Abstract and Introduction
Abstract
Objective Recent studies in animal models and on human cells have shown an effect of sodium chloride (NaCl) on Th17 cells promoting inflammation. The aim of this study was to evaluate the impact of NaCl intake on the risk of development of RA.
Methods A nested case–control study was performed using population-based prospective data from the Västerbotten Intervention Programme. The study included 386 individuals who had stated their dietary habits as part of a community intervention programme a median of 7.7 years before the onset of symptoms of RA. For comparison, 1886 matched controls were identified from the same database and co-analysed.
Results No significant association was found between sodium intake and the development of RA when all of the individuals were included. In analyses stratified for smoking status at the time of the examination, sodium intake more than doubled the risk for RA among smokers [odds ratio (OR) 2.26 (95% CI 1.06, 4.81)]. This was not observed among non-smokers. Additive interaction analysis of smoking and cases with the highest tertile of sodium intake revealed that 54% of the increased risk of developing RA from these exposures was due to interaction between them [attributable proportion 0.54 (95% CI 0.26, 0.82)]. The risk was further increased for the development of anti-CCP-positive and/or HLA shared epitope–positive RA.
Conclusion Although we were unable to confirm our stated hypothesis, our results that high sodium consumption among smokers was associated with the risk of RA may provide new insights into the impact of smoking in RA development.
Introduction
RA is a chronic inflammatory disease in which both genetic and environmental factors are considered to contribute to development of the disease. Smoking is a well-established lifestyle risk factor for RA, but other factors, e.g. education level, dyslipidaemia and increased BMI, have also been identified as risk factors. Diet has also received considerable attention, e.g. up to 40% of patients with RA believe that their diet had a significant impact on the onset of disease. Studies have suggested that fish, fruit and vegetables have a protective effect, while red meat and proteins have a deleterious effect; however, the results of these studies are inconsistent.
Recent studies in animal models and on human cells ex vivo have generated data on the importance of sodium in the development of autoimmune diseases through the induction of pathogenic Th17 cells in a process mediated by serum glucocorticoid kinase 1 (SGK1). Since Th17 cells may play a role in the pathogenesis of RA, particularly during the early stages of disease development, it is relevant to evaluate the aetiopathogenic role of dietary sodium in the disease course of RA. We have previously reported that detectable antibodies against CCPs and ACPAs predict the onset of RA by several years. Information on dietary habits from the same cohort of individuals is available, thereby allowing a prospective evaluation of diet, especially the intake of sodium, in the future risk of developing RA in a nested case–control study design. The hypothesis for this study was based on the aforementioned results from animal studies, i.e. that sodium intake is associated with an increased risk of disease development.