Lower N-terminal Pro-brain Natriuretic Peptide Research Articles

Prognostic value of N-terminal pro-brain natriuretic peptide in patients with heart failure and preserved left ventricular ejection fraction

Objective To evaluate the prognostic value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure and normal left ventricular (LV) ejection fraction (HFPEF). Methods From January 2008 to December 2008, 133 consecutive patients hospitalized who are satisfying the following conditions: (i) signs or symptoms of heart failure; (ii) preserved systolic LV function; (iii) evidence of diastolic LV dysfunction, and 78 heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF<50%) were included in this study. All patients evaluated heart function by NYHA class. Plasma concentrations of the NT-proBNP were measured by ECLIA on admission. LVEF was measured by Simpson's equation with Doppler echocardiography. All patients discharged were followed up a median of 240 days. The recurrent cardiac event was cardiac death or decompensated HF readmission. Results (1) Compared with HF and reduced LVEF group, HFPEF group had a significantly higher age and percentage of hypertension, lower NYHA class degree, lower left ventricular end-diastolic dimension and median plasma NT-proBNP level (2,016.0 vs. 4,787.0 Pg/ml), all P<0.01, higher percentage of CAD and diabetes, all P<0.05, but recurrent cardiovascular events were not significantly different in the two groups (26/78 vs. 30/133, P>0.05). (2) On a Cox proportional hazards analysis, LogNT-proBNP was found to be the strongest independent predictor of cardiac events. OR was 4.865 (95%CI: 1.607–14.726, P=0.005). (3) On a Kaplan–Meier survival curve, NT-proBNP>2,016 Pg/ml on admission was associated with increased cardiac events (HR–3.688, 95%CI: 1.502–9.056, P=0.003). Conclusions Plasma NT-proBNP level on admission is an important predictor of readmission and death within 240 days after hospital discharge in patients with HFPEF. NT-proBNP>2,016 Pg/ml predicted an unfavourable prognosis.

Reperfusion before percutaneous coronary intervention in ST-elevation myocardial infarction patients is associated with lower N-terminal pro-brain natriuretic peptide levels during follow-up, irrespective of pre-treatment with full-dose fibrinolysis

N-terminal pro-brain natriuretic peptide (NT-proBNP) levels predict outcomes in ST-elevation myocardial infarction patients treated with fibrinolysis or primary percutaneous coronary intervention (PCI). However, its role in facilitated PCI has not yet been assessed; it may be a tool to evaluate the lower event rates with primary PCI in ASSENT-4. In ASSENT-4, 1667 patients were randomized to tenecteplase (TNK) followed by PCI or primary PCI alone. Baseline, discharge/Day 7, and 90-day NT-proBNP levels were available for 1008, 971, and 813 patients. Increasing quartiles of baseline NT-proBNP levels were associated with a higher risk of the combined endpoint of death, heart failure, and shock at 90 days and 1-year mortality (P < 0.001). Events were more common with TNK + PCI, regardless of baseline NT-proBNP quartile. When analysing baseline NT-proBNP as a continuous variable, no treatment interaction was observed for the primary endpoint (P = 0.17) or 1-year mortality (P = 0.08). Overall, NT-proBNP levels at Day 7 or 90 were not different between the two treatments. In patients with TIMI 2-3 flow before PCI, NT-proBNP at Day 90 was lower in PCI-only patients (P = 0.01), although no interaction was observed (P = 0.14). In TNK-pre-treated patients without reperfusion (TIMI 0-1) after PCI, NT-proBNP levels at Day 7 or 90 were not significantly higher than in PCI patients. Baseline NT-proBNP predicts outcome at 90 days and 1 year in patients undergoing PCI with or without facilitation with TNK. A higher rate of reperfusion in lytic-pre-treated patients did not result in lower NT-proBNP during follow-up. Thus, baseline and subsequent NT-proBNP levels do not explain the lower mortality rate with PCI alone seen in this trial.

