natriuretic-peptide--brain and Cerebrovascular-Disorders

The plasma amino-terminal-pro-B-type natriuretic peptide (NT-proBNP) level predicted congestive heart failure, myocardial infarction, and ischaemic stroke in participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of the effects of blood pressure lowering on cardiovascular events among individuals with cerebrovascular disease. Active treatment comprised a flexible regimen based on perindopril, with the addition of indapamide at the discretion of treating physicians. Active treatment reduced cardiovascular events, and we therefore investigated whether active treatment modified NT-proBNP and other cardiovascular risk factors.. We measured NT-proBNP and other cardiovascular risk factors at randomization and after 13 months of therapy in a subset of 357 PROGRESS participants.. Baseline systolic and pulse pressures were higher in individuals with elevated baseline NT-proBNP levels. In comparison with placebo, active treatment reduced the blood pressure and NT-proBNP levels, and increased renin levels. Reduction of NT-proBNP levels by active treatment was most evident in individuals with baseline NT-proBNP levels in the highest quarter (> 26 pmol/l), with a median reduction of 16 pmol/l (interquartile range 0-51 pmol/l, P = 0.004), corresponding to a median decrease of 39% (interquartile range 0-69%). Active treatment reduced blood pressure similarly for individuals in each of the four quarters of baseline NT-proBNP. Active therapy had no effect on plasma lipid, C-reactive protein, homocysteine, or soluble vascular cell adhesion molecule 1 levels.. We conclude that plasma NT-proBNP level, in addition to predicting cardiovascular risk, may provide a measure of risk reduction by blood pressure-lowering therapy.

Topics: Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Cardiovascular Diseases; Cerebrovascular Disorders; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Perindopril; Risk Factors

Cardiac biomarkers, NT-proBNP (N-terminal probrain natriuretic peptide), hs-cTnT (high-sensitivity-cardiac troponin T), and GDF-15 (growth differentiation factor-15) have been proposed as important biomarkers of early vascular pathology. However, little is known of the longitudinal associations of these cardiac biomarkers with cerebrovascular disease and clinical events. We examine the association of blood-based cardiac biomarkers (NT-proBNP, hs-cTnT, and GDF-15) with cognitive decline, incident cerebrovascular disease, vascular events, and mortality.. Four hundred thirty-four memory-clinic patients provided blood samples at baseline, underwent 3 annual neuropsychological assessments and brain magnetic resonance imaging scans at baseline and follow-up. NT-proBNP and hs-cTnT concentrations were measured by electrochemiluminescence immunoassay and GDF-15 by quantitative sandwich immunoassay. Baseline and follow-up magnetic resonance imagings were graded for white matter hyperintensities, lacunes, cerebral microbleeds, cortical infarcts, and intracranial stenosis. Data on incident vascular events and mortality were obtained.. Patients with higher levels of NT-proBNP, hs-cTnT, and GDF-15 showed greater decline in memory domain. Additionally, hs-cTnT was associated with decline in global cognition, executive function, and visuomotor speed. Higher levels of NT-proBNP were associated with incident cerebral microbleeds and hs-cTnT with incident cortical infarcts. During a mean follow-up of 3 years, 26 (5.9%) patients died and 35 (8.1%) developed vascular events. Patients with higher levels of NTpro-BNP and hs-cTnT were at increased risk of vascular events whereas those with higher levels of NT-proBNP and GDF-15 were at risk of mortality.. Higher levels of blood-based cardiac biomarkers were associated with decline in memory and risk of vascular events and mortality. Moreover, NT-proBNP and hs-cTnT were associated with incident cerebral microbleeds and cortical infarcts. Thus, these biomarkers are potentially useful in identifying patients at risk of adverse vascular events and death.

