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Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis

Blondon, Marc ; Cushman, Mary ; Jenny, Nancy ; Michos, Erin D. ; Smith, Nicholas L. ; Kestenbaum, Bryan ; de Boer, Ian H.

In: The Journal of Clinical Endocrinology & Metabolism, 2016, vol. 101, no. 6, p. 2348-2357

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    Title
    • Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis
    Author
    • Blondon, Marc. Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland
    • Cushman, Mary. Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401
    • Jenny, Nancy. Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446
    • Michos, Erin D.. Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287
    • Smith, Nicholas L.. Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195
    • Kestenbaum, Bryan. Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195
    • de Boer, Ian H.. Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195
    Document Type
    • Postprint
    Language
    • English
    Published in
    • The Journal of Clinical Endocrinology & Metabolism, 2016, vol. 101, no. 6, p. 2348-2357. Oxford University Press
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:332295
    Summary
    Abstract Context: Mechanisms explaining documented associations of 25-hydroxyvitamin D [25(OH)D] deficiency with increased risks of cardiovascular disease (CVD) and venous thromboembolism may relate to adverse hemostatic and inflammatory responses. Objective: To evaluate whether 25(OH)D deficiency is associated with a prothrombotic and proinflammatory biological profile. Design: Cross-sectional analyses. Setting: The Multi-Ethnic Study of Atherosclerosis, a multicenter prospective cohort of American adults. Participants: Up to 6554 adults free of CVD. Main Outcome Measures: Ten hemostatic biomarkers (D-dimer, fibrinogen, factor VIII, plasmin-antiplasmin, and homocysteine [n = 6443]; von Willebrand factor, soluble tissue factor, plasminogen activator inhibitor-1 (PAI-1), total tissue factor pathway inhibitor (TFPI), and soluble thrombomodulin [n = 814]), and three inflammatory biomarkers (IL-6, C-reactive protein [n = 6443], and TNF-α soluble receptor [n = 3802]). Results: Among 6443 subjects (46.6% men; mean age, 62.1 years; mean body mass index, 28.3 kg/m2) of White (37.8%), Black (27.2%), Chinese (12.2%), and Hispanic (21.8%) race/ethnicity, mean 25(OH)D was 25.3 ng/mL. After multiple adjustment, 25(OH)D concentrations were associated with concentrations of IL-6 and homocysteine and also with concentrations of PAI-1 and TFPI: per 10 ng/mL decrement in 25(OH)D, 5.1% higher IL-6 (95% confidence interval [CI], 3.4-6.9; P < .001); 3.7% higher homocysteine (95% CI, 3.0-4.3; P < .001); 7.0% higher PAI-1 (95% CI, 0.9-13.6; P = .025); and 2.1% higher TFPI (95% CI, 0.0-4.2; P = .047), without racial/ethnic heterogeneity. No significant associations were observed for other hemostatic and inflammatory biomarkers. Conclusions: Increased inflammation as reflected by higher circulating IL-6 and increased homocysteine concentrations may represent mechanisms linking 25(OH)D deficiency to greater risks of CVD and perhaps venous thromboembolism. Low concentrations of 25(OH)D were also associated with PAI-1 and TFPI concentrations, but not with other hemostatic biomarkers.