High-Sensitivity CRP is Associated with Serum 25-Hydroxyvitamin D Levels, but is not Affected by 5-Year Supplementation with Cholecalciferol

Abstract

Background: Insufficient vitamin D status has been linked to insulin resistance and cardiovascular disease. Serum 25-hydroxyvitamin D (25(OH) D) is also involved in immune activation and inflammation. High-sensitivity C-reactive protein (hs-CRP) is an inflammatory biomarker that has been associated with increased risk of cardiovascular disease and metabolic syndrome in observational studies. We aimed to investigate the association between serum 25(OH)D and hs-CRP in an observational study (the sixth Tromsø study), and to evaluate whether supplementation with cholecalciferol has any effect on hs-CRP in an interventional study (the Tromsø vitamin D and type 2 diabetes mellitus trial). Methods: The association between serum 25(OH) D and hs-CRP was investigated with Pearson's correlation and a linear regression model after adjusting for age, sex, BMI, waist circumference and HbA₁C. Pre-diabetic subjects in the interventional study were randomized into two groups, receiving either 20,000 IU/week of vitamin D or a placebo; the intervention period was five years. Delta values of hs-CRP were recorded (calculated by subtracting hs-CRP at baseline from hs-CRP at the end of each year of intervention). Differences in hs-CRP delta values between the treatment and placebo groups were studied with ANOVA. The logistic regression model was applied to determine whether intervention with vitamin D was a predictor of decreased hs-CRP, after adjusting for age, sex, BMI, HbA 1 c and smoking. Results: The observational study included 10,118 non-smoking subjects, while the intervention included 556 subjects. In the observational study, we found a significant negative correlation between serum 25(OH) D and hs-CRP (r coefficient of −0.05 [P=0.001] and β coefficient of −0.02 [P=0.03]). In the interventional study, there were no significant differences in hs-CRP delta values between the vitamin D and placebo groups during any year of the 5-year intervention. Supplementation with cholecalciferol did not predict any significant decrease in hs-CRP after adjustments for other factors. Conclusion: Although there was a significant association between serum 25(OH) D and hs-CRP in the observational study, there was no lowering effect of cholecalciferol supplementation on hs-CRP levels during the 5-year intervention. Thus, the association between serum 25(OH) D and hs-CRP most likely has no obvious clinical importance.