natriuretic-peptide--brain and Brain-Ischemia

To identify clinical, ECG, and blood-based biomarkers associated with atrial fibrillation (AF) detection after ischaemic stroke or TIA that could help inform patient selection for cardiac monitoring.. We performed a systematic review and meta-analysis and searched electronic databases for cohort studies from January 15, 2000, to January 15, 2020. The outcome was AF ≥30 seconds within 1 year after ischemic stroke/TIA. We used random effects models to create summary estimates of risk. Risk of bias was assessed using the Quality in Prognostic Studies tool.. We identified 8,503 studies, selected 34 studies, and assessed 69 variables (42 clinical, 20 ECG, and 7 blood-based biomarkers). The studies included 11,569 participants and AF was detected in 1,478 (12.8%). Overall, risk of bias was moderate. Variables associated with increased likelihood of AF detection are older age (odds ratio [OR] 3.26, 95% confidence interval [CI] 2.35-4.54), female sex (OR 1.47, 95% CI 1.23-1.77), a history of heart failure (OR 2.56, 95% CI 1.87-3.49), hypertension (OR 1.42, 95% CI 1.15-1.75) or ischemic heart disease (OR 1.80, 95% CI 1.34-2.42), higher modified Rankin Scale (OR 6.13, 95% CI 2.93-12.84) or National Institutes of Health Stroke Scale score (OR 2.50, 95% CI 1.64-3.81), no significant carotid/intracranial artery stenosis (OR 3.23, 95% CI 1.14-9.11), no tobacco use (OR 1.93, 95% CI 1.48-2.51), statin therapy (OR 2.07, 95% CI 1.14-3.73), stroke as index diagnosis (OR 1.59, 95% CI 1.17-2.18), systolic blood pressure (OR 1.61, 95% CI 1.16-2.22), IV thrombolysis treatment (OR 2.40, 95% CI 1.83-3.16), atrioventricular block (OR 2.12, 95% CI 1.08-4.17), left ventricular hypertrophy (OR 2.21, 95% CI 1.03-4.74), premature atrial contraction (OR 3.90, 95% CI 1.74-8.74), maximum P-wave duration (OR 3.19, 95% CI 1.40-7.25), PR interval (OR 2.32, 95% CI 1.11-4.83), P-wave dispersion (OR 7.79, 95% CI 4.16-14.61), P-wave index (OR 3.44, 95% CI 1.87-6.32), QTc interval (OR 3.68, 95% CI 1.63-8.28), brain natriuretic peptide (OR 13.73, 95% CI 3.31-57.07), and high-density lipoprotein cholesterol (OR 1.49, 95% CI 1.17-1.88) concentrations. Variables associated with reduced likelihood are minimum P-wave duration (OR 0.53, 95% CI 0.29-0.98), low-density lipoprotein cholesterol (OR 0.73, 95% CI 0.57-0.93), and triglyceride (OR 0.51, 95% CI 0.41-0.64) concentrations.. We identified multimodal biomarkers that could help guide patient selection for cardiac monitoring after ischaemic stroke/TIA. Their prognostic utility should be prospectively assessed with AF detection and recurrent stroke as outcomes.

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Humans; Natriuretic Peptide, Brain; Risk Factors; Stroke

Acute ischemic stroke (AIS), is the second global cause of death after cardiovascular diseases, accounts for 80-85% of cerebrovascular disease. Stroke diagnosis could be challenging in the acute phase. Detection of biomarkers for evaluating the prognosis of diseases is essential for improving personalized treatment and decreasing mortality. At the present time, the absence of a broadly existing and rapid diagnostic test is an important limitation in the evaluation and treatment of diseases. The use of a biomarker-based diagnostic attitude has confirmed very valuable in acute coronary syndromes, which has been promoted in acute stroke to help early management decisions. Over the past decade, different detection procedures have developed for the assessment of human cardiac troponins (cTnI). This review emphasizes on summarizing optical, and electrochemical biosensors for the detection of cTnI, brain natriuretic peptide (BNP), and neuron-specific enolase (NSE) as a critical biomarker in stroke.

Topics: Biomarkers; Biosensing Techniques; Brain Ischemia; Humans; Nanostructures; Natriuretic Peptide, Brain; Prognosis; Stroke

Many studies have evaluated the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and its prognostic value in ischemic stroke. However, a widespread consensus has not been reached. Therefore, we completed a meta-analysis to evaluate the prognostic significance of NT-proBNP for mortality and functional outcome in patients with ischemic stroke.. We performed a systematic search and review using the PubMed and EMBASE databases to identify literature that reported a correlation between NT-proBNP and mortality and functional outcome in ischemic stroke patients.. Eleven studies inclusive of 10,498 patients met the inclusion criteria. Elevated plasma NT-proBNP levels were associated with increased risk of mortality in ischemic stroke patients (all-cause mortality: odds ratio [OR] = 2.43, 95% confidence interval [CI] 1.62-3.64, P < .001, I. This meta-analysis demonstrates that NT-proBNP could be a predictor of mortality and functional outcome in ischemic stroke patients.

Topics: Biomarkers; Brain Ischemia; Cause of Death; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Recovery of Function; Risk Assessment; Risk Factors; Stroke

Blood biomarkers are a cost-effective and valid method to diagnose ischemic stroke and differentiate its subtypes in countries with poor resources.. To perform a systematic review of published literature evaluating the diagnostic utility of blood-based biomarkers to diagnose and differentiate the etiology of ischemic stroke.. A comprehensive literature search was carried out till December 2017 in major scientific and medical databases including PubMed, Cochrane, OVID and Google Scholar. Modified Quality Assessment of Diagnostic Accuracy Studies questionnaire was used to assess the methodological quality of each study.. Twenty-six studies were identified relevant to our systematic review. Various biomarkers have been studied, though only a few biomarkers such as a B-type natriuretic peptide (BNP) and Ddimer have proved their clinical utility. None of the other tested biomarkers appeared to have consistent results to diagnose ischemic stroke subtypes. Most of the studies had limitations in the classification of ischemic stroke, sample size, sample collection time, methods, biomarker selection and data analysis.. Our systematic review does not recommend the use of any blood biomarker for clinical purposes based on the studies conducted to date. BNP and D-dimer may present optimal biomarker for diagnosis and differentiation of ischemic stroke. However, large well-designed clinical studies are required to validate utility of these biomarkers to differentiate subtypes of ischemic stroke.

Topics: Biomarkers; Brain Ischemia; Fibrin Fibrinogen Degradation Products; Humans; Natriuretic Peptide, Brain; Stroke

In Japan, stroke is a major cause of death and serious long-lasting neurological disabilities. Recently, the diagnosis and treatment of ischemic stroke has changed greatly. 1) Patients with TIA are more susceptible to ischemic stroke, and the susceptibility is predicted by the ABCD2score. 2) Brain natriuretic peptide (BNP) is a hormone released from the ventricular myocardium; BNP levels can predict new atrial fibrillation during hospitalization in patients with acute ischemic stroke. 3) In Japan, thrombolysis with intravenous recombinant tissue plasminogen activator (rt-PA) for acute ischemic stroke was approved in 2004, and the time window was extended up to 4.5 h in 2012. 4) Several novel oral anticoagulants (NOAC) have been developed over the last decade; the early initiation of NOACs in acute stroke and TIA patients with nonvalvular atrial fibrillation may be safe. More evidence-based treatment for stroke in Japanese people should be established.

Topics: Brain Ischemia; Fibrinolytic Agents; Humans; Japan; Natriuretic Peptide, Brain; Stroke; Tissue Plasminogen Activator

Previous studies demonstrated that elevated brain natriuretic peptide (BNP) level is associated with adverse clinical outcomes of acute cerebral infarction (ACI). Researchers hypothesized that BNP might be a potential neuroprotective factor against cerebral ischemia because of the antagonistic effect of the natriuretic peptide system on the renin-angiotensin system and regulation of cardiovascular homeostasis. However, whether decreasing the BNP level can improve the prognosis of ACI has not been studied yet. The main effect of sacubitril/valsartan is to enhance the natriuretic peptide system. We investigated whether the intervention of plasma BNP levels with sacubitril/valsartan could improve the prognosis of patients with ACI.. In a randomized, controlled, parallel-group trial of patients with ACI within 48 hours of symptom onset and need for antihypertensive therapy, patients have randomized within 24 hours to sacubitril/valsartan 200mg once daily (the intervention group) or to conventional medical medication (the control group). The primary outcome was a change in plasma BNP levels before and after sacubitril/valsartan administration. The secondary outcomes included plasma levels of brain-derived neurotrophic factor (BDNF), Corin and neprilysin (NEP) before and after medication, the modified Rankin scale, and the National Institutes of Health Stroke Scale (at onset, at discharge, 30 days, and 90 days after discharge).. We evaluated 80 eligible patients admitted to the Stroke Center of Lianyungang Second People's Hospital between 1st May, 2021 and 31st June, 2022. Except for 28 patients excluded before randomization and 14 patients who did not meet the criteria or dropped out or lost to follow-up during the trial, the remaining 38 patients (intervention group: 17, control group: 21) had well-balanced baseline features. In this trial, we found that plasma BNP levels (P = 0.003) decreased and NEP levels (P = 0.006) increased in enrolled patients after treatment with sacubitril/valsartan. There were no differences in plasma BDNF and Corin levels between the two groups. Furthermore, no difference in functional prognosis was observed between the two groups (all P values>0.05).. Sacubitril/valsartan reduced endogenous plasma BNP levels in patients with ACI and did not affect their short-term prognosis.

Topics: Acute Disease; Brain Ischemia; Brain-Derived Neurotrophic Factor; Cerebral Infarction; Humans; Natriuretic Peptide, Brain; Prognosis; Stroke; United States

Patients with atrial fibrillation (AF) and atrial thrombus are at high risk of thromboembolic events. We investigated whether BNP levels can serve as a biological marker of thrombus.. We prospectively enrolled patients with AF within 7days of an ischemic stroke and transient ischemic attack (TIA). We measured BNP levels in all patients while they underwent transesophageal echocardiography (TEE) and then assigned them to groups based on the presence (positive group) or absence (negative group) of left atrial thrombus. Factors associated with atrial thrombus were investigated using multivariate logistic regression analysis.. Of the 67 (male, n = 40; mean age, 76.5 ± 11.1 years) enrolled patients, 17 (25.4%) had left atrial thrombus. The incidence of hypertension was significantly higher in the positive, than in the negative group (88.2% vs. 58.0%, p = 0.020). The BNP level was also significantly higher in the positive, than in the negative group (median (interquartile range) 189.8 (141.4-473.2) vs. 117.9 (70.3-187.1) pg/ml, p=0.012). The optimal cut-off value, sensitivity, and specificity of BNP levels to distinguish the positive, from the negative group were 140.0 pg/ml, 76.5%, and 62.0%, respectively. Multivariate logistic regression analysis demonstrated that a BNP concentration of>140.0 pg/ml (odds ratio, 5.62; 95% CI, 1.39-22.66, p = 0.015) was an independent factor associated with thrombus.. Levels of BNP can serve as a marker of left atrial thrombus in acute ischemic stroke and TIA in patients with AF.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Comorbidity; Echocardiography, Transesophageal; Female; Heart Atria; Humans; Hypertension; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Factors; Sensitivity and Specificity; Thrombosis

and purpose N-terminal probrain natriuretic peptide, which is mainly produced by the heart, is increased in acute stroke. We aimed to determine if N-terminal probrain natriuretic peptide could be a biomarker for ischemic stroke with a cardioembolic cause.. Consecutive sample of acute stroke patients admitted to a Stroke Unit. Ischemic stroke subtype was classified using the TOAST classification. Blood samples were drawn within 72 h after stroke onset. Serum N-terminal probrain natriuretic peptide concentration was measured using an electrochemiluminescence immunoassay. Mean values of N-terminal probrain natriuretic peptide were compared between patients with hemorrhagic stroke vs. ischemic stroke, cardioembolic stroke vs. noncardioembolic stroke, cardioembolic stroke with atrial fibrillation vs. noncardioembolic stroke using t-test. Receiver operating characteristic curves were used to test the ability of N-terminal probrain natriuretic peptide values to identify cardioembolic stroke and cardioembolic stroke with atrial fibrillation.. Ninety-two patients were included (66 with ischemic stroke) with a mean age of 58·6 years. Twenty-eight (42·4%) ischemic strokes had a cardioembolic cause. Mean N-terminal probrain natriuretic peptide values for cardioembolic stroke were significantly higher (P<0·001) (491·6; 95% confidence interval 283·7-852·0 pg/ml) than for noncardioembolic ischemic stroke (124·7; 86·3-180·2 pg/ml). The area under the receiver operating characteristic curve for N-terminal probrain natriuretic peptide in cardioembolic stroke was 0·77. The cut-off point with the highest sensitivity and specificity was set at 265·5 pg/ml (71·4% and 73·7% respectively). The area under the curve of N-terminal probrain natriuretic peptide for cardioembolic stroke related to atrial fibrillation was 0·92, cut-off was set at 265·5 pg/ml (sensitivity 94·4%, specificity 72·9%).. N-terminal probrain natriuretic peptide is a biomarker with a good accuracy to predict ischemic stroke of cardioembolic cause, namely associated with atrial fibrillation.

Topics: Adult; Aged; Area Under Curve; Atrial Fibrillation; Biomarkers; Brain Ischemia; Cerebral Hemorrhage; Female; Heart Diseases; Humans; Intracranial Embolism; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; ROC Curve; Sensitivity and Specificity; Ultrasonography

In preclinical stroke models, high-dose human albumin confers robust neuroprotection. We investigated the safety and tolerability of this therapy in patients with acute ischemic stroke.. The ALIAS (Albumin in Acute Stroke) Pilot Clinical Trial used a multiple-tier, open-label, dose-escalation design. Subjects with acute ischemic stroke (NIH Stroke Scale [NIHSS] of 6 or above) received a 2-hour infusion of 25% human albumin (ALB) beginning within 16 hours of stroke onset. Six successive ALB dose tiers were assessed ranging from 0.34 to 2.05 g/kg. Neurologic and cardiac function was sequentially monitored. At 3 months, the NIHSS, modified Rankin Scale, and Barthel Index were measured.. Eighty-two subjects (mean age, 65 years) received ALB at 7.8+/-3.4 hours after stroke onset (mean+/-standard deviation). Forty-two patients also received standard-of-care intravenous tissue plasminogen activator (tPA). Vital signs were unaltered by ALB treatment. Dose-related increases in plasma albumin and mild hemodilution were maximal at 4 to 12 hours. Age-related plasma brain natriuretic peptide levels increased at 24 hours after ALB but did not predict cardiac adverse events. The sole ALB-related adverse event was mild or moderate pulmonary edema in 13.4% of subjects, which was readily managed with diuretics. In the tPA-treated subgroup, symptomatic intracranial hemorrhage occurred in only one of 42 subjects.. Twenty-five percent human albumin in doses ranging up to 2.05 g/kg was tolerated by patients with acute ischemic stroke without major dose-limiting complications. tPA therapy did not affect the safety profile of ALB. The companion article presents neurologic outcome data and efficacy analysis in these subjects.

Topics: Aged; Albumins; Brain Ischemia; Cerebral Hemorrhage; Diuretics; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fibrinolytic Agents; Humans; Injections, Intravenous; Male; Middle Aged; Natriuretic Peptide, Brain; Neuroprotective Agents; Pilot Projects; Pulmonary Edema; Serum Albumin; Stroke; Tissue Plasminogen Activator; Treatment Outcome

Interleukin-6 (IL-6) and interleukin-18 (IL-18), important cytokines implicated in atherosclerosis and inflammaging, were assessed for associations with global cardiovascular disease (CVD), atrial fibrillation (AF), and death in older adults.. Participants from Atherosclerosis Risk in Communities study Visit 5 (mean age 75.4 ± 5.1 years) with IL-6 and IL-18 measurements were included (n = 5672). Cox regression models were used to assess associations of IL-6 and IL-18 with coronary heart disease (CHD), ischaemic stroke, heart failure (HF) hospitalization, global CVD (composite of CHD, stroke, and HF), AF, and all-cause death. Over a median follow-up of 7.2 years, there were 1235 global CVD events, 530 AF events, and 1173 deaths. Higher IL-6 [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.44-1.72 per log unit increase] and IL-18 (HR 1.13, 95% CI 1.01-1.26) were significantly associated with global CVD after adjustment for cardiovascular risk factors. Association between IL-6 and global CVD remained significant after further adjustment for high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin T (hs-TnT) but was no longer significant for IL-18 after further adjustments. Interleukin-6 was also associated with increased risk for CHD, HF, and AF after adjustment for covariates. Both IL-6 and IL-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers.. Among older adults, both IL-6 and IL-18 were associated with global CVD and death. The association between IL-6 with CVD appears to be more robust and was independent of hs-CRP, NT-proBNP, and hs-TnT.. In older adults in the Atherosclerosis Risk in Communities study (average age 75 years), higher levels of interleukin-6 and interleukin-18, two proteins implicated in atherosclerosis and increased inflammation that occurs with ageing, significantly increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) during the next ∼7 years; interleukin-6 also increased risk for global cardiovascular disease, coronary heart disease, heart failure, and atrial fibrillation even after adjustment for other biomarkers of inflammation and subclinical myocardial injury, and both interleukin-6 and interleukin-18 were associated with increased risk for all-cause death independent of cardiovascular risk factors and other biomarkers. In older adults, higher levels of interleukin-6 and interleukin-18 were both associated with increased risk for global cardiovascular disease (including coronary heart disease, stroke, and heart failure) and death.The association between interleukin-6 and global cardiovascular disease appeared to be stronger than that for interleukin-18 and remained significant after adjustment for other biomarkers of inflammation and subclinical myocardial injury.

Topics: Aged; Aged, 80 and over; Atherosclerosis; Atrial Fibrillation; Biomarkers; Brain Ischemia; C-Reactive Protein; Cardiovascular Diseases; Coronary Disease; Heart Failure; Humans; Interleukin-18; Interleukin-6; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors; Stroke

Several biomarkers are associated with clinical outcomes in patients with atrial fibrillation (AF), but a causal relationship has not been established. This study aimed to evaluate angiopoietin-2, a novel candidate biomarker of endothelial inflammation and vascular remodelling, in patients with AF.. Angiopoietin-2 was measured in plasma obtained from patients with AF treated with aspirin monotherapy (exploration cohort, n = 2987) or with oral anticoagulation (validation cohort, n = 13 079). Regression models were built to assess the associations between angiopoietin-2, clinical characteristics, and outcomes. In both cohorts, plasma angiopoietin-2 was independently associated with AF on the baseline electrocardiogram and persistent/permanent AF, age, history of heart failure, female sex, tobacco use/smoking, body mass index, renal dysfunction, diabetes, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Angiopoietin-2 was independently associated with subsequent hospitalization for heart failure after adjusting for age, creatinine, and clinical characteristics in the exploration cohort [c-index 0.79, 95% confidence interval (CI) 0.75-0.82; third vs. first quartile, hazard ratio (HR) 1.74, 95% CI 1.26-2.41] and in the validation cohort (c-index 0.76, 95% CI 0.74-0.78; HR 1.58, 95% CI 1.37-1.82). In both cohorts, the association persisted when also adjusting for NT-proBNP (P ≤ 0.001). In full multivariable models also adjusted for NT-proBNP, angiopoietin-2 did not show statistically significant associations with ischaemic stroke, cardiovascular and all-cause death, or major bleeding that were consistent across the two cohorts.. In patients with AF, plasma levels of angiopoietin-2 were independently associated with subsequent hospitalization for heart failure and provided incremental prognostic value to clinical risk factors and NT-proBNP.

