ARYA Atherosclerosis Journal

The effect of vitamin D therapy in the improvement of cardiac performance and exercise capacity in patients with heart failure: A double-blind, randomized, placebo-controlled trial

Document Type : Original Article(s)

Authors

Mohammad Garakyaraghi 1
Mansour Siavash 2
Maryam Kerdegari 3

1 Professor, Herat Failure Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Isfahan Endocrine and Metabolism Research Center, Isfahan University of Medical Sciences, Isfahan, Iran

3 Cardiologist, Cardiac Rehabilitation Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran

https://doi.org/10.22122/arya.v17i0.2135
Abstract
BACKGROUND: Low vitamin D status may contribute to the pathogenesis of heart failure (HF), but therapeutic roles of vitamin D on cardiac performance are not well known. We evaluated vitamin D effects on left ventricular ejection fraction (LVEF) and New York Heart Association (NYHA) functional class in patients with HF for the first time.METHODS: This study was a double-blind, randomized, placebo-controlled trial. 110 patients with HF admitted to Shahid Chamran and Khorshid Hospitals, Isfahan, Iran, randomly received 500 mg calcium daily plus either 50000 IU vitamin D3 per week (case group) or placebo (control group) for 6 months. Biochemical variables, LVEF, and NYHA functional class were assessed at baseline and after 6 months.RESULTS: 81 patients completed the study. Vitamin D supplementation increased mean serum 25-hydroxyvitamin D [25(OH)D] concentration in the case group by 33.9 ng/ml (P < 0.001). After 6 months of treatment, both groups showed improvement in LVEF, but the extent of improvement was significant only in the case group (5.48% versus 0.44%, P < 0.001). The NYHA functional class improved in the case group but remained constant in the control group (P < 0.001).CONCLUSION: Vitamin D3 improved LVEF and NYHA functional class in patients with HF and might serve as a new agent for the future treatment of this disease. 

