Biomarker Commons

Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy.

Circulation. 2012 Apr 3;125(13):1605-16

Authors: Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, Reilly PA, Vinereanu D, Siegbahn A, Yusuf S, Wallentin L

Abstract
BACKGROUND: Cardiac biomarkers are strong predictors of adverse outcomes in several patient populations. We evaluated the prevalence of elevated troponin I and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their association to cardiovascular events in atrial fibrillation (AF) patients in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial.
METHODS AND RESULTS: Biomarkers at randomization were analyzed in 6189 patients. Outcomes were evaluated by Cox proportional hazards models adjusting for established cardiovascular risk factors and the CHADS(2) and CHA(2)DS(2)-VASc risk scores. Patients were stratified based on troponin I concentrations: <0.010 μg/L, n=2663; 0.010 to 0.019 μg/L, n=2006; 0.020 to 0.039 μg/L, n=1023; ≥0.040 μg/L, n=497; and on NT-proBNP concentration quartiles: <387; 387 to 800; 801 to 1402; >1402 ng/L. Rates of stroke were independently related to levels of troponin I with 2.09%/year in the highest and 0.84%/year in the lowest troponin I group (hazard ratio [HR], 1.99 [95% CI, 1.17-3.39]; P=0.0040), and to NT-proBNP with 2.30%/year versus 0.92% in the highest versus lowest NT-proBNP quartile groups, (HR, 2.40 [95% CI, 1.41-4.07]; P=0.0014). Vascular mortality was also independently related to biomarker levels with 6.56%/year in the highest and 1.04%/year the lowest troponin I group (HR, 4.38 [95% CI, 3.05-6.29]; P<0.0001), and 5.00%/year in the highest and 0.61%/year in the lowest NT-proBNP quartile groups (HR, 6.73 [3.95-11.49]; P<0.0001). Biomarkers increased the C-statistic from 0.68 to 0.72, P<0.0001, for a composite of thromboembolic events.
CONCLUSIONS: Elevations of troponin I and NT-proBNP are common in patients with AF and independently related to increased risks of stroke and mortality. Cardiac biomarkers seem useful for improving risk prediction in AF beyond currently used clinical variables.

PMID: 22374183 [PubMed - indexed for MEDLINE]

Evolving role of biomarkers in acute cerebrovascular disease.

Ann Neurol. 2012 Mar;71(3):289-303

Authors: Kernagis DN, Laskowitz DT

Abstract
The development of a clinically validated biomarker of acute cerebral ischemia would have the potential to facilitate the use of time-sensitive reperfusion strategies, allow for individualization of patient care by predicting relative risk of hemorrhage and volume of penumbral tissue, and add valuable prognostic information for patients presenting with acute stroke. Additionally, a stroke biomarker might benefit early stage clinical research by serving as a surrogate measure of ischemic injury. Although at present there are no clinically validated biomarkers of acute stroke, previous studies have focused on markers associated with different components of the ischemic cascade, including microglial activation, inflammation, oxidative stress, neuronal injury, hemostasis, and endothelial dysfunction. Evolving technologies have provided high throughput approaches to investigate potential gene and protein signatures, and methods to measure newly discovered markers of cell death and immune responses. Prior to defining the clinical utility of stroke biomarkers, it is critical to understand the inherent limitations of a biomarker-based approach and define its potential value for providing adjunctive diagnostic and prognostic information. The identification and validation of a clinically relevant biomarker, or panel of markers, of stroke will ultimately require incorporation of both stringent research design and assessment in the clinical context in which the marker will be used.

PMID: 22451199 [PubMed - indexed for MEDLINE]

Relations between plasma ox-LDL and carotid plaque among Chinese Han ethnic group.