Topics: Aged; Aged, 80 and over; Biomarkers; Cerebrovascular Disorders; Cognitive Dysfunction; Female; Follow-Up Studies; Growth Differentiation Factor 15; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neuropsychological Tests; Peptide Fragments; Risk Factors; Troponin T

Background Elevated natriuretic peptides (NP) are associated with adverse cerebrovascular conditions including stroke, cerebral small vessel disease, and dementia. However, the mechanisms underlying these associations remain unclear. In this study, we examined the relationship of NT-proBNP (N-terminal pro brain NP) and NT-proANP (N-terminal pro atrial NP) with cerebrovascular function, measured by cerebral autoregulation. Methods and Results We included 154 participants (mean age 56±4 years old) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort. NT-proBNP and NT-proANP were measured in blood samples from the year 25 examination using electrochemiluminescence Immunoassay and enzyme-linked immunoassay, respectively. Dynamic cerebral autoregulation (dCA) was assessed at the year 30 examination by transcranial Doppler ultrasound, using transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations, where lower phase and higher gain reflect less efficient cerebral autoregulation. We used multivariable linear regression models adjusted for demographics, vascular risk factors, and history of kidney and cardiac diseases. Higher NT-proBNP levels at year 25 were associated with lower phase (β [95% CI]=-5.30 lower degrees of phase [-10.05 to -0.54]) and higher gain (β [95% CI]=0.06 higher cm/s per mm Hg of gain [0.004-0.12]) at year 30. Similarly, higher NT-proANP levels were associated with lower phase (β [95% CI]=-9.08 lower degrees of phase [-16.46 to -1.70]). Conclusions Higher circulating levels of NT-proBNP and NT-proANP are associated with less efficient dCA 5 years later. These findings link circulating NP to cerebral autoregulation and may be one mechanism tying NP to adverse cerebrovascular outcomes.

Topics: Atrial Natriuretic Factor; Blood Flow Velocity; Brain; Cerebrovascular Circulation; Cerebrovascular Disorders; Dementia; Female; Heart Disease Risk Factors; Homeostasis; Humans; Longitudinal Studies; Male; Middle Aged; Middle Cerebral Artery; Natriuretic Peptide, Brain; Peptide Fragments; Ultrasonography, Doppler, Transcranial; United States

To analyze the incidence rates (IR) and spectrum of vascular events in people living with HIV (PLWH) in Spain from 2004 to 2015. Serial measurements of different plasma cardiovascular biomarkers were assessed in relation to disease development.. Longitudinal study in a nationwide contemporary multicenter cohort of PLWH. A nested case-control study was performed to evaluate the predictive value of cardiovascular biomarkers. Additive generalized and Cox mixed models were used for the analyses.. 9,712 PLWH and 48,341 person-years of follow-up were analysed. During 2004-2015, 147 persons developed 154 vascular events; 80 (54.42%) coronary-related; 65 (44.22%) cerebrovascular-related, and 9 (6.12%) peripheral arterial disease. The 2004-2015 IR (95% confidence interval) of vascular events was 3.17 (2.69-3.71) x1,000 person-years; 1.64 (1.30-2.05) for coronary events; 1.34 (1.03-1.70) for cerebrovascular events; and 0.19 (0.09-0.35) for peripheral arterial disease (p<0.001). IR of vascular events gradually increased from 0.37 (0.12-0.85) x1,000 patient-years in the stratum 25-34-years to 19.65 (6.38-45.85) x1,000 patient-years in the stratum 75-84-years. Compared to the general population, there was a higher incidence of acute myocardial infarction (AMI) in men (sIR ratio 1.29 [95% CI 1.16-1.42]), of cerebrovascular events in women (sIR ratio 2.44 [95% CI 1.68-3.19]), and of both types of events specifically among the younger age-strata. CD4 count (hazard ratio 0.80, [95% CI, 0.79-0.81]), age (1.86 [1.47-2.34] for 45-65 years and 3.44 [2.37-4.97] for >65 years) and vascular event (1.81 [1.12-2.94]) were associated with total mortality. Adjusted levels of intercellular-adhesion-molecule (sICAM), pro-b-type-natriuretic-peptide (pro-BNP) and marginally sCD14, were higher among patients who subsequently developed vascular events.. Vascular events in PLWH do preferentially occur in the older age-strata, they are associated with increased mortality and, compared to the general population, the excess risk occurs at younger ages. Peripheral arterial disease is unusual. Vascular events are preceded by increased levels of sICAM, pro-BNP and, marginally, sCD14.

