Related Articles

OBJECTIVES

This study sought to characterize factors influencing amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and to evaluate the ability of NT-proBNP to detect left ventricular (LV) dysfunction in a large community sample.

BACKGROUND

Secretion of BNP increases in cardiac disease, making BNP an attractive biomarker. Amino-terminal proBNP, a fragment of the BNP prohormone, is a new biomarker. We evaluated factors influencing NT-proBNP in normal patients and compared the ability of NT-proBNP and BNP to detect LV dysfunction in a large community sample.

METHODS

Amino-terminal pro-BNP was determined in plasma samples of a previously reported and clinically and echocardiographically characterized random sample (n = 1,869, age ≥ 45 years) of Olmsted County, Minnesota.

RESULTS

In normal patients (n = 746), female gender and older age were the strongest independent predictors of higher NT-proBNP. Test characteristics for detecting an LV ejection fraction ≤ 40% or ≤ 50% were determined in the total sample with receiver operating characteristic curves. Amino-terminal pro-BNP had significantly higher areas under the curve for detecting an LV ejection fraction ≤ 40% or ≤ 50% than BNP in the total population and in several male and age subgroups, whereas areas were equivalent in female subgroups. Age- and gender-adjusted cutpoints improved test characteristics of NT-proBNP. Both assays detected patients with systolic and/or moderate to severe diastolic dysfunction to a similar degree, which was less robust than the detection of LV systolic dysfunction alone.

CONCLUSIONS

Amino-terminal pro-BNP in normal patients is affected primarily by gender and age, which should be considered when interpreting values. Importantly, in the entire population sample NT-proBNP performed at least equivalently to BNP in detecting LV dysfunction and was superior in some subgroups in detecting LV systolic dysfunction.

Background

Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure.

Methodology/Principal Findings

We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%–8.0% in proBNP assay and from 7.0%–8.4% in total BNP assay, and between-run CVs ranged from 5.3–7.4% in proBNP assay and from 2.9%–9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998–1.00), and analytical recovery was 90–101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects.

Conclusions/Significance

Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma.

Background:

Although the cardiac biomarker troponin T (cTnT) is strongly related to mortality in end-stage renal disease, the independent association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cTnT in predicting outcomes is unknown.

Objective:

To determine factors associated with NT-proBNP and cTnT, and to determine whether these levels are associated with mortality.

Study Design:

Cohort Study

Settings and Participants:

Asymptomatic hemodialysis patients (n=150) in 4 university-affiliated hemodialysis units.

Exposure and Outcomes:

For cross-sectional analysis, echocardiographic variables as exposures and N-terminal proBNP and cardiac troponin T as outcomes; for longitudinal analysis, association of N-terminal proBNP and cardiac troponin T as exposures to all-cause and cardiovascular disease mortality as outcomes.

Results:

In a multivariate regression analysis, low midwall fractional shortening a measure of poor systolic function was an independent correlate of log NT-proBNP (p<0.01), while left ventricular mass index was an independent correlate of cTnT (p<0.01). Over a median follow-up of 24 months, 46 patients died of which, 26 died due to cardiovascular causes. NT-ProBNP had a strong graded relationship with all-cause (Hazard Ratio (HR) 1.54, 4.78 and 4.03 for increasing quartiles, Chi2 32.2, p<0.001) and cardiovascular mortality (HR 2.99, 10.95, 8.54 Chi2 23.66, p<0.01), while cTnT had a weaker relationship with all-cause (HR 1.57, 2.32, 3.39, Chi2 23.09, p<0.01) and cardiovascular mortality (HR 1, 0.81, 2.12, 2.14, Chi2 15.05, p=0.1). The combination of the two biomarkers did not improve the association with all-cause or cardiovascular mortality compared to NT-proBNP alone. NT-proBNP was a marker of mortality even after adjusting for left ventricular mass index and midwall fractional shortening.

Limitations:

Our cohort was predominantly black and of limited sample size.

Conclusion:

NT-proBNP strongly correlates with left ventricular systolic dysfunction and is more strongly associated with mortality than cTnT in asymptomatic hemodialysis patients.

Background

Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) is regarded as a sensitive marker of cardiovascular disease. Vascular disease plays an important role in cognitive impairment.

Method

In 447 elderly patients with mental illness, serum NT-proBNP level and the presence or absence of vascular disease according to the medical record were used to categorize patients in different subgroups of vascular disease.

