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Vitamin D and the cardiovascular system

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Abstract

Vitamin D, a secosteroid hormone, affects multiple biological pathways via both genomic and nongenomic signalling. Several pathways have potential benefit to cardiovascular health, including effects on parathyroid hormone, the renin–angiotensin–aldosterone system, vascular endothelial growth factor and cytokine production, as well as direct effects on endothelial cell function and myocyte calcium influx. Observational data supports a link between low vitamin D metabolite levels and cardiovascular health. Cross-sectional data shows associations between low 25-hydroxyvitamin D levels and stroke, myocardial infarction, diabetes mellitus, hypertension, and heart failure. Longitudinal data also suggests a relationship with incident hypertension and new cardiovascular events. However, these associations are potentially confounded by reverse causality and by the effects that other cardiovascular risk factors have on vitamin D metabolite levels. Intervention studies to date suggest a modest antihypertensive effect of vitamin D, no effect on serum lipids, a small positive effect on insulin resistance and fasting glucose, and equivocal actions on arterial stiffness and endothelial function. Analysis of cardiovascular event data collected from osteoporosis trials does not currently show a clear signal for reduced cardiovascular events with vitamin D supplementation, but results may be confounded by the coadministration of calcium, and by the secondary nature of the analyses. Despite mechanistic and observational data that suggest a protective role for vitamin D in cardiovascular disease, intervention studies to date are less promising. Large trials using cardiovascular events as a primary outcome are needed before vitamin D can be recommended as a therapy for cardiovascular disease.

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References

  1. Jones G, Strugnell SA, DeLuca HF (1998) Current understanding of the molecular actions of vitamin D. Physiol Rev 78:1193–1231

    PubMed  CAS  Google Scholar 

  2. Jean G, Terrat JC, Vanel T et al (2008) Evidence for persistent vitamin D 1-alpha-hydroxylation in hemodialysis patients: evolution of serum 1,25-dihydroxycholecalciferol after 6 months of 25-hydroxycholecalciferol treatment. Nephron Clin Pract 110:c58–c65

    Article  PubMed  CAS  Google Scholar 

  3. Gottfried E, Rehli M, Hahn J et al (2006) Monocyte-derived cells express CYP27A1 and convert vitamin D3 into its active metabolite. Biochem Biophys Res Commun 349:209–213

    Article  PubMed  CAS  Google Scholar 

  4. Norman AW (2008) From vitamin D to hormone D: fundamentals of the vitamin D endocrine system essential for good health. Am J Clin Nutr 88:491S–499S

    Article  PubMed  CAS  Google Scholar 

  5. Bischoff-Ferrari HA, Giovannucci E, Willett WC et al (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28

    PubMed  CAS  Google Scholar 

  6. Haussler MR, Jurutka PW, Mizwicki M et al (2011) Vitamin D receptor (VDR)-mediated actions of 1alpha,25(OH)(2)vitamin D(3): genomic and non-genomic mechanisms. Best Pract Res Clin Endocrinol Metab 25:543–559

    Article  PubMed  CAS  Google Scholar 

  7. DeLuca HF (2004) Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689S–1696S

    PubMed  CAS  Google Scholar 

  8. Li YC, Kong J, Wei M et al (2002) 1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system. J Clin Invest 110:229–238

    PubMed  CAS  Google Scholar 

  9. Tomaschitz A, Pilz S, Ritz E et al (2010) Independent association between 1,25-dihydroxyvitamin D, 25-hydroxyvitamin D and the renin-angiotensin system: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clin Chim Acta 411:1354–1360

    Article  PubMed  CAS  Google Scholar 

  10. Forman JP, Williams JS, Fisher ND (2010) Plasma 25-hydroxyvitamin D and regulation of the renin–angiotensin system in humans. Hypertension 55:1283–1288

    Article  PubMed  CAS  Google Scholar 

  11. Vaidya A, Sun B, Larson C et al (2012) Vitamin D3 therapy corrects the tissue sensitivity to angiotensin ii akin to the action of a converting enzyme inhibitor in obese hypertensives: an interventional study. J Clin Endocrinol Metab 97:2456–2465

    Article  PubMed  CAS  Google Scholar 

  12. Simpson RU, Hershey SH, Nibbelink KA (2007) Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol 103:521–524

    Article  PubMed  CAS  Google Scholar 

  13. Green JJ, Robinson DA, Wilson GE et al (2006) Calcitriol modulation of cardiac contractile performance via protein kinase C. J Mol Cell Cardiol 41:350–359

