Inflammatory markers, amino-terminal pro-brain natriuretic peptide, and mortality risk in dyspneic patients.

Cardiology Division and Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
American Journal of Clinical Pathology (Impact Factor: 3.01). 08/2008; 130(2):305-11. DOI: 10.1309/L7BP57F7UF7YNYKX
Source: PubMed

ABSTRACT Dyspnea is a common emergency department (ED) complaint, and it may be associated with significant mortality risk. We studied 599 dyspneic subjects enrolled in an ED. At 1 year, the role of inflammatory markers (including C-reactive protein [CRP]) and amino-terminal pro-brain natriuretic peptide (NT-proBNP) as independent predictors of mortality was assessed. By 1 year, 91 subjects (15.2%) had died. Among patients who died, the median CRP concentration at admission was significantly higher than in survivors: 47.2 mg/L (449.5 nmol/L; interquartile range [IQR], 10.2-101.9 mg/L [97.1-970.5 nmol/L]) vs 7.25 mg/L (69.5 nmol/L; IQR, 2.2-29.6 mg/L [21.0-281.9 nmol/L]; P < .001). For 1-year mortality, CRP had an area under the receiver operating characteristic curve of 0.76 (95% confidence interval [CI], 0.69-0.80; P < .001). In multivariable analysis, a CRP concentration greater than 14 mg/L was a strong predictor of mortality at 1 year (hazard ratio, 2.47; 95% CI, 1.51-4.02; P < .001). In multivariable models, CRP and NT-proBNP demonstrated independent and additive prognostic value. Among dyspneic patients, CRP levels are significantly associated with mortality at 1 year and show additive value to natriuretic peptide testing for prognosis.

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    ABSTRACT: Although numerous biomarkers may be prognostically meaningful in patients with acute dyspnea, few comparative analyses have addressed possible associations between a wide range of candidate biomarkers and clinical variables. Vital status was obtained for 517 acutely dyspneic patients at 4 years after emergency department presentation. A wide array of biomarkers was measured in this cohort, including natriuretic peptides, necrosis markers, inflammatory markers, hematologic markers, and renal markers. We performed statistical evaluation by using minimization of the Bayesian information criterion to evaluate predictors of 4-year mortality. Cox proportional hazards analysis was used to confirm results from the Bayesian information criterion. A final risk model was derived, and this model was then validated by applying it to patients from a separate cohort of acutely dyspneic patients. By 4 years, there were 186 deaths (36%). In addition to several clinical variables, several biomarkers were significant predictors of death, including log-transformed concentrations of hemoglobin (hazard ratio=0.77; P < 0.001), soluble ST2 (hazard ratio=1.38; P < 0.001), and amino-terminal pro-B-type natriuretic peptide (hazard ratio=1.19; P < 0.001). Risk models that used these significant variables were accurate in predicting 4-year mortality in both the training and validation sets. When added to traditional clinical variables, selected biomarkers added significant value for long-term prognostication in acute dyspnea.
    Clinical Chemistry 10/2010; 56(12):1814-21. · 7.77 Impact Factor
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    ABSTRACT: Stress myocyte biomarkers are used prognostically in patients with cardiovascular disease. We examined associations between amino-terminal pro-B-type natriuretic peptide (NT-proBNP), midregional pro-A-type natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM) concentrations and cardiac chamber volumes in chest pain patients without heart failure by use of computed tomography (CT). At the time of 64-slice CT scan, we acquired plasma and serum samples for these biomarkers from 346 patients [mean (SD) age 53 (12) years, 65% men]. Left atrial volume (LAV) and left ventricular volumes at end-diastole (LVEDV) and end-systole (LVESV) were measured and indexed to body surface area (LAVI, LVEDI, LVESI). Concentrations of both natriuretic peptides were correlated with LAV and LAVI (r = 0.19-0.32, all P <or= 0.0005) and MR-proADM with LV volumes and indices (r = -0.14 to -0.21, all P <or= 0.01). NT-proBNP and MR-proANP concentrations were higher in the top quartiles of patients than the lowest quartiles using LAV and LAVI, whereas MR-proADM concentrations were lower in the top quartiles of LV measures. In adjusted analyses, patients had 2- to 4-fold increased risk of LA enlargement for every incremental increase in log(10)NT-proBNP [LAV odds ratio (OR) 2.4, P = 0.03; LAVI OR 4.0, P = 0.003] and 10- to 13-fold increased risk of LA enlargement for every incremental increase in log(10)MR-proANP (LAV OR 10.7, P = 0.009; LAVI OR 13.1, P = 0.004). In patients without heart failure, both NT-proBNP and MR-proANP concentrations are independently associated with LA enlargement, whereas MR-proADM concentrations are correlated with LV volumes. This may partially explain the well-recognized value of natriuretic peptides for use in risk stratification.
    Clinical Chemistry 02/2010; 56(4):651-60. · 7.77 Impact Factor


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