Neurol Res. 2011 Jun;33(5):460-6

Authors: Fang R, Zhang N, Wang C, Zhao X, Liu L, Wang Y, Xu J, Wang X, Liu Z, Wang Y

Abstract
OBJECTIVES: To study the relationship between plasma oxidized low-density lipoprotein (ox-LDL) and carotid plaque, including plaque stability, of patients with acute ischemic stroke among Chinese Han ethnic group.
METHODS: A total of 181 patients with acute ischemic stroke were recruited and enrolled. The subjects were divided into a carotid plaque group and a no-plaque group by carotid ultrasound. The stability of carotid atheromas was assessed by ultrasound echo density, and the carotid plaque group was further divided into a vulnerable plaque group and a stable plaque group based on the echo results.
RESULTS: The study showed that the correlation between age [odds ratio (OR): 1.047; 95% confidence interval (CI): 1.014-1.082; P<0.01] and carotid plaque was significant. Plasma ox-LDL (OR: 1.020; 95%CI: 1.010-1.030; P<0.001) was also found to be significantly correlated with carotid plaque. Age was irrelevant to plaque stability (P = 0.0685). The ox-LDL of the vulnerable plaque group was found to be significantly higher than that of the stable plaque group (P = 0.015). By measuring the plasma ox-LDL in patients with ischemic stroke, the proportion under the receiver operating characteristic curve of vulnerable carotid plaques was 0.690 with a 95%CI of 0.613-0.767 (P<0.001). The point of cut-off was 94.5943, the sensitivity was 0.805, and the specificity was 0.505.
CONCLUSION: The plasma ox-LDL level and age are possible risk factors for carotid plaque among patients with ischemic stroke of the Chinese Han ethnic group. This study suggests that ox-LDL could be used as a biomarker in screening for vulnerable carotid plaque in clinical practice.

PMID: 21669113 [PubMed - indexed for MEDLINE]

Effects of treatment intensity in upper limb robot-assisted therapy for chronic stroke: a pilot randomized controlled trial.

Neurorehabil Neural Repair. 2011 Jul-Aug;25(6):503-11

Authors: Hsieh YW, Wu CY, Liao WW, Lin KC, Wu KY, Lee CY

Abstract
BACKGROUND AND OBJECTIVES: Robot-assisted therapy (RT) is a current promising intervention in stroke rehabilitation, but more research is warranted for examining its efficacy and the dose-benefit relation. The authors investigated the effects of higher intensity versus lower intensity RT on movements of forearm pronation-supination and wrist flexion-extension relative to conventional rehabilitation (CR) in patients poststroke for a mean of 21 months.
METHODS: In this pilot study, 18 patients with initial mean Fugl-Meyer Assessment (FMA) of 37 to 44 for the upper extremity were randomized to higher intensity RT, lower intensity RT, or CR intervention for 4 weeks. The dose of the higher intensity RT was twice the number of repetitions in the lower intensity RT. Outcome measures at pretreatment and posttreatment were administered to patients to evaluate beneficial and adverse effects of interventions. Primary outcomes were the FMA and Medical Research Council scale.
RESULTS: There were significant differences in motor function (P = .04) and daily performance (P = .03) among the 3 groups. The higher intensity RT group showed better improvement in motor function, muscle strength, performance of daily activities, and bimanual ability than the other 2 groups. The intensive RT intervention did not induce higher levels of an oxidative DNA biomarker.
CONCLUSIONS: Higher intensity of RT that assists forearm and wrist movements may lead to greater improvement in motor ability and functional performance in stroke patients. A sample size of only 20 to 25 in each arm of a larger randomized controlled trial is needed to confirm the findings for similar subjects.

PMID: 21436390 [PubMed - indexed for MEDLINE]

Homozygous c.14576G>A variant of RNF213 predicts early-onset and severe form of moyamoya disease.

Neurology. 2012 Mar 13;78(11):803-10

Authors: Miyatake S, Miyake N, Touho H, Nishimura-Tadaki A, Kondo Y, Okada I, Tsurusaki Y, Doi H, Sakai H, Saitsu H, Shimojima K, Yamamoto T, Higurashi M, Kawahara N, Kawauchi H, Nagasaka K, Okamoto N, Mori T, Koyano S, Kuroiwa Y, Taguri M, Morita S, Matsubara Y, Kure S, Matsumoto N

