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.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Epidemiology of Chronic Diseases Study Section (ECD)
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Serrate-Sztein, Susana
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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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
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
Baker, Joshua F; Giles, Jon T; Weber, David et al. (2017) Assessment of muscle mass relative to fat mass and associations with physical functioning in rheumatoid arthritis. Rheumatology (Oxford) 56:981-988

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