Comparison of Cardiac and Non-Cardiac Biomarkers for Risk Stratification in Elderly Patients with Non-Massive Pulmonary Embolism

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Biomarkers unrelated to myocardial necrosis, such as cystatin C, copeptin, and mid-regional pro-adrenomedullin (MR-proADM), showed promise for cardiovascular risk prediction. Knowing whether they are comparable to cardiac biomarkers such as high-sensitive cardiac-troponin T (hs-cTnT) or N-terminal pro-Brain natriuretic peptide (NT-proBNP) in elderly patients with acute non-massive pulmonary embolism (NMPE) remains elusive. This study aims at comparing the prognostic accuracy of cardiac and non-cardiac biomarkers in patients with NMPE aged ≥65 years over time. In the context of the SWITCO65+ cohort, we evaluated 227 elderly patients with an available blood sample taken within one day from diagnosis. The primary study endpoint was defined as PE-related mortality and the secondary endpoint as PE-related complications. The biomarkers’ predictive ability at 1, 3, 12 and 24 months was determined using C-statistics and Cox regression. For both study endpoints, C-statistics (95% confidence interval) were stable over time for all biomarkers, with the highest value for hs-cTnT, ranging between 0.84 (0.68–1.00) and 0.80 (0.70–0.90) for the primary endpoint, and between 0.74 (0.63–0.86) and 0.65 (0.57–0.73) for the secondary endpoint. For both study endpoints, cardiac biomarkers were found to be independently associated with risk, NT-proBNP displaying a negative predictive value of 100%. Among non-cardiac biomarkers, only copeptin and MR-proADM were independent predictors of PE-related mortality but they were not independent predictors of PE-related complications, and displayed lower negative predictive values. In elderly NMPE patients, cardiac biomarkers appear to be valuable prognostic to identify very low-risk individuals.

Trial Registration: ClinicalTrials.gov NCT00973596

Autoři: Nicolas Vuilleumier☯ ¹; Aurélien Simona☯ ^{2 *}; Marie Méan ^3,4; Andreas Limacher ⁵; Pierre Lescuyer ¹; Eric Gerstel ^2,6; Henri Bounameaux ⁷; Drahomir Aujesky ³; Marc Righini ⁷
Působiště autorů: Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland ¹; Department of Internal Medicine, Rehabilitation and Geriatrics, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland ²; Division of General Internal Medicine, Bern University Hospital and University of Bern, Bern, Switzerland ³; Service of Internal Medicine, Lausanne University Hospital, Lausanne, Switzerland ⁴; CTU Bern, Department of Clinical Research and Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland ⁵; Clinique de la Colline, Geneva, Switzerland ⁶; Division of Angiology and Haemostasis, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland ⁷
Vyšlo v časopise: PLoS ONE 11(5)
Kategorie: Research article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0155973

© 2016 Vuilleumier et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The electronic version of this article is the complete one and can be found online at: http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0155973

Souhrn

Zdroje

1. Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galiè N, Pruszczyk P et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J. 2008; 29:2276–315. doi: 10.1093/eurheartj/ehn310 PMID: 18757870

2. Aujesky D, Roy PM, Verschuren F, Righini M, Osterwalder J, Egloff M et al. Outpatient versus inpatient treatment for patients with acute pulmonary embolism: an international, open-label, randomised, noninferiority trial. Lancet. 2011; 378:41–8. doi: 10.1016/S0140-6736(11)60824-6 PMID: 21703676

3. Konstantinides S, Goldhaber SZ. Pulmonary embolism: risk assessment and management. Eur Heart J. 2012; 33:3014–22. doi: 10.1093/eurheartj/ehs258 PMID: 22961946

4. Kovacs MJ, Anderson D, Morrow B, Gray L, Touchie D, Wells PS. Outpatient treatment of pulmonary embolism with deltaparin. Thromb Haemost. 2000; 83:209–11. PMID: 10739374

5. Beer JH, Burger M, Gretener S, Bernard Bagattini S, Bounameaux H. Outpatient treatment of pulmonary embolism is feasible and safe in a substantial proportion of patients. J Thromb Haemost. 2003; 1:186–7. PMID: 12871557

6. Konstantinides S, Goldhaber SZ.Pulmonary embolism: risk assessment and management. Eur Heart J. 2012; 33:3014–22. doi: 10.1093/eurheartj/ehs258 PMID: 22961946

7. Lankeit M, Friesen D, Aschoff J, Dellas C, Hasenfuss G, Katus H et al. Highly sensitive troponin T assay in normotensive patients with acute pulmonary embolism. Eur Heart J. 2010; 31:1836–44. doi: 10.1093/eurheartj/ehq234 PMID: 20584774

8. Lankeit M, Jiménez D, Kostrubiec M, Dellas C, Hasenfuss G, Pruszczyk P et al. Predictive value of the high-sensitivity troponin T assay and the simplified Pulmonary Embolism Severity Index in hemodynamically stable patients with acute pulmonary embolism: a prospective validation study. Circulation. 2011; 124:2716–24. doi: 10.1161/CIRCULATIONAHA.111.051177 PMID: 22082681

