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Atherosclerosis in rheumatoid arthritis: is it all about inflammation?

Nature Reviews Rheumatology volume 11, pages 390–400 (2015)Cite this article

Subjects

Key Points

  • The prevalence and rate of progression of atherosclerosis is increased in rheumatoid arthritis (RA), and atherosclerotic plaques in patients with RA might have a rupture-prone phenotype

  • Atherosclerosis is a chronic inflammatory condition, and similarities exist in the cellular processes and cytokines involved in both atherosclerosis and rheumatoid synovitis

  • Cardiovascular disease (CVD) and RA share genetic and environmental risk factors, including polymorphisms in genes within the HLA region, smoking and obesity

  • The prevalence of some traditional CVD risk factors is increased in patients with RA, but traditional risk-prediction models perform poorly in this population

  • Chronic inflammation is closely linked with atherosclerosis in RA; burden of inflammation is associated with clinical and subclinical CVD, and PET can reveal arterial inflammation in patients with active RA

  • Although treatments for RA seem to have beneficial effects on cardiovascular event rates, mortality remains increased and further work is required to better estimate and treat cardiovascular risk in RA

Abstract

Rheumatoid arthritis (RA) has long been associated with increased cardiovascular risk, but despite substantial improvements in disease management, mortality remains high. Atherosclerosis is more prevalent in RA than in the general population, and atherosclerotic lesions progress at a faster rate and might be more prone to rupture, causing clinical events. Cells and cytokines implicated in RA pathogenesis are also involved in the development and progression of atherosclerosis, which is generally recognized as an inflammatory condition. The two diseases also share genetic and environmental risk factors, which suggests that patients who develop RA might also be predisposed to developing cardiovascular disease. In RA, inflammation and atherosclerosis are closely linked. Inflammation mediates its effects on atherosclerosis both through modulation of traditional risk factors and by directly affecting the vessel wall. Treatments such as TNF inhibitors might have a beneficial effect on cardiovascular risk. However, whether this benefit is attributable to effective control of inflammation or whether targeting specific cytokines, implicated in atherosclerosis, provides additional risk reduction is unclear. Further knowledge of the predictors of cardiovascular risk, the effects of early control of inflammation and of drug-specific effects are likely to improve the recognition and management of cardiovascular risk in patients with RA.

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Figure 1: Important pathological features common to both atherosclerotic plaque and the inflamed rheumatoid synovium.
Figure 2: Development of an atherosclerotic plaque.

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Acknowledgements

I.N.B. is a National Institute for Health Research (NIHR) Senior Investigator and is supported by Arthritis Research UK, the Manchester Academic Health Science Centre, the NIHR Manchester Musculoskeletal Biomedical Research Unit, the NIHR Manchester Wellcome Trust Clinical Research Facility and the Manchester Biomedical Research Centre. S.S. acknowledges funding from the North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics, which is funded by the Medical Research Council (grant number G1000417/94909) in partnership with ICON, GlaxoSmithKline, AstraZeneca and the Medical Evaluation Unit, and is also supported by the NIHR Manchester Musculoskeletal Biomedical Research Unit. The views expressed in this publication are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.

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Authors and Affiliations

  1. Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute of Inflammation and Repair, The University of Manchester, Manchester Academic Health Science Centre, Brunswick Street, Manchester, M13 9PL, UK

    Sarah Skeoch

  2. NIHR Manchester Musculoskeletal Biomedical Research Unit, and Kellgren Centre for Rheumatology, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, M13 9WL, UK

    Ian N. Bruce

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  1. Sarah Skeoch
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Both authors contributed to researching data for the article, discussing the content, writing the article and review and/or editing of the manuscript before submission.

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Correspondence to Ian N. Bruce.

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I.N.B. declares that he has received consultancy and/or speaker's fees from GSK, Pfizer, Medimmune, Merck Serono and UCB. S.S. declares no competing interests.

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Skeoch, S., Bruce, I. Atherosclerosis in rheumatoid arthritis: is it all about inflammation?. Nat Rev Rheumatol 11, 390–400 (2015). https://doi.org/10.1038/nrrheum.2015.40

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