Abstract
OBJECTIVE: RNF213 was recently reported as a susceptibility gene for moyamoya disease (MMD). Our aim was to clarify the correlation between the RNF213 genotype and MMD phenotype.
METHODS: The entire coding region of the RNF213 gene was sequenced in 204 patients with MMD, and corresponding variants were checked in 62 pairs of parents, 13 mothers and 4 fathers of the patients, and 283 normal controls. Clinical information was collected. Genotype-phenotype correlations were statistically analyzed.
RESULTS: The c.14576G>A variant was identified in 95.1% of patients with familial MMD, 79.2% of patients with sporadic MMD, and 1.8% of controls, thus confirming its association with MMD, with an odds ratio of 259 and p < 0.001 for either heterozygotes or homozygotes. Homozygous c.14576G>A was observed in 15 patients but not in the controls and unaffected parents. The incidence rate for homozygotes was calculated to be >78%. Homozygotes had a significantly earlier age at onset compared with heterozygotes or wild types (median age at onset 3, 7, and 8 years, respectively). Of homozygotes, 60% were diagnosed with MMD before age 4, and all had infarctions as the first symptom. Infarctions at initial presentation and involvement of posterior cerebral arteries, both known as poor prognostic factors for MMD, were of significantly higher frequency in homozygotes than in heterozygotes and wild types. Variants other than c.14576G>A were not associated with clinical phenotypes.
CONCLUSIONS: The homozygous c.14576G>A variant in RNF213 could be a good DNA biomarker for predicting the severe type of MMD, for which early medical/surgical intervention is recommended, and may provide a better monitoring and prevention strategy.

PMID: 22377813 [PubMed - indexed for MEDLINE]

Evidence that a panel of neurodegeneration biomarkers predicts vasospasm, infarction, and outcome in aneurysmal subarachnoid hemorrhage.

PLoS One. 2011;6(12):e28938

Authors: Siman R, Giovannone N, Toraskar N, Frangos S, Stein SC, Levine JM, Kumar MA

Abstract
Biomarkers for neurodegeneration could be early prognostic measures of brain damage and dysfunction in aneurysmal subarachnoid hemorrhage (aSAH) with clinical and medical applications. Recently, we developed a new panel of neurodegeneration biomarkers, and report here on their relationships with pathophysiological complications and outcomes following severe aSAH. Fourteen patients provided serial cerebrospinal fluid samples for up to 10 days and were evaluated by ultrasonography, angiography, magnetic resonance imaging, and clinical examination. Functional outcomes were assessed at hospital discharge and 6-9 months thereafter. Eight biomarkers for acute brain damage were quantified: calpain-derived α-spectrin N- and C-terminal fragments (CCSntf and CCSctf), hypophosphorylated neurofilament H,14-3-3 β and ζ, ubiquitin C-terminal hydrolase L1, neuron-specific enolase, and S100β. All 8 biomarkers rose up to 100-fold in a subset of patients. Better than any single biomarker, a set of 6 correlated significantly with cerebral vasospasm, brain infarction, and poor outcome. Furthermore, CSF levels of 14-3-3β, CCSntf, and NSE were early predictors of subsequent moderate-to-severe vasospasm. These data provide evidence that a panel of neurodegeneration biomarkers may predict lasting brain dysfunction and the pathophysiological processes that lead to it following aSAH. The panel may be valuable as surrogate endpoints for controlled clinical evaluation of treatment interventions and for guiding aSAH patient care.

PMID: 22174930 [PubMed - indexed for MEDLINE]

Interleukin-1 and stroke: biomarker, harbinger of damage, and therapeutic target.

Cerebrovasc Dis. 2011;32(6):517-27

Authors: Denes A, Pinteaux E, Rothwell NJ, Allan SM

Abstract
Inflammation is established as a contributor to cerebrovascular disease. Risk factors for stroke include many conditions associated with chronic or acute inflammation, and inflammatory changes in the brain after cerebrovascular events contribute to outcome in experimental studies, with growing evidence from clinical research. The brain is extremely susceptible to inflammatory challenge, but resident glia, endothelial cells and neurones can all mount a pronounced inflammatory response to infection or injury. Recent discoveries highlight the importance of peripherally-derived immune cells and inflammatory molecules in various central nervous system disorders, including stroke. The inflammatory cytokine, interleukin-1 (IL-1), plays a pivotal role in both local and systemic inflammation, and is a key driver of peripheral and central immune responses to infection or injury. Inhibition of IL-1 has beneficial effects in a variety of experimental paradigms of acute brain injury and is a promising clinical target in stroke. We propose that blockade of IL-1 could be therapeutically useful in several diseases which are risk factors for stroke, and there is already considerable pre-clinical and clinical evidence that inhibition of IL-1 by IL-1 receptor antagonist may be valuable in the management of acute stroke.

