BNP but Not s-cTnln Is Associated with Cardioembolic Aetiology and Predicts Short and Long Term Prognosis after Cerebrovascular Events

Nigro, N; Wildi, Karin; Müeller, Christian; Schuetz, Philipp; Müeller, Beat; Katan, Mira

doi:10.1371/journal.pone.0102704

Cited by 33 publications

(31 citation statements)

References 41 publications

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“…23 Recently, BNP and NT-pro-BNP were both found to be associated with incident stroke in a community-based sample free of stroke at baseline. 16 In this study, NT-pro-BNP was the protein on the chip by far being most closely related to stroke risk, despite adjustment for atrial fibrillation at baseline.…”

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Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip

Lind

Siegbahn

Lindahl

et al. 2015

Stroke

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Eligible subjects were 70 years of age and living in the city of Uppsala, Sweden. Subjects were chosen at random from the Total Background and Purpose-Emerging technologies have made it possible to simultaneously evaluate a large number of circulating proteins as potential new stroke risk markers. Methods-We explored associations between 85 cardiovascular proteins, assessed by a proteomics chip, and incident ischemic stroke in 2 independent cohorts of elderly (Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS]: n=977; 50% women, mean age=70.1 years, 71 fatal/nonfatal ischemic stroke events during 10.0 years; and Uppsala Longitudinal Study in Adult Men [ULSAM]: n=720, mean age=77.5 years, 75 ischemic stroke events during 9.5 years). The proteomics chip uses 2 antibodies for each protein and a polymerase chain reaction step to achieve a highspecific binding and the possibility to measure multiple proteins in parallel, but gives no absolute concentrations. Results-In PIVUS, 16 proteins were related to incident ischemic stroke using a false discovery rate of 5%. Of these, N-terminal pro-B-type natriuretic peptide (P=0.0032), adrenomedullin (P=0.018), and eosinophil cationic protein (P=0.0071) were replicated in ULSAM after adjustment for established stroke risk factors. In predefined secondary metaanalyses of individual data, interleukin-27 subunit α, growth/differentiation factor 15, urokinase plasminogen activator surface receptor, tumor necrosis factor receptor superfamily member 6, macrophage colony-stimulating factor 1, and matrix metalloproteinase-7 were also potential risk markers for ischemic stroke after adjustment for multiple comparisons (P<0.0006). The addition of N-terminal pro-B-type natriuretic peptide, adrenomedullin, and eosinophil cationic protein to a model with established risk factors increased the C-statistic from 0.629 to 0.689 (P=0.001). Conclusions-Our data suggest that large-scale proteomics analysis is a promising way of discovering novel biomarkers that could substantially improve the prediction of ischemic stroke. Lind et al New Risk Markers for Ischemic Stroke 3341Population Register. In total, 1016 individuals of 2025 invited took part in the investigation (50.1%) at age 70 years when also the blood sample for proteomics was collected. 12 A follow-up of incident ischemic stroke was performed after 10 years, without any loss of follow-up. After exclusion of the 39 individuals with stroke before the baseline investigation in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS), 71 of remaining 977 subjects experienced an ischemic stroke during a median follow-up of 10.0 years (range, 0.04-10.9 years), resulting in an incidence rate of 7.9 per 1000 person years at risk. ULSAM StudyUppsala Longitudinal Study in Adult Men (ULSAM) is a longitudinal population-based study including men born between 1920 and 1924 in Uppsala County, Sweden, being invited for the first time at age 50 years (n=2322). 13 This study used the 77-year examination cycle as base...

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confidence: 99%

Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip

Lind

Siegbahn

Lindahl

et al. 2015

Stroke

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“…Cardioembolic strokes are more severe and have worse outcome than noncardioembolic strokes27, 28; therefore, it is tentatively postulated that the beneficial effect of BNP could be masked in these subtypes of strokes.…”

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confidence: 99%

“…BNP receptors are widely expressed in the brain, and BNP has been found in different cerebral regions such as hypothalamus or cerebral cortex,1, 15, 17, 28 for instance. However, BNP‐mRNA has not been detected in cerebral tissue, suggesting a peripheral origin of this peptide 1, 29, 30.…”

