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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

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Volume 50, Issue 12


Vitamin D deficiency parallels inflammation and immune activation, the Ludwigshafen Risk and Cardiovascular Health (LURIC) study

Christian Murr / Stefan Pilz
  • Division of Endocrinology and Metabolism, Department of Internal Medicine, Graz Medical University, Graz, Austria
  • Other articles by this author:
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/ Tanja B. Grammer
  • Mannheim Medical Faculty, Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Marcus E. Kleber
  • Mannheim Medical Faculty, Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany
  • LURIC Study Nonprofit LLC, Freiburg, Germany
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  • De Gruyter OnlineGoogle Scholar
/ Andreas Meinitzer
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
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/ Bernhard O. Boehm
  • Division of Endocrinology and Diabetes, Department of Medicine, University Hospital, Ulm, Germany
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/ Winfried März
  • Mannheim Medical Faculty, Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany
  • Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria
  • Synlab Center of Laboratory Diagnostics Heidelberg, Heidelberg, Germany
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dietmar Fuchs
Published Online: 2012-07-13 | DOI: https://doi.org/10.1515/cclm-2012-0157


Background: Low vitamin D concentrations are detected in patients suffering from various clinical conditions which are characterized also by inflammation and immune activation. We investigated whether vitamin D levels in patients with coronary artery disease (CAD) are related to markers of immune activation.

Methods: Serum concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the immune activation markers neopterin and high sensitivity C-reactive protein (hsCRP) were measured in 2015 patients derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study, a cohort study among patients referred for coronary angiography.

Results: Serum concentrations of 25(OH)D and 1,25(OH)2D did not differ between patients with CAD [mean±SD: 25(OH)D: 17.4±9.4 μg/L; 1,25(OH)2D: 34.4±13.3 ng/L] and controls [25(OH)D: 18.4±11.7 μg/L; 1,25(OH)2D: 35.3±12.7 ng/L; Welch’s t-test: p=n.s.] but CAD patients had higher neopterin (8.6±7.4 nmol/L) and hsCRP (9.6±19.6 mg/L) concentrations compared to controls (neopterin: 7.5±4.8 nmol/L; p=0.0004; hsCRP: 5.4±10.0 mg/L; p<0.0001). There was an inverse correlation between serum 25(OH)D or 1,25(OH)2D concentrations and serum neopterin [Spearman’s rank correlation: 25(OH)D: rs=–0.183; 1,25(OH)2D: rs=–0.230] and hsCRP [25(OH)D: rs=–0.142; 1,25(OH)2D: rs=–0.130; all p<0.0001] concentrations.

Conclusions: Our results indicate increased inflammatory processes in patients with low vitamin D status. Further studies should clarify the underlying mechanisms for the observed associations of vitamin D status and inflammatory parameters.

Keywords: coronary artery disease; creatinine; C-reactive protein; cystatin C; neopterin; vitamin D


  • 1.

    Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.Google Scholar

  • 2.

    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.Web of ScienceGoogle Scholar

  • 3.

    Zhang R, Naughton DP. Vitamin D in health and disease: current perspectives. Nutr J 2010;9:65.CrossrefPubMedGoogle Scholar

  • 4.

    Wolf G. The discovery of vitamin D: the contribution of Adolf Windaus. J Nutr 2004;134:1299–302.Google Scholar

  • 5.

    Cavalier E, Delanaye P, Chapelle JP, Souberbielle JC. Vitamin D: current status and perspectives. Clin Chem Lab Med 2009;47:120–7.Web of ScienceGoogle Scholar

  • 6.

    Tomaschitz A, Pilz S, Ritz E, Grammer T, Drechsler C, Boehm BO, et al. 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 2010;411:1354–60.Web of ScienceGoogle Scholar

  • 7.

    Pilz S, Tomaschitz A, Friedl C, Amrein K, Drechsler C, Ritz E, et al. Vitamin D status and mortality in chronic kidney disease. Nephrol Dial Transplant 2011;11:3603–9.Google Scholar

  • 8.

    Murr C, Widner B, Wirleitner B, Fuchs D. Neopterin as a marker for immune system activation. Curr Drug Metab 2002;3:175–7.PubMedCrossrefGoogle Scholar

  • 9.

