Atherosclerotic Cardiovascular Disease in Rheumatoid Arthritis: Impact of Inflammation and Antirheumatic Treatment.
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ABSTRACT:
SUBMITTER: Kerola AM
PROVIDER: S-EPMC8145075 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and mortality, the characterization of therapies encompassing both RA and ASCVD management merit high priority. Despite little progress, several drugs discussed here promote remission and or lower rheumatoid disease activity while simultaneously conferring some level of atheroprotection. Methotrexate, a widely used disease-modifying drug used in RA, is associated with significant reduction in cardiovascular adverse events. MTX promotes cholesterol efflux from macrophages, upregulates free radical scavenging and improves endothelial function. Likewise, the sulfonamide drug sulfasalazine positively impacts the lipid profile by increasing HDL-C, and its use in RA has been correlated with reduced risk of myocardial infraction. In the biologic class, inhibitors of TNF-α and IL-6 contribute to improvements in endothelial function and promote anti-atherogenic properties of HDL-C, respectively. The immunosuppressant hydroxychloroquine positively affects insulin sensitization and the lipid profile. While no individual therapy has elicited optimal atheroprotection, further investigation of combination therapies are ongoing.
| S-EPMC8778152 | biostudies-literature
Project description:OBJECTIVES:To determine whether patients with early rheumatoid arthritis (ERA) have cardiovascular disease (CVD) that is modifiable with disease-modifying antirheumatic drug (DMARD) therapy, comparing first-line etanercept (ETN) + methotrexate (MTX) with MTX strategy. METHODS:Patients from a phase IV ERA trial randomised to ETN+MTX or MTX strategy±month 6 escalation to ETN+MTX, and with no CVD and maximum one traditional risk factor underwent cardiovascular magnetic resonance (CMR) at baseline, years 1 and 2. Thirty matched controls underwent CMR. Primary outcome measure was aortic distensibility (AD) between controls and ERA, and baseline to year 1 AD change in ERA. Secondary analyses between and within ERA groups performed. Additional outcome measures included left ventricular (LV) mass and myocardial extracellular volume (ECV). RESULTS:Eighty-one patients recruited. In ERA versus controls, respectively, baseline (geometric mean, 95% CI) AD was significantly lower (3.0×10-3 mm Hg-1 (2.7-3.3) vs 4.4×10-3 mm Hg-1 (3.7-5.2), p<0.001); LV mass significantly lower (78.2 g (74.0-82.7), n=81 vs 92.9 g (84.8-101.7), n=30, p<0.01); and ECV increased (27.1% (26.4-27.9), n=78 vs 24.9% (23.8-26.1), n=30, p<0.01). Across all patients, AD improved significantly from baseline to year 1 (3.0×10-3 mm Hg-1 (2.7-3.4) to 3.6×10-3 mm Hg-1 (3.1-4.1), respectively, p<0.01), maintained at year 2. The improvement in AD did not differ between the two treatment arms and disease activity state (Disease Activity Score with 28 joint count)-erythrocyte sedimentation rate-defined responders versus non-responders. CONCLUSION:We report the first evidence of vascular and myocardial abnormalities in an ERA randomised controlled trial cohort and show improvement with DMARD therapy. The type of DMARD (first-line tumour necrosis factor-inhibitors or MTX) and clinical response to therapy did not affect CVD markers. TRIAL REGISTRATION NUMBER:ISRCTN: ISRCTN89222125; ClinicalTrials.gov: NCT01295151.
| S-EPMC7569379 | biostudies-literature
Project description:ObjectiveTo scope the current published evidence on cardiovascular risk factors in rheumatoid arthritis (RA) focusing on the role of autoantibodies and the effect of antirheumatic agents.MethodsTwo reviews were conducted in parallel: A targeted literature review (TLR) describing the risk factors associated with cardiovascular disease (CVD) in RA patients; and a systematic literature review (SLR) identifying and characterizing the association between autoantibody status and CVD risk in RA. A narrative synthesis of the evidence was carried out.ResultsA total of 69 publications (49 in the TLR and 20 in the SLR) were included in the qualitative evidence synthesis. The most prevalent topic related to CVD risks in RA was inflammation as a shared mechanism behind both RA morbidity and atherosclerotic processes. Published evidence indicated that most of RA patients already had significant CV pathologies at the time of diagnosis, suggesting subclinical CVD may be developing before patients become symptomatic. Four types of autoantibodies (rheumatoid factor, anti-citrullinated peptide antibodies, anti-phospholipid autoantibodies, anti-lipoprotein autoantibodies) showed increased risk of specific cardiovascular events, such as higher risk of cardiovascular death in rheumatoid factor positive patients and higher risk of thrombosis in anti-phospholipid autoantibody positive patients.ConclusionAutoantibodies appear to increase CVD risk; however, the magnitude of the increase and the types of CVD outcomes affected are still unclear. Prospective studies with larger populations are required to further understand and quantify the association, including the causal pathway, between specific risk factors and CVD outcomes in RA patients.
