Background/Purpose:

Cardiovascular Disease (CVD) is now recognized to be a major comorbidity of patients with rheumatoid arthritis.  Predictors of CVD have been shown to include a variety of measures of RA disease activity and severity (1). Although subcutaneous nodules (SQN) are associated with more severe RA, until this time there had been no clinical phenotypic characteristic which was immediately recognizable as a marker of increased risk for CVD in patients with RA.

Methods:

Data are from the CORRONA database from Oct 2001 to Sept 2011 was evaluated.  23327 patients with RA, including 182,201 individual visits who have an average of 3 years of follow-up data  and with 70455 patient-years and 795 CV events are included in this analysis.   Presence or absence of SCN have been routinely collected over the entire 11 year history of the registry.  CV events (ischemic heart disease including MI, stroke/TIA, CHF and CV death ) were defined by MD reported events and exclusion of events not confirmed by the sites completing a follow up form.  Cox regression models were used to estimate HR for time to first event with entry into CORRONA as the origin.  Unadjusted and adjusted Hazard Ratios (HR) for SCN were estimated.   A multivariable model was fit that considered the following factors as possible covariates: age, gender, age of onset of RA, presence of diabetes mellitus (DM), hypertension, smoking, alcohol consumption,  use of a lipid lowering agent.  Significant factors were retained in the model.

Results:  

Table 1 shows the estimated HR for SCN unadjusted and then adjusted with the covariates considered in the model.   Unadjusted HR for SCN is 1.44, 95% CI: [1.23-1.67].  Adjusted HR is 1.25 [1.07-1.46]. An interaction of age and gender provided a better fit of the model, females with a steeper increase in risk with age than males. 

Conclusion:

We report for the first time, from a very large US observational registry, that SCN confer a significantly increased likelihood of CVD in patients with RA followed for a period of > 3 years.  While active RA is a risk factor for CVD the presence of subcutaneous nodules, an immediately assessable and accessible clinical phenotype, confers an increased risk for this major comorbidity.

1             Solomon DH, Kremer J, Curtis JR, Hochberg MC, Reed G, Tsao P, Farkouh ME, Setoguchi S, Greenberg JD. Explaining the cardiovascular risk associated with rheumatoid arthritis: traditional risk factors versus markers of rheumatoid arthritis severity. Ann Rheum Dis 2010; 69(11):1920-5.