Published online before print April 21, 2003, doi: 10.1161/01.CIR.0000065637.10517.A0
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2003;107:1991.)
© 2003 American Heart Association, Inc.
Clinical Investigation and Reports |
Uric Acid and Survival in Chronic Heart Failure
Validation and Application in Metabolic, Functional, and Hemodynamic Staging
From the Applied Cachexia Research Unit (S.D.A., W.D.) of the Department of Cardiology (K.J.O.), Charité, Campus Virchow-Klinikum, Berlin, Germany; Department of Clinical Cardiology (S.D.A., W.D., M.R., R.S., D.F., C.H.D., M.C., W.S., F.L., P.P., A.J.S.C.), NHLI, Imperial College, London, UK; German Heart Institute Berlin (C.K., R.H.), Germany; Department of Biochemistry (M.K.), Royal Brompton Hospital, London, UK; and Discovery Laboratories Inc (R.S.), Doylestown, Pa.
Correspondence to Dr Stefan Anker, NHLI, Dovehouse St, London SW3 6LY, UK. E-mail s.anker{at}ic.ac.uk
Background— Serum uric acid (UA) could be a valid prognostic marker and useful for metabolic, hemodynamic, and functional (MFH) staging in chronic heart failure (CHF).
Methods and Results— For the derivation study, 112 patients with CHF (age 59±12 years, peak oxygen consumption [
O2] 17±7 mL/kg per minute) were recruited. In separate studies, we validated the prognostic value of UA (n=182) and investigated the relationship between MFH score and the decision to list patients for heart transplantation (n=120). In the derivation study, the best mortality predicting UA cutoff (at 12 months) was 565 µmol/L (9.50 mg/dL) (independently of age, peak O2, left ventricular ejection fraction, diuretic dose, sodium, creatinine, and urea; P<0.0001). In the validation study, UA 
565 µmol/L predicted mortality (hazard ratio, 7.14; P<0.0001). In 16 patients (from both studies) with UA 565 µmol/L, left ventricular ejection fraction 
25% and peak O2 14 mL/kg per min (MFH score 3), 12-month survival was lowest (31%) compared with patients with 2 (64%), 1 (77%), or no (98%, P<0.0001) risk factor. In an independent study, 51% of patients with MFH score 2 and 81% of patients with MFH score 3 were listed for transplantation. The positive predictive value of not being listed for heart transplantation with an MFH score of 0 or 1 was 100%.
Conclusions— High serum UA levels are a strong, independent marker of impaired prognosis in patients with moderate to severe CHF. The relationship between serum UA and survival in CHF is graded. MFH staging of patients with CHF is feasible.
Key Words: heart failure • prognosis • hemodynamics
Related Article:
Circulation 2003 107: 1951-1953.
This article has been cited by other articles:
 |
|
 |
|
  J. M. Hare, B. Mangal, J. Brown, C. Fisher Jr, R. Freudenberger, W. S. Colucci, D. L. Mann, P. Liu, M. M. Givertz, R. P. Schwarz, et al. Impact of oxypurinol in patients with symptomatic heart failure. Results of the OPT-CHF study. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2301 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.H. W. Tang The ongoing search for a stratified medicine approach in heart failure. J. Am. Coll. Cardiol., June 17, 2008; 51(24): 2310 - 2312. [Full Text] [PDF]
|
|
|
|
 |
|
 E. Braunwald Biomarkers in Heart Failure N. Engl. J. Med., May 15, 2008; 358(20): 2148 - 2159. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Boueiz, M. Damarla, and P. M. Hassoun Xanthine oxidoreductase in respiratory and cardiovascular disorders Am J Physiol Lung Cell Mol Physiol, May 1, 2008; 294(5): L830 - L840. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Strasak, E. Ruttmann, L. Brant, C. Kelleher, J. Klenk, H. Concin, G. Diem, K. Pfeiffer, H. Ulmer, and and the VHM&PP Study Group Serum Uric Acid and Risk of Cardiovascular Mortality: A Prospective Long-Term Study of 83 683 Austrian Men Clin. Chem., February 1, 2008; 54(2): 273 - 284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kempf, S. von Haehling, T. Peter, T. Allhoff, M. Cicoira, W. Doehner, P. Ponikowski, G. S. Filippatos, P. Rozentryt, H. Drexler, et al. Prognostic Utility of Growth Differentiation Factor-15 in Patients With Chronic Heart Failure J. Am. Coll. Cardiol., September 11, 2007; 50(11): 1054 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. F. Baker, H. R. Schumacher, and E. Krishnan Serum Uric Acid Level and Risk for Peripheral Arterial Disease: Analysis of Data From the Multiple Risk Factor Intervention Trial Angiology, September 1, 2007; 58(4): 450 - 457. [Abstract] [PDF]
|
|
|
|
 |
|
 M. H. Alderman Podagra, Uric Acid, and Cardiovascular Disease Circulation, August 21, 2007; 116(8): 880 - 883. [Full Text] [PDF]
|
|
|
|
|
|
G. M. Felker, L. A. Allen, S. J. Pocock, L. K. Shaw, J. J.V. McMurray, M. A. Pfeffer, K. Swedberg, D. Wang, S. Yusuf, E. L. Michelson, et al. Red Cell Distribution Width as a Novel Prognostic Marker in Heart Failure: Data From the CHARM Program and the Duke Databank J. Am. Coll. Cardiol., July 3, 2007; 50(1): 40 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Nirenberg and M. C. Carroll Atypical Gout in the Foot and Ankle Secondary to Primary Hyperparathyroidism J Am Podiatr Med Assoc, May 1, 2007; 97(3): 245 - 247. [Full Text] [PDF]
