Skip to main content
Log in

Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure

  • Original Contribution
  • Published:
Basic Research in Cardiology Aims and scope Submit manuscript

Abstract

Biovariability, reference change values (RCV), and index of individuality (IOI) have not been previously described for NT-proANP or GDF15. Also, the relation of changes of these markers to other clinical variables or biomarkers is unknown. In 41 patients with stable chronic systolic dysfunction, NT-proANP and GDF15 were measured alongside with clinical variables/markers comprising NT-proBNP, hsTnT, and hsCRP at four sampling intervals (2 weeks, 1-, 2-, 3-month intervals). At 2 weeks, 1-, 2-, and 3-month-follow-up, individual NT-proANP variations were 27.1, 22.5, 28.9, 15.6%, respectively, corresponding to RCVs of 53.2, 62.4, 80.2, and 43.2%, respectively. For GDF15, the respective individual variations were 6.8, 4.1, 5.5, 6.8%, corresponding to RCVs of 18.8, 11.5, 15.3 and 18.8%. Neither changes of NT-proANP or GDF15 correlated with changes in any of the clinical variables or biomarkers examined except for GDF15 with renal function. Baseline hormonal levels and clinical variables did not consistently influence the extent of change. The IOI was 0.19–0.35 according to interval for NT-proANP and 0.06–0.09 for GDF 15. In patients with CHF preselected for clinical stability changes of NT-proANP at intermediate follow-up do not correlate with changes in other variables; changes of GDF15 inversely correlate with renal function. The extent of change in both markers is not related to baseline hormonal levels or other baseline variables. RCVs are high for NT-proANP and low for GDF15, while inter-individual variation is high in GDF15 and intermediate in NT-proANP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Azizi C, Maistre G, Kalotka H, Isnard R, Barthélemy C, Masson F, Pham P, Pousset F, Eurin J, Lechat P, Komajda M, Carayon A (1996) Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure. J Endocrinol 148:51–57

    Article  CAS  PubMed  Google Scholar 

  2. Berger R, Huelsmann M, Strecker K, Moertl D, Moser P, Bojic A, Pacher R (2005) Neurohormonal risk stratification for sudden death and death owing to progressive heart failure in chronic heart failure. Eur J Clin Invest 35:24–31

    Article  CAS  PubMed  Google Scholar 

  3. Brattelid T, Tveit K, Birkeland JA, Sjaastad I, Qvigstad E, Krobert KA, Hussain RI, Skomedal T, Osnes JB, Levy FO (2007) Expression of mRNA encoding G protein-coupled receptors involved in congestive heart failure—a quantitative RT-PCR study and the question of normalisation. Basic Res Cardiol 102:198–208

    Article  CAS  PubMed  Google Scholar 

  4. Clerico A, Carlo Zucchelli G, Pilo A, Passino C, Emdin M (2006) Clinical relevance of biological variation: the lesson of brain natriuretic peptide (BNP) and NT-proBNP assay. Clin Chem Lab Med 44(4):366–378

    Article  CAS  PubMed  Google Scholar 

  5. Clerico A, Recchia FA, Passino C, Emdin M (2006) Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol Heart Circ Physiol 290:H17–H29

    Article  CAS  PubMed  Google Scholar 

  6. Cortes R, Rivera M, Salvador A, Bertomeu V, de Burgos FG, Rosello-Lleti E, Portoles M, Paya R, Martinez-Dolz L, Climent V (2007) Variability of NT-proBNP plasma and urine levels in patients with stable heart failure: a 2-year follow-up study. Heart 93:957–962

    Article  CAS  PubMed  Google Scholar 

  7. Doust JA, Pietrzak E, Dobson A, Glasziou P (2005) How well does B-type natriuretic peptide predict death and cardiac events in patients with heart failure: systematic review. Br Med J 330:625

    Article  CAS  Google Scholar 

  8. Eda S, Kaufmann J, Roos W, Pohl S (1998) Development of a new microparticle-enhanced turbidimetric assay for C-reactive protein with superior features in analytical sensitivity and dynamic range. J Clin Lab Anal 12:137–144

