Important issues at heart: cardiovascular risk management in rheumatoid arthritis

Atherosclerosis remains the predominant cause of cardiovascular diseases (CVDs) and heart failure, which are the leading causes of death worldwide. It is now well established that patients with rheumatoid arthritis (RA) experience an accelerated atherosclerosis increasing their risk of CVD and related mortality compared with the general population [Nicola et al. 2005; Roubille and Tardif, 2013; Solomon et al. 2003]: a recent meta-analysis highlighted an increased risk of all CVDs of 48% in RA, as well as of myocardial infarction of 68% and of strokes of 41% [Avina-Zubieta et al. 2012]. Over the past decade, inflammation appeared to be the cornerstone of both atherosclerosis and RA. Indeed, atherosclerosis is no longer considered a condition in which lipids are being deposited passively in the arterial wall but rather fully recognized as an inflammatory, dynamic and complex disease involving multiple cell types, including inflammatory cells as well as endothelial and smooth muscle cells [Newby, 2010; Roubille et al. 2013c; Shah, 2009]. RA has long been recognized as a systemic inflammatory syndrome with several extra-articular manifestations such as interstitial lung disease and vasculitis. However, these features do not occur in all RA patients. In contrast, vascular inflammation and accelerated atherosclerosis may affect a larger RA population, probably all RA patients, especially in the early stage of the disease, as pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 and IL-6 as well as B cells contribute to the pathogenesis of both atherosclerosis and RA [Hansson, 2005]. Moreover, traditional cardiovascular risk factors should not be overlooked. Hence, assessment and management of cardiovascular risk factors is recommended for RA patients [Haraoui et al. 2012; Peters et al. 2010]. The treatment goal should be to achieve remission or at least low disease activity as early as possible [Smolen et al. 2010], not only to lead to better structural and functional outcomes, but also to reduce the cardiovascular risk [Peters et al. 2010].

In this issue, van den Oever and colleagues review the management of cardiovascular risk in RA. First, they present the main pathophysiological links between RA and the excess cardiovascular risk, emphasizing the early increased risk, even before RA diagnosis, and the contributing role of traditional risk factors, especially smoking which appears both as a potential predisposing factor for CVD but also a worsening factor for RA. Many studies have investigated the prevalence of traditional cardiovascular risk factors in RA (see Table 1 in the review by van den Oever and colleagues); nevertheless, traditional cardiovascular risk factors do not entirely account for the increased cardiovascular risk [del Rincon et al. 2001]. Therefore, a tight control of inflammation is required to prevent CVD in RA and the authors highlight the potential beneficial as well as deleterious impacts of RA therapy on cardiovascular events. Specific treatments targeting the inflammatory pathways are promising tools to control the burden of CVD in RA. Methotrexate, the cornerstone disease-modifying antirheumatic drug (DMARD) in RA, has been shown to decrease CVD [Westlake et al. 2010] and mortality in RA patients [Wasko et al. 2013]. Whether biological agents including TNF inhibitors (TNFi) are protective or not is open to discussion (Roubille et al. 2013b) and two systematic literature reviews identified so far a positive impact of TNFi on CVD in RA [Barnabe et al. 2011; Westlake et al. 2011]. An interesting study using positron emission tomography–computed tomography (PET-CT) scan recently demonstrated that RA patients had increased aortic inflammation which was reduced by TNFi [Maki-Petaja et al. 2012]. These results contrast with large clinical trials assessing TNFi in non-RA patients with heart failure which have been disappointing [Roubille et al. 2013b]. On the other hand, glucocorticoids and nonsteroidal anti-inflammatory drugs (NSAIDs) are generally considered harmful [Roubille et al. 2013a]. Furthermore, new drugs inhibiting or regulating inflammatory pathways, such as serine protease inhibitor SERP-1 and P-selectin inhibitors, remain of interest especially in atherosclerosis and further trials will address these issues [Roubille et al. 2013c].

The specific management of cardiovascular risk should combine control of disease activity (inflammation) and of traditional risk factors. It should become part of the daily practice in RA with the clinician focusing on achieving both inflammatory remission and optimal cardiovascular control [Haraoui et al. 2012]. The current practical issue for the routine management of RA patients is how to deal with CVD and prevention. The authors rightly point out the need for a coordinated effort on the part of both rheumatologists and primary care physicians. They recognize that systematic screening for cardiovascular risk factors is time-consuming and should involve a multidisciplinary team. The management of RA should involve a network of rheumatologists, general practitioners, cardiologists and specialized nurses. Educational programs should also promote awareness of risk and protective factors for CVD [Wartak et al. 2011]. Another important issue is what tools to use in assessing cardiovascular risk in an asymptomatic RA patient. Should we apply the 2010 American College of Cardiology Foundation/American Heart Association guidelines for the assessment of cardiovascular risk in asymptomatic adults [Greenland et al. 2010]? Should resting electrocardiography and/or echocardiography be done or more sophisticated tests such as stress test, assessment of arterial stiffness, or coronary artery calcium as is recommended in diabetes mellitus? In their review, van den Oever and colleagues draw a parallel between RA and diabetes mellitus, arguing that in both conditions, 15 years are added to the age of patients to express the excess cardiovascular risk. This similar cardiovascular excess risk between RA and diabetes emphasizes the significant cardiovascular burden in RA. Studies specifically designed to provide guidance will help clinicians in advising about lifestyle changes and the use of medical interventions to reduce patients’ cardiovascular risk in daily practice. We must recognize that RA is not just an arthritis disease but has huge consequences on major organs and physician should not treat a ‘disease’ but rather a ‘patient’ in a comprehensive way.