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 #
5R01AR050026-10
Application #
8601293
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
2013-12-01
Budget End
2014-11-30
Support Year
10
Fiscal Year
2014
Total Cost
$592,346
Indirect Cost
$148,750
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
Bathon, Joan M; Giles, Jon T; Solomon, Daniel H (2018) Editorial: Tumor Necrosis Factor Antagonists: Killing Two Birds With One Biologic Stone. Arthritis Rheumatol 70:326-329
Geraldino-Pardilla, Laura; Zartoshti, Afshin; Ozbek, Ayse Bag et al. (2018) Arterial Inflammation Detected With 18 F-Fluorodeoxyglucose-Positron Emission Tomography in Rheumatoid Arthritis. Arthritis Rheumatol 70:30-39
Konig, Maximilian F; Giles, Jon T; Teles, Ricardo P et al. (2018) Response to comment on ""Aggregatibacter actinomycetemcomitans-induced hypercitrullination links periodontal infection to autoimmunity in rheumatoid arthritis"". Sci Transl Med 10:
Tedeschi, Sara K; Bathon, Joan M; Giles, Jon T et al. (2018) Relationship Between Fish Consumption and Disease Activity in Rheumatoid Arthritis. Arthritis Care Res (Hoboken) 70:327-332
Giles, Jon T; Ferrante, Antony W; Broderick, Rachel et al. (2018) Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease-Related Indicators, and Associations With Cardiometabolic Risk Factors. Arthritis Care Res (Hoboken) 70:175-184
Amigues, Isabelle; Tugcu, Aylin; Russo, Cesare et al. (2018) Myocardial Inflammation, Measured Using 18-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET-CT) is Associated with Disease Activity in Rheumatoid Arthritis. Arthritis Rheumatol :
Darrah, Erika; Giles, Jon T; Davis, Ryan L et al. (2018) Autoantibodies to Peptidylarginine Deiminase 2 Are Associated With Less Severe Disease in Rheumatoid Arthritis. Front Immunol 9:2696
Geraldino-Pardilla, Laura; Russo, Cesare; Sokolove, Jeremy et al. (2017) Association of anti-citrullinated protein or peptide antibodies with left ventricular structure and function in rheumatoid arthritis. Rheumatology (Oxford) 56:534-540
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

Showing the most recent 10 out of 42 publications