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Vitamin D and the Cardiovascular System: An Overview of the Recent Literature

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Abstract

Since the discovery that the enzyme catalyzing the synthesis of the most active natural vitamin D metabolite (calcitriol) and the vitamin D-specific receptor (VDR) were expressed in a wide range of tissues and organs, not only involved in the mineral metabolism (MM), there has been increasing interest on the putative ‘non classical’ roles of vitamin D metabolites, particularly on their possible effects on the cardiovascular (CV) system. These hypothetical CV effects of vitamin D gained particular interest in the nephrology field, given the high prevalence of CV disease in patients affected by either acute or chronic kidney diseases. However, notwithstanding a huge amount of experimental data suggesting a possible protective role of vitamin D on the CV system, the conclusions of two recent meta-analyses from the Cochrane group and a recent statement from the Institute of Medicine, based on a complete revision of the available data, concluded that there is no clear evidence for a role of vitamin D other than that strictly associated with bone health. However, a continuous and increasing flow of new studies still continues to add information on this topic. In the present review, we have tried to critically address the data added on this topic in the last 2 years, considering separately the experimental, observational, and intervention studies that have appeared in PubMed in the last 2 years, discussing the data providing proof, pro or contra, the involvement of vitamin D in CV disease, both in the absence or presence of kidney function impairment.

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References

  1. McCollum EV, Simmonds N, Becker JE, et al. Studies on experimental rickets. XXI. An Experimental demonstration of the existence of a Vitamin which promotes calcium deposition. J Biol Chem. 1922;31:293–312.

    Google Scholar 

  2. Bischoff-Ferrari HA, Willett WC, Wong JB, et al. Prevention of nonvertebral fractures with oral vitamin D and dose dependency: a meta-analysis of randomized controlled trials. Arch Intern Med. 2009;169(6):551–61.

    CAS  PubMed  Google Scholar 

  3. Heaney RP. Vitamin D in health and disease. Clin J Am Soc Nephrol. 2008;3(5):1535–41.

    CAS  PubMed  Google Scholar 

  4. DeLuca HF. Evolution of our understanding of vitamin D. Nutr Rev. 2008;66(Suppl 2):73–87.

    Google Scholar 

  5. Mizwicki MT, Norman AW. The vitamin D sterol-vitamin D receptor ensemble model offers unique insights into both genomic and rapid-response signaling. Sci Signal. 2009;2(75):re4.

    PubMed  Google Scholar 

  6. Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology. 2006;147(12):5542–8.

    CAS  PubMed  Google Scholar 

  7. Chen J, Olivares-Navarrete R, Wang Y, et al. Protein-disulfide isomerase-associated 3 (Pdia3) mediates the membrane response to 1,25-dihydroxyvitamin D3 in osteoblasts. J Biol Chem. 2010;285(47):37041–50.

    CAS  PubMed  Google Scholar 

  8. Dusso A, Brown A, Slatopolsky E. Extrarenal production of calcitriol. Semin Nephrol. 1994;14(2):144–55.

    CAS  PubMed  Google Scholar 

  9. Zehnder D, Bland R, Williams MC, et al. Extrarenal expression of 25-hydroxyvitamin d(3)-1 alpha-hydroxylase. J Clin Endocrinol Metab. 2001;86(2):888–94.

    CAS  PubMed  Google Scholar 

  10. Messa P, Alfieri C, Rastaldi MP. Recent insights into vitamin D and its receptor. J Nephrol. 2011;24(Suppl 18):30–7.

    Google Scholar 

  11. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266–81.

    CAS  PubMed  Google Scholar 

  12. Verstuyf A, Carmeliet G, Bouillon R, et al. Vitamin D: a pleiotropic hormone. Kidney Int. 2010;78(2):140–5.

    CAS  PubMed  Google Scholar 

  13. Plum LA, DeLuca HF. Vitamin D disease and therapeutic opportunities. Nat Rev Drug Discov. 2010;9(12):941–55.

    CAS  PubMed  Google Scholar 

  14. Body JJ, Bergmann P, Boonen S, et al. Extraskeletal benefits and risks of calcium, vitamin D and anti-osteoporosis medications. Osteoporos Int. 2012;23(Suppl 1):1–23.