    Grammer TB, Fuchs D, Boehm BO, Winkelmann BR, Maerz W. Neopterin as a predictor of total and cardiovascular mortality in individuals undergoing angiography in the Ludwigshafen Risk and Cardiovascular Health study. Clin Chem 2009;55: 1135–46.PubMedCrossrefGoogle Scholar

  • 10.

    Fuchs D, Avanzas P, Arroyo-Espliguero R, Jenny M, Consuegra Sanchez L, Kaski JC. The role of neopterin in atherogenesis and cardiovascular risk stratification. Curr Med Chem 2009;16:4644–53.CrossrefGoogle Scholar

  • 11.

    Haug C, Müller F, Aukrust P, Frøland SS. Subnormal serum concentration of 1,25-vitamin D in human immunodeficiency virus infection: correlation with degree of immune deficiency and survival. J Infect Dis 1994;169:889–93.Google Scholar

  • 12.

    Scragg R, Wishart J, Stewart A, Ofanoa M, Kerse N, Dyall L, et al. No effect of ultraviolet radiation on blood pressure and other cardiovascular risk factors. J Hypertens 2011;29:1749–56.Web of ScienceCrossrefPubMedGoogle Scholar

  • 13.

    Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, et al. Rationale and design of the LURIC study: a resource for functional genomics, pharmacogenomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2001;2: S1–73.CrossrefGoogle Scholar

  • 14.

    Austen WG, Edwards JE, Frye RL, Gensini GG, Gott VL, Griffith LS, et al. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for Grading of Coronary Artery Disease, Council on Cardiovascular Surgery, American Heart Association. Circulation 1975;51(Suppl 4):5–40.Google Scholar

  • 15.

    Pilz S, Tomaschitz A, Drechsler C, Ritz E, Boehm BO, Grammer TB, et al. Parathyroid hormone level is associated with mortality and cardiovascular events in patients undergoing coronary angiography. Eur Heart J 2010;31:1591–8.CrossrefWeb of SciencePubMedGoogle Scholar

  • 16.

    Goswami R, Gupta N, Goswami D, Marwaha RK, Tandon N, Kochupillai N. Prevalence and significance of low 25-hydoxyvitamin D concentrations in healthy subjects in Delhi. Am J Clin Nutr 2000;72:472–5.Google Scholar

  • 17.

    Stevens LA, Coresh J, Schmid CH, Feldman HI, Froissart M, Kusek J, et al. Estimating GFR using serum cystatin C alone and in combination with serum creatinine: a pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 2008;51:395–406.Web of ScienceGoogle Scholar

  • 18.

    Murr C, Winklhofer-Roob BM, Schroecksnadel K, Maritschnegg M, Mangge H, Böhm BO, et al. Inverse association between serum concentrations of neopterin and antioxidants in patients with and without angiographic coronary artery disease. Atherosclerosis 2009;202:543–9.Web of ScienceGoogle Scholar

  • 19.

    Murr C, Pilz S, Grammer TB, Kleber ME, Böhm BO, März W, et al. Low serum zinc levels in patients undergoing coronary angiography correlate with immune activation and inflammation. J Trace Elem Med Biol 2012;26:26–30.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 20.

    Murr C, Talasz H, Artner-Dworzak E, Schroecksnadel K, Fiegl M, Fuchs D, et al. Inverse association between serum selenium concentrations and parameters of immune activation in patients with cardiac disorders. Clin Chem Lab Med 2007;45:1224–8.Web of ScienceGoogle Scholar

  • 21.

    Libby P, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation 1999;100:1148–50.Google Scholar

  • 22.

    Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med 1983;158:670–89.Google Scholar

  • 23.

    Fuchs D, Baier-Bitterlich G, Wede I, Wachter H. Reactive oxygen and apoptosis. In: Scandalios J, editor. Oxidative stress and the molecular biology of antioxidant defenses. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press, 1997: 139–67.Google Scholar

  • 24.

    Murr C, Fuith L-C, Widner B, Wirleitner B, Baier-Bitterlich G, Fuchs D. Increased neopterin concentrations in patients with cancer: indicator of oxidative stress? Anticancer Res 1999;19:1721–8.PubMedGoogle Scholar

  • 25.

