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Hypovitaminosis D in patients with heart failure: effects on functional capacity and patients’ survival

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Abstract

Chronic heart failure is a major cause of morbidity and mortality, but its prognosis remains poor. Vitamin D hormone has many extra-skeletal functions including a positive impact on the cardiovascular system, and has been proposed for mortality risk evaluation in heart failure patients. The aim of the present study was to evaluate vitamin D status in heart failure patients, measured by high performance liquid chromatography coupled with mass spectrometry and to correlate serum 25 hydroxy-vitamin D (25OHD) levels with functional (peak VO2%) and mortality (Metabolic Exercise Cardiac Kidney Index) heart failure parameters. We enrolled 261 consecutive patients diagnosed with heart failure; all patients underwent a comprehensive clinical and biochemical characterization, and serum 25OHD levels were measured by high performance liquid chromatography coupled with mass spectrometry. Cardiopulmonary test parameters and Metabolic Exercise Cardiac Kidney Index of mortality risk were measured in all patients. Serum 25OHD levels ranged between 2 and 45 ng/ml (mean 17 ± 9 ng/ml); most patients (87%) showed hypovitaminosis D, and 25% showed severe vitamin D deficiency (serum 25OHD < 10 ng/ml). Patients with 25OHD < 10 ng/ml had significantly lower cardiopulmonary test VO2/kg, peak VO2% and significantly higher N-terminalproBrain natriuretic peptide and Metabolic Exercise Cardiac Kidney Index, than patients with 25OHD > 10 ng/ml. Patients with peak VO2% < 50% showed significantly lower 25OHD compared to those with peak VO2% > 50%. There was a significant, positive correlation (r = 0.16, p = 0.008) between 25OHD levels and peak VO2%, and an inverse correlation with Metabolic Exercise Cardiac Kidney Index (r = −0.21, p < 0.001), even when adjusted for age, Body Mass Index, MDRD, N-terminalproBrain natriuretic peptide. In conclusion, our findings show that vitamin D levels are associated with functional and mortality heart failure prognosis parameters.

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References

  1. D. Aune, A. Sen, T. Norat, I. Janszky, P. Romundstad, S. Tonstad, L.J. Vatten, Body mass index, abdominal fatness, and heart failure incidence and mortality: a systematic review and dose-response meta-analysis of prospective studies. Circulation 133, 639–649 (2016)

    Article  PubMed  Google Scholar 

  2. Y.C. Li, J. Kong, M. Wei, Z.F. Chen, S.Q. Liu, L.P. Cao, 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J. Clin. Invest. 110, 229–238 (2002)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Y.C. Li, Vitamin D regulation of the renin-angiotensin system. J. Cell. Biochem. 88(2), 327–331 (2003)

  4. A. Rahman, S. Hershey, S. Ahmed, K. Nibbelink, R.U. Simpson, Heart extracellular matrix gene expression profile in the vitamin D receptor knockout mice. J. Steroid Biochem. Mol. Biol. 103, 416–419 (2007)

    Article  CAS  PubMed  Google Scholar 

  5. S.S. Schleithoff, A. Zittermann, G. Tenderich, H.K. Berthold, P. Stehle, R. Koerfer, Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial. Am. J. Clin. Nutr. 83, 754–759 (2006)

    CAS  PubMed  Google Scholar 

  6. M.F. Holick, N.C. Binkley, H.A. Bischoff-Ferrari, C.M. Gordon, D.A. Hanley, R.P. Heaney, M.H. Murad, C.M. Weaver, Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J. Clin. Endocrinol. Metab. 96, 1911–1930 (2011)

    Article  CAS  PubMed  Google Scholar 

  7. M.F. Holick, T.C. Chen, Vitamin D deficiency: a worldwide problem with health consequences. Am. J. Clin. Nutr. 87, 1080S–1086S (2008)

  8. J.F. Aloia, Clinical review: the 2011 report on dietary reference intake for vitamin D: where do we go from here? J. Clin. Endocrinol. Metab. 96, 2987–2996 (2011)

    Article  CAS  PubMed  Google Scholar 

  9. R.A. Bouillon, J.H. Auwerx, W.D. Lissens, W.K. Pelemans, Vitamin D status in the elderly: Seasonal substrate deficiency causes 1,25-dihydroxycholecalciferol deficiency. Am. J. Clin. Nutr. 45, 755–763 (1987)

    CAS  PubMed  Google Scholar 

  10. T. Skaaby, L.L.N. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, M. Fenger, A. Linneberg, Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 43, 618–625 (2013)

