Analysis of Potential Vitamin D Molecule Biomarkers: Association of Calcitriol and Its Hydroxylation Efficiency Ratio with Cardiovascular Disease Risk in Rheumatoid Arthritis Patients

Abstract

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which hypovitaminosis D by calcidiol quantification has been associated with disease severity. However, other vitamin D molecules could be implicated in RA pathophysiology and its comorbidities such as cardiovascular disease (CVD), which impacts the severity and mortality of RA patients. This study aimed to assess the relationship between calcidiol, calcitriol, its hydroxylation efficiency ratio, and the soluble vitamin D receptor (sVDR) and clinical and CVD risk variables to propose potential vitamin D molecule biomarkers for RA. A cross-sectional study of females was conducted on 154 RA patients and 201 healthy subjects (HS). Calcidiol, calcitriol, and the sVDR were measured in blood serum, and vitamin D hydroxylation efficiency was estimated using the calcitriol/calcidiol ratio score. CVD risk was calculated by the high-sensitivity C-reactive protein (hs-CRP) cutoff values. Disease activity was evaluated with the Disease Activity Score for 28 standard joints (DAS28-CRP). Results: The hydroxylation efficiency ratio and calcitriol serum levels were higher in RA patients with hypovitaminosis D (p < 0.001). Moreover, RA patients had a higher probability of a high hydroxylation efficiency ratio (OR = 2.02; p = 0.02), calcitriol serum levels (OR = 2.95; p < 0.001), and sVDR serum levels (OR = 5.57; p < 0.001) than HS. This same pattern was also observed in RA patients with high CVD risk using CRP serum levels; they showed a higher hydroxylation efficiency ratio (OR = 4.51; p = 0.04) and higher calcitriol levels (OR = 5.6; p < 0.01). Calcitriol correlates positively with the sVDR (r = 0.21, p = 0.03), CRP (r = 0.28, p < 0.001), and cardiometabolic indexes (p < 0.001) also showed discrimination capacity for CVD risk in RA patients with CRP ≥ 3 mg/L (AUC = 0.72, p < 0.01). In conclusion, hypovitaminosis D in RA patients was characterized by a pattern of a higher hydroxylation efficiency ratio and higher calcitriol and sVDR serum levels. Notably, higher calcitriol serum levels and a higher vitamin D hydroxylation efficiency ratio were associated with higher CVD risk in RA patients.