PMID: 22104408 [PubMed - indexed for MEDLINE]

Repurposing an old drug to improve the use and safety of tissue plasminogen activator for acute ischemic stroke: minocycline.

Pharmacotherapy. 2010 Jul;30(7 Pt 2):55S-61S

Authors: Hess DC, Fagan SC

Abstract
Tissue plasminogen activator (tPA) is the only drug approved by the United States Food and Drug Administration for treatment of acute ischemic stroke. Because the drug must be used soon after symptom onset and is associated with intracerebral hemorrhage, tPA remains underutilized. Research has therefore focused on identifying other drugs that can be used concomitantly with tPA to improve the odds of a favorable recovery and to reduce the risk of intracerebral hemorrhage. Minocycline is a broad-spectrum antibiotic that has been found to be a neuroprotective agent in preclinical ischemic stroke models. Minocycline inhibits matrix metalloproteinase-9, a biomarker for intracerebral hemorrhage associated with tPA use. Minocycline is also an antiinflammatory agent and inhibits poly(ADP-ribose) polymerase-1. Minocycline has been safe and well tolerated in clinical trials. Additional safety and efficacy data are needed, and a phase III trial of minocycline with tPA in patients experiencing acute ischemic stroke is planned.

PMID: 20575623 [PubMed - indexed for MEDLINE]

[Hormones as biomarkers for diagnosis and prognosis].

Praxis (Bern 1994). 2012 Feb 15;101(4):251-7

Authors: Winzeler BF, Christ-Crain M

Abstract
Procalcitonin is a biomarker for estimating the likelihood of a bacterial infection. Procalcitonin-guided antibiotic therapy can reduce antibiotic overuse in respiratory tract infections. The differential diagnosis of water-electrolyte imbalances is challenging. Copeptin is co-secreted with arginine vasopressin (AVP) and is a reliable surrogate of plasma AVP. Copeptin may become a useful diagnostic tool in patients with polydipsia-polyuria syndrome and hyponatremia. Copeptin is also known to mirror different levels of stress. It appears to have an interesting potential as a new prognostic biomarker in patients with ischemic stroke. Biomarkers should not be used without the clinical context. They are meant to complement clinical judgment based upon a synthesis of available clinical and laboratory features in each patients.

PMID: 22337515 [PubMed - indexed for MEDLINE]

Molecular biomarker of inflammatory response is associated with rebleeding in spontaneous intracerebral hemorrhage.

Eur Neurol. 2011;66(6):322-7

Authors: Wang KW, Cho CL, Chen HJ, Liang CL, Liliang PC, Tsai YD, Wang HK, Lu K

Abstract
BACKGROUND AND PURPOSE: Rebleeding in spontaneous intracerebral hemorrhage (ICH) is a major cause of morbidity and mortality among stroke survivors. Due to the links between inflammation and rebleeding, we hypothesized that the biomarkers of inflammation are associated with the pathogenesis of rebleeding in ICH. We sought to investigate whether these biomarkers and clinical variables on admission can provide prognostic information on the risk of rebleeding.
METHODS: This prospective study enrolled 59 consecutive patients with spontaneous ICH. We determined the concentrations of interleukin-10 (IL-10), intercellular adhesion molecule-1, and complement 3 in blood samples obtained on admission.
RESULTS: Univariate analysis indicated that hematoma volume, leukocyte count, hydrocephalus, and plasma IL-10 levels were associated with rebleeding. Multivariate logistic regression analysis indicated that hydrocephalus (95% CI of OR, 1.6-26.7) and IL-10 (95% CI of OR, 1.03-1.22) were independently associated with an increased probability of rebleeding.
CONCLUSION: These data suggest that IL-10, a molecular biomarker of inflammatory response in the early acute phase of ICH, is associated with subsequent rebleeding.

PMID: 22075847 [PubMed - indexed for MEDLINE]

Plasma biomarker and stroke.

Cerebrovasc Dis. 2011;32(4):406

Authors: Meng R, Ji X

PMID: 21986385 [PubMed - indexed for MEDLINE]

Fetuin-A: a multifunctional protein.