Topics: Angiopoietin-2; Atrial Fibrillation; Biomarkers; Brain Ischemia; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke

Ischemic stroke followed by cerebral artery occlusion is a main cause of chronic disability worldwide. Recombinant human brain natriuretic peptide (rhBNP) has been reported to alleviate sepsis-induced cognitive dysfunction and brain I/R injury. However, the function and molecular mechanisms of rhBNP in ischemic brain injury have not been clarified. For establishment of an animal model of ischemic brain injury, C57BL/6 mice were treated with middle cerebral artery occlusion (MCAO) surgery for 1 h and reperfusion for 24 h. After subcutaneous injection of rhBNP into model mice, neurologic deficits were assessed by evaluating behavior of mice according to Longa scoring system, and TTC staining was utilized to determine the brain infarct size of mice. The levels of oxidative stress markers, superoxide dismutase (SOD), catalase (CAT), glutathione (GSH) and malondialdehyde (MDA), were detected in hippocampal tissues of mice by corresponding kits. Cell apoptosis in hippocampus tissues was examined by TUNEL staining. Protein levels of antioxidant enzymes (HO-1 and NQO1) in cerebral cortex, apoptotic markers (Bax, Bcl-2, and cleaved caspase), and PI3K/AKT pathway-associated factors in hippocampus were tested by western blot analysis. The results revealed that injection of rhBNP decreased neurologic deficit scores, the percent of brain water content, and infarct volume. Additionally, rhBNP downregulated MDA level, upregulated the levels of SOD, CAT, and GSH in hippocampus of mice, and increased protein levels of HO-1 and NQO1 in the cortex. Cell apoptosis in hippocampus tissues of model mice was inhibited by rhBNP which was shown as the reduced TUNEL-positive cells, the decreased Bax, cleaved caspase-3, and cleaved caspase-9 protein levels, and the enhanced Bcl-2 protein level. In addition, rhBNP treatment activated the PI3K/AKT signaling pathway and upregulated the protein levels of HO-1 and NRF2. Overall, rhBNP activates the PI3K/AKT/HO-1/NRF2 pathway to attenuate ischemic brain injury in mice after MCAO by suppression of cell apoptosis and oxidative stress.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Brain Injuries; Brain Ischemia; Humans; Infarction, Middle Cerebral Artery; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; NF-E2-Related Factor 2; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Superoxide Dismutase

Ischemic Stroke is an acute and rapidly progressing neurological disease. Stroke is the second largest cause of global death (5.5 million) after ischemic heart disease. Numerous biomarkers have been identified and studied related to acute ischemic stroke but currently, none of the biomarkers are available for prognostication in such cases. In this study, we measured the levels of four widely available, rapidly measured biomarkers and evaluated their association with the functional outcome at discharge.. This was a prospective observational study conducted on 81 patients of acute ischemic stroke after obtaining informed consent. A detailed history was taken and clinical examination was done. Serum levels of homocysteine, uric acid, C-reactive protein (CRP), and Pro-brain natriuretic peptide (Pro-BNP) were measured at admission and their association with functional outcome using mRS (modified Rankin Scale) were analyzed.. During the study period, 81 cases of acute ischemic stroke were evaluated; among them, 13 had a cardioembolic stroke. Ischemic stroke was more common in the older age group. The mean age was 49 ± 16.2 years. 61.7 % of patients were males. Diabetes Mellitus (45.7%), Hypertension (45.7%), CAD (8.6%), Dyslipidemia (27.2%), Smoking (37%), and alcohol intake (29.6 %) were some major risk factors. The average duration of hospital stay was 13.3 ± 7.5 days. 22 cases expired during the hospital stay. Mean serum levels of homocysteine, CRP, and Pro-BNP were higher than normal values (22.7 ± 16.3 umol/l; 59.5 ± 42.7 mg/dl; 1949 ± 3265.7 pg/ml). The mean serum uric acid level was 6.1 ± 3.3 mg/dl. A significant association between MRS score and serum homocysteine was found [p=0.007]. There was also a significant association between Pro-BNP levels and MRS score in patients with cardioembolic stroke (p=<0.001).. Higher serum levels of homocysteine, CRP, and Pro-BNP are associated with a higher risk of acute ischemic stroke. Homocysteine level at admission can predict the poor outcome at discharge in patients of acute ischemic stroke. Pro-BNP levels can be used as a predictor of poor outcomes in cardioembolic stroke.

Topics: Adult; Aged; Biomarkers; Brain Ischemia; C-Reactive Protein; Embolic Stroke; Female; Homocysteine; Humans; Ischemic Stroke; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Stroke; Uric Acid

Topics: Aged; Biomarkers; Brain Ischemia; Heart Failure; Humans; Ischemic Stroke; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Registries; Stroke

Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH.. We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted.. Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p = 0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632).. Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.

Topics: Adult; Aged; Brain Ischemia; Female; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; ROC Curve; Subarachnoid Hemorrhage

B-type natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) are well-known surrogates of atrial fibrillation (AF) detection but studies usually present data on either BNP or NT-proBNP. The aim was to determine and directly compare the validity of the two biomarkers as a tool to predict AF and guide prolonged cardiac monitoring in cryptogenic stroke patients.. Non-lacunar acute ischaemic stroke (<72 h) patients over 55 years of age with cryptogenic stroke after standard evaluation were included in the Crypto-AF study and blood was collected. BNP and NT-proBNP levels were determined by automated immunoassays. AF was assessed by 28 days' monitoring. Highest (optimizing specificity) and lowest (optimizing sensitivity) quartiles were used as biomarker cut-offs to build predictive models adjusted by sex and age. The integrated discrimination improvement index (IDI) and DeLong test were used to compare the performance of the two biomarkers.. From 320 patients evaluated, 218 were included in the analysis. AF was detected in 50 patients (22.9%). NT-proBNP (P < 0.001) and BNP (P < 0.001) levels were higher in subjects with AF and their levels correlated (r = 0.495, P < 0.001). BNP showed an increased area under the curve (0.720 vs. 0.669; P = 0.0218) and a better predictive capacity (IDI = 3.63%, 95% confidence interval 1.36%-5.91%) compared to NT-proBNP. BNP performed better than NT-proBNP in a specific model (IDI = 3.7%, 95% confidence interval 0.87%-6.5%), whilst both biomarkers performed similarly in the case of a sensitive model.. Both BNP and NT-proBNP were increased in cryptogenic stroke patients with AF detection. Interestingly, BNP outperforms NT-proBNP, especially in terms of specificity.

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Humans; Ischemic Stroke; Natriuretic Peptide, Brain; Peptide Fragments; Stroke

Background Acute decompensated heart failure (ADHF) and respiratory tract infections (RTIs) are potentially life-threatening complications in patients experiencing stroke during hospitalization. We aimed to test whether blood biomarker panels might predict these complications early after admission. Methods and Results Nine hundred thirty-eight patients experiencing ischemic stroke were prospectively recruited in the Stroke-Chip study. Post-stroke complications during hospitalization were retrospectively evaluated. Blood samples were drawn within 6 hours after stroke onset, and 14 biomarkers were analyzed by immunoassays. Biomarker values were normalized using log-transformation and

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Early Diagnosis; Female; Fibrin Fibrinogen Degradation Products; Follow-Up Studies; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Protein Precursors; Respiratory Tract Infections; Risk Factors; ROC Curve

In recent years, LRG1 was found to be closely related to atrial fibrillation, heart failure, and myocardial remodeling after myocardial infarction. While its role in cerebral infarction was still controversial. We aimed to explore the value of LRG1 to identify the cardioembolic stroke.. 283 acute ischemic stroke(AIS) patients and 169 controls were enrolled. The AIS patients were divided into a CE(cardiogenic embolism) group and a non-CE group. Serum LRG1 levels were quantified by ELISA.. The serum LRG1 levels were decreased in the AIS patients. CE group had higher serum LRG1 levels than the non-CE group. LRG1 was an independent risk factor for cardioembolic stroke. The area under the curve (AUC) was 0.768 with a sensitivity of 72.5% and specificity of 69.5%, which was not second to BNP and LAD. The combined predictive model we designed, including LRG1, BNP, and LAD, greatly improved the prediction effect. A positive correlation was shown between LRG1 and stroke severity in the CE group. Those who experienced poor outcomes had higher serum LRG1 levels compared with good ones.. Serum LRG1 was a promising indicator to predict cardioembolic stroke, as well as stroke severity and the 3-month prognosis of it.

Topics: Biomarkers; Brain Ischemia; Embolic Stroke; Glycoproteins; Humans; Natriuretic Peptide, Brain; Stroke

The present study aimed to investigate the role of vascular endothelial growth factor (VEGF) in the neuroprotective effect of Crocus sativus (saffron) against cerebral ischemia/reperfusion injury (I/R) in rats. Four groups of a total forty I/R rats with 60-min occlusion followed by 48 h reperfusion or sham surgery were used. The sham and left-brain I/R control groups where treated with normal saline. The rats of the other two groups received saffron extract (100 or 200 mg/kg, ip, respectively) for 3 successive weeks prior to left-brain I/R. Other four doses of saffron extract were received by the rats of the last 2 groups 60 min prior to operation, during the surgery, and on days 1 and 2 following reperfusion. I/R group showed marked neurobehavioral, neurochemical and histopathological alterations. The results revealed a significant reduction in neurological deficit scores in the saffron-treated rats at both doses. Saffron significantly attenuated lipid peroxidation, decreased NO and brain natriuretic peptide (BNP) contents in I/R-brain tissue. On the other hand, saffron reversed the depletion of GSH in the injured brain. Moreover, saffron treatment evidently reduced apoptosis as revealed by a decrease in caspase-3 and Bax protein expression with a marked decrease in the apoptotic neuronal cells compared to I/R group. In addition, saffron administration effectively upregulated the expression of VEGF in I/R-brain tissue. In conclusion, saffron treatment offers significant neuroprotection against I/R damage possibly through diminishing oxidative stress and apoptosis and enhancement of VEGF.

Topics: Animals; Behavior, Animal; Brain; Brain Ischemia; Crocus; Lipid Peroxidation; Male; Natriuretic Peptide, Brain; Neuroprotective Agents; Nitric Oxide; Plant Extracts; Rats; Rats, Wistar; Reperfusion Injury; Tandem Mass Spectrometry; Vascular Endothelial Growth Factor A

N-terminal pro-B-type natriuretic peptide (NT-proBNP), frequently used as a biochemical marker for detecting and monitoring heart failure, is also a risk marker for development of coronary heart disease and total stroke. However, studies that explore subtypes of ischemic stroke with regard to NT-proBNP are scarce. Here, we examined NT-proBNP and its impact upon subtypes of ischemic stroke (lacunar stroke, large-artery occlusive stroke and embolic stroke) among Japanese.. We measured NT-proBNP and categorized 4,393 participants of the Circulatory Risk in Communities Study into four groups (＜55, 55-124, 125-399, and ≥ 400 pg/ml). We used a multivariable Cox proportional hazards model to examine association with risks of stroke and subtypes.. During 4.7 years of follow-up, we identified 50 strokes, including 35 ischemic (15 lacunar, 6 largeartery occlusive, 10 embolic strokes) and 14 hemorrhagic strokes. NT-proBNP was associated with stroke risk: the multivariable hazard ratio of total strokes was 7.29 (2.82-18.9) for the highest and 2.78 (1.25-6.16) for the second highest NT-proBNP groups compared with the lowest group. The respective hazard ratios for the highest NT-proBNP group were 9.37 (3.14-28.0) for ischemic stroke and 6.81 (1.11-41.7) for lacunar stroke. Further adjustment for atrial fibrillation did not attenuate these associations. The associations were similarly observed for large-artery occlusive and embolic strokes.. We found that even moderate serum levels of NT-proBNP were associated with the risk of total and ischemic strokes among Japanese whose NT-proBNP levels were relatively low compared with Westerners.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Follow-Up Studies; Humans; Ischemic Stroke; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Survival Rate; Young Adult

Topics: Biomarkers; Brain Ischemia; Humans; Japan; Natriuretic Peptide, Brain; Peptide Fragments; Stroke

The detection of Nonvalvular atrial fibrillation (NVAF) in AIS patients may be elusive and require further investigation such as electrocardiography (ECG) and Holter monitoring. The objective of this study is to evaluate the N-terminal pro B-type natriuretic peptide (NT-proBNP) diagnostic value for NVAF and the clinical outcome of AIS patients.. We conducted a retrospective study of AIS patients in ten hospitals of the Shaanxi province. All NVAF patients and matched patients without NVAF admitted within 7 days after stroke onset were included in our study. The admission NT-proBNP receiver operating characteristic curve was drawn to determine the discriminative power of NT-proBNP in NVAF identification. Multivariate logistic regression analysis was used to examine the odds ratios (OR) of NT-proBNP for NVAF and identify the potential factors associated with the clinical outcomes in AIS patients.. A total of 275 NVAF cases and 275-matched controls were included in the current study. NT-proBNP was independently associated with NVAF (OR = 64.047, 95% confidence interval [CI]: 30.298-135.390, p < .001) in AIS patients. The optimal cutoff point for the NT-proBNP level to distinguish the NVAF group from the non-NVAF group was 431.0 pg/ml, with an area under curve [AUC] of 0.910 (95% CI: 0.885-0.935, p < .001). The high NT-proBNP level (OR: 3.284, 95% CI: 1.830-5.896, p < .001) was an independent indicator that was positively related to hospitalization mortality.. The rise of the serum NT-proBNP level at first admission added great contributions to the NVAF diagnosis after AIS, and was independently associated with the hospitalization mortality of AIS patients.

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Case-Control Studies; Humans; Ischemic Stroke; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Stroke

N-terminal pro-brain natriuretic peptide (NT-proBNP) and galectin-3 are important biomarkers related to ischemic stroke. However, the predictive value of the combination of them has not been examined in previous studies.. The aim of this study was to investigate the combined effect of NT-proBNP and galectin-3 on clinical outcomes in ischemic stroke patients.. A total of 2694 patients (63.62% males; mean age = 62.4 in admission) with serum NT-proBNP and galectin-3 measured simultaneously were included in this study. The primary outcome was composite outcome of death or major disability 1 year after stroke onset. Secondary outcomes were separately death, major disability, vascular events and the composite outcome of vascular events or death. The participants were divided into 4 groups according to NT-proBNP and galectin-3. Odd ratios (ORs; for nonevent outcome without time variables: primary outcome, major disability) or hazard ratios (HRs; for event outcome with time variables: death, vascular events, and the composite outcome of vascular events or death) were calculated to assess the association of NT-proBNP and galectin-3 status with adverse outcomes.. At the 1-year follow-up, 589 patients experienced a primary outcome after stroke onset. After adjustment for potential confounders, high NT-proBNP/high galectin-3 group were associated with increased risks of primary outcome (OR: 1.43; 95% confidence interval [CI], 1.02-2.00; P value = 0.039), death (HR: 2.74; 95% CI, 1.42-5.29; P value = 0.003), and the composite outcome of vascular events or death (HR: 1.66; 95% CI, 1.06-2.58; P value = 0.026). Statistical tests for interactions between the 4 groups and primary outcome or death were not significant (all P interaction > 0.05).. Simultaneously increased NT-proBNP and galectin-3 significantly increased the risk of poor clinical outcomes 1 year after ischemic stroke. Using NT-proBNP and galectin-3 together can result in an accurate prediction of ischemic stroke prognosis.

Topics: Biomarkers; Brain Ischemia; Female; Galectin 3; Humans; Ischemic Stroke; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors; Stroke

Topics: Aged; Aged, 80 and over; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Disease-Free Survival; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Neurofilament Proteins; Peptide Fragments; Predictive Value of Tests; Prospective Studies; S100 Proteins; Stroke; Survival Rate; Tomography, X-Ray Computed

It is unclear whether biomarkers of cardiac dysfunction are associated with cryptogenic stroke (CS).. We retrospectively evaluated consecutive ischemic stroke patients. Patients underwent transthoracic echocardiography to evaluate left atrial diameter and the peak transmitral filling velocity/mean mitral annular velocity during early diastole (E/e'). Patent foramen ovale (PFO) and left atrial appendage flow velocity were evaluated by transesophageal echocardiography. We compared clinical characteristics and biomarkers of cardiac dysfunction (brain natriuretic peptide [BNP], left atrial diameter, E/e', and left atrial appendage flow velocity) between CS or CS without large PFO and other causative stroke subtypes.. Among 1,514 patients with ischemic stroke, 264 patients were classified as having CS. Of these, transesophageal echocardiography revealed 27/158 (17%) large PFOs. In comparison, for the noncardioembolic stroke group, which consisted of large artery and small vessel subtypes, patients with CS without large PFO had higher log10 BNP (adjusted OR 2.70; 95% CI 1.92-3.78; p < 0.001), higher log10 E/e' (3.41; 1.21-13.15; p = 0.019), and lower left atrial appendage flow velocity (0.98; 0.97-1.00; p = 0.031). Left atrial diameter was similar for noncardioembolic stroke and CS without large PFO (p = 0.380). Cutoff values of BNP, E/e', and left atrial appendage flow velocity capable of distinguishing CS without large PFO from noncardioembolic stroke were 65.0 pg/mL (sensitivity 55.3%; specificity 70.9%), 13.0 (45.5%; 68.0%), and 46.0 cm/s (37.1%; 87.5%), respectively.. Patients with CS without large PFO could have biomarkers of cardiac dysfunction.

