Serum 25-hydroxyVitamin D and the risk of cardiovascular disease: Dose-response meta-analysis of prospective studies1-3

American Journal of Clinical Nutrition

Volumn 105, Issue 4, 2017, Pages 810-819

  Zhang, Runhua ^a,b   Li, Bohong ^a   Gao, Xiang ^c   Tian, Rui ^a   Pan, Yuesong ^a,b   Jiang, Yong ^a,b   Gu, Hongqiu ^a,b   Wang, Yilong ^a,b   Wang, Yongjun ^a,b   Liu, Gaifen ^a,b  

^a CAPITAL MEDICAL UNIVERSITY   (China)

^b BEIJING INSTITUTE FOR BRAIN DISORDERS   (China)

^c PENNSYLVANIA STATE UNIVERSITY   (United States)

Author keywords

25 hydroxyVitamin D; Cardiovascular disease; CVD mortality; Dose response; Metaanalysis

Indexed keywords

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

AGE; ARTICLE; BLOOD PRESSURE; BODY MASS; CARDIOVASCULAR MORTALITY; CARDIOVASCULAR RISK; DIABETES MELLITUS; DISEASE ASSOCIATION; HUMAN; HYPERTENSION; PHYSICAL ACTIVITY; PUBLICATION; SEX DIFFERENCE; SYSTEMATIC REVIEW; VITAMIN BLOOD LEVEL; ADULT; AGED; ANALOGS AND DERIVATIVES; BLOOD; CARDIOVASCULAR DISEASES; COMPLICATION; META ANALYSIS; MIDDLE AGED; MORTALITY; PROSPECTIVE STUDY; RISK FACTOR; VERY ELDERLY; VITAMIN D DEFICIENCY;

ADULT; AGED; AGED, 80 AND OVER; CARDIOVASCULAR DISEASES; HUMANS; MIDDLE AGED; PROSPECTIVE STUDIES; RISK FACTORS; VITAMIN D; VITAMIN D DEFICIENCY;

EID: 85020533533     PISSN: 00029165     EISSN: 19383207     Source Type: Journal    
DOI: 10.3945/ajcn.116.140392     Document Type: Article

References (78)

