Troponin I Explained

Troponin T
Test Of:Troponin

Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack.[1] It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.[2]

Three paralogs with unique tissue-specific expression patterns are expressed in humans, listed below with their locations and OMIM accessions:

cTnI

Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by a single isoform with a molecular weight of 23.9 kDa. It consists of 209 amino acid residues. The theoretical pI of cTnI is 9.05.[3] cTnI differs from other troponins due to its N-terminal extension of 26 amino acids. This extension contains two serines, residues 23 and 24, which are phosphorylated by protein kinase A in response to beta-adrenergic stimulation and important in increasing the inotropic response.[4] Phosphorylation of cTnI changes the conformation of the protein and modifies its interaction with other troponins as well as the interaction with anti-TnI antibodies. These changes alter the myofilament response to calcium, and are of interest in targeting heart failure. Multiple reaction monitoring of human cTnI has revealed that there are 14 phosphorylation sites and the pattern of phosphorylation observed at these sites is changed in response to disease.[5] cTnI has been shown to be phosphorylated by protein kinase A, protein kinase C, protein kinase G, and p21-activated kinase 3.[6]

A significant part of cTnI released into the patient's blood stream is phosphorylated.[7] For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in the diagnosis of myocardial infarction than the "golden marker" of the last decades – CK-MB, as well as total creatine kinase, myoglobin and lactate dehydrogenase isoenzymes.

Troponin I is not entirely specific for myocardial damage secondary to infarction. Other causes of raised troponin I include chronic kidney failure, heart failure, subarachnoid haemorrhage and pulmonary embolus.[8] [9]

In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle.[10]

High-sensitivity troponin I testing

The high sensitive troponin I test is a chemiluminescence microparticle immunoassay, which is used to quantitatively determine cardiac troponin I in human plasma and serum.  The test can be used to aid in diagnosing myocardial infarction, as a prognostic marker in patients with acute coronary syndrome and to identify the risk (low, moderate and elevated) of future cardiovascular diseases such as myocardial infarction, heart failure, ischaemic stroke, coronary revascularisation, and cardiovascular death in asymptomatic people.[11] [12] [13] [14] [15]

High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment[16] and skeletal muscle disease.[17] [18] It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD.[19]

Prognostic use

The basis for the modern prevention of CVD lies in the prognosis of the risk of the development of myocardial infarction, stroke or heart failure in the future. Currently, most prognostic models of cardiovascular risk (European SCORE scale, Framingham scale, etc.) are based on the evaluation of traditional risk factors of CVD. This stratification system is indirect and has several limitations, which include the inaccurate forecasting of risks.[20] These risk scales are heavily dependent on the age of the person. Research data bears evidence that the high sensitive troponin I test enables higher precision in determining the cardiovascular risk group of the individual, if used together with the results of clinical and diagnostic examinations.

The efficiency of  the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects.[26]

The ability of high sensitive troponin I to identify individual's cardiovascular risk in asymptomatic people enables physicians to use it in outpatient/ambulatory practice during preventive check-ups, complex health examinations, or examinations of patients with known risk factors. Knowing which cardiovascular risk group a person belongs to allows physicians to promptly determine patient care tactics well before the development of symptoms, and to prevent adverse outcomes.

Indications for testing

High sensitive troponin I test is recommended for asymptomatic women and men to assess and stratify their cardiovascular risk.

Individuals may or may not have known established cardio-vascular risk factors:

  1. high blood pressure;
  2. obesity;
  3. congenital factors, history of cardiovascular diseases;
  4. pre-diabetes, diabetes;
  5. sedentary lifestyle;
  6. metabolic syndrome;
  7. dislipidaemia;
  8. smoking.

Incorporating the high sensitive troponin I test into initial screening will improve the prediction of future CV events and help individuals be more compliant with lifestyle changes and possible medication recommended by their physician.

This might be a step forward for personalized preventive medicine, being especially relevant at an individual level, when clinicians need to weigh the importance of each risk factor and determine if the person needs therapy in addition to lifestyle advice.

