Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients

  • Susana Mellor-Pita
  • Pablo Tutor-Ureta
  • Silvia Rosado
  • Khusama Alkadi
  • Fernando Granado
  • Carlos Jimenez-Ortiz
  • Raquel CastejonEmail author
Original Article



Low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with a higher frequency of risk factors and cardiovascular disease. The aim of this study is to evaluate the association of 25(OH)D, cardiovascular risk factors, and subclinical atherosclerosis in systemic lupus erythematosus (SLE) patients.


Forty-seven female SLE patients were studied. Data collected included demographics, SLE activity, disease damage, cardiovascular risk factors, and markers of subclinical atherosclerosis. Patient treatments and vitamin D and calcium supplementation (VitD-Ca) were recorded. Vitamin D deficiency was defined as serum 25(OH)D < 50 nmol/l measured by ultra-high-performance liquid chromatography. Atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry and intima-media thickness (IMT) by B-mode ultrasound scanning.


61.7% of patients were vitamin D deficient with a mean level of 31.91 ± 10.21 nmol/l. Serum vitamin D concentration was significantly higher in the 23 patients taking VitD-Ca supplements than that in patients not supplemented (p = 0.004). No significant association was found between 25(OH)D serum levels and cardiovascular risk factors, disease activity, or different treatments for SLE. A significant positive correlation was found between 25(OH)D levels, PWV (p = 0.02), and IMT (p = 0.01); moreover, patients taking VitD-Ca supplements presented an increased arterial stiffness.


Patients with arterial stiffness showed higher levels of serum vitamin D and most of them were on VitD-Ca supplements. Although prospective studies with a larger number of patients and follow-up are needed, our findings suggest that VitD-Ca supplementation may have effects on SLE patients’ arterial stiffness.


25-Hydroxyvitamin D Subclinical atherosclerosis Systemic lupus erythematosus Vit D-calcium supplementation 



We acknowledge the technical assistance of Concepcion Lorences and Gloria Peraile and data analysis support from Isabel Millan in the Biostatistics Department.

Funding information

This work has been supported by a grant from Instituto de Salud Carlos III, Spain (expedient PI16/01480).

Compliance with ethical standards

The study was approved by the Research Ethics Committee of the Hospital Universitario Puerta de Hierro and written informed consent was obtained from all participants.




