis had one or the other risk factor for carotid atherosclerosis. In other words, there was no patient with carotid artery stenosis, without any risk factor in present study. Hence asymptomatic patients with these risk factors should be screened for carotid stenosis to prevent stroke.

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