Netherlands Heart Journal

, Volume 18, Issue 4, pp 190–196 | Cite as

Neurohormonal profile of patients with heart failure and diabetes

  • I. C. C. van der Horst
  • R. A. de Boer
  • H. L. Hillege
  • F. Boomsma
  • A. A. Voors
  • D. J. van Veldhuisen
Original article
Heart Failure Neurotransmitter Agents Diabetes Mellitus 


Background. Neurohormonal activation is generally recognised to play an important role in the pathophysiology, prognosis and treatment of chronic heart failure (HF). While the number of patients with diabetes increases, little if anything is known about neurohormonal activation in HF patients with diabetes.

Methods. The study population consisted of 371 patients with advanced HF who were enrolled in a multicentre survival trial. Ten different plasma neurohormones were measured (noradrenaline, adrenaline, dopamine, aldosterone, renin, endothelin, atrial natriuretic peptide [ANP], N-terminal (pro)ANP, brain natriuretic peptide [BNP] and N-terminal (pro)BNP. Comparisons were made between patients with diabetes (n=81) and those without (n=290).

Results. At baseline, the two groups were comparable regarding age (mean 68 years), left ventricular ejection fraction (23%), severity and aetiology of HF, while body weight was higher in those with diabetes (77.4 vs. 74.2 kg, p=0.04). Most plasma neurohormones were similar between groups, but patients with diabetes had higher values of BNP (94 vs. 47 pmol/l, p=0.03), while a similar trend was observed for N-terminal (pro)BNP (750 vs. 554 pmol/l, p=0.10). During almost five years of follow-up, 51/81 patients with diabetes died (63%), as compared with 144 of 290 non-diabetic patients (50%) who died (p=0.046). Natriuretic peptides and noradrenaline were the most powerful predictors of mortality in both diabetic and non-diabetic HF patients.

Conclusion. HF patients with diabetes have higher (N-terminal (pro)) BNP levels than non-diabetic patients, while other neurohormones are generally similar. Natriuretic peptides are also good prognostic markers in diabetic HF patients. (Neth Heart J 2010;18:190-6.)