    CAS  Google Scholar 

  15. Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease will it live up to its hype? J Am Coll Cardiol. 2011;58(15):1547–56.

    CAS  PubMed  Google Scholar 

  16. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53–8.

    CAS  PubMed  Google Scholar 

  17. Palmer SC, McGregor DO, Craig JC, et al. Vitamin D compounds for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2009;(4):CD008175.

  18. Palmer SC, McGregor DO, Craig JC, et al. Vitamin D compounds for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2009;(4):CD005633.

  19. Kovesdy CP, Kalantar-Zadeh K. Vitamin D receptor activation and survival in chronic kidney disease. Kidney Int. 2008;73(12):1355–63.

    CAS  PubMed  Google Scholar 

  20. Schmidt N, Brandsch C, Kühne H, et al. Vitamin D receptor deficiency and low vitamin D diet stimulate aortic calcification and osteogenic key factor expression in mice. PLoS One. 2012;7(4):e35316.

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Weng S, Sprague JE, Oh J, et al. Vitamin D deficiency induces high blood pressure and accelerates atherosclerosis in mice. PLoS One. 2013;8(1):e54625.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Li YC, Kong J, Wei M, et al. 1,25-Dihydroxyvitamin D3 is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest. 2002;110(2):229–38.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Wu J, Garami M, Cheng T, et al. 1,25 (OH)2 Vitamin D3 and retinoic acid antagonize endothelin stimulated hypertrophy of neonatal rat cardiac myocytes. J Clin Invest. 1996;97(7):1577–88.

    CAS  PubMed Central  PubMed  Google Scholar 

  24. Koleganova N, Piecha G, Ritz E, et al. Calcitriol ameliorates capillary deficit and fibrosis of the heart in subtotally nephrectomized rats. Nephrol Dial Transplant. 2009;24(3):778–87.

    CAS  PubMed  Google Scholar 

  25. Mizobuchi M, Nakamura H, Tokumoto M, et al. Myocardial effects of VDR activators in renal failure. J Steroid Biochem Mol Biol. 2010;121(1–2):188–92.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Meems LM, Cannon MV, Mahmud H, et al. The vitamin D receptor activator paricalcitol prevents fibrosis and diastolic dysfunction in a murine model of pressure overload. J Steroid Biochem Mol Biol. 2012;132(3–5):282–9.

    CAS  PubMed  Google Scholar 

  27. Riek AE, Oh J, Bernal-Mizrachi C. 1,25(OH)(2) vitamin D suppresses macrophage migration and reverses atherogenic cholesterol metabolism in type 2 diabetic patients. J Steroid Biochem Mol Biol. 2013;136:309-12.

    Google Scholar 

  28. Ärnlöv J, Carlsson AC, Sundström J, Ingelsson E, Larsson A, Lind L, Larsson TE. Serum FGF23 and risk of cardiovascular events in relation to mineral metabolism and cardiovascular pathology. Clin J Am Soc Nephrol. 2013;8(5):781–6.

    PubMed  Google Scholar 

  29. Kuro-o M. Klotho in health and disease. Curr Opin Nephrol Hypertens. 2012;21(4):362–8.

    CAS  PubMed  Google Scholar 

  30. Kim HR, Nam BY, Kim DW, Kang MW, Han JH, Lee MJ, Shin DH, Doh FM, Koo HM, Ko KI, Kim CH, Oh HJ, Yoo TH, Kang SW, Han DS, Han SH. Circulating α-Klotho levels in CKD and relationship to progression. Am J Kidney Dis. 2013;61(6):899–909.

    CAS  PubMed  Google Scholar 

  31. Lau WL, Leaf EM, Hu MC, et al. Vitamin D receptor agonists increase Klotho and osteopontin while decreasing aortic calcification in mice with chronic kidney disease fed a high phosphate diet. Kidney Int. 2012;82(12):1261–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Lim K, Tzong-Shi L, Guerman M, et al. Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation. 2012;125(18):2243–55.

    CAS  PubMed  Google Scholar 

  33. Aoshima Y, Mizobuchi M, Ogata H, et al. Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α. Nephrol Dial Transplant. 2012;27(5):1800–6.

