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Clinical Review State of the Art Review

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

BMJ 2018; 361 doi: (Published 23 April 2018) Cite this as: BMJ 2018;361:k1036
  1. Bryant R England, assistant professor of medicine1 2,
  2. Geoffrey M Thiele, professor of internal medicine1 2,
  3. Daniel R Anderson, associate professor of internal medicine3,
  4. Ted R Mikuls, Umbach professor of rheumatology1 2
  1. 1Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, USA
  2. 2Division of Rheumatology and Immunology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
  3. 3Division of Cardiology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA
  1. Correspondence to: T R Mikuls tmikuls{at}


Rheumatoid arthritis is a systemic autoimmune disease characterized by excess morbidity and mortality from cardiovascular disease. Mechanisms linking rheumatoid arthritis and cardiovascular disease include shared inflammatory mediators, post-translational modifications of peptides/proteins and subsequent immune responses, alterations in the composition and function of lipoproteins, increased oxidative stress, and endothelial dysfunction. Despite a growing understanding of these mechanisms and their complex interplay with conventional cardiovascular risk factors, optimal approaches of risk stratification, prevention, and treatment in the context of rheumatoid arthritis remain unknown. A multifaceted approach to reduce the burden posed by cardiovascular disease requires optimal management of traditional risk factors in addition to those intrinsic to rheumatoid arthritis such as increased disease activity. Treatments for rheumatoid arthritis seem to exert differential effects on cardiovascular risk as well as the mechanisms linking these conditions. More research is needed to establish whether preferential rheumatoid arthritis therapies exist in terms of prevention of cardiovascular disease. Ultimately, understanding the unique mechanisms for cardiovascular disease in rheumatoid arthritis will aid in risk stratification and the identification of novel targets for meaningful reduction of cardiovascular risk in this patient population.


  • Series explanation: State of the Art Reviews are commissioned on the basis of their relevance to academics and specialists in the US and internationally. For this reason they are written predominantly by US authors

  • Contributors: BRE did the literature review and prepared the initial draft of the manuscript. All authors were involved in the conception, drafting, and editing of the manuscript. TRM is the guarantor.

  • Funding: BRE is supported by a University of Nebraska Medical Center (UNMC) internal medicine scientist development award, the UNMC Mentored Scholars Program, and the UNMC College of Medicine Physician-Scientist Training Program. TRM is supported by grants from the National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (P50AR060772), National Institute of Alcohol Abuse and Alcoholism (R25AA020818), National Institute of General Medical Sciences (U54GM115458), Veterans Affairs Office of Research and Development (Merit Award, CX000896), Bristol Myers Squibb, and Ironwood Pharmaceuticals. DRA is supported by the Harry R and Sarah H Caspersen Coronary Artery Disease Research Fund and the Division of Cardiovascular Medicine, Department of Internal Medicine, UNMC. GMT is supported by grants from the Rheumatology Research Foundation and a Bristol Myers Squibb investigator initiated grant.

  • Competing interests: We have read and understood the BMJ policy on declaration of interests and declare the following interests: TRM serves as a consultant for Pfizer.

  • Provenance and peer review: Commissioned; externally peer reviewed.

  • Patient involvement: No patients were involved in the creation of this article.

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