Sensitive troponin I assay in early diagnosis of acute myocardial infarction.

BACKGROUND: Cardiac troponin testing is central to the diagnosis of acute myocardial infarction. We evaluated a sensitive troponin I assay for the early diagnosis and risk stratification of myocardial infarction. METHODS: In a multicenter study, we determined levels of troponin I as assessed by a sensitive assay, troponin T, and traditional myocardial necrosis markers in 1818 consecutive patients with suspected acute myocardial infarction, on admission and 3 hours and 6 hours after admission. RESULTS: For samples obtained on admission, the diagnostic accuracy was highest with the sensitive troponin I assay (area under the receiver-operating-characteristic curve [AUC], 0.96), as compared with the troponin T assay (AUC, 0.85) and traditional myocardial necrosis markers. With the use of the sensitive troponin I assay (cutoff value, 0.04 ng per milliliter) on admission, the clinical sensitivity was 90.7%, and the specificity was 90.2%. The diagnostic accuracy was virtually identical in baseline and serial samples, regardless of the time of chest-pain onset. In patients presenting within 3 hours after chest-pain onset, a single sensitive troponin I assay had a negative predictive value of 84.1% and a positive predictive value of 86.7%; these findings predicted a 30% rise in the troponin I level within 6 hours. A troponin I level of more than 0.04 ng per milliliter was independently associated with an increased risk of an adverse outcome at 30 days (hazard ratio, 1.96; 95% confidence interval, 1.27 to 3.05; P=0.003). CONCLUSIONS: The use of a sensitive assay for troponin I improves early diagnosis of acute myocardial infarction and risk stratification, regardless of the time of chest-pain onset.

Asymmetric dimethylarginine and the risk of cardiovascular events and death in patients with coronary artery disease: results from the AtheroGene Study.

As a competitive inhibitor of endothelial nitric oxide synthase, asymmetric dimethylarginine (ADMA) has been related to atherosclerotic disease. Little is known about the prognostic impact of baseline ADMA determination. In a prospective cohort of 1908 patients with coronary artery disease, we assessed baseline serum concentration of ADMA in 1874 consecutive patients with coronary artery disease. One hundred fourteen individuals developed the primary end point of death from cardiovascular causes or nonfatal myocardial infarction during a mean follow-up of 2.6+/-1.2 years. Median concentrations of ADMA levels were higher among individuals who subsequently developed the primary end point than among those who did not (0.70 versus 0.63 micromol/L; P<0.001). The risk of future cardiovascular event was associated with increasing thirds of baseline ADMA (P for trend, <0.001) such that individuals in the highest third at entry had a hazard ratio 2.48 times higher than those in the lowest third (95% confidence interval, 1.52 to 4.06; P<0.001). This relationship remained nearly unchanged after adjustment for most potential confounders. Prediction models that simultaneously incorporated ADMA, B-type natriuretic peptide, C-reactive protein, and creatinine in addition to traditional risk factors revealed B-type natriuretic peptide (hazard ratio, 1.96; 95% confidence interval, 1.3 to 3.0; P=0.002) and ADMA (hazard ratio, 1.90; 95% confidence interval, 1.3 to 2.8; P=0.001) as the strongest risk predictors. High levels of baseline ADMA independently predict future cardiovascular risk. ADMA has prognostic value beyond traditional risk factors and novel biomarkers and might guide therapeutic strategies.

Method comparison of cardiac marker assays on PATHFAST, StratusCS, AxSYM, Immulite 2000, triage, elecsys and cardiac reader.

The purpose of this evaluation was to perform a method comparison of the assays for cardiac troponin I (cTnl), CK-MB, myoglobin, and NT-proBNP on the automated PATHFAST Immuno-Assay Analyzer with respective immunoassays on other commercially available immunoanalyzers. The PATHFAST assays are immunochemiluminescent assays (in single reagent cartridges) employing two mono- or polyclonal antibodies in a sandwich test format. The calibration materials for cTnI and CK-MB are standardized to the reference materials NIST SRM 2921 (troponin CIT complex) and IRMM-IFCC 455 (CK-MB mass). The PATHFAST assays for cTnI, CK-MB, myoglobin, and NT-proBNP on the PATHFAST Analyzer were compared using 118 (NT-proBNP: 90) plasma samples from patients with different cardiovascular diseases with those on the Dade Behring StratusCS Analyzer, on the Abbott AxSYM System, on the DPC IMMMULITE 2000 Analyzer, on the Biosite Triage Meter Plus System, on the Roche Elecsys Immuno Analyzer 2010 and Roche Cardiac Reader System, respectively. The correlation coefficients for the comparison of cTnI methods ranged from 0.953 to 0.982, those for the comparison of myoglobin methods ranged from 0.776 to 0.992, and those for the comparison of CK-MB methods ranged from 0.835 to 0.999, with the Triage System giving in all comparisons the lowest correlation. Also the comparison of PATHFAST NTproBNP against the Roche Elecsys assay yielded a very good correlation (r = 0.992). The slopes of the regression line among methods showed considerable variation indicating that standardization efforts by international groups are indispensable to achieve harmonization of results. In summary, this evaluation study confirms the overall good correlation of the results obtained with assays for cardiac markers developed on the PATHFAST analyzer with those on other immunoassay platforms and thus the analytical reliability of the developed methods.

LC-electron capture-APCI(-)-MS determination of nitrobenzoxadiazole derivatives.

Nitrobenzoxadiazole (NBD) derivatives are determined with limits of detection ranging down to 20 nmol l(-1) using liquid chromatography-mass spectrometry (LC-MS) with electron capture (EC) ionisation. An atmospheric pressure chemical ionisation (APCI) interface operated in the negative ion mode is used as ionisation source. Amine derivatives of 4-chloro-7-nitro-2,1,3-benzoxadiazole (NBDCl) as well as the isocyanate derivatives of 4-nitro-7-piperazino-2,1,3-nitrobenzoxadiazole (NBDPZ) have been analysed using this technique. The parameters favouring electron capture mechanisms have been investigated thoroughly under consideration of the competing mechanism of deprotonation to allow a better understanding of the electron capture process and to improve selectivity of the analysis.

LC-electron capture APCI-MS for the determination of nitroaromatic compounds.

The determination of selected nitroaromatic compounds in liquid chromatography-mass spectrometry with electron capture (EC) ionisation using a commercial atmospheric pressure chemical ionisation (APCI) interface in the negative mode is described. The electron capture effect is observed for nitroaromatics which do not easily undergo deprotonation under these conditions. Depending on the structure of the analytes, either dissociative or, for the first time in LC-MS, non-dissociative electron capture is observed. Limits of detection and linear range for the determination of the analytes match those obtained for nitroaromatics which undergo deprotonation. The investigated substances comprise numerous substituted nitrobenzenes and nitrobenzooxadiazoles.