Abstract 2466: Increased Plasma Concentrations of N-Terminal Pro Brain Natriuretic Peptide is a More Sensitive Marker of Subclinical Diastolic Dysfunction and Arterial Remodeling in Hypertension: Analytical Performance Comparison with BNP

Concentrations of plasma N-terminal pro brain natriuretic peptide (NT-proBNP) is inversely related to metabolic cardiovascular risk factors and is a valuable prognostic marker of cardiovascular events in arterial hypertension. Whether NT-proBNP levels are connected with diastolic function and arterial function was determined in hypertension. NT-proBNP was measured in 40 untreated patients with hypertension (mean BP 166/96 mmHg) without heart failure and 20 age and gender matched healthy, controls. Hypertensive patients were studied by pulsed Doppler and color M-mode Doppler echocardiography to evaluate LV diastolic function. Plasma NT-proBNP was significantly elevated in patients with hypertension (75.1 ± 75.2 [SD] pg/ml compared with 37.9 ± 38.5 in controls p &lt; 0.05). In hypertensive patients, NT-proBNP values were negatively correlated with the ratio of color M-mode flow propagation velocity to transmitral E velocity (r=−0.33, p&lt;0.05) while those of BNP had no correlation, suggesting that higher plasma NT-proBNP is indicative of subclinical diastolic dysfunction. Moreover, hypertensive patients with higher NT-proBNP values above the mean value in the control group (NT-proBNP &gt; 38 pg/ml) had significantly increased brachial intimal-medial thickness (0.36 ± 0.08 mm vs. 0.32 ± 0.05, p &lt; 0.05) and reduced wall stress (112.4 ± 29.5 kPa vs. 142.2 ± 30.8, p &lt; 0.05) compared with those with lower NT-proBNP, suggesting that the reference value of NT-proBNP plasma concentrations in uncomplicated hypertensives is 38pg/ml and higher NT-proBNP levels were associated with favorable remodeling of the peripheral arteries. Elevation of plasma NT-proBNP can be useful to identify subclinical LV diastolic dysfunction and peripheral arterial remodeling in asymptomatic patients with hypertension.

Prognostic value of plasma N-terminal probrain natriuretic peptide levels in the acute respiratory distress syndrome*

Patients with acute respiratory distress syndrome suffer from profound cardiac and pulmonary derangement, including right ventricular strain and noncardiogenic pulmonary edema, which may potentially alter concentrations of cardiac natriuretic peptides. We sought to determine whether N-terminal probrain natriuretic peptide (NT-proBNP) levels are elevated in acute respiratory distress syndrome and whether they can serve as a marker of prognosis in this setting. Prospective study. Tertiary-care academic medical center. One hundred seventy-seven acute respiratory distress syndrome subjects enrolled in a prospective intensive care unit cohort. None. NT-proBNP was measured from blood taken within 48 hrs of acute respiratory distress syndrome onset. Patients were followed for the primary outcome of 60-day mortality and secondary outcomes of organ dysfunction and ventilator-free days. Seventy patients died (40%). Median NT-proBNP level was 3181 ng/L (interquartile range 723-9246 ng/L). NT-proBNP levels were significantly higher among nonsurvivors (p < .0001). Receiver operating curve analysis revealed an optimal NT-proBNP cut-point of 6813 ng/L for predicting death. Patients with levels above the cut-point had significantly higher odds of mortality on multivariable analysis (odds ratio 2.36, 95% confidence interval 1.11-4.99, p = .02) than those with levels below the cut-point. Kaplan-Meier survival analysis showed that this difference emerged early and was sustained (p < .0001). Patients with elevated NT-proBNP also had higher organ dysfunction scores (p < .0001) and fewer ventilator free days (p = .03) than those with lower NT-proBNP levels. NT-proBNP levels are elevated among acute respiratory distress syndrome patients and parallel the severity of the syndrome and likelihood for morbidity and mortality. This demonstrates the potential utility of this biomarker for prognosis in this disease.

Pathophysiologic mechanisms of persistent cardiac troponin I elevation in stabilized patients after an episode of acute coronary syndrome

Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients. Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 microg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation. Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

Perception of symptoms is out of proportion to cardiac pathology in patients with “diastolic heart failure”

Background:Epidemiological studies suggest that “diastolic heart failure” (DHF) is common and has a prognosis similar to that of systolic heart failure (SHF). We wanted to assess whether patients with breathlessness...