Results and Conclusion

Patients with vascular disease and elevated serum NT-proBNP level had a lower cognition level, shorter survival time, lower renal function and a higher percentage of pathological brain imaging than patients with vascular disease and normal NT-proBNP level. Thus, elevated serum NT-proBNP level might be helpful to detect patients who have a more severe cardiovascular disease.

B-type natriuretic peptide (BNP) and its N-terminal fragment (NT-proBNP) are released from ventricular cardiomyocytes in response to an increase in ventricular wall stress and to myocardial ischemia. Both BNP and NT-proBNP have proven to be reliable diagnostic and prognostic biomarkers in patients with heart failure. Recently, the diagnostic roles of BNP and NT-proBNP in patients with coronary artery disease (CAD) have been investigated. For patients with acute coronary syndromes, data have been derived from a great number of studies, whereas in patients with stable CAD, only a limited amount of recent data is available; although limited, these data show that elevations in BNP and NT-proBNP levels are associated with the extent of CAD, thus providing prognostic information for an unfavourable clinical outcome. However, clinical and therapeutic implications are indistinct and need to be elucidated in further studies.

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) plasma levels are commonly high at the early phase of septic shock and have been suggested to be prognostic markers for this condition. It is uncertain, however, whether this increase reflects sepsis related cardiac dysfunction. In a recent issue of Critical Care, Mokart and coworkers showed the accuracy of NT-proBNP in predicting intensive care unit mortality in cancer patients with septic shock, which could help in identifying high risk cancer patients. Results from repeated transthoracic echocardiographs show that NT-proBNP on day 2 after admission was higher in patients presenting with cardiac dysfunction, whereas NT-proBNP on day 1 did not predict cardiac dysfunction. These data suggest that after an initial overexpression of NT-proBNP in all septic patients, patients with cardiac dysfunction will present persistent high levels of NT-proBNP.

N-terminal pro B-type natriuretic peptide (NT-proBNP) is a product of cleavage of the cardiac prohormone pro B-type natriuretic peptide into its active form. It has proven to be a useful biomarker in left heart failure. However, studies examining the utility of serial measurements of NT-proBNP in pulmonary arterial hypertension (PAH) patients have shown mixed results. We compared three methods of predicting adverse clinical outcomes in PAH patients: the change in 6 minute walk distance (6MWD), the change in absolute levels of NT-proBNP and the change in log-transformed levels of NT-proBNP. All PAH patients presenting from March-June 2007 were screened. Patients who were clinically unstable, had abnormal renal function or hemoglobin levels or lacked a prior NT-proBNP were excluded. 63 patients were followed up for adverse clinical outcomes (defined as death, transplantation, hospitalisation for right heart failure, or need for increased therapy). Three methods were used to predict adverse events, i.e.: (a) comparing a 6MWD performed in March-June 2007 and a previous 6MWD. A decrease in 6MWD of ≥30m was used to predict clinical deterioration; (b) comparing a NT-proBNP value measured in March-June 2007 and a previous NT-proBNP. An increase in NT-proBNP of ≥250pg/ml was used to predict clinical deterioration (250pg/ml represented approximately 30% change from the baseline median value of NT-proBNP for this cohort); and (c) comparing the loge equivalents of two consecutive NT-proBNP values. We used the formula: loge(current NT-proBNP) - loge(previous NT-proBNP)=x. A value of x≥+0.26 was used to predict adverse events. This is equivalent to a 30% change from baseline, and hence is comparable to the chosen cut-off for absolute levels of NT-proBNP. A loge difference of ≥+0.26 identifies patients at risk of adverse events with a specificity of 98%, a sensitivity of 60%, a positive predictive value of 89%, and a negative predictive value of 90%. A drop in 6MWD of ≥30m has a specificity of 29%, a sensitivity of 73%, a positive predictive value of 24% and a negative predictive value of 24%. It seems possible to risk-stratify apparently stable PAH patients by following the changes in their serial log-transformed NT-proBNP values. In this small pilot study, this method was better than relying on changes in the actual levels of NT-proBNP or changes in 6MWD. This needs to be validated prospectively in a larger cohort.

Background

The inferior vena cava (IVC) diameter and degree of inspiratory collapse are used as echocardiographic indices in the estimation of right atrial pressure. Brain-natriuretic peptides (BNPs) are established biomarkers of myocardial wall stress. There is no information available regarding the association between the IVC diameter and BNPs in patients with heart failure and various degrees of systolic performance. The purpose of this investigation is to quantify the degree to which natriuretic peptides (BNP and N-terminal pro-B natriuretic peptide [NT-ProBNP]) and echocardiographic-derived indices of right atrial pressure correlate in this patient population.

