Association between baseline vitamin D metabolite levels and long-term cardiovascular events in patients with rheumatoid arthritis from the CIMESTRA trial: protocol for a cohort study with patient-record evaluated outcomes

Abstract

IntroductionCardiovascular morbidity and mortality is increased in patients with rheumatoid arthritis (RA), and among these patients, the prevalence of hypovitaminosis D is high. Moreover, low vitamin D levels have been associated with increased cardiovascular risk in healthy subjects.ObjectiveTo evaluate the long-term risk of cardiovascular events in patients having low total 25-hydroxyvitamin D levels at baseline compared with patients with normal levels, in an efficiently treated, closed cohort of patients with an early diagnosis of RA.Methods and analysisThis study is a prospective, closed, blinded endpoint cohort study, based on secondary analyses from a previous randomised trial (CIMESTRA study; NCT00209859, approved September 1999) including 160 patients with an early diagnosis of RA from Danish University clinics. Primary outcome will be the proportion of patients with any cardiovascular event in the follow-up period, evaluated using systematic journal audits. Logistic regression models will test the hypothesis that there are more cardiovascular events in enrolled patients with a low level of vitamin D (< 50 nmol/L). Secondarily, Cox regression models, based on survival analysis, will determine the extent to which independent variables (including different levels of vitamin D at baseline) predict whether a cardiovascular event will occur, and also when this will be.Ethics and disseminationAll patients have received verbal and written information before enrolment, and have given written consent at baseline. To disseminate comprehension of factors of prognostic importance to cardiovascular outcome in RA, we will attempt to have a first draft ready no later than 1 year after the adjudication process has finished. If low vitamin D levels can predict cardiovascular events in RA, it is relevant to take into account in a prediction model, to be considered by patients, physicians and other decision-makers.Trial registration numberThe parental controlled trial is registered as NCT00209859.

Mechanisms of vascular comorbidity in autoimmune diseases

“…The CIMESTRA trial has recently shown the importance of optimal vitamin D serum levels in patients with rheumatoid arthritis. The study found that low baseline vitamin D metabolite levels associate with long-term CVEs in patients suffering from rheumatoid arthritis [ 38 ▪ ]. Neuropathic pain is often a therapeutic challenge in chronic inflammatory diseases.…”

Serum paraoxonase activity in patients with rheumatoid arthritis, its relationship with the clinical course and cardiovascular compications

“…Currently much attention is focused on metabolic and immunologic markers which are likely to play one of the key roles in atherogenesis of autoimmune diseases. Recent studies provide convincing evidence that anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor IgM, circulating immune complexes, antiinflammatory cytokines (TNF-alfa, ІL-6), Th0/Th1 of Т-cells, homocysteine, dyslipidemia, decreased folic acid level, impaired vitamin metabolism as well as disturbances in paraoxonase activity can be involved in the development of cardiovascular diseases in RA (Yang et al, 2015;Batún Garrido et al, 2016;Rodríguez-Carrio et al, 2016;Tocci et al, 2016;Bernardes et al, 2017;Herly et al, 2017). Nowadays low paraoxonase activity is generally recognized as an independent risk factor of cardiovascular diseases involved in pathologic remodeling of the heart and vessels as well as thrombosis in the general population (Kerekes et al, 2008;Tang et al, 2012;Patra et al, 2013;Kovalenko et al, 2014;Wang et al, 2015;Kunutsor et al, 2016).…”