Little is known about the long-term prognostic value of N-terminal pro B-type natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) in low-risk patients with chest pain.

Between June 1997 and January 2000, a standard rule-out protocol was performed in patients presenting to the emergency department within 6 hours of onset of chest pain with a normal or nondiagnostic electrocardiogram (ECG) on admission at the Academic Medical Center Amsterdam, VU University Medical Center Amsterdam and Medical Center Alkmaar, The Netherlands. Patients with acute coronary syndrome were identified by troponin T, recurrent angina, and serial ECGs. CRP and NT-proBNP on admission were measured using standardized methods.

A total of 524 patients were included (145 with acute coronary syndrome and 379 with rule-out acute coronary syndrome). Long-term follow-up was successfully carried out in 96% of the study population. Death occurred in 78 patients (15%), 43 (11%) in the rule-out acute coronary syndrome group and 35 (24%) in the acute coronary syndrome group (P<.001). In the rule-out acute coronary syndrome group, 21 patients (42%) died of a cardiovascular cause compared with 24 patients (69%) in the acute coronary syndrome group (P<.001). In multivariate Cox regression analysis, age more than 65 years, previous myocardial infarction, known chronic heart failure, a nondiagnostic ECG on admission, and elevated NT-proBNP levels (>87 pg/mL, as derived from the receiver operating characteristic curve) were independent predictors of long-term cardiovascular mortality in the rule-out acute coronary syndrome group. In the acute coronary syndrome group, these predictors were age more than 65 years, documented coronary artery disease, and elevated NT-proBNP levels. Elevated levels of CRP were an independent predictor for cardiovascular mortality in patients with rule-out acute coronary syndrome at 3-year follow-up only. In patients with rule-out acute coronary syndrome with normal CRP and NT-proBNP levels, the cardiovascular mortality incidence rate was 4.7 per 1000 person-years, compared with a death rate of 20 in patients with both biomarkers elevated, which was comparable to the 17.9 per 1000 person-years incidence rate in patients with acute coronary syndrome.

A positive biomarker panel discriminates patients with rule-out acute coronary syndrome chest pain with a normal or nondiagnostic ECG who have a high risk for long-term cardiovascular mortality.