Calcium-Binding Proteins and RAGE pp 385-406 | Cite as
Sensible Use of High-Sensitivity Troponin Assays
Abstract
The first intracellular Ca2+-sensor protein to be described was the troponin complex. Only later it was discovered that cardiac-specific isoforms of troponin I (cTnI) and troponin T (cTnT) exist, and nowadays, measurement of cardiac troponins is a corner stone in the diagnosis of patients with acute coronary syndrome (ACS). High-sensitivity (hs-) assays have been developed that can record slightly elevated plasma concentrations of cardiac troponins as early as 3 h after onset of clinical symptoms. International guidelines defined a diagnostic cut-off at cardiac troponin levels corresponding to the 99th percentile of a healthy reference population and require that hs-assays measure this concentration with an interassay coefficient of variation ≤10%. This review provides an overview of the diagnostic and prognostic use of cardiac troponins.
Key words
Acute coronary syndrome Cardiovascular disease High-sensitivity assay NSTEMI STEMI Cardiac troponin Laboratory medicine Calcium EF-handReferences
- 1.Schaub MC, Heizmann CW (2008) Calcium, troponin, calmodulin, S100 proteins: from myocardial basics to new therapeutic strategies. Biochem Biophys Res Commun 369:247–264PubMedCrossRefGoogle Scholar
- 2.Cummins B, Auckland ML, Cummins P (1987) Cardiac-specific troponin-I radioimmunoassay in the diagnosis of acute myocardial infarction. Am Heart J 113:1333–1344PubMedCrossRefGoogle Scholar
- 3.Gordon AM, Homsher E, Regnier M (2000) Regulation of contraction in striated muscle. Physiol Rev 80:853–924PubMedGoogle Scholar
- 4.Manning EP, Tardiff JC, Schwartz SD (2011) A model of calcium activation of the cardiac thin filament. Biochemistry 50:7405–7413PubMedCrossRefGoogle Scholar
- 5.Jin JP, Zhang Z, Bautista JA (2008) Isoform diversity, regulation, and functional adaptation of troponin and calponin. Crit Rev Eukaryot Gene Expr 18:93–124PubMedCrossRefGoogle Scholar
- 6.Wei B, Jin JP (2011) Troponin T isoforms and posttranscriptional modifications: evolution, regulation and function. Arch Biochem Biophys 505:144–154PubMedCrossRefGoogle Scholar
- 7.Solaro RJ, van der Velden J (2010) Why does troponin I have so many phosphorylation sites? Fact and fancy. J Mol Cell Cardiol 48:810–816PubMedCrossRefGoogle Scholar
- 8.Zhang J et al (2011) Phosphorylation, but not alternative splicing or proteolytic degradation, is conserved in human and mouse cardiac troponin T. Biochemistry 50:6081–6092PubMedCrossRefGoogle Scholar
- 9.Di Lisa F et al (1995) Specific degradation of troponin T and I by mu-calpain and its modulation by substrate phosphorylation. Biochem J 308:57–61PubMedGoogle Scholar
- 10.Stary HC et al (1995) A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 92:1355–1374PubMedCrossRefGoogle Scholar
- 11.Stary HC et al (1994) A definition of initial, fatty streak, and intermediate lesions of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation 89:2462–2478PubMedCrossRefGoogle Scholar
- 12.Libby P, Ridker PM, Hansson GK (2011) Progress and challenges in translating the biology of atherosclerosis. Nature 473:317–325PubMedCrossRefGoogle Scholar
- 13.Libby P (2009) Molecular and cellular mechanisms of the thrombotic complications of atherosclerosis. J Lipid Res 50(Suppl):S352–357PubMedCrossRefGoogle Scholar
- 14.Arbustini E et al (1999) Plaque erosion is a major substrate for coronary thrombosis in acute myocardial infarction. Heart 82:269–272PubMedGoogle Scholar
- 15.Hamm CW et al (2011) ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999–3054PubMedCrossRefGoogle Scholar
- 16.Rioufol G et al (2002) Multiple atherosclerotic plaque rupture in acute coronary syndrome: a three-vessel intravascular ultrasound study. Circulation 106:804–808PubMedCrossRefGoogle Scholar
