25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: A cross sectional analysis in the 1958 british birth cohort

Background: Vitamin D deficiency has been suggested as a cardiovascular risk factor, but little is known about underlying mechanisms or associations with inflammatory or hemostatic markers. Our aim was to investigate the association between 25-hydroxyvitamin D [25(OH)D, a measure for vitamin D status] concentrations with pre-clinical variations in markers of inflammation and hemostasis. Methodology/Principal Findings: Serum concentrations of 25(OH)D, C-reactive protein (CRP), fibrinogen, D-dimer, tissue plasminogen activator (tPA) antigen, and von Willebrand factor (vWF) were measured in a large population based study of British whites (aged 45y). Participants for the current investigation were restricted to individuals free of drug treated cardiovascular disease (n = 6538). Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p≤0.015 for all), but associations with CRP, fibrinogen, and vWF were explained by adiposity. Association with tPA persisted after full adjustment (body mass index, waist circumference, physical activity, TV watching, smoking, alcohol consumption, social class, sex, and month), and average concentrations were 18.44% (95% CI 8.13, 28.75) lower for 25(OH)D ≥75 nmol/l compared to <25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50-90nmol/l compared to others (quadratic term p = 0.01). We also examined seasonal variation in hemostatic and inflammatory markers, and evaluated 25(OH)D contribution to the observed patterns using mediation models. TPA concentrations varied by season (p = 0.02), and much of this pattern was related to fluctuations in 25(OH)D concentrations (p≤0.001). Some evidence of a seasonal variation was observed also for fibrinogen, D-dimer and vWF (p<0.05 for all), with 25(OH)D mediating some of the pattern for fibrinogen and D-dimer, but not vWF. Conclusions: Current vitamin D status was associated with tPA concentrations, and to a lesser degree with fibrinogen and D-dimer, suggesting that vitamin D status/intake may be important for maintaining antithrombotic homeostasis.