The Role of High-Sensitivity C-Reactive Protein in Asymptomatic Intra- and Extracranial Large Artery Diseases

Takahashi, Wakoh; Ohnuki, Tomohide; Ohnuki, Yohichi; Kawada, Shiaki; Takagi, Shigeharu

doi:10.1159/000160212

Cited by 19 publications

(12 citation statements)

References 61 publications

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“…We found that CRP levels were significantly higher in subjects with ECAD than in those with ICAD, similar to previously reported. 15,19 Resistin is a protein secreted by adipocytes and related to insulin resistance in rodents, whereas in humans it is mainly secreted by inflammatory cells and has been reported as a marker of coronary and carotid atherosclerosis. 21,22 In the present study, resistin was independently associated with atherosclerotic burden, especially with combined ECAD and ICAD.…”

Section: Discussionmentioning

confidence: 99%

“…Few retrospective studies have evaluated inflammatory and metabolic markers associated with the different location (extra-versus intracranial) of cerebral atherosclerosis, [15][16][17][18] with only one study performed in asymptomatic subjects. 19 A proinflammatory state and an impaired fibrinolysis have also been associated with progression of symptomatic intracranial atherosclerosis. 20 Prospective studies on biomarkers associated with asymptomatic intracranial atherosclerosis are lacking.…”

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confidence: 99%

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Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis

López‐Cancio

Galán²,

Dorado³

et al. 2012

Stroke

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Background and Purpose-Intracranial atherosclerotic disease (ICAD) remains a challenge for stroke primary and secondary prevention. Molecular pathways involved in the development of ICAD from its asymptomatic stages are largely unknown. In our population-based study, we aimed to compare the risk factor and biomarker profiles associated with intracranial and extracranial asymptomatic cerebral atherosclerosis. Methods-The Asymptomatic Intracranial Atherosclerosis (AsIA) study cohort includes a random sample population of 933 white subjects Ͼ50 years with a moderate to high vascular risk (based on REGICOR score) and without a history of stroke (64% males; mean age, 66 years). Carotid and intracranial atherosclerosis were screened by cervical and transcranial color-coded Duplex ultrasound, being moderate to severe stenoses confirmed by MR angiography. We registered clinical and anthropometric data and created a biobank with blood samples at baseline. A panel of biomarkers involved in atherothrombogenesis was determined: C-reactive protein, asymmetric-dimethylarginine, resistin, and plasminogen activator inhibitor-1. Insulin resistance was quantified by Homeostasis Model Assessment index. Results-After multinomial regression analyses, male sex, hypertension, smoking, and alcoholic habits were independent risk factors of isolated extracranial atherosclerotic disease. Diabetes and metabolic syndrome conferred a higher risk for ICAD than for extracranial atherosclerotic disease. Moreover, metabolic syndrome and insulin resistance were independent risk factors of moderate to severe ICAD but were not risk factors of moderate to severe extracranial atherosclerotic disease. Regarding biomarkers, asymmetric-dimethylarginine was independently associated with isolated ICAD and resistin with combined ICAD-extracranial atherosclerotic disease. Conclusions-Our

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis

López‐Cancio

Galán²,

Dorado³

et al. 2012

Stroke

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“…In support of this mechanism, several inflammatory biomarkers, and particularly high sensitivity C-reactive protein, have been identified as predictors of the risk of recurrent stroke in individuals with intracranial atherosclerosis [5]. The role of these markers is, however, less clear in predicting a first stroke in individuals with asymptomatic intracranial atherosclerotic stenosis [53]. …”

