Vitamin-D concentrations, cardiovascular risk and events - a review of epidemiological evidence

Reviews in Endocrine and Metabolic Disorders

Volumn 18, Issue 2, 2017, Pages 259-272

  Grübler, Martin Robert ^a,b   März, Winfried ^b,c,d   Pilz, Stefan ^b,e   Grammer, Tanja B ^c   Trummer, Christian ^b   Müllner, Christian ^b   Schwetz, Verena ^b   Pandis, Marlene ^b   Verheyen, Nicolas ^b   Tomaschitz, Andreas ^b,f   Fiordelisi, Antonella ^g   Laudisio, Daniela ^g   Cipolletta, Ersilia ^h   Iaccarino, Guido ^h  

^a BERN UNIVERSITY HOSPITAL   (Switzerland)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

^c UNIVERSITY OF HEIDELBERG   (Germany)

^d SYNLAB ACADEMY   (Germany)

^e VU UNIVERSITY MEDICAL CENTER   (Netherlands)

^f Klinikum Bad Gleichenberg   (Austria)

^g IOS and COLEMAN Srl   (Italy)

^h UNIVERSITY OF SALERNO   (Italy)

Author keywords

Cardiovascular; Cardiovascular risk; Epidemiology; Mortality; Review; Vitamin D; Vitamin D receptor

Indexed keywords

25 HYDROXYVITAMIN D; VITAMIN D; VITAMIN D RECEPTOR; 25-HYDROXYVITAMIN D;

ATHEROSCLEROSIS; CARDIOVASCULAR RISK; CEREBROVASCULAR ACCIDENT; ENDOTHELIAL DYSFUNCTION; EPIDEMIOLOGICAL DATA; HEART FAILURE; HEART INFARCTION; HUMAN; HYPERTENSION; MENDELIAN RANDOMIZATION ANALYSIS; META ANALYSIS (TOPIC); NONHUMAN; OBSERVATIONAL STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RICKETS; VITAMIN SUPPLEMENTATION; ANALOGS AND DERIVATIVES; ANIMAL; BLOOD; CARDIOVASCULAR DISEASE; CARDIOVASCULAR SYSTEM; COMPLICATION; DRUG EFFECTS; METABOLISM; RISK FACTOR; VITAMIN D DEFICIENCY;

ANIMALS; CARDIOVASCULAR DISEASES; CARDIOVASCULAR SYSTEM; HUMANS; RISK FACTORS; VITAMIN D; VITAMIN D DEFICIENCY;

EID: 85018259292     PISSN: 13899155     EISSN: 15732606     Source Type: Journal    
DOI: 10.1007/s11154-017-9417-0     Document Type: Review

References (194)

1. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266–81.
2. Bouillon R, Suda T. Vitamin D: calcium and bone homeostasis during evolution. Bonekey Rep. 2014;3:480.
3. Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: lessons from vitamin D receptor null mice. Endocr Rev. 2008;29:726–76.
4. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, 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;96:53–8.
5. Cashman KD, Kiely M. Recommended dietary intakes for vitamin D: where do they come from, what do they achieve and how can we meet them? J Hum Nutr Diet. 2014;27:434–42.
6. German Nutrition Society. New reference values for vitamin D. Ann. Nutr. Metab. 2014;60:241–6.
7. H.A. Bischoff-Ferrari, W.C. Willett, E.J. Orav, P. Lips, P.J. Meunier, R.A. Lyons, et al. A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 367 (2012) 40–49.
8. Bolland MJ, Grey A. A case study of discordant overlapping meta-analyses: vitamin d supplements and fracture. PLoS One. 2014;9:e115934.
9. Avenell A, Mak JC, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4:CD000227.
10. Bolland MJ, Grey A, Gamble GD, Reid IR. The effect of vitamin D supplementation on skeletal, vascular, or cancer outcomes: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2:307–20.
11. Reid IR, Bolland MJ, Grey A. Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet. 2014;383:146–55.
12. Bolland MJ, Grey A, Reid IR. Differences in overlapping meta-analyses of vitamin D supplements and falls. J Clin Endocrinol Metab. 2014;99:4265–72.
13. Bolland MJ, Grey A, Gamble GD, Reid IR. Vitamin D supplementation and falls: a trial sequential meta-analysis. Lancet Diabetes Endocrinol. 2014;2:573–80.
14. Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016;27:367–76.
15. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med. 2016;176:175–83.
16. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.
17. Kanis JA, McCloskey EV, Johansson H, Cooper C, Rizzoli R, Reginster JY, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int. 2013;24:23–57.
18. Brouwer-Brolsma EM, Bischoff-Ferrari HA, Bouillon R, Feskens EJ, Gallagher CJ, Hypponen E, et al. Vitamin D: do we get enough? A discussion between vitamin D experts in order to make a step towards the harmonisation of dietary reference intakes for vitamin D across Europe. Osteoporos Int. 2013;24:1567–77.
19. Reid IR, Bolland MJ. Skeletal and nonskeletal effects of vitamin D: is vitamin D a tonic for bone and other tissues? Osteoporos Int. 2014;25:2347–57.
20. Rostand SG. Ultraviolet light may contribute to geographic and racial blood pressure differences. Hypertension. 1997;30:150–6.
21. Rathish N, Arun M. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012;3:118–26.
22. Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.
23. Pramyothin P, Holick MF. Vitamin D supplementation guidelines and evidence for subclinical deficiency. Curr Opin Gastroenterol. 2012;28:139–50.
24. Muscogiuri G, Altieri B, Annweiler C, Balercia G, Pal HB, Boucher BJ. Vitamin D and chronic diseases: the current state of the art. Arch Toxicol. 2017;91:97–107.
25. Kienreich K, Tomaschitz A, Verheyen N, Pieber T, Gaksch M. MR Grübler. S Pilz Vitamin D and cardiovascular disease Nutrients. 2013;5:3005–21.
26. Kienreich K, Grubler M, Tomaschitz A, Schmid J, Verheyen N, Rutters F, Dekker JM, Pilz S. Vitamin D, arterial hypertension & cerebrovascular disease. Indian J Med Res. 2013;137:669–79.
27. Poulter NR, Prabhakaran D, Caulfield M. Hypertension Lancet. 2015;386:801–12.
28. Wacker M, Holick MF. Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol. 2013;5:51–108.
29. Zittermann A. Vitamin D and cardiovascular disease. Anticancer Res. 2014;34:4641–8.
30. Kummerow FA. Nutrition imbalance and angiotoxins as dietary risk factors in coronary heart disease. Am J Clin Nutr. 1979;32:58–83.
31. Drüeke TB, Massy ZA. Role of vitamin D in vascular calcification: bad guy or good guy? Nephrol Dial Transplant. 2012;27:1704–7.
32. Linden V. Vitamin D and myocardial infarction. BMJ. 1974;3:647–50.
33. Schmidt-Gayk H, Goossen J, Lendle F, Seidel D. Serum 25-hydroxycalciferol in myocardial infarction. Atherosclerosis. 1977;26:55–8.
34. Lund B, Badskjaer J, Lund B, Soerensen OH. Vitamin D and ischaemic heart disease. Horm Metab Res. 1978;10:553–6.
35. Vik B, Try K, Thelle DS, Førde OH. Tromsø heart study: vitamin D metabolism and myocardial infarction. BMJ. 1979;2:176.
36. Scragg R. Seasonality of cardiovascular disease mortality and the possible protective effect of ultra-violet radiation. Int J Epidemiol. 2012;10:337–41.
37. Giovannucci E, Liu Y, Hollis BW, Rimm EB. 25-hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med. 2008;168:1174–80.
38. Dobnig H, Pilz S, Scharnagl H, Renner W, Seelhorst U, Wellnitz B, et al. Independent association of low serum 25-hydroxyvitamin d and 1,25-dihydroxyvitamin d levels with all-cause and cardiovascular mortality. Arch Intern Med. 2008;168:1340–9.