    CAS  PubMed  Google Scholar 

  34. Guerrero F, Montes de Oca A, Aguilera-Tejero E, et al. The effect of vitamin D derivatives on vascular calcification associated with inflammation. Nephrol Dial Transplant. 2012;27(6):2206–12.

    CAS  PubMed  Google Scholar 

  35. Kono K, Fujii H, Nakai K, et al. Anti-oxidative effect of vitamin D analog on incipient vascular lesion in non-obese type 2 diabetic rats. Am J Nephrol. 2013;37(2):167–74.

    CAS  PubMed  Google Scholar 

  36. Absi M, Ward DT. Increased endothelin-1 responsiveness in human coronary artery smooth muscle cells exposed to 1,25-dihydroxyvitamin D3. Am J Physiol Cell Physiol. 2013;304(7):666–72.

    Google Scholar 

  37. Zebger-Gong H, Müller D, Diercke M, et al. 1,25-Dihydroxyvitamin D3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix. J Hypertens. 2011;29(2):339–48.

    CAS  PubMed  Google Scholar 

  38. Martínez-Moreno JM, Muñoz-Castañeda JR, Herencia C, et al. In vascular smooth muscle cells paricalcitol prevents phosphate-induced Wnt/β-catenin activation. Am J Physiol Renal Physiol. 2012;303(8):1136–44.

    Google Scholar 

  39. Hirata M, Katsumata K, Endo K, et al. In subtotally nephrectomized rats 22-oxacalcitriol suppresses parathyroid hormone with less risk of cardiovascular calcification or deterioration of residual renal function than 1,25(OH)2 vitamin D3. Nephrol Dial Transplant. 2003;18(9):1770–6.

    CAS  PubMed  Google Scholar 

  40. Cardus A, Panizo S, Parisi E, et al. Differential effects of vitamin D analogs on vascular calcification. J Bone Miner Res. 2007;22(6):860–6.

    CAS  PubMed  Google Scholar 

  41. Wu-Wong JR, Nakane M, Ma J, et al. Effects of vitamin D analogs on gene expression profiling in human coronary artery smooth muscle cells. Atherosclerosis. 2006;186(1):20–8.

    CAS  PubMed  Google Scholar 

  42. Mizobuchi M, Finch JL, Martin DR, et al. Differential effects of vitamin D receptor activators on vascular calcification in uremic rats. Kidney Int. 2007;72(6):709–15.

    CAS  PubMed  Google Scholar 

  43. Noonan W, Koch K, Nakane M, et al. Differential effects of vitamin D receptor activators on aortic calcification and pulse wave velocity in uraemic rats. Nephrol Dial Transplant. 2008;23(12):3824–30.

    CAS  PubMed  Google Scholar 

  44. Lopez I, Mendoza FJ, Aguilera-Tejero E, et al. The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats. Kidney Int. 2008;73(3):300–7.

    CAS  PubMed  Google Scholar 

  45. Forman JP, Curhan GC, Taylor EN. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension. 2008;52(5):828–32.

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Bhandari SK, Pashayan S, Liu IL, et al. 25-Hydroxyvitamin D levels and hypertension rates. J Clin Hypertens (Greenwich). 2011;13(3):170–7.

    CAS  Google Scholar 

  47. Burgaz A, Orsini N, Larsson SC, et al. Blood 25- hydroxyvitamin D concentration and hypertension: a metaanalysis. J Hypertens. 2011;29(4):636–45.

    CAS  PubMed  Google Scholar 

  48. Sun Q, Pan A, Hu FB, et al. 25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke. 2012;43(6):1470–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  49. Kojima G, Bell C, Abbott RD, et al. Low dietary vitamin D predicts 34-year incident stroke: the Honolulu Heart Program. Stroke. 2012;43(8):2163–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Joergensen C, Reinhard H, Schmedes A, et al. Vitamin D levels and asymptomatic coronary artery disease in type 2 diabetic patients with elevated urinary albumin excretion rate. Diabetes Care. 2012;35(1):168–72.

    CAS  PubMed  Google Scholar 

  51. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, Collins R, Clarke R. Vitamin D and risk of death from vascular and non-vascular causes in the Whitehall study and meta-analyses of 12,000 deaths. Eur Heart J. 2013;34(18):1365–74.