Topics: Aged; Aged, 80 and over; Atrial Appendage; Atrial Function, Left; Biomarkers; Brain Ischemia; Echocardiography, Transesophageal; Female; Foramen Ovale, Patent; Heart Diseases; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Risk Assessment; Risk Factors; Stroke

Optimization of the detection of atrial fibrillation following stroke is mandatory. Unfortunately, access to long-term cardiac monitoring is limited in many centers. The aim of this study was to assess the potential usefulness of three routine biological markers, troponin, D-dimers and BNP, measured in acute stroke phase in the selection of patients at risk of cardio-embolic stroke.. Troponin, D-Dimers and BNP were measured within 48 h after admission for ischemic stroke in 634 patients. Stroke mechanism was defined at the 3 months follow-up visit using ASCOD classification using a standardized work-up. Association between clinical, radiological and biological markers and stroke mechanism was evaluated using logistic regression analyses.. 159 patients (25.1% of total study population) had a cardiac mechanism. On multivariate analysis, admission initial stroke severity (OR 1.04, 95 CI% 1.004-1.07, p < 0.05) history of heart failure (OR 3.03, 95% CI 1.19-7.73, p < 0.05), ECG abnormalities and high BNP value (OR 4.34, 95% CI 2.59-7.29, p < 0.05) were associated with pure cardiac stroke mechanism.. High BNP value measured within 48 h after stroke admission is an independent predictor of cardiac stroke mechanism. Its measurement might be used to improve the selection of patients for whom further cardiologic investigations such as continuous long term ECG monitoring would be the most useful. BNP should be added to the standard admission-work-up for stroke patients.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Female; Fibrin Fibrinogen Degradation Products; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Recurrence; Risk Factors; Stroke; Troponin I

Our study aimed to determine the prognostic value of elevated Brain Natriuretic Peptide (BNP) among patients who received intravenous thrombolysis (IVT) in acute ischemic stroke (AIS).. The elevation in BNP level is correlated with infarct size, poststroke mortality, and CHADS2 score. Currently, there is a lack of validated biomarker to predict the outcome in patients with acute ischemic stroke, and there is a complex interaction amongst multiple variables.. A retrospective review of medical records of patients admitted to our institution with acute ischemic stroke was performed. The patients who received intravenous thrombolysis were selected for analysis and divided into 2 groups based on the level of BNP. We compared the baseline demographics, past medical history, stroke etiology, discharge disposition, and 3-month mRS between both groups. Multivariate logistic regression analysis was performed to identify the predictors of poor outcome following intravenous thrombolysis in acute ischemic stroke.. A total of 90 patients were recruited in the study; 53 patients were found to have an elevated BNP (high BNP was defined as >100 pg/mL) level, whereas 37 had low BNP levels. Our study showed that patients with elevated BNP were more likely to have an elevation in admission and discharge NIHSS, serum creatinine, left atrial size, and blood glucose (P<0.05). Atrial fibrillation and cardioembolic strokes were seen most often in the population with elevated BNP (P<0.05). The patients with elevated BNP were less likely to be discharged home, and 3-month mRS was found to be higher, but these were not significant. On multivariate analysis, elevated BNP was not found to be an independent factor for poor outcome.. Elevated BNP level was not found to be an independent marker of poor outcome in AIS patients following IVT.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Chi-Square Distribution; Female; Fibrinolytic Agents; Humans; Injections, Intraventricular; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Risk Factors; Stroke

Background and Purpose- NT-proBNP (N-terminal pro-B-type natriuretic peptide) is a risk factor for atrial fibrillation and a marker of cardiac function used in the detection of heart failure. Given the link between cardiac dysfunction and stroke, NT-proBNP is a candidate marker of stroke risk. Our aim was to evaluate the association of NT-proBNP with stroke and to determine the predictive value beyond a panel of established risk factors. Methods- Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-Consortium, we analyzed data of 58 173 participants (50% men; mean age 52 y) free of stroke from 6 community-based cohorts. NT-proBNP measurements were performed in the central Biomarkers for Cardiovascular Risk Assessment in Europe laboratory. The outcomes considered were total stroke and subtypes of stroke (ischemic/hemorrhagic). Results- During a median follow-up time of 7.9 years, we observed 1550 stroke events (1176 ischemic). Increasing quarters of the NT-proBNP distribution were associated with increasing risk of stroke ( P for trend <0.0001; multivariable Cox regression analysis adjusted for risk factors and cardiac diseases). Individuals in the highest NT-proBNP quarter (NT-proBNP >82.2 pg/mL) had 2-fold (95% CI, 75%-151%) greater risk of stroke than individuals in the lowest quarter (NT-proBNP <20.4 pg/mL). The association remained unchanged when adjusted for interim coronary events during follow-up, and though it was somewhat heterogeneous across cohorts, it was highly homogenous according to cardiovascular risk profile or subtypes of stroke. The addition of NT-proBNP to a reference model increased the C-index discrimination measure by 0.006 ( P=0.0005), yielded a categorical net reclassification improvement of 2.0% in events and 1.4% in nonevents and an integrated discrimination improvement of 0.007. Conclusions- In European individuals free of stroke, levels of NT-proBNP are positively associated with risk of ischemic and hemorrhagic stroke, independently from several other risk factors and conditions. The addition of NT-proBNP to variables of established risk scores improves prediction of stroke, with a medium effect size.

Topics: Adult; Atrial Fibrillation; Biomarkers; Brain Ischemia; Cohort Studies; Europe; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Factors; Sex Factors; Stroke; Treatment Outcome

It is well-known that in ischemia-induced hypoxia, hypoxia-inducible factor -1α (HIF-1α) is critical in triggering expression of its downstream target genes to produce several products, such as erythropoietin (EPO), vascular endothelial growth factor (VEGF), nitric oxide synthesis (NOS), glucose transportor-1 (GLUT-1), insulin-like growth factor (IGF), which further promote erythropoiesis, angiogenesis, vasodilation and capitalization of glucose to overcome hypoxia. Meanwhile, as the factors with opposite effects on blood vessels, endothelin-1 (ET-1) and brain natriuretic peptide (BNP) also stand out strikingly in ischemic pathophysiology. To this day, several preconditioning manners have been used to induce tolerance to ischemia. During our research, exercise preconditioning was applied and it was demonstrated that HIF-1α triggered expression of ET-1 and BNP, which confirmed their downstream target genes for HIF-1α. And ET-1 may influcence expression of BNP to some degree but not the only factor which regulates BNP expression. Therefore, our findings suggest exercise preconditioning may provide protection to the ischemic brain tissue via HIF-1α which in turn increases expression of BNP to cause vasodilation in cooperation with some other factors, such as VEGF and EPO, to increase the blood flow in the ischemic area and then relieve the injuries induced by ischemia.

Topics: Animals; Brain Ischemia; Corpus Striatum; Endothelin-1; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemic Preconditioning; Male; Natriuretic Peptide, Brain; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Risk Factors; Stroke

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Risk Factors; Stroke

Emerging evidence suggests that an underlying atrial cardiopathy may result in thromboembolism before atrial fibrillation (AF) develops. We examined the association between various markers of atrial cardiopathy and the risk of ischemic stroke.. The CHS (Cardiovascular Health Study) prospectively enrolled community-dwelling adults ≥65 years of age. For this study, we excluded participants diagnosed with stroke or AF before baseline. Exposures were several markers of atrial cardiopathy: baseline P-wave terminal force in ECG lead V. Among 3723 participants who were free of stroke and AF at baseline and who had data on all atrial cardiopathy markers, 585 participants (15.7%) experienced an incident ischemic stroke during a median 12.9 years of follow-up. When all atrial cardiopathy markers were combined in 1 Cox model, we found significant associations with stroke for P-wave terminal force in ECG lead V. In addition to clinically apparent AF, other evidence of abnormal atrial substrate is associated with subsequent ischemic stroke. This finding is consistent with the hypothesis that thromboembolism from the left atrium may occur in the setting of several different manifestations of atrial disease.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Cohort Studies; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Heart Atria; Heart Diseases; Humans; Incidence; Male; Natriuretic Peptide, Brain; Organ Size; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Stroke

There is no definitive data regarding the usefulness of Brain microbleeds (BMBs) as an imaging marker with homeostatic markers to predict intracerebral hemorrhage (ICH) and ischemic stroke risk to personalize decisions on anticoagulation in AF. In this study, we prospectively evaluated clinical, radiological homeostatic biomarkers and their association with stroke outcomes in 73 AF-related ischemic stroke patients.. All BMBs were measured manually on Susceptibility-Weighted Imaging (SWI). The levels of NT-pro-BNP, hs-CRP, FVII, FVIII and vWF were studied as homeostatic markers. For all patients, we calculated CHADS2, CHA2DS2-VASc, HAS-BLED scores and modified Rankin Scale (mRS) scores. Functional independence and good clinical outcome were defined as a mRS score of 0-2.. The mean age of the study population was 69.74 ± 9.79 years, and 36 patients were female. The leading vascular risk factor was hypertension (61%). BMBs were determined in 20 patients (27.4%) on SWI, 12 patients had less than five lesions. Presence of BMBs lesions on SWI was significantly associated with age and hypertension (p = .020) and congestive heart failure (p = .011). The median CHA2DS2-VASc score in patients was 4.96 ± 1.54. CHA2DS2-VASc score (p = .042), CHADS2 score (p = .037) and HAS- BLED score (p = .033) were significantly related with the presence of BMBs in the study patients. Among homeostatic markers, the levels of NT-pro-BNP, hs-CRP, and vWF were significantly associated with the presence of microbleeds (p = .013, p = .029, p = .020, respectively).. Pathogenesis of AF is involved abnormal changes of hemostasis, endothelial dysfunction, antithrombotic state and inflammation. The homeostatic markers, which play role in these pathways, and the presence of BMBs could use to form a prognostic clinic assessment tool to predict bleeding risk.

Topics: Aged; Aged, 80 and over; Brain Ischemia; C-Reactive Protein; Cohort Studies; Female; Homeostasis; Humans; Image Processing, Computer-Assisted; Intracranial Hemorrhages; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke; Thrombolytic Therapy; von Willebrand Factor

To evaluate long-term mortality in patients with acute ischemic stroke (AIS) by exploring the correlation between death and plasma concentrations of copeptin and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a cohort study.. In a prospective, multicenter observational study of 4,215 patients with AIS, copeptin and NT-proBNP levels were measured with a standardized method when patients were admitted to hospital. The primary endpoint was all-cause mortality or cardiovascular disease (CVD) mortality within 1 year.. During a follow-up period, 906 patients (20.1%, 95% confidence interval [CI] 18.9-21.2) died, including 589 cases of CVD mortality (13.1%, 95% CI 12.1-14.0). With the use of a multivariate analysis, both markers were found to have prognostic value in the same model (CVD mortality: odds ratio [OR] for fourth quartile of copeptin and NT-proBNP 1.68 and 2.58, 95% CI 1.22-2.49 and 1.76-4.05, respectively; all-cause mortality: OR for fourth quartile of copeptin and NT-proBNP 1.48 and 2.47, 95% CI 1.22-2.03 and 1.68-3.95, respectively). In a receiver operating characteristics analysis of CVD mortality, the area under the curve varied from 0.80 to 0.83 (95% CI 0.79-0.87) when the index of NT-proBNP was added and increased to 0.86 (95% CI 0.83-0.90) when both markers were added.. Copeptin and NT-proBNP may be useful independent prognostic markers of all-cause or CVD mortality in Chinese patients with AIS.

Topics: Aged; Area Under Curve; Biomarkers; Brain Ischemia; Cardiovascular Diseases; China; Female; Follow-Up Studies; Glycopeptides; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prognosis; Prospective Studies; ROC Curve; Stroke

Stroke diagnosis could be challenging in the acute phase. We aimed to develop a blood-based diagnostic tool to differentiate between real strokes and stroke mimics and between ischemic and hemorrhagic strokes in the hyperacute phase.. The Stroke-Chip was a prospective, observational, multicenter study, conducted at 6 Stroke Centers in Catalonia. Consecutive patients with suspected stroke were enrolled within the first 6 hours after symptom onset, and blood samples were drawn immediately after admission. A 21-biomarker panel selected among previous results and from the literature was measured by immunoassays. Outcomes were differentiation between real strokes and stroke mimics and between ischemic and hemorrhagic strokes. Predictive models were developed by combining biomarkers and clinical variables in logistic regression models. Accuracy was evaluated with receiver operating characteristic curves.. From August 2012 to December 2013, 1308 patients were included (71.9% ischemic, 14.8% stroke mimics, and 13.3% hemorrhagic). For stroke versus stroke mimics comparison, no biomarker resulted included in the logistic regression model, but it was only integrated by clinical variables, with a predictive accuracy of 80.8%. For ischemic versus hemorrhagic strokes comparison, NT-proBNP (N-Terminal Pro-B-Type Natriuretic Peptide) >4.9 (odds ratio, 2.40; 95% confidence interval, 1.55-3.71;. The studied biomarkers were not sufficient for an accurate differential diagnosis of stroke in the hyperacute setting. Additional discovery of new biomarkers and improvement on laboratory techniques seem necessary for achieving a molecular diagnosis of stroke.

Topics: Aged; Aged, 80 and over; Amine Oxidase (Copper-Containing); Apolipoprotein C-III; Biomarkers; Brain Ischemia; Case-Control Studies; Caspase 3; Cell Adhesion Molecules; Cerebral Hemorrhage; Chemokine CXCL1; Endostatins; Fas Ligand Protein; Female; Fibrin Fibrinogen Degradation Products; Fibronectins; HSC70 Heat-Shock Proteins; Humans; Insulin-Like Growth Factor Binding Protein 3; Interleukin Receptor Common gamma Subunit; Interleukin-17; Interleukin-6; Logistic Models; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Nerve Growth Factor; Neural Cell Adhesion Molecules; Odds Ratio; Peptide Fragments; Phosphopyruvate Hydratase; Prospective Studies; Receptors, Tumor Necrosis Factor, Type I; ROC Curve; S100 Calcium Binding Protein beta Subunit; Stroke; von Willebrand Factor

Cardiac diseases are established risk factors for ischemic stroke incidence and severity. Conversely, there is increasing evidence that brain ischemia can cause cardiac dysfunction. The mechanisms underlying this neurogenic heart disease are incompletely understood. Although it is established that ischemic stroke is associated with cardiac arrhythmias, myocardial damage, elevated cardiac enzymes, and plasma catecholamines in the acute phase, nothing is known about the delayed consequences of ischemic stroke on cardiovascular function.. To determine the long-term cardiac consequences of a focal cerebral ischemia, we subjected young and aged mice to a 30-minute transient middle cerebral artery occlusion and analyzed cardiac function by serial transthoracic echocardiography and hemodynamic measurements up to week 8 after surgery. Finally, animals were treated with metoprolol to evaluate a pharmacologic treatment option to prevent the development of heart failure.. Focal cerebral ischemia induced a long-term cardiac dysfunction with a reduction in left ventricular ejection fraction and an increase in left ventricular volumes; this development was associated with higher peripheral sympathetic activity. Metoprolol treatment prevented the development of chronic cardiac dysfunction by decelerating extracellular cardiac remodeling and inhibiting sympathetic signaling relevant to chronic autonomic dysfunction.. Focal cerebral ischemia in mice leads to the development of chronic systolic dysfunction driven by increased sympathetic activity. If these results can be confirmed in a clinical setting, treating physicians should be attentive to clinical signs of heart failure in every patient after ischemic stroke. Therapeutically, the successful β-blockade with metoprolol in mice could also have future clinical implications. Ann Neurol 2017;82:729-743.

Topics: Adrenergic beta-1 Receptor Antagonists; Animals; Brain Ischemia; Echocardiography; Epinephrine; Heart Failure; Hemodynamics; Hydrocortisone; Infarction, Middle Cerebral Artery; Male; Metoprolol; Mice; Natriuretic Peptide, Brain; Norepinephrine; Stroke; Sympathetic Nervous System

Besides 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.. A 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.. These clinical and experimental evidences support the potential role of BNP as a protective factor against cerebral ischemia.

Topics: Animals; Biomarkers; Brain Ischemia; Chi-Square Distribution; Disability Evaluation; Disease Models, Animal; Infarction, Middle Cerebral Artery; Logistic Models; Male; Motor Activity; Natriuretic Peptide, Brain; Neuroprotective Agents; Odds Ratio; Prognosis; Protective Factors; Rats, Sprague-Dawley; Recovery of Function; Registries; Retrospective Studies; Risk Factors; Sensory Thresholds; Stroke; Time Factors

Subcutaneous implantable electrocardiographs are highly effective in detecting covert atrial fibrillation (AF) in cryptogenic stroke. However, these invasive devices are not indicated for all cryptogenic stroke patients, and noninvasive improvements over conventional Holter-type ambulatory electrocardiography are needed. We evaluated the clinical application and effectiveness of Duranta (ImageONE Co., Ltd.), a wireless patch-type electrocardiographic monitoring system developed in Japan for chronically ill patients or home-based patients at the end of life. A Duranta device was used to detect covert AF in patients with acute ischemic stroke of undetermined source with no sign of AF during cardiographic monitoring ≥24 hours postadmission.. A 72-year-old man with severe aortic stenosis was admitted to our hospital with dysarthria and right upper limb weakness. Diffusion-weighted plain head magnetic resonance imaging (MRI) showed acute cerebral infarctions across the left middle cerebral artery territory. Twelve-lead electrocardiography, Holter-type ambulatory electrocardiography, and cardiographic monitoring for ≥24 hours revealed no AF, indicating a probable diagnosis of artery-to-artery embolism following left common carotid artery stenosis detected by carotid ultrasound imaging and cerebral angiography.. However, because of high blood brain natriuretic peptide (BNP) and valvular heart disease, continuous monitoring using Duranta was performed from the 2nd to 13th days after onset to exclude possible cardioembolic stroke. Waveform and heart rate trend graph analysis showed paroxysmal AF (PAF) occurred on the 5th and 9th days after onset. PAF did not occur at any other time during the observation period. The quality of the cardiograms sufficed for analysis and diagnosis of AF. The lightweight compact device can be placed quickly with no movement restriction. These features and our findings show the usefulness of the Duranta device for long-term continuous monitoring.. A noninvasive wireless patch-type electrocardiographic monitoring system, Duranta, placed at the precordium, was useful in detecting covert AF in cryptogenic stroke patients, warranting further investigation.