    Schroecksnadel S, Jenny M, Kurz K, Klein A, Ledochowski M, Ueberall F, et al. LPS-induced NF-kappaB expression in THP-1Blue cells correlates with neopterin production and activity of indoleamine 2,3-dioxygenase. Biochem Biophys Res Commun 2010;399:642–6.Web of ScienceGoogle Scholar

  • 26.

    Overbergh L, Stoffels K, Waer M, Verstuyf A, Bouillon R, Mathieu C. Immune regulation of 25-hydroxyvitamin D-1a-hydroxylase in human monocytic THP1 cells: mechanisms of interferon-gamma-mediated induction. J Clin Endocrinol Metab 2006;91:3566–74.Google Scholar

  • 27.

    Zittermann A, Frisch S, Berthold HK, Götting C, Kuhn J, Kleesiek K, et al. Vitamin D supplementation enhances the beneficial effects of weight loss on cardiovascular disease risk markers. Am J Clin Nutr 2009;89:1321–7.Web of ScienceGoogle Scholar

  • 28.

    Witham MD, Crighton LJ, Gillespie ND, Struthers AD, McMurdo ME. 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 2010;3: 195–201.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 29.

    Geldmeyer-Hilt K, Heine G, Hartmann B, Baumgrass R, Radbruch A, Worm M. 1,25-Dihydroxyvitamin D3 impairs NF-κB activation in human naïve B cells. Biochem Biophys Res Commun 2011;407:699–702.Web of ScienceGoogle Scholar

  • 30.

    Chen Y, Kong J, Sun T, Li G, Szeto FL, Liu W, et al. 1,25-Dihydroxyvitamin D3 suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-κB activation. Arch Biochem Biophys 2011;507:241–7.Web of ScienceGoogle Scholar

  • 31.

    Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J Biol Chem 2003;278:38084–93.Google Scholar

  • 32.

    Zehnder D, Hewison M. The renal function of 25-hydroxyvitamin D3-1a-hydroxylase. Mol Cell Endocrinol 1999;151:213–20.Google Scholar

  • 33.

    Neurauter G, Schröcksnadel K, Scholl-Bürgi S, Sperner-Unterweger B, Schubert C, Ledochowski M, et al. Chronic immune stimulation correlates with reduced phenylalanine turnover. Curr Drug Metab 2008;9:622–7.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 34.

    Zangerle R, Kurz K, Neurauter G, Kitchen M, Sarcletti M, Fuchs D. Increased blood phenylalanine to tyrosine ratio in HIV-1 infection and correction following effective antiretroviral therapy. Brain Behav Immun 2010;24:403–8.Web of SciencePubMedGoogle Scholar

  • 35.

    Fuchs JE, Huber RG, Wallnoefer HG, Von Grafenstein S, Spitzer GM, Fuchs D, et al. Side chain oxidation modulates local dynamics of phenylalanine hydroxylase. Pteridines 2011;23:31–2.Google Scholar

  • 36.

    Schroeder BO, Wu Z, Nuding S, Groscurth S, Marcinowski M, Beisner J, et al. Reduction of disulphide bonds unmasks potent antimicrobial activity of human β-defensin 1. Nature 2011;469:419–23.Web of ScienceGoogle Scholar

  • 37.

    Moriyama Y, Yasue H, Yoshimura M, Mizuno Y, Nishiyama K, Tsunoda R, et al. The plasma levels of dehydroepiandrosterone are decreased in patients with chronic heart failure in proportion to the severity. J Clin Endocrinol Metab 2000;85:1834–40.Google Scholar

  • 38.

    Wede I, Fuchs D, Barker JE, Clark JB, Heales JR. Neopterin and 7,8-dihydroneopterin modulate peroxynitrite-induced inhibition of mitochondrial function. In: Pfleiderer W, Rokos H, editors. Chemistry and biology of pteridines and folates. Berlin: Blackwell Science, 1997:803–6.Google Scholar

  • 39.

    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.Web of SciencePubMedCrossrefGoogle Scholar

About the article

Corresponding author: Dietmar Fuchs, Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innrain 80, 6020 Innsbruck, Austria Phone: +43 512 9003 70350, Fax: +43 512 9003 73330

Received: 2012-03-14

Accepted: 2012-06-14

Published Online: 2012-07-13

Published in Print: 2012-12-01

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 50, Issue 12, Pages 2205–2212, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/cclm-2012-0157.

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