- 17.Naghavi M et al (2003) From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation 108:1772–1778PubMedCrossRefGoogle Scholar
- 18.Naghavi M et al (2003) From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation 108:1664–1672PubMedCrossRefGoogle Scholar
- 19.Van de Werf F et al (2008) Management of acute myocardial infarction in patients presenting with persistent ST-segment elevation: the Task Force on the Management of ST-Segment Elevation Acute Myocardial Infarction of the European Society of Cardiology. Eur Heart J 29:2909–2945PubMedCrossRefGoogle Scholar
- 20.Bleier J et al (1998) Different intracellular compartmentations of cardiac troponins and myosin heavy chains: a causal connection to their different early release after myocardial damage. Clin Chem 44:1912–1918PubMedGoogle Scholar
- 21.Gerhardt W et al (1991) S-troponin T in suspected ischemic myocardial injury compared with mass and catalytic concentrations of S-creatine kinase isoenzyme MB. Clin Chem 37:1405–1411PubMedGoogle Scholar
- 22.Morrow DA et al (2007) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Circulation 115:e356–375PubMedCrossRefGoogle Scholar
- 23.Thomas L (2005) Labor und Diagnose, 6th edn. TH-Books Verlagsgesellschaft, FrankfurtGoogle Scholar
- 24.Apple FS et al (2007) National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 53:547–551PubMedCrossRefGoogle Scholar
- 25.Morrow DA et al (2007) National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: clinical characteristics and utilization of biochemical markers in acute coronary syndromes. Clin Chem 53:552–574PubMedCrossRefGoogle Scholar
- 26.Anderson JL et al (2007) ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non ST-Elevation Myocardial Infarction): developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons: endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. Circulation 116:e148–304PubMedCrossRefGoogle Scholar
- 27.Saenger AK, Jaffe AS (2008) Requiem for a heavyweight: the demise of creatine kinase-MB. Circulation 118:2200–2206PubMedCrossRefGoogle Scholar
- 28.Thygesen K et al (2007) Universal definition of myocardial infarction. Circulation 116:2634–2653PubMedCrossRefGoogle Scholar
- 29.Collinson P et al (2008) How well do laboratories follow guidelines on cardiac markers? The cardiac marker guideline uptake in Europe study. Clin Chem 54:448–449PubMedCrossRefGoogle Scholar
- 30.Collinson P et al (2011) Evidence-based laboratory medicine: how well do laboratories follow recommendations and guidelines? The Cardiac Marker Guideline Uptake in Europe (CARMAGUE) study. Clin Chem 58:305–306PubMedCrossRefGoogle Scholar
- 31.Than M et al (2011) A 2-h diagnostic protocol to assess patients with chest pain symptoms in the Asia-Pacific region (ASPECT): a prospective observational validation study. Lancet 377:1077–1084PubMedCrossRefGoogle Scholar
- 32.Bates KJ et al (2010) Circulating immunoreactive cardiac troponin forms determined by gel filtration chromatography after acute myocardial infarction. Clin Chem 56:952–958PubMedCrossRefGoogle Scholar
- 33.Giuliani I et al (1999) Determination of cardiac troponin I forms in the blood of patients with acute myocardial infarction and patients receiving crystalloid or cold blood cardioplegia. Clin Chem 45:213–222PubMedGoogle Scholar
- 34.Katrukha AG et al (1997) Troponin I is released in bloodstream of patients with acute myocardial infarction not in free form but as complex. Clin Chem 43:1379–1385PubMedGoogle Scholar
- 35.Wu AH et al (1998) Characterization of cardiac troponin subunit release into serum after acute myocardial infarction and comparison of assays for troponin T and I. American Association for Clinical Chemistry Subcommittee on cTnI Standardization. Clin Chem 44:1198–1208PubMedGoogle Scholar
- 36.Katrukha AG et al (1998) Degradation of cardiac troponin I: implication for reliable immunodetection. Clin Chem 44:2433–2440PubMedGoogle Scholar