Topics: Acute Disease; Aged; Aortic Valve Stenosis; Atrial Fibrillation; Brain Ischemia; Carotid Stenosis; Electrocardiography, Ambulatory; Humans; Male; Natriuretic Peptide, Brain; Stroke

There is increasing evidence that left atrial dysfunction or cardiopathy is associated with ischemic stroke risk independently of atrial fibrillation. We aimed to determine the prevalence of atrial cardiopathy biomarkers in patients with cryptogenic stroke.. We included consecutive patients with ischemic stroke enrolled in the New York Columbia Collaborative Specialized Program of Translational Research in Acute Stroke registry between December 1, 2008, and April 30, 2012. Medical records were reviewed and patients with a diagnosis of cryptogenic stroke were identified. Atrial cardiopathy was defined as at least one of the following: serum N-terminal probrain natriuretic peptide (NT-proBNP) level greater than 250 pg/mL, P-wave terminal force velocity in lead V1 (PTFV1) on electrocardiogram (ECG) greater than 5000 µV⋅ms, or severe left atrial enlargement (LAE) on echocardiogram. We compared clinical, echocardiographic, and radiological characteristics between patients with and without atrial cardiopathy.. Among 40 patients with cryptogenic stroke, 63% had at least one of the biomarkers of atrial cardiopathy; 49% had elevated NT-proBNP levels, 20% had evidence of increased PTFV1 on ECG, and 5% had severe LAE. Patients with atrial cardiopathy were more likely to be older (76 versus 62 years, P = .012); have hypertension (96% versus 33%, P < .001), hyperlipidemia (60% versus 27%, P = .05), or coronary heart disease (28% versus 0%, P = .033); and less likely to have a patent foramen ovale (4% versus 40%, P = .007).. There is a high prevalence of biomarkers indicative of atrial cardiopathy in patients with cryptogenic stroke. Clinical trials are needed to determine whether these patients may benefit from anticoagulation to prevent stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Atrial Function, Left; Biomarkers; Brain Ischemia; Cardiomegaly; Comorbidity; Coronary Disease; Cross-Sectional Studies; Electrocardiography; Female; Foramen Ovale, Patent; Heart Diseases; Humans; Hyperlipidemias; Hypertension; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Prevalence; Prospective Studies; Registries; Smoking; Ultrasonography; Young Adult

Epicardial fat, a metabolically active tissue, has emerged as a risk factor and active player in metabolic and cardiovascular diseases. We investigated epicardial fat thickness in patients who had sustained an acute ischemic stroke, and we evaluated the relationship of epicardial fat thickness with other prognostic factors. We enrolled 61 consecutive patients (age, ≥18 yr) who had sustained a first acute ischemic stroke and had been admitted to our hospital within 24 hours of the onset of stroke symptoms. The control group comprised 82 consecutive sex- and age-matched patients free of past or current stroke who had been admitted to our cardiology clinics. Blood samples were taken for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) levels at admission. Aortic stiffness indices and epicardial fat thickness were measured by means of transthoracic echocardiography within the first 48 hours. In comparison with the control group, the patients with acute ischemic stroke had significantly higher epicardial fat thickness (4.8 ± 0.9 vs 3.8 ± 0.7 mm; P <0.001), lower aortic distensibility (2.5 ± 0.8 vs 3.4 ± 0.9 cm(2) ·dyn(-1); P <0.001) and lower aortic strain (5.5% ± 1.9% vs 6.4% ± 1.8%; P=0.003). We found a significant association between epicardial fat thickness, NT-proBNP levels, and arterial dysfunction in patients who had sustained acute ischemic stroke. Increased epicardial fat thickness might be a novel risk factor and might enable evaluation of subclinical target-organ damage in these patients.

Topics: Acute Disease; Adipose Tissue; Aged; Aorta, Thoracic; Brain Ischemia; Echocardiography; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pericardium; Predictive Value of Tests; Retrospective Studies; Risk Factors; Time Factors; Tomography, X-Ray Computed; Vascular Stiffness

This study aimed to investigate changes of corrected QT (QTc) interval during acute ischemic stroke and its correlation with high-sensitivity troponin I (hsTnI), brain natriuretic peptide (BNP), neurological outcome, and 1-year mortality.. We registered electrocardiogram in 69 patients immediately after admission to the intensive care unit and then after 24 and 48 hours. Computed tomography was performed on admission to determine brain infarct size and localization. Neurological outcome was assessed by modified Rankin scale (mRS) at discharge.. Forty-five (65.2%) patients had prolonged QTc at baseline; only 18 (26.1%) patients had prolonged QTc after 48 hours. Baseline QTc was not associated with neurological outcome (P = .27). However, prolonged QTc after 48 hours was associated with worse mRS at discharge (4.5 [4.0-6.0] versus 2.0 [1.0-3.0]; P < .0001). Patients who deceased during hospitalization (n = 7 [10.1%]) as compared with survivors had more frequently prolonged QTc after 48 hours (38.9 versus 0%; P < .0001), higher level of hsTnI (48.4 [36.1-75.0] versus 8.6 [3.4-26.5]; P = .003), and BNP (334 [224-866] versus 109 [30-190]; P = .014). In univariate analysis, 1-year mortality was associated with prolonged QTc after 48 hours, hsTnI, and BNP. In multivariate analysis, only BNP remained to be associated with 1-year mortality (odds ratio 3.41, 95% confidence interval 1.06-11.03).. QTc interval in patients with acute ischemic stroke is a dynamic parameter. Prolonged QTc after 48 hours, but not baseline QTc, correlated with neurological outcome and 1-year mortality. Patients with prolonged QTc had higher level of hsTnI.

Topics: Action Potentials; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Cerebral Angiography; Computed Tomography Angiography; Disability Evaluation; Electrocardiography; Female; Heart Conduction System; Heart Rate; Hospital Mortality; Humans; Intensive Care Units; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neurologic Examination; Odds Ratio; Patient Admission; Predictive Value of Tests; Recovery of Function; Risk Factors; Stroke; Time Factors; Treatment Outcome; Troponin I

The aim of this study was to identify whether subacute diffusion-weighted imaging (DWI) lesion volume could predict long-term outcome in patients who had undergone intravenous thrombolysis.. Patients underwent DWI at baseline and 7days after thrombolysis. Outcomes included complete independence (modified Rankin scale [mRS] score 0 to 1), unfavorable outcome (mRS score 4 to 6) at 90days, and mortality within 90days. Multivariate logistic regression analysis was used to identify outcome predictors.. Of 164 patients, 72 patients (43%) achieved complete independence. Poor outcomes were observed in 45 patients (27%) with an unfavorable outcome and 10 patients (6%) who died. Subacute DWI lesion volume was 3.4mL (interquartile range, 1.1-11.6) in patients with complete independence, 90.1mL (23.8-180.2) in patients with unfavorable outcome and 155.5mL (78.4-377.5) in patients who died. In multivariate logistic regression analysis, subacute DWI lesion volume was an independent predictor of complete independence (odds ratio [OR], 0.939; 95% confidence interval [CI], 0.914-0.965; p<0.001), unfavorable outcome (OR, 1.023; 95% CI, 1.014-1.033; p<0.001), and mortality (OR, 1.016; 95% CI, 1.005-1.028; p=0.005).. Subacute DWI lesion volume is a critical determinant of 90-day functional outcome and mortality after thrombolysis.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Glucose; Brain; Brain Ischemia; C-Reactive Protein; Diffusion Magnetic Resonance Imaging; Female; Fibrinolytic Agents; Glomerular Filtration Rate; Humans; Image Processing, Computer-Assisted; Injections, Intravenous; Male; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Stroke; Tissue Plasminogen Activator; Treatment Outcome

Topics: Brain Ischemia; Cerebrovascular Disorders; Cohort Studies; Glycopeptides; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Recurrence; Stroke

The study aimed to evaluate the prognostic role and discriminative power of aortic stiffness and plasma brain natriuretic peptide levels in a cohort of patients hospitalized for acute ischemic stroke.. Three hundred and ten consecutive patients aged 50 years and older with a first episode of acute ischemic stroke were prospectively evaluated. All patients were admitted to the hospital within 24 h of the onset of stroke symptoms. The type of acute ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment classification. Blood samples were taken for measurement of brain natriuretic peptide levels at admission. Aortic stiffness indices, aortic strain and distensibility, were calculated from the aortic diameters measured by transthoracic echocardiography. The patients were followed for one-year or until death, whichever came first. Death occurred in 51 (16·5%) patients. On multivariate logistic regression analysis, National Institutes of Health Stroke Scale score >13, diabetes, brain natriuretic peptide >235 pg/mL, aortic distensibility, and aortic strain were associated with all-cause mortality. The optimal cutoff level of brain natriuretic peptide to distinguish the deceased group from the survival group was 235 pg/mL (sensitivity 71·0% and specificity 63·0%) and to distinguish cardioembolic stroke from noncardioembolic stroke was 155 pg/mL (sensitivity 81% and specificity 63%).. Aortic stiffness and brain natriuretic peptide predict mortality in patients with first-ever acute ischemic stroke. Brain natriuretic peptide also differentiates cardioembolic stroke from noncardioembolic stroke.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Echocardiography; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Factors; Stroke; Vascular Stiffness

Brain natriuretic peptide (BNP) is believed to be a diagnostic marker for cardiovascular diseases, including atrial fibrillation (AF). Recent studies have incriminated BNP as a marker of cardioembolic stroke. We aimed at investigating association of plasma BNP levels in acute ischemic stroke subtypes and their outcome in Indian patients.. We recruited 270 acute ischemic stroke patients within 48 hours of symptom onset and compared with 110 age- and sex-matched control subjects. This study was carried out at Yashoda Hospital, Hyderabad, India between April 2011 and March 2013. Serum BNP levels were estimated in stroke patients and control subjects. Good functional outcome at 3 months was defined as modified Rankin score (mRS) 2 or less.. Elevated BNP levels was significantly more in patients with acute ischemic stroke patients 119 (44%) compared with controls 4 (3.6%; P < .0001). Among stroke subtypes, elevated BNP levels were observed in 75% of cardioembolic strokes, 45.8% of small artery disease, 43.1% of larger artery atherosclerosis, and 34.5% of stroke of undetermined etiology. On multiple logistic regression analysis, elevated BNP levels were significantly associated with acute ischemic stroke (odds ratio [OR], 13.0; 95% confidence interval [CI], 8.1-15.4). Among stroke subtypes, significant association was seen with cardioembolic stroke (OR, 3.5; 95% CI, 2.2-7.2). Elevated BNP levels were independently associated with poor outcome (OR, 3.4; 95% CI, 1.2-13.7; P < .0001) and higher mortality (OR, 3.4; 95% CI, 1.2-13.7; P < .0001).. Elevated BNP level is an independent marker for cardioembolic stroke and poor outcome at 90 days follow-up. No significant association was seen with other stroke subtypes.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Brain Ischemia; Female; Follow-Up Studies; Humans; India; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Stroke; Young Adult

Because B-type natriuretic peptide is a powerful predictor of heart failure, its capability to predict a fatal outcome in stroke might be limited to the cardioembolic stroke subtype. In this study, we attempt to ascertain the difference in the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) between cardioembolic and noncardioembolic stroke subgroups.. 410 acute stroke patients were included. According to the presence of a cardioembolic source (CES), there were 221 patients with CES and 189 patients without CES. Logistic regression analysis was performed to ascertain the association between NT-proBNP and 6-month mortality/functional outcome in each group.. The mean age of our patients was 67.2 years (range, 18-97 years). NT-proBNP was a multivariate independent predictor of mortality in the CES group alone, whereas it was only a univariate predictor of 6-month mortality in the total patient and non-CES groups with its association disappearing in the multivariate model. In addition, it was only a univariate predictor of good functional outcome in all of the groups.. Our data suggest that NT-proBNP can more reliably predict 6-month mortality in patients with cardioembolic stroke than in patients with other stroke subtypes.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Case-Control Studies; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke

High plasma levels of brain natriuretic peptide (BNP) may also be observed in patients with non-cardioembolic infarction (CEI). We aimed to evaluate the relation between plasma BNP level, clinical parameters, and functional outcome in patients with and without CEI.. This study analyzed consecutive Japanese patients with acute ischemic stroke. Correlations between plasma BNP level and conventional risk factors for ischemic stroke were examined. Values of P less than .05 were considered statistically significant.. This study analyzed 718 acute ischemic stroke patients (445 men and 273 women; mean age, 73.9 years). Mean plasma level of BNP was significantly higher for CEI (366.6 pg/ml) than for non-CEI (105.6 pg/ml; P < .01). Poor outcome (modified Rankin Scale score ≥3) at hospitalization and discharge were associated with significantly higher plasma BNP level than good outcome (modified Rankin Scale score ≤2) for both CEI and non-CEI. On multiple regression analysis, log-BNP was significantly associated with female sex, smoking, triglyceride, and creatinine clearance in CEI. In non-CEI, log-BNP was significantly associated with systolic/diastolic blood pressure, triglyceride, high-density lipoprotein cholesterol, and creatinine clearance.. Irrespective of the presence of CEI, plasma BNP offers a marker of prognostic functional outcome. We clarified the characteristics and differences associated with plasma BNP in CEI and non-CEI, and our results suggest that plasma BNP can provide a useful marker of brain damage and neurohumoral dynamics in acute ischemic stroke.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; ROC Curve; Severity of Illness Index; Stroke; Stroke, Lacunar

Topics: Biomarkers; Brain Ischemia; Embolism; Heart Diseases; Humans; Natriuretic Peptide, Brain; Stroke

The prognostic value of the N-amino terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP) in acute ischemic stroke (AIS) is uncertain. We sought to determine whether NT-proBNP levels were associated with functional outcomes after AIS. From August 2012 to October 2013, consecutive first-ever AIS patients admitted to the Department of Emergency of the First Affiliated Hospital of Xinxiang Medical University, China, were included in this study. Plasma NT-proBNP levels were measured from admission. Outcomes were measured as 90-day modified Rankin Scale score ('good outcome'=0-2 vs. 'poor'). Multivariate logistic regression was used to assess associations between NT-proBNP levels and outcomes. Predictive performance of NT-proBNP as compared with the clinical model was assessed by comparing receiver-operating characteristic curves. During this study period, 217 consecutive patients with AIS were included and completed 90 days of follow-up. There was a strong positive correlation between the plasma level of NT-proBNP and the National Institutes of Health Stroke Scale score (r=0.415, P=0.000). Plasma levels of NT-proBNP in patients with an unfavorable outcome were significantly higher than those in patients with a favorable outcome [3432 (interquartile range, 1100-54991) vs. 978 (interquartile range, 123-1705) pg/ml; P=0.000]. In multivariate analyses, after adjusting for all other significant outcome predictors, the NT-proBNP level that remained can be seen as an independent unfavorable outcome predictor, with an adjusted odds ratios of 4.14 (95% confidence interval, 2.72-7.99; P=0.000). Our results show that plasma NT-proBNP levels were significantly elevated in patients with an unfavorable outcome and might be of clinical importance as a supplementary tool for the assessment of functional outcomes in patients with AIS.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Recovery of Function; ROC Curve; Severity of Illness Index; Stroke

We investigated whether brain natriuretic peptide (BNP) levels could be used as a marker to predict recurrent stroke in ischemic stroke survivors.. From April 2007 to March 2011, consecutive patients within 24h of onset of ischemic stroke were prospectively enrolled, and admission plasma BNP levels were measured. Survivors were followed up to 12 months after stroke onset. Patients were divided into two groups: the recurrence group and the non-recurrence group. Factors associated with stroke recurrence were investigated by multiple logistic regression analysis.. A total of 793 patients who were alive at hospital discharge were included; 42 (5%) patients had recurrent stroke. There were no differences in BNP levels between groups. With respect to 257 patients with atrial fibrillation (AF), BNP levels were significantly higher in the recurrence group than in the non-recurrence group (426.0 vs. 192.0 pg/mL, P = 0.0007). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the recurrence group from the non-recurrence group were 300.0 pg/mL, 80%, and 73%, respectively. After adjustment for age and sex, plasma BNP ≥ 300.0 pg/mL (OR, 9.2; 95% CI, 1.87-45.01, P = 0.0062) was found to be independently associated with recurrent stroke in stroke survivors with AF.. Admission BNP levels can predict recurrent stroke in stroke survivors with AF.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Female; Follow-Up Studies; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Recurrence; Risk Factors; Sex Factors; Stroke; Survival Analysis

Our previous retrospective study demonstrated that a brain natriuretic peptide (BNP) level of >140 pg/ml on admission was useful to distinguish cardioembolism (CE) from non-CE. The aim of the present study was to prospectively investigate the utility of this predefined threshold.. Two hundred and twenty-one consecutive patients were prospectively enrolled. On admission, the BNP levels of the patients were measured and classified according to low BNP (≤140.0 pg/ml) or high BNP (>140.0 pg/ml) levels. Final diagnosis of stroke subtype on discharge was made using the TOAST criteria. Measured parameters included the sensitivity, specificity, positive predictive value, and negative predictive value for CE in the high BNP group.. There were 81 patients in the high BNP group and 140 patients in the low BNP group. A total of 76 (34.4%) patients were diagnosed with CE, including 59 (72.8%) patients in the high BNP group and 17 (12.1%) patients in the low BNP group (p < 0.001). A BNP level >140.0 pg/ml corresponded to a sensitivity of 77.6%, specificity of 84.8%, positive predictive value of 72.8%, and negative predictive value of 87.9% for a diagnosis of CE.. A BNP level of >140.0 pg/ml on admission in patients with acute ischemic stroke is a strong biochemical predictor for CE.

Topics: Aged; Aged, 80 and over; Algorithms; Atrial Fibrillation; Brain Ischemia; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Regression Analysis; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Stroke

There has been debate regarding whether natriuretic peptides can be used as a marker to distinguish cardioembolic (CE) origin of ischemic stroke from other subtypes. Therefore, the aim of this study was to study the value of N-terminal pro B-type natriuretic peptide (NT-proBNP) in differentiating CE from other subtypes of stroke in patients with acute ischemic stroke.. All 125 consecutive patients with acute ischemic stroke in a 1-year period were included. Admission blood samples of all patients were analyzed for the serum level of NT-proBNP. Patients were evaluated for etiology of stroke by imaging modalities and classified based on Trial of Org 10172 in Acute Stroke Treatment criteria. Medical history and risk factors for vascular diseases were also obtained. Receiver operating characteristic (ROC) analysis was used for estimating the diagnostic performance of NT-proBNP levels.. Patients were a mean of 67.5 ± 12.6 years of age, and 60 (48%) were men. The most frequent subtype of stroke (57 patients) was CE (45.6%). Levels of NT-proBNP at admission were significantly higher in the CE group (P = .001). After omitting confounding variables, NT-proBNP levels and age were independent predictors of CE stroke subtype. ROC analysis revealed that the diagnostic performance of NT-proBNP levels (area under the curve), optimum cutoff point and its sensitivity and specificity were 0.882 ± 0.031pg/mL, 342 pg/mL, 93%, and 75%, respectively.. NT-proBNP has an acceptable diagnostic value in distinguishing CE ischemic stroke from other subtypes. It can be used to differentiate the stroke subtype and facilitate the treatment process in these patients.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Biomarkers; Brain Ischemia; Chi-Square Distribution; Diagnosis, Differential; Embolism; Female; Heart Diseases; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; ROC Curve; Stroke

Studies suggest that N-terminal-pro-brain natriuretic peptide (NT-proBNP) can be a biomarker of cardioembolic stroke. However, the best time to measure it after stroke is unknown. We studied the time course of NT-proBNP in patients with ischemic stroke.. Consecutive acute ischemic stroke patients were admitted over 10 months to a Stroke Unit. Stroke type was classified according to TOAST. Blood samples were drawn within 24, 48, and 72 hours after stroke. Friedman test was used to compare NT-proBNP values across the 3 times in all, cardioembolic and non-cardioembolic stroke patients. Post hoc analysis with Wilcoxon signed-rank tests was conducted with a Bonferroni correction. Mann-Whitney test was used to compare median values of NT-proBNP between cardioembolic and non-cardioembolic stroke patients. ROC curves were drawn to determine NT-proBNP accuracy to diagnose cardioembolic stroke at 24, 48, and 72 hours after stroke onset.. One hundred and one patients were included (29 cardioembolic) with a mean age of 64.5±12.3 years. NT-proBNP values for cardioembolic stroke were significantly higher (P < 0.001) than for non-cardioembolic stroke in the 3 time points. NT-proBNP was highest in the first 24-48 h after ischemic stroke and decreased significantly 72 h after stroke onset. The area under the curve for the three time points was similar.. NT-proBNP levels were highest in the first 2 days after ischemic stroke and declined significantly thereafter. However, the area under the curve for the three time points was similar. The first 72 hours after ischemic stroke have a similar diagnostic accuracy to diagnose cardioembolic stroke.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Brain; Brain Ischemia; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Observation; Peptide Fragments; Prospective Studies; Radiography; ROC Curve; Statistics, Nonparametric; Stroke; Time Factors; Tomography Scanners, X-Ray Computed