39. Pilz S, Gaksch M, O'Hartaigh B, Tomaschitz A, März W. The role of vitamin D deficiency in cardiovascular disease: where do we stand in 2013? Arch Toxicol. 2013;87:2083–103.
40. Pilz S, Verheyen N, Grübler MR, Tomaschitz A, März W. Vitamin D and cardiovascular disease prevention. Nat Rev Cardiol. 2016;13:404–17.
41. Christakos S, Dhawan P, Verstuyf A, Verlinden L, Carmeliet G. Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects. Physiol Rev. 2016;96:365–408.
42. Wang Y, DeLuca HF. Is the vitamin d receptor found in muscle? Endocrinology. 2011;152:354–63.
43. Norman PE, Powell JT. Vitamin D and cardiovascular disease. Circ Res. 2014;114:379–93.
44. Gardner DG, Chen S, Glenn DJ. Vitamin D and the heart. Am J Physiol Regul Integr Comp Physiol. 2013;305:R969–77.
45. Asano L, Watanabe M, Ryoden Y, Usuda K, Yamaguchi T, Khambu B, Takashima M, Sato S-I, Sakai J, Nagasawa K, Uesugi M. Vitamin D metabolite, 25-hydroxyvitamin D, regulates lipid metabolism by inducing degradation of SREBP/SCAP. Cell Chemical Biology. 2017;24(2):207–17.
46. Mark KA, Dumas KJ, Bhaumik D, Schilling B, Davis S, Oron TR, Sorensen DJ, Lucanic M, Brem RB, Melov S, Ramanathan A, Gibson BW, Lithgow GJ. Vitamin D promotes protein homeostasis and longevity via the stress response pathway genes skn-1, ire-1, and xbp-1. Cell Rep. 2016;17(5):1227–37.
47. Chen S, Law CS, Grigsby CL, Olsen K, Hong TT, Zhang Y, et al. Cardiomyocyte-specific deletion of the vitamin D receptor gene results in cardiac hypertrophy. Circulation. 2011;124:1838–47.
48. Ni W, Watts SW, Ng M, Chen S, Glenn DJ, Gardner DG. Elimination of vitamin D receptor in vascular endothelial cells alters vascular function. Hypertension. 2014;64:1290–8.
49. Oh J, Riek AE, Darwech I, Funai K, Shao J, Chin K, et al. Deletion of macrophage vitamin D receptor promotes insulin resistance and monocyte cholesterol transport to accelerate atherosclerosis in mice. Cell Rep. 2015;10:1872–86.
50. Chen S, Villalta SA, Agrawal DK. FOXO1 mediates vitamin D deficiency-induced insulin resistance in skeletal muscle. J Bone Miner Res. 2016;31:585–95.
51. Schmidt N, Brandsch C, Schutkowski A, Hirche F, Stangl GI. Dietary vitamin D inadequacy accelerates calcification and osteoblast-like cell formation in the vascular system of LDL receptor knockout and wild-type mice. J Nutr. 2014;144:638–46.
52. Gupta GK, Agrawal T, Rai V, Del Core MG, Hunter 3rd WJ, Agrawal DK. Vitamin D supplementation reduces intimal hyperplasia and restenosis following coronary intervention in atherosclerotic swine. PLoS One. 2016;11:e0156857.
53. Ellam T, Hameed A, ul Haque R, Muthana M, Wilkie M, Francis SE, et al. Vitamin D deficiency and exogenous vitamin D excess similarly increase diffuse atherosclerotic calcification in apolipoprotein E knockout mice. PLoS One. 2014;9:e88767.
54. Bikle DD. Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol. 2014;21(3):319–29.
55. Weishaar RE, Simpson RU. Involvement of vitamin D3 with cardiovascular function. II. Direct and indirect effects. Am. J. Physiol. 1987;253:E675–83.
56. Pilz S, Tomaschitz A, Drechsler C, Dekker JM, März W. Vitamin D deficiency and myocardial diseases. Mol Nutr Food Res. 2010;54:1103–13.
57. Assalin HB, Rafacho BP, dos Santos PP, Ardisson LP, Roscani MG, Chiuso-Minicucci F, et al. Impact of the length of vitamin D deficiency on cardiac remodeling. Circ Heart Fail. 2013;6:809–16.
58. van Ballegooijen AJ, Reinders I, Visser M, Brouwer IA. Parathyroid hormone and cardiovascular disease events: a systematic review and meta-analysis of prospective studies. Am Heart J. 2013;165:655–64.
59. Tomaschitz A, Ritz E, Pieske B, Rus-Machan J, Kienreich K, Verheyen N. Aldosterone and parathyroid hormone interactions as mediators of metabolic and cardiovascular disease. Metabolism. 2014;63:20–31.
60. Fitzpatrick LA, Bilezikian JP, Silverberg SJ. Parathyroid hormone and the cardiovascular system. Curr Osteoporos Rep. 2008;6:77–83.
61. Rutledge MR, Farah V, Adeboye AA, Seawell MR, Bhattacharya SK, Weber KT. Parathyroid hormone, a crucial mediator of pathologic cardiac remodeling in aldosteronism. Cardiovasc Drugs Ther. 2013;27:161–70.
62. Peterlik M, Kállay E, Cross HS. Calcium nutrition and extracellular calcium sensing: relevance for the pathogenesis of osteoporosis, cancer and cardiovascular diseases. Nutrients. 2013;5:302–27.
63. Yousefzadeh P, Shapses SA, Wang X. Vitamin D binding protein impact on 25-Hydroxyvitamin D levels under different physiologic and pathologic conditions. International Journal of Endocrinology. 2014:e981581.
64. Zebger-Gong H, Müller D, Diercke M, Haffner D, Hocher B, Verberckmoes S, 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;29:339–48.
65. Lomashvili KA, Wang X, O'Neill WC. Role of local versus systemic vitamin D receptors in vascular calcification. Arterioscler Thromb Vasc Biol. 2014;34:146–51.