Methods

We examined 77 patients (mean age 61 ± 17 years, 44% male) with decompensated heart failure who underwent transthoracic echocardiography and, within a timeframe of 24 hours, determination of BNP and NT-ProBNP levels in venous blood. BNP and NT-ProBNP were analyzed after log transformation. The degree of association was measured by the correlation coefficient using the Pearson’s method.

Results

The mean ejection fraction was 50% ± 20%, and 33% of the study cohort had a remote history of heart failure. The mean IVC diameter was 1.85 cm ± 0.5, the mean BNP was 274 pg/mL, the confidence interval (CI) was 95% (95% CI: 197–382), and the mean NT-ProBNP was 1994 pg/mL (95% CI: 1331–2989). There was a positive, albeit small, association between IVC diameter and BNP (r = 0.24, 95% CI: 0.01–0.44; P = 0.03) and NT-ProBNP (r = 0.27, 95% CI: 0.05–0.47; P = 0.01). Among patients with different degrees of IVC collapse in response to inspiration, values for BNP and NT-ProBNP did not differ substantially (P = 0.36 and 0.46 for BNP and NT-ProBNP, respectively).

Conclusion

Natriuretic peptides correlate weakly with IVC size and do not predict changes in response to intrathoracic pressure.

This study evaluated the relationship between natriuretic peptide levels and a wide range of echocardiography parameters in a population of thirty-three patients with poorly regulated type 2 diabetes, and no known heart failure. Natriuretic peptides brain natriuretic peptide (BNP) and N-terminal prohormone BNP (NT-proBNP) were measured. Transthoracic echocardiography was performed and cardiac volumes and ejection fraction were measured. Doppler and tissue Doppler were measured and diastolic function was stratified according to recent guidelines. Very few echocardiography parameters were correlated with BNP or NT-proBNP levels. However, left atrial end-systolic volume indexed for body surface area was correlated with natural logarithm (ln) BNP and ln NT-proBNP (r = 0.62 and r = 0.60; P < 0.05). There were significant differences in ln BNP and ln NT-proBNP levels between those with normal and those with abnormal diastolic function (1.4 vs 3.1; P < 0.001 and 3.4 vs 5.8; P < 0.001). This study showed that very few echocardiography parameters were correlated with BNP or NT-proBNP levels in patients with poorly regulated type 2 diabetes, which in part contradicts previous studies in other diabetic populations. The exception was left atrial end-systolic volume that showed a moderate correlation with BNP or NT-proBNP levels. There were significant differences in BNP and NT-proBNP levels between the group with normal left ventricular diastolic function and the group with abnormal diastolic function.

Background

Plasma levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP) provide useful prognostic predictors in patients after cardiac surgery. However, predictive accuracy of NT-proBNP levels has varied significantly according to renal dysfunction. The purpose of this study was to assess whether preoperative NT-proBNP levels could be used as predictors of early postoperative outcomes on the basis of renal function in patients undergoing off-pump coronary artery bypass surgery (OPCAB).

Methods

In 219 patients undergoing elective OPCAB, NT-proBNP and an estimated glomerular filtration rate (eGFR) were assessed preoperatively. All patients were divided into 3 groups according to tertiles of eGFR: the first (eGFR ≥ 90 ml/min/1.73 m2), the second (90 ml/min/1.73 m2 > eGFR ≥ 72 ml/min/1.73 m2) and the third tertile group (eGFR < 72 ml/min/1.73 m2). End point was the composite of early postoperative complications defined as myocardial infarction, new onset atrial fibrillation, ventricular dysfunction, prolonged mechanical ventilator care (> 48 hr), prolonged ICU stay (≥ 3 days), and in hospital mortality.

Results

There was no difference in early postoperative complications among groups. A preoperative NT-proBNP level of 228 pg/ml and 302 pg/ml (sensitivity 70%, specificity 67%, P < 0.001 and sensitivity 73%, specificity 63%, P = 0.001, respectively) were optimal cut-off values predicting complicated early postoperative course in second and third tertile group, respectively.

Conclusions

Preoperative NT-proBNP levels seem to be predictive of early postoperative complications in patients with eGFR < 90 ml/min/1.73 m2 undergoing OPCAB.

