Funding Agency:

National Institute of Health

Total Project Period:

1/15/09 - 1/14/10

Total Project Award:

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Principal Investigator:

Larry W. Moreland, PhD, (Department of Medicine)

Co-Investigator:

Yue-Fang Chang, PhD

Project Summary:

Rheumatoid arthritis is associated with increase prevalence of cardiovascular disease and excess mortality. The Women’s Health Initiative (WHI) provides a unique opportunity to explore potential mechanisms involved in higher total mortality and cardiovascular disease incidence see in patients with rheumatoid arthritis.

We are proposing to test several hypotheses about the etiology of excess cardiovascular disease associated mortality in patients with rheumatoid arthritis. These hypotheses can be tested by identifying subjects with prevalent as well as incident rheumatoid arthritis, and non-RA controls, and testing samples for RA and cardiovascular related biomarkers, as well as determining cardiovascular related outcomes.

A major goal of the study will be to determine how many of the participants who report RA have serum anti-cyclic citrulinated peptide (CCP) autoantibodies or rheumatoid factor. The group with anti-CCP and rheumatoid factor (RF) can then be further subclassed by their HLA-DR status.

We propose to determine whether women who report RA and have anti-CCP antibodies and a RF have a different distribution of inflammatory markers and risk factors than those who do not have anti-CCP antibody and RF and presumably do not have RA.

We propose to determine whether the women with anti-CCP antibody and RF have a higher increased risk of cardiovascular disease and total mortality, and to evaluate whether increased mortality is secondary to the inflammation, activation of vascular and coagulation markers (D-dimer, fibrogenin, VCAM, ICAM) and traditional risk factors (Lipids).

The University of Pittsburgh investigative team combines the expertise in clinical and epidemiological experience of both senior and junior investigators and the collaborations from University of Colorado, Stanford University and Medstar Research Institute to appropriately phenotype the subjects with reported RA in the WHI and to perform the mechanistic studies as proposed