    Article  CAS  PubMed  Google Scholar 

  11. L. Wang, Y. Song, J.E. Manson, S. Pilz, W. März, K. Michaëlsson, A. Lundqvist, S.K. Jassal, E. Barrett-Connor, C. Zhang, C.B. Eaton, H.T. May, J.L. Anderson, H.D. Sesso, Circulating levels of 25hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ. Cardiovasc. Qual. Outcomes 5, 819–829 (2012)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. S.T. Lugg, P.A. Howells, D.R. Thickett, Optimal vitam in D supplementation levels for cardiovascular disease protection. Dis. Markers 2015, 1–10 (2015)

  13. S.E. Judd, V. Tangpricha, Vitamin D deficiency and risk for cardiovascular disease. Am. J. Med. Sci. 338, 40–44 (2009)

    Article  PubMed  PubMed Central  Google Scholar 

  14. B. Kestenbaum, R. Katz, I. De Boer, A. Hoofnagle, M.J. Sarnak, M.G. Shlipak, N.S. Jenny, D.S. Siscovick, Vitamin D, Parathyroid hormone, and cardiovascular events among older adults. J. Am. Coll. Cardiol. 58, 1433–1441 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. G. Muscogiuri, V. Nuzzo, A. Gatti, A. Zuccoli, S. Savastano, C. Di Somma, R. Pivonello, F. Orio, A. Colao, Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes? Endocrine 51(2), 268–273 (2015)

  16. T. Skaaby, L.L.N. Husemoen, C. Pisinger, T. Jørgensen, B.H. Thuesen, K. Rasmussen, M. Fenger, P. Rossing, A. Linneberg, Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population. Endocrine 44, 473–480 (2013)

    Article  CAS  PubMed  Google Scholar 

  17. J. Kendrick, G. Targher, G. Smits, M. Chonchol, 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis 205, 255–260 (2009)

    Article  CAS  PubMed  Google Scholar 

  18. J.M. El-Khoury, E.Z. Reineks, S. Wang, Progress of liquid chromatography-mass spectrometry in measurement of vitamin D metabolites and analogues. Clin. Biochem. 44, 66–76 (2011)

  19. G.D. Carter, Accuracy of 25-hydroxyvitamin D assays: confronting the issues. Curr. Drug. Targets 12, 19–28 (2011)

    Article  CAS  PubMed  Google Scholar 

  20. B.W. Hollis, Measuring 25-hydroxyvitamin D in a clinical environment: challenges and needs. Am. J. Clin. Nutr. 88, 507S–510S (2008)

  21. J.O. O’Neill, J.B. Young, C.E. Pothier, M.S. Lauer, Peak oxygen consumption as a predictor of death in patients with heart failure receiving beta-blockers. Circulation 111, 2313–2318 (2005)

    Article  PubMed  Google Scholar 

  22. R. Arena, J. Myers, J. Abella, M.A. Peberdy, D. Bensimhon, P. Chase, M. Guazzi, Development of a ventilatory classification system in patients with heart failure. Circulation 115, 2410–2417 (2007)

    Article  PubMed  Google Scholar 

  23. J. Crespo, C.J. Lavie, R.V. Milani, Y.E. Gilliland, H.M. Patel, H.O. Ventura, Metabolic parameters derived from cardiopulmonary stress testing for prediction of prognosis in patients with heart failure: the ochsner experience. Ochsner J. 9, 46–53 (2009)

    PubMed  PubMed Central  Google Scholar 

  24. U. Corrà, P. Agostoni, A. Giordano, G. Cattadori, E. Battaia, R. La Gioia, A.B. Scardovi, M. Emdin, M. Metra, G. Sinagra, G. Limongelli, R. Raimondo, F. Re, M. Guazzi, R. Belardinelli, G. Parati, D. Magrì, C. Fiorentini, M. Cicoira, E. Salvioni, M. Giovannardi, F. Veglia, A. Mezzani, D. Scrutinio, A. Di Lenarda, R. Ricci, A. Apostolo, A.M. Iorio, S. Paolillo, P. Palermo, M. Contini, C. Vassanelli, C. Passino, P. Giannuzzi, M.F. Piepoli, The metabolic exercise test data combined with Cardiac and Kidney Indexes (MECKI) score and prognosis in heart failure. A validation study. Int. J. Cardiol. 203, 1067–1072 (2016)

    Article  PubMed  Google Scholar 

  25. V. Carubelli, M. Metra, U. Corrà, D. Magrì, C. Passino, C. Lombardi, D. Scrutinio, M. Correale, G. Cattadori, M.F. Piepoli, E. Salvioni, M. Giovannardi, R. Raimondo, M. Cicoira, R. Belardinelli, M. Guazzi, G. Limongelli, F. Clemenza, G. Parati, A.B. Scardovi, A. Di Lenarda, M. Bussotti, R. La Gioia, P. Agostoni, Exercise performance is a prognostic indicator in elderly patients with chronic heart failure–application of metabolic exercise cardiac kidney indexes score. Circ. J. 79, 2608–2615 (2015)