- 37.McDonough JL, Arrell DK, Van Eyk JE (1999) Troponin I degradation and covalent complex formation accompanies myocardial ischemia/reperfusion injury. Circ Res 84:9–20PubMedCrossRefGoogle Scholar
- 38.McDonough JL et al (2001) Cardiac troponin I is modified in the myocardium of bypass patients. Circulation 103:58–64PubMedCrossRefGoogle Scholar
- 39.Labugger R et al (2000) Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction. Circulation 102:1221–1226PubMedCrossRefGoogle Scholar
- 40.Tate JR et al (2010) Standardisation of cardiac troponin I measurement: past and present. Pathology 42:402–408PubMedCrossRefGoogle Scholar
- 41.Koshida S et al (2010) Prevalence of human anti-mouse antibodies (HAMAs) in routine examinations. Clin Chim Acta 411:391–394PubMedCrossRefGoogle Scholar
- 42.Todd DJ et al (2011) Erroneous augmentation of multiplex assay measurements in patients with rheumatoid arthritis due to heterophilic binding by serum rheumatoid factor. Arthritis Rheum 63:894–903PubMedCrossRefGoogle Scholar
- 43.Eriksson S et al (2005) Negative interference in cardiac troponin I immunoassays by circulating troponin autoantibodies. Clin Chem 51:839–847PubMedCrossRefGoogle Scholar
- 44.Eriksson S et al (2005) Comparison of cardiac troponin I immunoassays variably affected by circulating autoantibodies. Clin Chem 51:848–855PubMedCrossRefGoogle Scholar
- 45.Adamczyk M, Brashear RJ, Mattingly PG (2009) Circulating cardiac troponin-I autoantibodies in human plasma and serum. Ann N Y Acad Sci 1173:67–74PubMedCrossRefGoogle Scholar
- 46.Adamczyk M, Brashear RJ, Mattingly PG (2009) Prevalence of autoantibodies to cardiac troponin T in healthy blood donors. Clin Chem 55:1592–1593PubMedCrossRefGoogle Scholar
- 47.Adamczyk M, Brashear RJ, Mattingly PG (2010) Coprevalence of autoantibodies to cardiac troponin I and T in normal blood donors. Clin Chem 56:676–677PubMedCrossRefGoogle Scholar
- 48.Body R et al (2011) Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay. J Am Coll Cardiol 58:1332–1339PubMedCrossRefGoogle Scholar
- 49.Januzzi JL et al (2010) High-sensitivity troponin T concentrations in acute chest pain patients evaluated with cardiac computed tomography. Circulation 121:1227–1234PubMedCrossRefGoogle Scholar
- 50.Antman EM et al (2000) The TIMI risk score for unstable angina/non-ST elevation MI: a method for prognostication and therapeutic decision making. JAMA 284:835–842PubMedCrossRefGoogle Scholar
- 51.Eagle KA et al (2004) A validated prediction model for all forms of acute coronary syndrome: estimating the risk of 6-month postdischarge death in an international registry. JAMA 291:2727–2733PubMedCrossRefGoogle Scholar
- 52.Morrow DA et al (2000) TIMI risk score for ST-elevation myocardial infarction: a convenient, bedside, clinical score for risk assessment at presentation: an intravenous nPA for treatment of infarcting myocardium early II trial substudy. Circulation 102:2031–2037PubMedCrossRefGoogle Scholar
- 53.Morrow DA et al (2001) Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial. JAMA 286:2405–2412PubMedCrossRefGoogle Scholar
- 54.Apple FS et al (2009) Role of monitoring changes in sensitive cardiac troponin I assay results for early diagnosis of myocardial infarction and prediction of risk of adverse events. Clin Chem 55:930–937PubMedCrossRefGoogle Scholar
- 55.Celik S et al (2011) Cardiac troponin T concentrations above the 99 th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy. Clin Res Cardiol 100:1077–1085PubMedCrossRefGoogle Scholar
- 56.Kavsak PA et al (2009) Short- and long-term risk stratification using a next-generation, high-sensitivity research cardiac troponin I (hs-cTnI) assay in an emergency department chest pain population. Clin Chem 55:1809–1815PubMedCrossRefGoogle Scholar