Stroke is a leading cause of long-term morbidity and mortality affecting several hundred-thousand people annually in the Western Countries. Various panels of biomarkers of neural damage have been developed and validated. The primary objective of this investigation was to measure the correlation between the clinical severity of stroke and the serum/plasma concentrations of neural damage biomarkers.. A prospective investigation was conducted on a panel of biomarkers composed of S100β, matrix metalloproteinase-9 (MMP-9), N-terminal pro-B-type natriuretic peptide (NT pro-BNP) and D-dimer at admission and after 24 hours, in a cohort patients with a confirmed diagnosis of stroke in an emergency setting (STROke-MArkers STROMA).. A total of 58 consecutive patients were enrolled, no participant was excluded; according to clinical severity measured by National Institute of Health Stroke Scale (NIHSS) there were 29 minor strokes, 24 moderate, 3 moderate-severe, 2 severe. The Spearman's rank correlation test was used to assess the relationship between the baseline NIHSS value and the concentrations of the four biomarkers: all the studied biomarkers showed a statistically significant correlation with baseline NIHSS at 24 hours. A multivariate ordinal regression model was used to analyze the correlation of markers with stroke severity, stratified, according to NIHSS score: MMP-9 and S100β showed a statistically significant correlation after 24 hours.. MMP-9, S100β, NT pro-BNP and D-dimer showed a good correlation with the clinical severity of stroke which may become an additional resource in the acute patient evaluation and potentially follow-up.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; S100 Calcium Binding Protein beta Subunit; Severity of Illness Index; Stroke

To determine the value of the use of plasma B-type natriuretic peptide (BNP) among acute ischemic stroke patients in a Chinese emergency department (ED).. In our ED, the emergency physicians prospectively assessed consecutive adult patients with acute phase of ischemic stroke and measured plasma BNP by Biosite Triage(®)BNP POCT platform on admission, then followed up these patients. And the stroke neurologists evaluated patients' functional outcome at hospital discharge, and also made discharge diagnosis and stroke etiologic subtypes according to TOAST criteria: large-artery atherosclerosis (LAA), cardioembolism (CE), small-artery occlusion (SAO), stroke of other determined etiology (SOE) and stroke of other undetermined etiology (SUE).. In this study, 142 of 238 acute ischemic stroke patients met the study criteria [mean age 70.84 ± 11.48 years, 74 (52.11%) female]. Of the 142 patients, 35.92% were diagnosed with LAA at discharge, 25.35% with CE, 27.46% with SAO, 11.27% with SOE or SUE. Age, previous cardiac disease, atrial fibrillation, the length of hospital stays, SSS score on admission ≤ 25 and mRS ≥ 3 or death at discharge were all significantly higher in the CE patients compared to other subtypes (p<0.01). And the mean BNP concentration was significantly higher in the CE group than in other three subtypes (p<0.001). The optimal cut-off concentration, sensitivity and specificity of the plasma BNP concentration suitable to distinguish CE from non-CE were 66.50 pg/ml, 75.0% and 88.7%, respectively.. Plasma BNP level is significantly higher in CE patients than in other TOAST subtypes, and by using Biosite Triage(®)BNP POCT platform, emergency physicians should strongly consider CE subtype with the plasma BNP level of over 66.50 pg/ml. However, the single BNP biomarker panel cannot be used to confidently rule out or identify stroke subtypes as a diagnosis and must be taken in context with clinical assessment and judgment before making management decisions in the ED.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Arterial Occlusive Diseases; Asian People; Atherosclerosis; Biomarkers; Brain Ischemia; China; Data Interpretation, Statistical; Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Factors; ROC Curve; Stroke

Topics: Brain Ischemia; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Matrix Metalloproteinase 9; Natriuretic Peptide, Brain; Peptide Fragments; S100 Calcium Binding Protein beta Subunit; Stroke

Inflammation and activation of the neuroendocrine systems comprise important aspects of stroke pathophysiology. The present study investigated whether baseline plasma brain natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), cortisol and copeptin levels on admission can predict short-term outcomes and mortality after acute ischaemic stroke. The study group consisted of 189 patients who had their first acute ischaemic stroke. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were evaluated to determine their value with respect to predicting functional outcome and mortality within 3 months. As a result of cardiovascular and neurological investigations (including imaging techniques), lesion size, stroke subtype classification and clinical outcome after 3 months were determined. Plasma levels of BNP, NT-proBNP, cortisol and copeptin were associated with stroke severity, as well as short-term functional outcomes. After adjusting for all other significant outcome predictors, NT-proBNP, cortisol and copeptin remained as independent outcome predictors. In the receiver operating characteristic curve analysis, the biomarker panel (including BNP, NT-proBNP, cortisol and copeptin) predicted functional outcome and death within 90 days significantly more efficiently than the National Institute of Health Stroke Scale (NIHSS) or the biomarker alone. Copeptin showed a significantly greater discriminatory ability as a single biomarker compared to BNP, NT-proBNP, cortisol and NIHSS score. These results suggest that a biomarker panel may add valuable and time-sensitive prognostic information in the early evaluation of acute ischaemic stroke. This may provide a channel for interventional therapy in acute stroke.

Topics: Aged; Biomarkers; Brain; Brain Ischemia; Female; Glycopeptides; Humans; Hydrocortisone; Male; Middle Aged; Natriuretic Peptide, Brain; Neuroimaging; Peptide Fragments; Prognosis; Prospective Studies; Severity of Illness Index; Stroke

Previous research has revealed a higher prevalence of elevated cardiac troponin T or I levels amongst patients admitted with stroke, which has been associated with increased cardiovascular events, higher mortality rates, and poor inpatient prognosis. Because cardiac comorbidities account for almost 20% of deaths after ischemic stroke, it is important to understand the relationship between troponin elevation, cardiac events, and acute ischemic stroke (AIS).. We evaluated 137 consecutive patients ≥ 18 years of age who presented within 48 hours of AIS onset. All patients had laboratory markers drawn on admission, including troponin and brain natriuretic peptide, along with transthoracic echocardiogram with Doppler. The mean age of our study population was 71.7 ± 14.6 years.. Twenty-four of 137 patients (17.5%) had a positive troponin level. Sixteen of 24 (67%) patients with a positive troponin level had a new wall motion abnormality on echocardiogram that was suggestive of unstable atherosclerotic disease. On statistical analysis, we found a significant association between troponin and brain natriuretic peptide elevation with positive segmental wall motion abnormality on echocardiogram.. These study findings represent a new paradigm of interpreting elevated cardiac biomarkers and may help with risk stratification and diagnosis of patients presenting with AIS.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke; Troponin

Detection of new atrial fibrillation (AF) after ischemic stroke is challenging. The aim of the TARGET-AF study was to identify relevant markers for ruling out delayed AF in stroke patients. Early and prolonged Holter electrocardiography (ECG) monitoring during hospitalization was performed systematically in consecutive acute stroke patients naive to AF (no history of AF or no AF on baseline ECG). All clinical and paraclinical data for routine etiologic assessment were collected. The diagnostic value of all parameters significantly associated with AF was assessed by comparison of area under the receiver operating characteristic curve (AUC). Of the 300 stroke patients enrolled (mean age, 62.5 ± 15.5 years; sex ratio: 1.7; mean National Institutes of Health Stroke Scale score, 7.1 ± 7.9, median duration of Holter ECG monitoring, 6.8 days), 52 (17.3%) had newly diagnosed AF. Parameters significantly associated with AF were classified by increasing AUC: anterior circulation localization (AUC, 0.604; 95% confidence interval [CI], 0.546-0.660), P-wave initial force (AUC, 0.608; 95% CI, 0.545-0.669), left atrial dilatation (AUC, 0.657; 95% CI, 0.600-0.711), National Institutes of Health Stroke Scale score (AUC, 0.667; 95% CI, 0.611-0.720), sex (AUC, 0.683; 95% CI, 0.627-0.736), age (AUC, 0.755; 95% CI, 0.707-0.797), CHA2DS2-VASc score (AUC, 0.796; 95% CI, 0.746-0.841), STAF (score for the targeting of AF) score (AUC, 0.842; 95% CI, 0.796-0.882), and plasma brain natriuretic peptide (BNP) level (AUC, 0.868; 95% CI, 0.825-0.904). The use of all parameters combined (AUC, 0.910; 95% CI, 0.872-0.940) was not significantly more efficient in diagnosing AF than BNP alone (P = .248). At the Youden plot, the diagnostic properties for BNP >131 pg/mL were sensitivity, 98.1% (95% CI, 89.7-99.7); specificity, 71.4% (95% CI, 65.3-76.9); and negative predictive value, 99.4% (95% CI, 96.9-99.9). Our data indicate that a BNP level ≤ 131 pg/mL might rule out delayed AF in stroke survivors and could be included in algorithms for AF detection.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Electrocardiography, Ambulatory; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Stroke

Clinical scores are recommended for predicting cardiovascular risk in patients with cerebral ischaemia to inform secondary prevention. Blood biomarkers may improve prediction beyond clinical scores.. Within the observational Find-AF trial (ISRCTN46104198), 197 patients >18 years of age with cerebral ischaemia and without atrial fibrillation had blood sampled at baseline. The predictive value of five biomarkers for a combined vascular endpoint (acute coronary syndrome, stroke, cardiovascular death) and all-cause mortality was determined, alone and in addition to the Essen Stroke Risk Score (ESRS), Stroke Prognostic Instrument 2 (SPI-2) and National Institutes of Health Stroke Scale (NIH-SS).. There were 23 vascular events (11.7%) and 13 deaths (6.6%) to 1 year follow-up. In multivariate analyses of all markers, only high-sensitivity troponin T (hsTropT) remained independently predictive for vascular events (p=0.045) and all-cause mortality (p=0.004). hsTropT was higher in patients with a vascular event (median 12.7 ng/ml vs 5.1 ng/ml), and patients with hsTropT above the median of 6.15 ng/ml had vascular events more frequently (HR 3.86, p=0.008). For prediction of vascular events as well as all-cause mortality, hsTropT significantly improved multivariate Cox regression models with ESRS, SPI-2 or NIH-SS. The c-statistic increased non-significantly from 0.695 (ESRS) or 0.710 (hsTropT) to 0.747 (ESRS+hsTropT) and from 0.699 (SPI-2) to 0.763 (SPI-2+hsTropT). No patient with a low-risk ESRS and an hsTropT below the median had a vascular event or died.. hsTropT predicts vascular events and all-cause mortality in patients with acute cerebral ischaemia and improves prediction beyond established clinical scores.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Brain Ischemia; Cardiovascular Diseases; Cohort Studies; Endpoint Determination; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Stroke; Survival Analysis; Troponin; Troponin T

Recent studies have demonstrated that aldosterone levels measured in patients with heart failure or acute myocardial infarction (MI) are associated with long-term mortality, but the association with aldosterone levels in patients with coronary artery disease (CAD) outside these specific settings remains unknown. In addition, no clear mechanism has been elucidated to explain these observations. The present study was designed to evaluate the relationship between the level of aldosterone and the risk of death and acute ischaemic events in CAD patients with a preserved left ventricular (LV) function and no acute MI.. In 799 consecutive CAD patients referred for elective coronary angioplasty measurements were obtained before the procedure for: aldosterone (median = 25 pg/mL), brain natriuretic peptide (BNP) (median = 35 pg/mL), hsC-reactive protein (median = 4.17 mg/L), and left ventricular ejection fraction (mean = 58%). Patients with acute MI or coronary syndrome (ACS) who required urgent revascularization were not included in the study. The primary endpoint, cardiovascular death, occurred in 41 patients during a median follow-up period of 14.9 months. Secondary endpoints-total mortality, acute ischaemic events (acute MI or ischaemic stroke), and the composite of death and acute ischaemic events-were observed in 52, 54, and 94 patients, respectively. Plasma aldosterone was found to be related to BMI, hypertension and NYHA class, and inversely related to age, creatinine clearance, and use of beta-blockers. Multivariate Cox model analysis demonstrated that aldosterone was independently associated with cardiovascular mortality (P = 0.001), total mortality (P = 0.001), acute ischaemic events (P = 0.01), and the composite of death and acute ischaemic events (P = 0.004). Reclassification analysis, using integrated discrimination improvement (IDI) and net reclassification improvement (NRI), demonstrated incremental predictive value of aldosterone (P < 0.0001).. Our results demonstrate that, in patients with CAD but without heart failure or acute MI, the level of aldosterone is strongly and independently associated with mortality and the occurrence of acute ischaemic events.

Topics: Age Factors; Aged; Aldosterone; Angioplasty, Balloon, Coronary; Body Mass Index; Brain Ischemia; C-Reactive Protein; Coronary Artery Disease; Creatinine; Death, Sudden, Cardiac; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Stroke; Stroke Volume; Ventricular Function, Left

The prediction of death or disability ("poor outcome") after stroke by validated clinical models might be improved by the addition of blood biomarker measurements. We investigated whether such measurements improved the classification of patients into 4 categories of predicted risk of poor outcome: very high, intermediate high, intermediate low, and very low.. We prospectively recruited symptomatic patients within 24 hours of ischemic cerebrovascular events. We measured clinical prognostic variables in each patient. We drew blood soon after admission and measured markers of inflammation, thrombosis, cardiac strain, and cerebral damage. We assessed poor outcome at 3 months with the modified Rankin Scale and recovery of symptoms at 24 hours. We measured the association between blood marker levels and poor outcome after adjustment for stroke severity and age with multivariate logistic regression. Where these associations were statistically significant, we calculated the net reclassification index.. We recruited 270 patients with acute ischemic cerebrovascular events. At 3 months, 112 patients had a poor outcome. After adjustment for stroke severity and age, only interleukin-6 and N-terminal pro-brain natriuretic peptide were significantly associated with poor outcome. The addition of either interleukin-6 or N-terminal pro-brain natriuretic peptide to National Institutes of Health Stroke Scale and age did not improve the prediction of a poor outcome.. Neither interleukin-6 nor N-terminal pro-brain natriuretic peptide had sufficient predictive power to be of clinical use to predict poor outcome after stroke. The search for better markers to improve the classification of patients across clinically relevant boundaries of predicted probabilities of outcome events needs to continue.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Follow-Up Studies; Humans; Interleukin-6; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Severity of Illness Index; Stroke

Elevated serum levels of brain natriuretic peptide (BNP) have been associated with cardioembolic stroke and increased poststroke mortality. We sought to determine whether BNP levels were associated with functional outcome after ischemic stroke.. We measured BNP in consecutive patients aged ≥ 18 years admitted to our stroke unit between 2002 to 2005. BNP quintiles were used for analysis. Stroke subtypes were assigned using Trial of ORG 10172 in Acute Stroke Treatment criteria. Outcomes were measured as 6-month modified Rankin Scale score ("good outcome"=0-2 versus "poor") as well as mortality. Multivariate logistic regression was used to assess association between the quintiles of BNP and outcomes. Predictive performance of BNP as compared with clinical model alone was assessed by comparing receiver operating characteristic curves.. Of 569 patients with ischemic stroke, 46% were female; mean age was 67.9 ± 15 years. In age- and gender-adjusted analysis, elevated BNP was associated with lower ejection fraction (P<0.0001) and left atrial dilatation (P<0.001). In multivariate analysis, elevated BNP decreased the odds of good functional outcome (OR, 0.64; 95% CI, 0.41-0.98) and increased the odds of death (OR, 1.75; 95% CI, 1.36-2.24) in these patients. Addition of BNP to multivariate models increased their predictive performance for functional outcome (P=0.013) and mortality (P<0.03) after cardioembolic stroke.. Serum BNP levels are strongly associated with cardioembolic stroke and functional outcome at 6 months after ischemic stroke. Inclusion of BNP improved prediction of mortality in patients with cardioembolic stroke.

Topics: Aged; Brain; Brain Ischemia; Cohort Studies; Female; Follow-Up Studies; Heart Atria; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Recovery of Function; Stroke; Stroke Volume; Tomography, X-Ray Computed; Treatment Outcome

The aim of this study was to investigate the relation between brain natriuretic peptide (BNP) levels and the detection rate of new documented atrial fibrillation (AF) after ischemic stroke. Consecutive patients with ischemic stroke prospectively enrolled within 24 hours of onset. Patients with AF on admission electrocardiography or with histories of AF were excluded. The plasma BNP level was measured on admission, and the factors associated with new documented AF were investigated by multivariate logistic regression analysis. Furthermore, the detection rates of AF according to BNP level were evaluated. A total of 584 patients were enrolled. AF was detected in 40 patients (new AF group; 6.8%). The median BNP level of the new AF group was significantly higher than for the non-AF group (186.6 pg/ml [interquartile range 68.7 to 386.3] vs 35.2 pg/ml [interquartile range 15.9 to 80.1], p <0.0001). The cut-off level, sensitivity, and specificity of BNP levels to distinguish the new AF group from the non-AF group were 65.0 pg/ml, 80%, and 70%, respectively. Multivariate logistic regression analysis demonstrated that National Institutes of Health Stroke Scale score >7 (odds ratio 3.4, 95% confidence interval 1.685 to 7.006, p = 0.0007) and a plasma BNP level >65.0 pg/ml (odds ratio 6.8, 95% confidence interval 2.975 to 15.359, p <0.0001) were independently associated with new AF. The detection rates of AF according to BNP level were as follows: 2% of patients with <50 pg/ml, 4% of those with 50 to <100 pg/ml, 12% of those with 100 to <200 pg/ml, 26% of those with 200 to <400 pg/ml, and 38% of those with ≥400 pg/ml. In conclusion, BNP levels can predict new AF in patients with acute ischemic stroke. Elevated BNP levels result in an increase in the frequency of detection of new AF.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Hospitalization; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial

The risk of recurrent stroke is likely related to etiology. Therefore it is important to identify which patients are at highest early risk. We evaluated whether selected blood biomarkers may aid in the diagnosis of stroke etiology. We studied consecutive non-lacunar stroke patients between November 2006 and January 2007, and selected undetermined origin strokes. Blood samples were drawn at arrival to test brain natriuretic peptide (BNP), D-dimer, CK-MB, myoglobin, and troponin. Second harmonic transthoracic echocardiography (SHTTE) and ECG-24 h monitoring were also performed within the first 24 h. We evaluated 294 patients with ischemic stroke; 89 had an initial undetermined origin. After a cardiological work-up, 49 were diagnosed as embolic including atrial fibrillation (4), severe aortic arch atheromatosis (24), severe wall abnormalities (12), valve disease (3), dilated cardiomyopathy (1), and patent foramen (5). Higher levels of CK-MB, BNP, and myoglobin were found in patients with embolic source in SHTTE, but only CK-MB >1.5 ng/ml and BNP >64 pg/ml remained as independent predictors: BNP (OR 8.86; CI 95 % 2.79-28.09), CK-MB (OR 6.28; CI 95 % 1.66-23.69). BNP showed specificity of 75 %, sensitivity of 63.4 %, and positive predictive value (PPV) of 75.6 %. CK-MB had specificity of 85 %, sensitivity of 47.9 %, and PPV of 79.3 %. Measuring both biomarkers improves the finding of embolic source, increasing specificity to 95 % and PPV to 88.2 %. High-level CK-MB and BNP during the acute phase of ischemic stroke are associated with an embolic source. Measurement of both biomarkers may improve the diagnosis, guiding the need to perform a heart exploration.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Creatine Kinase, MB Form; Echocardiography; Embolism; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Stroke

Patients hospitalized with heart failure (HF) have elevated B-type natriuretic peptide (BNP) levels and increased risk for thromboembolic events. Associations between BNP level and thromboembolic events in patients with HF without atrial fibrillation (AF) are not well studied.. We linked data from the ADHERE registry for 2003 through 2006 with Medicare claims to identify patients ≥65 years who were hospitalized with HF, did not have AF, and did not receive warfarin at discharge. We estimated rates of all-cause mortality, thromboembolic events, myocardial infarction (MI), and stroke using Kaplan-Meier methods and the cumulative incidence function. We used Cox models to assess associations between log BNP level and each outcome after adjustment for potential confounders.. The study population included 11,679 patients from 146 sites. Patients in the highest quartile of BNP level were older and more often male and African American. They had higher rates of coronary artery disease, renal insufficiency, and peripheral vascular disease and lower rates of diabetes mellitus and chronic obstructive pulmonary disease. After multivariable adjustment, each 30% increase in BNP level was associated with increased risks of death (hazard ratio 1.07, 95% CI 1.05-1.08) and MI (1.07, 1.04-1.10) but not thromboembolism or stroke.. Higher BNP level upon admission with HF among older patients without AF was associated with increased risks of MI and mortality; however, higher BNP level was not associated with subsequent thromboembolism or stroke.

