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.