    Article  PubMed  CAS  Google Scholar 

  14. Lehto S, Niskanen L, Suhonen M et al (1996) Medial artery calcification. A neglected harbinger of cardiovascular complications in non-insulin-dependent diabetes mellitus. Arterioscler Thromb Vasc Biol 16:978–983

    Article  PubMed  CAS  Google Scholar 

  15. Watson KE, Abrolat ML, Malone LL et al (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96:1755–1760

    Article  PubMed  CAS  Google Scholar 

  16. Niederhoffer N, Bobryshev YV, Lartaud-Idjouadiene I et al (1997) Aortic calcification produced by vitamin D3 plus nicotine. J Vasc Res 34:386–398

    Article  PubMed  CAS  Google Scholar 

  17. Demer LL, Tintut Y (2008) Vascular calcification: pathobiology of a multifaceted disease. Circulation 117:2938–2948

    Article  PubMed  Google Scholar 

  18. Hruska KA, Mathew S, Saab G (2005) Bone morphogenetic proteins in vascular calcification. Circ Res 97:105–114

    Article  PubMed  CAS  Google Scholar 

  19. Saleh FN, Schirmer H, Sundsfjord J et al (2003) Parathyroid hormone and left ventricular hypertrophy. Eur Heart J 24:2054–2060

    Article  PubMed  CAS  Google Scholar 

  20. Kosch M, Hausberg M, Vormbrock K et al (2000) Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy. Cardiovasc Res 47:813–818

    Article  PubMed  CAS  Google Scholar 

  21. Kestenbaum B, Katz R, de Boer I et al (2011) Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol 58:1433–1441

    Article  PubMed  CAS  Google Scholar 

  22. Molinari C, Uberti F, Grossini E et al (2011) 1 Alpha,25-dihydroxycholecalciferol induces nitric oxide production in cultured endothelial cells. Cell Physiol Biochem 27:661–668

    Article  PubMed  CAS  Google Scholar 

  23. Cardus A, Panizo S, Encinas M et al (2009) 1,25-Dihydroxyvitamin D3 regulates VEGF production through a vitamin D response element in the VEGF promoter. Atherosclerosis 204:85–89

    Article  PubMed  CAS  Google Scholar 

  24. Grundmann M, Haidar M, Placzko S et al (2012) Vitamin D improves the angiogenic properties of endothelial progenitor cells. Am J Physiol Cell Physiol. doi:10.1152/ajpcell.00030.2012

  25. Stach K, Kalsch AI, Nguyen XD et al (2011) 1 Alpha,25-dihydroxyvitamin D3 attenuates platelet activation and the expression of VCAM-1 and MT1-MMP in human endothelial cells. Cardiology 118:107–115

    Article  PubMed  CAS  Google Scholar 

  26. Aihara K, Azuma H, Akaike M et al (2004) Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice. J Biol Chem 279:35798–35802

    Article  PubMed  CAS  Google Scholar 

  27. Pitocco D, Crino A, Di Stasio E et al (2006) The effects of calcitriol and nicotinamide on residual pancreatic beta-cell function in patients with recent-onset Type 1 diabetes (IMDIAB XI). Diabet Med 23:920–923

    Article  PubMed  CAS  Google Scholar 

  28. Borissova AM, Tankova T, Kirilov G et al (2003) The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 57:258–261

    PubMed  CAS  Google Scholar 

  29. Norman AW, Frankel JB, Heldt AM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209:823–825

    Article  PubMed  CAS  Google Scholar 

  30. Fadda GZ, Akmal M, Lipson LG et al (1990) Direct effect of parathyroid hormone on insulin secretion from pancreatic islets. Am J Physiol 258:E975–E984

    PubMed  CAS  Google Scholar 

  31. Kolb H, Mandrup-Poulsen T (2005) An immune origin of type 2 diabetes? Diabetologia 48:1038–1050

    Article  PubMed  CAS  Google Scholar 

  32. Schleithoff SS, Zittermann A, Tenderich G et al (2006) 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

    PubMed  CAS  Google Scholar 

  33. Equils O, Naiki Y, Shapiro AM et al (2006) 1,25-Dihydroxyvitamin D inhibits lipopolysaccharide-induced immune activation in human endothelial cells. Clin Exp Immunol 143:58–64

    Article  PubMed  CAS  Google Scholar 

  34. Jablonski KL, Chonchol M, Pierce GL (2011) 25-Hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial dysfunction in middle-aged and older adults. Hypertension 57:63–69

