# Association Between Serum 25(OH)-Vitamin D and Heart Involvement in a Single-Centre Cohort of Children with Acute Rheumatic Fever During the Years 2004–2024

## TL;DR

This study found that low vitamin D levels in children with acute rheumatic fever are linked to a higher risk of developing heart disease.

## Contribution

The study identifies hypovitaminosis D as a potential risk factor for rheumatic heart disease in children with acute rheumatic fever.

## Key findings

- Children with heart involvement had significantly lower vitamin D levels than those without.
- Vitamin D levels below 30 ng/mL were strongly associated with rheumatic heart disease in a multivariate analysis.
- No seasonal pattern was found between vitamin D levels and ARF/RHD diagnosis.

## Abstract

Background: An aberrant immune response against Streptococcus pyogenes combined with yet-unraveled genetic inference can induce acute rheumatic fever (ARF), but factors determining the specific development of rheumatic heart disease (RHD) are obscure. Objectives: To retrospectively assess general and laboratory data at the onset of ARF in a single-centre cohort of children managed between 2004 and 2024, and to evaluate any potential relationship between serum vitamin D and the occurrence of RHD. Patients and Methods: Children with ARF diagnosed according to the revised Jones criteria, hospitalized and managed at the Department of Life Sciences and Public Health in our University, were considered; out of 90 eligible patients with post-streptococcal illness, 11 were not considered because they were diagnosed with post-streptococcal arthritis, while 1 was excluded due to incomplete inpatient data. A total final number of 78 consecutive children with ARF (39 males and 39 females) with a mean age of 10.6 ± 2.7 years was assessed via retrospective evaluation of medical records. Their demographic, clinical, and laboratory variables at disease onset, including C-reactive protein, anti-streptolysin-O titer, and 25-hydroxyvitamin D [25(OH)-vitamin D], were analyzed. Results: Sixty-six children (84.6% of the whole cohort) were found to have echocardiographic evidence of RHD. By dividing patients based on the presence of carditis, at the univariate analysis, we observed serum 25(OH)-vitamin D levels significantly lower in patients with cardiac involvement compared to those without (18 ± 6 versus 38 ± 8 ng/mL, p < 0.001). In addition, the proportion of patients with normal serum vitamin D levels was significantly higher among those without cardiac involvement (92%, p < 0.001). To account for any potential confounding factors, we performed a multivariate analysis using logistic regression, adjusted for sex and age, finding that 25(OH)-vitamin D levels lower than 30 ng/mL were the only variable associated with RHD (OR 27.752; 95% CI: 2.885–266.996). No relationship between vitamin D and the month of the year at diagnosis of ARF and RHD was found. Conclusions: Hypovitaminosis D was identified as a factor potentially associated with RHD occurrence in a single-centre cohort of children with ARF evaluated over two decades. This result may suggest that vitamin D deficiency contributes to the occurrence of carditis in ARF.