Cardiovascular Risk In Rheumatoid Arthritis Patients Research Articles

Cardiovascular Disease and Rheumatoid Arthritis: An Update

Patients with rheumatoid arthritis (RA) suffer significantly increased cardiovascular (CV) morbidity and mortality, when compared with the general population. Both traditional CV risk factors and high levels of systemic inflammation have been linked to the increased CV risk in RA patients, but significant uncertainty remains regarding the mechanisms through which these factors contribute to CV disease (CVD). In addition, ongoing questions remain regarding how best to identify RA patients at high risk for CVD and what primary and secondary prevention strategies are effective at influencing CV outcome. The present review summarizes recent research in this field.

The Effects of Tumor Necrosis Factor Inhibitors on Cardiovascular Risk in Rheumatoid Arthritis

There is abundant evidence that rheumatoid arthritis (RA), a chronic inflammatory disorder, is associated with an increased risk for cardiovascular (CV) disease. While there may be several mechanisms contributing to a higher CV risk in RA patients, inflammation is considered to be the main cause explaining the excess CV burden. Inflammatory processes appear pivotal to the atherothrombotic process and are linked to endothelial dysfunction, fatty streak initiation and progression, deterioration of fatty streaks into (unstable) plaques, and plaque rupture. Moreover, systemic inflammation, through tumor necrosis factor (TNF) or related cytokines, appears to accelerate atherothrombosis either directly or via effects on conventional and novel CV risk factors, such as lipids and lipoproteins, blood pressure, haemostatic factors, and insulin resistance. New and highly specific therapeutic agents (TNF inhibitors) may significantly lower CV risk in RA. This review summarizes the evidence base supporting the notion that TNF inhibitors confer benefit CV disease risk in RA.

Kardiovaskuläre Komorbidität und ihre Risikofaktoren bei rheumatoider Arthritis

Rheumatoid arthritis (RA) is still associated with an increased mortality mainly due to an increase in cardiovascular risk. This increase is not solely explained by traditional cardiovascular risk factors but also by disease characteristics, e.g. inflammation, positive rheumatoid factor and anti-citrullinated peptide antibodies (ACPA). Control of disease activity with disease-modifying drugs (DMARDs) was shown to reduce cardiovascular risk in RA patients. Use of non-steroidal antirheumatic drugs (NSAIDs) and glucocorticoids might be associated with an increased risk. The EULAR recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis have been established. These recommendations are based on national guidelines regarding control of traditional cardiovascular risk factors.

The interplay between inflammation, lipids and cardiovascular risk in rheumatoid arthritis: why ratios may be better

There is abundant evidence that patients with rheumatoid arthritis (RA) are at elevated cardiovascular (CV) risk. The contribution of lipids in general is well recognised, but is as yet unclear in inflammatory diseases such as RA in part because inflammation appears inversely associated with lipid levels in RA. The CARRE study is a cohort study of 353 randomly selected RA outpatients followed since their enrollment in 2001-2002. We used data from this cohort to (i) evaluate the relationship at baseline between lipid levels [total cholesterol (TC), high-density lipoprotein (HDL)-cholesterol and the TC:HDLc ratio] and inflammation [by means of C-reactive protein (CRP)]; and (ii) determine the association of baseline TC and TC:HDLc ratio with incident (fatal and non-fatal) CV events. C-reactive protein correlated negatively with TC (r = -0.184, p = 0.002), more so with HDLc (r = -0.327, p = 0.001) and therefore positively with TC:HDLc ratio (r = 0.204, p = 0.001). These associations were most evident when CRP exceeded 10 mg/l. Furthermore, the TC:HDLc ratio, but not TC, was positively related to event risk, again most marked in those with elevated CRP. Our observations support use of TC:HDLc ratio rather than TC alone in assessing cardiovascular risk in RA patients, especially in those with high inflammatory activity.

