Skip to main content
Log in

Association of increased parathyroid hormone with neuroendocrine activation and endothelial dysfunction in elderly men with heart failure

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

High PTH levels have been reported in patients with chronic heart failure (CHF). Similarly, its levels increase with aging and are related to impaired survival in elderly adults. However, its relationship with neuroendocrine activation and endothelial dysfunction in CHF has not been previously studied. Seventy-three CHF males with New York Heart Association (NYHA) classes II and III and 20 control subjects aged >55 yr were recruited. PTH, 25-hydroxyvita-min D [25(OH)D], N-terminal pro-brain natriuretic peptide (NT-pro-BNP), adiponectin, and osteoprotegerin were measured. Endothelial function (brachial flow mediated dilation), echocardiography, physical performance, and quality of life were assessed, as well. CHF patients had markedly increased serum PTH (77±33 vs 40±11 pg/ml, p<0.0001), NT-pro-BNP [1809 (2742) vs 67 (74) pg/ml, p<0.0001], adiponectin (17±9 vs 10±2 µg/ml, p<0.0001), osteoprotegerin, whereas 25(OH)D levels were decreased compared to controls. Increased PTH is positively correlated with NT-pro-BNP (r=0.399, p<0.0001), adiponectin (r=0.398, p<0.0001), and osteoprotegerin, whereas negatively with 25(OH)D in CHF patients. Additionally, increased serum PTH was associated with endothelial dysfunction, echocardiographic variables of heart failure progression, impaired physical performance, and deteriorated quality of life. In a multivariate linear regression analysis, increased serum PTH was independently associated with neuroendocrine activation (NT-pro-BNP, adiponectin) and endothelial dysfunction in elderly CHF men (R2=0.455). Additionally, demonstrated relations with other well-established variables of heart failure severity suggest the potential role of serum PTH in the pathogenesis and non-invasive monitoring of heart failure progression. Future studies are needed to evaluate the predictive value of serum PTH for clinical outcomes as well as beneficial potential of PTH suppression in CHF patients.

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. Hobbs FD. The scale of heart failure: diagnosis and management issues for primary care. Heart 1999, 82: IV8–10.

    PubMed Central  PubMed  Google Scholar 

  2. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, et al. Long-term trends in the incidence of and survival with heart failure. N Engl J Med 2002, 347: 1397–402.

    Article  PubMed  Google Scholar 

  3. Braunwald E. Biomarkers in heart failure. N Engl J Med 2008, 358: 2148–59.

    Article  CAS  PubMed  Google Scholar 

  4. Gunnarsson O, Indridason OS, Franzson L, Sigurdsson G. Factors associated with elevated or blunted PTH response in vitamin D insufficient adults. J Intern Med 2009, 265: 488–95.

    Article  CAS  PubMed  Google Scholar 

  5. Premaor MO, Scalco R, da Silva MJ, Furlanetto TW. Secondary hyperparathyroidism is associated with increased risk of hospitalization or death in elderly adults living in a geriatric institution. Gerontology 2009, 55: 405–10.

    Article  CAS  PubMed  Google Scholar 

  6. Shane E, Mancini D, Aaronson K, et al. Bone mass, vitamin D deficiency, and hyperparathyroidism in congestive heart failure. Am J Med 1997, 103: 197–207.

    Article  CAS  PubMed  Google Scholar 

  7. Sugimoto T, Tanigawa T, Onishi K, et al. Serum intact parathyroid hormone levels predict hospitalization for heart failure. Heart 2009, 95: 395–8.

    Article  CAS  PubMed  Google Scholar 

  8. Bhattacharya SK, Ahokas RA, Carbone LD, et al. Macro- and micronutrients in African-Americans with heart failure. Heart Fail Rev 2006, 11: 45–55.

    Article  CAS  PubMed  Google Scholar 

  9. Alsafwah S, Laguardia SP, Arroyo M, et al. Congestive heart failure is a systemic illness: a role for minerals and micronutrients. Clin Med Res 2007, 5: 238–43.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Chhokar VS, Sun Y, Bhattacharya SK, et al. Hyperparathyroidism and the calcium paradox of aldosteronism. Circulation 2005, 111: 871–8.