Topics: Adult; Age Factors; Biomarkers; Case-Control Studies; Cerebrovascular Disorders; Female; Follow-Up Studies; HIV Infections; Humans; Incidence; Intercellular Adhesion Molecule-1; Lipopolysaccharide Receptors; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Arterial Disease; Predictive Value of Tests; Risk Assessment; Risk Factors; Sex Factors; Spain

Perioperative major adverse cardiovascular and cerebrovascular events (MACCEs) are incompletely understood, and risk prediction is imprecise. Atherogenic leukocytes are crucial in cardiovascular events. However, it is unclear if surgical interventions affect leukocyte counts or activation status. Therefore, we investigated whether noncardiac surgery in patients with elevated cardiovascular risk is associated with changes in atherogenic leukocyte subsets and if these changes are related to perioperative MACCEs.. We enrolled 40 patients in this single-center prospective observational cohort study. Total leukocytes and subpopulations, including classical, intermediate, and nonclassical monocytes and natural killer and regulatory T cells, were quantified before surgery, at 2 and 6 hours after skin incision, and at postoperative days 1 and 2 (POD1+2). The monocyte activation marker presepsin (sCD14-ST) was measured post hoc to determine differentiation of classical to nonclassical monocytes. We evaluated presepsin for prediction of the composite primary end point MACCE (cardiovascular death, myocardial infarction, myocardial ischemia, and stroke) at 30 days. Its additive value to risk assessment based on high-sensitive cardiac troponin T and N-terminal probrain natriuretic peptide (NT-proBNP) was analyzed.. We evaluated 38 patients, of whom 5 (13%) reached MACCE. In the entire cohort, classical monocytes continuously increased and peaked at POD1 (0.35 [0.23-0.43] cells per nanoliter blood [nL] vs 0.45 [0.31-0.66] cells·nL, preoperative [pre-OP] vs POD1, P = .002). Intermediate monocytes doubled by POD1 (0.017 [0.013-0.021] vs 0.036 [0.022-0.043] cells·nL, pre-OP versus POD1, P = .0003). Nonclassical monocytes decreased (0.022 [0.012-0.032] vs 0.012 [0.005-0.023] cells·nL, pre-OP vs 6 hours, P = .003). In our patient population, we did not detect changes in any of the other predefined leukocyte subsets investigated. In patients experiencing a MACCE, classical monocyte expansion was reduced (0.081 [-0.16 to 0.081] cells·nL vs 0.179 [0.081 to 0.292] cells·nL, MACCE versus non-MACCE, P = .016). Patients in the event group presented with elevated pre-OP presepsin (1528 [406-1897] pg·mL vs 123 [82.2-174] pg·mL, MACCE versus non-MACCE, P = .0001). Presepsin was associated with MACCE (area under the curve = 0.964, [0.846-0.998], P = .001). Presepsin above the calculated threshold >184 pg·mL was superior to high-sensitive cardiac troponin T for improvement of NT-proBNP-based risk prediction (28 [74%] vs 22 [58%] correctly classified patients, P = .014).. Noncardiac surgery was associated with an increase in atherogenic leukocyte subsets. In a post hoc analysis, elevated pre-OP presepsin was associated with MACCE and improved NT-proBNP-based risk assessment. After validation in an independent data set, a presepsin cutoff of 184 pg·mL might qualify to complement NT-proBNP-based risk prediction, thereby increasing the proportion of correctly identified high-risk patients.