66. Bas A, Lopez I, Perez J, Rodriguez M, Aguilera-Tejero E. Reversibility of calcitriol-induced medial artery calcification in rats with intact renal function. J Bone Miner Res. 2006;21:484–90.
67. Razzaque MS. The dualistic role of vitamin D in vascular calcifications. Kidney Int. 2011;79:708–14.
68. Lau WL, Leaf EM, Hu MC, Takeno MM, Kuro-o M, Moe OW, 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;82:1261–70.
69. Aoshima Y, Mizobuchi M, Ogata H, Kumata C, Nakazawa A, Kondo F, et al. Vitamin D receptor activators inhibit vascular smooth muscle cell mineralization induced by phosphate and TNF-α. Nephrol Dial Transplant. 2012;27:1800–6.
70. Hirata M, Serizawa K, Aizawa K, Yogo K, Tashiro Y, Takeda S, et al. 22-Oxacalcitriol prevents progression of endothelial dysfunction through antioxidative effects in rats with type 2 diabetes and early-stage nephropathy. Nephrol Dial Transplant. 2013;28:1166–74.
71. Negri AL. Fibroblast growth factor 23: associations with cardiovascular disease and mortality in chronic kidney disease. Int Urol Nephrol. 2014;46:9–17.
72. Wu-Wong JR, Li X, Chen YW. Different vitamin D receptor agonists exhibit differential effects on endothelial function and aortic gene expression in 5/6 nephrectomized rats. J Steroid Biochem Mol Biol. 2015;148:202–9.
73. Wu-Wong JR, Noonan W, Nakane M, Brooks KA, Segreti JA, Polakowski JS, et al. Vitamin d receptor activation mitigates the impact of uremia on endothelial function in the 5/6 nephrectomized rats. Int J Endocrinol. 2010;2010:625852.
74. Dong J, Wong SL, Lau CW, Liu J, Wang YX, Dan He Z, et al. Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor. Kidney Int. 2013;84:54–63.
75. Andrukhova O, Slavic S, Zeitz U, Riesen SC, Heppelmann MS, Ambrisko TD, et al. Vitamin D is a regulator of endothelial nitric oxide synthase and arterial stiffness in mice. Mol Endocrinol. 2014;28:53–64.
76. Bozic M, Álvarez Á, de Pablo C, Sanchez-Niño MD, Ortiz A, Dolcet X, et al. Impaired vitamin D signaling in endothelial cell leads to an enhanced leukocyte-endothelium interplay: implications for atherosclerosis development. PLoS One. 2015;10:e0136863.
77. Beveridge LA, Struthers AD, Kahn F, Jorde R, Scragg R, Macdonald HM, et al. Effect of vitamin D supplementation on blood pressure: a systematic review and meta-analysis incorporating individual patient data. JAMA Intern Med. 2015;175:745–54.
78. Autier P, Boniol M, Pizot C, Mullie P. Vitamin D status and ill health: a systematic review. Lancet Diabetes Endocrinol. 2014;2:76–89.
79. Reid D, Toole BJ, Knox S, Talwar D, Harten J, O'Reilly DS, et al. The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty. Am J Clin Nutr. 2011;93:1006–11.
80. 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;94:581–4.
81. Yilmaz O, Olgun H, Ciftel M, Kilic O, Kartal I, Iskenderoglu NY, et al. Dilated cardiomyopathy secondary to rickets-related hypocalcaemia: eight case reports and a review of the literature. Cardiol Young. 2015;25:261–6.
82. Tiosano D, Gepstein V. Vitamin D action: lessons learned from hereditary 1,25-dihydroxyvitamin-D-resistant rickets patients. Curr Opin Endocrinol Diabetes Obes. 2012;19:452–9.
83. Tiosano D, Schwartz Y, Braver Y, Hadash A, Gepstein V, Weisman Y, et al. The renin-angiotensin system, blood pressure, and heart structure in patients with hereditary vitamin D-resistance rickets (HVDRR). J Bone Miner Res. 2011;26:2252–60.
84. Kunutsor SK, Apekey TA, Steur M. Vitamin D and risk of future hypertension: meta-analysis of 283,537 participants. Eur J Epidemiol. 2013;28:205–21.
85. Ullah MI, Uwaifo GI, Nicholas WC, Koch CA. Does vitamin D deficiency cause hypertension? Current evidence from clinical studies and potential mechanisms. Int J Endocrinol. 2010;2010:1–11.
86. Ullah M, Koch C, Tamanna S, Rouf S, Shamsuddin L. Vitamin D deficiency and the risk of Preeclampsia and Eclampsia in Bangladesh. Horm Metab Res. 2013;45(09):682–87.
87. Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM. American Heart Association. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296–308.
88. Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, et al. Blood 25-hydroxy vitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care. 2013;36:1422–8.
89. Lu M, Xu Y, Lv L, Zhang M. Association between vitamin D status and the risk of gestational diabetes mellitus: a meta-analysis. Arch. Gynecol. Obstet. 2016;293:959–66.
90. Khan H, Kunutsor S, Franco OH, Chowdhury R. Vitamin D, type 2 diabetes and other metabolic outcomes: a systematic review and meta-analysis of prospective studies. Proc. Nutr. Soc. 2013;72:89–97.
91. Ju SY, Jeong HS, Kim do H. Blood vitamin D status and metabolic syndrome in the general adult population: a dose-response meta-analysis. J. Clin. Endocrinol. Metab. 2014;99:1053–63.
92. Pilz S, Kienreich K, Rutters F, de Jongh R, van Ballegooijen AJ, Grübler M, Tomaschitz A, Dekker JM. Role of vitamin D in the development of insulin resistance and type 2 diabetes. Curr Diab Rep. 2013;13:261–70.