The precise frequency of examinations is not pre-determined; it depends on the specific case, risk category and individual characteristics of a patient. The test may be added to the check-up programs or used as a stand along in conjunction with other clinical and diagnostic findings.[24]

History

Troponin was discovered in 1965. It was initially named heart myofibrillar apparatus protein component but was later renamed troponin. In 1971, Grieser and Gergely proved that troponin complex consists of three components, which, considering their specific properties, were named TnC, TnI and TnT. Over the following ten years, several groups of researchers started to demonstrate interest in the research of troponin, and the awareness of these proteins increased rapidly. When, finally, the amino acid sequences of troponin isoforms were determined, the opportunity to research functionally significant regions appeared.[27]

See also

Notes and References

  1. Web site: Troponin. labtestsonline. 27 January 2021 .
  2. Web site: Troponin. 2019-01-09. labtestsonline.org/. 2019-07-16.
  3. Kozlowski. LP. IPC - Isoelectric Point Calculator.. Biology Direct. 21 October 2016. 11. 1. 55. 10.1186/s13062-016-0159-9. 27769290. 5075173 . free .
  4. Solaro RJ, Moir AJ, Perry SV . Phosphorylation of troponin I and the inotropic effect of adrenaline in the perfused rabbit heart . Nature . 262 . 5569 . 615–616. 1976 . 10.1038/262615a0. 958429 . 1976Natur.262..615S . 4216390 .
  5. Zhang P, Kirk, JA, Ji W, dos Remedios CG, Kass DA, Van Eyk JE, Murphy AM . Multiple Reaction Monitoring to Identify Site-Specific Troponin I Phosphorylated Residues in the Failing Human Heart . Circulation . 126 . 15 . 1828–1837 . 2012 . 10.1161/circulationaha.112.096388 . 22972900 . 3733556.
  6. Layland J, Solaro RJ, Shah AM . Regulation of cardiac contractile function by troponin I phosphorylation . Cardiovascular Research . 66 . 1 . 12–21 . 2005 . 10.1016/j.cardiores.2004.12.022. 15769444 . free .
  7. Labugger R, Organ L, Collier C, Atar D, Van Eyk JE . Extensive troponin I and T modification detected in serum from patients with acute myocardial infarction . Circulation. 102 . 11 . 1221–1226. 2000 . 10.1161/01.cir.102.11.1221. 10982534 . free .
  8. Mannu GS, The non-cardiac use and significance of cardiac troponins. Scott Med J, 2014. 59(3): p. 172-8.
  9. Tanindi. Asil. Cemri. Mustafa. Troponin elevation in conditions other than acute coronary syndromes. Vascular Health and Risk Management. 3212425. 22102783. 10.2147/VHRM.S24509. 7. 597–603. 2011 . free .
  10. 10.3389/fvets.2020.00531. free. Comparison of Two Commercially Available Immunoassays for the Measurement of Bovine Cardiac Troponin I in Cattle with Induced Myocardial Injury. 2020. Smith. Joe S.. Varga. Anita. Schober. Karsten E.. Frontiers in Veterinary Science. 7. 531. 33062647. 7481330.
  11. Web site: 2021-01-27 . Troponin . 2022-04-13 . Testing.com . en-US.
  12. Strandberg . Love S. . Roos . Andreas . Holzmann . Martin J. . 2021-01-01 . Stable high-sensitivity cardiac troponin T levels and the association with frailty and prognosis in patients with chest pain . American Journal of Medicine Open . en . 1-6 . 100001 . 10.1016/j.ajmo.2021.100001 . 244507759 . 2667-0364. free . 11256254 .
