EXPLORING THE ASSOCIATION BETWEEN EXTRA-CARDIAC TROPONIN ELEVATIONS AND RISK OF FUTURE MORTALITY

  • Giuseppe Lippi
  • Fabian Sanchis-Gomar
Keywords: mortality, myocardial infarction, cardiac injury, troponin

Abstract


Although the measurement of cardiac troponin I (cTnI) and T (cTnT) has now become the cornerstone for diagnosing cardiac injury, both ischemic and non-ischemic, recent evidence has become available that many patients display extra-cardiac causes of cTn elevations and carry a considerably enhanced risk of future mortality. The current literature data suggests that cTn elevations may be equally common in patients with cardiac and extra-cardiac diseases. Among the latter cohort of patients, the leading extra-cardiac diseases which may be responsible for either cTnI or cTnT elevations include infectious diseases/sepsis, pulmonary disorders, renal failure, malignancy, as well as gastrointestinal, neurological and musculoskeletal diseases. What also emerges rather clearly from the current literature data, is that the risk of dying for extra-cardiac diseases is higher (i.e., between two- to three-fold) in patients with extra-cardiac cTn elevations than in those with cardiac pathologies, and that the most frequent cause of death would then be infections/sepsis, followed by malignancy, respiratory disorders, myocardial infarction, gastrointestinal and neurological diseases, heart failure, stroke, cardiac arrhythmias, renal failure, psychiatric, metabolic, urogenital and musculoskeletal disorders. These figures would lead to conclude that there is a considerable risk that the underlying pathology causing cardiac injury and cTn elevation would then become the cause of death in these patients. This important evidence shall lead the way to defining appropriate and effective strategies for managing patients with extra-cardiac cTn elevations, so that their risk of future death could be prevented or limited.

References

Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J 2019; 40: 237–69.

Lippi G, Plebani M. Understanding cardiac troponin biology: all other cardiac biomarkers shall rest in peace? J Lab Precis Med 2019; 4: 9.

Lippi G, Cervellin G. Is one cardiac troponin better than the other? J Lab Precis Med 2019; 4: 19.

Clerico A, Lippi G. The state-of-the-art of »high-sensitivity« immunoassay for measuring cardiac troponin I and T. J Lab Precis Med 2018; 3: 53.

van der Hagen EAE, Cobbaert CM, Meijer R, Thelen MHM. Fast 0/1-h algorithm for detection of NSTEMI: are current high-sensitivity cardiac troponin assays fit for purpose? An EQA-based evaluation. Clin Chem Lab Med 2019; 57: 1999–2007.

Galli C, Lippi G. High-sensitivity cardiac troponin testing in routine practice: economic and organizational advantages. Ann Transl Med 2016; 4: 257.

Lippi G, Sanchis-Gomar F. »Ultra-sensitive« cardiac troponins: Requirements for effective implementation in clinical practice. Biochem Med (Zagreb) 2018; 28: 030501.

Collinson PO, Saenger AK, Apple FS. High sensitivity, contemporary and point-of-care cardiac troponin assays: educational aids developed by the IFCC Committee on Clinical Application of Cardiac Bio-Markers. Clin Chem Lab Med 2019; 57: 623–32.

McKie PM, Heublein DM, Scott CG, Gantzer ML, Mehta RA, Rodeheffer RJ et al. Defining high-sensitivity cardiac troponin concentrations in the community. Clin Chem 2013; 59: 1099–107.

Lippi G, Cervellin G, Banfi G, et al. Cardiac troponins and physical exercise. It's time to make a point. Biochem Med (Zagreb) 2011; 21: 55–62.

de Lemos JA. Increasingly sensitive assays for cardiac troponins: a review. JAMA 2013; 309: 2262–9.

Lippi G, Cervellin G, Sanchis-Gomar F. Predicting mortality with cardiac troponins: recent insights from metaanalyses. Diagnosis (Berl). 2019 Oct 17. doi: 10.1515/dx-2019-0061. [Epub ahead of print].

Lippi G, Cervellin G, Sanchis-Gomar F. Prognostic Value of Troponins in Patients With or Without Coronary Heart Disease: Is it Dependent on Structure and Biology? Heart Lung Circ. 2019 Nov 21. doi: 10.1016/j.hlc.2019.10.005. [Epub ahead of print].

van der Linden N, Klinkenberg LJ, Bekers O, Loon LJ, Dieijen-Visser MP, Zeegers MP, et al. Prognostic value of basal high-sensitive cardiac troponin levels on mortality in the general population: A meta-analysis. Medicine (Baltimore) 2016; 95: e5703.