Topics: Aged; Aged, 80 and over; Brain Ischemia; Comorbidity; Data Collection; Female; Heart Failure; Hospitalization; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Registries; Stroke; Venous Thromboembolism

Determining the prognoses of patients with acute ischemic stroke is difficult. Therefore, the aim of this study was to evaluate whether the combined assessment of plasma N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and the National Institutes of Health Stroke Scale (NIHSS) variables is relevant to the prognosis of patients with acute cerebral ischemic infarction in-hospital.. We enrolled 122 patients who were within three days of onset of acute ischemic stroke. We measured the plasma NT-pro-BNP level of each patient within 72 hours and recorded the NIHSS score on admission. The factors associated with death were investigated using a multivariate logistic regression analysis.. Twenty-three patients (18.85%) died during hospitalization. The frequency of atrial fibrillation (AF), the NIHSS score on admission (8.69±4.87 in the survival group vs. 14.48±2.54 in the deceased group, p<0.001) and the plasma NT-pro-BNP level (median: 926.30 pg/mL in the survival group vs. 3,280 pg/mL in the deceased group, p<0.001; Lg NT-pro-BNP 2.82±0.66 in the survival group vs. 3.46±0.52 in the deceased group, p<0.001) were each significantly higher in the deceased group than in the survival group. The optimal cut-off levels for the NT-pro-BNP level and NIHSS score to distinguish the deceased group from the survival group were 1,583.50 pg/mL and 12.5, respectively. Patients with both elevated NT-pro-BNP levels (>1,583.50 pg/mL) and NIHSS scores on admission (NIHSS >12.5) had a substantially higher mortality rate than those without elevated NT-pro-BNP levels and NIHSS scores (89.47% vs. 9.84%, p<0.001). A multivariate logistic regression analysis demonstrated that a NT-pro-BNP level >1,583.50 pg/mL (OR, 5.001; 95% CI, 1.233 to 20.287, p=0.024) and a NIHSS score >12.5 (OR, 1.465; 95% CI, 1.191 to 1.801, p<0.001) were each independent factors associated with in-hospital death.. The plasma NT-pro-BNP level and the NIHSS score added independent and incremental contributions to the prognostic stratification of patients with acute ischemic stroke.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Humans; Male; Middle Aged; National Institutes of Health (U.S.); Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Severity of Illness Index; Stroke; United States

atrial fibrillation (AF) is the most powerful predictor of early death in patients with acute ischaemic stroke. We investigated whether the plasma brain natriuretic peptide (BNP) level on admission can serve as a biological marker of in-hospital death in acute ischaemic stroke and transient ischaemic attack (TIA) patients with AF.. we prospectively enrolled ischaemic stroke and TIA patients with AF within 24 h of onset and measured plasma BNP on admission. Patients were divided into two groups: the deceased group, who died during hospitalization, and the survival group. The factors associated with in-hospital death were investigated by multivariate logistic regression analysis.. a total of 221 patients with AF were enrolled. Death occurred in 24 (10.9%) patients. The mean ± SD of the plasma BNP level of the deceased group was significantly higher than that of the survival group (714.1 ± 716.3 vs. 320.0 ± 380.7 pg/ml, P < 0.0001). The optimal cutoff level, sensitivity, and specificity of BNP levels to distinguish the deceased group from the survival group were 320 pg/ml, 79.2, and 69.0%, respectively. Multivariate logistic regression analysis demonstrated that age per 10 years increase (OR, 3.56; 95% CI, 1.728-7.346, P = 0.0006), internal carotid artery occlusion (OR, 10.20; 95% CI, 2.525-41.177, P = 0.0011), NIHSS score of >17 (OR, 4.68; 95% CI, 1.137-19.286, P = 0.0325), and plasma BNP level of > 320 pg/ml (OR, 4.74; 95% CI, 1.260-17.800, P = 0.0213) were independent factors associated with in-hospital death.. the plasma BNP level on admission can predict in-hospital death in acute ischaemic stroke and TIA patients with AF.

Topics: Age Factors; Aged; Aged, 80 and over; Atrial Fibrillation; Brain Ischemia; Female; Hospitalization; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Prognosis; Prospective Studies; Risk Factors; Statistics, Nonparametric; Stroke

To investigate comorbidities that predict cardiac mortality and re-hospitalization in chronic heart failure (CHF) patients.. Five hundred eighty patients (mean age 63 ± 13 years, 373 male, 207 female, mean ejection fraction (EF) 26 ± 9%) with mild, moderate or severe CHF [NYHA class II-IV] were included in this prospective observational study. We evaluated all comorbidities such as history of ischemic stroke, coronary artery disease, peripheral arterial disease, chronic obstructive lung disease, hypertension, diabetes mellitus and chronic kidney disease in CHF patients who were hospitalized due to decompensated heart failure in Kocaeli University, Faculty of Medicine's Hospital between January 2003 and July 2009. Cox regression and Kaplan-Meier survival analyses were used to establish predictors of unfavorable outcomes.. Of 580 patients 207 (36%) patients died due to cardiovascular reasons. In multivariable Cox regression analysis age (HR-1.06, 95% CI 1.04-1.08, p<0.001), NYHA functional class (HR-3.20 95% CI, 1.90-5.41, p<0.001), history of ischemic stroke (HR-2.48, 95% CI 1.14-5.37, p=0.022), high-sensitive C-reactive protein (HR-1.09, 95% CI, 1.04-1.15, p=0.001), brain natriuretic peptide (HR-1.00, 95% CI 1.00-1.00, p=0.01) and hemoglobin (HR-0.90, 95% CI 0.81-0.99, p=0.038) were independent predictors of cardiac death in the present study. History of ischemic stroke was demonstrated as an important comorbidity that predicts cardiovascular mortality beyond other co-morbidities in CHF patients. NYHA functional class (HR-2.85, 95% CI 1.80-4.65, p<0.001), left ventricular EF [(HR-0.98, 95% CI 0.95-0.99, p=0.039) and ischemic stroke history (HR-2.41, 95% CI 1.15-5.05, p=0.019) were independent predictors for recurrence hospitalization. The stroke history was only predictor showing recurrent hospitalization at least in one year among the other comorbid conditions, which were evaluated during study.. History of ischemic stroke may be an important risk factor for increased cardiac mortality and recurrence hospitalization in CHF patients.

Topics: Aged; Brain Ischemia; Cardiovascular Diseases; Chronic Disease; Comorbidity; Female; Heart Failure; Hemoglobins; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors; Stroke; Turkey

Stroke is an emergency which threatens life and the third leading cause of death in developed countries and the leading cause of long-term disability. By means of this study, it was aimed to evaluate the position of triage stroke panel in differential diagnosis of acute hemorrhagic stroke and ischemic stroke and sub-types of ischemic stroke.. Patients with acute stroke admitted to Emergency Department were prospectively recruited between June 2008-January 2009. BNP, D-dimer, MMP-9, S-100b levels were asseyed. Statistical significance for intergroup differences was assessed by Pearson's chi2 for categorical variables and Mann-Whitney U test or Kruskal-Wallis test for continuous variables.. A total of 100 consecutive patients with a diagnosis of stroke were evaluated. Of these, 29 (29%) patients had brain hemorrhages on the computed tomography scan performed the Emergency Department, 71 (71%) patients had ischemic stroke. It was observed that the intercept obtained as a result of jointly evaluating BNP, D-dimer, MMP9 and S100b is more important in differential diagnosis (p < 0.005). We suggest that using a combination of plasma biomarkers may be usefull to ischemic or hemorrhagic stroke for differential diagnosis (Tab. 4, Ref. 22).

Topics: Aged; Biomarkers; Brain Ischemia; Diagnosis, Differential; Female; Fibrin Fibrinogen Degradation Products; Humans; Intracranial Hemorrhages; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; S100 Proteins; Stroke

We tested the hypothesis that, in elderly survivors of ischemic stroke, high NT-proBNP levels are related with frequent diastolic dysfunction. We prospectively measured NT-proBNP, left ventricular ejection fraction (LVEF) and echographic parameters of diastolic function in 55 elderly consecutive patients, 6.8+/-2.6 days after acute ischemic stroke. We found that all the patients had systolic or diastolic dysfunction (14 had LVEF<50%, 26 mild diastolic dysfunction+LVEF > or = 50%, and 15 moderate or severe diastolic dysfunction+LVEF > or = 50%). The most powerful predictors of NT-proBNP were LVEF (R=0.38, p=0.004) and ratio of mitral E to the early diastolic velocity of the mitral annulus:E/E'(R=0.34, p=0.01).

Topics: Aged; Aged, 80 and over; Brain Ischemia; Diastole; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Ventricular Dysfunction, Left

We investigated whether the brain natriuretic peptide (BNP) level can serve as a predictive biological marker of delayed atrial fibrillation (AF).. Two hundred and thirty seven consecutive patients admitted to our institution with acute ischaemic stroke or transient ischaemic attack (TIA) within 24 h of onset were enrolled. The patients were classified according to the presence or absence of AF upon admission [AF and sinus rhythm (SR) groups]. The SR group was subdivided based on the development of AF after admission (new- and non-AF groups). We compared the characteristics between the AF and SR groups, and between the new- and non-AF groups. The factors associated with new-AF were investigated by multivariate logistic regression analysis.. Amongst the enrolled patients, 72 (30.4%) had AF upon admission (AF group), and 13 (5.5%) developed AF thereafter (new-AF group). The plasma BNP level was significantly higher in the AF, than in the SR group (401.7 vs. 92.1 pg/ml, P < 0.001). Moreover, the plasma BNP level was significantly higher in the new-, than in the non-AF group (184.7 vs. 84.1 pg/ml, P < 0.001). The optimal cutoff BNP level required to distinguish new-, from non-AF groups was 85.0 pg/ml, and the sensitivity and specificity was 83.3% and 76.2%, respectively. On multivariate logistic regression analysis, plasma BNP level >85.0 pg/ml (odds ratio, 7.20; 95% confidence interval, 1.71 to 30.43, P = 0.007) was an independent factor associated with new-AF.. High plasma BNP level should be a strong predictor of delayed AF after ischaemic stroke or TIA.

Topics: Acute Disease; Aged; Atrial Fibrillation; Biomarkers; Brain Ischemia; Female; Humans; Ischemic Attack, Transient; Logistic Models; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors; ROC Curve; Stroke; Time Factors

In acute stroke patients treated with intravenous tissue plasminogen activator (t-PA), early recanalization can improve patient outcome. Heart failure may result in reduction of brain perfusion, which limits the ability of the blood stream to wash out emboli. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. Most stroke patients with atrial fibrillation (AF) have elevated BNP levels. We investigated the relationships of plasma BNP levels before t-PA infusion and AF with early recanalization after t-PA infusion.. Patients with a major brain artery occlusion were studied prospectively. MRAs were performed before and within 60 min after t-PA infusion. The relationship between BNP levels before t-PA infusion and the presence of AF with early recanalization was examined.. Seventy-nine patients (49 men; mean age, 75.5+/-10.4 years; ICA occlusion in 25 patients, M1 in 32, M2 in 13, PCA in 3, and BA in 6) were enrolled. Follow-up MRA within 60 min after t-PA infusion revealed recanalization in 35 (44.3%) patients and no recanalization in 44 (55.7%). Patients with AF (57.1% vs. 75.0%, P=0.0294) and BNP>150pg/dl (39.0% vs. 73.7%, P=0.0019) less frequently had early recanalization than those without AF and with BNP< or =150pg/dl. The combination of AF and BNP>150pg/ml was a useful predictor for no early recanalization (positive predictive value, 79.4%; negative predictive value, 62.2%; sensitivity, 61.4%; specificity, 80.0%).. The presence of AF and elevated BNP was associated with no early recanalization after IV-t-PA therapy. We should need further study to ascertain its predictive ability.

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain; Brain Ischemia; Cerebrovascular Circulation; Female; Fibrinolytic Agents; Heart Failure; Humans; Intracranial Embolism; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Stroke; Time Factors; Tissue Plasminogen Activator; Treatment Failure; Up-Regulation

Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) has been reported as a predictor for ischemic stroke in general population. However, predictive value of plasma NT-proBNP for acute ischemic stroke in patients on chronic hemodialysis has not been well established. The aim of this study was to determine whether NT-proBNP could predict acute ischemic stroke in patients on chronic hemodialysis.. This study was designed prospectively. Clinical, laboratory, and echocardiographic variables were assessed in 72 patients on chronic hemodialysis. The plasma levels of NT-proBNP were measured by immunoassay.. During the follow-up period of 45 months, 11 patients had an acute ischemic stroke. The Kaplan-Meier plot showed an increased frequency of acute ischemic stroke in patients with plasma levels of NT-proBNP above the median values compared to patients with lower concentrations (P = 0.028). The multivariate Cox proportional hazard models showed that the NT-proBNP was a significant independent predictor of acute ischemic stroke after adjustment for age, sex, mean blood pressure, diabetes, serum cholesterol levels, left ventricular mass index, and left ventricular fractional shortening (HR 6.66, 95% CI, 1.22-36.48, P = 0.029).. Our data suggest that plasma NT-proBNP levels predict the risk of acute ischemic stroke in patients on chronic hemodialysis.

Topics: Acute Disease; Brain Ischemia; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Renal Dialysis; Risk Factors; Stroke

Increased circulating amino-terminal pro-B-type natriuretic (NT-proBNP) levels are a marker of cardiac dysfunction but also associate with coronary heart disease and stroke. We aimed to investigate whether increased circulating NT-proBNP levels have additive prognostic value for first cardiovascular and cerebrovascular events beyond classic risk factors. In a community-based cohort of 5063 participants free of cardiovascular disease, aged > or =55 years, circulating NT-proBNP levels and cardiovascular risk factors were measured. Participants were followed for the occurrence of first major fatal or nonfatal cardiovascular event. A total of 420 participants developed a first cardiovascular event (108 fatal). After adjustment for classic risk factors, the hazard ratio for cardiovascular events was 2.32 (95% CI: 1.55 to 2.70) in men and 3.08 (95% CI: 1.91 to 3.74) in women for participants with NT-proBNP in the upper compared with the lowest tertile. Corresponding hazard ratios for coronary heart disease, heart failure, and ischemic stroke were 2.01 (95% CI: 1.14 to 2.59), 2.90 (95% CI: 1.33 to 4.34), and 2.06 (95% CI: 0.91 to 3.18) for men and 2.95 (95% CI: 1.30 to 4.55), 5.93 (95% CI: 2.04 to 11.2), and 2.07 (95% CI: 1.00 to 2.97) for women. Incorporation of NT-proBNP in the classic risk model significantly improved the C-statistic both in men and women and resulted in a net reclassification improvement of 9.2% (95% CI: 3.5% to 14.9%; P=0.001) in men and 13.3% (95% CI: 5.9% to 20.8%; P<0.001) in women. We conclude that, in an asymptomatic older population, NT-proBNP improves risk prediction not only of heart failure but also of cardiovascular disease in general beyond classic risk factors, resulting in a substantial reclassification of participants to a lower or higher risk category.