| S-EPMC8246480 | biostudies-literature
Project description:ObjectivePatient refusal of and nonadherence to treatment with disease-modifying antirheumatic drugs (DMARDs) can adversely affect disease outcomes in rheumatoid arthritis (RA). This qualitative study describes how RA patients' feelings in response to experiences and information affected their decisions to accept (agree to adopt, initiate, and implement) or resist (refuse, avoid, and discontinue) DMARD treatment regimens.MethodsA total of 48 RA patients were interviewed about their experiences making decisions about DMARDs. The interviews were transcribed, coded, and analyzed for themes related to their internal motivations for accepting or resisting treatment regimens, using a narrative analysis approach.ResultsIn addition to feelings about the necessity and dangers of medications, patients' feelings towards their identity as an ill person, the act of taking medication, and the decision process itself were important drivers of patient's decisions. For patients' motivations to accept treatment regimens, 2 themes emerged: a desire to return to a normal life, and fear of future disability due to RA. For motivations to resist treatment regimens, 5 themes emerged: fear of medications, maintaining control over health, denial of sick identity, disappointment with treatment, and feeling overwhelmed by the cognitive burden of deciding.ConclusionFeelings in response to experiences and information played a major role in how patients weighed the benefits and costs of treatment options, suggesting that addressing patients' feelings may be important when rheumatologists counsel about therapeutic options. Further research is needed to learn how best to address patients' feelings throughout the treatment decision-making process.
| S-EPMC5712284 | biostudies-literature
Project description:Rheumatoid arthritis (RA) patients have a 50% increased risk of cardiovascular (CV)-related morbidity and mortality. This excess CV risk is closely linked to RA disease severity and chronic inflammation, hence is largely underestimated by traditional risk calculators such as the Framingham Risk Score. Epidemiological studies have shown that patients with RA are more likely to have silent ischemic heart disease, develop heart failure, and experience sudden death compared with controls. Elevations in pro-inflammatory cytokines, circulating autoantibodies, and specific T cell subsets, are believed to drive these findings by promoting atherosclerotic plaque formation and cardiac remodeling. Current European League Against Rheumatism (EULAR) guidelines state that rheumatologists are responsible for the assessment and coordination of CV disease (CVD) risk management in patients with RA, yet the optimal means to do so remain unclear. While these guidelines focus on disease activity control to mitigate excess CV risk, rather than providing a precise algorithm for choice of therapy, studies suggest a differential impact on CV risk of non-biologic disease-modifying anti-rheumatic drugs (DMARDs), biologic DMARDs, and small molecule-based therapy. In this review, we explore the mechanisms linking the pathophysiologic intrinsic features of RA with the increased CVD risk in this population, and the impact of different RA therapies on CV outcomes.
| S-EPMC7021876 | biostudies-literature
Project description:Clinical evidence demonstrates coadministration of tumour necrosis factor inhibitor (TNFi) agents and methotrexate (MTX) is more efficacious than administration of TNFi agents alone in patients with rheumatoid arthritis, leading to the perception that coadministration of MTX with all biologic agents or oral disease-modifying antirheumatic drugs is necessary for maximum efficacy. Real-life registry data reveal approximately one-third of patients taking biologic agents use them as monotherapy. Additionally, an analysis of healthcare claims data showed that when MTX was prescribed in conjunction with a biologic agent, as many as 58% of patients did not collect the MTX prescription. Given this discrepancy between perception and real life, we conducted a review of the peer-reviewed literature and rheumatology medical congress abstracts to determine whether data support biologic monotherapy as a treatment option for patients with rheumatoid arthritis. Our analysis suggests only for tocilizumab is there evidence that the efficacy of biologic monotherapy is comparable with combination therapy with MTX.
| S-EPMC3841743 | biostudies-literature
Project description:BackgroundRheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a "natural experiment" to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease.MethodsA review of current literature on heart disease and RA was conducted.ResultsPatients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk.ConclusionsInvestigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease.
