Cardiovascular disease (CVD) is one of the most important comorbidities in patients with RA. Individuals with RA have an approximately 1.5-fold increased risk of experiencing a CV event compared with those without RA. Although RA-related CVD risk is not as great as that associated with diabetes, it is still appreciably elevated, and data suggest that many patients are unaware that RA confers incremental CVD risk. The 10-year risk for a CV event can be calculated using the Framingham Risk Calculator or the Reynolds Risk Score. According to European League Against Rheumatism guidelines, the calculated score is then multiplied by a factor of 1.5.

There are several potential explanations for the heightened risk of CVD events such as myocardial infarction and stroke in patients with RA. Although a less favorable profile for traditional CV risk factors (eg, smoking) may be present for some patients with RA, it is clear that other factors are also involved. In particular, it is generally accepted that systemic inflammation is an important driver of this increased risk. Rheumatologists should educate their patients about this risk and be sure that they are getting appropriate risk stratification and management of traditional risk factors. While rheumatologists might not wish to be responsible for managing CVD risk factors, they are certainly interested in managing their patients’ RA—and RA therapies affect those risk factors. But controlling both traditional CVD risk factors and RA-related inflammation is key in mitigating a patient’s CVD risk. Corticosteroid therapy, even at modest doses (ie, ≥5 mg/day prednisone equivalent), is associated with an increased CVD risk, so decreasing the dose or getting patients off of glucocorticoids should be a goal. There is also evidence that tumor necrosis factor inhibitor (TNFi) therapy is associated with a lower risk of CVD events (ie, up to a 20%-30% reduction), particularly if patients have a good clinical response and experience reduced levels of systemic inflammation. Further, data suggest that CVD risk reduction is at least as favorable with interleukin 6 receptor inhibitors as it is with TNFi therapy. A 2018 real-world observational study of 88,463 patients with RA found that the use of tocilizumab was associated with a CVD risk that was comparable to etanercept and a number of other RA biologics. A randomized controlled trial comparing etanercept to tocilizumab provides even stronger evidence that the effects of interleukin 6 receptor inhibition is comparable to TNFi treatment in terms of CVD risk. This is important because there was concern that the increased lipid levels linked to tocilizumab use would increase CVD events. There is also evidence that methotrexate has a cardioprotective effect that is additive to biologics. It is currently unknown whether these same observations apply to some of the newer drugs, such as Janus kinase/signal transducer and activator of transcription inhibitors. But if reducing systemic inflammation and disease activity is favorable toward the CV system, then one might think that these agents may have a similarly favorable profile with respect to CVD risk.