1. de Boer IH, Kestenbaum B, Siscovick DS. Vitamin D insufficiency. N Engl J Med 2011;364:1379-80; author reply: 80.
2. Lieben L, Carmeliet G. Vitamin D signaling in osteocytes: effects on bone and mineral homeostasis. Bone 2013;54:237-43.
3. Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, Liu S, Looker AC, Wallace TC, Wang DD. Calcium plus Vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int 2016;27:367-76.
4. 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.
5. Halfon M, Phan O, Teta D. Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty. Biomed Res Int 2015;2015: 953241.
6. Ke L, Graubard BI, Albanes D, Fraser DR, Weinstein SJ, Virtamo J, Brock KE. Hypertension, pulse, and other cardiovascular risk factors and Vitamin D status in Finnish men. Am J Hypertens 2013;26: 951-6.
7. Lim S, Kim MJ, Choi SH, Shin CS, Park KS, Jang HC, Billings LK, Meigs JB. Association of Vitamin D deficiency with incidence of type 2 diabetes in high-risk Asian subjects. Am J Clin Nutr 2013;97:524-30.
8. Gagnon C, Lu ZX, Magliano DJ, Dunstan DW, Shaw JE, Zimmet PZ, Sikaris K, Grantham N, Ebeling PR, Daly RM. Serum 25-hydroxyVitamin D, calcium intake, and risk of type 2 diabetes after 5 years: results from a national, population-based prospective study (the Australian Diabetes, Obesity and Lifestyle Study). Diabetes Care 2011;34:1133-8.
9. Pham TM, Ekwaru JP, Setayeshgar S, Veugelers PJ. The effect of changing serum 25-hydroxyVitamin D concentrations on metabolic syndrome: a longitudinal analysis of participants of a preventive health program. Nutrients 2015;7:7271-84.
10. Wang TJ, Pencina MJ, Booth SL, Jacques PF, Ingelsson E, Lanier K, Benjamin EJ, D'Agostino RB, Wolf M, Vasan RS. Vitamin D deficiency and risk of cardiovascular disease. Circulation 2008;117: 503-11.
11. Michos ED, Reis JP, Post WS, Lutsey PL, Gottesman RF, Mosley TH, Sharrett AR, Melamed ML. 25-HydroxyVitamin D deficiency is associated with fatal stroke among whites but not blacks: the NHANES-III linked mortality files. Nutrition 2012;28:367-71.
12. Chandler PD, Buring JE, Manson JE, Giovannucci EL, Moorthy MV, Zhang S, Lee IM, Lin JH. Circulating Vitamin D levels and risk of colorectal cancer in women. Cancer Prev Res (Phila) 2015;8:675-82.
13. McDonnell SL, Baggerly C, French CB, Baggerly LL, Garland CF, Gorham ED, Lappe JM, Heaney RP. Serum 25-hydroxyVitamin D concentrations $40 ng/ml are associated with .65% lower cancer risk: pooled analysis of randomized trial and prospective cohort study. PLoS One 2016;11:e0152441.
14. Skaaby T, Husemoen LL, Pisinger C, Jorgensen T, Thuesen BH, Fenger M, Linneberg A. Vitamin D status and cause-specific mortality: a general population study. PLoS One 2012;7:e52423.
15. Pilz S, Dobnig H, Nijpels G, Heine RJ, Stehouwer CDA, Snijder MB, Van Dam RM, Dekker JM. Vitamin D and mortality in older men and women. Clin Endocrinol (Oxf) 2009;71:666-72.
16. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, 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.
17. Smith SC Jr., Collins A, Ferrari R, Holmes DR Jr., Logstrup S, McGhie DV, Ralston J, Sacco RL, Stam H, Taubert K, et al. Our time: a call to save preventable death from cardiovascular disease (heart disease and stroke). Glob Heart 2012;7:297-305.
18. Peterlik M, Boonen S, Cross HS, Lamberg-Allardt C. Vitamin D and calcium insufficiency-related chronic diseases: an emerging world-wide public health problem. Int J Environ Res Public Health 2009;6:2585-607.
19. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ 2014;348:g2035.
20. Bassuk SS, Manson JE, Lee IM, Cook NR, Christen WG, Bubes VY, Gordon DS, Copeland T, Friedenberg G, D'Agostino DM, et al. Baseline characteristics of participants in the VITamin D and OmegA-3 TriaL (VITAL). Contemp Clin Trials 2016;47:235-43.