Osteopontin Is Associated with Increased Arterial Stiffness in Rheumatoid Arthritis

Rheumatoid arthritis (RA) patients are characterized by increased arterial stiffness, an independent predictor of cardiovascular risk. It has been suggested that osteopontin (OPN), a cytokine involved in RA pathogenesis, might have vascular effects. To study a possible relationship between OPN and arterial stiffness, aortic pulse wave velocity (PWV) was measured by tonometry in 69 patients (41 with RA, 28 with systemic sclerosis [SSc]) and 18 healthy controls. Plasma OPN levels, oxidative stress markers, and endothelin 1 (ET-1) were assessed. OPN levels were significantly (P < 0.05) higher in RA (median 9.93, range 4.36-47.80 ng/mL) than in SSc (4.3, 2.1-19.7 ng/mL) or controls (5.2, 4.1-9.4 ng/mL). In RA patients, log-OPN was related to log-C-reactive protein (log-CRP) (r = 0.30, P < 0.05), age (r = 0.38, P < 0.01), Health Assessment Questionnaire (HAQ) (r = 0.58, P < 0.0001), and inversely related to total cholesterol (r = -0.33, P < 0.05) and apolipoprotein A (apoA) (r = -0.58, P < 0.001), but not to oxidative stress markers and ET-1. PWV was similar in RA (median 8.1, range 4.7-16.4 m/s) and SSc (median 8.7, range 7.1-13.1 m/s), but significantly greater (P < 0.01) than controls (median 7.5, range 4.1-10.4 m/s). Aortic PWV was related to log-OPN (r = 0.40, P < 0.01) only in RA patients. It also was related to age (r = 0.34, P < 0.05), mean blood pressure (r = 0.44, P < 0.001), and HAQ (r = 0.48, P < 0.001). In multiple regression analysis (r(2) = 0.36), including confounders, log-OPN remained a significant predictor (P < 0.05) of PWV in RA. Elevated plasma OPN levels are associated with increased arterial stiffness in RA patients, suggesting that this protein might represent a bridge protein between inflammation and the consequent joint damage and cardiovascular risk in RA patients.

High ten‐year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients: A population‐based cohort study

To estimate the 10-year absolute risk of cardiovascular (CV) events in newly diagnosed rheumatoid arthritis (RA) patients and the potential contribution of CV risk factors to absolute risk assessment. A population-based incidence cohort of RA patients (defined according to the American College of Rheumatology 1987 criteria) was assembled and compared with an age- and sex-matched non-RA cohort. Data were collected on CV risk factors and CV events. Cox regression models were used to estimate the 10-year risk of a combined CV end point, adjusting for CV risk factors. Subjects were classified into 5 risk categories based on their 10-year absolute risk. The absolute CV risk in RA patients was similar to that in non-RA subjects who were 5-10 years older. The absolute risk varied substantially according to the presence of CV risk factors. The 10-year absolute CV risk among 60-69-year-old RA patients with no risk factors was 16.8%, but rose to 60.4% if risk factors such as smoking, hypertension, dyslipidemia, diabetes, and obesity were present. Among RA patients with a low body mass index, in addition to the above risk factors, the 10-year absolute CV risk rose to 86.2%. More than half of the newly diagnosed RA patients who were 50-59 years of age and all of those >60 years of age had a >10% risk of CV disease within 10 years of their RA incidence and should be targeted for specific CV risk reduction strategies tailored to their personal risk profiles.

Effect of anti-TNFα treatment on circulating endothelial progenitor cells (EPCs) in rheumatoid arthritis

Abstract Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality, which may be attenuated by anti-inflammatory treatment. Endothelial progenitor cells (EPCs) have the ability to differentiate into mature endothelium and have a potentially reparative role protecting against ischemia and atherosclerosis. Objective To investigate the effect of treatment with infliximab on the number and functional capacity of endothelial progenitor cells (EPCs) in patients with RA, as a possible mechanism for reducing cardiovascular morbidity in this disorder. Methods Patients: Active seropositive RA patients ( N = 14) considered candidates for starting infliximab treatment, were recruited. Assessment, based on DAS-28, was performed before treatment and 14 days later. Peripheral blood mononuclear cells were isolated and EPC numbers evaluated by the colony-forming unit (CFU) method. Endothelial phenotyping of CFU was performed by immunofluorescence employing antibodies to Tie-2 VEGF-receptor 2, and CD31. EPC Functional properties were evaluated by fibronectin adherance. Results A significant 33.4% increase ( p < 0.001) in EPC levels was observed after infliximab. A 60% increase was noted in the EPC differentiation scale, ( p < 0.002) while a 37.6% increase was observed in mean EPC adhesion ( p < 0.001). These changes were associated with a 17.5% decrease in the DAS-28 ( p < 0.0001). A significant correlation was observed between the clinical response, reflected by changes in DAS-28 and the degree of increase in EPC CFUs. Conclusion A single dose of infliximab improved the number and functional properties of EPCs, in parallel with an early clinical effect, suggesting a possible mechanism by which anti-inflammatory treatment may reduce cardiovascular risk in RA patients.