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Nancy A. Shadick, MD, MPH; Nancy R. Cook, ScD; Elizabeth W. Karlson, MD; Paul M Ridker, MD, MPH; Nancy E. Maher, MPH; JoAnn E. Manson, MD, DrPH; Julie E. Buring, ScD; I.-Min Lee, MBBS, ScD

Arch Intern Med. 2006;166:2490-2494.

Background  The purpose of this study was to examine whether levels of C-reactive protein (CRP), a sensitive marker of disease activity in rheumatoid arthritis (RA), are associated with increased risk of subsequent RA.

Methods  Eligible subjects were 39 876 healthy women from the Women's Health Study, a completed randomized trial of aspirin and vitamin E in cardiovascular disease and cancer prevention, begun in 1992. We included 27 939 women who provided blood samples at baseline that could be assayed for CRP.

Results  During 9.9 years of follow-up, 398 women reported a new diagnosis of RA. Of these, 90 cases were confirmed on medical chart review using American College of Rheumatology criteria. In age-adjusted analysis, the relative risks for developing confirmed, incident RA associated with increasing tertiles of CRP (first, second, and third) were 1.00 (reference value), 0.94 (0.54-1.61), and 1.29 (0.78-2.12) (P = .30 for trend). Further adjustment for randomized treatment, age, body mass index, and smoking demonstrated corresponding relative risks of 1.00 (reference value), 0.95 (0.55-1.65), and 1.33 (0.77-2.30) (P = .48 for trend). When we examined whether CRP levels predicted incident RA within 4 years, between 5 to 8 years, and 9 or more years after CRP measurement, we found no significant associations for any time period.

Conclusions  In this prospective study of healthy women, a single CRP level did not predict increased risk of RA. Furthermore, CRP measurement closer to the time of diagnosis was not predictive. The consistency of this effect throughout different time periods from diagnosis suggests that CRP does not have a large effect in predicting incident RA.

Author Affiliations: Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Harvard Medical School (Drs Shadick and Karlson and Ms Maher); Divisions of Preventive Medicine (Drs Cook, Ridker, Manson, Buring, and Lee), Cardiovascular Medicine (Dr Ridker), and Aging (Dr Buring), Department of Medicine, Brigham and Women's Hospital, Harvard Medical School; Department of Ambulatory Care and Prevention, Harvard Medical School (Dr Buring); and Department of Epidemiology, Harvard School of Public Health (Drs Cook, Ridker, Manson, Buring, and Lee); Boston, Mass.

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