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  • Review Article
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Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease

Nature Reviews Rheumatology volume 19, pages 417–428 (2023)Cite this article

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Abstract

The association between chronic inflammation and increased risk of cardiovascular disease in rheumatoid arthritis (RA) is well established. In the general population, inflammation is an established independent risk factor for cardiovascular disease, and much interest is placed on controlling inflammation to reduce cardiovascular events. As inflammation encompasses numerous pathways, the development of targeted therapies in RA provides an opportunity to understand the downstream effect of inhibiting specific pathways on cardiovascular risk. Data from these studies can inform cardiovascular risk management in patients with RA, and in the general population. This Review focuses on pro-inflammatory pathways targeted by existing therapies in RA and with mechanistic data from the general population on cardiovascular risk. Specifically, the discussions include the IL-1, IL-6 and TNF pathways, as well as the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) signalling pathway, and the role of these pathways in RA pathogenesis in the joint alongside the development of atherosclerotic cardiovascular disease. Overall, some robust data support inhibition of IL-1 and IL-6 in decreasing the risk of cardiovascular disease, with growing data supporting IL-6 inhibition in both patients with RA and the general population to reduce the risk of cardiovascular disease.

Key points

  • Rheumatoid arthritis (RA) and atherosclerotic cardiovascular disease share pro-inflammatory pathways that promote the pathogenesis of both conditions, including the IL-1 and IL-6 pathways.

  • Inflammation encompasses numerous pathways, and data from studies of targeted therapies developed for RA can provide insight into the potential effects of these therapies on cardiovascular risk.

  • Targeting IL-6 is considered more effective in controlling RA disease activity than targeting IL-1 and robust data also suggest that this therapy can reduce atherosclerotic cardiovascular disease risk in the general population.

  • Targeting some pro-inflammatory pathway(s), such as the TNF pathway, might be more beneficial than targeting others, such as JAK–STAT signalling, in reducing cardiovascular risk.

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Fig. 1: Shared inflammatory pathways of rheumatoid arthritis and atherosclerosis.

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Acknowledgements

The authors would like to acknowledge the following grant funding support: BNW, National Institutes of Health (NIH) K23 HL159276-01 and the American Heart Association 21CDA851511; KPL NIH R01 HL127118, the Harold and DuVal Bowen Fund and the Be Brave Fund.

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Authors and Affiliations

  1. Division of Cardiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA

    Brittany N. Weber

  2. Columbia University, Vagelos College of Physicians & Surgeons, New York, NY, USA

    Jon T. Giles

  3. Division of Rheumatology, Inflammation, and Immunity, Brigham and Women’s Hospital/Harvard Medical School, Boston, MA, USA

    Katherine P. Liao

  4. Rheumatology Section, VA Boston Medical Center, Boston, MA, USA

    Katherine P. Liao

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K.P.L. and B.N.W. researched data for the article. All authors contributed substantially to discussion of the content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Katherine P. Liao.

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Competing interests

J.T.G. has consulted for AbbVie, Bristol Myers Squibb, Eli Lilly, Gilead, Novartis, Pfizer and UCB. J.T.G. served as a co-author on secondary analyses for studies from the ORAL Surveillance study for which he received no compensation. B.N.W. has consulted for Horizon Therapeutics, Kinisika and NovoNordisk. K.P.L. declares no competing interests.

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Weber, B.N., Giles, J.T. & Liao, K.P. Shared inflammatory pathways of rheumatoid arthritis and atherosclerotic cardiovascular disease. Nat Rev Rheumatol 19, 417–428 (2023). https://doi.org/10.1038/s41584-023-00969-7

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