Cardiovascular events in early RA are a result of inflammatory burden and traditional risk factors: a five year prospective study

Abstract

IntroductionCo-morbidity and mortality due to cardiovascular disease (CVD) are increased in patients with rheumatoid arthritis (RA). Most published studies in this field are retrospective or cross sectional. We investigated the presence of traditional and disease related risk factors for CVD at the onset of RA and during the first five years following diagnosis. We also evaluated their potential for predicting a new cardiovascular event (CVE) during the five-year follow-up period and the modulatory effect of pharmacological treatment.MethodsAll patients from the four northern-most counties of Sweden with early RA are, since December 1995, consecutively recruited at diagnosis (T0) into a large survey on the progress of the disease. Information regarding cardiovascular co-morbidity and related predictors was collected from clinical records and supplemented with questionnaires. By April 2008, 700 patients had been included of whom 442 patients had reached the five-year follow-up (T5).ResultsAmong the 442 patients who reached T5 during the follow-up period, treatment for hypertension increased from 24.5 to 37.4% (P < 0.001)), diagnosis of diabetes mellitus (DM) from 7.1 to 9.5% (P < 0.01) whilst smoking decreased from 29.8 to 22.4% (P < 0.001) and the BMI from 26.3 to 25.8 (P < 0.05), respectively. By T5, 48 patients had suffered a new CVE of which 12 were fatal. A total of 23 patients died during the follow-up period. Age at disease onset, male sex, a previous CVE, DM, treatment for hypertension, triglyceride level, cumulative disease activity (area under the curve (AUC) disease activity score (DAS28)), extra-articular disease, corticosteroid use, shorter duration of treatment with disease modifying anti-rheumatic drugs (DMARDs) and use of COX-2 inhibitors increased the hazard rate for a new CVE. A raised erythrocyte sedimentation rate (ESR) at inclusion and AUC DAS28 at six months increased the hazard rate of CVE independently whilst DMARD treatment was protective in multiple Cox extended models adjusted for sex and CV risk factors. The risk of a CVE due to inflammation was potentiated by traditional CV risk factors.ConclusionsThe occurrence of new CV events in very early RA was explained by traditional CV risk factors and was potentiated by high disease activity. Treatment with DMARDs decreased the risk. The results may have implications for cardio-protective strategies in RA.

Altered profile of circulating microparticles in rheumatoid arthritis patients

“…Additionally, although PCA component scores are independent in the whole RA group, rheumatic-and traditional CV-related components were positively correlated in the patients who had a history of CV events (r = 0.602, P = 0.008; n = 18) but not in the CV-free group (r = 0.032, P = 0.759), revealing the relationship between these two features. These results are in line with recent evidence about the interplay of traditional CV risk factors and disease parameters in RA [38,39]. Moreover, disease-specific factors In vitro effects analysed according to different MP subsets The in vitro effect of MPs (measured as number of branching points) was analysed separately according to the different subsets studied.…”

“…associated with MP subsets in the present study (disease duration, DAS28 and age at diagnosis) have been associated with CV disease in RA [38,40,41], thereby supporting the relevance of MPs as biomarkers of endothelial activation and damage in RA patients.…”

Polymorphisms of the Genes EncodingCD40and Growth Differentiation Factor 15 and in the 9p21.3 Region in Patients with Rheumatoid Arthritis and Cardiovascular Disease

“…Risk factors for CVD in patients with RA show a pattern different from that of the general population 5,6 [with the exception of hypertension (HTN)], one that is highly prevalent in RA 7 . However, other traditional risk factors for CVD, such as age, being male, current smoking, and hypertriglyceridemia, have also been shown to affect CVD in patients with RA in prospective studies 8 .…”

Cardiovascular Events in Early Rheumatoid Arthritis — Role of Tumor Necrosis Factor Inhibition

“…It has been suggested that there is a "window of opportunity" soon after disease debut, where control of inflammation can modify the risk of CV comorbidity 10 . The importance of inflammatory control is further emphasized by the association of treatment with synthetic disease-modifying antirheumatic drugs (DMARD) with a reduced risk of CV disease in both established and early RA, as observed in several studies 8,9,11 . Because biological DMARD such as tumor necrosis factor inhibitors (TNFi) are not only efficient in lowering disease activity but also might block cytokines immediately involved in the atherosclerotic process, these therapies have gained extra interest.…”

“…Accumulated disease activity during the earliest stages of RA disease has been associated with risk of CV events, and reduction in disease activity during the first year with an improved prognosis 8,9 . It has been suggested that there is a "window of opportunity" soon after disease debut, where control of inflammation can modify the risk of CV comorbidity 10 .…”