21. 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.
22. 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.
23. Kühn T, Kaaks R, Teucher B, Hirche F, Dierkes J,Weikert C, Katzke V, Boeing H, Stangl GI, Buijsse B. Plasma 25-hydroxyVitamin D and its genetic determinants in relation to incident myocardial infarction and stroke in the European prospective investigation into cancer and nutrition (EPIC)-Germany study. PLoS One 2013;8:e69080.
24. Perna L, Schöttker B, Holleczek B, Brenner H. Serum 25-hydroxyVitamin D and incidence of fatal and nonfatal cardiovascular events: a prospective study with repeated measurements. J Clin Endocrinol Metab 2013;98: 4908-15.
25. Durup D, Jørgensen HL, Christensen J, Tjønneland A, Olsen A, Halkjær J, Lind B, Heegaard AM, Schwarz P. 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.
26. Michaëlsson K, Baron JA, Snellman G, Gedeborg R, Byberg L, Sundström J, Berglund L, Ärnlöv J, Hellman P, Blomhoff R, et al. Plasma Vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 2010;92:841-8.
27. Khaw KT, Luben R, Wareham N. Serum 25-hydroxyVitamin D, mortality, and incident cardiovascular disease, respiratory disease, cancers, and fractures: a 13-y prospective population study. Am J Clin Nutr 2014;100:1361-70.
28. Drechsler C, Pilz S, Obermayer-Pietsch B, Verduijn M, Tomaschitz A, Krane V, Espe K, Dekker F, Brandenburg V, Mrz W, 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.
29. Pilz S, Dobnig H, Fischer JE, Wellnitz B, Seelhorst U, Boehm BO, Mrz W. Low Vitamin D levels predict stroke in patients referred to coronary angiography. Stroke 2008;39:2611-3.
30. Wang L, Song Y, Manson JE, Pilz S, Marz W, Michaelsson K, Lundqvist A, Jassal SK, Barrett-Connor E, Zhang C, et al. Circulating 25-hydroxy-Vitamin D and risk of cardiovascular disease: a metaanalysis of prospective studies. Circ Cardiovasc Qual Outcomes 2012;5:819-29.
31. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB; Meta-analysis Of Observational Studies in Epidemiology (MOOSE) Group. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008-12.
32. Wells GA, Shea B, O'Connell D, Peterson J, Welch V, Losos M, Tugwell P. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses [Internet]. [cited 2017 Jan 8]. Available from: http://www.ohri.ca/programs/clinical-epidemiology/oxford.asp.
33. Berger S, Raman G, Vishwanathan R, Jacques PF, Johnson EJ. Dietary cholesterol and cardiovascular disease: a systematic review and metaanalysis. Am J Clin Nutr 2015;102:276-94.
34. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 1992;135:1301-9.
35. Orsini N, Bellocco R, Greenland S. Generalized least squares for trend estimation of summarized dose-response data. Stata J 2006;6:40-57.
36. Durrleman S, Simon R. Flexible regression models with cubic splines. Stat Med 1989;8:551-61.
37. Bekkering GE, Harris RJ, Thomas S, Mayer AM, Beynon R, Ness AR, Harbord RM, Bain C, Smith GD, Sterne JA. How much of the data published in observational studies of the association between diet and prostate or bladder cancer is usable for meta-analysis? Am J Epidemiol 2008;167:1017-26.
38. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539-58.
39. Duval S, Tweedie R. Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455-63.
40. 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.
41. Kilkkinen A, Knekt P, Aro A, Rissanen H, Marniemi J, Heliövaara M, Impivaara O, Reunanen A. Vitamin D status and the risk of cardiovascular disease death. Am J Epidemiol 2009;170:1032-9.
42. Cawthon PM, Parimi N, Barrett-Connor E, Laughlin GA, Ensrud KE, Hoffman AR, Shikany JM, Cauley JA, Lane NE, Bauer DC, et al. Serum 25-hydroxyVitamin D, parathyroid hormone, and mortality in older men. J Clin Endocrinol Metab 2010;95:4625-34.