    Article  PubMed  CAS  Google Scholar 

  35. Reid D, Toole BJ, Knox S et al (2011) The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr 93:1006–1011

    Article  PubMed  CAS  Google Scholar 

  36. Scragg R, Sowers M, Bell C (2007) Serum 25-hydroxyvitamin D, ethnicity, and blood pressure in the Third National Health and Nutrition Examination Survey. Am J Hypertens 20:713–719

    Article  PubMed  CAS  Google Scholar 

  37. Fraser A, Williams D, Lawlor DA (2010) Associations of serum 25-hydroxyvitamin D, parathyroid hormone and calcium with cardiovascular risk factors: analysis of 3 NHANES cycles (2001–2006). PLoS One 5:e13882

    Article  PubMed  CAS  Google Scholar 

  38. Martins D, Wolf M, Pan D et al (2007) Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamin D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 167:1159–1165

    Article  PubMed  CAS  Google Scholar 

  39. Hypponen E, Boucher BJ, Berry DJ et al (2008) 25-Hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort. Diabetes 57:298–305

    Article  PubMed  CAS  Google Scholar 

  40. Ganji V, Zhang X, Shaikh N et al (2011) Serum 25-hydroxyvitamin D concentrations are associated with prevalence of metabolic syndrome and various cardiometabolic risk factors in US children and adolescents based on assay-adjusted serum 25-hydroxyvitamin D data from NHANES 2001–2006. Am J Clin Nutr 94:225–233

    Article  PubMed  CAS  Google Scholar 

  41. Al Mheid I, Patel R, Murrow J et al (2011) Vitamin D status is associated with arterial stiffness and vascular dysfunction in healthy humans. J Am Coll Cardiol 58:186–192

    Article  PubMed  CAS  Google Scholar 

  42. Yiu YF, Chan YH, Yiu KH et al (2011) Vitamin D deficiency is associated with depletion of circulating endothelial progenitor cells and endothelial dysfunction in patients with type 2 diabetes. J Clin Endocrinol Metab 96:E830–E835

    Article  PubMed  CAS  Google Scholar 

  43. Poole KE, Loveridge N, Barker PJ et al (2006) Reduced vitamin D in acute stroke. Stroke 37:243–245

    Article  PubMed  CAS  Google Scholar 

  44. Zittermann A, Schleithoff SS, Tenderich G (2003) Low vitamin D status: a contributing factor in the pathogenesis of congestive heart failure? J Am Coll Cardiol 41:105–112

    Article  PubMed  CAS  Google Scholar 

  45. Scragg R, Jackson R, Holdaway IM et al (1990) Myocardial infarction is inversely associated with plasma 25-hydroxyvitamin D3 levels: a community-based study. Int J Epidemiol 19:559–563

    Article  PubMed  CAS  Google Scholar 

  46. Cigolini M, Iagulli MP, Miconi V et al (2006) Serum 25-hydroxyvitamin D3 concentrations and prevalence of cardiovascular disease among type 2 diabetic patients. Diabetes Care 29:722–724

    Article  PubMed  CAS  Google Scholar 

  47. Forman JP, Giovannucci E, Holmes MD et al (2007) Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension 49:1063–1069

    Article  PubMed  CAS  Google Scholar 

  48. Forman JP, Curhan GC, Taylor EN (2008) Plasma 25-hydroxyvitamin D levels and risk of incident hypertension among young women. Hypertension 52:828–832

    Article  PubMed  CAS  Google Scholar 

  49. Pittas AG, Chung M, Trikalinos T et al (2010) Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med 152:307–314

    Article  PubMed  Google Scholar 

  50. Burgaz A, Orsini N, Larsson SC (2011) Blood 25-hydroxyvitamin D concentration and hypertension: a meta-analysis. J Hypertens 29:636–645

    Article  PubMed  CAS  Google Scholar 

  51. Margolis KL, Martin LW, Ray RM et al (2012) A prospective study of serum 25-hydroxyvitamin D levels, blood pressure, and incident hypertension in postmenopausal women. Am J Epidemiol 175:22–32

    Article  PubMed  Google Scholar 

  52. Pittas AG, Sun Q, Manson JE et al (2010) Plasma 25-hydroxyvitamin D concentration and risk of incident type 2 diabetes in women. Diabetes Care 33:2021–2023

    Article  PubMed  CAS  Google Scholar 

  53. Pittas AG, Nelson J, Mitri J et al (2012) Plasma 25-hydroxyvitamin D and progression to diabetes in patients at risk for diabetes: an ancillary analysis in the Diabetes Prevention Program. Diabetes Care 35:565–573

