Cardiovascular Comorbidity in Rheumatoid Arthritis
An abstract review session titled “Diagnosis, Manifestations, & Outcomes II: Cardiovascular Comorbidities” was held on November 10 at the 2019 ACR/ARP Annual Meeting in Atlanta, GA. Studies presented in this session were linked by the overarching question of how to meaningfully impact cardiovascular (CV) risk in patients with rheumatoid arthritis (RA).
Following the presentation, our featured expert, Alan L. Epstein, MD, who attended this session, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Epstein’s clinical perspectives on this session are presented here.
“There is great interest in improving our ability to impact CV risk in meaningful ways in patients with RA, but I do think that there is room for improvement as we put this expanding knowledge base into practice.”
We are well aware that the risks of cardiovascular disease (CVD) and CV mortality are increased in patients with RA. This being the case, we would like to know which patients with RA are at the highest risk, how we can better identify them, and how we can impact that risk in meaningful ways. In abstract 922, researchers from the Mayo Clinic, in Rochester, MN, evaluated the incidence of major CVD events in patients with incident RA in the 1980s, 1990s, and 2000s and found that those with incident RA in the 2000s had a markedly lower cumulative incidence of any CVD events as compared with those diagnosed with RA in the 1980s and 1990s. A question posed at the end of the presentation was whether the reduction was driven primarily by improvements in CV care or advances in RA treatment. I think that improvements likely reflect multiple factors, but this particular study was not designed to answer that question. Accurately identifying patients with RA who are at a higher CV risk remains a challenge, and this abstract review session also included interesting related work by Karpouzas et al, who studied the use of high-sensitivity cardiac troponin I and beta-2-glycoprotein-I immunoglobulin A antibodies to screen patients with RA and presented their findings in abstract 924.
We do have data that support cardioprotective effects from modern RA therapies. For instance, methotrexate (MTX) appears to mitigate some of the risk of CVD in patients with RA, although the mechanisms that may account for this reduction are uncertain. Investigators presenting abstract 926 aimed to determine whether the association of MTX with reduced CVD risk in RA was related to modulation of RA disease activity or to direct effects. In their multicenter cohort of 2168 patients with RA, MTX use was associated with a 30% reduced risk of composite CVD events and a 60% reduced risk of congestive heart failure hospitalizations. In their multivariable models to assess direct and indirect effects, adjustment for post-MTX disease activity did not significantly alter the association of MTX use with composite or individual CVD events, leading researchers to conclude that the modification of RA disease activity did not appear to be the primary driver in the lower CV risk observed with MTX use in patients with RA.
Differences in CV risk related to RA treatment is an active area of research. Singh et al recently published results of a systematic review and meta-analysis (data not presented at ACR/ARP 2019) to evaluate the comparative effects of tumor necrosis factor inhibitors (TNFis), non-TNFi biologics, and conventional synthetic disease-modifying antirheumatic drugs on CV risk in RA. The interleukin 6 receptor antagonist tocilizumab reduced the risk of major adverse CV events more significantly compared with TNFis or abatacept. There is increased interleukin 6 signaling in RA, and that increased signaling may, in fact, be very important in driving the increased CV risk seen in patients with RA. Authors of abstract 923 noted that the chronic inflammation of RA is linked to increased risk that may manifest as venous thromboembolism in addition to atherosclerotic CVD. There is a 1.5- to 2-fold increased risk of atherosclerotic CVD and a 2- to 3-fold increased risk of venous thromboembolism in RA. Moreover, the potential association between the use of Janus kinase inhibitors and an increased risk of deep vein thrombosis and pulmonary embolism in patients with RA is a topic of much interest and controversy at the present time.
There is great interest in improving our ability to impact CV risk in meaningful ways in patients with RA, but I do think that there is room for improvement as we put this expanding knowledge base into practice. The CV risk in RA is comparable to that of diabetes, but RA is frequently overlooked as a CV risk factor.
Johnson T, Baker J, Roul P, et al. Methotrexate is associated with reduced cardiovascular risk in rheumatoid arthritis independent of disease activity modification [abstract 926]. Arthritis Rheumatol. 2019;71(suppl 10). https://acrabstracts.org/abstract/methotrexate-is-associated-with-reduced-cardiovascular-risk-in-rheumatoid-arthritis-independent-of-disease-activity-modification/. Accessed November 14, 2019.
Karpouzas GA, Estis J, Rezaeian P, Todd J, Budoff MJ. High-sensitivity cardiac troponin I is a biomarker for occult coronary plaque burden and cardiovascular events in patients with rheumatoid arthritis. Rheumatology (Oxford). 2018;57(6):1080-1088.
Karpouzas G, Ormseth S, Hernandez E, Budoff M. Highly-sensitive cardiac troponin-I and beta-2-glycoprotein-I IgA antibodies inform the utility of screening and follow-up non-invasive coronary atherosclerosis evaluation and optimize cardiovascular risk assessment in rheumatoid arthritis [abstract 924]. Arthritis Rheumatol. 2019;71(suppl 10). https://acrabstracts.org/abstract/highly-sensitive-cardiac-troponin-i-and-beta-2-glycoprotein-i-iga-antibodies-inform-the-utility-of-screening-and-follow-up-non-invasive-coronary-atherosclerosis-evaluation-and-optimize-cardiovascular/. Accessed November 14, 2019.
Kim SC, Solomon DH, Liu J, Franklin JM, Glynn RJ, Schneeweiss S. Risk of venous thromboembolism in patients with rheumatoid arthritis: initiating disease-modifying antirheumatic drugs. Am J Med. 2015;128(5):539.e7-e17.
Myasoedova E, Davis J, Roger V, Achenbach S, Crowson C. Improved incidence of cardiovascular disease in patients with incident rheumatoid arthritis in 2000s: a population-based cohort study [abstract 922]. Arthritis Rheumatol. 2019;71(suppl 10). https://acrabstracts.org/abstract/improved-incidence-of-cardiovascular-disease-in-patients-with-incident-rheumatoid-arthritis-in-2000s-a-population-based-cohort-study/.
Ozen G, Pedro S, Schumacher R, Simon T, Michaud K. First cardiovascular event in rheumatoid arthritis: do patients with venous thromboembolism have a different risk profile than patients with atherosclerotic cardiovascular disease [abstract 923]? Arthritis Rheumatol. 2019;71(suppl 10). https://acrabstracts.org/abstract/first-cardiovascular-event-in-rheumatoid-arthritis-do-patients-with-venous-thromboembolism-have-a-different-risk-profile-than-patients-with-atherosclerotic-cardiovascular-disease/.
Ridker PM. From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res. 2016;118(1):145-156.
Singh S, Fumery M, Singh AG, et al. Comparative risk of cardiovascular events with biologic and synthetic disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis: a systematic review and meta-analysis. Arthritis Care Res (Hoboken). 2019 Mar 15. doi: 10.1002/acr.23875. [Epub ahead of print]
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