Abstract
Objective: The objective of this study was to assess the association of carotid intima-media thickness (CIMT), and also the presence of atheromatous plaque, with biological and targeted synthetic disease-modifying antirheumatic drugs, in an established cohort of patients with rheumatoid arthritis (RA). Patients and Methods: We conducted a cross-sectional observational study based on a cohort of patients with RA and a registry of healthy controls, in whom the CIMT and presence of atheromatous plaque were assessed by ultrasound. Data were collected on disease activity, lab results and treatments. Descriptive and bivariate analyses were performed and two multivariate linear regression models (with CIMT as the dependent variable) were constructed to identify variables independently associated with CIMT in our sample of patients with RA. Results: A total of 176 individuals (146 patients with RA and 30 controls) were included. A higher percentage of patients than controls had atheromatous plaque (33.8% vs. 12.5%, p = 0.036), but no differences were found in terms of CIMT (0.64 vs. 0.61, p = 0.444). Compared to values in patients on other therapies, the CIMT was smaller among patients on tumour necrosis factor alpha (TNFα) inhibitors (mean [SD]: 0.58 [0.10] vs. 0.65 [0.19]; p = 0.013) and among those on Janus kinase inhibitors (mean [SD]: 0.52 [0.02] vs. 0.64 [0.18]; p < 0.001), while no differences were found as a function of the use of the other therapies considered. The multivariate linear regression analysis to identify factors associated with CIMT in our patients, adjusting for traditional cardiovascular risk factors such as hypertension, high levels of low-density lipoproteins, diabetes mellitus and smoking, showed that male sex, older age and having a greater cumulative erythrocyte sedimentation rate were independently associated with a larger CIMT, while patients on TNFα inhibitors had a CIMT 0.075 mm smaller than those on other treatments. Conclusions: The use of TNFα inhibitors may protect against subclinical atherosclerosis in patients with RA, patients on this biologic having smaller CIMTs than patients on other disease-modifying antirheumatic drugs. Nonetheless, these results should be confirmed in prospective studies with larger sample sizes.
Highlights
Patients with rheumatoid arthritis (RA) have an elevated cardiovascular risk, associated with higher mortality rates and a relative risk of a cardiovascular event of approximately 2 compared to individuals of the same age and sex without the disease [1,2,3].Between a third and half of premature deaths in patients with RA are due to cardiovascular disease [2,4,5]
Among studies that have investigated this issue, a few have assessed the effects of methotrexate, antimalarial drugs and other conventional synthetic disease-modifying antirheumatic drugs (DMARDs) such as leflunomide and sulfasalazine [19,20] and we have found one assessing the effect of biological therapies [21]
Our results indicate that patients treated with TNFα inhibitors, but not other biological therapies, have the smallest carotid intima-media thickness (CIMT), and a lower rate of subclinical atherosclerosis
Summary
Between a third and half of premature deaths in patients with RA are due to cardiovascular disease (including ischaemic heart disease and stroke) [2,4,5] This is attributable to accelerated atherogenesis [6], which is influenced by both traditional and non-traditional cardiovascular risk factors (CVRFs), including systemic inflammation [3,7,8,9,10]. For this reason, the early detection of cardiovascular disease is essential in these patients. Even in the absence of atheromatous plaque, CIMT is a marker of high cardiovascular risk and a significant predictor of the development of atheromatous plaque [14]
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