Objectives

Determine if serial measurement of N-terminal pro B-type natriuretic peptide (NT-proBNP) in community dwelling elderly would provide additional prognostic information to traditional risk factors.

Background

Accurate cardiovascular risk stratification is challenging in the elderly.

Methods

NT-proBNP was measured at baseline and 2-3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal Cardiovascular Health Study. This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular (CV) causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders.

Results

NT-proBNP levels in the highest quintile (>267.7 pg/mL) were independently associated with greater risks of HF (hazard ratio [HR] =3.05 (95%CI [confidence interval] 2.46-3.78) and CV death (HR=3.02, 95%CI 2.36-3.86) compared to the lowest quintile (<47.5 pg/mL). The inflection point for elevated risk occurred at NT-proBNP=190 pg/mL. Among participants with initially low NT-proBNP (<190 pg/mL), those who developed a >25% increase on follow-up to >190 pg/mL (21%) were at greater adjusted risk of HF (HR=2.13, 95%CI=1.68-2.71) and CV death (HR=1.91, 95%CI=1.43-2.53) compared to those with sustained low levels. Among participants with initially high NT-proBNP, those who developed >25% increase (40%) were at higher risk of HF (HR=2.06 95%CI 1.56 −2.72) and cardiovascular death (HR=1.88, 95%CI 1.37-2.57), whereas those who developed >25% decrease to ≤190pg/mL (15%) were at lower risk of HF (HR=0.58, 95%CI 0.36-0.93) and CV death (HR=0.57, 95%CI 0.32 −1.01) compared to those with unchanged high values.

Conclusion

NT-proBNP levels independently predict heart failure and cardiovascular death in older adults. NT-proBNP levels frequently change over time and these fluctuations reflect dynamic changes in cardiovascular risk.

Backgraound/Aims

N-terminal pro-B-type natriuretic peptide (NT-proBNP) has recently been introduced as a useful marker in diagnosing underlying disease in patients with dyspnea and for determining the prognosis of patients with heart failure. The purpose of this study was to evaluate the value of the NT-proBNP as a marker of disease severity in patients with pericardial effusions.

Methods

We enrolled 69 consecutive patients who showed moderate or large pericardial effusion with preserved left ventricular (LV) systolic function; 42 patients finally participated in the study, and 13 (31.0%) of them showed cardiac tamponade. We analyzed the etiologies, the clinical and echocardiographic variables, and the serum NT-proBNP levels in these patients.

Results

The mean NT-proBNP level was 751±1002 ng/L (range 5 to 5289), and the median level was 385 ng/L (interquartile range 152 to 844). The NT-proBNP levels were higher in those patients with jugular venous distension (p=0.002), pulsus paradoxus (p=0.016), heart rate ≥100/min (p=0.006), cardiac tamponade (p=0.001), large pericardial effusion (p=0.029), exaggerated respiratory variation of the transmitral inflow (p=0.006), or plethora of the inferior vena cava (p=0.01). The NT-proBNP levels showed significant correlation with heart rate (r=0.517, p<0.001) and the diameter of the inferior vena cava (r=0.329, p=0.03).

Conclusion

NT-proBNP may be useful as a marker of disease severity in patients suffering from pericardial effusion, but further prospective studies with more patients will be needed.

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a population prevalence of about 1%. Natriuretic peptide level is elevated in patients with AF with diastolic dysfunction even with a normal left ventricular (LV) ejection fraction. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level and Doppler echocardiographic parameters for diastolic function have shown correlation with LV filling pressures. We aimed to evaluate the relationship between echocardiographic parameters and serum NT-proBNP in patients with AF with preserved LV ejection fraction.

Methods

We examined transthoracic echocardiography and NT-proBNP levels in the patients with AF and patients with sinus rhythm. Blood samples were taken for serum NT-proBNP measurements within 24 hours of echocardiographic examination. The group 1 was the patients with sinus rhythm (n = 30, mean age 68 ± 13 years) and the group 2 was the patients with AF (n = 33, mean age 70 ± 14 years).

Results

The group 2 patients had significantly higher mitral E, E' (lateral annulus), E/E' (septal annulus), left atrial (LA) volume index, LA size, pulmonary vein diastolic velocity, and NT-proBNP level than those of group 1 patients (p < 0.05). The area under the receiver-operating characteristic curve showed a NT-proBNP had good diagnostic power for E/E' (septal annulus) > 15 in patients with AF at cutoff value of 433 pg/mL.

