title: Subcutaneous nodules are associated with cardiovascular events in patients with rheumatoid arthritis: results from a large US registry.
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.
authors.affiliation: Division of Rheumatology Stratton VAMC, Albany, NY, USA. prashant.kaushik@va.gov.|Department of Internal Medicine Albany Medical College, Albany, NY, USA. prashant.kaushik@va.gov.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kaushik
authors.affiliation: Divisions of Rheumatology & Pharmacoepidemiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. dsolomon@partners.org.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
authors.affiliation: New York University School of Medicine, New York, USA. jgreenberg@corrona.org.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Greenberg
authors.affiliation: Albany Medical College, Albany, NY, USA. jta0210@gmail.com.
authors.forename: James T
authors.initials: JT
authors.lastname: Anderson
authors.affiliation: University of Massachusetts Medical School, Worcester, MA, USA. greed@corrona.org.
authors.forename: George
authors.initials: G
authors.lastname: Reed
authors.affiliation: University of Miami Miller School of Medicine, Miami, FL, USA. dr_ozlem@hotmail.com.
authors.forename: Ozlem
authors.initials: O
authors.lastname: Pala
authors.affiliation: Division of Rheumatology, University of Nevada School of Medicine, Reno, NV, USA. dr.sumbulyuksel@gmail.com.
authors.forename: Bahar
authors.initials: B
authors.lastname: Sumbul-Yuksel
authors.affiliation: Medical Registrar, Sydney, Australia. Pooja.libra27@gmail.com.
authors.forename: Pooja
authors.initials: P
authors.lastname: Kadam
authors.affiliation: Albany Medical College and Director of Research, The Center for Rheumatology, Albany, NY, USA. jkremer@joint-docs.com.
authors.forename: Joel M
authors.initials: JM
authors.lastname: Kremer
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000150:complications* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000453:epidemiology; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000150:complications / Q000453:epidemiology; D014481:United States
keywords: Cardiovascular disease events; Rheumatoid arthritis; Subcutaneous nodules