Background: Patients with rheumatoid arthritis (RA) are at increased risk of developing heart failure (HF) and cardiovascular (CV) events compared to age- and gender-matched non-RA controls. The widening gap in survival between RA and the general population emphasizes the urgency to understand the causes, and to develop effective interventions to reduce, CV related morbidity and mortality in RA. Rationale: 1) Preliminary data suggest that anti-cyclic citrullinated peptides (-CCP) antibodies may be involved in an autoimmune-based attack to the myocardium in RA. We hypothesize that titers of anti-CCP antibodies may be associated with subclinical myocardial dysfunction in RA patients. If proven, this association may allow the early identification of a subgroup at higher risk of developing HF/CV disease. 2) Antagonists of the tumor necrosis factor-? (anti-TNF) are highly effective in treating RA signs and symptoms, however, these drugs proved of no effect or even harmful in advanced HF patients. So far, no studies have directly investigated the effect of anti-TNF therapy on myocardial function in RA. It is crucial to clarify the cardiac effects of these treatment agents in RA, as it may have significant impact on CV outcome in these patients. Objectives: 1) In cross-sectional design, to ascertain whether serum concentrations of anti- CCP antibodies are correlated with subclinical left ventricular (LV) systolic and diastolic dysfunctionin patients with RA and no signs or symptoms of CVD. 2) In prospective design, we will evaluate the effect of treatment with anti-TNF therapy on parameters of LV systolic and diastolic function, compared with usual medical care. Methods: The present study will be an ancillary study of the Escape II Myocardium, an NIH- funded study (P.I. Dr. Joan Bathon) aimed at identifying the correlates of LV structure and perfusion abnormalities in RA patients, and at evaluating the effect of anti-TNF therapy on myocardial perfusion/inflammation. We will analyze myocardial function using speckle-tracking strain echocardiography, a technique able to detect subclinical abnormalities in LV function not detectable using traditional methods. Following the parent study design, a cross-sectional analysis will be performed in 150 RA patients, to assess the correlation of anti-CCP antibody titers with LV systolic/diastolic function by speckle-tracking echocardiography.
For aim 2, LV systolic/diastolic function will be assessed in 50 patients with severe RA activity randomized to anti-TNF therapy or standard treatment, and the effect of treatment on cardiac function will be evaluated after 6 months therapy.

Public Health Relevance

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects 1-2% of the population, and is associated with significantly higher cardiovascular morbidity and mortality compared to subjects without RA. Identifying the pathways and predictors of cardiac dysfunction in RA will enable more aggressive treatment, thereby reducing cardiovascular morbidity and mortality in RA. The questions that this proposal will answer are crucial in order to identify subjects with RA at higher risk of cardiovascular disease, and to evaluate the effects on cardiac function of a class of medications that are widely used in RA treatment, but that some studies showed to be potentially harmful to the heart.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Small Research Grants (R03)
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Special Emphasis Panel (ZAR1-EHB (M1))
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Witter, James
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Columbia University
Internal Medicine/Medicine
Schools of Medicine
New York
United States
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