• Crowson, Cynthia (PI)
  • Crowson, Cindy (PI)
  • Gabriel, Sherine E (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)

Project: Research project

Project Details


DESCRIPTION: (Applicant's Abstract) The hypotheses to be tested in this
proposal are built on findings from two intriguing, but rather disparate lines
of investigation. The first is the recent data suggesting that the excess
mortality experienced by people with rheumatoid arthritis (RA) may result from
increased rates of coronary heart disease (CHD) among RA patients compared to
the general population. The second is the rapidly growing body of evidence
indicating that chronic systemic inflammation (such as that which occurs in RA)
plays an important role of chronic inflammation in CHD. We propose 3 specific
aims to investigate this subject: First, we will use a cohort study to test the
hypothesis that the incidence of acute MI (the central manifestation of CHD) is
higher in RA subjects compared to controls. Second, we will identify high-risk
RA subgroups and, using a novel adaptation of the case-cohort design,
investigate interactions between RA and the major CHD risk factors (e.g.
smoking, hyperlipidemia, exogenous estrogens). Third, we will conduct studies
on archived autopsy heart tissue to test the hypothesis that coronary
atherosclerosis is more extensive in RA subjects compared to matched controls.

A unique set of circumstances allows us to address each of these aims
rigorously and efficiently. We will incorporate and extend our already
assembled population-based RA incidence cohort and identify validated definite
acute MI outcomes using the cardiovascular surveillance techniques developed
through out NIH-funded companion study, "Coronary Disease Morbidity and
Mortality in a Population" (HL59205). Our population-based data resources, with
essentially complete enumeration of a geographically defined population,
allowed us to design an analytic plan which nearly quadruples the statistical
power of our risk factor analyses, compared with typical cohort analyses.
Third, the availability of extensive autopsy material (the autopsy rate in this
community is four-fold higher than the national rate and all autopsies have
been performed at the same center since 1930) provides us with a unique
opportunity to assess the pathologic characteristics of atherosclerosis among
RA subjects compared to controls. When combined with our experienced
multidisciplinary investigative team, these resources lend us a capability, not
available elsewhere, to rigorously examine the risks and determinants of
coronary heart disease in patients with RA. These results will lay the
foundation for a program of research aimed at elucidating the mechanisms for
CHD in RA patients and at improving our understanding of the role of
inflammation in the pathogenesis of CHD in the general population.
Effective start/end date9/1/002/28/17


  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $646,540.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $647,324.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $639,388.00
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases: $667,898.00


  • Medicine(all)


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