Probrain Natriuretic Peptide for assessment of efficacy in heart failure treatment

N-terminal probrain natriuretic peptide (NT-proBNP) is elevated in patients with heart failure. Numerous clinical trials have evaluated the efficacy of spironolactone in heart failure; however, no studies have directly examined the effects of spironolactone treatment on NT-proBNP level. This study investigated whether NT-proBNP levels decrease with daily spironolactone treatment. The study consisted of 117 adult patients with heart failure. All participants were divided into 3 groups, class I, class II, and class III, according to the New York Heart Association classification system. Patients were randomly assigned to receive spironolactone or were treated with another drug, other than spironolactone, as placebo. NT-proBNP plasma samples were taken at baseline and after 6 mo of treatment. A total of 62 patients were treated with daily spironolactone; 55 patients were followed with available treatment without spironolactone. The baseline demographic and laboratory parameters were similar for patients in all groups. At the end of 6 mo, spironolactone-treated patients had significantly lower NT-proBNP levels and significantly better ejection fractions than did patients in all New York Heart Association classes who were not treated with spironolactone. Results suggest that spironolactone decreases plasma NT-proBNP concentrations, and that the measurement of plasma NT-proBNP levels may be helpful in assessing therapeutic efficacy in patients who are treated for heart failure.

PO1-24 HEPATIC CELL-SPECIFIC ATP-BINDING CASSETTE (ABC) TRANSPORTER PROFILING IDENTIFIES PUTATIVE NOVEL CANDIDATES FOR MACROPHAGE CHOLESTEROL HOMEOSTASIS IN MICE

Recently, a high prevalence of small persistent cardiac troponin I (cTnI) elevations has been reported in patients who had been stabilized after a recent episode of acute coronary syndrome (ACS). We now have studied the associations of persistently elevated cTnI levels to cardiac performance, inflammation, coagulation, coronary status, and treatment strategy in these patients.Cardiac troponin I was determined at 6 weeks, 3 months, and 6 months after randomization in 898 stabilized ACS patients from the FRagmin and Fast Revascularization during InStability in Coronary artery disease (FRISC) II trial and using the high-sensitive Access AccuTnI assay (Beckman Coulter, Fullerton, CA). All patients were followed up for at least 5 years. Persistent cTnI elevation >0.01 μg/L at the 3 measurement instances was detected in 233 patients (26%). N-terminal pro-brain natriuretic peptide (NT-proBNP) at 6 months (OR 2.5, 95% CI 2.0-3.1), male sex (OR 2.2, 95% CI 1.4-3.7), and randomization to an early invasive strategy (OR 1.8, 95% CI 1.2-2.7) independently predicted persistently elevated cTnI levels. Persistently cTnI-positive patients in the invasive cohort had significantly lower NT-proBNP levels compared to noninvasively treated patients, indicating that the mechanisms causing cTnI elevation in this group may be prognostically less harmful. No independent associations were found for markers of inflammation or coagulation.Persistent cTnI elevation occurs frequently late after an ACS. The NT-proBNP level at 6 months was the strongest predictor for elevated cTnI levels that thus appear to be predominantly related to impaired left ventricular function.

Multicentre evaluation of a new point-of-care test for the determination of NT-proBNP in whole blood

