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Subcutaneous nodules are associated with cardiovascular events in patients with rheumatoid arthritis: results from a large US registry

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Abstract

Subcutaneous nodules are the most common conspicuous extra-articular manifestation of rheumatoid arthritis (RA). Cardiovascular disease (CVD) is the leading cause of death in patients with RA. The objective of this study is to examine the possibility of a relationship between subcutaneous nodules and “first ever” cardiovascular disease event, i.e., myocardial infarction (MI), stroke, or cardiovascular death in a large registry-cohort of patients with RA. Patient information was collected from the CORRONA registry from October 2001 to September 2011. A total of 26,042 patients with RA were studied for the presence or absence of subcutaneous nodules. Cox proportional hazards regression models were constructed to estimate the hazard ratios (HR) for CVD events in relation to subcutaneous nodules at baseline. Three statistical models were used to examine the association between subcutaneous nodules and CVD: Model A adjusted for age and sex associated risk, model B adjusted for traditional CV risk factors, and model C adjusted for factors in models A and B plus underlying RA-specific measures. The definition of primary exposure was “subcutaneous nodules at baseline.” A total of 3908 patients had subcutaneous nodules at baseline. Of the 566 total composite CVD events, 138 occurred in the group that had SCN at baseline. Incidence rate-ratio values (patients with subcutaneous nodules at baseline vs. no subcutaneous nodules at baseline) for composite CVD events, MI, stroke, and cardiovascular death were 1.55, 1.65, 1.37, and 1.68, respectively. Adjusted HR values (95 % CI) for composite CVD events based on “subcutaneous nodules-status at baseline” (primary exposure) were as follows: 1.35 (1.11–1.63) for model A, 1.25 (1.03–1.52) for model B, and 1.03 (0.831–1.277) for model C. Subcutaneous nodules were associated with increased CVD events in RA. This association persisted after adjusting for age, sex, and traditional CV risk factors.

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Abbreviations

RA:

Rheumatoid arthritis

CVD:

Cardiovascular disease

CORRONA:

Consortium of Rheumatology Researchers of North America

ACR:

American College of Rheumatology

MI:

Myocardial infarction

BMI:

Body mass index

DM:

Diabetes mellitus

CDAI:

Clinical disease activity index

mHAQ:

Modified health assessment questionnaire

NSAID:

Nonsteroidal anti-inflammatory drugs

IR:

Incidence rate

IRR:

Incidence rate ratio

HR:

Hazard ratio

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Acknowledgments

We are grateful to Ms. SP Messing and Ms. J Arora (University of Rochester School of Medicine and Dentistry, Rochester, NY), and Ms. KC Saunders (CORRONA, Inc., Southborough, MA) for help with CORRONA database.

Disclosures

None.

Competing interests

Dr. Solomon has no personal financial relationships with any pharmaceutical company; he receives salary support through research contracts to his institutions from Lilly, Amgen, Pfizer, and CORRONA, serves in unpaid roles on trials sponsored by Pfizer, Lilly, and Bristol Myers Squibb, and receives royalties from UpToDate for unrelated work.

Dr. Greenberg has received consulting fees from Celgene, Merck, Novartis, and Pfizer and receives salary and shares from CORRONA. Dr. Kremer owns stock in CORRONA and receives a salary from CORRONA. He has received research support from Abbott, Amgen, BMS, Janssen, Genentech, Pfizer, and Roche. In the last 2 years, Abbott, Amgen, AstraZeneca, BMS, Janssen, Genentech, Lilly, Pfizer, Roche, Vertex, and UCB have supported CORRONA through contracted subscriptions to the database. The study design, data analysis, and reporting of results in this presentation were performed independent of all funding sources. No financial or nonfinancial conflicts of interest exist for any of the authors.

Authors’ contributions

All authors (1) have made substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data, (2) have been involved in drafting the manuscript or revising it critically for important intellectual content, (3) have given final approval of the version to be published, and (4) agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Each author has participated sufficiently in the work to take public responsibility for appropriate portions of the content.

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Authors and Affiliations

  1. Division of Rheumatology Stratton VAMC, Albany, NY, USA

    Prashant Kaushik

  2. Department of Internal Medicine Albany Medical College, Albany, NY, USA

    Prashant Kaushik

  3. Divisions of Rheumatology & Pharmacoepidemiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA

    Daniel H. Solomon

  4. New York University School of Medicine, New York, USA

    Jeffrey D. Greenberg

  5. Albany Medical College, Albany, NY, USA

    James T Anderson

  6. University of Massachusetts Medical School, Worcester, MA, USA

    George Reed

  7. University of Miami Miller School of Medicine, Miami, FL, USA

    Ozlem Pala

  8. Division of Rheumatology, University of Nevada School of Medicine, Reno, NV, USA

    Bahar Sumbul-Yuksel

  9. Medical Registrar, Sydney, Australia

    Pooja Kadam

  10. Albany Medical College and Director of Research, The Center for Rheumatology, Albany, NY, USA

    Joel M. Kremer

Authors
  1. Prashant Kaushik
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  2. Daniel H. Solomon
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  8. Pooja Kadam
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  9. Joel M. Kremer
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on behalf of the CORRONA investigators

Corresponding author

Correspondence to Prashant Kaushik.

Additional information

Bullet points

1. Subcutaneous nodules are the most readily apparent extra-articular manifestation of RA on a thorough clinical examination.

2. There is a significant association between subcutaneous nodules and CV events (MI, stroke and CV death) in RA patients with longstanding disease, with subcutaneous nodules when first examined.

3. The presence of subcutaneous nodules can function as an immediate and tangible indicator that the RA patient in the examination room may be at increased risk for the major comorbidity of CVD, independent of age, sex, and traditional CV risk-factors.

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Kaushik, P., Solomon, D.H., Greenberg, J.D. et al. Subcutaneous nodules are associated with cardiovascular events in patients with rheumatoid arthritis: results from a large US registry. Clin Rheumatol 34, 1697–1704 (2015). https://doi.org/10.1007/s10067-015-3032-9

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  • DOI: https://doi.org/10.1007/s10067-015-3032-9

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