  1. 1.
    Urowitz MB, Bookman AAM, Koehler BE, Gordon DA, Smythe HA, Ogryzlo MA (1976) The bimodal mortality pattern of systemic lupus erythematosus. Am J Med 60:221–225CrossRefGoogle Scholar
  2. 2.
    Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, D’Agostino RB, Kuller LH (1997) Age-specific rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am J Epidemiol 145:408–415CrossRefGoogle Scholar
  3. 3.
    Petri M, Perez-Gutthann S, Spence D, Hochberg M (1992) Risk factors for coronary artery disease in patients with systemic lupus erythematosus. Am J Med 93:513–519CrossRefGoogle Scholar
  4. 4.
    Bruce IN, Urowitz M, Gladman D, Ibañez D, Steiner G (2003) Risk factors for coronary heart disease in women with systemic lupus erythematosus. Arthritis Rheum 48:3159–3167CrossRefGoogle Scholar
  5. 5.
    Esdaile JM, Abrahamowicz M, Grodzicky T, Li Y, Panaritis C, du Berger R, Côte R, Grover SA, Fortin PR, Clarke AE, Senécal JL (2001) Traditional Framingham risk factors fail to fully account for accelerated atherosclerosis in systemic lupus erythematosus. Arthritis Rheum 44:2331–2337CrossRefGoogle Scholar
  6. 6.
    Holick MF (2007) Vitamin D deficiency. N Engl J Med 357:266–281CrossRefGoogle Scholar
  7. 7.
    Hewison M (2010) Vitamin D and the immune system: new perspectives on and old theme. Endocrinol Metab Clin N Am 39:365–379CrossRefGoogle Scholar
  8. 8.
    Martins D, Wolf M, Pan D, Zadshir A, Tareen N, Thadhani R, Felsenfeld A, Levine B, Mehrotra R, Norris K (2007) Prevalence of cardiovascular risk factors and the serum levels of 25-hydroxyvitamina D in the United States: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 167:1159–1165CrossRefGoogle Scholar
  9. 9.
    Kunutsor SK, Apekey TA, Steur M (2013) Vitamin D and risk of future hypertension: meta-analysis of 283-537 participants. Eur J Epidemiol 28:205–211CrossRefGoogle Scholar
  10. 10.
    Song Y, Wang L, Pittas AG, Del Gobbo LC, Zhang C, Manson JE, Hu FB (2013) Blood 25-hydroxyvitamin D levels and incident type 2 diabetes: a meta-analysis of prospective studies. Diabetes Care 36:1422–1428CrossRefGoogle Scholar
  11. 11.
    Skaaby T, Husemoen LL, Pisinger C, Jørgensen T, Thuesen BH, Rasmussen K, Fenger M, Rossing P, Linneberg A (2013) Vitamin D status and 5-year changes in urine albumin creatinine ratio and parathyroid hormone in a general population. Endocrine 44:473–480CrossRefGoogle Scholar
  12. 12.
    Watson KE, Abrolat ML, Malone LL, Hoeg JM, Doherty T, Detrano R, Demer LL (1997) Active serum vitamin D levels are inversely correlated with coronary calcification. Circulation 96:1755–1760CrossRefGoogle Scholar
  13. 13.
    Jablonski KL, Chonchol M, Pierce GL, Walker AE, Seals DR (2011) 25-hydroxyvitamin D deficiency is associated with inflammation-linked vascular endothelial in middle-aged and older adults. Hypertension 57:63–69CrossRefGoogle Scholar
  14. 14.
    Giovannucci E, Liu Y, Hollis BW, Rimm EB (2008) 25-Hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 168:1174–1180CrossRefGoogle Scholar
  15. 15.
    Kendrick J, Targher G, Smits G, Chonchol M (2009) 25-Hydroxyvitamin D deficiency is independently associated with cardiovascular disease in the Third National Health and Nutrition Examination Survey. Atherosclerosis 205:255–260CrossRefGoogle Scholar
  16. 16.
    Nsengiyumva V, Fernando ME, Moxon JV, Krishna SM, Pinchbeck J, Omer SM, Morris DR, Jones RE, Moran CS, Seto SW, Golledge J (2015) The association of circulating 25-hydroxyvitamin D concentration with peripheral arterial disease: a meta-analysis of observational studies. Atherosclerosis 243:645–651CrossRefGoogle Scholar
  17. 17.
    Sun Q, Pan A, Hu FB, Manson JE, Rexrode KM (2012) 25-hydroxyvitamin D levels and the risk of stroke: a prospective study and meta-analysis. Stroke 43:1470–1477CrossRefGoogle Scholar
  18. 18.