Section: Pathophysiology Of Intracranial Atherosclerosismentioning

confidence: 99%

Intracranial arterial stenoses: current viewpoints, novel approaches, and surgical perspectives

et al. 2012

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Ten percent of all strokes occurring in the USA are caused by intracranial arterial stenosis (IAS). Symptomatic IAS carries one of the highest rates of recurrent stroke despite intensive medical therapy (25 % in high-risk groups). Clinical results for endovascular angioplasty and stenting have been disappointing. The objectives of this study were to review the contemporary understanding of symptomatic IAS and present potential alternative treatments to resolve factors not addressed by current therapies. We performed a literature review on IAS pathophysiology, natural history, and current treatment. We present an evaluation of the currently deficient aspects in its treatment and explore the role of alternative surgical approaches. There is a well-documented interrelation between hemodynamic and embolic factors in cerebral ischemia caused by IAS. Despite the effectiveness of medical therapy, hemodynamic factors are not addressed satisfactorily by medications alone. Collateral circulation and severity of stenosis are the strongest predictors of risk for stroke and death. Indirect revascularization techniques, such as encephaloduroarteriosynangiosis, offer an alternative treatment to enhance collateral circulation while minimizing risk of hemorrhage associated with hyperemia and endovascular manipulation, with promising results in preliminary studies on chronic cerebrovascular occlusive disease. Despite improvements in medical management for IAS, relevant aspects of its pathophysiology are not resolved by medical treatment alone, such as poor collateral circulation. Surgical indirect revascularization can improve collateral circulation and play a role in the treatment of this condition. Further formal evaluation of indirect revascularization for IAS is a logical and worthy step in the development of intracranial atherosclerosis treatment strategies.

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“…Degradation of extracellular matrix components particularly by matrix metalloproteinases (MMPs), together with an increased inflammatory reaction is the main reason for plaque progression to rupture and consequent neurological symptoms [3,5,6]. Thus, MMPs and inflammatory factors may also serve as possible markers of plaque instability [7,8,9,10,11,12]. Several studies have already demonstrated increased levels of some MMPs and inflammatory proteins in the blood of patients with advanced carotid atherosclerosis [13,14,15,16,17,18].…”

Section: Introductionmentioning

confidence: 99%

Multiple Biological Predictors for Vulnerable Carotid Lesions

Pelisek¹,

Rudelius²,

Zepper

et al. 2009

Cerebrovasc Dis

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Background: In this study a multiscore analysis of various biomarkers including matrix metalloproteinases (MMPs), inflammatory factors and other clinical parameters was performed to establish a set of reliable biomarkers for improved detection of plaque instability in patients with advanced carotid stenosis. Methods: Study patients (n = 101) were classified as histologically stable (n = 37) or unstable (n = 64). Serum levels of MMP-1, -2, -3, -7, -8, -9, MMP inhibitors TIMP-1, -2, and inflammatory factors such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, -6, -8, -10, and -12 were measured by ELISA assays. Multiscore analysis was performed using multiple receiver operating characteristics analysis and determination of appropriate cutoff values. Results: Circulating levels of MMP-1, -7, TIMP-1, TNF-α, and IL-8 were significantly enhanced in patients with unstable plaques compared to individuals with stable lesions, mean differences being 1.2 (p = 0.032), 2.5 (p = 0.004), 30.0 (p = 0.014), 1.3 (p = 0.047), and 2.2 (p = 0.033), respectively. The combination of MMP-1, -7, TIMP-1 and IL-8 demonstrated the highest positive predictive value of 89.4% and negative predictive value of 60.1% for patients correctly classified as individuals with unstable and stable carotid lesions by means of blood sample analysis. Conclusions: Multiple relevant biomarkers that play a decisive role in plaque instability can improve the correct determination of vulnerable carotid plaques in patients with advanced carotid artery stenosis.

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The Role of High-Sensitivity C-Reactive Protein in Asymptomatic Intra- and Extracranial Large Artery Diseases

Cited by 19 publications

References 61 publications

Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis

Biological Signatures of Asymptomatic Extra- and Intracranial Atherosclerosis

Intracranial arterial stenoses: current viewpoints, novel approaches, and surgical perspectives

Multiple Biological Predictors for Vulnerable Carotid Lesions

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