Topics: Aged; Atherosclerosis; Cardiovascular Diseases; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Leukocytes; Lipopolysaccharide Receptors; Male; Middle Aged; Monocytes; Natriuretic Peptide, Brain; Peptide Fragments; Postoperative Complications; Postoperative Period; Prospective Studies; Risk Assessment; Treatment Outcome; Troponin T

To study the association of N-terminal pro-brain natriuretic peptide (NT-proBNP) with several brain MRI markers of brain vascular disease in a sample of participants free of stroke and dementia.. NT-proBNP plasma level was determined by means of a sandwich immunoassay method in a cohort study comprising 278 hypertensive patients. The presence of silent brain infarcts, brain microbleeds, enlarged perivascular spaces, and white matter hyperintensity volumes was assessed by brain MRI. We performed univariate and multivariate analyses to determine whether NT-proBNP was independently associated with these imaging markers, individually or combined.. Median age was 63 years, and 41.4% were women. NT-proBNP remained independently associated with silent brain infarcts (odds ratio [OR] per 1-SD increase in NT-proBNP 2.11, 95% confidence interval [CI] 1.44-3.10), brain microbleeds (OR 1.79, 95% CI 1.15-2.78), basal ganglia enlarged perivascular spaces (OR 1.55, 95% CI 1.12-2.15), and white matter hyperintensity volumes (β 1.60, 95% CI 0.47-2.74), even after controlling for vascular risk factors, cardiovascular risk, atrial fibrillation, previous heart disease, duration of hypertension, and preventive treatments. A score combining several imaging markers was also related to NT-proBNP levels (common OR per 1-SD increase 1.74, 95% CI 1.21-2.50).. NT-proBNP is independently associated with silent cerebrovascular lesions and could be a surrogate marker of vascular brain damage in hypertension.

Topics: Aged; Biomarkers; Cerebrovascular Disorders; Cohort Studies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Risk Assessment; Risk Factors

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

To evaluate the impact of chronic obstructive pulmonary disease (COPD) on left ventricular (LV) diastolic function in hospitalized elderly patients.. This was a case-control observational study of 148 consecutive hospitalized elderly patients (≥65 years old): 73 subjects without COPD as controls and 75 patients with COPD. Mild-to-moderate COPD was defined as stages 1 and 2, while severe and very severe COPD was defined as stages 3 and 4, according to the Global Initiative for Chronic Obstructive Lung Disease guidelines. Clinical characteristics and echocardiographic parameters were analyzed and compared.. Compared with the control group, patients with COPD had a higher frequency of LV diastolic dysfunction and heart failure with preserved ejection fraction. Smoking frequency, frequency of cerebrovascular diseases and diabetes, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were higher in the COPD group (all P<0.05). COPD patients showed more abnormalities in diastolic function (E/e': 11.51±2.50 vs 10.42±3.25, P=0.047), but no differences in systolic function and right ventricular function (all P>0.05). Patients with severe/very severe COPD showed no differences in LV diastolic function compared to patients with mild/moderate COPD (P>0.05), but serum NT-proBNP levels were higher in severe/very severe COPD (P<0.05).. Results suggest that early-stage COPD may have an impact on the LV diastolic function. Severe COPD mainly affected right ventricular function. In hospitalized elderly patients with COPD, LV diastolic dysfunction should be taken into account together with right ventricular function.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Cerebrovascular Disorders; China; Diabetes Mellitus; Echocardiography; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Disease, Chronic Obstructive; Risk Factors; Severity of Illness Index; Smoking; Ventricular Dysfunction, Left

