Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.

Increased Risk of Total Mortality with Anti-Cyclic Citrullinated Peptide (Anti-CCP) Positivity among Postmenopausal Women Reporting RA.

Mackey5,  Rachel H., Kuller5,  Lewis H., Holers4,  Michael, Deane4,  Kevin, Walitt2,  Brian, Robinson3,  Bill, Chang5,  Yuefang

Brown University
Georgetown University
Stanford University
University of Colorado
University of Pittsburgh


The objective of this report is to evaluate the relationship between rheumatoid arthritis (RA) and total mortality among postmenopausal women from the Women's Health Initiative (WHI). Among the 161,808 postmenopausal women aged 50–79 years who enrolled in the Women's Health Initiative (WHI) at baseline and who have been followed up for ~ ten years, we evaluated total mortality risk for women who reported rheumatoid arthritis (RA) at baseline or followup (n= 16,461 (10.2%) compared with women with no reported RA (n=125,372). A study in 2 WHI centers documented that ~15% of self-reported RA was probable clinical RA, and that self-reported use of disease-modifying anti-rheumatic drugs (DMARDS) improved the positive predictive value of the self-report RA to 62%. To further improved classification we measured anti-cyclic citrullinated peptide (anti-CCP), a sensitive and specific marker of RA.


We sampled n=9,988 (66%) of the white, black, or Hispanic WHI participants who reported RA at baseline or followup and who had adequate stored serum specimens, and measured anti-CCP via 2nd generation ELISA. Cox proportional hazards regression was used to model the relationships of self-reported RA, DMARD use and anti-CCP positivity to total mortality using followup data through April 2009.


At baseline, mean(SD) age was 64(7) years, 24.5% were African-American and 10% were Hispanic. The overall prevalence of anti-CCP positivity was 8.13% (n=812), but was much higher (~51%) among women reporting both RA at baseline and DMARD use (Table.)

Table: Anti-CCP positivity and age-adjusted mortality rates by self-reported RA and DMARD use

Reported RADMARD*Anti-CCPN%Total Mortality rate/1000 Person Years
At BL (or BL & followup     
 No-465095.8%14.16 (12.50, 16.06)
 n=4855+2054.2%22.38 (15.12, 33.34)
 Yes-39549.3%18.35 (10.84, 32.34)
 n=802+40750.7%25.74 (17.01, 39.23)
At followup only     
 No-385296.5%10.45 (8.91, 12.26)
 n=3992+1403.5%18.70 (10.65, 33.49)
 Yes-27982.3%23.14 (10.40, 51.50)
 n=339+6017.7%32.05 (8.02, 128.14)
Nevern/an/a128,758-8.39 (8.15, 8.64)

Age-adjusted all-cause mortality rates were strikingly higher among anti-CCP positive women, regardless of reported DMARD use. Compared with women in WHI who never reported RA, total mortality was also substantially elevated among women who reported RA but did not report DMARD use and who were negative for anti-CCP.(Table) Among those who reported RA at baseline (excluding women with CVD or cancer at baseline), the hazard ratio (HR)(95% CI) for total mortality was 1.74 (1.33, 2.27) for anti-CCP positivity and 1.90 (1.42, 2.53) for reported DMARD use, in Cox models adjusted for age, white blood cell count (WBC), ethnicity, smoking, waist circumference, hypertension, diabetes, education and hormone therapy. Age, smoking, diabetes and WBC were also significant predictors.


Among postmenopausal women in WHI, anti-CCP positivity was associated with a substantial excess in total mortality compared with women who reported RA but were anti-CCP negative (regardless of self-reported DMARD use), or with women who did not report RA. Evaluation of additional risk markers is in progress to understand the reasons for this anti-CCP -associated excess mortality in older women.

To cite this abstract, please use the following information:
Mackey, Rachel H., Kuller, Lewis H., Holers, Michael, Deane, Kevin, Walitt, Brian, Robinson, Bill, et al; Increased Risk of Total Mortality with Anti-Cyclic Citrullinated Peptide (Anti-CCP) Positivity among Postmenopausal Women Reporting RA. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :71
DOI: 10.1002/art.27840

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