  13. Thygesen . Kristian . Alpert . Joseph S. . Jaffe . Allan S. . Chaitman . Bernard R. . Bax . Jeroen J. . Morrow . David A. . White . Harvey D. . 2018-10-30 . Fourth Universal Definition of Myocardial Infarction (2018) . Journal of the American College of Cardiology . en . 72 . 18 . 2231–2264 . 10.1016/j.jacc.2018.08.1038 . 30153967 . 52110825 . 0735-1097. free . 10044/1/73052 . free .
  14. Kerr . Gillian . Ray . Gautamananda . Wu . Olivia . Stott . David J. . Langhorne . Peter . 2009 . Elevated troponin after a stroke: a systematic review . Cerebrovascular Diseases . 28 . 3 . 220–226 . 10.1159/000226773 . 1421-9786 . 19571535 . free.
  15. Danese . E . Montagnana . M . 2016 . An historical approach to the diagnostic biomarkers of acute coronary syndrome. . Annals of Translational Medicine . 4 . 10 . 194. 10.21037/atm.2016.05.19 . 27294090 . 4885896 . free .
  16. Gunsolus . I . 2017 . Renal Dysfunction Influences the Diagnostic and Prognostic Performance of High-Sensitivity Cardiac Troponin I . Journal of the American Society of Nephrology . 29 . 2 . 636–643. 10.1681/asn.2017030341 . 29079658 . 5791068 .
  17. Jaffe . A.S. . etal . 2011 . Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T . Journal of the American College of Cardiology . 58 . 17 . 1819–1824. 10.1016/j.jacc.2011.08.026 . 21962825 . 25530497 . free .
  18. Wens . S.C.A. . etal . 2016 . Elevated Plasma Cardiac Troponin T Levels Caused by Skeletal Muscle Damage in Pompe Disease . Circulation: Cardiovascular Genetics . 9 . 1 . 6–13. 10.1161/CIRCGENETICS.115.001322 . 26787432 . 10306074 . free .
  19. Klinkenberg . L.J.J. . etal . 2016 . Diurnal Rhythm of Cardiac Troponin: Consequences for the Diagnosis of Acute Myocardial Infarction . Clinical Chemistry . 62 . 12 . 1602–1611. 10.1373/clinchem.2016.257485 . 27707754 . free .
  20. Farmakis, D., Mueller, C. . Apple, F.S. . 2020 . High-sensitivity cardiac troponin assays for cardiovascular risk stratification in the general population . European Heart Journal . 41 . 41 . 4050–4056. 10.1093/eurheartj/ehaa083 . 32077940 .
  21. Sigurdardottir . F.D. . etal . 2018 . Relative Prognostic Value of Cardiac Troponin I and C-Reactive Protein in the General Population (from the Nord-Trøndelag Health [HUNT] Study) . The American Journal of Cardiology . 121 . 8 . 949–955. 10.1016/j.amjcard.2018.01.004 . 29496193 . 10852/97228 . free .
  22. Ford . I. . etal . 2016 . High-Sensitivity Cardiac Troponin, Statin Therapy, and Risk of Coronary Heart Disease . Journal of the American College of Cardiology . 68 . 25 . 2719–2728. 10.1016/j.jacc.2016.10.020 . 28007133 . 5176330 .
  23. Everett . B.M. . etal . 2015 . High-sensitivity cardiac troponin I and B-type natriuretic Peptide as predictors of vascular events in primary prevention: impact of statin therapy . Circulation . 131 . 21 . 1851–1860. 10.1161/circulationaha.114.014522 . 25825410 . 4444427 .
  24. Web site: World Health Organization . 2020 . The top 10 causes of death .
  25. Jülicher, P. . Varounis, C. . Estimating the cost-effectiveness of screening a general population for cardiovascular risk with high-sensitivity troponin-I . European Heart Journal - Quality of Care & Clinical Outcomes. 2022 . 8 . 3 . 342–351 . 10.1093/ehjqcco/qcab005 . 33502472 . 9071558 .
  26. Web site: Kardioloģiskie marķieri – NMS laboratorija . 2022-03-10 . www.nms-laboratorija.lv.
  27. Book: Fuster, V., Kelly, B.B. . Promoting Cardiovascular Health in the Developing World: A Critical Challenge to Achieve Global Health. . National Academies Press . 2010.

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