title: Associations of Serum 25-Hydroxyvitamin D With Hemostatic and Inflammatory Biomarkers in the Multi-Ethnic Study of Atherosclerosis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Cross-sectional analyses.
  
  
  METHODS
  The Multi-Ethnic Study of Atherosclerosis, a multicenter prospective cohort of American adults.
  
  
  METHODS
  Up to 6554 adults free of CVD.
  
  
  METHODS
  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/m(2)) 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.
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Marc
authors.initials: M
authors.lastname: Blondon
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Nancy
authors.initials: N
authors.lastname: Jenny
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Erin D
authors.initials: ED
authors.lastname: Michos
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Bryan
authors.initials: B
authors.lastname: Kestenbaum
authors.affiliation: Division of Angiology and Hemostasis (M.B.), Geneva University Hospitals and Faculty of Medicine, 1205 Geneva, Switzerland; Department of Medicine and Pathology & Laboratory Medicine (M.C.), University of Vermont College of Medicine, Burlington, Vermont 05401; Department of Pathology & Laboratory Medicine (N.J.), University of Vermont College of Medicine, Burlington, Vermont 05446; Department of Medicine (Cardiology) (E.D.M.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Department of Epidemiology (N.L.S.), University of Washington, Seattle, Washington 98195; Group Health Research Institute (N.L.S.), Group Health Cooperative, Seattle, Washington 98112; Seattle Epidemiologic Research and Information Center (N.L.S.), Veterans Affairs Office of Research and Development, Seattle, Washington 98108; and Department of Epidemiology and Nephrology (B.K., I.H.d.B.), University of Washington, Seattle, Washington 98195.
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D044383:Black People; D005260:Female; D006487:Hemostasis / Q000502:physiology*; D006630:Hispanic or Latino; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D044465:White People
chemical_list: D015415:Biomarkers; D014807:Vitamin D; C104450:25-hydroxyvitamin D