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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Arthritis, Connective Tissue and Skin Study Section (ACTS)
Program Officer
Witter, James
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Columbia University (N.Y.)
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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Morgenstern, Rachelle; Amigues, Isabelle; Giles, Jon T et al. (2017) Coronary Artery Inflammation in Rheumatoid Arthritis Using Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography. J Clin Rheumatol 23:454-455
Sammut, Amanda; Shea, Steven; Blumenthal, Roger S et al. (2017) Albuminuria in Rheumatoid Arthritis: Associations With Rheumatoid Arthritis Characteristics and Subclinical Atherosclerosis. Arthritis Care Res (Hoboken) 69:1799-1808
Bathon, Joan M; Giles, Jon T; Solomon, Daniel H (2017) TNF Antagonists: Killing Two ""Birds"" with one Biologic ""Stone"". Arthritis Rheumatol :
Kim, Hyun Keol; Montejo, Ludguier D; Jia, Jingfei et al. (2017) Frequency-domain optical tomographic image reconstruction algorithm with the simplified spherical harmonics (SP3) light propagation model. Int J Therm Sci 116:265-277
Ferraz-Amaro, Iván; Winchester, Robert; Gregersen, Peter K et al. (2017) Coronary Artery Calcification and Rheumatoid Arthritis: Lack of Relationship to Risk Alleles for Coronary Artery Disease in the General Population. Arthritis Rheumatol 69:529-541
Tedeschi, Sara K; Bathon, Joan M; Giles, Jon T et al. (2017) The relationship between fish consumption and disease activity in rheumatoid arthritis. Arthritis Care Res (Hoboken) :
Konig, Maximilian F; Abusleme, Loreto; Reinholdt, Jesper et al. (2016) Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis. Sci Transl Med 8:369ra176
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
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
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