In the present study, we have shown that hs-CRP is higher in AA, and this ethnic difference is attenuated by adjustment for vitamin D status. Moreover, hs-CRP is positively associated with PWV (a measure of arterial stiffness) and vitamin D may influence this association. These observations suggest that relatively low circulating concentrations of 25(OH)D may increase risk for inflammation and endothelial dysfunction, even in healthy young adults.
Serum hs-CRP is an independent risk factor for development of hypertension, endothelial dysfunction, arterial stiffness, and atherosclerosis [5
]. We confirmed that AA have poorer vascular function indices, lower 25(OH)D concentrations, and higher hs-CRP, as shown in other studies [16
]. AA subjects also reportedly have a greater prevalence of coronary heart disease and mortality rates [35
]. Although ethnic differences in vascular function are well known, the pathophysiological basis for these differences remains elusive. It is conceivable that vitamin D deficiency may trigger acute phase-reactant production, equivalent to a low-grade systemic inflammation. After adjustment for percent fat and serum 25(OH)D, the difference in hs-CRP between AA and EA was diminished, which may have relevant clinical implications and partially explain these ethnic differences.
In our cohort, hs-CRP was associated with serum 25(OH)D which is consistent with previous reports [36
]. Nevertheless, in our data, serum 25(OH)D was strongly associated with hs-CRP only in EA and the association persisted even after adjusting for BMI and percent fat. One explanation for the absence of an association of 25(OH)D and hs-CRP in AA could be masked by their almost ubiquitous vitamin D deficiency. As most of the AA subjects had a 25(OH)D <20
ng/mL, a large number of subjects may be required to detect an association. In our sample, the EA were predominantly responsible for the observed relationship between hs-CRP and 25(OH)D. With a larger sample size of AA subject, a possible association may manifest. A noteworthy observation by Amer and Qayyum [36
] in a large cohort of asymptomatic adults shows that there was reduction in CRP for each 10
ng/mL increase in serum 25(OH)D as long as serum 25(OH)D was ≤ 21
ng/mL, and CRP started increasing with increasing 25(OH)D concentrations above > 21
ng/mL. They have not reported ethnic-specific cutoffs for this finding. Although the implications of these observations are not clear, there could be different threshold levels in AA and EA above which raising the 25(OH)D concentrations may not be helpful in improving the hs-CRP.
In this study, we observed an association between CRP and PWV. It has been reported that PWV is an independent predictor of cardiovascular events [37
]. We found that adjustment for serum 25(OH)D, attenuated the association between hs-CRP and PWV, suggesting that vitamin D status influences this relationship. Several reports have previously alluded to the fact that vitamin D can serve as an anti-inflammatory agent. Vitamin D3 supplementation was found to reduce the proinflammatory cytokine tumor necrosis factor α
and enhance the anti-inflammatory interleukin 10, in a cohort of subjects with congestive heart failure. However, their CRP did not change [38
]. Because of the inflammatory component of atherosclerosis and because elevated hs-CRP is reportedly associated with cardiovascular disease, it is critical to understand the factors responsible for elevated hs-CRP. Vitamin D supplementation may be an additive therapeutic option for conditions accompanied by increased inflammation and a subsequent decline in cardiovascular health.
Limitations of the study are cross-sectional nature and relatively smaller sample size which limits our ability to conclude causality based on observational associations. Controlled clinical trials are required to clarify whether vitamin D supplementation reduces ethnicity differences in hs-CRP and whether vitamin D supplementation influences the associations between hs-CRP and vascular health indices.
Strengths of the study are inclusion of subjects with body mass index <32
, inclusion of DXA measure of body fat, and inclusion of young healthy adults—a population where preventive interventions could have a profound impact on health. Moreover, we were able to utilize direct accurate measures of arterial stiffness, endothelial function, and central BP parameters.
We conclude that ethnic differences in hs-CRP may be mediated by unequal vitamin D status. Likewise, hs-CRP is higher in subjects with vitamin D deficiency. Furthermore, serum 25(OH)D influences the association between hs-CRP and PWV, a direct measure of arterial stiffness.