C-reactive protein (CRP) predicts future cardiovascular events in apparently healthy individuals, but what is the significance of CRP levels in patients with heart failure?

Few studies have actually been published in this area, however CRP is increased in heart failure, and related to mortality (1-3) and readmission rates (4). In patients with heart failure, ACE inhibitor and beta blocker use have been associated with lower CRP levels although no relationship has yet been observed between aspirin or statin use and CRP levels in these patients (5).

Statins lower CRP levels by altering the regulation of CRP production in the liver, and there is evidence to suggest that statins have differential effects on inflammatory markers in patients with coronary artery disease (CAD) compared to those with heart failure. In the Ludwigshafen Risk and Cardiovascular Health Study for example, it was found in patients with CAD that statin therapy reduced CRP levels but not IL-6 levels (6), although both IL-6 and TNF-alpha levels were found to be reduced by statin treatment in patients with heart failure (dilated cardiomyopathy) (7). Prof. Anker also discusses potential sources of CRP variability such as measurement problems (lack of agreement between different test kits), and the effects of physical exercise, altitude, metabolic syndrome, insulin resistance and genetic factors.

Soluble TNF-receptor 1 is one inflammatory marker that has been found to predict mortality in heart failure patients (8). Other inflammatory markers in heart failure include the presence of anemia (9) and high uric acid levels (10). In patients with cachexia in heart failure, weight loss itself can also be considered an inflammatory marker (11). Prof. Anker discusses the relationship between cholesterol levels and prognosis in heart failure (findings from the ELITE II study), and whether it's more important to assess inflammation in tissue rather than plasma in heart failure patients, as it is in tissue and not blood vessels where the damage occurs.

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After viewing this presentation the participant will be able to discuss:

- What is known about CRP in heart failure
- Effects of statins on inflammatory markers in heart failure versus CAD
- Potential sources of CRP variability
- sTNF-R1 and other inflammatory markers in CHF

1. Berton G, Cordiano R, Palmieri R, Pianca S, Pagliara V, Palatini P.C-reactive protein in acute myocardial infarction: association with heart failure American Heart Journal, Volume 145, Issue 6, June 2003, Pages 1094-1101.

2. Wei-Hsian Yin, Jaw-Wen Chen, Hsu-Lung Jen, Meng-Cheng Chiang, Wen-Pin Huang, An-Ning Feng , Mason Shing Young and Shing-Jong Lin. Independent prognostic value of elevated high-sensitivity C-reactive protein in chronic heart failure American Heart Journal. Volume 147, Issue 5, Pages 931-938 (May 2004).

3. Janoskuti L, Forhecz Z, Hosszufalusi N, Kleiber M, Walentin S, Balint O, Duba J, Rugonfalvi-Kiss S, Romics L, Karadi I, Fust G, Prohaszka Z.High levels of C-reactive protein with low total cholesterol concentrations additively predict all-cause mortality in patients with coronary artery disease European Journal of Clinical Investigation. Volume 35 Issue 2 Page 104 - February 2005.

4. Alonso-Martinez JL, Llorente-Diez B, Echegaray-Agara M, Olaz-Preciado F, Urbieta-Echezarreta M, Gonzalez-Arencibia C.C-reactive protein as a predictor of improvement and readmission in heart failure European Journal of Heart Failure, Volume 4, Issue 3, June 2002, Pages 331-336.

5. Joynt KE, Gattis WA, Hasselblad V, Fuzaylov SY, Serebruany VL, Gurbel PA, Gaulden LH, Felker GM, Whellan DJ, O'Connor CM.Effect of angiotensin-converting enzyme inhibitors, beta blockers, statins, and aspirin on C-reactive protein levels in outpatients with heart failure The American Journal of Cardiology, Volume 93, Issue 6, 15 March 2004, Pages 783-785.

6. Winfried März MD, Karl Winkler MD, Markus Nauck MD, Bernhard O. Böhm MD and Bernhard R. Winkelmann MD. Effects of statins on C-reactive protein and interleukin-6 (the Ludwigshafen Risk and Cardiovascular Health study) The American Journal of Cardiology
Volume 92, Issue 3 , 1 August 2003, Pages 305-308.

7. Koichi Node, MD, PhD; Masashi Fujita, MD; Masafumi Kitakaze, MD, PhD; Masatsugu Hori, MD; James K. Liao, MD. Short-Term Statin Therapy Improves Cardiac Function and Symptoms in Patients With Idiopathic Dilated Cardiomyopathy Circulation. 2003;108:839.

8. Mathias Rauchhaus, MD; Wolfram Doehner, MD; Darrel P. Francis, MD; Constantinos Davos, MD, PhD; Michael Kemp, FRCPath; Christa Liebenthal; Josef Niebauer, MD, PhD; James Hooper, MD; Hans-Dieter Volk, MD; Andrew J. S. Coats, DM; Stefan D. Anker, MD, PhD. Plasma Cytokine Parameters and Mortality in Patients With Chronic Heart Failure Circulation. 2000;102:3060.

9. Bolger AP et al. presented at AHA 2002.

10. F. Leyva, S.D. Anker, I.F. Godsland, M. Teixeira, P.G. Hellewell, W.J. Koxc, P.A. Poole-Wilson and A.J.S. CoatsUric acid in chronic heart failure: a marker of chronic inflammation Eur Heart J. 1998 Dec;19(12):1814-22.

11. B Levine, J Kalman, L Mayer, HM Fillit, and M PackerElevated circulating levels of tumor necrosis factor in severe chronic heart failure NEJM.Volume 323:236-241.July 26, 1990.