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25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: a cross sectional analysis in the 1958 British Birth Cohort.

Hyppönen E, Berry D, Cortina-Borja M, Power C - PLoS ONE (2010)

Bottom Line: Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p < or =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 > or =75 nmol/l compared to < 25 nmol/l.D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/l compared to others (quadratic term p = 0.01).

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Centre for Epidemiology of Child Health and Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, UK. e.hypponen@ich.ucl.ac.uk

ABSTRACT

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 45 y). 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 < or =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 > or =75 nmol/l compared to < 25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/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 < or =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.

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Related in: MedlinePlus

Seasonal variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E).Values are from the partial regression of the harmonic components; Model 1 (solid line) adjusted for respiratory infections, alcohol consumption, PC/TV time, physical activity and social class at birth and adulthood, and Model 2 (dashed line, shown with 95% confidence intervals) in addition to above adjusted for 25-hydroxyvitamin D. Tick marks denote average concentrations (SDS, predicted from random effects models) with 95% confidence intervals shown by error bars. Predicted means for CRP from linear models, no seasonal pattern observed (p>0.8). *p-values from the product of coefficient mediation test used to assess the 25(OH)D mediation effect on the seasonal patterns in the outcomes.
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pone-0010801-g003: Seasonal variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E).Values are from the partial regression of the harmonic components; Model 1 (solid line) adjusted for respiratory infections, alcohol consumption, PC/TV time, physical activity and social class at birth and adulthood, and Model 2 (dashed line, shown with 95% confidence intervals) in addition to above adjusted for 25-hydroxyvitamin D. Tick marks denote average concentrations (SDS, predicted from random effects models) with 95% confidence intervals shown by error bars. Predicted means for CRP from linear models, no seasonal pattern observed (p>0.8). *p-values from the product of coefficient mediation test used to assess the 25(OH)D mediation effect on the seasonal patterns in the outcomes.

Mentions: Given the strong influence of season on 25(OH)D concentrations [19], we evaluated seasonal variation in hemostatic and inflammatory markers, and tested mediation effects of 25(OH)D in the observed patterns. Fibrinogen, tPA, D-dimer, and vWF but not CRP had significant seasonal patterns (p = 0.03, p = 0.02, p = 0.02, p = 0.01 and p = 0.8, respectively, Figure 3). The strongest effect mediation by 25(OH)D was seen in the pattern of tPA (p<0.001), with 25(OH)D contributing to a lesser extent to seasonal variation in D-dimer and fibrinogen. The seasonal variation seen in vWF was not affected by 25(OH)D (p = 0.99).


25-Hydroxyvitamin D and pre-clinical alterations in inflammatory and hemostatic markers: a cross sectional analysis in the 1958 British Birth Cohort.

Hyppönen E, Berry D, Cortina-Borja M, Power C - PLoS ONE (2010)

Seasonal variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E).Values are from the partial regression of the harmonic components; Model 1 (solid line) adjusted for respiratory infections, alcohol consumption, PC/TV time, physical activity and social class at birth and adulthood, and Model 2 (dashed line, shown with 95% confidence intervals) in addition to above adjusted for 25-hydroxyvitamin D. Tick marks denote average concentrations (SDS, predicted from random effects models) with 95% confidence intervals shown by error bars. Predicted means for CRP from linear models, no seasonal pattern observed (p>0.8). *p-values from the product of coefficient mediation test used to assess the 25(OH)D mediation effect on the seasonal patterns in the outcomes.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2875406&req=5

pone-0010801-g003: Seasonal variation in C-reactive protein (A), fibrinogen (B), D-dimer (C), tissue plasminogen activator (D), and von Willebrand factor (E).Values are from the partial regression of the harmonic components; Model 1 (solid line) adjusted for respiratory infections, alcohol consumption, PC/TV time, physical activity and social class at birth and adulthood, and Model 2 (dashed line, shown with 95% confidence intervals) in addition to above adjusted for 25-hydroxyvitamin D. Tick marks denote average concentrations (SDS, predicted from random effects models) with 95% confidence intervals shown by error bars. Predicted means for CRP from linear models, no seasonal pattern observed (p>0.8). *p-values from the product of coefficient mediation test used to assess the 25(OH)D mediation effect on the seasonal patterns in the outcomes.
Mentions: Given the strong influence of season on 25(OH)D concentrations [19], we evaluated seasonal variation in hemostatic and inflammatory markers, and tested mediation effects of 25(OH)D in the observed patterns. Fibrinogen, tPA, D-dimer, and vWF but not CRP had significant seasonal patterns (p = 0.03, p = 0.02, p = 0.02, p = 0.01 and p = 0.8, respectively, Figure 3). The strongest effect mediation by 25(OH)D was seen in the pattern of tPA (p<0.001), with 25(OH)D contributing to a lesser extent to seasonal variation in D-dimer and fibrinogen. The seasonal variation seen in vWF was not affected by 25(OH)D (p = 0.99).

Bottom Line: Adjusted for sex and month, 25(OH)D was inversely associated with all outcomes (p < or =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 > or =75 nmol/l compared to < 25 nmol/l.D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/l compared to others (quadratic term p = 0.01).

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council Centre for Epidemiology of Child Health and Centre for Paediatric Epidemiology and Biostatistics, University College London Institute of Child Health, London, UK. e.hypponen@ich.ucl.ac.uk

ABSTRACT

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 45 y). 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 < or =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 > or =75 nmol/l compared to < 25 nmol/l. D-dimer concentrations were lower for participants with 25(OH)D 50-90 nmol/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 < or =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.

Show MeSH
Related in: MedlinePlus