Recent Pat Endocr Metab Immune Drug Discov. 2011 May;5(2):124-46

Authors: Mori K, Emoto M, Inaba M

Abstract
Sixty-six years have elapsed since the discovery of fetuin in 1944, but its importance in mammalian physiology has only recently been appreciated. Fetuin, first isolated from fetal bovine serum and now most commonly known as either fetuin-A, alpha-2-HS-glycoprotein (recommended name by UniprotKB and PIR), or α2-Heremans-Schmid glycoprotein, functions as an important component of diverse normal and pathological processes, including vascular calcification and bone metabolism regulation, insulin resistance, protease activity control, keratinocytes migration, and breast tumor cell proliferative signaling. Fetuin-A has also been identified as a biomarker for neurodegenerative disease. Here, we summarize recent publications focusing on the structural and functional properties of fetuin-A. The emerging importance of fetuin-A for both diagnosis and therapeutics has come to the attention of the pharmaceutical industry. Therefore, we will discuss the status of patents based on fetuin-A.

PMID: 22074587 [PubMed - indexed for MEDLINE]

Hyperacute detection of neurofilament heavy chain in serum following stroke: a transient sign.

Neurochem Res. 2011 Dec;36(12):2287-91

Authors: Sellner J, Patel A, Dassan P, Brown MM, Petzold A

Abstract
Serological biomarkers which enable quick and reliable diagnosis or measurement of the extent of irreversible brain injury early in the course of stroke are eagerly awaited. Neurofilaments (Nf) are a group of proteins integrated into the scaffolding of the neuronal and axonal cytoskeleton and an established biomarker of neuro-axonal damage. The Nf heavy chain (NfH(SMI35)) was assessed together with brain-specific astroglial proteins GFAP and S100B in hyperacute stroke (6 and 24 h from symptom onset) and daily for up to 6 days. Twenty-two patients with suspected stroke (median NIHSS 8) were recruited in a prospective observational study. Evidence for an ischaemic or haemorrhagic lesion on neuroimaging was found in 18 (ischaemia n = 16, intracerebral haemorrhage n = 2). Serum NfH(SMI35) levels became detectable within 24 h post-stroke (P < 0.0001) and elevated levels persisted over the study course. While GFAP was not detectable during the entire course, S100B levels peaked at the end of the observation period. The data indicate that significant in vivo information on the pathophysiology of stroke may be obtained by the determination of NfH(SMI35). Further studies are required to evaluate whether NfH(SMI35) in hyperacute stroke reflects the extent of focal ischaemic injury seen on neuroimaging or is a consequence of more diffuse neuro-axonal damage.

PMID: 21792676 [PubMed - indexed for MEDLINE]

Biomarkers to predict clinical progression in small vessel disease strokes: prognostic role of albuminuria and oxidized LDL cholesterol.

Atherosclerosis. 2011 Nov;219(1):368-72

Authors: Cuadrado-Godia E, Ois A, Garcia-Ramallo E, Giralt E, Jimena S, Rubio MA, Rodríguez-Campello A, Jiménez-Conde J, Roquer J

Abstract
OBJECTIVE: Clinical progression in lacunar strokes (LS) is an unpredictable and fearful complication. Endothelial dysfunction (ED) is believed to be the first step in the pathophysiology of LS therefore we aimed to analyze the association of three markers of ED: albuminuria, von Willebrand factor (vWF), and oxidized LDL cholesterol (ox-LDL) with LS progression.
METHODS: From December 2007 to December 2010, 127 LS patients admitted within 6 h of symptom onset were prospectively assessed. Progression was defined as initial NIHSS score worsening ≥4 points within the first 72 h. Analysis of vWF and ox-LDL was done at admission. Albuminuria was measured in the first morning spot urine. Association between 3 biomarkers and progression was tested using logistic regression analysis. Other clinical variables of interest were also studied. Discriminative power was analyzed with a receiver operator curve.
RESULTS: Twenty-two patients (17.3%) progressed. Progression was associated with worse outcome at 90 days. Albuminuria and ox-LDL were associated in univariate analysis; vWF was not. Adjusted OR were: ox-LDL [OR: 1.03; 95% CI: 1.01-1.07, p=0.019], albuminuria [OR: 2.07; 95% CI: 1.04-4.13, p=0.039]. Association was linear without a cut-off point. Clinical variables were not associated with progression. The model including albuminuria and ox-LDL had a good predictive value [AUC: 0.80 [0.70-0.89)].
CONCLUSIONS: Albuminuria and ox-LDL levels are independently associated with higher risk of progression in LS. The lack of reliable clinical predictors makes biomarker research a priority to improve progression detection in this subtype of ischemic strokes.