    Article  PubMed  CAS  Google Scholar 

  54. Mitri J, Muraru MD, Pittas AG (2011) Vitamin D and type 2 diabetes: a systematic review. Eur J Clin Nutr 65:1005–1015

    Article  PubMed  CAS  Google Scholar 

  55. Forouhi NG, Ye Z, Rickard AP et al (2012) Circulating 25-hydroxyvitamin D concentration and the risk of type 2 diabetes: results from the European Prospective Investigation into Cancer (EPIC)-Norfolk cohort and updated meta-analysis of prospective studies. Diabetologia 55:2173–2182

    Article  PubMed  CAS  Google Scholar 

  56. Parker J, Hashmi O, Dutton D et al (2010) Levels of vitamin D and cardiometabolic disorders: systematic review and meta-analysis. Maturitas 65:225–236

    Article  PubMed  CAS  Google Scholar 

  57. Wang TJ, Pencina MJ, Booth SL et al (2008) Vitamin D deficiency and risk of cardiovascular disease. Circulation 117:503–511

    Article  PubMed  CAS  Google Scholar 

  58. Thomas GN, Hartaigh B, Bosch JA et al (2012) 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 35:1158–1164

    Article  PubMed  CAS  Google Scholar 

  59. Sun Q, Pan A, Hu FB (2012) 25-Hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke 43:1470–1477

    Article  PubMed  CAS  Google Scholar 

  60. Brondum-Jacobsen P, Nordestgaard BG, Schnohr P et al (2012) 25-Hydroxyvitamin D and symptomatic ischemic stroke: An Original Study and Meta-Analysis. Ann Neurol. doi:10.1002/ana.23738

  61. Chowdhury R, Stevens S, Ward H et al (2012) Circulating vitamin D, calcium and risk of cerebrovascular disease: a systematic review and meta-analysis. Eur J Epidemiol 27:581–591

    Article  PubMed  CAS  Google Scholar 

  62. Brondum-Jacobsen P, Benn M, Jensen GB et al (2012) 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 32:2794–2802

    Article  PubMed  CAS  Google Scholar 

  63. Scragg R (2011) Vitamin D and public health: an overview of recent research on common diseases and mortality in adulthood. Public Health Nutr 14:1515–1532

    Article  PubMed  Google Scholar 

  64. Grandi NC, Breitling LP, Brenner H (2010) Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Prev Med 51:228–233

    Article  PubMed  CAS  Google Scholar 

  65. Pilz S, Iodice S, Zittermann A (2011) Vitamin D status and mortality risk in CKD: a meta-analysis of prospective studies. Am J Kidney Dis 58:374–382

    PubMed  CAS  Google Scholar 

  66. Witham MD, Crighton LJ, Gillespie ND (2010) The effects of vitamin D supplementation on physical function and quality of life in older patients with heart failure: a randomized controlled trial. Circ Heart Fail 3:195–201

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  68. Pilz S, Marz W, Wellnitz B et al (2008) 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 93:3927–3935

    Article  PubMed  CAS  Google Scholar 

  69. Boxer RS, Kenny AM, Cheruvu VK et al (2010) Serum 25-hydroxyvitamin D concentration is associated with functional capacity in older adults with heart failure. Am Heart J 160:893–899

    Article  PubMed  CAS  Google Scholar 

  70. Gotsman I, Shauer A, Zwas DR et al (2012) 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

    Article  PubMed  CAS  Google Scholar 

  71. Anderson JL, May HT, Horne BD et al (2010) Relation of vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 106:963–968

    Article  PubMed  CAS  Google Scholar 

  72. Rienstra M, Cheng S, Larson MG et al (2011) Vitamin D status is not related to development of atrial fibrillation in the community. Am Heart J 162:538–541

    Article  PubMed  CAS  Google Scholar 

  73. Smith MB, May HT, Blair TL et al (2011) Vitamin D excess is significantly associated with risk of atrial fibrillation. Circulation 124:A14699

    Google Scholar 

  74. Isaia G, Giorgino R, Rini GB et al (2003) Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Osteoporos Int 14:577–582

    Article  PubMed  CAS  Google Scholar 

  75. Oplander C, Volkmar CM, Paunel-Gorgulu A et al (2009) Whole body UVA irradiation lowers systemic blood pressure by release of nitric oxide from intracutaneous photolabile nitric oxide derivates. Circ Res 105:1031–1040