93. Grübler MR, Gaksch M, Kienreich K, Verheyen N, Schmid J, Hartaigh BÓ, et al. Effects of vitamin D supplementation on glycated haemoglobin and fasting glucose levels in hypertensive patients: a randomized controlled trial. Diabetes Obes Metab. 2016;18:1006–12.
94. Dong JY, Zhang WG, Chen JJ, Zhang ZL, Han SF, Qin LQ. Vitamin D intake and risk of type 1 diabetes: a meta-analysis of observational studies. Nutrients. 2013;5:3551–62.
95. Rewers M, Ludvigsson J. Environmental risk factors for type 1 diabetes. Lancet. 2016;387:2340–8.
96. Pereira-Santos M, Costa PR, Assis AM, Santos CA, Santos DB. Obesity and vitamin D deficiency: a systematic review and meta-analysis. Obes Rev. 2015;16:341–9.
97. Pourshahidi LK. Vitamin D and obesity: current perspectives and future directions. Proc Nutr Soc. 2015;74:115–24.
98. Challoumas D. Vitamin D supplementation and lipid profile: what does the best available evidence show? Atherosclerosis. 2014;235:130–9.
99. Jorde R, Grimnes G. Vitamin D and metabolic health with special reference to the effect of vitamin D on serum lipids. Prog Lipid Res. 2011;50:303–12.
100. Prietl B, Treiber G, Pieber TR, Amrein K. Vitamin D and immune function. Nutrients. 2013;5:2502–21.
101. Hewison M. An update on vitamin D and human immunity. Clin Endocrinol. 2012;76:315–25.
102. Liu WC, Wu CC, Hung YM, Liao MT, Shyu JF, Lin YF, et al. Pleiotropic effects of vitamin D in chronic kidney disease. Clin Chim Acta. 2016;453:1–12.
103. Dusso AS, Tokumoto M. Defective renal maintenance of the vitamin D endocrine system impairs vitamin D renoprotection: a downward spiral in kidney disease. Kidney Int. 2011;79:715–29.
104. Liu T, Zhong S, Liu L, Liu S, Li X, Zhou T, et al. Vitamin D deficiency and the risk of anemia: a meta-analysis of observational studies. Ren Fail. 2015;37:929–34.
105. Derakhshanian H, Shab-Bidar S, Speakman JR, Nadimi H, Djafarian K. Vitamin D and diabetic nephropathy: a systematic review and meta-analysis. Nutrition. 2015;31:1189–94.
106. Michalska-Kasiczak M, Sahebkar A, Mikhailidis DP, Rysz J, Muntner P, Toth PP, et al. Analysis of vitamin D levels in patients with and without statin-associated myalgia - a systematic review and meta-analysis of 7 studies with 2420 patients. Int J Cardiol. 2015;178:111–6.
107. Lv WS, Zhao WJ, Gong SL, Fang DD, Wang B, Fu ZJ, et al. Serum 25-hydroxyvitamin D levels and peripheral neuropathy in patients with type 2 diabetes: a systematic review and meta-analysis. J Endocrinol Investig. 2015;38:513–8.
108. Zittermann A, Iodice S, Pilz S, Grant WB, Bagnardi V, Gandini S. Vitamin D deficiency and mortality risk in the general population: A meta-analysis of prospective cohort studies. Am J Clin Nutr. 2012;95:91–100.
109. Wang L, Song Y, Manson JE, Pilz S, März W, Michaëlsson K, et al. Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ. Cardiovasc. Qual. Outcomes. 2012;5:819–29.
110. 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.
111. Sokol SI, Tsang P, Aggarwal V, Melamed ML, Srinivas VS. Vitamin D status and risk of cardiovascular events: lessons learned via systematic review and meta-analysis. Cardiol Rev. 2011;19:192–201.
112. Grandi NC, Breitling LP, Brenner H. Vitamin D and cardiovascular disease: systematic review and meta-analysis of prospective studies. Prev Med. 2010;51:228–33.
113. Pittas AG, Chung M, Trikalinos T, Mitri J, Brendel M, Patel K, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann. Intern. Med. 2010;152:307–14.
114. Tomson J, Emberson J, Hill M, Gordon A, Armitage J, Shipley M, et al. 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;34:1365–74.
115. Fan H, Yu W, Cao H, Li J, Liu B, Wang J, et al. Meta-analysis of circulating 25-hydroxyvitamin D levels and risk of cardiovascular and all-cause mortality in elderly population. Int J Cardiol. 2014;176:1025–9.
116. Chowdhury R, Kunutsor S, Vitezova A, Oliver-Williams C, Chowdhury S, Kiefte-de-Jong JC, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ. 2014;348:g1903.
117. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.
118. Schöttker B, Jorde R, Peasey A, Thorand B, Jansen EH, Groot L, et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656.
119. Brøndum-Jacobsen P, Nordestgaard BG, Schnohr P, Benn M. 25-hydroxyvitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol. 2013;73:38–47.
120. Sogomonian R, Alkhawam H, Jolly J, Vyas N, Ahmad S, Moradoghli Haftevani E, et al. Serum vitamin D levels correlate to coronary artery disease severity: a retrospective chart analysis. Expert Rev Cardiovasc Ther. 2016;14:977–82.
121. Karohl C, Vaccarino V, Veledar E, Goldberg J, Tangpricha V, Bellasi A, Raggi P. Vitamin D status and coronary flow reserve measured by positron emission tomography: a co-twin control study. J Clin Endocrinol Metabol. 2013;98(1):389–97.