    CAS  PubMed  Google Scholar 

  52. Deo R, Katz R, Shlipak M, et al. Vitamin D, parathyroid hormone, and sudden cardiac death results from the Cardiovascular Health Study. Hypertension. 2011;58(6):1021–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Kestenbaum B, Katz R, de Boer I, et al. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol. 2011;58(14):1433–41.

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Schierbeck LL, Rejnmark L, Tofteng CL, et al. Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study. Eur J Endocrinol. 2012;167(4):553–60.

    CAS  PubMed  Google Scholar 

  55. Brøndum-Jacobsen P, Benn M, Jensen GB, Nordestgaard BG. 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17 studies. Arterioscler Thromb Vasc Biol. 2012;32:2794–802.

    PubMed  Google Scholar 

  56. Schottker B, Haug U, Schomburg L, et al. Strong associations of 25-hydroxyvitamin D concentrations with all-cause, cardiovascular, cancer, and respiratory disease mortality in a large cohort study. Am J Clin Nutr. 2013;97(4):782–93.

    PubMed  Google Scholar 

  57. Wang L, Song Y, Manson JE, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes. 2012;5(6):819–29.

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Sun Q, Shi L, Rimm EB, et al. Vitamin D intake and risk of cardiovascular disease in US men and Women. Am J Clin Nutr. 2011;94(2):534–42.

    CAS  PubMed  Google Scholar 

  59. Drechsler C, Pilz S, Obermayer-Pietsch B, et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J. 2010;31(18):2253–61.

    CAS  PubMed  Google Scholar 

  60. Pilz S, Tomaschitz A, Friedl C, et al. Vitamin D status and mortality in chronic kidney disease. Nephrol Dial Transpl. 2011;26(11):3603–9.

    CAS  Google Scholar 

  61. Drechsler C, Verduijn M, Pilz S, et al. Vitamin D status and clinical outcomes in incident dialysis patients: results from the NECOSAD study. Nephrol Dial Transpl. 2011;26(3):1024–32.

    CAS  Google Scholar 

  62. Kramer H, Sempos C, Cao G, et al. Mortality rates across 25 hydroxyvitamin D (25[OH]D) levels among adults with and without estimated glomerular filtration rate, 60 ml/min/1.73 m2: The Third National Health and Nutrition Examination Survey. PLoS One. 2012;7(10):e47458.

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Lee SY, Kim HY, Gu SW, et al. 25-Hydroxyvitamin D levels and vascular calcification in predialysis and dialysis patients with chronic kidney disease. Kidney Blood Press Res. 2012;35(5):349–54.

    CAS  PubMed  Google Scholar 

  64. García-Canton C, Bosch E, Ramírez A, et al. Vascular calcification and 25-hydroxyvitamin D levels in non-dialysis patients with chronic kidney disease stages 4 and 5. Nephrol Dial Transpl. 2011;26(7):2250–6.

    Google Scholar 

  65. Zhao G, Ford ES, Li C, et al. Serum 25-hydroxyvitamin D levels and all-cause and cardiovascular disease mortality among US adults with hypertension: the NHANES linked mortality study. J Hypertens. 2012;30(2):284–9.

    PubMed  Google Scholar 

  66. Correia LC, Sodré F, Garcia G, et al. Relation of severe deficiency of vitamin D to cardiovascular mortality during acute coronary syndromes. Am J Cardiol. 2013;111(3):324–7.

    CAS  PubMed  Google Scholar 

  67. Ng LL, Sandhu JK, Squire IB, et al. Vitamin D and prognosis in acute myocardial infarction. Int J Cardiol. 2013;. doi:10.1016/j.ijcard.2013.01.030.

    Google Scholar 

  68. Thomas GN, ó Hartaigh B, Bosch JA, Pilz S, Loerbroks A, Kleber ME, Fischer JE, Grammer TB, Böhm BO, März W. Vitamin D levels predict all-cause and cardiovascular disease mortality in subjects with the metabolic syndrome: the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study. Diabetes Care. 2012;35(5):1158–64.