  1. 1.
    De Groote P, Lamblin N, Mouquet F, et al. Impact of diabetes mellitus on long-term survival in patients with congestive heart failure. Eur Heart J. 2004;25:656-62.Google Scholar
  2. 2.
    Dries DL, Sweitzer NK, Drazner MH, Stevenson LW, Gersh BJ. Prognostic impact of diabetes mellitus in patients with heart failure according to the etiology of left ventricular systolic dysfunction. J Am Coll Cardiol. 2001;38:42-8.Google Scholar
  3. 3.
    Jaarsma T, Van der Wal MH, Lesman-Leegte I, et al., for the COACH Study Group. Effect of moderate or intensive disease management program on outcome in patients with heart failure. The Coordinating study evaluating Outcomes of Advising and Counseling in Heart failure (COACH). Arch Intern Med. 2008;168:316-24. Google Scholar
  4. 4.
    McMurray JJ, Teerlink JR, Cotter G, et al., for the VERITAS Investigators. Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure. The VERITAS randomized controlled trials. JAMA. 2007;298:2009-19.Google Scholar
  5. 5.
    Dickstein K, Cohen-Solal A, Filippatos G, et al., on behalf of the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Guidelines for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008. Eur J Heart Fail. 2008;10:933-89.Google Scholar
  6. 6.
    Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol. 1974;34:29-34.Google Scholar
  7. 7.
    Shindler DM, Kostis JB, Yusuf S, et al. Diabetes mellitus, a predictor of morbidity and mortality in the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry. Am J Cardiol. 1996;77:1017-20.Google Scholar
  8. 8.
    Levine TB, Francis GS, Goldsmith SR, Simon AB, Cohn JN. Activity of the sympathetic nervous system and renin-angiotensin system assessed by plasma hormone levels and their relation to hemodynamic abnormalities in congestive heart failure. Am J Cardiol. 1982;49:1659-66.Google Scholar
  9. 9.
    Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol. 1992;20:248-54.Google Scholar
  10. 10.
    Schrier RW, Abraham WT. Hormones and hemodynamics in heart failure. N Engl J Med. 1999;341:577-85.Google Scholar
  11. 11.
    Miller JA, Floras JS, Zinman B, Skorecki KL, Logan AG. Effect of hyperglycaemia on arterial pressure, plasma renin activity and renal function in early diabetes. Clin Sci (Lond). 1996;90:189-95.Google Scholar
  12. 12.
    Hampton JR, Van Veldhuisen DJ, Kleber FX, et al, for the Second Prospective Randomised Study of Ibopamine on Mortality and Efficacy (PRIME-II) Investigators. Randomised study of effect of ibopamine on survival in patients with advanced severe heart failure. Lancet. 1997;349:97-7.Google Scholar
  13. 13.
    Tuinenburg AE, Van Veldhuisen DJ, Boomsma F, Van den Berg MP, De Kam PJ, Crijns HJ. Comparison of plasma neurohormones in congestive heart failure patients with atrial fibrillation versus patients with sinus rhythm. Am J Cardiol. 1998;81:1207-10.Google Scholar
  14. 14.
    Hogenhuis J, Voors AA, Jaarsma T, Hillege HL, Boomsma F, Van Veldhuisen DJ. 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. 2005;7:8-6. Google Scholar
  15. 15.
    Rienstra M, Van Gelder IC, Van den Berg MP, Boomsma F, Van Veldhuisen DJ. Natriuretic peptides in patients with atrial fibrillation and advanced chronic heart failure: determinants and prognostic value of (NT-) ANP and (NT-pro) BNP. Europace. 2006;8:482-7. Google Scholar
  16. 16.
    Swedberg K, Eneroth P, Kjekshus J, Wilhelmsen L. Hormones regulating cardiovascular function in patients with severe congestive heart failure and their relation to mortality. CONSENSUS Trial Study Group. Circulation. 1990;82:1730-6.Google Scholar
  17. 17.
    Latini R, Masson S, Anand I, et al. The comparative prognostic value of plasma neurohormones at baseline in patients with heart failure enrolled in Val-HeFT. Eur Heart J. 2004;25:292-9.Google Scholar
  18. 18.
    Magnusson M, Melander O, Israelsson B, Grubb A, Groop L, Jovinge S. Elevated plasma levels of Nt-proBNP in patients with type 2 diabetes without overt cardiovascular disease. Diabetes Care. 2004;27:1929-35.Google Scholar
  19. 19.
    Bhalla MA, Chiang A, Epshteyn VA, et al. Prognostic role of B-type natriuretic peptide levels in patients with type 2 diabetes mellitus. J Am Coll Cardiol. 2004;44:1047-52.Google Scholar
  20. 20.
    Albertini JP, Cohen R, Valensi P, Sachs RN, Charniot JC. B-type natriuretic peptide, a marker of asymptomatic left ventricular dysfunction in type 2 diabetic patients. Diabetes Metab. 2008;34:355-62.Google Scholar
  21. 21.
    Kindermann M, Reil JC, Piekse B, Van Veldhuisen DJ, Böhm M. Heart failure with normal left ventricular ejection fraction (HFNEF): what is the evidence? Trends Cardiovasc Med 2008; 2008;18:280-92. Google Scholar
  22. 22.
    Pieske B, Wachter R. Impact of diabetes and hypertension on the Heart. Curr Opin Cardiol. 2008;23:340-9.Google Scholar
  23. 23.
    Hartog JW, Voors AA, Bakker SJ, Smit AJ, Van Veldhuisen DJ. Advanced glycation end-products (AGEs) and heart failure; pathophysiological and clinical implications [review]. Eur J Heart Fail. 2007;9:1146-55.Google Scholar
  24. 24.
    Voors AA, De Jong RM. Treating diastolic heart failure. Heart. 2008;94:97-2.Google Scholar
  25. 25.
    Miller JA, Floras JS, Zinman B, Skorecki KL, Logan AG. Effect of hyperglycaemia on arterial pressure, plasma renin activity and renal function in early diabetes. Clin Sci (Lond). 1996;90:189-95.Google Scholar
  26. 26.
    Hopfner RL, Gopalakrishnan V. Endothelin: emerging role in diabetic vascular complications. Diabetologia. 1999;42:1383-94.Google Scholar
  27. 27.
    Van Veldhuisen DJ, Charlesworth A, Crijns HJGM, Lie KI, Hampton JR. Differences in drug treatment of chronic heart failure between European countries. Eur Heart J. 1999; 20:666-72.Google Scholar
  28. 28.
    Nosadini R, Fioretto P, Giorato C, et al. Sodium metabolism in insulin dependent diabetic patients. Role of insulin and atrial natriuretic peptide. Diabete Metab. 1989;15:30-5.Google Scholar
  29. 29.
    Barents M, Van der Horst IC, Voors AA, Hilege JL, Muskiet FA, De Jongste MJ. Prevalance and misdiagnosis of chronic heart failure in nursing home residents: the role of B-type natriuretic peptide. Neth Heart J. 2008;16:123-8. Google Scholar

Copyright information

© Bohn Stafleu van Loghum 2010

Authors and Affiliations

  • I. C. C. van der Horst
    • 1
    • 2
  • R. A. de Boer
  • H. L. Hillege
  • F. Boomsma
  • A. A. Voors
  • D. J. van Veldhuisen
  1. 1.Department of CardiologyUniversity Medical Center Groningen, University of GroningenGroningenthe Netherlands
  2. 2.

Personalised recommendations