    Article  CAS  PubMed  Google Scholar 

  9. Frankenstein L, Nelles M, Slavutsky M, Schellberg D, Doesch A, Katus H, Remppis A, Zugck C (2007) Beta-blockers influence the short-term and long-term prognostic information of natriuretic peptides and catecholamines in chronic heart failure independent from specific agents. J Heart Lung Transplant 26:1033–1039

    Article  PubMed  Google Scholar 

  10. Hogenhuis J, Voors AA, Jaarsma T, Hillege HL, Boomsma F, van Veldhuisen DJ (2005) Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT-ANP and BNP/NT-proBNP. Eur J Heart Fail 7:81–86

    Article  CAS  PubMed  Google Scholar 

  11. Iglesias N, Petersen PH, Ricós C (2005) Power function of the reference change value in relation to cut-off points, reference intervals and index of individuality. Clin Chem Lab Med 43:441–448

    Article  CAS  PubMed  Google Scholar 

  12. Jourdain P, Jondeau G, Funck F, Gueffet P, Le Helloco A, Donal E, Aupetit JF, Aumont MC, Galinier M, Eicher JC, Cohen-Solal A, Juillière Y (2007) Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study. J Am Coll Cardiol 49:1733–1739

    Article  CAS  PubMed  Google Scholar 

  13. Katoh Y, Katoh M (2006) Comparative integromics on BMP/GDF family. Int J Mol Med 17:951–955

    CAS  PubMed  Google Scholar 

  14. Kempf T, Eden M, Strelau J, Naguib M, Willenbockel C, Tongers J, Heineke J, Kotlarz D, Xu J, Molkentin JD, Niessen HW, Drexler H, Wollert KC (2006) The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury. Circ Res 98:351–360

    Article  CAS  PubMed  Google Scholar 

  15. Kempf T, Horn-Wichmann R, Brabant G, Peter T, Allhoff T, Klein G, Drexler H, Johnston N, Wallentin L, Wollert KC (2007) Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay. Clin Chem 53:284–291

    Article  CAS  PubMed  Google Scholar 

  16. Kempf T, von Haehling S, Peter T, Allhoff T, Cicoira M, Doehner W, Ponikowski P, Filippatos GS, Rozentryt P, Drexler H, Anker SD, Wollert KC (2007) Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure. J Am Coll Cardiol 50:1054–1060

    Article  CAS  PubMed  Google Scholar 

  17. Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Angelici L, Barlera S, Parrinello G, Maggioni AP, Tognoni G, Cohn JN, Val-HeFT Investigators (2007) Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation 116:1242–1249

    Article  CAS  PubMed  Google Scholar 

  18. Laukkanen JA, Kurl S, Ala-Kopsala M, Vuolteenaho O, Ruskoaho H, Nyyssönen K, Salonen JT (2006) Plasma N-terminal fragments of natriuretic propeptides predict the risk of cardiovascular events and mortality in middle-aged men. Eur Heart J 27:1230–1237

    Article  CAS  PubMed  Google Scholar 

  19. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D (1999) A more accurate method to estimate glomerular filtration rate from serum creatinine A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461–470

    CAS  PubMed  Google Scholar 

  20. Luchner A, Schunkert H (2004) Interactions between the sympathetic nervous system and the cardiac natriuretic peptide system. Cardiovasc Res 63:443–449

    Article  CAS  PubMed  Google Scholar 

  21. Missbichler A, Hawa G, Schmal N, Woloszczuk W (2001) Sandwich ELISA for proANP 1-98 facilitates investigation of left ventricular dysfunction. Eur J Med Res 6:105–111

    CAS  PubMed  Google Scholar 

  22. Pedersen EB, Pedersen HB, Jensen KT (1999) Pulsatile secretion of atrial natriuretic peptide and brain natriuretic peptide in healthy humans. Clin Sci (Lond) 97:201–206