Markers of cardiac dysfunction such as amino terminal pro-brain natriuretic peptide (NTpro-BNP) and high sensitivity cardiac troponin T (hs-cTnT) may be associated with dementia. However, limited data exist on their association with either pre-dementia stages, that is, cognitive impairment no dementia (CIND), or the burden of cerebrovascular diseases (CeVD).We therefore, examined the association of these biomarkers of cardiac dysfunction with CeVD in both CIND and dementia.A case-control study, with cases recruited from memory clinics and controls from memory clinics and community. All subjects underwent collection of blood samples, neuropsychological assessment, and neuroimaging. Subjects were classified as CIND and dementia based on clinical criteria whilst significant CeVD was defined as the presence of cortical infarcts and/or more than 2 lacunes and/or confluent white matter lesions in two regions of brain on Age-Related White Matter Changes Scale.We included a total of 35 controls (mean age: 65.9 years), 78 CIND (mean age: 70.2 years) and 80 cases with dementia (mean age: 75.6 years). Plasma concentrations of hs-cTnT were associated significantly with CeVD in both CIND (odds ratios [OR]: 9.05; 95% confidence interval [CI]: 1.64-49.79) and dementia (OR: 16.89; 95%CI: 2.02-142.67). In addition, NTpro-BNP was associated with dementia with CeVD (OR: 7.74; 95%CI: 1.23-48.58). These associations were independent of other vascular risk factors.In this study, we showed that plasma NTproBNP and hs-cTnT are associated with dementia and CIND, only when accompanied by presence of CeVD.

Topics: Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Cerebrovascular Disorders; Cognitive Dysfunction; Dementia; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Amino-terminal pro-B-type natriuretic peptide (NT-proBNP) is a predictor of heart disease. It has also been related to stroke, but its association with transient ischaemic attacks (TIAs) is unclear. Moreover, it is unknown how clinical heart disease influences this relation. Within the prospective population-based Rotterdam Study, the association of NT-proBNP with stroke and TIA was examined and the role of heart disease on this association was investigated.. NT-proBNP was measured in 1997-2001 in 5611 participants (mean age 68.7 years; 57.7% women) without a history of stroke, TIA or heart failure. Follow-up for stroke and TIA finished in 2012. Models were adjusted for age and cardiovascular risk factors, and were stratified by sex.. During 22 058 person-years 195 men suffered a stroke and 118 a TIA. During 31 825 person-years 230 women suffered a stroke and 187 a TIA. Higher NT-proBNP was associated with a higher risk of stroke in men [hazard ratio (HR) per SD increase 1.50; 95% confidence interval (CI) 1.29-1.76] and in women (HR 1.24; 95% CI 1.05-1.46). Associations with TIA were only present in women (HR 1.51; 95% CI 1.26-1.82) but not in men (HR 1.02; 95% CI 0.83-1.26). Excluding persons with a history of clinical coronary heart disease, heart failure or atrial fibrillation and censoring for clinical heart disease during follow-up did not change the associations.. Higher NT-proBNP is associated with incident stroke in men and women and with incident TIA only in women. These associations are independent of clinical heart disease preceding cerebrovascular disease.

Topics: Aged; Aged, 80 and over; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Prospective Studies; Risk Factors; Stroke

The purpose of this study was describe the cardiovascular phenotype of the aneurysms-osteoarthritis syndrome (AOS) and to provide clinical recommendations.. AOS, caused by pathogenic SMAD3 variants, is a recently described autosomal dominant syndrome characterized by aneurysms and arterial tortuosity in combination with osteoarthritis.. AOS patients in participating centers underwent extensive cardiovascular evaluation, including imaging, arterial stiffness measurements, and biochemical studies.. We included 44 AOS patients from 7 families with pathogenic SMAD3 variants (mean age: 42 ± 17 years). In 71%, an aortic root aneurysm was found. In 33%, aneurysms in other arteries in the thorax and abdomen were diagnosed, and in 48%, arterial tortuosity was diagnosed. In 16 patients, cerebrovascular imaging was performed, and cerebrovascular abnormalities were detected in 56% of them. Fifteen deaths occurred at a mean age of 54 ± 15 years. The main cause of death was aortic dissection (9 of 15; 60%), which occurred at mildly increased aortic diameters (range: 40 to 63 mm). Furthermore, cardiac abnormalities were diagnosed, such as congenital heart defects (6%), mitral valve abnormalities (51%), left ventricular hypertrophy (19%), and atrial fibrillation (22%). N-terminal brain natriuretic peptide (NT-proBNP) was significantly higher in AOS patients compared with matched controls (p < 0.001). Aortic pulse wave velocity was high-normal (9.2 ± 2.2 m/s), indicating increased aortic stiffness, which strongly correlated with NT-proBNP (r = 0.731, p = 0.005).. AOS predisposes patients to aggressive and widespread cardiovascular disease and is associated with high mortality. Dissections can occur at relatively mildly increased aortic diameters; therefore, early elective repair of the ascending aorta should be considered. Moreover, cerebrovascular abnormalities were encountered in most patients.

