Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept

Ilva, Tuomo; Eriksson, Susann; Lund, Juha; Porela, Pekka; Mustonen, Harri; Pettersson, Kim; Pulkki, Kari; Voipio-Pulkki, Liisa Maria

doi:10.1111/j.1365-2362.2005.01466.x

Cited by 22 publications

(14 citation statements)

References 18 publications

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“…Several clinical biomarkers are commonly used for the early detection of heart disease including the MB isoenzyme of creatine kinase (CK-MB), and myoglobin (Adams et al, 1993;Apple, 2001;Babuin and Jaffe, 2005;Eriksson et al, 2006;Howie-Esquivel and White, 2008;Jaffe et al, 2006). But troponin I has rapidly become the biomarker of choice due to its high specificity and selectivity for AMI (Casals et al, 2007;Ilva et al, 2005;Labugger et al, 2000;Melanson et al, 2008;Panteghini, 2005;Wallace et al, 2004). Although the specific details of the mechanism of troponin I release from damaged cardiac cells are not fully understood, cardiac troponin I levels are measurable in serum within 4-6 h after the onset of AMI.…”

Section: Introductionmentioning

confidence: 99%

High affinity peptides for the recognition of the heart disease biomarker troponin I identified using phage display

Park

Banta

2009

Biotech & Bioengineering

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Troponin I is a specific and sensitive clinical biomarker for myocardial injury. In this study we have used polyvalent phage display to isolate unique linear peptide motifs which recognize both the human and rat homologs of troponin I. The peptide specific for human troponin I has a sequence of FYSHSFHENWPS and the peptide specific for the rat troponin I has a sequence of FHSSWPVNGSTI. Enzyme-linked immunosorbent assays (ELISAs) were used to evaluate the binding interactions, and the two phage-displayed peptides exhibited some cross-reactivity, but they were both more specific for the troponin I homolog they were selected against. The binding affinities of the phage-displayed peptides were decreased by the presence of complex tissue culture media (MEM), and the addition of 10% calf serum further interfered with the binding of the target proteins. Kinetic indirect phage ELISAs revealed that both troponin I binding peptides were found to have nanomolar affinities for the troponin proteins while attached to the phage particles. To our knowledge, this is the first example of isolation and characterization of troponin I binders using phage display technology. These new peptides may have potential utility in the development of new clinical assays for cardiac injury as well as in monitoring of cardiac cells grown in culture.

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Section: Introductionmentioning

confidence: 99%

High affinity peptides for the recognition of the heart disease biomarker troponin I identified using phage display

Park

Banta

2009

Biotech & Bioengineering

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“…The minimum detectable concentration of the assay is 0.012 g/L, and the cutoff value for myocardial infarction defined as the concentration with a 10% CV is 0.06 g/L. The 99th percentile reference concentration was determined to be 0.025 g/L (19 ). Thus, a cTnI concentration Ͼ0.03 g/L was deemed to be increased in this study.…”

Section: Biochemical Measurementsmentioning

confidence: 99%

Free vs Total Pregnancy-Associated Plasma Protein A (PAPP-A) as a Predictor of 1-Year Outcome in Patients Presenting with Non–ST-Elevation Acute Coronary Syndrome

Lund¹,

Wittfooth

Qin

et al. 2010

Clinical Chemistry

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Background: The free fraction of pregnancy-associated plasma protein A (FPAPP-A) was found to be the PAPP-A form released to the circulation in acute coronary syndrome (ACS). We estimated the prognostic value of FPAPP-A vs total PAPP-A (TPAPP-A) concentrations in forecasting death and nonfatal myocardial infarction (combined endpoint) in patients with non–ST-elevation ACS. Methods: We recruited 267 patients hospitalized for symptoms consistent with non–ST-elevation ACS and followed them for 12 months. FPAPP-A, TPAPP-A, C-reactive protein (CRP), and cardiac troponin I (cTnI) were measured at admission; cTnI was also measured at 6–12 h and 24 h. Because of the recently shown interaction between PAPP-A and heparin, we excluded patients treated with any heparin preparations before the admission blood sampling. Results: During the follow-up, 57 (21.3%) patients met the endpoint (22 deaths and 35 nonfatal myocardial infarctions). According to FPAPP-A (<1.27, 1.27–1.74, >1.74 mIU/L) and TPAPP-A (<1.98, 1.98–2.99, >2.99 mIU/L) tertiles, this endpoint was met by 12 (13.5%), 18 (20.2%), 27 (30.3%) (P = 0.02), and 17 (19.1%), 17 (19.1%), 23 (25.8%) (P = 0.54) patients, respectively. After adjusting for age, sex, diabetes, previous myocardial infarction, and ischemic electrocardiogram (ECG) findings, FPAPP-A >1.74 mIU/L [risk ratio (RR) 2.0; 95% CI 1.0–4.1, P = 0.053), increased cTnI, and CRP ≥2.0 mg/L were independent predictors of an endpoint. The prognostic performance of TPAPP-A was inferior to that of FPAPP-A. Conclusions: FPAPP-A seems to be superior as a prognostic marker compared to TPAPP-A, giving independent and additive prognostic information when measured at the time of admission in patients hospitalized for non–ST-elevation ACS.

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“…According to our results (4,13), one of the most noteworthy consequences of circumventing the inhibiting effect on cTnI assays by careful selection of assay design is unhindered recognition of the small and/or early cTnI releases in chest pain patients. The troponins have generally been considered markers of high specificity but with a relatively slow release.…”

Section: To the Editormentioning

confidence: 99%

Beliefs in Cardiac Troponin Testing

Eriksson¹,

Pettersson

2005

Clinical Chemistry

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Improved early risk stratification and diagnosis of myocardial infarction, using a novel troponin I assay concept

Abstract: The novel cTnI assay considerably improves the performance of cTnI as an early rule-in biomarker for MI.

Cited by 22 publications

References 18 publications

High affinity peptides for the recognition of the heart disease biomarker troponin I identified using phage display

High affinity peptides for the recognition of the heart disease biomarker troponin I identified using phage display

Free vs Total Pregnancy-Associated Plasma Protein A (PAPP-A) as a Predictor of 1-Year Outcome in Patients Presenting with Non–ST-Elevation Acute Coronary Syndrome

Beliefs in Cardiac Troponin Testing

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