There are many peer-reviewed papers covering cardiac markers, and it is frequently difficult for healthcare professionals to keep up with the literature. As a special service to our readers, CLI presents a few key literature abstracts from the clinical and scientific literature chosen by our editorial board as being particularly worthy of attention.
Incremental value of copeptin for rapid rule out of acute myocardial infarction.
Reichlin T et al. J Am Coll Cardiol 2009; 54(1): 60-8.
The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress, may be useful in this setting. This study examined the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI). Levels of copeptin were measured in 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by two independent cardiologists using all available data. The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses. The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/L in combination with a troponin T < or =0.01 microg/L correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%. The additional use of copeptin appears to allow a rapid and reliable rule out of AMI already at presentation and may thus obviate the need for prolonged monitoring and serial blood sampling in the majority of patients.
Copeptin: diagnostic parameter, biomarker, or both?
Rutishauser J. Ther Umsch 2009; 66(11): 731-4.
Copeptin denominates the C-terminal fragment of the vasopressin (AVP) precursor hormone. Circulating copeptin levels reflect the activity of the AVP system and correlate closely with plasma osmolality. The measurement of stimulated plasma AVP levels is crucial in the differential diagnosis of diabetes insipidus, particulary the characterisation of partial forms, and is used to diagnose primary polydipsia. However, determination of AVP levels is technically demanding, and validated assays are not readily available for clinical routine. Recently, a reliable sandwich immunoassay for measurement of serum or plasma copeptin levels has been introduced. Assaying stimulated copeptin levels will be helpful in the differential diagnosis of diabetes insipidus. Recent studies suggest that measurement of copeptin, once the assay is commercially available, might prove useful in the workup of hyponatremic disorders. Moreover, copeptin has been found to be a prognostically relevant biomarker in a variety of illnesses such as sepsis, shock, pneumonia, acute exacerbation of COPD, heart failure and myocardial infarction.
C-terminal provasopressin (copeptin) is a strong prognostic marker in patients with heart failure after an acute myocardial infarction: results from the OPTIMAAL study.
Voors AA et al. Eur Heart J 2009; 30(10): 1187-94.
The present study compared the prognostic value of a novel and promising marker, copeptin, with B-type natriuretic peptide (BNP), and N-terminal pro-BNP (NT-proBNP), on death or a composite cardiovascular endpoint in patients who developed heart failure after an acute myocardial infarction (AMI). From a subset of 224 patients of the OPTIMAAL study, blood samples were drawn at a mean of three days after AMI when all patients had signs and/or symptoms of heart failure or a left ventricular ejection fraction <0.35. Endpoints of interest were mortality and a composite cardiovascular endpoint, including death, MI, stroke and/or resuscitated cardiac arrest. Higher levels of copeptin, BNP, and NT-proBNP were all significantly related to both mortality and the composite cardiovascular endpoint (all P < 0.01). In a multivariable Cox proportional hazards model, including all three biomarkers and other relevant covariates, a doubling of copeptin was related to a 1.83 (1.26-2.64) times increased risk of mortality (P < 0.0001) and a 1.35 (1.05-1.72) times increased risk of the composite cardiovascular endpoint (P = 0.018). Receiver operating characteristic curves indicated that copeptin [area under curve (AUC) 0.81] was a stronger predictor of mortality compared with both BNP (AUC 0.66; P = 0.0063 vs. copeptin) and NT-proBNP (AUC 0.67; P = 0.0016 vs. copeptin). Finally, changes of copeptin levels after one month significantly added prognostic information to the baseline value. Copeptin is a strong and novel marker for mortality and morbidity in patients with heart failure after AMI. In this population, the predictive value of copeptin was even stronger than BNP and NT-proBNP.
Investigation of a multimarker approach to the initial assessment of patients with acute chest pain.
McCann CJ et al. Adv Ther 2009; 26(5):531-4.
Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article, previously published research is summarised, which assesses the value of myocyte injury, vascular inflammation, haemostatic and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, the study measures heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. the results demonstrated that, in patients presenting within four hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.
