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David A. Morrow, MD, MPH; James A. de Lemos, MD; Michael A. Blazing, MD; Marc S. Sabatine, MD, MPH; Sabina A. Murphy, MPH; Petr Jarolim, MD, PhD; Harvey D. White, DSc; Keith A. A. Fox, MB, ChB; Robert M. Califf, MD; Eugene Braunwald, MD; for the A to Z Investigators

JAMA. 2005;294:2866-2871.

Context  Elevated concentrations of B-type natriuretic peptide (BNP) at presentation in patients with acute coronary syndrome (ACS) are associated with long-term mortality. Few data exist regarding serial assessment of BNP levels during follow-up.

Objective  To determine whether concentrations of BNP at study entry (prior to hospital discharge for ACS) and at outpatient follow-up at 4 months and 12 months are associated with subsequent clinical outcomes.

Design, Setting, and Patients  Prospective observational substudy of 4497 patients with non–ST-elevation or ST-elevation ACS who were enrolled in phase Z of the A to Z trial, which was conducted in 41 countries at 322 acute care hospitals between 1999 and 2003.

Main Outcome Measure  Death from any cause or new onset of congestive heart failure (CHF) through 2 years.

Results  Levels of BNP were available in 4266 patients at study entry (prior to hospital discharge), 3618 patients at 4 months, and 2966 patients at 12 months. During follow-up there were 230 deaths and 163 incident cases of CHF. Adjusting for age, sex, index event, renal function, hypertension, prior heart failure, and diabetes, elevated levels of BNP (>80 pg/mL) were associated with subsequent death or new CHF when measured at study entry (111 [21%] vs 246 [7%]; adjusted hazard ratio [HR], 2.5; 95% confidence interval [CI], 2.0-3.3), at 4 months (34 [19%] vs 125 [4%]; adjusted HR, 3.9; 95% CI, 2.6-6.0), and at 12 months (19 [11%] vs 37 [1%]; adjusted HR, 4.7; 95% CI, 2.5-8.9). Patients with newly elevated levels of BNP at 4 months were at increased risk of death or new CHF (10 [15%] vs 105 [3%]); HR, 4.5; 95% CI, 2.3-8.6). Patients with elevated levels of BNP at study entry and with BNP levels lower than 80 pg/mL at 4 months tended to have only modestly increased risk (HR, 1.7; 95% CI, 1.0-2.9) compared with patients with BNP levels lower than 80 pg/mL at both visits.

Conclusions  Serial determinations of BNP levels during outpatient follow-up after ACS predict the risk of death or new CHF. Changes in BNP levels over time are associated with long-term clinical outcomes and may provide a basis for enhanced clinical decision making in patients after onset of ACS.

Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251576

Author Affiliations: Cardiovascular Division and Department of Medicine (Drs Morrow, Sabatine, and Braunwald and Ms Murphy) and Department of Pathology (Dr Jarolim), Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass; Donald W. Reynolds Cardiovascular Clinical Research Center, University of Texas Southwestern Medical Center, Dallas (Dr de Lemos); Duke Clinical Research Institute, Duke University Medical Center, Durham, NC (Drs Blazing and Califf); Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand (Dr White); and Royal Infirmary of Edinburgh, Edinburgh, Scotland (Dr Fox).

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