    Kamen DL, Cooper GS, Bouali H, Shaftman SR, Hollis BW, Gilkeson GS (2006) Vitamin D deficiency in systemic lupus erythematosus. Autoimmun Rev 5:114–117CrossRefGoogle Scholar
  19. 19.
    Borba V, Vieira JG, Kasamatsu T, Radominski SC, Sato E, Lazaretti-Castro M (2009) Vitamin D deficiency in patients with active systemic lupus erythematosus. Osteoporosis Int 20:427–433CrossRefGoogle Scholar
  20. 20.
    Amital H, Szekanecz Z, Szücs G, Dankó K, Nagy E, Csépány T, Kiss E, Rovensky J, Tuchynova A, Kozakova D, Doria A, Corocher N, Agmon-Levin N, Barak V, Orbach H, Zandman-Goddard G, Shoenfeld Y (2010) Serum concentrations of 25-OH vitamin D in patients with systemic lupus erythematosus (SLE) are inversely related to disease activity: is it time to routinely supplement patients with SLE with vitamin D? Ann Rheum Dis 69:1155–1157CrossRefGoogle Scholar
  21. 21.
    Wu PW, Rhew EY, Dyer AR, Dunlop DD, Langman CB, Price H, Sutton-Tyrrell K, McPherson DD, Edmundowicz D, Kondos GT, Ramsey-Goldman R (2009) 25-Hydroxyvitamin D and cardiovascular risk factors in women with systemic lupus eryhematosus. Arthritis Rheum 61:1387–1395CrossRefGoogle Scholar
  22. 22.
    Cusack C, Danby C, Fallon JC, Ho WL, Murray B, Brady J, O’Kelly P, Ambrose N, Kearns G, Murphy GM (2008) Photoprotective behaviour and sunscreen use: impact on vitamin D levels in cutaneous lupus erythematosus. Photodermatol Photoimmunol Photomed 24:260–267CrossRefGoogle Scholar
  23. 23.
    Reference Values for Arterial Stiffness’ Collaboration (2010) Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’. Eur Heart J 31:2338–2350CrossRefGoogle Scholar
  24. 24.
    Ruiz-Irastorza G, Egurbide V, Olivares N, Martínez-Berriotxoa A, Aguirre C (2008) Vitamin D deficiency in systemic lupus erythematosus: prevalence, predictors and clinical consequences. Rheumatology 47:920–923CrossRefGoogle Scholar
  25. 25.
    Lopez-Robles C, Rios-Fernandez R, Callejas-Rubio JL, Ortego-Centeno N (2011) Vitamin D deficiency in a cohort of patients with systemic lupus erythematosus from the South of Spain. Lupus 20:330–331CrossRefGoogle Scholar
  26. 26.
    Reynolds JA, Haque S, Berry JL, Pemberton P, Teh LS, Ho P, Gorodkin R, Bruce IN (2012) 25-Hydroxivitamin D deficiency is associated with increased aortic stiffness in patients with systemic lupus erythematosus. Rheumatology 51:544–551CrossRefGoogle Scholar
  27. 27.
    Lertratanakul A, Wu P, Dyer A, Urowitz M, Gladman D, Fortin P, Bae SC, Gordon C, Clarke A, Bernatsky S, Hanly JG, Isenberg D, Rahman A, Merrill J, Wallace DJ, Ginzler E, Khamashta M, Bruce I, Nived O, Sturfelt G, Steinsson K, Manzi S, Dooley MA, Kalunian K, Petri M, Aranow C, Font J, van Vollenhoven R, Stoll T, Ramsey-Goldman R (2014) 25-hydroxyvitamin D and cardiovascular disease in patients with systemic lupus erythematosus: data from a large international inception cohort. Arthritis Care Res (Hoboken) 66:1167–1176CrossRefGoogle Scholar
  28. 28.
    Mok CC, Birmingham DJ, Leung HW, Hebert LA, Song H, Rovin BH (2012) Vitamin D levels in Chinese patients with systemic lupus erythematosus: relationship with disease activity, vascular risk factors and atherosclerosis. Rheumatology (Oxford) 51:644–652CrossRefGoogle Scholar
  29. 29.
    Karimzadeh H, Shirzadi M, Karimifar M (2017) The effect of vitamin D supplementation in disease activity of systemic lupus erythematosus patients with vitamin D deficiency: a randomized clinical trial. J Res Med Sci 22:4CrossRefGoogle Scholar
  30. 30.
    Sabio JM, Vargas-Hitos JA, Martinez Bordonado J, Mediavilla-Garcia JD (2018) Association between non-dipper hypertension and vitamin D deficiency in women with systemic lupus erythematosus. Clin Exp Rheumatol Aug 29Google Scholar
  31. 31.