    Article  CAS  Google Scholar 

  23. Petersen PH, Sandberg S, Fraser CG, Goldschmidt H (2001) Influence of index of individuality on false positives in repeated sampling from healthy individuals. Clin Chem Lab Med 39:160–165

    Article  CAS  PubMed  Google Scholar 

  24. Rubattu S, Sciarretta S, Valenti V, Stanzione R, Volpe M (2008) Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases. Am J Hypertens 21:733–741

    Article  CAS  PubMed  Google Scholar 

  25. Schou M, Gustafsson F, Kjaer A, Hildebrandt PR (2007) Long-term clinical variation of NT-proBNP in stable chronic heart failure patients. Eur Heart J 28:177–182

    Article  CAS  PubMed  Google Scholar 

  26. Schou M, Gustafsson F, Nielsen PH, Madsen LH, Kjaer A, Hildebrandt PR (2007) Unexplained week-to-week variation in BNP and NT-proBNP is low in chronic heart failure patients during steady state. Eur J Heart Fail 9:68–74

    Article  CAS  PubMed  Google Scholar 

  27. Stanton E, Hansen M, Wijeysundera HC, Kupchak P, Hall C, Rouleau JL, PRAISE-2 study investigators (2005) A direct comparison of the natriuretic peptides and their relationship to survival in chronic heart failure of a presumed non-ischaemic origin. Eur J Heart Fail 7:557–565

    Article  CAS  PubMed  Google Scholar 

  28. Swedberg K, Cleland J, Dargie H, Drexler H, Follath F, Komajda M, Tavazzi L, Smiseth OA, Gavazzi A, Haverich A, Hoes A, Jaarsma T, Korewicki J, Levy S, Linde C, Lopez-Sendon JL, Nieminen MS, Pierard L, Remme WJ, Task Froce for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology (2005) Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology. Eur Heart J 26:1115–1140

    Article  PubMed  Google Scholar 

  29. Troughton RW, Frampton CM, Yandle TG, Espiner EA, Nicholls MG, Richards AM (2000) Treatment of heart failure guided by plasma aminoterminal terminal brain natriuretic peptide (N-BNP) concentrations. Lancet 355:1126–1130

    Article  CAS  PubMed  Google Scholar 

  30. White M, Rouleau JL, Hall C, Arnold M, Harel F, Sirois P, Greaves S, Solomon S, Ajani U, Glynn R, Hennekens C, Pfeffer M (2001) Changes in vasoconstrictive hormones, natriuretic peptides, and left ventricular remodeling soon after anterior myocardial infarction. Am Heart J 142:1056–1064

    Article  CAS  PubMed  Google Scholar 

  31. Wollert KC (2007) Growth-differentiation factor-15 in cardiovascular disease: from bench to bedside, and back. Basic Res Cardiol 102:412–415

    Article  CAS  PubMed  Google Scholar 

  32. Wu AH, Smith A (2004) Biological variation of the natriuretic peptides and their role in monitoring patients with heart failure. Eur J Heart Fail 6:355–358

    Article  CAS  PubMed  Google Scholar 

  33. Xu J, Kimball TR, Lorenz JN, Brown DA, Bauskin AR, Klevitsky R, Hewett TE, Breit SN, Molkentin JD (2006) GDF15/MIC-1 functions as a protective and antihypertrophic factor released from the myocardium in association with SMAD protein activation. Circ Res 98:342–350

    Article  CAS  PubMed  Google Scholar 

  34. Yeo KT, Wu AH, Apple FS, Kroll MH, Christenson RH, Lewandrowski KB, Sedor FA, Butch AW (2003) Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay. Clin Chim Acta 338:107–115

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lutz Frankenstein.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Frankenstein, L., Remppis, A., Frankenstein, J. et al. Reference change values and determinants of variability of NT-proANP and GDF15 in stable chronic heart failure. Basic Res Cardiol 104, 731–738 (2009). https://doi.org/10.1007/s00395-009-0027-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00395-009-0027-1

Keywords

Navigation