43. Hutchinson MS, Grimnes G, Joakimsen RM, Figenschau Y, Jorde R. Low serum 25-hydroxyVitamin D levels are associated with increased all-cause mortality risk in a general population: the Tromsø study. Eur J Endocrinol 2010;162:935-42.
44. Semba RD, Houston DK, Bandinelli S, Sun K, Cherubini A, Cappola AR, Guralnik JM, Ferrucci L. Relationship of 25-hydroxyVitamin D with allcause and cardiovascular disease mortality in older community-dwelling adults. Eur J Clin Nutr 2010;64:203-9.
45. Eaton CB, Young A, Allison MA, Robinson J, Martin LW, Kuller LH, Johnson KC, Curb JD, Van Horn L, McTiernan A, 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.
46. Kestenbaum B, Katz R, de Boer I, Hoofnagle A, Sarnak MJ, Shlipak MG, Jenny NS, Siscovick DS. Vitamin D, parathyroid hormone, and cardiovascular events among older adults. J Am Coll Cardiol 2011;58:1433-41.
47. Kritchevsky SB, Tooze JA, Neiberg RH, Schwartz GG, Hausman DB, Johnson MA, Bauer DC, Cauley JA, Shea MK, Cawthon PM, et al. 25-HydroxyVitamin D, parathyroid hormone, and mortality in black and white older adults: the Health ABC Study. J Clin Endocrinol Metab 2012;97:4156-65.
48. Lin SW, Chen W, Fan JH, Dawsey SM, Taylor PR, Qiao YL, Abnet CC. Prospective study of serum 25-hydroxyVitamin D concentration and mortality in a Chinese population. Am J Epidemiol 2012; 176:1043-50.
49. Messenger W, Nielson CM, Li H, Beer T, Barrett-Connor E, Stone K, Shannon J. Serum and dietary Vitamin D and cardiovascular disease risk in elderly men: a prospective cohort study. Nutr Metab Cardiovasc Dis 2012;22:856-63.
50. Brøndum-Jacobsen P, Nordestgaard Bø G, Schnohr P, Benn M. 25-HydroxyVitamin D and symptomatic ischemic stroke: an original study and meta-analysis. Ann Neurol 2013;73:38-47.
51. Deng X, Song Y, Manson JE, Signorello LB, Zhang SM, Shrubsole MJ, Ness RM, Seidner DL, Dai Q. Magnesium, Vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med 2013; 11:187.
52. Robinson-Cohen C, Hoofnagle AN, Ix JH, Sachs MC, Tracy RP, Siscovick DS, Kestenbaum BR, de Boer IH. Racial differences in the association of serum 25-hydroxyVitamin D concentration with coronary heart disease events. JAMA 2013;310:179-88.
53. Rohrmann S, Braun J, Bopp M, Faeh D. Inverse association between circulating Vitamin D and mortality-dependent on sex and cause of death? Nutr Metab Cardiovasc Dis 2013;23:960-6.
54. Schöttker B, Haug U, Schomburg L, Köhrle J, Perna L, Müller H, Holleczek B, Brenner H. 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;97:782-93.
55. Skaaby T, Husemoen LLN, Pisinger C, Jørgensen T, Thuesen BH, Fenger M, Linneberg A. Vitamin D status and incident cardiovascular disease and all-cause mortality: a general population study. Endocrine 2013;43:618-25.
56. Bansal N, Zelnick L, Robinson-Cohen C, Hoofnagle AN, Ix JH, Lima JA, Shoben AB, Peralta CA, Siscovick DS, Kestenbaum B, 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.
57. Formiga F, Ferrer A, Megido MJ, Boix L, Contra A, Pujol R, Almeda J, Sanz H, Badia T, Lobato A, et al. Low serum Vitamin D is not associated with an increase in mortality in oldest old subjects: the Octabaix Three-Year Follow-up Study. Gerontology 2014;60:10-5.
58. di Giuseppe R, Buijsse B, Hirche F, Wirth J, Arregui M, Westphal S, Isermann B, Hense HW, Dierkes J, Boeing H, et al. Plasma fibroblast growth factor 23, parathyroid hormone, 25-hydroxyVitamin D3, and risk of heart failure: a prospective, case-cohort study. J Clin Endocrinol Metab 2014;99:947-55.
59. Lee DM, Vanderschueren D, Boonen S, O'Neill TW, Pendleton N, Pye SR, Ravindrarajah R, Gielen E, Claessens F, Bartfai G, et al. Association of 25-hydroxyVitamin D, 1,25-dihydroxyVitamin D and parathyroid hormone with mortality among middle-aged and older European men. Age Ageing 2014;43:528-35.
