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(Circulation. 2005;112:1428-1434.)
© 2005 American Heart Association, Inc.

Heart Failure

C-Reactive Protein in Heart Failure

Prognostic Value and the Effect of Valsartan

Inder S. Anand, MD, FRCP, DPhil (Oxon); Roberto Latini, MD; Viorel G. Florea, MD; Michael A. Kuskowski, PhD; Thomas Rector, PhD; Serge Masson, PhD; Stefano Signorini, BiolD; Paolo Mocarelli, MD; Allen Hester, PhD; Robert Glazer, MD; Jay N. Cohn, MD, for the Val-HeFT Investigators

From VA Medical Center (I.S.A., T.R.) and University of Minnesota (I.S.A., V.G.F., J.N.C.), Minneapolis, Minn; Geriatric Research, Education and Clinical Center (M.A.K.), VA Medical Center, Minneapolis, Minn; Istituto di Ricerche Farmacologiche Mario Negri (R.L., S.M.), Milan, Italy; Department of Medicine, New York Medical College (R.L.), Valhalla, NY; Milano-Bicocca University (S.S., P.M.), Department of Laboratory Medicine-Desio Hospital, Desio, Milan, Italy; and Novartis Pharmaceuticals Corporation (A.H., R.G.), East Hannover, NJ.

Correspondence to Inder S. Anand, MD, VA Medical Center, Cardiology 111-C, One Veterans Dr, Minneapolis, MN 55417. E-mail anand001{at}umn.edu

Received September 22, 2004; revision received May 11, 2005; accepted June 2, 2005.

Background— The role of C-reactive protein (CRP) in heart failure is not well studied. We assessed the prognostic value of CRP in patients randomized in Val-HeFT (Valsartan Heart Failure Trial) and studied changes in CRP that were associated with valsartan.

Methods and Results— Characteristics of patients with baseline CRP levels above and below the median value were compared. Univariable and multivariable Cox proportional hazards regression models were used to examine the relationship of CRP to mortality and morbidity. Interactions were tested to determine whether differences in CRP changes from baseline to 4 and 12 months between groups randomly assigned to valsartan or placebo depended on baseline ACE inhibitor use. Median plasma CRP was 3.23 mg/L (interquartile range 1.42 to 7.56 mg/L), which is higher than in the general population. Patients with CRP above the median had features of more severe heart failure than those with CRP levels below the median. The cumulative likelihood of death and first morbid event increased with increasing quartile of CRP. Relative to the lowest CRP quartile, the risk of mortality (hazard ratio 1.51, 95% CI 1.2 to 1.9) and first morbid event (hazard ratio 1.53, 95% CI 1.28 to 1.84) was increased in the highest CRP quartile in multivariable models. CRP added incremental prognostic information to that provided by brain natriuretic peptide alone. CRP did not change significantly over time in the placebo group; however, after 12 months, valsartan was associated with a decrease in CRP in patients not receiving ACE inhibitors but not in those receiving ACE inhibitors at 12 months.

Conclusions— CRP is increased in heart failure. Higher levels are associated with features of more severe heart failure and are independently associated with mortality and morbidity. The ability of treatments to reduce CRP levels and the prognostic importance of reducing CRP require further study.

Key Words: heart failure • C-reactive protein • prognosis • angiotensin receptor blockers • inflammation

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