Clinical and preclinical pulmonary disease in newly diagnosed rheumatoid arthritis: a two-year follow-up study.

OBJECTIVE: Pulmonary disease is a major cause of excess mortality among patients with rheumatoid arthritis (RA). Interstitial lung disease (ILD) is a feared complication, but the benefit of screening is unknown. The aim of this study was to assess the frequency of pulmonary disease, including ILD, in early RA. METHOD: Patients with newly diagnosed RA were recruited prospectively at a single centre and underwent systematic pulmonary function tests (PFTs) and computed tomography (CT) scans at inclusion and after two years. RESULTS: The study included 150 patients (mean age 57 years, 63% female; 59% current or former smokers). Of these, 136 underwent baseline PFTs and 137 CT. Mean forced expiratory volume in one second was 99% predicted and forced vital capacity 106%. Mean diffusing capacity of the lungs for carbon monoxide (DLCO) was 84% predicted. Frequently detected CT abnormalities were pulmonary nodules (42%), bronchiectasis (29%), and emphysema (20%). Two patients had clinically significant ILD and six had mild reticulation suggestive of preclinical ILD. No ILD progression was identified at two-year follow-up. Smoking was associated with DLCO<80% (p=0.004), combined hyperinflation and diffusion impairment (residual volume>120% and DLCO<80%) (p=0.004), and visual emphysema on CT (p<0.001). CONCLUSION: Emphysema and bronchiectasis were common, but most patients had mild disease with preserved lung function. Preclinical or clinical ILD was seen in a minority in this early phase of RA. These findings suggest symptom-based screening and primary intervention focusing on smoking cessation rather than screening for ILD at the time of RA diagnosis.

Impact of season on the association between vitamin D levels at diagnosis and one-year remission in early Rheumatoid Arthritis.

The study evaluates associations between serum vitamin D metabolites at diagnosis and one-year remission, in early diagnosed rheumatoid arthritis(RA). The CIMESTRA-cohort comprised 160 newly diagnosed RA patients, treated aiming at remission. Vitamin D supplementation was recommended according to national guidelines. Dtotal(25OHD2 + 25OHD3) was dichotomized at 50 nmol/L, 1,25(OH)2D was categorized in tertiles. Primary outcome was remission(DAS28-CRP ≤ 2.6) after one year. Associations were evaluated using logistic regression, further adjusted for pre-specified potential confounders: Age, sex, symptom-duration before diagnosis, DAS28-CRP and season of diagnosis. Results are presented as Odds Ratios(OR) with 95% Confidence Intervals(95%CIs). In univariate analyses, neither Dtotal nor 1,25(OH)2D were associated with remission. In adjusted analyses, low Dtotal was associated with higher odds for remission; OR 2.6, 95%CI (1.1; 5.9) p = 0.03, with season impacting results the most. One-year remission was lower in patients with diagnosis established at winter. In conclusion, low Dtotal at diagnosis was associated with increased probability of achieving one-year remission in early RA when adjusting for covariates. Diagnosis in winter was associated with lower odds for one-year remission. Results suggest that season act as a contextual factor potentially confounding associations between vitamin D and RA disease-course. The finding of low Dtotal being associated with higher one-year remission remains speculative.

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.

INTRODUCTION: Cardiovascular 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. OBJECTIVE: To 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 ANALYSIS: This 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 DISSEMINATION: All 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 NUMBER: The parental controlled trial is registered as NCT00209859.

Left ventricular function at two-year follow-up in treatment-naive rheumatoid arthritis patients is associated with anti-cyclic citrullinated peptide antibody status: a cohort study.

OBJECTIVES: In rheumatoid arthritis (RA), the role of autoimmunity, especially anti-cyclic citrullinated peptide antibody (anti-CCP) level, and the time-course of left ventricular (LV) function is unknown. The objective was to assess LV function and the amount of coronary calcium in relation to anti-CCP levels in a cohort of treatment-naive RA patients, and to assess changes in these parameters during a 2 year follow-up period. METHOD: Sixty-six steroid- and disease-modifying anti-rheumatic drug-naive RA patients were treated with methotrexate according to the Danish national guidelines. We assessed LV function by conventional echocardiography and speckle-tracking echocardiography. We estimated the amount and progression of coronary calcium by coronary computed tomography. Patients were examined at the time of diagnosis and after 2 years. RESULTS: Patients with elevated anti-CCP at baseline and after 2 years, compared to those with non-persistently elevated anti-CCP, had significantly less improvement in S´ (1 ± 1.4 cm/s vs 0.2 ± 0.9 cm/s; p = 0.04) and a worsening in global longitudinal systolic strain (GLS) (0.6 ± 1.8% vs -1 ± 2.8%; p = 0.04). There was a significant correlation between ΔGLS over 2 years and anti-CCP at 2 year follow-up (r = 0.36; p = 0.006). We observed a small progression of coronary calcium score during the 2 year follow-up period. No differences in progression were found between patients with high anti-CCP titres at baseline and 2 year follow-up (n = 12) and patients with normal/low anti-CCP titres (n = 32) (23.8 ± 40.3 vs 22.6 ± 68.9; p = 0.96). CONCLUSIONS: Deformation analysis by speckle-tracking echocardiography is a valuable tool to detect early development of myocardial dysfunction despite normal ejection fraction in RA.