Inflammation in chronic heart failure.
OBJECTIVE
To summarize findings regarding the association of inflammatory processes with chronic heart failure (HF).


METHODS
We conducted PubMed/MEDLINE searches (1966-January 2008) of primary literature using the following key words: ACE inhibitors, allopurinol, angiotensin-receptor antagonists, cardiomyopathy, chemokines, cytokines, diuretics, heart failure, inflammation, interleukins, HMG-CoA reductase inhibitors, immunotherapy, medications used in heart failure, thalidomide, tumor necrosis factor, and uric acid.


METHODS
All articles that appeared to be relevant were read; of 305 articles examined, 87 were selected for discussion. Articles were selected if they were written in English and focused on any of the key words or appeared to have substantial content addressing inflammation in HF.


RESULTS
Cytokines, uric acid, and other inflammatory mediators are associated with physiologic effects that are also prominent features of HF (eg, reduced contractility and cardiac output, endothelial dysfunction, hypercoagulability, autonomic dysfunction as evidenced by reduced resting heart rate variability, insulin resistance). With the exception of elevated tumor necrosis factor-alpha as a cause of insulin resistance, it is not clear whether elevated inflammatory mediators directly cause HF signs and symptoms or whether they are incidental markers. Awareness of these associations has occurred relatively recently; there have been few clinical studies of efforts to directly modify inflammatory mediators. Most currently accepted drug therapies of HF reduce concentrations of circulating cytokines, but the significance of these findings awaits directed study.


CONCLUSIONS
Loss of myocardial function, autonomic dysfunction, and glucose intolerance are interrelated and linked by underlying chronic low-grade inflammation. Drug therapy with statins, pentoxifylline, and perhaps urate-lowering agents, in addition to current therapies, holds promise for treatment of HF.
Parish
Roy C
RC
Department of Clinical and Administrative Sciences, College of Pharmacy, The University of Louisiana, Monroe, LA, USA. rparis@lsuhsc.edu
Evans
Jeffery D
JD
D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000032:analysis; D002908:Chronic Disease; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D019255:NADPH Oxidases / Q000097:blood; D018384:Oxidative Stress; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014527:Uric Acid / Q000097:blood
D000893:Anti-Inflammatory Agents; D000959:Antihypertensive Agents; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D014527:Uric Acid; D002097:C-Reactive Protein; D019255:NADPH Oxidases