Cardiovascular risk and mortality in rheumatoid arthritis compared with diabetes mellitus and the general population.
About: This article is published in Rheumatology.The article was published on 2021-11-03. It has received 2 citations till now. The article focuses on the topics: Population & Rheumatoid arthritis.
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TL;DR: It is hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.
Abstract: Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.
248 citations
TL;DR: CV benefits or safety signals associated with DMARD treatments can differ despite similar drug efficacy against RA, suggesting that both anti-inflammatory and drug-specific mechanisms are involved in altering CV risk.
Abstract: Increased cardiovascular (CV) risk and associated mortality in rheumatoid arthritis (RA) are not fully explained by traditional CV risk factors. This review discusses the epidemiology and mechanisms of increased CV risk in RA and treatment effects on CV risk focusing on biologic disease-modifying anti-rheumatic drugs (DMARDs) and JAK inhibitors. Intermediary metabolic changes by inflammatory cytokines are observed in body composition, lipid profile, and insulin sensitivity of RA patients, leading to accelerated atherosclerosis and increased CV risk. Successful treatment with DMARDs has shown beneficial effects on these metabolic changes and ultimately CV outcomes, in proportion to the treatment efficacy in general but also with drug-specific mechanisms. Recent data provide further information on comparative CV safety between biologic DMARDs or JAK inhibitors as well as their safety signals for non-atherosclerotic CV events. CV benefits or safety signals associated with DMARD treatments can differ despite similar drug efficacy against RA, suggesting that both anti-inflammatory and drug-specific mechanisms are involved in altering CV risk.
25 citations
TL;DR: It is demonstrated that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.
Abstract: Objectives To compare risk of cardiovascular disease and mortality in patients with incident RA, diabetes mellitus (DM) and the general population (GP). Methods Patients diagnosed with incident RA were matched 1:5 by age, sex and year of RA diagnosis with the GP. In the same period, patients with incident DM were included. Outcomes were heart failure (HF), myocardial infarction (MI), coronary revascularization, stroke, major adverse cardiovascular events (MACE) and death up to 10 years after diagnosis. Results We included 15 032 patients with incident RA, 301 246 patients with DM and 75 160 persons from the GP. RA patients had an increased risk of HF [hazard ratio (HR) 1.51, 95% CI: 1.38, 1.64], MI (HR 1.58, 95% CI: 1.43, 1.74), percutaneous coronary intervention (PCI; HR 1.44, 95% CI: 1.27, 1.62), coronary artery bypass grafting (CABG; HR 1.30, 95% CI: 1.05, 1.62) and stroke (HR 1.22, 95% CI: 1.12-1.33) compared with the GP. However, the 10-year all-cause mortality was at the same level as observed in the GP. Cardiac death and MACE were increased in RA compared with the GP. When compared with patients with DM, RA patients had a lower adjusted risk of HF (HR 0.79, 95% CI: 0.73, 0.85), CABG (HR 0.62, 95% CI: 0.51, 0.76) and stroke (HR 0.82, 95% CI: 0.76, 0.89), and similar risk of MI and PCI. DM patients had the highest risk of 10-year mortality, cardiac death and MACE. Conclusion This study demonstrates that RA is associated with an increased risk of HF, MI, stroke and coronary revascularization than found in the GP but without reaching the risk levels observed in DM patients.
24 citations
TL;DR: Meta-analysis of registries and long-term extension studies showed no increased risk for total malignancies as well as for non-melanoma skin cancer when comparing TNF-inhibitors and the classical disease modifying anti-rheumatic drugs (DMARDs) treatment.
Abstract: Rheumatoid arthritis (RA) is associated with increased cardiovascular risk. Treatment with tumor necrosis factor (TNF)-inhibitors leads to about a 50% reduction in the first cardiovascular event. TNF-inhibitors could transiently improve flow-mediated vasodilation and improve carotid intima-media thickness (ccIMT) during the treatment of RA. Treatment with TNF-inhibitors is associated with an increased total cholesterol (TC) and HDL-cholesterol (HDLc) level, without sustained change of the atherogenic index. The overall cancer risk in RA patients is comparable to that of the general population, but patients with RA slightly more often have lymphomas and lung tumors, and less often have colorectal and breast tumors in comparison to the general population. In randomized controlled trials (RCT) TNF-inhibitors did not increase the risk of solid malignancies, except for non-melanoma skin cancer (risk doubled compared to control treatment). Meta-analysis of registries and long-term extension studies showed no increased risk for total malignancies as well as for non-melanoma skin cancer when comparing TNF-inhibitors and the classical disease modifying anti-rheumatic drugs (DMARDs) treatment.
14 citations