Topics: Aged; Blood Pressure; Brain Ischemia; Cardiovascular Diseases; Coronary Disease; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Predictive Value of Tests; Proportional Hazards Models; Risk Factors; Sex Distribution; Stroke

One of the significant limitations in the evaluation and management of patients with suspected acute cerebral ischemia is the absence of a widely available, rapid, and sensitive diagnostic test. The objective of the current study was to assess whether a test using a panel of biomarkers might provide useful diagnostic information in the early evaluation of stroke by differentiating patients with cerebral ischemia from other causes of acute neurological deficit.. A total of 1146 patients presenting with neurological symptoms consistent with possible stroke were prospectively enrolled at 17 different sites. Timed blood samples were assayed for matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and protein S100beta. A separate cohort of 343 patients was independently enrolled to validate the multiple biomarker model approach.. A diagnostic tool incorporating the values of matrix metalloproteinase 9, brain natriuretic factor, d-dimer, and S-100beta into a composite score was sensitive for acute cerebral ischemia. The multivariate model demonstrated modest discriminative capabilities with an area under the receiver operating characteristic curve of 0.76 for hemorrhagic stroke and 0.69 for all stroke (likelihood test P<0.001). When the threshold for the logistic model was set at the first quartile, this resulted in a sensitivity of 86% for detecting all stroke and a sensitivity of 94% for detecting hemorrhagic stroke. Moreover, results were reproducible in a separate cohort tested on a point-of-care platform.. These results suggest that a biomarker panel may add valuable and time-sensitive diagnostic information in the early evaluation of stroke. Such an approach is feasible on a point-of-care platform. The rapid identification of patients with suspected stroke would expand the availability of time-limited treatment strategies. Although the diagnostic accuracy of the current panel is clearly imperfect, this study demonstrates the feasibility of incorporating a biomarker based point-of-care algorithm with readily available clinical data to aid in the early evaluation and management of patients at high risk for cerebral ischemia.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Cerebral Hemorrhage; Cohort Studies; Female; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Nerve Growth Factors; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; S100 Calcium Binding Protein beta Subunit; S100 Proteins; Stroke; Time Factors; Young Adult

Congestive heart failure is a risk factor for ischemic stroke. Brain natriuretic peptide (BNP) is used as a biological marker of heart failure. We hypothesized that heart failure was associated with the onset of ischemic stroke patients with atrial fibrillation (AF).. Between June 2006 and December 2007, we prospectively enrolled consecutive acute ischemic stroke patients with AF within 24 h of onset. Plasma BNP was measured twice, on admission and on days 28 or at discharge. As a control, we measured plasma BNP of chronic phase of stroke outpatients with AF. We investigated whether plasma BNP was elevated in the acute phase of stroke.. One hundred and nine patients (58 females; mean age, 76.3 years) were enrolled in the present study. Mean+/-SD of NIHSS score on admission and mRS score at discharge were 12.6+/-8.3 and 3.7+/-1.8, respectively. The interval from stroke onset to plasma BNP measurement on admission was 6.8+/-6.3 h. Moreover, follow up BNP was measured at mean of 26+/-9 days after stroke onset. The plasma BNP level in the acute phase of stroke was significantly higher than that of the subacute phase of stroke (median (interquartile range, IQR) 299.0 (176.8-469.5) vs. 149.5 (68.1-347.0) pg/ml, p<0.001). There was no significant difference in plasma BNP level between the subacute phase of stroke and control group (median (IQR) 149.5 (68.1-347.0) vs. 165.0 (64.6-224.0) pg/ml, p=0.543).. Plasma BNP was elevated in the acute phase of stroke. Heart failure may be associated with the onset of ischemic stroke patients with AF.

Topics: Aged; Atrial Fibrillation; Brain Ischemia; Diabetes Complications; Female; Heart Failure; Humans; Hyperlipidemias; Hypertension; Linear Models; Longitudinal Studies; Male; Natriuretic Peptide, Brain; Risk Factors; Smoking; Stroke

High levels of B-type natriuretic peptide (BNP), a serum marker of congestive heart failure, are associated with an increased risk for cognitive decline. However, no study has yet assessed this marker in different subtypes of dementia. We tested the hypothesis that BNP has a more significant association with vascular dementia than Alzheimer disease. Plasma BNP was measured in 15 patients with subcortical vascular dementia, in 19 Alzheimer patients without evidence of vascular comorbidity, and in age-matched controls. Compared with controls (28+/-7 ng/l), BNP was elevated in subcortical vascular dementia (63+/-17 ng/l; P=0.03), but not in Alzheimer disease (36+/-5 ng/l). In conclusion, subcortical vascular dementia is indeed associated with moderately elevated BNP levels, whereas this could not be shown for Alzheimer disease. This probably reflects the larger cardiovascular burden in patients with subcortical vascular dementia.

Topics: Aged; Alzheimer Disease; Biomarkers; Brain; Brain Ischemia; Causality; Cerebral Arteries; Cerebrovascular Circulation; Comorbidity; Dementia, Vascular; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Up-Regulation

Structural heart diseases including atrial fibrillation are precursors for ischemic stroke. Plasma B-type natriuretic peptide (BNP) has been reported to be increased in patients with several types of structural heart diseases. However, the predictive value of plasma BNP for ischemic stroke remains unknown. We have studied the predictive ability of plasma BNP for future development of stroke in community dwelling adults.. Subjects of this community-based study were recruited from the general population (n=13,466). Plasma BNP levels and cardiovascular risk factors were determined at baseline. The incidence of ischemic stroke in the cohort was identified from regional stroke registry data. A multivariate Cox regression analysis was performed to analyze the relationship between plasma BNP levels and the risk of stroke.. During a mean follow-up period of 2.8 years, 102 participants (65 males, 37 females) experienced a first ischemic stroke. In men, after adjustment for classical cardiovascular risk factors and atrial fibrillation, the hazard ratio (HR) for ischemic stroke was significantly elevated in the highest plasma BNP quartile (HR=2.38; 95% CI=1.07-5.29). In women, the relationship between plasma BNP levels and risk of ischemic stroke was of marginal significance after adjusting for the presence or absence of atrial fibrillation (HR=3.03; 95% CI=0.84-10.92, P=0.09).. Elevated plasma BNP levels predict the risk of ischemic stroke within men from the general population.

Topics: Aged; Biological Factors; Brain Ischemia; Female; Humans; Incidence; Japan; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Registries; Risk Assessment; Risk Factors; Sex Factors; Stroke; Up-Regulation

Acute-phase levels of B-type natriuretic peptide (BNP) and the N-terminal fragment of the BNP prohormone (NT-pro-BNP) have been associated with mortality when measured in patients with an acute ischemic stroke; however, data regarding the longer-term value of NT-pro-BNP for long-term prognostication after ischemic stroke are limited. Two hundred sixteen patients (mean age 67 +/- 13 years) with acute ischemic stroke were seen 6 months after index admission at which time a structured evaluation including measurement of plasma NT-pro-BNP was performed. Patients were followed for 45 months, with all-cause mortality as the clinical end point. Median NT-pro-BNP concentration for the entire group was 147 pg/ml (10th to 90th percentiles 37 to 869). At follow-up 45 patients (21%) had died. NT-pro-BNP concentrations were significantly higher in decedents (308 pg/ml, 10th to 90th percentiles 74 to 2,279) than in the 171 survivors (132 pg/ml, 10th to 90th percentiles 35 to 570, p <0.001). Patients with NT-pro-BNP < or =147 pg/ml had a significantly improved survival rate on univariate analysis (p <0.001). In multivariate analysis after adjustment for age, stroke severity, heart and renal failures, levels of NT-pro-BNP were an independent predictor of mortality >6 months after stroke (adjusted hazard ratio 1.5, 95% confidence interval 1.1 to 1.9, p = 0.005). In conclusion, NT-pro-BNP concentrations measured during the stable phase after acute ischemic stroke are strongly predictive of long-term mortality.

Topics: Acute Disease; Aged; Area Under Curve; Brain Ischemia; Confidence Intervals; Denmark; Female; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Prognosis; Prospective Studies; Risk Assessment; ROC Curve; Sensitivity and Specificity; Stroke; Time Factors

Because there is no biologic marker offering precise information about stroke etiology, many patients receive a diagnosis of undetermined stroke even after all available diagnostic tests are done, precluding correct treatment.. To examine the diagnostic value of a panel of biochemical markers to differentiate stroke etiologies, consecutive acute stroke patients were prospectively evaluated. Brain computed tomography, ultrasonography, cardiac evaluations, and other tests were done to identify an etiologic diagnosis according to TOAST classification. Blood samples were drawn on Emergency Department arrival (<24 hours) to test selected biomarkers: C-reactive protein, D-dimer, soluble receptor for advanced glycation end products, matrix metalloproteinase-9, S-100b, brain natriuretic peptide (BNP), neurotrophin-3, caspase-3, chimerin, and secretagogin (assayed by ELISA).. Of 707 ischemic stroke patients included, 36.6% were cardioembolic, 21.4% atherothrombotic, 18.1% lacunar, and 23.9% of undetermined origin. High levels of BNP, soluble receptor for advanced glycation end products, and D-dimer (P<0.0001) were observed in patients with cardioembolic stroke. Independent predictors (odds ratios with CIs are given) of cardioembolic stroke were as follows: atrial fibrillation 15.3 (8.4-27.7, P<0.001); other embolic cardiopathies 14.7 (4.7-46, P<0.001); total anterior circulation infarction 4 (2.3-6.8, P<0.001); BNP >76 pg/mL 2.3 (1.4-3.7, P=0.001); and D-dimer >0.96 microg/mL 2.2 (1.4-3.7, P=0.001). Even among patients with transient symptoms (n=155), a high BNP level identified cardioembolic etiology (6.7, 2.4-18.9; P<0.001). A model combining clinical and biochemical data had a sensitivity of 66.5% and a specificity of 91.3% for predicting cardioembolism.. Using a combination of biomarkers may be a feasible strategy to improve the diagnosis of cardioembolic stroke in the acute phase, thus rapidly guiding other diagnostic tests and accelerating the start of optimal secondary prevention.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; C-Reactive Protein; Calcium-Binding Proteins; Caspase 3; Chimerin Proteins; Coronary Vessels; Female; Fibrin Fibrinogen Degradation Products; Humans; Intracranial Embolism; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Neurotrophin 3; Predictive Value of Tests; Prospective Studies; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Risk Factors; Secretagogins; Sensitivity and Specificity; Severity of Illness Index; Stroke

Takotsubo cardiomyopathy, which is characterized by transient left ventricular apical ballooning, is a known complication of subarachnoid hemorrhage. The aim of this study was to identify the clinical characteristics of acute ischemic stroke patients who experienced development of takotsubo cardiomyopathy.. Seven patients who were diagnosed as having takotsubo cardiomyopathy based on their electrocardiographic and echocardiographic findings were studied. They were selected from among 569 consecutive patients who were admitted to our stroke center within 24 hours after onset of acute ischemic stroke. The findings of nine previously published cases were also reviewed.. All seven patients were women, and six were 75 years or older. The initial National Institutes of Health Stroke Scale score ranged from 3 to 28. The culprit infarcts included or were close to the insular cortex in six patients and were located extensively in the vertebrobasilar arterial territory in the other patient. Abnormal findings on electrocardiographic monitoring appeared within 10 hours after stroke onset in five patients and at 6 and 12 days, respectively, in the other two patients. The cardiomyopathy was symptomatic in only two patients. Plasma brain natriuretic peptide levels exceeded the upper normal limit by 10-fold in all patients. The previously published cases were mostly women and had mainly vertebrobasilar stroke.. Takotsubo cardiomyopathy is not a rare complication of acute ischemic stroke. It most often occurred soon after stroke onset and was commonly asymptomatic. Female sex and insular damage were predominant features of the stroke patients who experienced development of takotsubo cardiomyopathy.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Brain Stem; Brain Stem Infarctions; Cerebral Cortex; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Stroke; Takotsubo Cardiomyopathy; Vertebrobasilar Insufficiency

Cardioembolic stroke generally results in severer disability, since it typically has a larger ischemic area than the other types of ischemic stroke. However, it is difficult to differentiate cardioembolic from noncardioembolic stroke (atherothrombotic and lacunar stroke), whenever ischemic stroke patients have sinus rhythm at the time of presentation.. In this study, we evaluated the levels of plasma brain natriuretic peptide in acute ischemic stroke patients with cardioembolic or noncardioembolic stroke and assessed whether this could provide a basis for differentiating cardioembolic stroke (especially due to paroxysmal atrial fibrillation) from noncardioembolic stroke. Our patient cohort consisted of 99 consecutive patients with acute cerebral infarction who were admitted to Kagawa University School of Medicine Hospital from January 1, 2005, to December 31, 2006. We excluded 23 patients with valve disease, heart failure, myocardial infarction or chronic renal failure. The mean age of the remaining 76 patients (51 males, 25 females) was 70.0 +/- 10.1 years.. Thirty-six patients had cardioembolic stroke with atrial fibrillation (including permanent and paroxysmal atrial fibrillation); the remaining 40 had noncardioembolic stroke. The plasma brain natriuretic peptide was evaluated on the first morning after admission in all patients. In cardioembolic stroke with atrial fibrillation (permanent and paroxysmal atrial fibrillation), the plasma brain natriuretic peptide, ratio of peak early filling velocity to peak atrial systolic velocity (E/A) and left atrial diameter were significantly increased (p < 0.001), and the left atrial appendage flow was significantly decreased (p < 0.001), compared with noncardioembolic stroke. Analyzed in those 4 factors, cardioembolic stroke was strongly predicted with >95% accuracy assessed by plasma brain natriuretic peptide and left atrial appendage flow.. From our results, it was suggested that the first-day brain natriuretic peptide and left atrial appendage flow measurements would be helpful in differentiating cardioembolic stroke with atrial fibrillation from noncardioembolic stroke.

Topics: Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain Ischemia; Cohort Studies; Diagnosis, Differential; Echocardiography; Female; Humans; Intracranial Embolism; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Sensitivity and Specificity; Stroke; Stroke Volume; Ventricular Function, Left

We tested the hypothesis that plasma brain natriuretic peptide (BNP) levels are elevated in patients with acute cerebrovascular diseases (CVD) independent of heart disease, and reflect CVD severity. After careful evaluations for heart disease, the study included 79 consecutive patients with CVD without any evidence of heart disease admitted within 48 h after onset (71+/-10 years), and 26 control subjects without CVD (CT, 67+/-12 years). Ischemic stroke subtypes were defined by the TOAST classification. Large-artery atherosclerosis (LAA, n=27), small-artery occlusion (SAO, n=27), and intracerebral hemorrhage (ICH, n=25) were included. The plasma BNP levels were measured at admission and 1 month later. Stroke severity and brain infarct volume were evaluated. There were no significant differences in the clinical profiles including echocardiographic parameters among the groups. The plasma BNP level (pg/mL) upon admission was higher in LAA (70.6+/-53.9) than in SAO (38.2+/-28.4) and CT (28.5+/-19.9) (both p<0.05). The level in ICH (47.3+/-28.6) was not significantly different from that in CT. The BNP level in ischemic stroke was positively correlated with the NIH Stroke Scale (NIHSS) (rho=0.42, p<0.05) and infarct volume (r=0.34, p<0.05). Brain infarct volume and NIHSS were independent contributors to the plasma BNP level in ischemic stroke. One month later, the BNP level was significantly decreased and was similar in all CVD groups. The plasma BNP level transiently increased in patients with LAA independently of heart disease, and reflected infarct volume and the severity of acute ischemic stroke.

Topics: Acute Disease; Aged; Aged, 80 and over; Brain Ischemia; Cerebral Hemorrhage; Cerebral Infarction; Echocardiography; Female; Heart Diseases; Humans; Intracranial Arteriosclerosis; Male; Middle Aged; Natriuretic Peptide, Brain; Severity of Illness Index; Stroke

Adrenomedullin (AM), a vasorelaxant peptide, is secreted into the cerebrospinal fluid (CSF) from the choroid plexus and can exert natriuretic effects in the kidney. CSF AM concentration is elevated 7-10 days after the onset of aneurysmal subarachnoid hemorrhage (SAH). The aim of the present study was to determine whether CSF AM concentrations correlate with hyponatremia and delayed ischemic neurological deficits (DIND) after SAH.. CSF and plasma concentrations of AM, brain natriuretic peptide, and atrial natriuretic peptide concentrations were measured in 32 patients with SAH who underwent aneurysmal clipping within 48 h of onset. CSF and blood samples were obtained from these patients during the early period (days 1-3, day 0 being regarded as the day of SAH onset) and the late period (days 8-10).. In all patients, AM concentration during the early and late periods was significantly higher in the CSF than in the plasma (p = 0.0028 and p < 0.0001). In addition, CSF AM concentration was significantly higher during the late period than during the early period (p < 0.0001). Hyponatremia (plasma sodium <135 mmol/l) was present in 11 patients (34.4%) during the late period, and DIND developed in 6 patients (19%) between day 5 and day 13. Logistic regression analysis demonstrated that late-period CSF AM concentration correlated with hyponatremia and DIND (95% CI: 1.003-1.069, p = 0.0074 and 95% CI: 1.003-1.052, p = 0.0108).. The present study demonstrated that CSF AM during the late period following SAH correlates with hyponatremia and DIND.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Brain Ischemia; Case-Control Studies; Cohort Studies; Female; Humans; Hyponatremia; Intracranial Aneurysm; Male; Middle Aged; Natriuretic Peptide, Brain; Subarachnoid Hemorrhage; Time Factors

Stroke is sometimes seen in patients with congestive heart failure (CHF). The factors that best predict incident stroke in hospitalized CHF patients are not well known. We performed this pilot study to explore the clinical markers of incident stroke in CHF patients. We studied 111 hospitalized patients with CHF (mean age, 67+/-11 years). Ambulatory blood pressure (BP) monitoring, blood tests, and echocardiography were performed in these patients just before they left the hospital, and all cardiovascular events during the study period were followed for an average of 18+/-9 months. Cox regression analysis was performed to explore the predictors of incident stroke using age, sex, body mass index (BMI), casual and ambulatory systolic BP (SBP), and brain-type natriuretic peptide (BNP). There were 10 stroke events (9%) during the follow-up period. The stroke group had higher nocturnal SBP and plasma BNP levels than the non-stroke group. With Cox regression analysis, both nocturnal SBP and BNP were significant predictors of incident stroke independent of other covariates. When nocturnal BP of 120 mmHg and BNP of 600 pg/mL (75th percentile) were used as cutoffs, nocturnal SBP > or =120 mmHg was associated with a 7-fold increase in the risk of incident stroke, while BNP > or =600 pg/mL was associated with a 46.6-fold increase. However, abnormal circadian BP patterns were not associated with incident stroke. In this pilot study, elevated nocturnal BP and high plasma BNP just before patients left the hospital were significant predictors of stroke events in CHF patients. Further study is needed to confirm this hypothesis.

Topics: Aged; Blood Pressure; Brain Ischemia; Circadian Rhythm; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Pilot Projects; Stroke

Anaemia is a negative prognostic factor for patients with heart failure and impaired renal function, but its role in stroke patients is unknown. Furthermore, anaemia has been shown to influence the level of N-terminal pro-brain natriuretic peptide (NT-proBNP), but this is only investigated in patients with heart failure, not in stroke patients. Two-hundred-and-fifty consecutive, well-defined ischemic stroke patients were investigated. Mortality was recorded at 6 months follow-up. Anaemia was diagnosed in 37 patients (15%) in whom stroke severity was worse than in the non-anaemic group, whilst the prevalence of renal affection, smoking and heart failure was lower. At 6 months follow-up, 23 patients were dead, and anaemia had an odds ratio of 4.7 when adjusted for age, Scandinavian Stroke Scale and a combined variable of heart and/or renal failure and/or elevation of troponin T using logistic regression. The median NT-proBNP level in the anaemic group was significantly higher than in the non-anaemic group, and in a multivariate linear regression model, anaemia remained an independent predictor of NT-proBNP. Conclusively, anaemia was found to be a negative prognostic factor for ischemic stroke patients. Furthermore, anaemia influenced the NT-proBNP level in ischemic stroke patients, an important aspect when interpreting NT-proBNP in these patients.