PMID: 21862014 [PubMed - indexed for MEDLINE]

Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke.

Clin Chem. 2012 Jan;58(1):237-45

Authors: Foerch C, Niessner M, Back T, Bauerle M, De Marchis GM, Ferbert A, Grehl H, Hamann GF, Jacobs A, Kastrup A, Klimpe S, Palm F, Thomalla G, Worthmann H, Sitzer M,

Abstract
BACKGROUND: Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach.
METHODS: Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic.
RESULTS: The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 μg/L (0.41-17.66) vs 0.08 μg/L (0.02-0.14), P<0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847-0.982), P<0.001]. A GFAP cutoff of 0.29 μg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic.
CONCLUSIONS: Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.

PMID: 22125303 [PubMed - indexed for MEDLINE]

Treatment of fever after stroke: conflicting evidence.

Pharmacotherapy. 2011 Nov;31(11):1085-91

Authors: Wrotek SE, Kozak WE, Hess DC, Fagan SC

Abstract
Approximately 50% of patients hospitalized for stroke develop fever. In fact, experimental evidence suggests that high body temperature is significantly correlated to initial stroke severity, lesion size, mortality, and neurologic outcome. Fever occurring after stroke is associated with poor outcomes. We investigated the etiology of fever after stroke and present evidence evaluating the efficacy and safety of interventions used to treat stroke-associated fever. Oral antipyretics are only marginally effective in lowering elevated body temperature in this population and may have unintended adverse consequences. Nonpharmacologic approaches to cooling have been more effective in achieving normothermia, but whether stroke outcomes can be improved remains unclear. We recommend using body temperature as a biomarker and a catalyst for aggressive investigation for an infectious etiology. Care must be taken not to exceed the new standard of a maximum acetaminophen dose of 3 g/day to avoid patient harm.

PMID: 22026396 [PubMed - indexed for MEDLINE]

Elevated BNP is associated with vasospasm-independent cerebral infarction following aneurysmal subarachnoid hemorrhage.

Neurocrit Care. 2011 Aug;15(1):13-8

Authors: Taub PR, Fields JD, Wu AH, Miss JC, Lawton MT, Smith WS, Young WL, Zaroff JG, Ko NU

Abstract
BACKGROUND: Elevated levels of B-type natriuretic peptide (BNP) have been associated with cardiac dysfunction and adverse neurological outcomes after subarachnoid hemorrhage (SAH). We sought to determine whether elevated levels of BNP are independently associated with radiographic cerebral infarction after SAH.
METHODS: Plasma BNP levels were measured after admission, a mean of 5.5 ± 3.0 days after SAH onset. Cerebral infarction was determined by retrospective review of computerized tomography (CT) scans. Cerebral vasospasm was confirmed by the presence of vascular narrowing on cerebral angiogram. The association between BNP and cerebral infarction was quantified using multivariable logistic regression and reverse stepwise elimination of clinical covariates. A stratified analysis was performed to quantify the association between BNP levels and infarction in patients with and without angiographic vasospasm.
RESULTS: BNP levels were measured from 119 subjects. The median BNP level was 105 pg/ml (interquartile range 37-275 pg/ml). In our multivariable model, the top quartile of BNP levels (≥ 276 pg/ml) were associated with an increased odds of cerebral infarction (OR 4.2, P = 0.009). The stratified analysis showed that the association between BNP and infarction was strongest in patients without angiographic vasospasm (OR 7.8, P = 0.006).
CONCLUSIONS: Elevated levels of BNP are strongly and independently associated with cerebral infarction, and the association is most pronounced in patients without angiographic vasospasm. These results provide further evidence that other mechanisms can contribute to infarction, and BNP may be a useful biomarker in detecting patients at risk for adverse outcomes without large vessel vasospasm.

PMID: 21479679 [PubMed - indexed for MEDLINE]