Concentrations of C-Reactive Protein and B-type Natriuretic Peptide 30 Days after Acute Coronary Syndromes Independently Predict Hospitalization for Heart Failure and Cardiovascular Death Benjamin M. Scirica, * Christopher P. Cannon, Marc S. Sabatine, Petr Jarolim, Sarah Sloane, Nader Rifai, Eugene Braunwald, and David A. Morrow, for the PROVE IT–TIMI 22 Investigators BACKGROUND: Heart failure (HF) is an important cause of morbidity in patients with acute coronary syn- dromes (ACS). C-reactive protein (CRP) has been implicated in experimental models as exacerbating myocardial injury, but data regarding the clinical rela- tionship of high-sensitivity CRP (hsCRP) and B-type natriuretic peptide (BNP) concentrations with the risk of HF after ACS are few. METHODS: PROVE IT–TIMI 22 randomized 4162 pa- tients who had been stabilized after ACS to either in- tensive or moderate statin therapy. hsCRP and BNP were measured 30 days after randomization. Hospital- izations for HF and cardiovascular death occurring af- ter day 30 were assessed for a mean follow-up of 24 months. RESULTS: Patients who developed HF had higher con- centrations of hsCRP (3.7 mg/L vs 1.9 mg/L, P  0.001) and BNP (59 ng/L vs 22 ng/L, P  0.0001). HF in- creased in a stepwise manner with hsCRP quartile [ad- justed hazard ratio (HR adj ) for Q4 vs Q1, 2.5; P = 0.01] and BNP quartile (HR adj for Q4 vs Q1, 5.8; P  0.001), with similar results obtained for cardiovascular death. In a multivariable analysis, higher concentrations of hsCRP and BNP were both independently associated with HF [HR adj , 1.9 for hsCRP 2.0 mg/L (P = 0.01) and 4.2 for BNP 80 ng/L (P  0.001)]. Patients with increases in both markers were at the greatest risk of HF, compared with patients without an increased marker concentration (HR adj , 8.3; P = 0.01). The ben- efit of intensive statin therapy in reducing HF was con- sistent among all patients, regardless of hsCRP or BNP concentration. CONCLUSIONS: Both hsCRP and BNP measured 30 days after ACS are independently associated with the risk of HF and cardiovascular death, with the greatest risk oc- curring when both markers are increased. © 2008 American Association for Clinical Chemistry Current treatment strategies for patients admitted with acute coronary syndrome (ACS) 1 focus primarily on preventing recurrent ischemia or infarction, whereas therapy targeted specifically to prevent heart failure (HF) has generally been a secondary objective. None- theless, the development of HF after ACS carries an especially poor overall prognosis (1, 2). Both the iden- tification of patients at high risk for developing HF af- ter ACS and determining whether specific therapy can modify that risk are therefore of clinical importance. The use of cardiac biomarkers, especially B-type natri- uretic peptide (BNP) (3, 4), has greatly improved the ability to identify patients who are at high risk of death or HF after ACS. In particular, those patients with per- sistently high markers of hemodynamic stress several weeks after ACS are at highest risk (4, 5). When measured immediately after the onset of is- chemic symptoms, C-reactive protein (CRP), a marker of inflammation, has also been associated with poor cardiovascular outcomes (6, 7). Because of the acute- phase response, however, the concentration of high- sensitivity CRP (hsCRP) varies widely in the days after ACS, and the association can be confounded by the extent of necrosis (8) and the timing of the measure- ment (6). The association of CRP with subsequent risk of death or myocardial infarction has been well docu- mented in the convalescent phase after ACS, when TIMI Study Group, Cardiovascular Division, Department of Medicine, and Depart- ment of Pathology, Brigham and Women’s Hospital, Harvard Medical School; Children’s Hospital, Harvard Medical School, Boston, MA. * Address correspondence to this author at: TIMI Study Group, Cardiovascular Division, Brigham and Women’s Hospital, 75 Francis St., Boston, MA 02115. Fax 617.734.7329; e-mail bscirica@partners.org. Received September 1, 2008; accepted November 10, 2008. Previously published online at DOI: 10.1373/clinchem.2008.117192 1 Nonstandard abbreviations: ACS, acute coronary syndrome; HF, heart failure; BNP, B-type natriuretic peptide; CRP, C-reactive protein; hsCRP, high-sensitivity CRP; PROVE IT, Pravastatin or Atorvastatin Evaluation and Infection Trial; TIMI, Thrombolysis in Myocardial Infarction; PO 2 , oxygen pressure; HR, hazard ratio; HR adj , adjusted HR; Q4, quartile 4. Clinical Chemistry 55:2 000 – 000 (2009) Lipids, Lipoproteins, and Cardiovascular Risk Factors 1 http://www.clinchem.org/cgi/doi/10.1373/clinchem.2008.117192 The latest version is at Papers in Press. Published December 16, 2008 as doi:10.1373/clinchem.2008.117192 Copyright (C) 2008 by The American Association for Clinical Chemistry