9. Vuilleumier N, Limacher A, Méan M, Choffat J, Lescuyer P, Bounameaux H et al. Cardiac biomarkers and clinical scores for risk stratification in elderly patients with non-high-risk pulmonary embolism. J Intern Med. 2015; 277:707–16. doi: 10.1111/joim.12316 PMID: 25285747

10. Vuilleumier N, Le Gal G, Verschuren F, Perrier A, Bounameaux H, Turck N et al.Cardiac biomarkers for risk stratification in non-massive pulmonary embolism: a multicenter prospective study. J Thromb Haemost. 2009; 7:391–8. doi: 10.1111/j.1538-7836.2008.03260.x PMID: 19087222

11. Reichlin T, Hochholzer W, Stelzig C, Laule K, Freidank H, Morgenthaler NG et al.Incremental value of copeptin for rapid rule out of acute myocardial infarction. J Am Coll Cardiol. 2009; 54:60–8. doi: 10.1016/j.jacc.2009.01.076 PMID: 19555842

12. Xue Y, Taub P, Iqbal N, Fard A, Clopton P, Maisel A. Mid-region pro-adrenomedullin adds predictive value to clinical predictors and Framingham risk score for long-term mortality in stable outpatients with heart failure. Eur J Heart Fail. 2013; 15:1343–9. doi: 10.1093/eurjhf/hft116 PMID: 23887059

13. Potocki M, Ziller R, Mueller C. Mid-regional pro-adrenomedullin in acute heart failure: a better biomarker or just another biomarker? Curr Heart Fail Rep. 2012; 9:244–51. doi: 10.1007/s11897-012-0096-6 PMID: 22733501

14. Kostrubiec M, Łabyk A, Pedowska-Włoszek J, Dzikowska-Diduch O, Wojciechowski A, Garlińska M et al. Neutrophil gelatinase-associated lipocalin, cystatin C and eGFR indicate acute kidney injury and predict prognosis of patients with acute pulmonary embolism. Heart. 2012; 98:1221–8. doi: 10.1136/heartjnl-2012-301884 PMID: 22705926

15. Pedowska-Włoszek J, Kostrubiec M, Kurnicka K, Ciurzynski M, Palczewski P, Pruszczyk P. Midregional proadrenomedullin (MR-proADM) in the risk stratification of patients with acute pulmonary embolism. Thromb Res. 2013; 132:506–10. doi: 10.1016/j.thromres.2013.08.008 PMID: 24060192

16. Zwierzina D, Limacher A, Méan M, Righini M, Jaeger K, Beer HJ et al. Prospective comparison of clinical prognostic scores in elderly patients with pulmonary embolism. J Thromb Haemost. 2012; 10:2270–6. doi: 10.1111/j.1538-7836.2012.04929.x PMID: 22985129

17. Méan M, Righini M, Jaeger K, Beer HJ, Frauchiger B, Osterwalder J et al. The Swiss cohort of elderly patients with venous thromboembolism (SWITCO65+): rationale and methodology. J Thromb Thrombolysis. 2013; 36:475–83. doi: 10.1007/s11239-013-0875-2 PMID: 23359097

18. Méan M, Aujesky D, Lämmle B, Gerschheimer C, Trelle S, Angelillo-Scherrer A. Design and establishment of a biobank in a multicenter prospective cohort study of elderly patients with venous thromboembolism (SWITCO65+). J Thromb Thrombolysis. 2013; 36:484–91. doi: 10.1007/s11239-013-0922-z PMID: 23584599

19. Apple FS, Jaffe AS. Clinical implications of a recent adjustment to the high-sensitivity cardiac troponin T assay: user beware. Clin Chem. 2012; 58:1599–600. doi: 10.1373/clinchem.2012.194985 PMID: 22968106

20. Thygesen K, Alpert JS, Jaffe AS, Simoons ML, Chaitman BR, White HD et al. Third universal definition of myocardial infarction. J Am Coll Cardiol. 2012; 60:1581–98. doi: 10.1016/j.jacc.2012.08.001 PMID: 22958960

21. Januzzi JL Jr, Camargo CA, Anwaruddin S, Baggish AL, Chen AA, Krauser DG et al. The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study. Am J Cardiol. 2005; 95:948–54. PMID: 15820160

22. Wicki J, Perrier A, Perneger TV, Bounameaux H, Junod AF. Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost. 2000; 84:548–52. PMID: 11057848

23. Hanley JA, McNeil BJ. The meaning and use of the area under a receiver operating characteristic (ROC) curve. Radiology 1982; 143:29–36. PMID: 7063747

24. Meyer G, Vicaut E, Danays T, Agnelli G, Becattini C, Beyer-Westendorf J et al. Fibrinolysis for Patients with Intermediate-Risk Pulmonary Embolism. N Engl J Med 2014; 370:1402–1411. doi: 10.1056/NEJMoa1302097 PMID: 24716681

25. Brouwers FP, de Boer RA, van der Harst P, Struck J, de Jong PE, de Zeeuw D et al. Influence of age on the prognostic value of mid-regional pro-adrenomedullin in the general population. Heart. 2012; 98:1348–53. doi: 10.1136/heartjnl-2012-302390 PMID: 22821276

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