This chapter explains normal heart function and provides an overview of these cardiac disorders: coronary heart disease, heart failure and hypertension. For each analyte used in the cardiac field the biological function is explained, with the clinical applications of the test and its limitations. Typical assay technology is described, with desirable assay performance characteristics. The type of sample and frequency of use are included, with an example reference interval (for background information only). The analytes included are: CK-MB, myoglobin, FABP, Apo AI, AII and B, Lp(a), homocysteine, CRP, Lp-PLA₂, BNP and NT-PRO-BNP, galectin-3, sST2 and plasma renin.

Pre-pro-vasopressin is the precursor protein that is proteolytically cleaved into vasopressin, also known as antidiuretic hormone, neurophysin II and copeptin.  Copeptin is a glycosylated 39-amino acid peptide whose biological function is unknown.  However, because vasopressin is a 9-amino acid peptide with a short half-life and poor in vitro stability, measurement of copeptin is a surrogate for vasopressin release into blood.

Copeptin: 1-2 pmol/L

While cardiac troponin is the “gold standard” biomarker for diagnosis of acute myocardial infarction, results are not increased above the 99th percentile until there is substantial amount of myocardial injury.  Therefore, results are within the normal range when blood is tested within the first few hours after the onset of AMI.  A biomarker that can reliably rule out AMI during these initial hours after the onset of chest pain can be very useful for the early triage and potentially discharge of patients suspected of AMI but who are at low risk (due to history or presentation).

As AMI is a highly stressful event, vasopressin and copeptin are released into the circulation within the first few minutes after disease onset. In studies conducted on chest patients presenting to the emergency room, a normal result for both copeptin and cardiac troponin has a negative predictive value of 99%.

Like other early markers of AMI, e.g., fatty acid binding protein and myoglobin, increased concentration of copeptin is not specific for AMI.   Any clinical situation that is associated with stress can increase copeptin and the positive predictive value is poor.  Results of copeptin must be interpreted within the clinical context the clinical presentation and other serum biomarkers such as cardiac troponin.

All assays for copeptin are based on a two-site immunometric assay format.

Commercial assays for copeptin are available for research use only and are not currently used in clinical laboratories in the USA but it has received CE Mark approval for use in Europe.

1. Maisel, A., Mueller, C., Neath, S.X., Christenson, R.H., Morgenthaler, N.G., McCOrd, J., Nowak, R.M., Vilke, G., Daniels, L.B., Hollander, J.E., Apple, F.S., Cannon, C., Nagurney, J.T., Schreiber, D., deFilippi, C., Hogan, C., Diercks, D.B., Stein, J.C., Headden, G., Limkakeng, A.T., Anand, I., Wu, A.H.B., Papassotiriou, J., Hartmann, O., Ebmeyer, S., Clopton, P., Jaffe, A.S., and Peacock, W.F.  Copeptin helps in the early detection of patients with acute myocardial infarction. J. Am. Coll. Cardiol.  62, 150-160 (2013).
2. Morgenthaler, N.G., Struck, J, Alonso, C, and Bergmann, A.  Assay for the measurement of copeptin, a stable peptide derived form the precursor of vasopressin. Clin. Chem. 52, 112-119 (2006).

Deborah French obtained her Ph.D. in Biochemistry at the University of Strathclyde in Glasgow, Scotland, and then completed a postdoctoral fellowship in pharmacogenetics research at St Jude Children’s Research Hospital in Memphis, Tennessee under the direction of Dr Mary Relling. She then completed a ComACC accredited Clinical Chemistry Postdoctoral Fellowship at the University of California San Francisco with Dr Alan Wu. Deborah is currently the Director of Mass Spectrometry and the Assistant Director of Chemistry at the University of California San Francisco Medical Center Clinical Laboratories.

Dr. Alan H. B. Wu is Professor of Laboratory Medicine, and Chief, Clinical Chemistry Laboratory, San Francisco General Hospital. His area of research is focused on “personalized therapeutics,” i.e., the use of biomarkers to determine proper selection and dosing of drugs to maximize efficacy and minimize adverse reactions. Many future drugs will require biomarker testing prior to use on individual patients and clinical trials are needed to validate their use. In the area of pharmacogenomics, he is interested in drug dosing studies for warfarin, irinotecan, tamoxifen, phenytoin and lipid-lowering drugs. He is also performing research on validating novel protein markers for cardiovascular diseases such as stroke, acute coronary syndromes and heart failure. His awards include the 2002 American Association for Clinical Chemistry Outstanding Contributions to Education Award.

Coronary artery disease, atherosclerosis, angina, ischemia, myocardial infarction, heart failure, hypertension, CK-MB, myoglobin, FABP, Apo AI, AII and B, Lp(a), homocysteine, CRP, Lp-PLA₂, BNP, NT-PRO-BNP, galectin-3, sST2, renin.