|
|
|
|
|
|
J. George, E. Carr, J. Davies, J.J.F. Belch, and A. Struthers High-Dose Allopurinol Improves Endothelial Function by Profoundly Reducing Vascular Oxidative Stress and Not by Lowering Uric Acid Circulation, December 5, 2006; 114(23): 2508 - 2516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Hilfiker-Kleiner, U. Landmesser, and H. Drexler Molecular Mechanisms in Heart Failure: Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis J. Am. Coll. Cardiol., October 27, 2006; 48(9_Suppl_A): A56 - A66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H J E M Janssens, E H van de Lisdonk, M Janssen, H J M van den Hoogen, and A L M Verbeek Gout, not induced by diuretics? A case-control study from primary care Ann Rheum Dis, August 1, 2006; 65(8): 1080 - 1083. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Zoccali, R. Maio, F. Mallamaci, G. Sesti, and F. Perticone Uric Acid and Endothelial Dysfunction in Essential Hypertension J. Am. Soc. Nephrol., May 1, 2006; 17(5): 1466 - 1471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. C. Levy, D. Mozaffarian, D. T. Linker, S. C. Sutradhar, S. D. Anker, A. B. Cropp, I. Anand, A. Maggioni, P. Burton, M. D. Sullivan, et al. The Seattle Heart Failure Model: Prediction of Survival in Heart Failure Circulation, March 21, 2006; 113(11): 1424 - 1433. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Pacher, A. Nivorozhkin, and C. Szabo Therapeutic effects of xanthine oxidase inhibitors: renaissance half a century after the discovery of allopurinol. Pharmacol. Rev., March 1, 2006; 58(1): 87 - 114. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Kang, S.-K. Park, I.-K. Lee, and R. J. Johnson Uric Acid-Induced C-Reactive Protein Expression: Implication on Cell Proliferation and Nitric Oxide Production of Human Vascular Cells J. Am. Soc. Nephrol., December 1, 2005; 16(12): 3553 - 3562. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Duncan, R. Ravi, L. B. Stull, and A. M. Murphy Chronic xanthine oxidase inhibition prevents myofibrillar protein oxidation and preserves cardiac function in a transgenic mouse model of cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2005; 289(4): H1512 - H1518. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mellin, M. Isabelle, A. Oudot, C. Vergely-Vandriesse, C. Monteil, B. Di Meglio, J. P. Henry, B. Dautreaux, L. Rochette, C. Thuillez, et al. Transient reduction in myocardial free oxygen radical levels is involved in the improved cardiac function and structure after long-term allopurinol treatment initiated in established chronic heart failure Eur. Heart J., August 1, 2005; 26(15): 1544 - 1550. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Kittleson and J. M. Hare Xanthine oxidase inhibitors: an emerging class of drugs for heart failure Eur. Heart J., August 1, 2005; 26(15): 1458 - 1460. [Full Text] [PDF]
|
|
|
|
 |
|
 W Doehner and S D Anker Xanthine oxidase inhibition for chronic heart failure: is allopurinol the next therapeutic advance in heart failure? Heart, June 1, 2005; 91(6): 707 - 709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Authors/Task Force Members, K. Swedberg, Writing Committee:, J. Cleland, H. Dargie, H. Drexler, F. Follath, M. Komajda, L. Tavazzi, O. A. Smiseth, et al. Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology Eur. Heart J., June 1, 2005; 26(11): 1115 - 1140. [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Brotman, E. Walker, M. S. Lauer, and R. G. O'Brien In Search of Fewer Independent Risk Factors Arch Intern Med, January 24, 2005; 165(2): 138 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Engberding, S. Spiekermann, A. Schaefer, A. Heineke, A. Wiencke, M. Muller, M. Fuchs, D. Hilfiker-Kleiner, B. Hornig, H. Drexler, et al. Allopurinol Attenuates Left Ventricular Remodeling and Dysfunction After Experimental Myocardial Infarction: A New Action for an Old Drug? Circulation, October 12, 2004; 110(15): 2175 - 2179. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rossig, S. Fichtlscherer, C. Heeschen, J. Berger, S. Dimmeler, and A. M. Zeiher The pro-apoptotic serum activity is an independent mortality predictor of patients with heart failure Eur. Heart J., September 2, 2004; 25(18): 1620 - 1625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. E. Berry and J. M. Hare Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications J. Physiol., March 15, 2004; 555(3): 589 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. T. Kearney, J. Nolan, and For the UK-HEART Study Investigators Uric Acid and Prognosis in Chronic Heart Failure Circulation, November 25, 2003; 108 (21): e148 - e148. [Full Text] [PDF]
|
|
|
|
|
|
J. M. Hare and R. J. Johnson Uric Acid Predicts Clinical Outcomes in Heart Failure: Insights Regarding the Role of Xanthine Oxidase and Uric Acid in Disease Pathophysiology Circulation, April 22, 2003; 107(15): 1951 - 1953. [Full Text] [PDF]
|
|