122. Degerud E, Løland KH, Nygård O, Midttun Ø, Ueland PM, Seifert R, et al. Vitamin D status was not associated with 'one-year' progression of coronary artery disease, assessed by coronary angiography in statin-treated patients. Eur J Prev Cardiol. 2015;22:594–602.
123. Alsancak Y, Cengel A, Akyel A, Ozkan S, Sezenoz B, Unlu S. S, et al. Relationship between serum vitamin D levels and angiographic severity and extent of coronary artery disease. Eur J Clin Investig. 2015;45:940–8.
124. Verdoia M, Schaffer A, Sartori C, Barbieri L, Cassetti E, Marino P, Galasso G, De Luca G. Vitamin D deficiency is independently associated with the extent of coronary artery disease. Eur J Clin Investig. 2014;44:634–42.
125. Lim S, Shin H, Kim MJ, Ahn HY, Kang SM, Yoon JW, et al. Vitamin D inadequacy is associated with significant coronary artery stenosis in a community-based elderly cohort: the Korean longitudinal study on health and aging. J Clin Endocrinol Metab. 2012;97:169–17.
126. C. Joergensen, Reinhard, A. Schmedes, P.R. Hansen, N. Wiinberg, C. L. Petersen, et al. Vitamin D Levels and Asymptomatic Coronary Artery Disease in Type 2 Diabetic Patients With Elevated Urinary Albumin Excretion Rate. Diabetes Care 35 (2012) 168–172.
127. Aggarwal R, Akhthar T, Jain SK. Coronary artery disease and its association with vitamin D deficiency. J Midlife Health. 2016;7:56–60.
128. Zittermann A, Kuhn J, Dreier J, Knabbe C, Gummert JF, Börgermann J. Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur. Heart J. 2013;34:1358–64.
129. Durup D, Jørgensen HL, Christensen J, Tjønneland A, Olsen A, Halkjær J, et al. A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD study. J Clin Endocrinol Metab. 2015;100:2339–46.
130. Dror Y, Giveon SM, Hoshen M, Feldhamer I, Balicer RD, Feldman BS. Vitamin D levels for preventing acute coronary syndrome and mortality: evidence of a nonlinear association. J Clin Endocrinol Metab. 2013;98:2160–7.
131. Grant WB, Karras SN, Bischoff-Ferrari HA, Annweiler C, Boucher BJ, Juzeniene A, et al. Do studies reporting 'U'-shaped serum 25-hydroxyvitamin D-health outcome relationships reflect adverse effects? Dermatoendocrinol. 2016;8:e1187349.
132. Zittermann A, Prokop S, Gummert JF, Börgermann J. Safety issues of vitamin D supplementation. Anti Cancer Agents Med Chem. 2013;13:4–10.
133. Pilz S, März 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;93:3927–35.
134. Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, et al. Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J. 2010;31:2253–61.
135. Deo R, Katz R, Shlipak MG, Sotoodehnia N, Psaty BM, Sarnak MJ, et al. Vitamin D, parathyroid hormone, and sudden cardiac death: results from the cardiovascular health study. Hypertension. 2011;58:1021–8.
136. Naesgaard PA, León De La Fuente RA, Nilsen ST, Woie L, Aarsland T, Brede C, et al. Serum 25(OH)D is a 2-year predictor of all-cause mortality, cardiac death and sudden cardiac death in chest pain patients from northern Argentina. PLoS One. 2012;7:e43228.
137. Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M. RECORD Trial Group. Cardiovascular disease and vitamin D supplementation: trial analysis, systematic review, and meta-analysis. Am J Clin Nutr. 2014;100:746–55.
138. Sun Q, Pan A, Hu FB, Manson JE, Rexrode KM. 25-hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke. 2012;43:1470–7.
139. Brøndum-Jacobsen P, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. 25-hydroxyvitamin D concentrations and risk of venous thromboembolism in the general population with 18,791 participantsJ Thromb Haemost. 2013;11:423–31.
140. Folsom AR, Roetker NS, Rosamond WD, Heckbert SR, Basu S, Cushman M, et al. Serum 25-hydroxyvitamin D and risk of venous thromboembolism: the atherosclerosis risk in communities (ARIC) study. J Thromb Haemost. 2014;12:1455–60.
141. Brodin E, Lerstad G, Grimnes G, Brækkan SK, Vik A, Brox J, et al. Serum levels of vitamin D are not associated with future risk of venous thromboembolism. The Tromsø study. Thromb. Haemost. 2013;109:885–90.
142. Thompson J, Nitiahpapand R, Bhatti P, Kourliouros A. Vitamin D deficiency and atrial fibrillation. Int J Cardiol. 2015;184:159–62.
143. Deleskog A, Piksasova O, Silveira A, Gertow K, Baldassarre D, Veglia F, et al. Serum 25-hydroxyvitamin D concentration in subclinical carotid atherosclerosis. Arterioscler Thromb Vasc Biol. 2013;33:2633–8.
144. Blondon M, Sachs M, Hoofnagle AN, Ix JH, Michos ED, Korcarz C, et al. 25-hydroxyvitamin D and parathyroid hormone are not associated with carotid intima-media thickness or plaque in the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol. 2013;33:2639–45.
145. Gepner AD, Colangelo LA, Blondon M, Korcarz CE, de Boer IH, Kestenbaum B, et al. 25-hydroxyvitamin D and parathyroid hormone levels do not predict changes in carotid arterial stiffness: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol. 2014;34:1102–9.