    Article  PubMed  CAS  Google Scholar 

  76. Wood AD, Secombes KR, Thies F et al (2012) Vitamin D3 supplementation Has no effect on conventional cardiovascular risk factors. a parallel-group, double-blind, placebo-controlled RCT. J Clin Endocrinol Metab 97:3557–3568

    Article  PubMed  CAS  Google Scholar 

  77. Carter GD (2012) 25-hydroxyvitamin D: a difficult analyte. Clin Chem 58:486–488

    Article  PubMed  CAS  Google Scholar 

  78. Witham MD, Nadir MA, Struthers AD (2009) Effect of vitamin D on blood pressure: a systematic review and meta-analysis. J Hypertens 27:1948–1954

    Article  PubMed  CAS  Google Scholar 

  79. Wu SH, Ho SC, Zhong L et al (2010) Effects of vitamin D supplementation on blood pressure. South Med J 103:729–737

    Article  PubMed  Google Scholar 

  80. Larsen T, Mose FH, Bech JN (2012) Effect of cholecalciferol supplementation during winter months in patients with hypertension: a randomized, placebo-controlled trial. Am J Hypertens 25:1215–1222

    Article  PubMed  CAS  Google Scholar 

  81. Thadhani R, Appelbaum E, Pritchett Y et al (2012) Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial. JAMA 307:674–684

    Article  PubMed  CAS  Google Scholar 

  82. Wang H, Xia N, Yang Y (2012) Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis 11:42

    Article  PubMed  CAS  Google Scholar 

  83. Perez-Castrillon JL, Vega G, Abad L et al (2007) Effects of Atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol 99:903–905

    Article  PubMed  CAS  Google Scholar 

  84. Rejnmark L, Vestergaard P, Heickendorff L (2010) Simvastatin does not affect vitamin D status, but low vitamin D levels are associated with dyslipidemia: results from a randomised, controlled trial. Int J Endocrinol 2010:957174

    PubMed  Google Scholar 

  85. Yavuz B, Ertugrul DT, Cil H et al (2009) Increased levels of 25 hydroxyvitamin D and 1,25-dihydroxyvitamin D after rosuvastatin treatment: a novel pleiotropic effect of statins? Cardiovasc Drugs Ther 23:295–299

    Article  PubMed  CAS  Google Scholar 

  86. Schwartz JB (2009) Effects of vitamin D supplementation in atorvastatin-treated patients: a new drug interaction with an unexpected consequence. Clin Pharmacol Ther 85:198–203

    Article  PubMed  CAS  Google Scholar 

  87. Witham MD, Dove FJ, Khan F et al (2012) Effects of vitamin D supplementation on markers of vascular function after myocardial infarction—a randomised controlled trial. Int J Cardiol. doi:10.1016/j.ijcard.2012.03.054

  88. Witham MD, Dove FJ, Dryburgh M et al (2010) The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial. Diabetologia 53:2112–2119

    Article  PubMed  CAS  Google Scholar 

  89. Witham MD, Dove FJ, Sugden JA et al (2012) The effect of vitamin D replacement on markers of vascular health in stroke patients—a randomised controlled trial. Nutr Metab Cardiovasc Dis 22:864–870

    Article  PubMed  CAS  Google Scholar 

  90. Tarcin O, Yavuz DG, Ozben B et al (2009) Effect of vitamin D deficiency and replacement on endothelial function in asymptomatic subjects. J Clin Endocrinol Metab 94:4023–4030

    Article  PubMed  CAS  Google Scholar 

  91. Sugden JA, Davies JI, Witham MD et al (2008) Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diab Med 25:320–325

    Article  CAS  Google Scholar 

  92. Harris RA, Pedersen-White J, Guo DH et al (2011) Vitamin D3 supplementation for 16 weeks improves flow-mediated dilation in overweight African-American adults. Am J Hypertens 24:557–562

    Article  PubMed  CAS  Google Scholar 

  93. Hsia J, Heiss G, Ren H et al (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation 115:846–854

    Article  PubMed  CAS  Google Scholar 

  94. de Boer IH, Tinker LF, Connelly S et al (2008) Calcium plus vitamin D supplementation and the risk of incident diabetes in the Women’s Health Initiative. Diabetes Care 31:701–707

    Article  PubMed  CAS  Google Scholar 

  95. Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469

    Article  PubMed  CAS  Google Scholar 

  96. Elamin MB, Abu Elnour NO, Elamin KB et al (2011) Vitamin D and cardiovascular outcomes: a systematic review and meta-analysis. J Clin Endocrinol Metab 96:1931–1942