| S-EPMC3890244 | biostudies-literature
Project description:Multiple studies demonstrate an increased cardiovascular (CV) risk associated with RA compared with the general population. While part of this risk appears to be mediated by RA-specific factors, such as long-term inflammation, traditional CV comorbidities also play an important role. We review evidence from previous studies of the relationship between RA and traditional CV comorbidities such as dyslipidaemia, obesity, insulin resistance and diabetes, hypertension, cigarette smoking and physical inactivity. We examine the prevalence and consider the effect of inflammation and RA treatments on these risk factors. Finally, we discuss three widely used CV risk estimators, the Framingham Risk Score, Reynolds Risk Score and the Systematic Coronary Risk Evaluation, and their performance in patients with RA. The traditional CV risk factors that appear to differ significantly between RA cases and controls include insulin resistance, abnormal fat distribution, cigarette smoking and lack of physical activity. Dyslipidaemia, diabetes and hypertension may also be elevated in RA; however, the evidence is conflicting. Overall, we found that the majority of information regarding CV risk factors in RA stems from data collected as covariates for studies on CV disease. A gap in knowledge exists regarding detailed information on individual risk factors in RA, their prevalence and modifications that occur as a result of inflammation or treatment. More studies are needed to develop methods for accurate CV risk estimation in RA.
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Project description:The endothelial glycocalyx (EG) is essential for proper function of the endothelium and for vascular integrity, but its role in premature atherogenesis in rheumatoid arthritis (RA) has not been studied yet. EG impairment can play a role in pathogenesis of vascular disease, and one of its characteristics is shedding of syndecan-1 from endothelial cells. Syndecan-1 shedding is mediated by matrix metalloproteinase-9 (MMP-9) and counteracted by tissue inhibitor of metalloproteinases (TIMP)-1. Cardiovascular disease risk in RA is reversible by disease modifying antirheumatic drugs (DMARDs), but the exact modes of action are still unclear. Therefore, we examined effects of DMARDs on syndecan-1, MMP-9 and TIMP-1 in RA patients, and searched for associations between these parameters and inflammatory activity. From the observational PSARA study, we examined 39 patients starting with methotrexate (MTX) monotherapy (in MTX naïve patients, n = 19) or tumor necrosis factor inhibitors (TNFi) in combination with MTX (in MTX non-responders, n = 20) due to active RA. Serum syndecan-1, MMP-9 and TIMP-1 were measured at baseline and after six weeks of treatment. Serum syndecan-1 (p = 0.008) and TIMP-1 (p<0.001) levels decreased after six weeks of anti-rheumatic treatment. Levels of MMP-9 also decreased, but the difference was not statistically significant. The improvement in syndecan-1 levels were independent of changes in inflammatory activity. There was no significant difference in changes in syndecan-1 levels from baseline to 6 weeks between the MTX and TNFi groups, however the change was significant within the MTX group. Six weeks of antirheumatic treatment was associated with reduction in serum levels of syndecan-1, which might reflect reduced syndecan-1 shedding from EG. Thus, it is possible that EG-preserving properties of DMARDs might contribute to their cardioprotective effects. These effects may be at least partly independent of their anti-inflammatory actions. Our findings do not support the notion that syndecan-1 shedding in RA is mediated mainly by increased MMP-9 or decreased TIMP-9 serum concentration.
| S-EPMC8270157 | biostudies-literature
Project description:With the increased pro-inflammatory response in both rheumatoid arthritis and thyroid autoimmune diseases, treatment with biological antirheumatic agents (BAAs) of the former may affect the course of the latter. In hepatitis C and cancer patients, treatment with biological agents substantially increases the risk of developing thyroid autoimmunity. As the use of BAAs in the treatment of rheumatoid arthritis is increasing, this review aimed to investigate if such use affected thyroid status in rheumatoid arthritis patients. We conducted a systematic literature search and included six studies with a total of 311 patients as well as three case reports. The patients were treated with tumor necrosis factor-α inhibitors (infliximab, etanercept, or adalimumab) or the monoclonal CD20-antibody rituximab. There was a non-significant trend of slight improvement of both thyroid function and autoantibody status: a reduction of thyroid peroxidase and thyroglobulin antibody concentrations, and a reduction of thyrotropin levels in hypothyroid patients. Despite the small number of studies, they presented compliant data. The BAAs used in rheumatoid arthritis thus did not seem to negatively affect thyroid status in patients with rheumatoid arthritis and can be considered safe with regard to thyroid autoimmunity. However, the well-established association between rheumatic diseases and thyroid autoimmunity necessitates continued monitoring of thyroid function in patients with rheumatoid arthritis. Each new BAA should be scrutinized for its effect on thyroid as well as other autoimmune diseases in order to establish concise recommendations for patient follow-up for each agent and each disease.
| S-EPMC5534470 | biostudies-other