Topics: Adolescent; Adult; Aged; Aneurysm; Aortic Aneurysm, Thoracic; Aortic Dissection; Aortography; Cardiovascular Diseases; Cause of Death; Cerebrovascular Disorders; Chromosome Aberrations; Cohort Studies; Female; Genes, Dominant; Genomic Structural Variation; Humans; Image Interpretation, Computer-Assisted; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Osteoarthritis; Peptide Fragments; Phenotype; Pregnancy; Smad3 Protein; Survival Analysis; Syndrome; Vascular Stiffness; Young Adult

The aim of the present study was to assess whether elevated B-type natriuretic peptide (BNP) levels, as an objective marker of heart failure, is a predictor of subsequent thromboembolic events in patients with atrial fibrillation (AF) during oral anticoagulant therapy. This was a post hoc analysis of a single-center, prospective, observational study. Consecutive patients with AF (261 patients, 74 ± 9 years old, 153 paroxysmal AF) treated with warfarin were included for the analysis. BNP level at baseline examination was measured to assess the relationship of this parameter with subsequent thromboembolic events. BNP levels at the time of entry were 161 ± 188 (5-1,500, median 105) pg/ml. During an average follow-up time of 762 ± 220 (median 742) days, nine (1.8%/year) thromboembolic events occurred. Receiver operating characteristic curve showed that an optimal cut-off value for BNP to predict thromboembolic events was 218 pg/ml. There were six thromboembolic events observed among patients with a baseline BNP levels ≥200 pg/ml (n = 73) as compared to three such events in those with baseline BNP levels <200 pg/ml (n = 188). Kaplan-Meier curves for BNP level showed that elevated BNP level (≥200 pg/ml) was significantly associated with thromboembolic events (p < 0.01). Cox-proportional hazard analysis also revealed that a high BNP level (≥200 pg/ml) was a significant predictor of subsequent thromboembolic events (hazard ratio 5.32, p = 0.018). Elevated BNP levels (≥200 pg/ml) could be a useful marker of subsequent thromboembolic events in patients with AF during oral anticoagulant therapy. However, the number of patients and events in this study was small and drawing a definite conclusion was not possible with this small sample size. Therefore, further larger-scale, multicenter studies are needed to confirm these findings.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Cerebrovascular Disorders; Chi-Square Distribution; Heart Failure; Humans; Japan; Kaplan-Meier Estimate; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Thromboembolism; Treatment Outcome; Up-Regulation; Warfarin

Serum N-terminal-pro brain natriuretic peptide (NT-proBNP) is regarded as a marker of vascular disease and has previously been shown to exhibit an increased frequency of pathological values in elderly patients with mental illness with vascular disease compared to patients without vascular disease. Vascular disease plays an important role in cognitive impairment in elderly patients with mental illness.. We have investigated the relation between NT-proBNP, vascular disease and cognition in consecutively enrolled elderly patients with mental illness.. NT-proBNP level is increased in patients with vascular disease compared to patients without vascular disease, and a logistic regression analysis showed that NT-proBNP was a significant predictor of vascular disease. However, NT-proBNP level did not predict cognition as assessed by MMSE score. NT-proBNP level also showed a highly significant relation to mortality in all patients.. Determinations of NT-proBNP could be used in elderly patients with mental illness to detect patients in need of control and treatment of vascular risk factors. The levels of NT-proBNP may also provide prognostic information.