    CAS  PubMed  Google Scholar 

  69. Zittermann A, Kuhn J, Dreier J, et al. Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur Heart J. 2013;34(18):1358–64.

    CAS  PubMed  Google Scholar 

  70. Ameri P, Canepa M, Milaneschi Y, et al. Relationship between vitamin D status and left ventricular geometry in a healthy population: results from the Baltimore Longitudinal Study of Aging. Intern Med. 2013;273(3):253–62.

    CAS  Google Scholar 

  71. Van de Luijtgaarden KM, Voûte MT, Hoeks SE, et al. Vitamin D deficiency may be an independent risk factor for arterial disease. Eur J Vasc Endovasc Surg. 2012;44(3):301–6.

    PubMed  Google Scholar 

  72. Gouveri E, Papanas N, Hatzitolios AI, et al. Hypovitaminosis D and peripheral arterial disease: emerging link beyond cardiovascular risk factors. Eur J Intern Med. 2012;23(8):674–81.

    CAS  PubMed  Google Scholar 

  73. Naves-Díaz M, Cabezas-Rodríguez I, Barrio-Vázquez S, et al. Low calcidiol levels and risk of progression of aortic calcification. Osteoporos Int. 2012;23(3):1177–82.

    PubMed  Google Scholar 

  74. Jorde R, Figenschau Y, Emaus N, et al. Serum 25-hydroxyvitamin D levels are strongly related to systolic blood pressure but do not predict future hypertension. Hypertension. 2010;55(3):792–8.

    CAS  PubMed  Google Scholar 

  75. Fall T, Shiue I, Bergeå af Geijerstam P, et al. Relations of circulating vitamin D concentrations with left ventricular geometry and function. Eur J Heart Fail. 2012;14(9):985–91.

    CAS  PubMed  Google Scholar 

  76. Kamycheva E, Wilsgaard T, Schirmer H, et al. Serum 25-hydroxyvitamin D and left ventricular systolic function in a non-smoking population: the Tromso Study. Eur J Heart Fail. 2013;15(5):490–5.

    CAS  PubMed  Google Scholar 

  77. van Ballegooijen AJ, Snijder MB, Visser M, van den Hurk K, Kamp O, Dekker JM, Nijpels G, Stehouwer CD, Henry RM, Paulus WJ, Brouwer IA. Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study. Ann Nutr Metab. 2012;60(1):69–77.

    PubMed  Google Scholar 

  78. Jassal SK, Chonchol M, von Mühlen D, et al. Vitamin D, parathyroid hormone, and cardiovascular mortality in older adults: the Rancho Bernardo study. Am J Med. 2010;123(12):1114–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Van Ballegooijen AJ, Visser M, Cotch MF, et al. Serum vitamin D and parathyroid hormone in relation to cardiac structure and function: The ICELAND-MI Substudy of AGES-Reykjavik. J Clin Endocrinol Metab. 2013;98(6):2544–52.

    PubMed  Google Scholar 

  80. Skaaby T, Husemoen LL, Pisinger C, et al. Vitamin D status and cause-specific mortality: a general population study. PLoS One. 2012;7(12):e52423.

    CAS  PubMed Central  PubMed  Google Scholar 

  81. Welsh P, Doolin O, McConnachie A, et al. Circulating 25OHD, dietary vitamin D, PTH, and calcium associations with incident cardiovascular disease and mortality: the MIDSPAN Family Study. J Clin Endocrinol Metab. 2012;97(12):4578–87.

    CAS  PubMed  Google Scholar 

  82. Deleskog A, Piksasova O, Silveira A, et al. Serum 25-hydroxyvitamin D concentration, established and emerging cardiovascular risk factors and risk of myocardial infarction before the age of 60 years. Atherosclerosis. 2012;223(1):223–9.

    CAS  PubMed  Google Scholar 

  83. Bittner V, Wenger NK, Waters DD, et al. Vitamin D levels do not predict cardiovascular events in statin-treated patients with stable coronary disease. Am Heart J. 2012;164(3):387–93.

    CAS  PubMed  Google Scholar 

  84. Trummer O, Pilz S, Hoffmann MM, et al. Vitamin d and mortality: a mendelian randomization study. Clin Chem. 2013;59(5):793–7.

