Recommendations for the management of cardiovascular risk in patients with rheumatoid arthritis: Scientific evidence and expert opinion

Abstract

Objectives

Last recommendations regarding cardiovascular risk (CVR) in rheumatoid arthritis (RA) patients were developed by the EULAR group in 2010. The aim is to update evidence-based recommendations about this worrying health problem.

Methods

We assembled a multidisciplinary workgroup (rheumatologists, endocrinologist, cardiologist, and epidemiologist) and a panel of 28 expert rheumatologists. The study was carried out in two big phases: identifying key areas in the prevention and management of CVR and developing a set of recommendations based on a review of the available scientific evidence and use of the Delphi consensus technique. All this has been developed according to an updating process of evidence-based recommendations.

Results

Overall, 25 recommendations were made addressing three complementary areas: CVR assessment tools, patient eligibility for assessment, and treatment strategies for control of CVR. The grade of the recommendations was not substantially modified compared to the original EULAR recommendations, except in two of them, which were upgraded from C to B. These two recommendations are the ones related to the use of corticosteroids and smoking cessation. The new developed recommendations address these two areas: CVR assessment and treatment strategies for control of CVR.

Conclusions

There are substantial gaps in the current knowledge that do not allow classifying properly RA patients based on their actual CVR and to accurately identify those patients who would benefit from CVR assessment. Consequently, studies designed to determine the causal effects of RA disease characteristics on cardiovascular morbidity/mortality and to identify patients at high risk of cardiovascular disease are still needed.

Introduction

Rheumatoid arthritis (RA) is a chronic multisystem inflammatory disease of unknown etiology affecting between 0.5% and 1% of the adult population [1], [2]. Moreover, it has been associated with an increase in global mortality rates [3], [4]. Meta-analyses of observational studies showed that RA patients׳ morbidity and mortality risks stemming from cardiovascular causes were, respectively, close to 50% and up to 60% higher than those of the general population [5], [6], [7], [8]. This excess in morbidity and mortality is mainly due to an accelerated atherogenesis process [9], [10], [11], one that cannot be fully explained by the classic atherosclerosis risk factors [12], [13]. In this regard, the mechanisms leading to an elevated cardiovascular mortality rate in RA patients are complex, and the presence of chronic inflammation [12], [13] and/or of a possible genetic component [14], [15] is a factor likely to contribute to the increased prevalence of cardiovascular disease (CVD) in RA patients [12], [16], [17], [18]. Therefore, in practical terms, comprehensive assessment and treatment of traditional and non-traditional cardiovascular risk (CVR) factors should form part of the routine care of RA patients [19].

An important aspect in managing patients with elevated CVR is the accurate assessment and grading of such a risk. Some research have shown that the tools used for risk assessment in the general population underestimate the true risk when they are applied to patients with pro-atherogenic diseases such as diabetes or chronic renal disease [20], [21], [22], [23]. Evidence suggests that this is also the case with RA [24], [25]. To address this issue, the European League Against Rheumatism (EULAR) Working Group proposed the adaptation of the Systematic Coronary Risk Evaluation (SCORE) system to estimate CVR in RA patients. The EULAR task force proposed multiplying the SCORE׳s risk by 1.5 in those RA patients who present at least two of the following conditions: (1) disease duration >10 years, (2) rheumatoid factor (RF) or anti-cyclic citrullinated peptide (ACCP) positivity, and (3) the presence of extra-articular manifestations [26]. After reviewing the published evidence, the EULAR group suggested future research to establish the efficacy of the risk functions to assess CVR in RA, as well as to review in the near future the validity of the 1.5 weighting factor, as up to when EULAR recommendations were developed there had not been found prospective cohort studies that allowed the validation of this factor [26]. Articles published in recent years show that, in daily clinical practice, it is not uncommon to see RA patients being classified as having moderate CVR, based on the adapted SCORE, who have subclinical atherosclerosis. This is especially true when non-invasive tools such as carotid ultrasonography are used [27], [28]. The results from studies were published after the EULAR recommendations were developed, along with an increasing amount of scientific publications and the need to address the management of CVR factors in RA patients such as lifestyle modification (diet control and physical activity) and control of classic CVR factors (hypercholesterolemia and hypertension, HT), which were not included in the EULAR recommendations, justifying the need of the present study.

This updated evidence review goes in line with current recommendations regarding the update of Clinical Practice Guidelines (CPG) or any other type of evidence-based recommendations, which state that evidence should be reviewed at least every 3–5 years in order to keep its validity [29], [30]. Therefore, the aim of this study is to update evidence-based recommendations for the assessment and CVR management in RA patients, taking as reference the 2010 EULAR recommendations for CVR management.