Etiologic Diagnosis of Ischemic Stroke Subtypes With Plasma Biomarkers

Montaner, Joan; Perea-Gainza, Mila; Delgado, Pilar; Ribó, Marc; Chacón, Pilar; Rosell, Anna; Quintana, Manuel; Palacios, M; Molina, Carlos A.; Álvarez-Sabín, José

doi:10.1161/strokeaha.107.505354

Cited by 272 publications

(242 citation statements)

References 34 publications

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“…A number of biomarkers have been found to distinguish cardioembolic from non-cardioembolic ischemic stroke. In 707 ischemic stroke patients, cardioembolic stroke was predicted by levels of BNP >76 pg/ml with 72% sensitivity and 69% specificity [35]. In the same study, D-dimer >0.96 g/mL predicted cardioembolic etiology with a 56% sensitivity and 64% specificity.…”

Section: Biomarkers Of Ischemic Stroke Etiologymentioning

confidence: 77%

Blood Biomarkers of Ischemic Stroke

2011

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This review provides a summary of the protein and RNA biomarkers that have been studied for the diagnosis and assessment of ischemic stroke. Many of the biomarkers identified relate to the pathophysiology of ischemic stroke, including ischemia of CNS tissue, acute thrombosis and inflammatory response. These biomarkers are summarized by their intended clinical application in ischemic stroke including diagnosis, prediction of stroke severity and outcome, and stratification of patients for stroke therapy. Among the biomarkers discussed are recent whole genome studies using RNA expression profiles to diagnose ischemic stroke and stroke etiology. Though many candidate blood based biomarkers for ischemic stroke have been identified, none are currently used in clinical practice. With further well designed study and careful validation, the development of blood biomarkers to improve the care of patients with ischemic stroke may be achieved.

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Section: Biomarkers Of Ischemic Stroke Etiologymentioning

confidence: 77%

Blood Biomarkers of Ischemic Stroke

2011

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“…While several markers, such as NT-BNP, 5,20,21 CRP, [21][22][23][24] D-Dimers, 20,25,26 Interleukin-6, 21,24,27 von Willebrand factor, 28, 29 S-100β, 30 and neuron specific enolase (NSE), 31 have been associated with functional outcome or mortality, only a few biomarkers added to prognosis based on clinical assessment. None of these markers, however, were fully evaluated including assessment of accuracy (i.e.…”

Section: Discussionmentioning

confidence: 99%

Copeptin adds prognostic information after ischemic stroke

et al. 2013

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OBJECTIVE: To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables. METHODS: In this prospective, multicenter, cohort study, we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The 2 primary end points were unfavorable functional outcome (modified Rankin Scale score 3-6) and mortality within 90 days. Secondary end points were any of 5 prespecified complications during hospitalization. RESULTS: In multivariate analysis, higher copeptin independently predicted unfavorable outcome (adjusted odds ratio 2.17 for any 10-fold copeptin increase [95% confidence interval CI, 1.46-3.22], p < 0.001), mortality (adjusted hazard ratio 2.40 for any 10-fold copeptin increase [95% CI, 1.60-3.60], p < 0.001), and complications (adjusted odds ratio 1.93 for any 10-fold copeptin increase [95% CI, 1.33-2.80], p = 0.001). The discriminatory accuracy, calculated with the area under the receiver operating characteristic curve, improved significantly for all end points when adding copeptin to the NIH Stroke Scale score and the multivariate models. Moreover, the combination of copeptin with a validated score encompassing both the NIH Stroke Scale and age led to a net reclassification improvement of 11.8% for functional outcome and of 37.2% for mortality. CONCLUSIONS: In patients with ischemic stroke, copeptin is a validated blood marker that adds predictive information for functional outcome and mortality at 3 months beyond stroke severity and age. Copeptin seems to be a promising new blood marker for prediction of in-hospital complications. Authors Contribution:As principal investigators, Dr De Marchis (GMDM), Dr Katan (MK) and Dr Arnold (MA) had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Methods:In this prospective, multicenter cohort study we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The two primary endpoints were unfavorable functional outcome (modified Rankin Scale score 3-6) and mortality within 90 days. Secondary endpoints were any of five prespecified complications during hospitalization.

