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      N-Terminal pro-B-Type Natriuretic Peptide in Risk Stratification after Acute Myocardial Infarction in Patients on Long-Term Beta-Adrenergic Receptor Blocker Therapy

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          Background: N-terminal pro-B-type natriuretic peptide (NT-proBNP) appears to be a strong risk marker of mortality in patients with acute coronary syndrome. However, little information is available on NT-proBNP as a predictor of long-term serious cardiovascular events beyond that of left ventricular ejection fraction in patients with acute myocardial infarction (AMI), most of them treated with an early invasive strategy and on a uniform optimal secondary preventive medication including long-term beta-adrenergic receptor blockade. Objective: To assess the prognostic impact of plasma NT-proBNP in patients with AMI who received optimal medical treatment including long-term beta-adrenergic receptor blockade. Methods: Plasma NT-proBNP was measured in 219 patients (age range 31–80 years) with AMI at baseline, and then followed for a median duration of 1.63 years. The first occurrences of a serious cardiovascular event including cardiac mortality, nonfatal MI, and congestive heart failure were registered. Results: Ninety serious cardiovascular events occurred. Left ventricular ejection fraction and reperfusion therapy with thrombolysis or percutaneous coronary intervention were identified as confounders. When adjusting for these factors in multivariate analysis, NT-proBNP was a strong predictor of serious cardiovascular events in patients with a plasma NT-proBNP of >162.2 pmol/l and aged <60 years (p = 0.001). The incidence rate was related to increasing NT-proBNP (p = 0.0017). The risk of serious cardiovascular events was higher in patients with NT-proBNP levels in the highest quartile (≧162.2 pmol/l) than in those with levels in the three lowest quartiles (rate ratio = 2.5, 95% confidence interval = 1.6–3.9, p = 0.0001). Conclusion: AMI patients with high plasma NT-proBNP seem to be at an increased risk of serious cardiovascular events, but only those ≤60 years of age.

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          The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes.

          Brain (B-type) natriuretic peptide is a neurohormone synthesized predominantly in ventricular myocardium. Although the circulating level of this neurohormone has been shown to provide independent prognostic information in patients with transmural myocardial infarction, few data are available for patients with acute coronary syndromes in the absence of ST-segment elevation. We measured B-type natriuretic peptide in plasma specimens obtained a mean (+/-SD) of 40+/-20 hours after the onset of ischemic symptoms in 2525 patients from the Orbofiban in Patients with Unstable Coronary Syndromes-Thrombolysis in Myocardial Infarction 16 study. The base-line level of B-type natriuretic peptide was correlated with the risk of death, heart failure, and myocardial infarction at 30 days and 10 months. The unadjusted rate of death increased in a stepwise fashion among patients in increasing quartiles of base-line B-type natriuretic peptide levels (P< 0.001). This association remained significant in subgroups of patients who had myocardial infarction with ST-segment elevation (P=0.02), patients who had myocardial infarction without ST-segment elevation (P<0.001), and patients who had unstable angina (P<0.001). After adjustment for independent predictors of the long-term risk of death, the odds ratios for death at 10 months in the second, third, and fourth quartiles of B-type natriuretic peptide were 3.8 (95 percent confidence interval, 1.1 to 13.3), 4.0 (95 percent confidence interval, 1.2 to 13.7), and 5.8 (95 percent confidence interval, 1.7 to 19.7). The level of B-type natriuretic peptide was also associated with the risk of new or recurrent myocardial infarction (P=0.01) and new or worsening heart failure (P<0.001) at 10 months. A single measurement of B-type natriuretic peptide, obtained in the first few days after the onset of ischemic symptoms, provides powerful information for use in risk stratification across the spectrum of acute coronary syndromes. This finding suggests that cardiac neurohormonal activation may be a unifying feature among patients at high risk for death after acute coronary syndromes.
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            N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes.

            B-type natriuretic peptide (BNP) is a predictor of short- and medium-term prognosis across the spectrum of acute coronary syndromes (ACS). The N-terminal fragment of the BNP prohormone, N-BNP, may be an even stronger prognostic marker. We assessed the relation between subacute plasma N-BNP levels and long-term, all-cause mortality in a large, contemporary cohort of patients with ACS. Blood samples for N-BNP determination were obtained in the subacute phase in 204 patients with ST-elevation myocardial infarction (MI): 220 with non-ST segment elevation MI and 185 with unstable angina in the subacute phase. After a median follow-up of 51 months, 86 patients (14%) had died. Median N-BNP levels were significantly lower in long-term survivors than in patients dying (442 versus 1306 pmol/L; P<0.0001). The unadjusted risk ratio of patients with supramedian N-BNP levels was 3.9 (95% confidence interval, 2.4 to 6.5). In a multivariate Cox regression model, N-BNP (risk ratio 2.1 [95% confidence interval, 1.1 to 3.9]) added prognostic information above and beyond Killip class, patient age, and left ventricular ejection fraction. Adjustment for peak troponin T levels did not markedly alter the relation between N-BNP and mortality. In patients with no evidence of clinical heart failure, N-BNP remained a significant predictor of mortality after adjustment for age and ejection fraction (risk ratio, 2.4 [95% confidence interval, 1.1 to 5.4]). N-BNP is a powerful indicator of long-term mortality in patients with ACS and provides prognostic information above and beyond conventional risk markers.
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              N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy.

              Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients. NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.5 hours from symptom onset in 6809 of 7800 ACS patients in the Global Utilization of Strategies To Open occluded arteries-IV (GUSTO-IV) trial. Levels of NT-proBNP were correlated independently with age, female gender, low body weight, diabetes, renal dysfunction, history of MI, heart failure, heart rate, ongoing myocardial damage, and time since onset of ischemia. Increasing quartiles of NT-proBNP were related to short- and long-term mortality that reached 1.8%, 3.9%, 7.7%, and 19.2%, (P<0.001), respectively, at 1 year. Levels of troponin T, CRP, heart rate, and creatinine clearance, in addition to ST-segment depression, were also correlated independently with 1-year mortality, but NT-proBNP was the marker with the strongest relation. In contrast, only troponin T, creatinine clearance, and ST-segment depression were independently related to future MI. The combination of NT-proBNP and creatinine clearance provided the best prediction, with a 1-year mortality of 25.7% with both markers in the top quartile vs 0.3% with both markers in the bottom quartile. The use of NT-proBNP appears to add critical prognostic insight to the assessment of patients with ACS.

                Author and article information

                S. Karger AG
                August 2006
                16 August 2006
                : 106
                : 2
                : 102-108
                aDepartment of Cardiology, bCenter of Clinical Research, Unit of Epidemiology and Biostatics, Departments of cClinical Chemistry, dNuclear Medicine and eNephrology, Ullevaal University Hospital, Oslo, Norway
                92743 Cardiology 2006;106:102–108
                © 2006 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 6, References: 27, Pages: 7
                Original Research


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