    Article  CAS  PubMed  Google Scholar 

  11. Saleh FN, Schirmer H, Sundsfjord J, Jorde R. Parathyroid hormone and left ventricular hypertrophy. Eur Heart J 2003, 24: 2054–60.

    Article  CAS  PubMed  Google Scholar 

  12. Tastan I, Schreckenberg R, Mufti S, Abdallah Y, Piper HM, Schlüter KD. Parathyroid hormone improves contractile performance of adult rat ventricular cardiomyocytes at low concentrations in a nonacute way. Cardiovasc Res 2009, 82: 77–83.

    Article  CAS  PubMed  Google Scholar 

  13. Okamoto H. Can adiponectin be a novel metabolic biomarker for heart failure? Circ J 2009, 73: 1012–3.

    Article  CAS  PubMed  Google Scholar 

  14. von Haehling S, Jankowska EA, Morgenthaler NG, et al. Comparison of midregional pro-atrial natriuretic peptide with N-terminal pro-B-type natriuretic peptide in predicting survival in patients with chronic heart failure. J Am Coll Cardiol 2007, 50: 1973–80.

    Article  Google Scholar 

  15. Katz SD, Hryniewicz K, Hriljac I, et al. Vascular endothelial dysfunction and mortality risk in patients with chronic heart failure. Circulation 2005, 111: 310–4.

    Article  PubMed  Google Scholar 

  16. Fischer D, Rossa S, Landmesser U, et al. Endothelial dysfunction in patients with chronic heart failure is independently associated with increased incidence of hospitalization, cardiac transplantation, or death. Eur Heart J 2005, 26: 65–9.

    Article  CAS  PubMed  Google Scholar 

  17. Corretti MC, Anderson TJ, Benjamin EJ, et al. International Brachial Artery Reactivity Task Force. Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol 2002, 39: 257–65.

    Article  PubMed  Google Scholar 

  18. Anker SD, Chua TP, Ponikowski P, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation 1997, 96: 526–34.

    Article  CAS  PubMed  Google Scholar 

  19. ATS statement: guidelines for the six-minute walk test. ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. Am J Respir Crit Care Med 2002, 166: 111–7.

    Article  Google Scholar 

  20. Silvestry FE, Kerber RE, Brook MM, et al. Echocardiography-guided interventions. J Am Soc Echocardiogr 2009, 22: 213–31.

    Article  PubMed  Google Scholar 

  21. Devereux RB, Roman MJ, de Simone G, et al. Relations of left ventricular mass to demographic and hemodynamic variables in American Indians: the Strong Heart Study. Circulation 1997, 96: 1416–23.

    Article  CAS  PubMed  Google Scholar 

  22. Rector TS, Cohn JN. Assessment of patient outcome with the Minnesota Living with Heart Failure questionnaire: Reliability and validity during a randomized, double-blind, placebo-controlled trial of pimobendan. Pimobendan Multicenter Research Group. Am Heart J 1992, 124: 1017–25.

    Article  CAS  PubMed  Google Scholar 

  23. Cockroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976, 16: 31–41.

    Article  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  25. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Körfer R, Stehle P. Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003, 41: 105–12.

    Article  CAS  PubMed  Google Scholar 

  26. George J, Patal S, Wexler D, et al. Circulating adiponectin concentrations in patients with congestive heart failure. Heart 2006, 92: 1420–24.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Tamura T, Furukawa Y, Taniguchi R, et al. Serum adiponectin level as an independent predictor of mortality in patients with congestive heart failure. Circ J 2007, 71: 623–30.

    Article  CAS  PubMed  Google Scholar 

  28. Sahota O, Masud T, San P, Hosking DJ. Vitamin D insufficiency increases bone turnover markers and enhances bone loss at the hip in patients with established vertebral osteoporosis. Clin Endocrinol (Oxf) 1999, 51: 217–21.