The Roche CARDIAC proBNP point-of-care (POC) test is the first test intended for the quantitative determination of N-terminal pro-brain natriuretic peptide (NT-proBNP) in whole blood as an aid in the diagnosis of suspected congestive heart failure, in the monitoring of patients with compensated left-ventricular dysfunction and in the risk stratification of patients with acute coronary syndromes. A multicentre evaluation was carried out to assess the analytical performance of the POC NT-proBNP test at seven different sites. The majority of all coefficients of variation (CVs) obtained for within-series imprecision using native blood samples was below 10% for both 52 samples measured ten times and for 674 samples measured in duplicate. Using quality control material, the majority of CV values for day-to-day imprecision were below 14% for the low control level and below 13% for the high control level. In method comparisons for four lots of the POC NT-proBNP test with the laboratory reference method (Elecsys proBNP), the slope ranged from 0.93 to 1.10 and the intercept ranged from 1.8 to 6.9. The bias found between venous and arterial blood with the POC NT-proBNP method was < or =5%. All four lots of the POC NT-proBNP test investigated showed excellent agreement, with mean differences of between -5% and +4%. No significant interference was observed with lipaemic blood (triglyceride concentrations up to 6.3 mmol/L), icteric blood (bilirubin concentrations up to 582 micromol/L), haemolytic blood (haemoglobin concentrations up to 62 mg/L), biotin (up to 10 mg/L), rheumatoid factor (up to 42 IU/mL), or with 50 out of 52 standard or cardiological drugs in therapeutic concentrations. With bisoprolol and BNP, somewhat higher bias in the low NT-proBNP concentration range (<175 ng/L) was found. Haematocrit values between 28% and 58% had no influence on the test result. Interference may be caused by human anti-mouse antibodies (HAMA) types 1 and 2. No significant influence on the results with POC NT-proBNP was found using volumes of 140-165 muL. High NT-proBNP concentrations above the measuring range of the POC NT-proBNP test did not lead to false low results due to a potential high-dose hook effect. The POC NT-proBNP test showed good analytical performance and excellent agreement with the laboratory method. The POC NT-proBNP assay is therefore suitable in the POC setting.

Obese subjects with heart failure have lower N‐terminal pro‐brain natriuretic peptide plasma levels irrespective of aetiology

N-terminal pro-brain natriuretic peptide (NT-proBNP) may be useful in the diagnosis of heart failure and ventricular dysfunction. Obesity is an independent cardiovascular risk factor. The purpose of this study was to measure NT-proBNP plasma levels in obese and non-obese subjects with heart failure and to compare levels in subjects with ischaemic and dilated aetiology. In this study, obese subjects had 63% lower NT-proBNP plasma levels than non-obese subjects (p < 0.01). In multivariate analysis, BMI was inversely associated with NT-proBNP plasma levels (p < 0.05) and a 17% decrease in natriuretic peptide levels was attributed to obesity (p < 0.036). When we analyzed data according to the aetiology of heart failure, we found that both groups (ischaemic and dilated) had a 65% decrease in NT-proBNP plasma levels in obese subjects compared to non-obese subjects.

N-Terminal Pro-Brain Natriuretic Peptide as an Indicator of Right Ventricular Dysfunction

Background Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) are elevated in most patients with acute pulmonary embolism (APE) that results in right ventricular overload. Therefore, APE should be considered in the differential diagnosis of patients with acute dyspnea and abnormal levels of BNPs. Moreover, plasma BNPs have been proved to predict outcome in APE. Methods and Results Low NT-proBNP or BNP levels characterize an uneventful hospital course, and NT-proBNP levels of <500 pg/mL identify patients who could potentially be candidates for care on a complete outpatient basis. Moreover, plasma NT-proBNP and BNP reflect the degree of right ventricular overload in APE. Plasma BNPs can also be elevated in chronic precapillary pulmonary hypertension and are strongly related to total pulmonary resistance. Elevated plasma levels of BNP/NT-proBNP and especially their further increase during follow-up are a potent predictor of poor survival. Conclusion Because levels of brain natriuretic peptides are elevated significantly not only in pathologic conditions that affect the left ventricle but also in clinical conditions that lead to isolated acute or chronic right ventricular overload, it could be proposed that these peptides should not be regarded as biomarkers of congestive heart failure, but as indicators of cardiovascular dyspnea.