    Article  PubMed  CAS  Google Scholar 

  97. Wang L, Manson JE, Song Y et al (2010) Systematic review: vitamin D and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 152:315–323

    Article  PubMed  Google Scholar 

  98. Chlebowski RT, Johnson KC, Kooperberg C et al (2008) Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst 100:1581–1591

    Article  PubMed  CAS  Google Scholar 

  99. Marckmann P, Agerskov H, Thineshkumar S et al (2012) Randomized controlled trial of cholecalciferol supplementation in chronic kidney disease patients with hypovitaminosis D. Nephrol Dial Transplant 27:3523–3531

    Article  PubMed  CAS  Google Scholar 

  100. Kandula P, Dobre M, Schold JD et al (2011) Vitamin D supplementation in chronic kidney disease: a systematic review and meta-analysis of observational studies and randomized controlled trials. Clin J Am Soc Nephrol 6:50–62

    Article  PubMed  CAS  Google Scholar 

  101. Palmer SC, McGregor DO, Macaskill P (2007) Meta-analysis: vitamin D compounds in chronic kidney disease. Ann Intern Med 147:840–853

    Article  PubMed  Google Scholar 

  102. de Zeeuw D, Agarwal R, Amdahl M et al (2010) Selective vitamin D receptor activation with paricalcitol for reduction of albuminuria in patients with type 2 diabetes (VITAL study): a randomised controlled trial. Lancet 376:1543–1551

    Article  PubMed  CAS  Google Scholar 

  103. Cheng J, Zhang W, Zhang X et al (2012) Efficacy and safety of paricalcitol therapy for chronic kidney disease: a meta-analysis. Clin J Am Soc Nephrol 7:391–400

    Article  PubMed  CAS  Google Scholar 

  104. George PS, Pearson ER, Witham MD (2012) Effect of vitamin D supplementation on glycaemic control and insulin resistance: a systematic review and meta-analysis. Diabet Med 29:e142–e150

    Article  PubMed  CAS  Google Scholar 

  105. Avenell A, Cook JA, Maclennan GS et al (2009) Vitamin D supplementation and type 2 diabetes: a substudy of a randomised placebo-controlled trial in older people (RECORD trial, ISRCTN 51647438). Age Ageing 38:606–609

    Article  PubMed  Google Scholar 

  106. Rajasree S, Rajpal K, Kartha CC et al (2001) Serum 25-hydroxyvitamin D3 levels are elevated in South Indian patients with ischemic heart disease. Eur J Epidemiol 17:567–571

    Article  PubMed  CAS  Google Scholar 

  107. Durup D, Jorgensen HL, Christensen J (2012) A reverse J-shaped association of all-cause mortality with serum 25-hydroxyvitamin D in general practice: the CopD study. J Clin Endocrinol Metab 97:2644–2652

    Article  PubMed  CAS  Google Scholar 

  108. de Boer IH, Levin G, Robinson-Cohen C et al (2012) Serum 25-hydroxyvitamin D concentration and risk for major clinical disease events in a community-based population of older adults: a cohort study. Ann Intern Med 156:627–634

    Article  PubMed  Google Scholar 

  109. Bolland MJ, Avenell A, Baron JA et al (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691

    Article  PubMed  CAS  Google Scholar 

  110. Avenell A, Maclennan GS, Jenkinson DJ et al (2012) Long-term follow-up for mortality and cancer in a randomized placebo-controlled trial of vitamin D(3) and/or calcium (RECORD trial). J Clin Endocrinol Metab 97:614–622

    Article  PubMed  CAS  Google Scholar 

  111. Bolland MJ, Grey A, Avenell A (2011) 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 342:d2040

    Article  PubMed  Google Scholar 

  112. Rejnmark L, Avenell A, Masud T et al (2012) Vitamin D with calcium reduces mortality: patient level pooled analysis of 70,528 patients from eight major vitamin D trials. J Clin Endocrinol Metab 97:2670–2681

    Article  PubMed  CAS  Google Scholar 

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Conflicts of interest

Dr Witham has received grant funding for vitamin D research from Chief Scientist Office, Scottish Government, Diabetes UK, Heart Research UK, Chest Heart and Stroke Scotland, Tenovus Tayside, ME Research UK.

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Beveridge, L.A., Witham, M.D. Vitamin D and the cardiovascular system. Osteoporos Int 24, 2167–2180 (2013). https://doi.org/10.1007/s00198-013-2281-1

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