146. Nsengiyumva V, Fernando ME, Moxon JV, Krishna SM, Pinchbeck J, Omer SM, et al. The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: a meta-analysis of observational studies. Atherosclerosis. 2015;243:645–51.
147. Zheng Z, Shi H, Jia J, Li D, Lin S. Vitamin D supplementation and mortality risk in chronic kidney disease: a meta-analysis of 20 observational studies. BMC Nephrol. 2013;14:199.
148. Levin GP, Robinson-Cohen C, de Boer IH, Houston DK, Lohman K, Liu Y, et al. Genetic variants and associations of 25-hydroxyvitamin D concentrations with major clinical outcomes. JAMA. 2012;308:1898–905.
149. Grübler MR, Gaksch M, Kienreich K, Verheyen ND, Schmid J, Müllner C. Effects of Vitamin D3 on asymmetric- and symmetric dimethylarginine in arterial hypertension. J Steroid Biochem Mol Biol. (2016) In press, Corrected Proof DOI: 10.1016/j.jsbmb.2016.12.014.
150. Bansal N, Zelnick L, Robinson-Cohen C, Hoofnagle AN, Ix JH, Lima JA, et al. Serum parathyroid hormone and 25-hydroxyvitamin D concentrations and risk of incident heart failure: the multi-ethnic study of atherosclerosis. J Am Heart Assoc. 2014;3:e001278.
151. van Ballegooijen AJ, Visser M, Cotch MF, Arai AE, Garcia M, Harris TB, 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;98:2544–52.
152. van Ballegooijen AJ, Snijder MB, Visser M, van den Hurk K, Kamp O, Dekker JM, et al. Vitamin D in relation to myocardial structure and function after eight years of follow-up: the Hoorn study. Ann Nutr Metab. 2012;60:69–77.
153. van Ballegooijen AJ, Visser M, Kestenbaum B, Siscovick DS, de Boer IH, Gottdiener JS, et al. Relation of vitamin D and parathyroid hormone to cardiac biomarkers and to left ventricular mass (from the cardiovascular health study). Am J Cardiol. 2013;111:418–24.
154. Pekkanen MP, Ukkola O, Hedberg P, Piira OP, Lepojärvi S, Lumme J, et al. Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease. Nutr Metab Cardiovasc Dis. 2015;25:471–8.
155. Zittermann A, Ernst JB. Calciotropic and phosphaturic hormones in heart failure. Dis: Nutr. Metab. Cardiovasc; 2017. doi:10.1016/j.numecd.2016.06.007.
156. M.M. Donneyong, C.A. Hornung, K.C. Taylor, R. N. Baumgartner, J.A. Myers, C.B. Eaton, et. al. Risk of heart failure among postmenopausal women: a secondary analysis of the randomized trial of vitamin D plus calcium of the women's health initiative. Circ Heart Fail 8 (2015) 49–56.
157. Dalbeni A, Scaturro G, Degan M, Minuz P, Delva P. Effects of six months of vitamin D supplementation in patients with heart failure: a randomized double-blind controlled trial. Nutr Metab Cardiovasc Dis. 2014;24:861–8.
158. 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. JACC. 2016;67:2593–603.
159. Davey Smith G, Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23:R89–98.
160. Wang L, Chu A, Buring JE, Ridker PM, Chasman DI, Sesso HD. Common genetic variations in the vitamin D pathway in relation to blood pressure. Am J Hypertens. 2014;27:1387–95.
161. Tizaoui K, Kaabachi W, Hamzaoui A, Hamzaoui K. Contribution of VDR polymorphisms to type 1 diabetes susceptibility: systematic review of case-control studies and meta-analysis. J Steroid Biochem Mol Biol. 2014;143:240–9.
162. Li L, Wu B, Liu JY, Yang LB. Vitamin D receptor gene polymorphisms and type 2 diabetes: a meta-analysis. Arch Med Res. 2013;44:235–41.
163. Zhu B, Zhao HL, Ou C, Huang LS, Li PZ, Lao M. Association of vitamin D receptor BsmI gene polymorphism with the risk of type 2 diabetes mellitus. J Recept Signal Transduct Res. 2014;34:458–62.
164. Liu Z, Liu L, Chen X, He W, Yu X. Associations study of vitamin D receptor gene polymorphisms with diabetic microvascular complications: a meta-analysis. Gene. 2014;546:6–10.
165. Mao S, Huang S. Lack of an association between vitamin D receptor BsmI gene polymorphism and the risk of end-stage renal disease: a meta-analysis. Intern Med. 2013;52:2423–30.
166. Chun RF, Liu PT, Modlin RL, Adams JS, Hewison M. Impact of vitamin D on immune function: lessons learned from genome-wide analysis. Front Physiol. 2014;5:151.
167. Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376:180–8.
168. Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19:2739–45.
169. Verduijn M, Siegerink B, Jager KJ, Zoccali C, Dekker FW. Mendelian randomization: use of genetics to enable causal inference in observational studies. Nephrol Dial Transplant. 2010;25:1394–8.
170. Vimaleswaran KS, Berry DJ, Lu C, Tikkanen E, Pilz S, Hiraki LT, et al. Causal relationship between obesity and vitamin D status: Bi-directional mendelian randomization analysis of multiple cohorts. PLoS Med. 2013;10:e1001383.
171. Leong A, Rehman W, Dastani Z, Greenwood C, Timpson N, Langsetmo L, et al. The causal effect of vitamin D binding protein (DBP) levels on calcemic and cardiometabolic diseases: a mendelian randomization study. PLoS Med. 2014;11:e1001751.
