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Abstract

ATTACH = Anti-TNF-α Therapy Against Chronic Heart failure; CHF = congestive heart failure; CVD = cardiovascular disease; IL = interleukin; LV = left ventricular; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MMP = matrix metalloproteinase; OA = osteoarthritis; RA = rheumatoid arthritis; RECOVER = Research into Etanercept: Cytokine Antagonism in Ventricular Dysfunction Trial; RENNAISANCE = Randomized Etanercept North American Strategy to Study Antagonism of Cytokines; RF rheumatoid factor; TACE = TNF-α converting enzyme; TIMP = tissue inhibitor of matrix metalloproteinase; TNF-α = tumor necrosis factor-α.Available online http://arthritis-research.com/content/7/5/195 AbstractData from population-and clinic-based epidemiologic studies of rheumatoid arthritis patients suggest that individuals with rheumatoid arthritis are at risk for developing clinically evident congestive heart failure. Many established risk factors for congestive heart failure are over-represented in rheumatoid arthritis and likely account for some of the increased risk observed. In particular, data from animal models of cytokine-induced congestive heart failure have implicated the same inflammatory cytokines produced in abundance by rheumatoid synovium as the driving force behind maladaptive processes in the myocardium leading to congestive heart failure. At present, however, the direct effects of inflammatory cytokines (and rheumatoid arthritis therapies) on the myocardia of rheumatoid arthritis patients are incompletely understood. IntroductionUnique cardiac complications of rheumatoid arthritis (RA), such as cardiac rheumatoid nodules, have been recognized for over a century. It has only been appreciated in the last decades, however, that certain chronic autoimmune inflammatory diseases, such as RA and systemic lupus erythematosis, increase the risk of developing cardiovascular disease (CVD), particularly atherosclerosis and congestive heart failure (CHF) [1][2][3][4][5]. In fact, striking commonalities in the cellular and cytokine profiles of the rheumatoid synovial lesion and atherosclerotic plaque [6][7][8] have prompted speculation that the inflammatory pathways of RA may initiate and/or accelerate plaque formation and that this effect may be ameliorated by anti-inflammatory therapies [9].The link between RA and CHF is less well studied. The CHF phenotype can evolve from a variety of pathogenic conditions, many of which may be promoted by the RA disease process. Yet to date, only a handful of investigations have attempted to dissect this complex issue. A particular source of confusion has been the apparent contradiction between pre-clinical studies linking inflammation to CHF and the lack of efficacy of anti-cytokine therapy in clinical trials in advanced CHF (discussed below). Because anti-cytokine therapy has become a cornerstone in the treatment of RA, it is particularly critical to understand the contribution of cytokine-induced inflammation to myocardial structure and function in RA. Here, we review the curre...

The Influence of Rheumatoid Arthritis Disease Characteristics on Heart Failure

“…Some measures of RA activity including RF positivity and increased ESR were previously linked to HF in RA in ours and other studies (5, 7, 8, 10). The association of increased ESR at RA incidence with the risk of HF in RA corroborates our earlier observations regarding ESR as a potential signal for the subsequent development of HF (8).…”

“…These findings suggest a potential role for RA-specific mechanisms in HF development and emphasize the need for understanding the determinants of HF in RA. RA disease activity and severity have been previously linked to HF development in RA (5, 7-10). Furthermore, antirheumatic medications, particularly methotrexate and more recently biologic response modifiers, but not corticosteroids, appear to have a beneficial effect on risk of HF in RA (11-13).…”

Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population

“…Associations between RA disease characteristics at baseline and the subsequent progression of early changes in diastolic function contribute to the knowledge that RA is an independent risk factor for myocardial disease (9,30,31,39). Particularly, the associations between the RAPID3 score and the 5-year changes in the A velocity, as well as the E/e′ ratio, suggest that inflammatory disease activity associated with RA contributes to subclinical progression of diastolic dysfunction.…”

Ramipril attenuates lipid peroxidation and cardiac fibrosis in an experimental model of rheumatoid arthritis

“…Fibrosis is a hallmark of CV diseases and is often associated with inflammation. It has been proposed that mediators of inflammation, including cytokines such as TNFα, IL1β, and IL-6, leads to microvascular dysfunction and ultimately to myocardial remodeling and fibrosis [44,45]. …”