Giannitsis E, Mueller C, Katus HA. Skeletal myopathies as a non-cardiac cause of elevations of cardiac troponin concentrations. Diagnosis (Berl) 2019; 6: 189[201.

Irfan A, Twerenbold R, Reiter M, Reichlin T, Stelzig C, Freese M, et al. Determinants of high-sensitivity troponin T among patients with a noncardiac cause of chest pain. Am J Med 2012; 125: 491[8.

Bardají A, Cediel G, Carrasquer A, de Castro R, Sánchez R, Boqué C. Troponin elevation in patients without acute coronary syndrome. Rev Esp Cardiol (Engl Ed) 2015; 68: 469–76.

Wu C, Singh A, Collins B, Fatima A, Qamar A, Gupta A, et al. Causes of Troponin Elevation and Associated Mortality in Young Patients. Am J Med 2018; 131: 284–92.

González-Del-Hoyo M, Cediel G, Carrasquer A, Bonet G, Consuegra-Sánchez L, Bardají A. Diagnostic and prognostic implications of troponin elevation without chest pain in the emergency department. Emergencias 2018; 30: 77–83.

Campbell AR, Rodriguez AJ, Larson DM, Strauss CE, Garberich RF, Partridge MF, et al. Resource utilization and outcome among patients with selective versus nonselective troponin testing. Am Heart J 2018; 199: 68–74.

AlQassas I, Hassan W, Sunni N, Lhmdi M, Nazzal A, et al. The Prognostic Significance of Elevated Cardiac Troponin in Non-Cardiac Medical Disorders. Pilot Study. Int J Clin Cardiol 2019; 6: 136.

Lee KK, Noaman A, Vaswani A, Gibbins M, Griffiths M, Chapman AR, et al. Prevalence, Determinants, and Clinical Associations of High-Sensitivity Cardiac Troponin in Patients Attending Emergency Departments. Am J Med 2019; 132: 110.e8-110.e21.

Korley FK, Schulman SP, Sokoll LJ, DeFilippis AP, Stolbach AI, Bayram JD, et al. Troponin elevations only detected with a high-sensitivity assay: clinical correlations and prognostic significance. Acad Emerg Med 2014; 21: 727–35.

Oluleye OW, Folsom AR, Nambi V, Lutsey PL, Ballantyne CM. Troponin T, B-type natriuretic peptide, C-reactive protein, and cause-specific mortality. Ann Epidemiol 2013; 23: 66–73.

Dhesi S, Shanks M, Tymchak WJ. Troponin rise in hospitalized patients with nonacute coronary syndrome: retrospective assessment of outcomes and predictors. Can J Cardiol 2015; 31: 296–301.

Campbell AR, Rodriguez AJ, Larson DM, Strauss CE, Garberich RF, Partridge MF, et al. Resource utilization and outcome among patients with selective versus nonselective troponin testing. Am Heart J 2018; 199: 68–74.

Lee KK, Noaman A, Vaswani A, Gibbins M, Griffiths M, Chapman AR, et al. Prevalence, Determinants, and Clinical Associations of High-Sensitivity Cardiac Troponin in Patients Attending Emergency Departments. Am J Med 2019; 132: 110.e8-110.e21.

Kaura A, Panoulas V, Glampson B, Davies J, Mulla A, Woods K, et al. Association of troponin level and age with mortality in 250 000 patients: cohort study across five UK acute care centres. BMJ 2019; 367: l6055.

Roos A, Kadesjö E, Sartipy U, Holzmann MJ. Causes of death in relation to stable troponin levels including chronic myocardial injury. Int J Cardiol. 2019 Nov 28. doi: 10.1016/j.ijcard.2019.11.150. [Epub ahead of print].

Mariathas M, Allan R, Ramamoorthy S, Olechowski B, Hinton J, Azor M, et al. True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ 2019; 364: l729.

World Health Association. Mortality Database. https://www.who.int/healthinfo/global_burden_disease/estimates/en/. Last access: July 4, 2019.

Published
2020/02/17
Section
Oppinion paper