Biomarker Testing and Pre-emptive Therapy in Preventing Heart Failure

  • Ken McDonald
  • Mark Ledwidge
  • Joe Gallagher
  • Chris Watson
Heart Failure Prevention (W Tang)
Part of the following topical collections:
  1. Topical Collection on Heart Failure Prevention


In an attempt to reduce the heart failure epidemic, screening and prevention will become an increasing focus of management in the wider at-risk population. Refining risk prediction through the use of biomarkers in isolation or in combination is emerging as a critical step in this process. The utility of biomarkers to identify disease manifestations before the onset of symptoms and detrimental myocardial damage is proving to be valuable. In addition, biomarkers that predict the likelihood and rate of disease progression over time will help streamline and focus clinical efforts and therapeutic strategies. Importantly, several recent early intervention studies using biomarker strategies are promising and indicate that not only can new-onset heart failure be reduced but also the development of other cardiovascular conditions.


Biomarkers Heart failure Cardiovascular disease prediction and prevention 



This work was supported by the European Commission FP7 project FIBRO-TARGETS and HOMAGE and the Health Research Board of Ireland [grant numbers 602904; 305507; CSA-2012-36, respectively].

Compliance with Ethics Guidelines

Conflict of Interest

Chris Watson, Mark Ledwidge, Ken McDonald and Joe Gallagher have no relevant disclosures to report.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.


Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Van Heerebeek L, Borbély A, Niessen HW, et al. Myocardial structure and function differ in systolic and diastolic heart failure. Circulation. 2006;113:1966–73.CrossRefPubMedGoogle Scholar
  2. 2.
    Westermann D, Lindner D, Kasner M, et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail. 2011;4:44–52.CrossRefPubMedGoogle Scholar
  3. 3.
    Wang TJ, Larson MG, Levy DE, et al. Plasma natriuretic peptide levels and the risk of cardiovascular events and death. N Engl J Med. 2004;350:655–63.CrossRefPubMedGoogle Scholar
  4. 4.
    Vellaichamy E, Kaur K, Pandey K. Enhanced activation of pro-inflammatory cytokines in mice lacking natriuretic peptide receptor-A. Peptides. 2007;28(4):893–9.CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Phelan D, Watson CJ, Martos R, et al. Modest elevation in BNP in asymptomatic hypertensive patients reflects sub-clinical cardiac remodeling, inflammation and extracellular matrix changes. PLoS One. 2012;7(11).Google Scholar
  6. 6.
    Murtagh G, Dawkins IR, O’Connell R, et al. Screening to prevent heart failure (STOP-HF): expanding the focus beyond asymptomatic left ventricular systolic dysfunction. Eur J Heart Fail. 2012;14:480–6.CrossRefPubMedGoogle Scholar
  7. 7.
    McGrady M, Reid CM, Shiel L, et al. NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction; results of the SCReening Evaluation of the Evolution of New Heart Failure study(SCREEN-HF). Int J Cardiol. 2013;169:133–8.CrossRefPubMedGoogle Scholar
  8. 8.
    Nadir MA, Gandy S, Ireland S, et al. An increased B-type natriuretic peptide in the absence of a cardiac abnormality identifies those in whose left ventricular mass will increase over time. JACC Heart Fail. 2015;3(1):87–93.CrossRefPubMedGoogle Scholar
  9. 9.
    Seliger S, de Lemos J, Neeland I, et al. Older adults, “malignant” left ventricular hypertrophy and associated cardiac specific biomarker phenotypes to identify the differential risk of new-onset reduced versus preserved ejection fraction heart failure—JACC Heart Failure 2015 (in press).Google Scholar
  10. 10.•
    Wang TJ, Wollert KC, Larson MG, et al. Prognostic utility of novel biomarkers of cardiovascular stress. Framingham Heart Study Circ. 2012;126:1596–604. This important paper highlights that the value of measuring cardiovascular stress biomarkers in adding prognostic value to standard risk factors for predicting death, overall cardiovascular events, and heart failure.CrossRefGoogle Scholar
  11. 11.
    Saunders JT, Nambi V, de Lemos JA, et al. 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. 2011;123:1367–76.CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Nadir MA, Rekhraj S, Wei L, et al. Improving the primary prevention of cardiovascular events by using biomarkers to identify individuals with silent heart disease. J Am Coll Cardiol. 2012;60:960–8.CrossRefPubMedGoogle Scholar
  13. 13.
    de Lemos JA, Drazner MH, Omland T, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304:2503–12.CrossRefPubMedGoogle Scholar
  14. 14.
    de Filippi CR, de Lemos JA, Christenson RH, et al. Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults. JAMA. 2010;304:2494–502.CrossRefGoogle Scholar
  15. 15.
    Weinberg EO, Shimpo M, De Keulenaer GW, et al. Expression and regulation of ST2, an interleukin-1 receptor family member, in cardiomyocytes and myocardial infarction. Circulation. 2002;106:2961–6.CrossRefPubMedCentralPubMedGoogle Scholar
  16. 16.
    Sanada S, Hakuno D, Higgins LJ, et al. IL-33 and ST2 comprise acritical biomechanically induced and cardioprotective signaling system. J Clin Invest. 2007;117:1538–49.CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Hughes MF, Appelbaum S, Havulinna AS, et al. ST2 may not be a useful predictor for incident cardiovascular events, heart failure and mortality. Heart. 2014;100:1715–21.CrossRefPubMedGoogle Scholar
  18. 18.
    Chen LQ, de Lemos JA, Das SR, Ayers CR, Rohatgi A. Soluble ST2 is associated with all cause and cardiovascular mortality in a population based cohort. Dallas Heart Study Clin Chem. 2013;59:536–46.CrossRefGoogle Scholar
  19. 19.
    Lok DJ, Van Der Meer P, de la Porte PW, et al. Prognostic value of galectin-3, a novel marker of fibrosis in patients with chronic heart failure. Clin Res Cardiol. 2010;99:323–8.CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Ho JE, Liu C, Lyass A, et al. Galectin-3, a marker of cardiac fibrosis, predicts incident heart failure in the community. J Am Coll Cardiol. 2012;60:1249–56.CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.•
    Browers FP, van Gilst WH, Dammen K, et al. Clinical risk stratification optimises value of biomarkers to predict new-onset heart failure in a community based cohort. Circ Heart Fail. 2014;7:723–31. This is an important paper highlighting a multi-marker approach to risk stratify patients in the prediction of new onset heart failure.CrossRefGoogle Scholar
  22. 22.
    Neeland IJ, Drazner MH, Berry JD, et al. Biomarkers of chronic cardiac injury and hemodynamic stress identify a malignant phenotype of left ventricular hypertrophy in the general population. J Am Coll Cardiol. 2013;61(2):187–95.CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Neuhold S, Resl M, Huelsmann M, et al. Repeat measurements of glycated haemoglobin A and N-terminal pro-B-type natriurietic peptide: divergent behaviour in diabetes mellitus. Eur J Clin Investig. 2011;41(12):1292–8.CrossRefGoogle Scholar
  24. 24.
    Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355:2631–9.CrossRefPubMedGoogle Scholar
  25. 25.
    McMurray JJ. CONSENSUS to EMPHASIS: the overwhelming evidence which makes blockade of the renin angiotensin aldosterone system the cornerstone of therapy for systolic heart failure. Eur J Heart Fail. 2011;13:929–36.CrossRefPubMedGoogle Scholar
  26. 26.
    Minguet L, Sutton G, Ferrero C, Gomez T. Bramlage P.LCZ 696: a new paradigm for the treatment of heart failure? Expert Opin Pharmacother. 2015;16:435–46.PubMedGoogle Scholar
  27. 27.•
    Ledwidge M, Gallagher J, Conlon C, et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA. 2013;310(1):66–74. This study provides the first evidence that natriuretic peptide screening and collaborative of patients at risk of heart failure can reduce the combined rates of left ventricular systolic dysfunction, diastolic dysfunction, and heart failure.CrossRefPubMedGoogle Scholar
  28. 28.
    Huelsmann M, Neuhold S, Resl M. PONTIAC (NT-proBNP selected PreventiOn of cardiac eveNts in a population of diabetic patients without a history of Cardiac disease): a prospective randomized controlled trial. J Am Coll Cardiol. 2013;62:1365–72.CrossRefPubMedGoogle Scholar
  29. 29.
    Madamanchi C, Alhosaini H, Sumida A, Runge MS. Obesity and natriuretic peptides, BNP and NT-proBNP: mechanism and diagnostic implications for heart failure. Int J Cardiol. 2014;17:611–7.CrossRefGoogle Scholar
  30. 30.
    Davis ME, Richards M, Nicholls G, Yandle TG, Frampton CM, Troughton RW. Introduction of metoprolol increases plasma B-type natriuretic peptides in mild stable heart failure. 2006;113:977–85.Google Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Ken McDonald
    • 1
    • 2
  • Mark Ledwidge
    • 1
  • Joe Gallagher
    • 1
  • Chris Watson
    • 1
    • 2
  1. 1.St Vincent’s University HospitalDublin 4Ireland
  2. 2.University College DublinDublinIreland

Personalised recommendations