Cardiovascular (CV) disease is a major cause of morbidity and mortality in rheumatoid arthritis (RA). This increased CV risk is thought to be mediated through shared inflammatory pathways;however, this has been difficult to prove. This proposal is an application for renewal of an existing R01, """"""""RA and Cardiovascular Disease"""""""" (AR050026-05) funded by NIAMS. We have been very productive in the current funding period. Some of our findings include a higher prevalence of subclinical coronary and carotid artery atherosclerosis, and significant reduction in left ventricular mass, in RA compared to nonRA subjects. In addition, we have noted that RA exerts its pro-atherogenic effect, in part, indirectly through """"""""conventional"""""""" CV risk factor pathways. In this renewal, we propose to interrogate the role of inflammation in mediating accelerated atherosclerosis and myocardial dysfunction in RA by directly imaging the blood vessels and myocardia for characteristics of inflammation or its sequelae (fibrosis). Furthermore, we wish to confirm preliminary observations that RA susceptibility genes (the HLA-B1* """"""""shared epitopes"""""""") are also risk factors for more severe subclinical atherosclerosis. Our overall hypothesis is that rheumatoid inflammation of blood vessels and myocardium predisposes to accelerated atherosclerosis and myocardial dysfunction, and that these effects are mediated in part by RA susceptibility genes. We propose the following aims:
Specific Aim 1. In cross-sectional analyses, we will compare blood vessel wall and plaque characteristics of carotid arteries of RA vs nonRA subjects using carotid MRI.
Specific Aim 2. In cross-sectional analyses of RA subjects, we will investigate the association of measures of LV structure and function with myocardial fibrosis and perfusion using cardiac MRI with delayed enhancement, first pass perfusion and tagging.
Specific Aim 3. In cross-sectional analyses of several combined RA populations, we will evaluate the association of the RA-associated HLA-DRB1 """"""""shared epitope"""""""" (SE) genes with the presence and severity of atherosclerosis. These studies will contribute important new information that will be useful in CV risk stratifying RA patients for earlier aggressive intervention, thus potentially reducing CV associated morbidity and mortality in RA.

Public Health Relevance

The proposed studies, we hypothesize that enhanced systemic and/or local inflammation contributes significantly to the increased risk for cardiovascular events in individuals with rheumatoid arthritis. We will utilize state-of-the art imaging techniques that highlight inflammation both within blood vessels and in the myocardium. In addition, we will examine a genetic risk factor, associated with susceptibility to developing rheumatoid arthritis, to determine whether it also conveys risk for accelerated heart disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR050026-09
Application #
8435473
Study Section
Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Witter, James
Project Start
2003-09-27
Project End
2015-11-30
Budget Start
2012-12-01
Budget End
2013-11-30
Support Year
9
Fiscal Year
2013
Total Cost
$687,197
Indirect Cost
$182,423
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Winchester, Robert; Giles, Jon T; Nativ, Simona et al. (2016) Association of Elevations of Specific T Cell and Monocyte Subpopulations in Rheumatoid Arthritis With Subclinical Coronary Artery Atherosclerosis. Arthritis Rheumatol 68:92-102
Geraldino-Pardilla, Laura; Giles, Jon T; Sokolove, Jeremy et al. (2016) Association of Anti-Citrullinated Peptide Antibodies with Coronary Artery Calcification in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) :
Giles, Jon T; Danielides, Stamatina; Szklo, Moyses et al. (2015) Insulin resistance in rheumatoid arthritis: disease-related indicators and associations with the presence and progression of subclinical atherosclerosis. Arthritis Rheumatol 67:626-36
Jia, Jingfei; Kim, Hyun K; Hielscher, Andreas H (2015) Fast linear solver for radiative transport equation with multiple right hand sides in diffuse optical tomography. J Quant Spectrosc Radiat Transf 167:10-22
Liu, Ying L; Szklo, Moyses; Davidson, Karina W et al. (2015) Differential Association of Psychosocial Comorbidities With Subclinical Atherosclerosis in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 67:1335-44
Lusa, Amanda L; Amigues, Isabelle; Kramer, Henry R et al. (2015) Indicators of walking speed in rheumatoid arthritis: relative influence of articular, psychosocial, and body composition characteristics. Arthritis Care Res (Hoboken) 67:21-31
Geraldino-Pardilla, Laura; Dhaduvai, Shanthi; Giles, Jon T et al. (2015) Lack of association of oral calcium supplementation with coronary artery calcification in rheumatoid arthritis. Arthritis Rheumatol 67:1465-73
Giles, Jon T; Darrah, Erika; Danoff, Sonye et al. (2014) Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 with rheumatoid arthritis-associated interstitial lung disease. PLoS One 9:e98794
Giles, Jon T; Danoff, Sonye K; Sokolove, Jeremy et al. (2014) Association of fine specificity and repertoire expansion of anticitrullinated peptide antibodies with rheumatoid arthritis associated interstitial lung disease. Ann Rheum Dis 73:1487-94
Chung, Cecilia P; Giles, Jon T; Kronmal, Richard A et al. (2013) Progression of coronary artery atherosclerosis in rheumatoid arthritis: comparison with participants from the Multi-Ethnic Study of Atherosclerosis. Arthritis Res Ther 15:R134

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