Topics: Aged; Aged, 80 and over; Cerebrovascular Disorders; Female; Humans; Male; Mental Disorders; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Patients with stroke or transient ischemic attack are at high risk of another stroke, and there is need for improved strategies to predict recurrent stroke.. To assess the prognostic value of levels of soluble vascular cell adhesion molecule 1 (sVCAM-1), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size in patients with previous stroke or transient ischemic attack.. A nested case-control study of participants of the Perindopril Protection Against Recurrent Stroke Study was performed. The Perindopril Protection Against Recurrent Stroke Study was a placebo-controlled trial of a perindopril erbumine-based, blood pressure-lowering regimen that reduced ischemic stroke risk by 24% among individuals with previous stroke or transient ischemic attack. Each of 252 patients who experienced ischemic stroke during a mean follow-up of 3.9 years was matched to 1 to 3 control patients. Matching variables were age, sex, treatment allocated, region, and most recent qualifying event at randomization.. Risk of ischemic stroke predicted by baseline levels of sVCAM-1, NT-proBNP, C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size.. Levels of sVCAM-1 and NT-proBNP predicted recurrent ischemic stroke. The odds ratio for patients in the highest, as compared with the lowest, quarter was 2.24 (95% confidence interval, 1.35-3.73) for sVCAM-1 level and 1.62 (95% confidence interval, 0.98-2.69) for NT-proBNP level, after adjustment for matching and other risk factors. Patients in the highest quarters for both sVCAM-1 and NT-proBNP levels had 3.6 times the risk of recurrent ischemic stroke compared with patients in the lowest quarters for both biologic markers. Level of sVCAM-1 was similarly predictive of ischemic stroke in patients allocated to placebo and perindopril-based therapy. Baseline plasma levels of C-reactive protein, homocysteine, renin, and lipids and lipoprotein particle concentration and size did not predict recurrent ischemic stroke risk.. Measurement of sVCAM-1 and NT-proBNP levels provides prognostic information for recurrent ischemic stroke beyond traditional risk factors.

Topics: Aged; C-Reactive Protein; Case-Control Studies; Cerebrovascular Disorders; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; International Cooperation; Male; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Stroke; Vascular Cell Adhesion Molecule-1

B-type natriuretic peptide (BNP) and C-reactive protein (CRP) are elevated in persons at risk for congestive heart failure (CHF). However, limited data are available directly comparing BNP-related peptides and CRP in persons at risk of CHF. To evaluate amino terminal-pro-BNP (NT-proBNP) and CRP, separately and together, for assessment of risk of CHF, we performed a nested case-control study of the 6105 participants of the Perindopril pROtection aGainst REcurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack (TIA). Each of 258 subjects who developed CHF resulting in death, hospitalization, or withdrawal of randomized therapy during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. NT-proBNP and CRP predicted CHF; the odds ratio for subjects in the highest compared with the lowest quarter was 4.5 (95% confidence interval, 2.7 to 7.5) for NT-proBNP and 2.9 (confidence interval, 1.9 to 4.7) for CRP, and each remained a predictor of CHF after adjustment for all other predictors. Screening for both markers provided better prognostic information than screening for either alone. Elevation of NT-proBNP above 50 pmol/L and CRP above 0.84 mg/L predicted CHF with sensitivity of 64% and specificity of 66%. NT-proBNP and CRP predicted CHF in subjects receiving perindopril-based therapy. We conclude that NT-proBNP and CRP are independent predictors of CHF risk after stroke or TIA. Moreover, NT-proBNP and CRP may be markers of mechanisms of CHF pathogenesis distinct from those responsive to angiotensin-converting enzyme inhibitor-based therapy.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Case-Control Studies; Cerebrovascular Disorders; Female; Follow-Up Studies; Heart Failure; Humans; Hypertension; Incidence; Ischemic Attack, Transient; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Perindopril; Predictive Value of Tests; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity; Stroke

