The Utility of Biomarkers in Sorting Out the Complex Patient Christopher Moriates, MD, Alan Maisel, MD  The American Journal of Medicine  Volume 123, Issue 5, Pages 393-399 (May 2010) DOI: 10.1016/j.amjmed.2009.07.034 Copyright © 2010 Terms and Conditions

Figure 1 Current and possible future biomarkers related to cardiac disease. IMA = ischemia-modified albumin; FABP = fatty acid binding protein; PIGF = placental growth factor; MPO = myeloperoxidase; TnI/TnT = troponin I/troponin T; Myo = myoglobin; CKMB = creatinine kinase MB isotype; CRP = C-reactive protein; TNFα = tumor-necrosis factor α; sCD40L = soluble CD40 ligand; ST2 = soluble ST2 receptor; PCT = procalcitonin; HgA1c = glycosylated hemoglobin; LDL = low-density lipoprotein; OxLDL = oxidized low-density lipoprotein; HCY = homocysteine; BNP = B-type natriuretic peptide; NT-proBNP = amino-terminal fragment of pro-B-type natriuretic peptide; MMP = metalloproteinases; MR-proANP = midregional pro-A-type natriuretic peptide; Gal-3 = galectin-3; GDF-15 = growth differentiation factor 15; NGAL = neutrophil gelatinase-associated lipocalin; Myo. ischemia = myocardial ischemia; LV = left ventricular. The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 2 B-type natriuretic peptide (BNP) nomogram: using BNP values to determine confidence in the diagnosis of heart failure. A BNP nomogram can be used to determine the final probability of acute heart failure based on the initial clinical judgment (pretest probability) and the BNP level. A patient that has approximately a 50% pretest probability of having heart failure may have vastly different post-test probabilities based on the BNP level, as shown by the 3 different lines drawn on the nomogram. Adapted from: McCullough PA, Nowak RM, McCord J, et al. B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation. 2002;106:416-422.13 The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 3 Missed diagnosis of congestive heart failure (CHF) in the emergency department in a study of 250 patients. In a study of 250 patients presenting to the emergency department with symptoms of dyspnea, 15 patients were diagnosed with having CHF by emergency physicians when they actually had other causes of dyspnea, while another 15 patients that ultimately did have CHF were misdiagnosed by emergency physicians. The B-type natriuretic peptide levels between these 2 groups differed significantly and if a cutoff B-type natriuretic peptide level of 80 pg/mL was used for diagnosis, 29 of the 30 initially misdiagnosed patients would have been correctly identified. Adapted from: Dao Q, Krishnaswamy P, Kazanegra R, et al. Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol. 2001;37:379-385.16 The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 4 The sensitivity and specificity of natriuretic peptides for the diagnosis of acute destabilized heart failure in short-of-breath patients presenting to an emergency department. The natriuretic peptides—BNP, NT-proBNP and the more novel MR-proANP—have similar sensitivities and specificities for the diagnosis of acute heart failure at different cut-points. BNP = B-type natriuretic peptide; NT-proBNP = amino-terminal fragment of pro-B-type natriuretic peptide; MR-proANP = midregional pro-A-type natriuretic peptide. Data from: Gegenhuber A, Struck J, Poelz W, et al. Midregional pro-A-type natriuretic peptide measurements for diagnosis of acute destabilized heart failure in short-of-breath patients: comparison with B-type natriuretic peptide (BNP) and amino-terminal proBNP. Clin Chem. 2006;52:827-831.18 The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 5 List of important biomarkers that may aid in the diagnosis and prognosis at various stages of coronary artery disease. MPO = myeloperoxidase; CRP = C-reactive protein; HCY = homocysteine; CD40L = CD40 ligand; OxLDL = oxidized low-density lipoprotein; MCP-1 = monocyte chemotactic protein-1; MMPs = matrix metalloproteinases; IL-6 = interleukin-6; IMA = ischemia-modified albumin; FABP = fatty acid binding protein; MDA-LDL = malondialdehyde-modified low-density lipoprotein; FFA = free fatty acids; BNP = B-type natriuretic peptide; Myo = myoglobin; CKMB = creatinine kinase MB isotype; TnI/TnT = troponin I/troponin T; NT-proBNP = amino-terminal fragment of proBNP. The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 6 The sensitivity and specificity of urine NGAL and creatinine for the diagnosis of acute kidney injury. Urine NGAL at a cut-point of 85 μg/g has sensitivity equal to a creatinine level of 1.4 mg/dL (93%), but has a much greater specificity (98% vs. 75%) at these cut-points. Urine NGAL may prove to be a more reliable marker for acute kidney injury than the current standard, creatinine. Urine NGAL = urine neutrophil gelatinase-associated lipocalin. Data from: Nickolas TL, O'Rourke MJ, Yang J, et al. Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med. 2008;148:810-819.37 The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions

Figure 7 Hypothetical paradigm whereby the combination of BNP, NGAL, and serum creatinine could help determine the euvolemic state in patients treated for acute decompensated heart failure, avoiding or mitigating the worsening renal function that often occurs in this setting. BNP = B-type natriuretic peptide; NGAL = neutrophil gelatinase-associated lipocalin. The American Journal of Medicine 2010 123, 393-399DOI: (10.1016/j.amjmed.2009.07.034) Copyright © 2010 Terms and Conditions