    Article  PubMed  Google Scholar 

  26. P. Ponikowski, A.A. Voors, S.D. Anker, H. Bueno, J.G.F. Cleland, A.J.S. Coats, V. Falk, J.R. González-Juanatey, V.P. Harjola, E.A. Jankowska, M. Jessup, C. Linde, P. Nihoyannopoulos, J.T. Parissis, B. Pieske, J.P. Riley, G.M.C. Rosano, L.M. Ruilope, F. Ruschitzka, F.H. Rutten, P. Van Der Meer, 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 37, 2129–2200m (2016)

    Article  PubMed  Google Scholar 

  27. S.A. Hsu, J. Soldo, M. Gupta, Evaluation of two automated immunoassays for 25-OH vitamin D: comparison against LC-MS/MS. J. Steroid Biochem. Mol. Biol. 136, 139–145 (2013)

  28. H.W. Moon, J.H. Cho, M. Hur, J. Song, G.Y. Oh, C.M. Park, Y.M. Yun, J.Q. Kim, Comparison of four current 25-hydroxyvitamin D assays. Clin. Biochem. 45, 326–330 (2012)

    Article  CAS  PubMed  Google Scholar 

  29. K.D. Cashman, K.G. Dowling, Z. Škrabáková, M. Gonzalez-Gross, J. Valtueña, S. De Henauw, L. Moreno, C.T. Damsgaard, K.F. Michaelsen, C. Mølgaard, R. Jorde, G. Grimnes, G. Moschonis, C. Mavrogianni, Y. Manios, M. Thamm, G.B.M. Mensink, M. Rabenberg, M.A. Busch, L. Cox, S. Meadows, G. Goldberg, A. Prentice, J.M. Dekker, G. Nijpels, S. Pilz, K.M. Swart, N.M. Van Schoor, P. Lips, G. Eiriksdottir, V. Gudnason, M.F. Cotch, S. Koskinen, C. Lamberg-Allardt, R.A. Durazo-Arvizu, C.T. Sempos, M. Kiely, Vitamin D deficiency in Europe: pandemic? Am. J. Clin. Nutr. 103, 1033–1044 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. E.A. Yetley, C.M. Pfeiffer, R.L. Schleicher, K.W. Phinney, D.A. Lacher, S. Christakos, J.H. Eckfeldt, J.C. Fleet, G. Howard, A.N. Hoofnagle, S.L. Hui, G.L. Lensmeyer, J. Massaro, M. Peacock, B. Rosner, D. Wiebe, R.L. Bailey, P.M. Coates, A.C. Looker, C. Sempos, C.L. Johnson, M.F. Picciano, NHANES monitoring of serum 25-hydroxyvitamin D: a roundtable summary. J. Nutr. 140, 2030S–2045S (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. G. Sarno, G. Daniele, G. Tirabassi, A.O. Chavez, O.O. Ojo, F. Orio, H. Kahleova, G. Balercia, W.B. Grant, P. De Rosa, A. Colao, G. Muscogiuri, The impact of vitamin D deficiency on patients undergoing kidney transplantation: focus on cardiovascular, metabolic, and endocrine outcomes. Endocrine 50, 568–574 (2015)

    Article  CAS  PubMed  Google Scholar 

  32. A. Di Nisio, L. De Toni, E. D’Addato, M.R. Pizzo, P. Sabatino, C. Foresta, 25-Hydroxyvitamin D insufficiency discriminates cardiovascular risk factors accumulation in peri-pubertal boys undergoing overweight screening. Endocrine 53, 530–537 (2016)

    Article  PubMed  Google Scholar 

  33. R.S. Boxer, A.M. Kenny, V.K. Cheruvu, M. Vest, J.J. Fiutem, I.I. Piña, Serum 25-hydroxyvitamin D concentration is associated with functional capacity in older adults with heart failure. Am. Heart J. 160, 893–899 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. A. Kaul, S. Gläser, A. Hannemann, C. Schäper, M. Nauck, S.B. Felix, T. Bollmann, R. Ewert, N. Friedrich, Vitamin D is associated with cardiopulmonary exercise capacity: results of two independent cohorts of healthy adults. Br. J. Nutr. 25, 1–9 (2015)

    Google Scholar 

  35. A.J. Coats, The “muscle hypothesis” of chronic heart failure. J. Mol. Cell. Cardiol. 28, 2255–2262 (1996)

    Article  CAS  PubMed  Google Scholar 

  36. H.C.J.P. Janssen, M.M. Samson, H.J.J. Verhaar, Vitamin D deficiency, muscle function, and falls in elderly people. Am. J. Clin. Nutr. 75, 611–615 (2002)