Diagnostic and Prognostic Performance of N-Terminal ProBNP in Primary Care Patients With Suspected Heart Failure

Background The value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in terms of diagnosis and prognosis in congestive heart failure (CHF) and left ventricular systolic dysfunction (LVSD) has been demonstrated previously in various populations, but data on primary care patients are sparse. The aim of this study was to evaluate the diagnostic and prognostic performance of NT-proBNP in primary care patients with suspected CHF. Methods and Results Three hundred sixty-seven consecutive patients (mean age, 68.8 years; range, 39.0–84.0 years) who had been referred by their general practitioner for echocardiographic evaluation because of suspected CHF. In all patients, NT-proBNP was measured at baseline and left ventricular ejection fraction (LVEF) was estimated with echocardiography. LVSD (LVEF ≤0.40) was found in 9% of the patients. NT-proBNP was significantly higher in patients with LVSD ( P < .0001). With predefined cut off values for NT-proBNP (125 pg/mL), the sensitivity, specificity, positive predictive value, and negative predictive value for the detection of LVSD were 0.97, 0.46, 0.15 and 0.99, respectively. Area under the receiver operating characteristic curve was 0.87. The application of an age-differentiated cut-off value for NT-proBNP (125 pg/mL for <75 years old and 450 pg/mL for ≥75 years old) did not increase diagnostic performance. Patients were followed for a median of 778 days; 8% of the patients died during the follow-up period. The mortality rate was higher in patients with NT-proBNP of >125 pg/mL than in patients with normal values ( P < .002, log rank), and the difference persisted after controlling for age, gender, and LVEF (hazard ratio per unit increase in log NT-proBNP, 2.2; range, 1.2–4.1; P = .015). Conclusion In primary care patients who were referred for echocardiography because of suspected CHF, NT-proBNP values <125 pg/mL effectively rule out LVSD. Furthermore low NT-proBNP values are associated with a lower risk of death, independently of age, gender, and LVEF.

N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients.

Heart failure (HF) is responsible for a huge burden in hospital care. Our goal was to evaluate the value of N-terminal-pro-brain natriuretic peptide (NT-proBNP) in predicting death or hospital readmission after discharge of HF patients. We included 182 patients consecutively admitted to hospital because of decompensated HF. Patients were followed up for 6 months. The primary end point was death or readmission. Twenty-six patients died in hospital. The median admission NT-proBNP level was 6778.5 pg/mL, and the median level at discharge was 4137.0 pg/mL (P<0.001). Patients were classified into 3 groups: (1) decreasing NT-proBNP levels by at least 30% (n=82), (2) no significant modifications on NT-proBNP levels (n=49), and (3) increasing NT-proBNP levels by at least 30% (n=25). The primary end point was observed in 42.9% patients. Variables associated with an increased hazard of death and/or hospital readmission in univariate analysis were length of hospitalization, heart rate, signs of volume overload, no use of ACE inhibitors, higher NYHA class at discharge, admission and discharge NT-proBNP, and the change in NT-proBNP levels. The variation in NT-proBNP was the strongest predictor of an adverse outcome. Independent variables associated with an increased risk of readmission or death were signs of volume overload and the change in NT-proBNP levels. Variations in NT-proBNP levels are related to hospital readmission and death within 6 months. NT-proBNP levels are potentially useful in the evaluation of treatment efficacy and might help clinicians in planning discharge of HF patients. Whether therapeutic strategies aimed to lower NT-proBNP levels modify prognosis warrants future investigation.

Combined measurements of cardiac troponin T and N-terminal pro-brain natriuretic peptide in patients with chronic heart failure

Objective: To examine the prognostic contribution of combined cardiac troponin T(cTnT) and N-terminal pro-brain natriuretic peptide(NT-proBNP) in patients with compensated and decompensated chronic heart failure(CHF) in absence of acute coronary syndrome. Design and patient population: Between July 2001 and March 2002, 73 consecutive patients (mean age = 68.2 ± 1.4years,39men) hospitalised for decompensated or stable CHF were studied and followed until December 2002. Main outcome measures: Serum cTnT and NT-proBNP were measured on admission. Actuarial rates of adverse cardiac events, including sudden or CHF death, or rehospitalisation for CHF during follow-up were compared among patients grouped according to initial serum cTnT and NT-proBNP concentrations, singly or in combination. Results: The cut-off value for NT-proBNP predictive of cardiac decompensation was 1050pg/ml. NT-proBNP was significantly higher among 46 patients with, than among 27 patients without, decompensated CHF(7167 ± 2318 vs.1360 ± 286pg/ml, P < 0.01). The serum concentration of cTnT upon admission was > 0.02ng/ml in 22 of the 73 patients. High cTnT values were measured in 17 of 46 patients(37%)(0.037 ± 0.004ng/ml) with, and in 5 of 27 patients(18.5%)(0.038 ± 0.002ng/ml) without, cardiac decompensation. The 18 patients with high concentrations of both cTnT and NT-proBNP had a lower adverse cardiac event-free rate than the 31 patients with low cTnT and low NT-proBNP on study entry(P < 0.005). Conclusions: Combined measurements of serum cTnT and NT-proBNP were reliable prognostic markers of adverse cardiac event in patients with CHF.