60. Wannamethee SG, Welsh P, Papacosta O, Lennon L, Whincup PH, Sattar N. Elevated parathyroid hormone, but not Vitamin D deficiency, is associated with increased risk of heart failure in older men with and without cardiovascular disease. Circ Heart Fail 2014; 7:732-9.
61. Chien KL, Hsu HC, Chen PC, Lin HJ, Su TC, Chen MF, Lee YT. Total 25-hydroxyVitamin D concentration as a predictor for allcause death and cardiovascular event risk among ethnic Chinese adults: a cohort study in a Taiwan community. PLoS One 2015;10: e0123097.
62. Lutsey PL, Michos ED, Misialek JR, Pankow JS, Loehr L, Selvin E, Reis JP, Gross M, Eckfeldt JH, Folsom AR. Race and Vitamin D binding protein gene polymorphisms modify the association of 25-hydroxyVitamin D and incident heart failure: the ARIC (Atherosclerosis Risk in Communities) study. JACC Heart Fail 2015;3: 347-56.
63. Jassal SK, Chonchol M, von Muhlen D, Smits G, Barrett-Connor E. Vitamin D, parathyroid hormone, and cardiovascular mortality in older adults: the Rancho Bernardo Study. Am J Med 2010;123: 1114-20.
64. Anderson JL, May HT, Horne BD, Bair TL, Hall NL, Carlquist JF, Lappe DL, Muhlestein JB. Relation of Vitamin D deficiency to cardiovascular risk factors, disease status, and incident events in a general healthcare population. Am J Cardiol 2010;106:963-8.
65. 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.
66. Karakas M, Thorand B, Zierer A, Huth C, Meisinger C, Roden M, Rottbauer W, Peters A, Koenig W, Herder C. Low levels of serum 25-hydroxyVitamin D are associated with increased risk of myocardial infarction, especially in women: results from the MONICA/KORA Augsburg case-cohort study. J Clin Endocrinol Metab 2013;98:272-80.
67. Metra M, Carubelli V, Ravera A, Stewart Coats AJ. Heart failure 2016: still more questions than answers. Int J Cardiol 2017;227:766-77.
68. Krumholz HM, Chen YT, Wang Y, Vaccarino V, Radford MJ, Horwitz RI. Predictors of readmission among elderly survivors of admission with heart failure. Am Heart J 2000;139:72-7.
69. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095-128. Erratum in: Lancet 2013;381:628.
70. Schierbeck LL, Rejnmark L, Tofteng CL, Stilgren L, Eiken P, Mosekilde L, Køber L, Jensen JEB. Vitamin D deficiency in postmenopausal, healthy women predicts increased cardiovascular events: a 16-year follow-up study. Eur J Endocrinol 2012;167:553-60.
71. Motiwala SR, Wang TJ. Vitamin D and cardiovascular risk. Curr Hypertens Rep 2012;14:209-18.
72. Ajabshir S, Asif A, Nayer A. The effects of Vitamin D on the reninangiotensin system. J Nephropathol 2014;3:41-3.
73. Al Mheid I, Patel RS, Tangpricha V, Quyyumi AA. Vitamin D and cardiovascular disease: is the evidence solid? Eur Heart J 2013;34: 3691-8.
74. Jouni ZE, Winzerling JJ, McNamara DJ. 1,25-DihydroxyVitamin D3-induced HL-60 macrophages: regulation of cholesterol and LDL metabolism. Atherosclerosis 1995;117:125-38.
75. Timms PM, Mannan N, Hitman GA, Noonan K, Mills PG, Syndercombe-Court D, Aganna E, Price CP, Boucher BJ. Circulating MMP9, Vitamin D and variation in the TIMP-1 response with VDR genotype: mechanisms for inflammatory damage in chronic disorders? QJM 2002; 95:787-96.
76. Mao PJ, Zhang C, Tang L, Xian YQ, Li YS, Wang WD, Zhu XH, Qiu HL, He J, Zhou YH. Effect of calcium or Vitamin D supplementation on vascular outcomes: a meta-analysis of randomized controlled trials. Int J Cardiol 2013;169:106-11.
77. Haddad JG Jr., Hahn TJ. Natural and synthetic sources of circulating 25-hydroxyVitamin D in man. Nature 1973;244:515-7.
78. Scragg R. Vitamin D and public health: an overview of recent research on common diseases and mortality in adulthood. Public Health Nutr 2011;14:1515-32.