Early medication use in new-onset rheumatoid arthritis may delay joint replacement: results of a large population-based study.

INTRODUCTION: Use of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis (RA) may prevent joint damage and potentially reduce joint replacement surgeries. We assessed the association between RA drug use and joint replacement in Quebec, Canada. METHODS: A cohort of new-onset RA patients was identified from Quebec's physician billing and hospitalization databases from 2002-2011. The outcome was defined using procedure codes submitted by orthopedic surgeons. Medication use was obtained from pharmacy databases. We used alternative Cox regression models with time-dependent variables measuring the cumulative effects of past use during different time windows (one model focussing on the first year after cohort entry) for methotrexate (MTX), and other DMARDs. Models were adjusted for baseline sociodemographics, co-morbidity and prior health service use, time-dependent cumulative use of other drugs (anti-tumor necrosis factor [anti-TNF] agents, other biologics, cyclooxygenase-2 inhibitors [COXIBs], nonselective nonsteroidal antiinflammatory drugs [NSAIDs], and systemic steroids), and markers of disease severity. RESULTS: During follow-up, 608 joint replacements occurred among 11,333 patients (median follow-up: 4.6 years). The best-fitting model relied on the cumulative early use (within the first year after cohort entry) of MTX and of other DMARDs, with an interaction between MTX and other DMARDs. In this model, greater exposure within the first year, to either MTX (adjusted hazard ratio, HR = 0.95 per 1 month, 95% confidence interval, 95% CI 0.93-0.97) or other DMARDs (HR = 0.97, 95% CI 0.95-0.99) was associated with longer time to joint replacement. CONCLUSIONS: Our results suggest that longer exposure to either methotrexate (MTX) or other DMARDs within the first year after RA diagnosis is associated with longer time to joint replacement surgery.

Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals.

AIMS: The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores. METHODS AND RESULTS: Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.8 years) with no known history of cardiovascular disease. No relationship was observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended to correlate but not significantly (p = 0.07). A lower FMD was related to a higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002, respectively) in the univariate analysis, and higher systolic blood pressure (p = 0.001) in the multivariate analysis. Elevated CRP levels independently correlated most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a weaker although statistically significant relationship was seen with individual traditional cardiovascular risk factors (p < 0.005). CONCLUSIONS: The current study provided evidence that brachial artery FMD had no relationship to CRP in a large cohort of healthy subjects. These observations suggest that the predictive value of CRP may be largely independent of abnormalities in endothelial function. The additive prognostic value of endothelial vasodilator testing remains to be established.

The fate of endothelial function testing: rationale and design of the Firefighters And Their Endothelium (FATE) study.

Endothelial dysfunction plays a pivotal role in the development and progression of atherosclerotic vascular disease. The endothelium is strategically located between blood and vascular smooth muscle, making it both vulnerable to a variety of injurious stimuli but also available for interrogation as a marker of vascular health. Firefighters And Their Endothelium (FATE) is a prospective, longitudinal cohort study designed to assess the relationship between endothelial function, emerging cardiovascular risk factors and ultimately atherosclerotic vascular disease. It is hypothesized that participants with impaired endothelial function will be at increased risk of atherosclerotic complications. This Canadian initiative will recruit 1600 middle-aged participants with no known history of cardiovascular disease to be followed for cardiovascular events over the next decade. Quantitative B-mode ultrasound will be employed to assess endothelial function and subclinical atherosclerosis. This research is designed to redefine the approach to the primary prevention of atherosclerosis.