Combined Measurements of Cardiac Troponin T and N-Terminal Pro-Brain Natriuretic Peptide in Patients With Heart Failure

To examine the prognostic contribution of combined cardiac troponin T (cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with heart failure (CHF) in the absence of acute coronary syndrome. Between July 2001 and March 2002, 71 consecutive patients (mean age = 68.4+/-1.4 years, 37 men), hospitalised for heart failure, were studied during hospitalisation and follow up until December 2002. Serum cTnT and NT-proBNP were measured on admission. Actuarial rates of adverse cardiac events, including sudden or CHF death, or rehospitalisation for CHF during follow up were compared with patients grouped according to initial serum cTnT and/or NT-proBNP concentrations. The adverse cardiac event-free rate among the 20 patients with cTnT > or 0.01 ng/ml was significantly lower than the 51 patients with cTnT <0.01 ng/ml (P<0.05). Similarly, the adverse cardiac event-free rate among the 36 patients with NT-proBNP > or =1,357 pg/ml (median) was significantly lower than the 35 patients with NT-proBNP <1,357 pg/ml (P<0.01). The 16 patients with high concentrations of both cTnT and NT-proBNP had a lower adverse cardiac event-free rate than the 31 patients with low cTnT and low NT-proBNP upon commencement of the study (P<0.005). Measurements of serum cTnT and NT-proBNP were reliable prognostic markers of adverse cardiac event in patients with CHF.

N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease

ObjectivesWe sought to examine whether measurements of N-terminal pro-brain natriuretic peptide (NT-proBNP), in addition to cardiac troponin T (cTnT) and interleukin-6 (IL-6), improve the ability to identify high-risk patients who benefit from an early invasive strategy. BackgroundBiochemical indicators of cardiac performance (e.g., NT-proBNP), inflammation (e.g., IL-6), and myocardial damage (e.g., cTnT) predict mortality in unstable coronary artery disease (UCAD) (i.e., unstable angina or non–ST-segment elevation myocardial infarction [MI]). In these patients, an early invasive treatment strategy improves the outcome. MethodsLevels of NT-proBNP, cTnT, and IL-6 were measured in 2,019 patients with UCAD randomized to an invasive or non-invasive strategy in the FRagmin and fast revascularization during InStability in Coronary artery disease (FRISC-II) trial. Patients were followed up for two years to determine death and MI. ResultsPatients in the third NT-proBNP tertile had a 4.1-fold (95% confidence interval [CI] 2.4 to 7.2) and 3.5-fold (95% CI 1.8 to 6.8) increased mortality in the non-invasive and invasive groups, respectively. An increased NT-proBNP level was independently associated with mortality. In patients with increased levels of both NT-proBNP and IL-6, an early invasive strategy reduced mortality by 7.3% (risk ratio 0.46, 95% CI 0.21 to 1.00). In patients with lower NT-proBNP or IL-6 levels, the mortality was not reduced. Only elevated cTnT was independently associated with future MI and a reduction of MI by means of an invasive strategy. ConclusionsN-terminal proBNP is independently associated with mortality. The combination of NT-proBNP and IL-6 seems to be a useful tool in the identification of patients with a definite survival benefit from an early invasive strategy. Only cTnT is independently associated with future MI and a reduction of MI by an invasive strategy.