    Article  CAS  Google Scholar 

  29. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007, 130: 456–69.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. Confavreux CB, Levine R, Karsent G. A paradigm of integrative physiology, the crosstalk between bone and energy metabolisms. Mol Cell Endocrinol 2009, 310: 21–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Omland T, Drazner MH, Uehland T, et al. Plasma osteoprotegerin levels in the general population: relation to indices of left ventricular structure and function. Hypertension 2007, 49: 1392–8.

    Article  CAS  PubMed  Google Scholar 

  32. Ueland T, Jemtland R, Godang K, et al. Prognostic value of osteoprotegerin in heart failure after acute myocardial infarction. J Am Coll Cardiol 2004, 44: 1970–6.

    Article  CAS  PubMed  Google Scholar 

  33. Wykretowicz A, Furmaniuk J, Smielecki J, et al. The oxygen stress index and levels of circulating interleukin-10 and interleukin-6 in patients with chronic heart failure. Int J Cardiol 2004, 94: 283–7.

    Article  PubMed  Google Scholar 

  34. McCarty MF. Secondary hyperparathyroidism promotes the acute phase response — a rationale for supplemental vitamin D in prevention of vascular events in the elderly. Med Hypotheses 2005, 64: 1022–6.

    Article  CAS  PubMed  Google Scholar 

  35. Qin L, Raggatt LJ, Partridge NC. Parathyroid hormone: a double-edged sword for bone metabolism. Trends Endocrinol Metab 2004, 15: 60–5.

    Article  CAS  PubMed  Google Scholar 

  36. Golledge J, Leicht AS, Crowther RG, et al. Determinants of endothelial function in a cohort of patients with peripheral artery disease. Cardiology 2008, 111: 51–6.

    Article  CAS  PubMed  Google Scholar 

  37. Shin JY, Shin YG, Chung CH. Elevated serum osteoprotegerin levels are associated with vascular endothelial dysfunction in type 2 diabetes. Diabetes Care 2006, 29: 1664–6.

    Article  CAS  PubMed  Google Scholar 

  38. Bittner V, Weiner DH, Yusuf S, et al. Prediction of mortality and morbidity with a 6-minute walk test in patients with left ventricular dysfunction. SOLVD Investigators. JAMA 1993, 270: 1702–7.

    Article  CAS  PubMed  Google Scholar 

  39. Nishimura R, Tajik AA. Quantitative hemodynamics by Doppler echocardiography: a noninvasive alternative to cardiac catheterization. Prog Cardiovasc Dis 1994, 36: 309–42.

    Article  CAS  PubMed  Google Scholar 

  40. Rihal C, Nishimura R, Hatle L, Bailey K, Tajik A. Systolic and diastolic dysfunction in patients with clinical diagnosis of dilated cardiomyopathy: relation to symptoms and prognosis. Circulation 1994, 90: 2772–9.

    Article  CAS  PubMed  Google Scholar 

  41. Rejnmark L, Vestergaard P, Brot C, Mosekilde L. Parathyroid response to vitamin D insufficiency: relations to bone, body composition and to lifestyle characteristics. Clin Endocrinol (Oxf) 2008, 69: 29–35.

    Article  CAS  Google Scholar 

  42. Cohen N, Gorelik O, Almoznino-Sarafian D, et al. Renal dysfunction in congestive heart failure, pathophysiological and prognostic significance. Clin Nephrol. 2004, 61: 177–84.

    Article  CAS  PubMed  Google Scholar 

  43. Zittermann A, Schleithoff SS, Koerfer R. Markers of bone metabolism in congestive heart failure. Clin Chim Acta 2006, 366: 27–36.

    Article  CAS  PubMed  Google Scholar 

  44. Pilz S, März W, Wellnitz B, et al. Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 2008, 93: 3927–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. Popovic MD, PhD, FRCP.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Loncar, G., Bozic, B., Dimkovic, S. et al. Association of increased parathyroid hormone with neuroendocrine activation and endothelial dysfunction in elderly men with heart failure. J Endocrinol Invest 34, e78–e85 (2011). https://doi.org/10.1007/BF03347080

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347080

Key-words

Navigation