    CAS  PubMed  Google Scholar 

  37. R. Boland, A. Norman, E. Ritz, W. Hasselbach, Presence of a 1,25-dihydroxy-vitamin D3 receptor in chick skeletal muscle myoblasts. Biochem. Biophys. Res. Commun. 128, 305–311 (1985)

    Article  CAS  PubMed  Google Scholar 

  38. H.A. Bischoff, M. Borchers, F. Gudat, U. Duermueller, R. Theiler, H.B. Stähelin, W. Dick, In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem. J. 33, 19–24 (2001)

    Article  CAS  PubMed  Google Scholar 

  39. H.C.J.P. Janssen, M.M. Samson, H.J.J. Verhaar, Muscle strength and mobility in vitamin D-insufficient female geriatric patients: a randomized controlled trial on vitamin D and calcium supplementation. Aging Clin. Exp. Res. 22, 78–84 (2010)

    Article  CAS  PubMed  Google Scholar 

  40. S. Nesby-O’Dell, K.S. Scanlon, M.E. Cogswell, C. Gillespie, B.W. Hollis, A.C. Looker, C. Allen, C. Doughertly, E.W. Gunter, B.A. Bowman, Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994. Am. J. Clin. Nutr. 76, 187–192 (2002)

    PubMed  Google Scholar 

  41. A.C. Looker, C.L. Johnson, D.A. Lacher, C.M. Pfeiffer, R.L. Schleicher, C.T. Sempos, Vitamin D status: United States, 2001-2006. NCHS Data Brief 127, 1–8 (2011)

    Google Scholar 

  42. L.M.G. Meems, P. van der Harst, W.H. van Gilst, R.A. de Boer, Vitamin D biology in heart failure: molecular mechanisms and systematic review. Curr. Drug. Targets 12, 29–41 (2011)

    Article  CAS  PubMed  Google Scholar 

  43. P. Agostoni, U. Corra, G. Cattadori, F. Veglia, R. La Gioia, A. Sardovii, F. Re, M. Guazzi, R. Belardinelli, D. Scrutinio, R. Ricci, L. Bettari, A. Lenarda, L. Pastormerlo, G. Pacileo, R. Vaninetti, A. Apostolo, A. Iorio, S. Paolillo, P. Palermo, M. Contini, M. Confalonieri, P. Gianuzzi, A. Passantino, L. Cas, M. Piepoli, C. Passino, Metabolic exercise test data combined with cardiac and kidney indexes, the MECKI score: a multiparametric approach to heart failure prognosis. Int. J. Cardiol. 167, 2710–2718 (2013)

    Article  PubMed  Google Scholar 

  44. I. Gotsman, A. Shauer, D.R. Zwas, Y. Hellman, A. Keren, C. Lotan, D. Admon, Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; Vitamin D supplementation improves outcome. Eur. J. Heart Fail. 14, 357–366 (2012)

    Article  CAS  PubMed  Google Scholar 

  45. E. Belen, A. Sungur, M.A. Sungur, Vitamin D levels predict hospitalization and mortality in patients with heart failure. Scand. Cardiovasc. J. 50(1), 1–23 (2015)

  46. W.-L. Jiang, H.-B. Gu, Y.-F. Zhang, Q.-Q. Xia, J. Qi, J.-C. Chen, Vitamin D supplementation in the treatment of chronic heart failure: a meta-analysis of randomized controlled trials. Clin. Cardiol. 39(1), 55–61 (2015)

    Google Scholar 

  47. A. Zittermann, S.S. Schleithoff, R. Koerfer, Vitamin D insufficiency in congestive heart failure: why and what to do about it? Heart Fail. Rev. 11, 25–33 (2006)

  48. A. Zittermann, S. Schulze Schleithoff, G. Tenderich, H.K. Berthold, R. Körfer, P. Stehle, Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J. Am. Coll. Cardiol. 41, 105–112 (2003)

    Article  CAS  PubMed  Google Scholar 

  49. E. Christ, A. Linka, G. Junga, M. Odermatt, H. Steinert, W. Kiowski, C. Schmid, Bone density and laboratory parameters of bone metabolism in patients with terminal heart disease. Schweiz. Med. Wochenschr. 126, 1553–1559 (1996)

    CAS  PubMed  Google Scholar 

  50. I. Garcia Delgado, L. Gil-Fraguas, E. Robles, G. Martinez, F. Hawkins, Clinical factors associated with bone mass loss previous cardiac transplantation. Med. Clin. (Barc.) 114, 761–764 (2000)

    Article  CAS  Google Scholar 

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Saponaro, F., Marcocci, C., Zucchi, R. et al. Hypovitaminosis D in patients with heart failure: effects on functional capacity and patients’ survival. Endocrine 58, 574–581 (2017). https://doi.org/10.1007/s12020-017-1282-9

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