- 57.Kurz K et al (2011) Comparison of the new high sensitive cardiac troponin T with myoglobin, h-FABP and cTnT for early identification of myocardial necrosis in the acute coronary syndrome. Clin Res Cardiol 100:209–215PubMedCrossRefGoogle Scholar
- 58.Lindahl B, Venge P, James S (2010) The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes. Am Heart J 160:224–229PubMedCrossRefGoogle Scholar
- 59.O’Connor RE et al (2010) Part 10: acute coronary syndromes: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 122:S787–817PubMedCrossRefGoogle Scholar
- 60.Scirica BM et al (2011) Assessment of multiple cardiac biomarkers in non-ST-segment elevation acute coronary syndromes: observations from the MERLIN-TIMI 36 trial. Eur Heart J 32:697–705PubMedCrossRefGoogle Scholar
- 61.Hochholzer W et al (2011) Incremental value of high-sensitivity cardiac troponin T for risk prediction in patients with suspected acute myocardial infarction. Clin Chem 57:1318–1326PubMedCrossRefGoogle Scholar
- 62.Meune C et al (2011) The GRACE score’s performance in predicting in-hospital and 1-year outcome in the era of high-sensitivity cardiac troponin assays and B-type natriuretic peptide. Heart 97:1479–1483CrossRefGoogle Scholar
- 63.Ndrepepa G et al. (2011) Comparison of prognostic value of high-sensitivity and conventional troponin T in patients with non-ST-segment elevation acute coronary syndromes. Clin Chim Acta 412: 1350–1356 Google Scholar
- 64.Mills NL et al (2011) Implementation of a sensitive troponin I assay and risk of recurrent myocardial infarction and death in patients with suspected acute coronary syndrome. JAMA 305:1210–1216PubMedCrossRefGoogle Scholar
- 65.Korff S, Katus HA, Giannitsis E (2006) Differential diagnosis of elevated troponins. Heart 92:987–993PubMedCrossRefGoogle Scholar
- 66.Roongsritong C, Warraich I, Bradley C (2004) Common causes of troponin elevations in the absence of acute myocardial infarction: incidence and clinical significance. Chest 125:1877–1884PubMedCrossRefGoogle Scholar
- 67.Omland T et al (2009) A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 361:2538–2547PubMedCrossRefGoogle Scholar
- 68.Reiter M et al (2011) Early diagnosis of acute myocardial infarction in patients with pre-existing coronary artery disease using more sensitive cardiac troponin assays. Eur Heart J 33:988–997. doi: "10.1093/eurheartj/ehr376", E-pub ahead of printPubMedCrossRefGoogle Scholar
- 69.Aviles RJ et al (2002) Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction. N Engl J Med 346:2047–2052PubMedCrossRefGoogle Scholar
- 70.Apple FS et al (2002) Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 106:2941–2945PubMedCrossRefGoogle Scholar
- 71.Dierkes J et al (2000) Cardiac troponin T predicts mortality in patients with end-stage renal disease. Circulation 102:1964–1969PubMedCrossRefGoogle Scholar
- 72.Ooi DS et al (1999) Increased mortality in hemodialyzed patients with elevated serum troponin T: a one-year outcome study. Clin Biochem 32:647–652PubMedCrossRefGoogle Scholar
- 73.Reiter M et al (2011) Early diagnosis of acute myocardial infarction in the elderly using more sensitive cardiac troponin assays. Eur Heart J 32:1379–1389PubMedCrossRefGoogle Scholar
- 74.Hickman PE et al (2010) Cardiac troponin may be released by ischemia alone, without necrosis. Clin Chim Acta 411:318–323PubMedCrossRefGoogle Scholar
- 75.Saunders JT et al (2011) Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the Atherosclerosis Risk in Communities Study. Circulation 123:1367–1376PubMedCrossRefGoogle Scholar
- 76.de Lemos JA et al (2010) Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA 304:2503–2512PubMedCrossRefGoogle Scholar
- 77.Blankenberg S et al (2010) Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts: the MONICA, risk, genetics, archiving, and monograph (MORGAM) biomarker project. Circulation 121:2388–2397PubMedCrossRefGoogle Scholar