Topics: Aged; Aged, 80 and over; Anemia; Brain Ischemia; Causality; Comorbidity; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Regional Blood Flow; Renal Insufficiency; Stress, Physiological; Stroke

Plasma levels of brain natriuretic peptide (BNP) are frequently elevated after an acute stroke and have been shown to be an independent predictor of mortality. However, the relationships between stroke and BNP concentrations have not yet been systematically investigated. Plasma BNP assay and echocardiography were performed in 48 patients with ischemic stroke or TIA with a mean delay of 12.7 h after onset. Median BNP concentration was 88.6 pg/mL (range 5-1270). Older age, chronic heart failure, atrial fibrillation, stroke severity, lower hemoglobin levels, lower left ventricular ejection fraction, and abnormalities of left atrium or appendage (LA/LAA) were univariately associated with increased BNP levels. At multivariable analysis, the presence of at least one LA/LAA abnormality (atrial dilatation, low flow velocity, spontaneous echocontrast or thrombus) had the strongest association with BNP, explaining 38.9% of the variance in the whole sample and 28.5% in patients without atrial fibrillation. In acute ischemic stroke patients, elevated plasma BNP levels have multiple determinants, among which left atrial disease appears to be the stronger, even in patients without atrial fibrillation. These results encourage further investigation of plasma BNP concentration as a potential marker of the presence of left atrial sources of emboli.

Topics: Acute Disease; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Brain; Brain Ischemia; Echocardiography; Female; Heart; Heart Failure; Humans; Intracranial Embolism; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Stroke; Up-Regulation

ST-segment depression and T-wave inversion (ST-T changes) in the electrocardiogram (ECG) and raised levels of natriuretic peptide have been observed in acute ischemic stroke patients. It is unknown whether any relation between ST-T changes and raised levels of natriuretic peptides in patients with an acute ischemic stroke exists.. Serial measurements of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and 12-lead ECGs were obtained in 192 consecutive patients with an acute ischemic stroke without ischemic heart disease, atrial fibrillation, heart- or renal failure.. ST-T changes suggestive of myocardial ischemia were observed in the 12 lead ECG of 47 patients (24%). In uni- and multivariate regression analysis after adjustment for age, stroke severity, female sex, systolic blood pressure, diabetes mellitus, and levels of troponin T > 0.03 microg/L, ST-T changes in the ECG remained associated with increased levels of NT-proBNP (beta=76.5, p=0.011).. ST-T changes suggestive of myocardial ischemia are independently associated with the levels of NT-proBNP in patients with acute ischemic stroke. The clinical importance of this observation remains to be defined.

Topics: Acute Disease; Aged; Biomarkers; Brain Ischemia; Electrocardiography; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index; Stroke

The association between plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognostic outcomes in patients after ischemic stroke remains unknown. The present study tested the hypothesis that NT-proBNP level is noticeably increased after ischemic stroke and that elevated NT-proBNP is associated with unfavorable clinical outcomes (UFCO).. Blood samples for NT-proBNP levels were collected serially and examined with sandwich immunoassay after acute ischemic stroke in 86 consecutive patients. The NT-proBNP levels were also measured in 30 healthy control volunteers and 30 at-risk control subjects. The NT-proBNP levels were significantly higher at 4 intervals after ischemic stroke than in healthy and at-risk control subjects (all p<0.001). The NT-proBNP decreased to a significantly lower level on day 21 and to a substantially lower level on day 90. Additionally, the NT-proBNP level at any of the 4 intervals was significantly higher in patients with than in patients without UFCO (defined as combined congestive heart failure > or = class 3, acute myocardial infarction, recurrent stroke or any cause of death) (all p<0.01). Multivariate analysis demonstrated that age and NIH Stroke Scale were the 2 strongest independent predictors of increased NT-proBNP levels (all p<0.01). Furthermore, increased NT-proBNP (> or = 150 pg/ml) was the strongest independent predictor of long-term (mean follow-up: 24 months) UFCO (26 patients) (all p<0.05).. The NT-proBNP level was markedly elevated after acute ischemic stroke and declined substantially thereafter. An increased NT-proBNP level was strongly and independently correlated with UFCO in patients after ischemic stroke.

Topics: Acute Disease; Aged; Biomarkers; Brain Ischemia; Case-Control Studies; Female; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Stroke; Time Factors; Treatment Outcome

B-type natriuretic peptide (BNP) is a neurohormone secreted mainly in the cardiac ventricles in response to volume expansion and pressure overload. The aim of this study was to assess plasma N-terminal proBNP (NT-proBNP) changes in acute ischemic stroke (AIS).. The study group consisted of 57 (37 women aged 64 +/- 12 years) patients who had their first AIS and no history or signs of cardiovascular disease. An age-matched control group was also included (n = 57, 36 women aged 61 +/- 6 years). NT-proBNP, troponin I (TnI), and creatine kinase-MB were evaluated. A thorough cardiovascular and neurological investigation, including imaging techniques and lesion size determination, was also performed.. The log NT-proBNP peak levels, TnI, and creatine kinase-MB levels were significantly higher in AIS compared with controls (7.25 +/- 1.77 vs 3.48 +/- 0.76 pg/mL, P < .0001; 0.76 +/- 0.54 vs 0.5 +/- 0.0 ng/mL, P < .001; 57 +/- 37 vs 13 +/- 4 U/L, P < .001, respectively). The log NT-proBNP correlated positively with TnI (r = 0.29, P = .03) and heart rate (r = 0.41, P = .002), and negatively with left ventricular ejection fraction (r = -0.67, P < .0001). Patients with signs of marked myocardial ischemia and patients with insular cortex involvement had even higher NT-proBNP levels. After adjustment for relevant factors, the relation between the log NT-proBNP and AIS as well as insular cortex involvement was observed to be insignificant (P > .05 for both).. Our results show that NT-proBNP plasma levels are significantly elevated in AIS and might be of clinical importance as a supplementary tool for the assessment of cardiovascular function in patients with AIS.

Topics: Adult; Aged; Aged, 80 and over; Brain Ischemia; Case-Control Studies; Echocardiography; Electrocardiography; Female; Heart; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stroke; Tomography, X-Ray Computed

The exact time-course of N-terminal pro-brain natriuretic peptide (NT-proBNP) and the prognostic importance in the immediate phase of ischemic stroke have not been established.. NT-proBNP was measured daily from admission to day 5 and again at 6-month follow-up in 250 consecutive patients with acute ischemic stroke.. NT-proBNP peaked the day after onset of symptoms (p = 0.007) followed by a decrease until day 5 (p = 0.001, ANOVA). At 6-month follow-up the difference in the level of NT-proBNP was unchanged compared to day 5 (p = 0.42). NT-proBNP levels > or =615 pg/ml at day 2 after onset of symptoms was associated with 6-month mortality.. NT-proBNP peaks the day after onset of symptoms in patients with acute ischemic stroke. A single measurement of NT-proBNP appears to be an indicator of 6-month mortality.

Topics: Acute Disease; Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Research Design; ROC Curve; Sensitivity and Specificity; Stroke; Time Factors

The prognostic value of cardiac troponins and natriuretic peptide in acute ischemic stroke is uncertain. We measured cardiac troponin T (cTnT), cardiac troponin I (cTnI), and N-terminal pro-brain natriuretic peptide (NT-proBNP) at admission in acute ischemic stroke patients without evident myocardial damage.. In 174 consecutive patients with MRI-confirmed ischemic stroke, serial measurements of cTnT, cTnI, and NT-proBNP were performed at 3 different time points in the hyperacute phase (at admission, on days 1 and 2). Relation of laboratory values to risk factors, stroke subtype classification, and clinical outcome after 3 months was analyzed.. The highest proportion of raised parameters was found at day 2 for cTnI in 8 of 103 (7.8%), at day 3 for cTnT in 8 of 174 (4.6%), and NT-proBNP in 114 of 174 (65.5%) patients. Proportion of patients with good outcome was significantly reduced in the group with highest NT-proBNP quartile. However, using multivariate regression analysis, no significant relation to morbidity and mortality was found for cTnT, cTnI, or NT-proBNP. Significant impact on the outcome was detected for lesion size, insular involvement, sex, age, and stroke severity.. NT-proBNP is raised in nearly two thirds of acute stroke patients, whereas elevated cardiac troponins are found only in a small number of acute ischemic stroke patients. Neither NT-proBNP nor cardiac troponins influence clinical outcome if other risk factors are considered.

Topics: Age Factors; Aged; Brain Ischemia; Electrocardiography; Female; Humans; Ischemia; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Structure, Tertiary; Regression Analysis; Risk Factors; Sex Factors; Stroke; Time Factors; Treatment Outcome; Troponin I; Troponin T

Acute blood pressure (BP) elevation and cardiac abnormalities are known to follow ischemic stroke. Brain natriuretic peptide (BNP), which is produced in response to such cardiovascular alterations, is expected to play a hemodynamic role. We measured plasma BNP concentrations in patients with cerebral infarction (CI) to determine the implications of BNP in acute ischemic stroke.. Eighty-eight patients with CI, 59 with essential hypertension, 44 with spontaneous intracerebral hemorrhage, 22 with asymptomatic atrial fibrillation (Af), and 20 age- and sex-matched healthy volunteers were recruited in the study. CI patients were divided into 2 subgroups either having Af (27 patients) or not (61 patients). BNP levels were repeatedly measured in 58 patients with CI. BNP levels were compared between ischemic subgroups categorized by size of infarction. Correlation was investigated between BNP levels and hemodynamic parameters.. BNP levels in CI patients were significantly higher, but they decreased in the subacute period. BNP levels in CI patients without Af were correlated with mean arterial blood pressure (MAP) on admission or the degree of reduction in MAP at day 1, while in CI patients with Af BNP levels showed negative correlation with MAP on admission. Follow-up serum sodium levels in CI patients with Af were negatively correlated with BNP levels on admission.. This study suggests the hemodynamic implications of BNP in acute ischemic patients.

Topics: Acute Disease; Aged; Atrial Fibrillation; Blood Pressure; Brain Ischemia; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Sodium; Stroke; Water-Electrolyte Balance

Serum brain natriuretic peptide (BNP) is elevated after subarachnoid hemorrhage (SAH), causes diuresis and natriuresis (cerebral salt wasting), and may exacerbate delayed ischemic neurological deficits. We examined the temporal relationship between serum BNP elevation, hyponatremia, and the onset of delayed ischemic neurological deficits and determined whether serum BNP levels correlated with the 2-week outcome after SAH.. Serum BNP and sodium were measured prospectively every 12 hours for 14 days in 40 consecutive patients admitted with SAH. All patients remained euvolemic, underwent transcranial Doppler assessment every 48 hours, and underwent angiography at the onset of delayed neurological deficits. New-onset neurological deficits were attributed to vasospasm only in the absence of other causes and when supported by transcranial Doppler or cerebral angiography.. Sixteen patients (40%) experienced symptomatic cerebral vasospasm after SAH. A more than threefold increase in admission serum BNP was associated with the onset of hyponatremia (P < 0.05). Mean BNP levels were similar between vasospasm and nonvasospasm patients fewer than 3 days after SAH (126 +/- 39 pg/ml versus 154 +/- 40 pg/ml; P = 0.61) but were elevated in the vasospasm cohort 4 to 6 days after SAH (285 +/- 67 pg/ml versus 116 +/- 30 pg/ml; P < 0.01), 7 to 9 days after SAH (278 +/- 72 pg/ml versus 166 +/- 45 pg/ml; P < 0.01), and 9 to 12 days after SAH (297 +/- 83 pg/ml versus 106 +/- 30 pg/ml; P < 0.01). BNP level remained independently associated with vasospasm adjusting for Fisher grade and Hunt and Hess grade (odds ratio, 1.28; 95% confidence interval, 1.1-1.6). In patients in whom vasospasm developed, mean serum BNP increased 5.4-fold within 24 hours after vasospasm onset and 11.2-fold the first 3 days after vasospasm onset. Patients with increasing BNP levels from admission demonstrated no change (0 +/- 3) in Glasgow Coma Scale score 2 weeks after SAH versus a 3.0 +/- 2 (P < 0.05) improvement in Glasgow Coma Scale score in patients without increasing serum BNP levels.. Increasing serum BNP levels independently were associated with hyponatremia, significantly increased the first 24 hours after onset of delayed ischemic neurological deficits, and predicted the 2-week Glasgow Coma Scale score.

Topics: Adult; Aged; Brain Ischemia; Female; Glasgow Coma Scale; Humans; Hyponatremia; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Subarachnoid Hemorrhage; Time Factors; Treatment Outcome

Brain natriuretic peptide (BNP) is a potent natriuretic factor responsible for hyponatremia observed in patients with SAH. Through its systemic effects (reduction of blood volume and blood pressure) BNP may augment cerebral blood flow reduction and ischemia secondary to vasospasm. The purpose of the present study was to evaluate the relationship between BNP plasma concentration during the first 12 days following SAH and the development of cerebral vasospasm (CVS). The authors propose a hypothesis for the role played by natriuretic peptides in the pathophysiology of cerebral vasospasm based on the present findings and review the literature.. Thirty eight patients with spontaneous SAH were prospectively included in the present study. BNP plasma concentrations were assessed at four different time periods following SAH (day 1-3, 4-6, 7-9, 10-12). TCD evidence of CVS was found in 26 patients (68.5%), fourteen patients (36.8%) had delayed ischemic neurological deficits (DIND).. Initial BNP plasma concentrations were significantly more elevated in patients who eventually did not develop DIND (95.07+/-107.65 pg/ml vs. 25.81+/-22.57 pg/ml, p=0.0053). However, in patients with DIND, the BNP plasma concentration increased by 3.69 ( p<0.05), 5.89 ( p<0.001) and 4.54 fold ( p<0.001) between days 1-3 to days 4-6, 7-9 and 10-12 respectively (day 1 was regarded as the day of hemorrhage). In patients without CVS or asymptomatic CVS the BNP plasma concentration decreased between days 1-3 to day 10-12. A similar trend in BNP plasma concentration was found in patients with severe SAH (Fisher's score 3-4) as compared with patients with non visible or moderate SAH (BNP concentration ratio day 7-9/1-3: 4.37 vs. 0.75, p=0.015; day 10-12/1-3: 3.37 vs. 0.3, p=0.0144). The trend in BNP plasma concentration between day 1-3 to day 7-9 was found to correlate with CVS severity with an average increase of 2.01, 3.8 and 5.44 fold for mild, moderate and severe VS respectively ( p<0.01, r=0.4174).. These results suggest that BNP secretion in SAH patients is closely related to the bleeding intensity and vasospasm severity as well as to development of DIND with a progressive and marked increase during the clinical course in patients who eventually develop cerebral ischemia. Taken together the local and systemic effects of BNP on CBF suggest that BNP might play a role in the pathophysiology of CVS through its systemic effects on blood pressure and plasma volume BNP leading to an aggravation of brain ischemia secondary to vasospasm.

Topics: Adult; Aged; Brain; Brain Ischemia; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Regional Blood Flow; Subarachnoid Hemorrhage; Vasospasm, Intracranial

-Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium-dependent relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8; pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.

Topics: Amino Acid Substitution; Animals; Atrial Natriuretic Factor; Base Sequence; Brain; Brain Ischemia; Cells, Cultured; Cerebrovascular Disorders; Chromosome Mapping; DNA Primers; Exons; Genetic Markers; Genetic Predisposition to Disease; Hypertension; Introns; Male; Muscle, Smooth, Vascular; Natriuretic Peptide, Brain; Point Mutation; Polymerase Chain Reaction; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley

Ischaemic stroke is a complex disorder caused by a combination of genetic and environmental factors. Clinical and epidemiological studies have provided strong evidence for genetic influences in the development of human stroke and several mendelian traits featuring stroke have been described. The genetic analysis of the non-mendelian, common ischaemic stroke in humans is hindered by the late onset of the disease and the mode of inheritance, which is complex, polygenic and multifactorial. An important approach to the study of such polygenic diseases is the use of appropriate animal models in which individual contributing factors can be recognized and analysed. The spontaneously hypertensive stroke-prone rat (SHRSP) is an experimental model of stroke characterized by a high frequency of spontaneous strokes as well as an increased sensitivity to experimentally induced focal cerebral ischaemia. Rubattu et al. performed a genomewide screen in an F2 cross obtained by mating SHRSP and SHR, in which latency to stroke on Japanese rat diet was used as a phenotype. This study identified three major quantitative trait loci (QTLs), STR-1-3. Of these, STR-2 and 3 conferred a protective effect against stroke in the presence of SHRSP alleles and STR-2 co-localized with the genes encoding for atrial natriuretic and brain natriuretic factors. Our investigation was designed to identify the genetic component responsible for large infarct volumes in the SHRSP in response to a focal ischaemic insult by performance of a genome scan in an F2 cross derived from the SHRSP and the normotensive reference strain, WKY rat. We identified a highly significant QTL on rat chromosome 5 with a lod score of 16.6 which accounts for 67% of the total variance, co-localizes with the genes encoding atrial and brain natriuretic factor and is blood pressure independent.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Brain Ischemia; Cerebral Arteries; Cerebrovascular Disorders; Chromosome Mapping; Crosses, Genetic; Disease Models, Animal; Female; Humans; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Rats; Rats, Inbred SHR; Rats, Inbred WKY

Cultured vascular endothelial and smooth muscle cells actively produce adrenomedullin, a novel vasodilator peptide discovered in human pheochromocytoma tissue. This present study was designed to determine whether the plasma level of adrenomedullin is a useful indicator for estimating the degree of endothelial injury in patients with atherosclerotic disease.. We used a radioimmunoassay to measure plasma adrenomedullin concentrations in 51 patients with chronic cerebrovascular disease (34 infarctions and 17 haemorrhages) and in 10 subjects without symptomatic cerebrovascular disease. We also measured the plasma concentrations of thrombomodulin and endothelin as markers of endothelial injury. The patients were divided into three groups (A, B, and C) on the basis of the number of risk factors for atherosclerosis: hypertension, hyperlipidemia, smoking, low HDL-cholesterol, diabetes mellitus, and hyperuricaemia. Group A (68.7+/-2.7 years) consisted of patients with 0 or 1 risk factors; B (68.3+/-4.2 years) those with 2 risk factors; and C (69.2+/-3.6 years) those with 3 or more risk factors.. The plasma concentration of adrenomedullin in these patients showed a significant positive correlation with age (r=0.33, p<0.05), as well as with the plasma concentrations of thrombomodulin (r=0.54, p<0.001) and endothelin (r=0.53, p<0.001). Moreover, the plasma concentrations of adrenomedullin and thrombomodulin (p<0.005 and p<0.02, respectively) tended to be higher in Group B and to be significantly higher in Group C as compared to Group A. Plasma adrenomedullin concentrations did not, however, significantly differ between the infarction and haemorrhage patients.. These findings suggest that the plasma adrenomedullin concentrations reflect the degree of endothelial injury in patients with atherosclerotic disease.

Topics: Adrenomedullin; Aged; Atrial Natriuretic Factor; Biomarkers; Blood Urea Nitrogen; Brain Ischemia; Cerebral Angiography; Cerebral Hemorrhage; Cholesterol; Chronic Disease; Endothelins; Female; Humans; Intracranial Arteriosclerosis; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptides; Risk Factors; Thrombomodulin; Tomography, X-Ray Computed; Vasodilator Agents