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Detrimental Impact Of Long-Term Cumulative Burden Of Rheumatoid Arthritis (RA) Disease Severity On Cardiovascular Outcomes In RA

Crowson, Cynthia S. MS
Myasoedova, Elena MD, PhD; Ilhan, Birkan ; Khun, Helen MS; Matteson, Eric L. MD, MPH
Sunday, October 27, 2013
Presenter Available:
9:00 am - 11:00 am
Poster Available:
8:30 am - 4:00 pm
Exhibit Hall B2-C-D
Session Title:
Rheumatoid Arthritis - Clinical Aspects I: Comorbidities in Rheumatoid Arthritis
Abstract Category:
Rheumatoid Arthritis - Clinical Aspects

Background/Purpose: Several studies have shown the associations of various measures of rheumatoid arthritis (RA) disease severity with unfavorable cardiovascular (CV) outcomes in RA. The association of cumulative RA severity burden on CV disease has not been investigated in longitudinal population-based studies. We aimed to examine the impact of long-term cumulative burden of RA disease severity on CV outcomes in RA.

Methods: A previously validated Claims-based Index of RA Severity (CIRAS; Ting et al. Arth Res Ther. 2008;10:R95) was used to estimate RA severity in a population-based incident cohort of patients with RA who were >/= 30 years old, fulfilled 1987 ACR criteria between 1/1/1988 and 1/1/2008, and had no history of CV disease. Claims-based data were used to calculate the CIRAS score: number of inflammatory marker tests, platelet counts, and chemistry panels; number of rheumatology visits, rehabilitation visits, assessment of rheumatoid factor, and the presence of Felty’s syndrome. CIRAS score was calculated at RA incidence and monthly during the follow-up using 12 months of prior information for each estimate. Data on antirheumatic medications (i.e. methotrexate, hydroxychloroquine, other disease-modifying antirheumatic drugs, biologics and corticosteroids), CV risk factors (i.e. hypertension, diabetes, smoking and dyslipidemia), incident CV events (myocardial infarction, CV death, angina, stroke, intermittent claudication, and heart failure) were collected from the medical records. Cox models with time-dependent covariates were used to assess the association of CIRAS score with the risk of CV events, adjusting for age, sex, calendar year of RA, CV risk factors and antirheumatic medication use.

Results: The study included 526 patients with RA (mean age at RA incidence 54.6 years, 71% female). The mean CIRAS score at RA incidence was 4.5 (standard deviation [SD] 1.9; min 0.6; max 9.5). During the mean follow-up of 7.3 years 103 CV events occurred. There was no apparent association of baseline CIRAS with the occurrence of CV events (hazard ratio [HR] 1.08 per 1 unit increase, 95% confidence interval [CI] 0.96, 1.22, p=0.20). The associations of the highest CIRAS value in the first year (HR 1.14 per 1 unit increase, 95%CI 0.99, 1.31, p=0.063) and monthly CIRAS (HR 1.13 per 1 unit increase, 95%CI 0.98, 1.31, p=0.096) with CV events approached statistical significance. Increase in cumulative moving average of monthly CIRAS was associated with significantly increased risk of CV events (HR 1.34 per 1 unit increase, 95%CI 1.09, 1.66). By cumulative moving percentage of time, patients who spent more time in medium  and high CIRAS tertiles were more likely to have an increased risk of CV events vs those who spent more time in the lower tertile (HR 1.07, 95%CI 0.97, 1.17 and HR 1.14, 95%CI 1.03, 1.25, respectively, per 10 unit increase in the amount of time in the tertile). 

Conclusion: Higher long-term burden of RA severity as expressed by cumulative moving average of monthly CIRAS and cumulative moving percentage of time in medium and high CIRAS tertiles was associated with significantly increased risk of CV events in RA suggesting accrued detrimental impact of RA severity over time.


E. Myasoedova, Genentech, Inc., 2; B. Ilhan, None; H. Khun, Genentech, Inc., 2; E. L. Matteson, Genentech, Inc., 2; C. S. Crowson, Genentech, Inc., 2.