    García-Carrasco M, Mendoza-Pinto C, Ayón-Aguilar J, Soto-Santillán P, Rodríguez-Gallegos A, Escamilla-Márquez MA, Méndez-Martínez S (2016) Serum levels of vitamin D in systemic lupus erythematosus patients (SLE) and their relationship with disease activity: longitudinal study. Gac Med Mex 152(Suppl 2):32–37Google Scholar
  32. 32.
    Reis JP, von Mühlen D, Michos ED, Miller ER 3rd, Appel LJ, Araneta MR, Barrett-Connor E (2009) Serum vitamin D, parathyroid hormone levels and carotid atherosclerosis. Atherosclerosis 207:585–590CrossRefGoogle Scholar
  33. 33.
    De Boer IH, Kestenbaum B, Shoben AB, Michos ES, Sarnak MJ, Siscovick DS (2009) 25-Hydroxyvitamin D levels inversely associate with risk for developing coronary artery calcification. J Am Soc Nephrol 20:1805–1812CrossRefGoogle Scholar
  34. 34.
    Brandenburg VM, Vervloet MG, Marx N (2012) The role of vitamin D in cardiovascular disease: from present evidence to future perspectives. Atherosclerosis 225:253–263CrossRefGoogle Scholar
  35. 35.
    Zittermann A, Kuhn J, Dreier J, Knabbe C, Gummert JF, Börgermann J (2013) Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur Heart J 34:1358–1364CrossRefGoogle Scholar
  36. 36.
    Durup D, Jørgensen HL, Christensen J, Tjønneland A, Olsen A, Halkjær J, Lind B, Heegaard AM, Schwarz P (2015) A reverse J-shaped association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: the CopD Study. J Clin Endocrinol Metab 100:2339–2346CrossRefGoogle Scholar
  37. 37.
    Ravenell RL, Kamen DL, Spence JD, Hollis BW, Fleury TJ, Janech MG, Almeida JS, Shaftman SR, Oates JC (2012) Premature atherosclerosis is associated with hypovitaminosis D and angiotensin-converting enzyme inhibitor non-use in lupus patients. Am J Med Sci 344:268–273CrossRefGoogle Scholar
  38. 38.
    Sabio JM, Vargas-Hitos JA, Martinez-Bordonado J, Navarrete-Navarrete N, Díaz-Chamorro A, Olvera-Porcel C, Zamora M, Jiménez-Alonso J (2015) Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus. Lupus 24:155–163CrossRefGoogle Scholar
  39. 39.
    Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 341:c3691CrossRefGoogle Scholar
  40. 40.
    Reid IR, Bristow SM, Bolland MJ (2015) Calcium supplements: benefits and risks. J Intern Med 278:354–368CrossRefGoogle Scholar
  41. 41.
    Reid IR, Gamble GD, Bolland MJ (2016) Circulating calcium concentrations, vascular disease and mortality: a systematic review. J Intern Med 279:524–540CrossRefGoogle Scholar
  42. 42.
    Norman PE, Powell JT (2014) Vitamin D and cardiovascular disease. Circ Res 114:379–393CrossRefGoogle Scholar
  43. 43.
    Hsia J, Heiss G, Ren H, Allison M, Dolan NC, Greenland P, Heckbert SR, Johnson KC, Manson JE, Sidney S, Trevisan M, Women’s Health Initiative Investigators (2007) Calcium/vitamin D supplementation and cardiovascular events. Circulation 115:846–1854CrossRefGoogle Scholar
  44. 44.
    Manson JE, Allison MA, Carr JJ, Langer RD, Cochrane BB, Hendrix SL, Hsia J, Hunt JR, Lewis CE, Margolis KL, Robinson JG, Rodabough RJ, Thomas AM, Women’s Health Initiative and Women’s Health Initiative-Coronary Artery Calcium Study Investigators (2010) Calcium/vitamin D supplementation and coronary artery calcification in the women’s health initiative. Menopause 17:683–691Google Scholar
  45. 45.
    Bolland MJ, Grey A, Avenell A, Gamble GD, Reid IR (2011) Calcium supplements with or without vitamin D and risk of cardiovascular even: reanalysis of the women’s health initiative limited access dataset and meta-analysis. BMJ 342:d2040CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Systemic Autoimmune Diseases Unit, Internal Medicine Service, IDIPHIM (University Hospital Puerta de Hierro Research Institute)Hospital Universitario Puerta de Hierro MajadahondaMajadahondaSpain
  2. 2.Biochemistry ServiceHospital Universitario Puerta de Hierro MajadahondaMajadahondaSpain
  3. 3.Neurology ServiceHospital Universitario Puerta de Hierro MajadahondaMajadahondaSpain

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