TY - JOUR
T1 - Associations of serum 25-hydroxyvitamin d with hemostatic and inflammatory biomarkers in the multi-ethnic study of atherosclerosis
AU - Blondon, Marc
AU - Cushman, Mary
AU - Jenny, Nancy
AU - Michos, Erin D.
AU - Smith, Nicholas L.
AU - Kestenbaum, Bryan
AU - De Boer, Ian H.
N1 - Funding Information:
This research was supported by National Heart, Lung, and Blood Institute and by Grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources
Publisher Copyright:
© 2016 by the Endocrine Society.
PY - 2016/6
Y1 - 2016/6
N2 - 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, plasminantiplasmin, 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.
AB - 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, plasminantiplasmin, 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.
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U2 - 10.1210/jc.2016-1368
DO - 10.1210/jc.2016-1368
M3 - Article
C2 - 27023449
AN - SCOPUS:84973539409
SN - 0021-972X
VL - 101
SP - 2348
EP - 2357
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 6
ER -