    CAS  PubMed  Google Scholar 

  85. Teng M, Wolf M, Lowrie E, et al. Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003;349(5):446–56.

    CAS  PubMed  Google Scholar 

  86. Teng M, Wolf M, Ofsthun MN, et al. Activated injectable vitamin D and hemodialysis survival: a historical cohort study. J Am Soc Nephrol. 2005;16(4):1115–25.

    CAS  PubMed  Google Scholar 

  87. Sugiura S, Inaguma D, Kitagawa A, et al. Administration of alfacalcidol for patients with predialysis chronic kidney disease may reduce cardiovascular disease events. Clin Exp Nephrol. 2010;14(1):43–50.

    CAS  PubMed  Google Scholar 

  88. Brancaccio D, Cozzolino M, Cannella G, et al. FARO Study Group. Secondary hyperparathyroidism in chronic dialysis patients: results of the Italian FARO survey on treatment and mortality. Blood Purif. 2011;32(2):124–32.

    CAS  PubMed  Google Scholar 

  89. Cozzolino M, Brancaccio D, Cannella G, et al. FARO Study Group. VDRA therapy is associated with improved survival in dialysis patients with serum intact PTH ≤ 150 pg/mL: results of the Italian FARO Survey. Nephrol Dial Transpl. 2012;27(9):3588–94.

    CAS  Google Scholar 

  90. Duranton F, Rodriguez-Ortiz ME, Duny Y, et al. Vitamin d treatment and mortality in chronic kidney disease: a systematic review and meta-analysis. Am J Nephrol. 2013;37(3):239–48.

    CAS  PubMed  Google Scholar 

  91. St Peter WL, Li S, Liu J, et al. Effects of monthly dose and regular dosing of intravenous active vitamin D use on mortality among patients undergoing hemodialysis. Pharmacotherapy. 2009;29(2):154–64.

    PubMed  Google Scholar 

  92. Hossein-Nezhad A, Spira A, Holick MF. Influence of vitamin D status and vitamin D3 supplementation on genome wide expression of white blood cells: a randomized double-blind clinical trial. PLoS One. 2013;8(3):e58725.

    CAS  PubMed Central  PubMed  Google Scholar 

  93. Bjelakovic G, Gluud LL, Nikolova D, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2011;7:CD007470.

    Google Scholar 

  94. Delanaye P, Weekers L, Warling X, et al. Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study. Nephrol Dial Transpl. 2013;28(7):1779–86.

    Google Scholar 

  95. Salehpour A, Shidfar F, Hosseinpanah F, et al. Vitamin D3 and the risk of CVD in overweight and obese women: a randomized controlled trial. Br J Nutr. 2012;108(10):1866–73.

    CAS  PubMed  Google Scholar 

  96. Muldowney S, Lucey AJ, Hill TR, et al. Incremental cholecalciferol supplementation up to 15 μg/d throughout winter at 51–55° N has no effect on biomarkers of cardiovascular risk in healthy young and older adults. J Nutr. 2012;142(8):1519–25.

    CAS  PubMed  Google Scholar 

  97. Wood AD, Secombes KR, Thies F, et al. Vitamin D3 supplementation has no effect on conventional cardiovascular risk factors: a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab. 2012;97(10):3557–68.

    CAS  PubMed  Google Scholar 

  98. Prentice RL, Pettinger MB, Jackson RD, et al. Health risks and benefits from calcium and vitamin D supplementation: Women’s Health Initiative clinical trial and cohort study. Osteoporos Int. 2013;24(2):567–80.

    CAS  PubMed Central  PubMed  Google Scholar 

  99. Witham MD, Price RJ, Struthers AD, Donnan PT, Messow CM, Ford I, McMurdo ME. Cholecalciferol treatment to reduce blood pressure in older patients with isolated systolic hypertension: the VitDISH Randomized Controlled Trial. JAMA Intern Med. 2013;. doi:10.1001/jamainternmed.2013.9043.

    PubMed  Google Scholar 

  100. Alvarez JA, Zughaier SM, Law J, et al. Effects of high-dose cholecalciferol on serum markers of inflammation and immunity in patients with early chronic kidney disease. Eur J Clin Nutr. 2013;67(3):264–9.

