Relationship between serum vitamin D levels and pro-inflammatory cytokines in patients with rheumatoid arthritis combined with cardiovascular disease.

OBJECTIVE

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation and a markedly elevated risk of cardiovascular disease (CVD), which contributes to increased morbidity and mortality rates. Vitamin D deficiency and systemic inflammation have been increasingly identified as significant factors in the heightened prevalence of CVD among RA patients. However, the association between serum vitamin D levels and pro-inflammatory cytokines in RA patients with concurrent CVD remains inadequately understood.

METHODS

In this study, 50 healthy controls (HC group), 50 patients with RA (RA group), and 78 patients with RA comorbid CVD (RA + CVD group) were recruited. Four pro-inflammatory cytokines, including IL-1β, IL-6, IFN-γ, and TNF-α, were quantified. A comparative analysis was conducted to evaluate demographic characteristics, Disease Activity Score 28 (DAS-28) scores, Atherogenic Index of Plasma (AIP) index, and serum pro-inflammatory cytokine levels among the HC, RA, and RA + CVD groups. Then, participants in the RA + CVD group were divided into two groups based on their initial vitamin D levels: the vitamin D deficiency group (< 20 µg/L) and the non-deficiency group (≥ 20 µg/L). A comparative analysis was conducted to evaluate demographic characteristics, DAS-28 scores, AIP index, and serum pro-inflammatory cytokine levels between the two groups. The relationship between vitamin D levels and DAS-28 scores, AIP index, and serum pro-inflammatory cytokines in patients with RA combined with CVD was assessed using Spearman's correlation analysis.

RESULTS

The RA + CVD group exhibited significantly lower serum vitamin D levels alongside significantly elevated AIP index and pro-inflammatory cytokine levels (IL-1β, IL-6, IFN-γ, and TNF-α) compared to the HC group (P < 0.05). The RA + CVD group had significantly higher AIP index and lower serum vitamin D levels than the RA group (P < 0.05). Moreover, in patients with RA comorbid CVD, the DAS-28 scores and AIP index were significantly elevated in the vitamin D deficiency group compared to the non-deficient group (P < 0.05). The serum levels of IL-1β, IL-6, IFN-γ, and TNF-α were significantly higher in the vitamin D deficiency group (P < 0.05). Furthermore, a positive correlation was observed between DAS-28 scores and AIP index in patients with RA combined with CVD (r = 0.295, P = 0.009). Additionally, serum vitamin D levels were negatively correlated with DAS-28 scores (r =  - 0.385, P = 0.001), AIP index (r =  - 0.387, P < 0.001), and serum concentrations of IL-1β (r =  - 0.227, P = 0.046), IL-6 (r =  - 0.458, P < 0.001), IFN-γ (r =  - 0.342, P = 0.002), and TNF-α (r =  - 0.392, P < 0.001) in this patient population.

CONCLUSION

These findings demonstrate a significant association between vitamin D deficiency and heightened systemic inflammation, disease activity, and atherogenic risk in patients with RA complicated by CVD. Key points In RA patients with CVD, those with vitamin D deficiency showed higher DAS-28 scores, AIP index, and pro-inflammatory cytokine levels compared to those with vitamin D non-deficiency. The DAS-28 was positively correlated to the AIP in patients with RA combined with CVD. The serum vitamin D levels were negatively correlated to the DAS-28 scores, AIP index, and serum concentrations of IL-6, IFN-γ, and TNF-α in patients with RA combined with CVD. The present study provides novel insights into the interplay between vitamin D deficiency and increased systemic inflammation, disease activity, and atherogenic risk in patients with RA and concurrent CVD.