Rheumatoid arthritis (RA) is associated with excess cardiovascular disease and excess mortality;the Women's Health Initiative (WHI) provides a unique opportunity to explore potential mechanisms. Anti-cyclic citrullinated peptide (anti-CCP) autoantibodies which has a very high sensitivity and specificity for the diagnosis of RA provide the opportunity to use the WHI database to identify women who have RA. A major goal of the study will be to determine how many of the WHI participants who have self-reported RA have serum anti-CCP autoantibodies. The group of WHI women with self-reported RA with anti-CCP can then be further subclassed by their HLA-DR status. We will include a large sample of African Americans and Hispanics so that comparison across race and ethnic groups will be possible. We propose to determine whether the women with anti-CCP antibody have a higher increased risk of cardiovascular disease and total mortality, and to evaluate whether increased mortality is secondary to the inflammation (cytokine profiles), activation of vascular and coagulation markers (D-dimer, fibrogen, VCAM, ICAM) and traditional risk factors (e.g. lipids). The University of Pittsburgh Investigative team combines the clinical and epidemiological research experience. We also have collaborations with investigators at University of Colorado, Stanford University and Medstar Research Institute. Further research is needed to determine optimal approaches to reducing CV morbidity and mortality in persons with RA, including the development of refined CV risk stratification algorithms that take into account the important role of non-traditional CV risk factors in this population.