Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). CV-related deaths, congestive heart failure, and acute CV events are increased 2-4 fold in RA patients compared to matched controls, but the prevalence of conventional risk factors for CVD is not increased. We hypothesize that inflammation due to RA promotes and exacerbates CVD, independent of conventional CV risk factors. This application is an ancillary proposal to the Multi-Ethnic Study of Atherosclerosis (MESA). We will compare the prevalence and progression of subclinical CVD in 200 RA patients to 1066 non-RA MESA participants from the Hopkins MESA Field Center. The degree to which inflammation contributes to increased CVD in RA patients will be examined, after adjusting for conventional CV risk factors.
Our specific aims are as follows:
Specific Aim 1. In a cross-sectional analysis we will compare a measure of atherosclerosis (coronary calcium) and measures of left ventricular (LV) dysfunction (by magnetic resonance imaging) between RA patients and controls. We will determine whether differences between the groups in coronary calcium and LV dysfunction are explained by serum markers of inflammation in RA (e.g., CRP, interleukin-6, soluble adhesion molecules).
Specific Aim 2. In a prospective analysis, we will compare the changes in coronary calcium between RA patients and controls. We will determine the degree to which elevated serum markers of inflammation contribute to differences in progression of coronary calcium.
Specific Aim 3. We will assess the associations of various markers of inflammation and disease activity/severity, as well as conventional CV risk factors, with coronary calcium and LV dysfunction at baseline and over three years, among RA patients. Particularly, the potential dose-response relationships of various markers of inflammation and disease activity/severity to coronary calcium and LV dysfunction will be examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR050026-03
Application #
7069647
Study Section
Epidemiology of Chronic Diseases Study Section (ECD)
Program Officer
Serrate-Sztein, Susana
Project Start
2004-05-01
Project End
2009-04-30
Budget Start
2006-05-01
Budget End
2007-04-30
Support Year
3
Fiscal Year
2006
Total Cost
$621,458
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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
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
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

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