172. Liefaard MC, Ligthart S, Vitezova A, Hofman A, Uitterlinden AG, Kiefte-de Jong JC, et al. Vitamin D and C-reactive protein: a mendelian randomization study. PLoS One. 2015;10:e0131740.
173. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Vitamin D concentration, obesity, and risk of diabetes: a mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2:298–306.
174. Ye Z, Sharp SJ, Burgess S, Scott RA, Imamura F, InterAct Consortium, et al. Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: A mendelian randomisation study. Lancet Diabetes Endocrinol. 2015;3:35–42.
175. Skaaby T, Husemoen LL, Martinussen T, Thyssen JP, Melgaard M, Thuesen BH, et al. Vitamin D status, filaggrin genotype, and cardiovascular risk factors: a mendelian randomization approach. PLoS One. 2013;8:e57647.
176. Ooi EM, Afzal S, Nordestgaard BG. Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: mendelian randomization study. Circ Cardiovasc Genet. 2014;7:650–8.
177. Vimaleswaran KS, Cavadino A, Berry DJ, Jorde R, Dieffenbach AK, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation study. Lancet Diabetes Endocrinol. 2014;2:719–29.
178. Pilz S, Gaksch M, Kienreich K, Grübler M, Verheyen N, Fahrleitner-Pammer A. Effects of vitamin D on blood pressure and cardiovascular risk factors: a randomized controlled trial. Hypertension. 2012;65:1195–201.
179. Husemoen LL, Skaaby T, Martinussen T, Jørgensen T, Thuesen BH, Kistorp C, et al. Investigating the causal effect of vitamin D on serum adiponectin using a mendelian randomization approach. Eur J Clin Nutr. 2014;68:189–95.
180. Manousaki D, Mokry LE, Ross S, Goltzman D, Richards JB. Mendelian randomization studies do not support a role for vitamin D in coronary artery disease. Circ Cardiovasc Genet. 2016;9:349–56. doi:10.1161/CIRCGENETICS.116.001396.
181. Brøndum-Jacobsen P, Benn M, Afzal S, Nordestgaard BG. No evidence that genetically reduced 25-hydroxyvitamin D is associated with increased risk of ischaemic heart disease or myocardial infarction: a mendelian randomization study. Int J Epidemiol. 2015;44:651–61.
182. Afzal S, Brøndum-Jacobsen P, Bojesen SE, Nordestgaard BG. Genetically low vitamin D concentrations and increased mortality: mendelian randomisation analysis in three large cohorts. BMJ. 2014;349:g6330.
183. Schmid J, Kienreich K, Gaksch M, Grübler M, Raggam R, Meinitzer A, et al. The importance of assays in vitamin D status classification: a comparison of four automated 25-hydroxyvitamin D immunoassays. Laboratoriumsmedizin. 2013;37:261–8.
184. Amrein K, Schnedl C, Holl A, Riedl R, Christopher KB, Pachler C, et al. Effect of high-dose vitamin D3 on hospital length of stay in critically ill patients with vitamin D deficiency: The VITdAL-ICU randomized clinical trial. JAMA. 2014;312:1520–30.
185. Kiely M, Cashman KD, on behalf of the ODIN Consortium. The ODIN project: Development of food-based approaches for prevention of vitamin D deficiency throughout life. Nutr. Bull. 2015;40:235–46.
186. Kiely M, Black LJ. Dietary strategies to maintain adequacy of circulating 25-hydroxyvitamin D concentrations. Scand J Clin Lab Invest Suppl. 2012;243:14–23.
187. Cashman KD, Dowling KG, Škrabáková Z, Gonzalez-Gross M, Valtueña J, De Henauw S, et al. Vitamin D deficiency in Europe: pandemic? Am J Clin Nutr. 2016;103:1033–44.
188. Rejnmark L, Avenell A, Masud T, Anderson F, Meyer HE, Sanders KM, 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;97:2670–81.
189. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, et al. Vitamin D supplementation for prevention of cancer in adults. Cochrane Database Syst Rev. 2014;6:CD007469.
190. Riley RD, Lambert PC, Abo-Zaid G. Meta-analysis of individual participant data: rationale, conduct, and reporting. BMJ. 2010;340:c221.
191. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815–22.
192. Eaton CB, Young A, Allison MA, Robinson J, Martin LW, Kuller LH, et al. Prospective association of vitamin D concentrations with mortality in postmenopausal women: Results from the Women's Health Initiative (WHI). Am J Clin Nutr. 2011;94:1471–8.
193. Gaksch M, Jorde R, Grimnes G, Joakimsen R, Schirmer H, Wilsgaard T, Mathiesen EB, Njølstad I, Løchen M-L, März W, Kleber ME, Tomaschitz A, Grübler M, Eiriksdottir G, Gudmundsson EF, Harris TB, Cotch MF, Aspelund T, Gudnason V, Rutters F, Beulens JWJ, van ‘t Riet E, Nijpels G, Dekker JM, Grove-Laugesen D, Rejnmark L, Busch MA, Mensink GBM, Scheidt-Nave C, Thamm M, Swart KMA, Brouwer IA, Lips P, van Schoor NM, Sempos CT, Durazo-Arvizu RA, Škrabáková Z, Dowling KG, Cashman KD, Kiely M, Pilz S, Zmijewski M. Vitamin D and mortality: individual participant data meta-analysis of standardized 25-hydroxyvitamin D in 26916 individuals from a European consortium. PLOS ONE. 2017;12(2):e0170791.
194. Bolland MJ, Bacon CJ, Horne AM, Mason BH, Ames RW, Wang TK, Grey AB, Gamble GD, Reid IR. Vitamin D insufficiency and health outcomes over 5 y in older women. Am J Clin Nutr. 2010;91:82–9.