Rheumatoid Arthritis Disadvantages Younger Patients for Cardiovascular Diseases: A Meta-Analysis.

INTRODUCTION: The incidence of cardiovascular diseases (CVD) is increased in rheumatoid arthritis (RA) patients. It remains unclear whether the load of RA increases cardiovascular (CV) risk especially in female and in younger RA patients. In the present study we aim to analyse the influence of age and gender on CV risk in RA relative to the general population, using meta-analysis of direct comparative studies. METHOD: Systematic literature search was performed in MEDLINE for studies reporting on occurrence of CV events in RA as compared to the general population, stratified for gender and/or age. Quality was appraised using the Newcastle-Ottawa scale. Meta-analysis was performed on rate ratios using inverse variance methods. RESULTS: There were 1372 records screened and 13 studies included. RA females and males have a similar higher risk (95%CI) to develop stroke with RR 1.35 (1.30-1.40) and RR 1.31 (1.21-1.43); coronary artery disease with RR 1.65 (1.54-1.76) versus RR 1.55 ((1.41-1.69) in men; cardiovascular disease with RR 1.56 (1.49-1.62) versus 1.50 (1.41-1.60). The highest incidence of CV events was observed in the youngest patients, RR 2.59 (1.77-3.79), whereas older patients had the lowest relative risk when compared to the general population, RR 1.27 (1.16-1.38). CONCLUSION: The relative risk of RA patients for CVD is age dependent, but does not depend on gender: the relative risk on CVD appears to be equally raised for males and females, while relatively young RA patients (<50 years) have the highest, and older patients the lowest relative risk.

Concurrent evolution of cancer cachexia and heart failure: bilateral effects exist.

Cancer cachexia is defined as a multifactorial syndrome of involuntary weight loss characterized by an ongoing loss of skeletal muscle mass and progressive functional impairment. It is postulated that cardiac dysfunction/atrophy parallels skeletal muscle atrophy in cancer cachexia. Cardiotoxic chemotherapy may additionally result in cardiac dysfunction and heart failure in some cancer patients. Heart failure thus may be a consequence of either ongoing cachexia or chemotherapy-induced cardiotoxicity; at the same time, heart failure can result in cachexia, especially muscle wasting. Therefore, the subsequent heart failure and cardiac cachexia can exacerbate the existing cancer-induced cachexia. We discuss these bilateral effects between cancer cachexia and heart failure in cancer patients. Since cachectic patients are more susceptible to chemotherapy-induced toxicity overall, this may also include increased cardiotoxicity of antineoplastic agents. Patients with cachexia could thus be doubly unfortunate, with cachexia-related cardiac dysfunction/heart failure and increased susceptibility to cardiotoxicity during treatment. Cardiovascular risk factors as well as pre-existing heart failure seem to exacerbate cardiac susceptibility against cachexia and increase the rate of cardiac cachexia. Hence, chemotherapy-induced cardiotoxicity, cardiovascular risk factors, and pre-existing heart failure may accelerate the vicious cycle of cachexia-heart failure. The impact of cancer cachexia on cardiac dysfunction/heart failure in cancer patients has not been thoroughly studied. A combination of serial echocardiography for detection of cachexia-induced cardiac remodeling and computed tomography image analysis for detection of skeletal muscle wasting would appear a practical and non-invasive approach to develop an understanding of cardiac structural/functional alterations that are directly related to cachexia.

Targeting the ACE2 and Apelin Pathways Are Novel Therapies for Heart Failure: Opportunities and Challenges.

Angiotensin-converting enzyme 2 (ACE2)/Ang II/Ang 1-7 and the apelin/APJ are two important peptide systems which exert diverse effects on the cardiovascular system. ACE2 is a key negative regulator of the renin-angiotensin system (RAS) where it metabolizes angiotensin (Ang) II into Ang 1-7, an endogenous antagonist of Ang II. Both the prolonged activation of RAS and the loss of ACE2 can be detrimental as they lead to functional deterioration of the heart and progression of cardiac, renal, and vascular diseases. Recombinant human ACE2 in an animal model of ACE2 knockout mice lowers Ang II. These interactions neutralize the pressor and subpressor pathologic effects of Ang II by producing Ang 1-7 levels in vivo, that might be cardiovascular protective. ACE2 hydrolyzes apelin to Ang II and, therefore, is responsible for the degradation of both peptides. Apelin has emerged as a promising peptide biomarker of heart failure. The serum level of apelin in cardiovascular diseases tends to be decreased. Apelin is recognized as an imperative controller of systemic blood pressure and myocardium contractility. Dysregulation of the apelin/APJ system may be involved in the predisposition to cardiovascular diseases, and enhancing apelin action may have important therapeutic effects.

The use of ω-3 poly-unsaturated fatty acids in heart failure: a preferential role in patients with diabetes.

PURPOSE: To review the evidence for a beneficial effect of ω-3 PUFAs in heart failure (HF) and its co-morbidities, their possible preferential effect in diabetes and the potential mechanism for their benefit. METHODS: We summarize the clinical studies which investigated the use of ω-3 PUFAs in patients with HF with an emphasis on diabetes. We briefly summarize the evidence for an effect of ω-3 PUFAs in patients with coronary artery disease (CAD), atrial fibrillation (AF) and ventricular arrhythmias. We also discuss the proposed mechanisms of ω-3 PUFA action in cardiovascular diseases. RESULTS: While there is emerging evidence for a beneficial effect of ω-3 PUFA supplementation in patients with HF, the evidence for other indications have been variable and conflicting. In HF patients with diabetes, ω-3 PUFAs may have a preferential therapeutic benefit. Randomized controlled trials did not show considerable beneficial effects of ω-3 PUFAs in other conditions such as CAD and AF. In a diabetic and insulin-resistant state, ω-3 PUFAs bind to the G-protein coupled receptor, GPR120, resulting in reduced cytokine production from inflammatory macrophages and improved signaling in adipocytes, leading to a reduction in insulin resistance. CONCLUSIONS: There is promising evidence showing that use of ω-3 PUFA supplementation improves clinical outcomes of HF patients with diabetes. Further clinical trials are needed in this regard.