PLoS One. 2016 Mar 15;11(3):e0151245.

Rheumatoid Arthritis and Incidence of Twelve Initial Presentations of Cardiovascular Disease: A Population Record-Linkage Cohort Study in England.

Pujades-Rodriguez M1,2, Duyx B1, Thomas SL3, Stogiannis D1, Rahman A4, Smeeth L1,3, Hemingway H1.

  • 1Farr Institute of Health Informatics Research, University College London, 222 Euston Road, London NW1 2DA, United Kingdom.
  • 2Leeds Institute of Biomedical and Clinical Sciences, MRC Medical Bioinformatics Centre, Worsley Building, University of Leeds, Leeds LS2 9JT, United Kingdom.
  • 3Department of Non-communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom.
  • 4Centre of Rheumatology Research, Division of Medicine, Faculty of Medical Sciences, University College London, London WC1E 6JF, United Kingdom.




While rheumatoid arthritis is an established risk factor for cardiovascular disease (CVD), our knowledge of how the pattern of risk varies for different cardiovascular phenotypes is incomplete. The association between rheumatoid arthritis and the initial presentation of 12 types of CVDs were examined in a contemporary population of men and women of a wide age range.


CALIBER data, which links primary care, hospital and mortality data in England, was analysed. A cohort of people aged ≥18 years and without history of CVD was assembled and included all patients with prospectively recorded rheumatoid arthritis from January 1997, until March 2010, matched with up to ten people without rheumatoid arthritis by age, sex and general practice. The associations between rheumatoid arthritis and the initial presentation of 12 types of CVDs were estimated using multivariable random effects Poisson regression models.


The analysis included 12,120 individuals with rheumatoid arthritis and 121,191 comparators. Of these, 2,525 patients with and 18,146 without rheumatoid arthritis developed CVDs during a median of 4.2 years of follow-up. Patients with rheumatoid arthritis had higher rates of myocardial infarction (adjusted incidence ratio [IRR] = 1.43, 95%CI 1.21-1.70), unheralded coronary death (IRR = 1.60, 95%CI 1.18-2.18), heart failure (IRR = 1.61, 95%CI 1.43-1.83), cardiac arrest (HR = 2.26, 95%CI 1.69-3.02) and peripheral arterial disease (HR = 1.36, 95%CI 1.14-1.62); and lower rates of stable angina (HR = 0.83, 95%CI 0.73-0.95). There was no evidence of association with cerebrovascular diseases, abdominal aortic aneurysm or unstable angina, or of interactions with sex or age.


The observed associations with some but not all types of CVDs inform both clinical practice and the selection of cardiovascular endpoints for trials and for the development of prognostic models for patients with rheumatoid arthritis.

PMID: 26978266



Rheumatoid arthritis is a common long-lasting disease that causes pain, swelling and stiffness in the joints. Previous studies have shown that people with rheumatoid arthritis might be more likely to suffer from cardiovascular diseases and die than people without this disease. The increased of cardiovascular risk might be partly related to the widespread inflammation that is present in people with this rheumatoid arthritis and to the use of certain types of medication used for its treatment.

The aim of the study was to compare the risk of developing different types of cardiovascular diseases in people with or without rheumatoid arthritis who had not been previously diagnosed with any cardiovascular disease and to examine whether a higher risk is found for all or only for some types of cardiovascular diseases. To do this work we analysed clinical information contained in electronic medical records routinely collected by general practitioners and during hospitalisation in England. We first classified people according to whether they had been diagnosed or not with rheumatoid arthritis and excluded those with prior history of cardiovascular disease in the records. We then identified people who were diagnosed with any of the most common types of cardiovascular diseases during the following months and years, for example angina, heart attack, cardiac arrest, heart failure and stroke. We finally compared the risk of each of these different types of cardiovascular diseases in people with and without rheumatoid arthritis.

The results of the study showed that people with rheumatoid arthritis had a higher risk of suffering from heart attack, coronary death, heart failure, cardiac arrest and peripheral arterial disease. This higher risk was found in both patients recently diagnosed with rheumatoid arthritis and in those who had the disease for ten years or more, in men and women and in all age groups. In our study population, people with rheumatoid arthritis did not have a higher risk of stroke and had a lower risk of being diagnosed with stable angina. The last finding suggests that people with rheumatoid arthritis and clinicians might not always easily recognise the symptoms of coronary diseases such as chest pain related angina.

Because we wanted to understand how important was the observed increase in risk of cardiovascular diseases related to rheumatoid arthritis, we compared this to the magnitude of risk found in patients with diabetes, and our data showed that the size of risk related to these two diseases was similar.

The importance of this study is two-fold: first, our findings suggest that people with rheumatoid arthritis are more likely to experience cardiovascular diseases than people without this disease, highlighting the importance of regularly assessing, monitoring and adequately managing cardiovascular risk in patients with rheumatoid arthritis. Second, the results suggest that some deaths could be prevented if patients with rheumatoid arthritis are adequately informed about the increased cardiovascular risk conferred by this disease and they are educated on how to recognise cardiovascular symptoms.