Keywords

Heart Failure
Vitamin D
Randomized Controlled Trial
  1. Jessup M, Brozena S. Heart failure. N Engl J Med 2003; 348(20): 2007-18.
  2. Barker WH, Mullooly JP, Getchell W. Changing incidence and survival for heart failure in a well-defined older population, 1970-1974 and 1990-1994. Circulation 2006; 113(6): 799-805.
  3. Curtis LH, Whellan DJ, Hammill BG, Hernandez AF, Anstrom KJ, Shea AM, et al. Incidence and prevalence of heart failure in elderly persons,
  4. -2003. Arch Intern Med 2008; 168(4): 418-24.
  5. Forman DE, Ahmed A, Fleg JL. Heart failure in very old adults. Curr Heart Fail Rep 2013; 10(4): 387-400.
  6. Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: Prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J 2004; 25(18): 1614-9.
  7. Loehr LR, Rosamond WD, Chang PP, Folsom AR, Chambless LE. Heart failure incidence and survival (from the Atherosclerosis Risk in Communities study). Am J Cardiol 2008; 101(7): 1016-22.
  8. Witte KK, Clark AL, Cleland JG. Chronic heart failure and micronutrients. J Am Coll Cardiol 2001; 37(7): 1765-74.
  9. Witte KK, Nikitin NP, Parker AC, von HS, Volk HD, Anker SD, et al. The effect of micronutrient supplementation on quality-of-life and left ventricular function in elderly patients with chronic heart failure. Eur Heart J 2005; 26(21): 2238-44.
  10. Zittermann A, Schleithoff SS, Tenderich G, Berthold HK, Korfer R, Stehle P. Low vitamin D status: A contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 2003; 41(1): 105-12.
  11. Zittermann A, Schleithoff SS, Koerfer R. Vitamin D insufficiency in congestive heart failure: why and what to do about it? Heart Fail Rev 2006; 11(1): 25-33.
  12. Garakyaraghi M, Kerdegari M, Siavash M. Calcium and vitamin D status in heart failure patients in Isfahan, Iran. Biol Trace Elem Res 2010; 135(1-3): 67-73.
  13. Zittermann A. Vitamin D and disease prevention with special reference to cardiovascular disease. Prog Biophys Mol Biol 2006; 92(1): 39-48.
  14. Weber KT, Simpson RU, Carbone LD. Vitamin D and calcium dyshomoeostasis-associated heart failure. Heart 2008; 94(5): 540-1.
  15. Zittermann A, Schleithoff SS, Koerfer R. Putting cardiovascular disease and vitamin D insufficiency into perspective. Br J Nutr 2005; 94(4): 483-92.
  16. Beuckelmann DJ, Nabauer M, Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation 1992; 85(3): 1046-55.
  17. De Boland AR, Boland RL. Non-genomic signal transduction pathway of vitamin D in muscle. Cell Signal 1994; 6(7): 717-24.
  18. Xiang W, Kong J, Chen S, Cao LP, Qiao G, Zheng W, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: Role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab 2005; 288(1): E125-E132.
  19. Criteria Committee of the New York Heart Association. Nomenclature and criteria for diagnosis of diseases of the heart and great vessels. Boston, MA: Little, Brown; 1994.
  20. Saadi HF, Kazzam E, Ghurbana BA, Nicholls MG. Hypothesis: Correction of low vitamin D status among Arab women will prevent heart failure and improve cardiac function in established heart failure. Eur J Heart Fail 2006; 8(7): 694-6.
  21. White HD, Norris RM, Brown MA, Brandt PW, Whitlock RM, Wild CJ. Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction. Circulation 1987; 76(1): 44-51.
  22. Majeed Babar MZ, Haider SS, Mustafa G. Effects of Vitamin D supplementation on physical activity of patients with Heart Failure. Pak J Med Sci 2016; 32(6): 1430-3.
  23. Witte KK, Byrom R, Gierula J, Paton MF, Jamil HA, Lowry JE, et al. Effects of vitamin D on cardiac function in patients with chronic HF: The VINDICATE Study. J Am Coll Cardiol 2016; 67(22): 2593-603.
  24. Schleithoff SS, Zittermann A, Tenderich G, Berthold HK, Stehle P, Koerfer R. Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2006; 83(4): 754-9.
  25. Vieth R, Kimball S. Vitamin D in congestive heart failure. Am J Clin Nutr 2006; 83(4): 731-2.
  26. Simpson RU, Hershey SH, Nibbelink KA. Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 2007; 103(3-5): 521-4.
  27. Weber KT, Weglicki WB, Simpson RU. Macro- and micronutrient dyshomeostasis in the adverse structural remodelling of myocardium. Cardiovasc Res 2009; 81(3): 500-8.
  28. Li YC, Qiao G, Uskokovic M, Xiang W, Zheng W, Kong J. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol 2004; 89-90(1-5): 387-92.
  29. Maiya S, Sullivan I, Allgrove J, Yates R, Malone M, Brain C, et al. Hypocalcaemia and vitamin D deficiency: An important, but preventable, cause of life-threatening infant heart failure. Heart 2008; 94(5): 581-4.
  30. Witte KK, Clark AL. Micronutrients and their supplementation in chronic cardiac failure. An update beyond theoretical perspectives. Heart Fail Rev 2006; 11(1): 65-74.
  31. Weishaar RE, Simpson RU. Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects. Am J Physiol 1987; 253(6 Pt 1): E675-E683.
  32. Mancuso P, Rahman A, Hershey SD, Dandu L, Nibbelink KA, Simpson RU. 1,25-Dihydroxyvitamin-D3 treatment reduces cardiac hypertrophy and left ventricular diameter in spontaneously hypertensive heart failure-prone (cp/+) rats independent of changes in serum leptin. J Cardiovasc Pharmacol 2008; 51(6): 559-64.
  33. Yuan W, Pan W, Kong J, Zheng W, Szeto FL, Wong KE, et al. 1,25-dihydroxyvitamin D3 suppresses renin gene transcription by blocking the activity of
  34. the cyclic AMP response element in the renin gene promoter. J Biol Chem 2007; 282(41): 29821-30.
  35. Kim DH, Sabour S, Sagar UN, Adams S, Whellan DJ. Prevalence of hypovitaminosis D in cardiovascular diseases (from the National Health and Nutrition Examination Survey 2001 to 2004). Am J Cardiol 2008; 102(11): 1540-4.
  36. McGonigle RJ, Fowler MB, Timmis AB, Weston MJ, Parsons V. Uremic cardiomyopathy: Potential role of vitamin D and parathyroid hormone. Nephron 1984; 36(2): 94-100.
  37. Price DI, Stanford LC, Jr., Braden DS, Ebeid MR, Smith JC. Hypocalcemic rickets: An unusual cause of dilated cardiomyopathy. Pediatr Cardiol 2003; 24(5): 510-2.
  38. Abdullah M, Bigras JL, McCrindle BW. Dilated cardiomyopathy as a first sign of nutritional vitamin D deficiency rickets in infancy. Can J Cardiol 1999; 15(6): 699-701.
  39. Amirlak I, Al DW, Narchi H. Dilated cardiomyopathy secondary to nutritional rickets. Ann Trop Paediatr 2008; 28(3): 227-30.
  40. Gillor A, Groneck P, Kaiser J, Schmitz-Stolbrink A. Congestive heart failure in rickets caused by vitamin D deficiency. Monatsschr Kinderheilkd 1989; 137(2): 108-10.
  41. Brunvand L, Haga P, Tangsrud SE, Haug E. Congestive heart failure caused by vitamin D deficiency? Acta Paediatr 1995; 84(1): 106-8.
  42. Olgun H, Ceviz N, Ozkan B. A case of dilated cardiomyopathy due to nutritional vitamin D deficiency rickets. Turk J Pediatr 2003; 45(2): 152-4.
  43. Alsafwah S, Laguardia SP, Nelson MD, Battin DL, Newman KP, Carbone LD, et al. Hypovitaminosis D in African Americans residing in Memphis, Tennessee with and without heart failure. Am J Med Sci 2008; 335(4): 292-7.
  44. Pilz S, Marz W, Wellnitz B, Seelhorst U, Fahrleitner-Pammer A, Dimai HP, 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(10): 3927-35.
  45. Michie C, Julies P. Treatments for heart failure in pregnancy: Is it time to consider vitamin D? Int J Clin Pract 2012; 66(3): 328.
ARYA Atherosclerosis Journal
Volume 17, Issue 1
January and February 2021
Pages 1-7

Home

Guide for Authors

Submit Manuscript

Reviewers

Contact Us