B-type natriuretic peptide (BNP), C-reactive protein (CRP), and renin are elevated in persons at risk for cardiovascular disease. However, data that directly compare these markers in the prediction of myocardial infarction (MI) are limited.. N-terminal-proBNP (NT-proBNP), CRP, and renin were measured in baseline blood samples from a nested case-control study of the 6105 participants of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS), a placebo-controlled study of a perindopril-based blood pressure-lowering regimen among individuals with previous stroke or transient ischemic attack. Each of 206 subjects who experienced MI, either fatal or nonfatal, during a mean follow-up of 3.9 years was matched to 1 to 3 control subjects. Most MI cases (67%) occurred in subjects without a history of coronary heart disease. NT-proBNP, CRP, and renin each predicted MI; the odds ratio for subjects in the highest compared with the lowest quarter was 2.2 (95% CI, 1.3 to 3.6) for NT-proBNP, 2.2 (95% CI, 1.3 to 3.6) for CRP, and 1.7 (95% CI, 1.1 to 2.8) for renin. NT-proBNP and renin, but not CRP, remained predictors of MI after adjustment for all other predictors, including LDL and HDL cholesterol levels. Individuals with both NT-proBNP and renin in their highest quarters had 4.5 times the risk of MI compared with subjects with both biological markers in their lowest quarters.. NT-proBNP and renin, but not CRP, are independent predictors of MI risk after stroke or transient ischemic attack, providing information additional to that provided by classic risk factors, and may enable more effective targeting of MI prevention strategies.

Topics: Aged; Biomarkers; C-Reactive Protein; Case-Control Studies; Cerebrovascular Disorders; Female; Humans; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Renin; Stroke

-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

We have previously shown that a locus on rat chromosome 5, termed STR 2, co-localizes with the genes encoding atrial natriuretic and brain natriuretic peptides, and is closely linked to the development of strokes in rats of a F2 hybrid cohort obtained by crossing stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats. We also demonstrated that there are significant differences in vascular functioning that are co-segregated with stroke latency of stroke-prone spontaneously hypertensive rats.. To investigate the vascular responses to natriuretic peptides in the stroke-prone phenotype of spontaneously hypertensive rats.. In view of the important vasoactive properties of natriuretic peptides, we tested the vascular responses to 10(-11)-10(-9) mol/l atrial natriuretic peptide and to 10(-11)-10(-7) mol/l brain natriuretic peptide in isolated rings of aortas and internal carotid arteries obtained from stroke-prone and stroke-resistant spontaneously hypertensive rats. The 6-week-old rats were exposed for 4 weeks either to their regular diet (n = 15 of both strains) or to the stroke-permissive Japanese-style diet (n = 14 of both strains). A group of 14 normotensive, age-matched and sex-matched Wistar-Kyoto rats was also studied.. Systolic blood pressures in stroke-prone and stroke-resistant spontaneously hypertensive rats were similar, and were significantly higher than those in Wistar-Kyoto rats. Vascular responses to nitroglycerin, atrial natriuretic peptide, and brain natriuretic peptide in rats of the two hypertensive strains and in Wistar-Kyoto rats fed their regular diet were comparable. In contrast, the vasorelaxant responses to atrial natriuretic peptide in stroke-prone spontaneously hypertensive rats fed Japanese diet were lower both in aortas and in internal carotid arteries than were those in spontaneously hypertensive rats (both P < 0.05 by analysis of variance) and in Wistar-Kyoto rats (both P < 0.05). Similarly, vasorelaxant responses to brain natriuretic peptide were lower both in aortas and in internal carotid arteries of stroke-prone spontaneously hypertensive rats than they were in spontaneously hypertensive rats (both P < 0.05) and in Wistar-Kyoto rats (P < 0.05). The responses to nitroglycerin in the stroke-prone spontaneously hypertensive rats and spontaneously hypertensive rats fed Japanese-style diet were also similar.. The vasorelaxant effects of natriuretic peptides are impaired in stroke-prone spontaneously hypertensive rats. This abnormality could play a role in the pathogenesis of stroke incidence in this hypertensive model.

Topics: Animals; Aorta, Thoracic; Atrial Natriuretic Factor; Carotid Artery, Internal; Cerebrovascular Disorders; Cyclic GMP; Hypertension; In Vitro Techniques; Male; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Nitroglycerin; Phenotype; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Vasodilation

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