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.

  • [Show abstract] [Hide abstract]
    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. DOI:10.1373/clinchem.2010.146506 · 7.77 Impact Factor
  • Clinical Research in Cardiology Supplements 04/2010; 5:21-26. DOI:10.1007/s11789-010-0008-9
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The study aim was to determine the prognostic value of a multimarker strategy for risk-assessment in patients presenting to the emergency department (ED) with dyspnea. Combining biomarkers with different pathophysiological backgrounds may improve risk stratification in dyspneic patients in the ED. The study prospectively investigated the prognostic value of the biomarkers N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), Cystatin-C (Cys-C), high-sensitivity C-reactive protein (hs-CRP), and Galectin-3 (Gal-3) for 90-day mortality in 603 patients presenting to the ED with dyspnea as primary complaint. hs-CRP, hs-cTnT, Cyst-C, and NT-proBNP were independent predictors of 90-day mortality. The number of elevated biomarkers was highly associated with outcome (odds ratio: 2.94 per biomarker, 95% confidence interval [CI]: 2.29 to 3.78, p < 0.001). A multimarker approach had incremental value beyond a single-marker approach. Our multimarker emergency dyspnea-risk score (MARKED-risk score) incorporating age ≥75 years, systolic blood pressure <110 mm Hg, history of heart failure, dyspnea New York Heart Association functional class IV, hs-cTnT ≥0.04 μg/l, hs-CRP ≥25 mg/l, and Cys-C ≥1.125 mg/l had excellent prognostic performance (area under the curve: 0.85, 95% CI: 0.81 to 0.89), was robust in internal validation analyses and could identify patients with very low (<3 points), intermediate (≥3, <5 points), and high risk (≥5 points) of 90-day mortality (2%, 14%, and 44% respectively; p < 0.001). A multimarker strategy provided superior risk stratification beyond any single-marker approach. The MARKED-risk score that incorporates hs-cTnT, hs-CRP, and Cys-C along with clinical risk factors accurately identifies patients with very low, intermediate, and high risk.
    Journal of the American College of Cardiology 09/2012; 60(17):1668-77. DOI:10.1016/j.jacc.2012.06.040 · 15.34 Impact Factor


Available from