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“…Several studies have shown that low levels of sRAGE may be not only predictive of not only of stroke risk, 31,32 but also associated with subclinical cerebrovascular disease, particularly in ethnic groups with increased risk for cerebrovascular disease. 33 In the recent analysis of the CARDS study, 20 the hazard ratio for sRAGE and stroke was 0.66, but it did not reach levels of significance owing to the relatively low number (n ¼ 44) of stroke events.…”

Section: Discussionmentioning

confidence: 99%

The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity

Höllerl

et al. 2012

Int J Obes

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OBJECTIVE:The increased cardiovascular (CV) disease risk in patients with morbid obesity (MO) cannot be fully explained by traditional CV risk factors. Activation of the receptor of Advanced Glycation Endproducts (RAGE) leads to inflammation via the NF kb (nuclear factor kb) pathway. The soluble form of RAGE (sRAGE), which is present in plasma, can bind to ligands of RAGE and avoids interaction of RAGE with proinflammatory ligands. We investigated sRAGE levels in patients with MO and compared them with healthy lean controls (CO), before and after bariatric surgery. DESIGN: We conducted a cross-sectional study and a 24-month longitudinal study. SUBJECTS: We included 85 patients (mean age: 41±12 years; mean body mass index (BMI): 45.4±7.9 kg m À 2 ) with MO in comparison with 40 CO (mean age: 42 ± 13 years; mean BMI: 26.0 ± 5.5 kg m À 2 ). All patients were investigated before and 2 years after bariatric surgery. Apart from weight and CV risk markers (blood pressure, lipids), a glucose tolerance test (75 g), renal and inflammation parameters were assessed. sRAGE levels were assessed by a commercial ELISA. To investigate the associations of the observed reductions of values, delta (D) of parameters were calculated. RESULTS: Patients with MO had significant lower sRAGE levels than CO: 1010 ± 514 vs 1501 ± 674 pg ml À 1 ; Po0.001. In the longitudinal study, sRAGE levels increased significantly after bariatric surgery from 1010±514 to 1261±710 pg ml À 1 ; P ¼ 0.008. In the correlation analysis, DsRAGE levels were associated with D1-h and D2-h postprandial glucose, Dfasting insulin, D2-h postprandial insulin, DHOMA (homeostatic model assessment)-insulin resistance (DHOMA-IR), Dg-glutamyl transferase and Dtriglycerides. In a multivariate model, D1-h and D2-h postprandial glucose, D2-h postprandial insulin and DHOMA-IR predicted DsRAGE. CONCLUSION: Patients with MO have significantly lower sRAGE levels compared with non-obese CO, but sRAGE levels increase significantly after weight loss induced by bariatric surgery. As high sRAGE levels inhibit the activation of inflammatory pathways, our results might help understand the beneficial effects of bariatric surgery regarding CV morbidity and mortality. Keywords: morbid obesity; sRAGE; insulin resistance; prospective INTRODUCTION Hyperglycemia leads to non-enzymatic glycation of intracellular and extracellular protein by forming advanced glycation endproducts (AGEs). 1 The RAGE (receptor of AGEs), a multi-ligand member of the immunoglobulin superfamily of transmembrane cell surface molecules, is a specific membrane-bound receptor for AGEs, 2 and activation of the RAGE by AGEs has a major role in the pathogenesis of diabetic vascular complications by way of activation of the NF kb (nuclear factor kb) pathway. 3 sRAGE is the soluble receptor of RAGE existing in the circulation. sRAGE levels have been found to be associated with chronic inflammatory diseases, including atherosclerosis and diabetes. 4-6 sRAGE acts as a decoy to prevent an interaction between AGE and RAGE and ther...

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Etiologic Diagnosis of Ischemic Stroke Subtypes With Plasma Biomarkers

Cited by 272 publications

References 34 publications

Blood Biomarkers of Ischemic Stroke

Blood Biomarkers of Ischemic Stroke

Copeptin adds prognostic information after ischemic stroke

The soluble form of the receptor of advanced glycation endproducts increases after bariatric surgery in morbid obesity

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