    CAS  PubMed  Google Scholar 

  101. Witham MD, Dove FJ, Sugden JA, et al. The effect of vitamin D replacement on markers of vascular health in stroke patients—a randomized controlled trial. Nutr Metab Cardiovasc Dis. 2012;22(10):864–70.

    CAS  PubMed  Google Scholar 

  102. Gepner AD, Ramamurthy R, Krueger DC, Korcarz CE, et al. A prospective randomized controlled trial of the effects of vitamin D supplementation on cardiovascular disease risk. PLoS One. 2012;7(5):e36617.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Bolland MJ, Grey A, Avenell A, et al. Calcium supplements with or without vitamin D and risk of cardiovascular events: reanalysis of the Women’s Health Initiative limited access dataset and meta-analysis. BMJ. 2011;342:d2040.

    PubMed Central  PubMed  Google Scholar 

  104. Rejnmark L, Avenell A, Masud T, et al. Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab. 2012;97(8):2670–81.

    CAS  PubMed  Google Scholar 

  105. Bolland MJ, Barber A, Doughty RN, et al. Differences between self-reported and verified adverse cardiovascular events in a randomised clinical trial. BMJ Open. 2013;3(3):e002334.

    PubMed Central  PubMed  Google Scholar 

  106. Tamez H, Zoccali C, Packham D, et al. Vitamin D reduces left atrial volume in patients with left ventricular hypertrophy and chronic kidney disease. Am Heart J. 2012;164(6):902–9.

    CAS  PubMed  Google Scholar 

  107. Thadhani R, Appelbaum E, Pritchett Y, et al. Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA. 2012;307(7):674–84.

    CAS  PubMed  Google Scholar 

  108. De Boer IH, Sachs M, Hoofnagle AN, et al. Paricalcitol does not improve glucose metabolism in patients with stage 3–4 chronic kidney disease. Kidney Int. 2013;83(2):323–30.

    PubMed Central  PubMed  Google Scholar 

  109. Zittermann A, Schleithoff SS, Koerfer R. Vitamin D and vascular calcification. Curr Opin Lipidol. 2007;18(1):41–6.

    CAS  PubMed  Google Scholar 

  110. Freedman BI, Register TC. Effect of race and genetics on vitamin D metabolism, bone and vascular health. Nat Rev Nephrol. 2012;8(8):459–66.

    CAS  PubMed  Google Scholar 

  111. Wang TJ, Zhang F, Richards JB, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Shen H, Bielak LF, Ferguson JF, et al. Association of the vitamin D metabolism gene CYP24A1 with coronary artery calcification. Arterioscler Thromb Vasc Biol. 2010;30(12):2648–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  113. Hu P, Xuan Q, Hu B, et al. Fibroblast growth factor-23 helps explain the biphasic cardiovascular effects of vitamin D in chronic kidney disease. Int J Biol Sci. 2012;8(5):663–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  114. Razzaque MS. The dualistic role of vitamin D in vascular calcifications. Kidney Int. 2011;79(7):708–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  115. Camargo CA Jr. Vitamin D, and cardiovascular disease: time for large randomized trials. J Am Coll Cardiol. 2011;58(14):1442–4.

    CAS  PubMed  Google Scholar 

  116. Manson JE, Bassuk SS, Lee IM, et al. The VITamin D and OmegA-3 TriaL (VITAL): rationale and design of a large randomized controlled trial of vitamin D and marine omega-3 fatty acid supplements for the primary prevention of cancer and cardiovascular disease. Contemp Clin Trials. 2012;33(1):159–71.

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

No external funding was used in the preparation of this review. MC, AR, and CMA have no potential conflicts of interest with the content of this review. The authors acknowledge the help of Dr. Marina Balderacchi and Mr. Andrea Centa for their help in editing this manuscript. PM has received lecture fees from Amgen, Abbott, Fresenius, and Roche.

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Correspondence to Piergiorgio Messa.

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Messa, P., Curreri, M., Regalia, A. et al. Vitamin D and the Cardiovascular System: An Overview of the Recent Literature. Am J Cardiovasc Drugs 14, 1–14 (2014). https://doi.org/10.1007/s40256-013-0047-y

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