Section: Discussionmentioning

confidence: 99%

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide

Fernández-Susavila

Rodríguez‐Yáñez

Dopico-López

et al. 2017

JAHA

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BackgroundBesides the relevant role of brain‐type natriuretic peptide (BNP) as biomarker of cardioembolic strokes, new experimental evidences suggest that this peptide may mediate neuroprotective effects. In this study, we have evaluated for the first time the clinical association between BNP (by means of proBNP) and good outcome in ischemic stroke patients, and analyzed the effect of blood BNP increase in an ischemic animal model.Methods and ResultsA retrospective study with 2 different cohorts (262 patients in cohort I and 610 in cohort II) from the same prospective stroke registry was performed. proBNP concentration was analyzed within the first 12 hours from stroke onset. The primary predictor variable was functional outcome evaluated by modified Rankin Scale at 3 months. For the experimental study, BNP pretreatment was tested in an ischemic animal model subjected to a transient occlusion of the cerebral artery, and the infarct volume and sensorimotor deficit were evaluated for 14 days. Cardioembolic strokes presented a positive correlation between proBNP concentration and modified Rankin Scale at 3 months; however, noncardioembolic strokes presented a negative correlation. In the logistic regression analysis, noncardioembolic strokes with concentrations of proBNP ≥340 pg/mL were associated with a good outcome. In line with these clinical findings, the experimental study revealed that those BNP pretreated animals presented a reduction on infarct volumes at 24 hours and functional recovery at days 7 and 14 compared with the control groups.ConclusionsThese clinical and experimental evidences support the potential role of BNP as a protective factor against cerebral ischemia.

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“…The clinical significance of this observation remains to be explored in further studies. A recent study in 447 patients with ischemic stroke and transient ischemic attack demonstrated that BNP improved the diagnostic accuracy for identifying the cardio-embolic etiology of the stroke [28], suggesting that BNP can be valuable tool in the stroke setting for the identification of patients who could potentially benefit from interventions aimed at preventing repeated embolization events. Emboli originating from heart atria can cause occlusion of major cerebral arteries, resulting in extensive cerebral infarction that is accompanied by severe neurological impairment.…”

Section: Discussionmentioning

confidence: 99%

Role of N-Terminal Pro-B-Type Natriuretic Peptide, High-Sensitivity C-Reactive Protein, and Inteleukin-6 in Predicting a Poor Outcome after a Stroke

Bunevičius

Kazlauskas²,

Raškauskienė³

et al. 2015

Neuroimmunomodulation

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Objective: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) concentrations can be important biomarkers in the acute stroke setting. In acute ischemic and hemorrhagic stroke patients, we investigated the association of NT-proBNP, hsCRP, and IL-6 serum concentrations with stroke severity and functional and cognitive outcomes at discharge. Methods: Seventy-eight patients (53 men; median age 72 years) admitted with ischemic or hemorrhagic stroke within 48 h of symptom onset were evaluated for clinical stroke severity (Scandinavian stroke scale; SSS), functional status before the stroke (modified Rankin scale; mRS), and cerebrovascular disease risk factors. Cognitive (Mini Mental State Examination) and functional (mRS) outcomes were evaluated at hospital discharge. Blood samples were drawn for the assessment of NT-proBNP, hsCRP, and IL-6 concentrations within 24 h of admission. Results: Greater NT-proBNP and hsCRP serum concentrations were associated with greater clinical stroke severity, adjusting for the patients' gender, age, stroke type, mRS score on admission, and presence of heart failure (β = -0.292, p = 0.012; β = -0.303, p = 0.009). In multivariate adjusted regression models with IL-6, hsCRP, and NT-proBNP considered together, IL-6 and hsCRP remained associated with worse functional (β = 0.210, p = 0.022) and cognitive (β = -0.269, p = 0.014) outcomes at discharge, respectively. In receiver operating characteristic analyses, the investigated blood biomarkers produced a minimal increase in predictive values for outcomes at discharge above the SSS score, age, and gender. Conclusions: In acute stroke patients, greater NT-proBNP and hsCRP serum concentrations are independently associated with greater clinical stroke severity. Elevated concentrations of IL-6 and hsCRP are associated with worse functional and cognitive outcomes at discharge, respectively.

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BNP but Not s-cTnln Is Associated with Cardioembolic Aetiology and Predicts Short and Long Term Prognosis after Cerebrovascular Events

Cited by 33 publications

References 41 publications

Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip

Discovery of New Risk Markers for Ischemic Stroke Using a Novel Targeted Proteomics Chip

Heads and Tails of Natriuretic Peptides: Neuroprotective Role of Brain Natriuretic Peptide

Role of N-Terminal Pro-B-Type Natriuretic Peptide, High-Sensitivity C-Reactive Protein, and Inteleukin-6 in Predicting a Poor Outcome after a Stroke

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