Conclusion

NT-proBNP level is well correlated with Doppler echocardiographic parameters of diastolic function in patients with AF and preserved LV ejection fraction. NT-proBNP level more than 433 pg/mL may suggest elevated LV filling pressure in patients with AF.

BACKGROUND:

The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP) is an established biomarker for cardiac failure.

OBJECTIVE:

To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG).

METHODS:

In 819 patients undergoing isolated CABG surgery preoperative serum NT-proBNP levels were measured. NT-proBNP was correlated with various postoperative outcome parameters and survival rate after a median follow-up time of 18 (0.5–44) months. Risk factors of mortality were identified using χ2, Mann–Whitney test, and Cox regression.

RESULTS:

NT-proBNP levels >430 ng/ml and >502 ng/ml predicted hospital and overall mortality (p<0.05), with an incidence of 1.6% and 4%, respectively. Kaplan–Meier analysis revealed decreased survival rates in patients with NT-proBNP >502 ng/ml (p = 0.001). Age, preoperative serum creatinine, diabetes, chronic obstructive pulmonary disease, low left ventricular ejection fraction and BNP levels >502 ng/ml were isolated as risk factors for overall mortality. Multivariate Cox regression analysis, including the known factors influencing NT-proBNP levels, identified NT-proBNP as an independent risk factor for mortality (OR = 3.079 (CI = 1.149-8.247), p = 0.025). Preoperative NT-proBNP levels >502 ng/ml were associated with increased ventilation time (p = 0.005), longer intensive care unit stay (p = 0.001), higher incidence of postoperative hemofiltration (p = 0.001), use of intra-aortic balloon pump (p<0.001), and postoperative atrial fibrillation (p = 0.031)

CONCLUSION:

Preoperative NT-proBNP levels >502 ng/ml predict mid-term mortality after isolated CABG and are associated with significantly higher hospital mortality and perioperative complications.

Children with single ventricle (SV) physiology have increased ventricular work and are at risk for heart failure (HF). However, HF diagnosis is especially difficult because there are few objective measures of HF validated in this cohort. We previously showed that plasma B-type natriuretic peptide (BNP) levels were sensitive and specific for detecting HF in a small, heterogeneous SV cohort. The aim of this study was to define the impact of SV morphology and stage of palliation on the correlation between BNP and HF. We also examined the utility of N-terminal pro-BNP (NT-proBNP), a more stable product of pre-BNP processing, as a biomarker of HF in these patients. A cross-sectional observational study of SV children 1 month–7 years was conducted. The presence of HF was defined as a Ross score >2. The association of BNP or NT-proBNP with HF was assessed using logistic regression and ROC curves. Twenty-two of 71 included children (31%) had clinical HF. A doubling of BNP was associated with an odds ratio for HF of 2.20 (95%CI 1.36–3.55, p=0.001) with a c-statistic >75%, yielding a detection threshold of ≥45 pg/ml. This threshold was preserved when patients were stratified by right ventricular morphology or stage of surgical palliation. Similarly, a doubling of NT-proBNP was associated with an odds ratio for HF of 1.92 (95% CI 1.17–3.14, p=0.009). In contrast with BNP, the threshold value of NT-proBNP for predicting HF decreased with stage of palliation. In conclusion, plasma BNP and NT-proBNP are reliable tests for clinical HF in young children with SV physiology, specifically those with right ventricular morphology, regardless of stage of palliation.

Objective: To compare head to head the diagnostic accuracy of B type natriuretic peptide (BNP) and the amino terminal fragment of its precursor hormone (NT-proBNP) for congestive heart failure (CHF) in an emergency setting.

Methods: 251 consecutive patients presenting to the emergency department with dyspnoea as a chief complaint were prospectively studied. Patients with acute coronary syndromes were excluded. The diagnosis of CHF was based on the Framingham score for CHF plus echocardiographic evidence of systolic or diastolic dysfunction. Blood concentrations of BNP and NT-proBNP were measured by two commercially available assays (Abbott and Roche methods). The diagnostic accuracies of BNP and NT-proBNP were assessed by receiver operating characteristic curve analysis.

Results: Areas under the curve for BNP and NT-proBNP in patients with dyspnoea caused by CHF (n  =  137) and in patients with dyspnoea attributable to other reasons (n  =  114) did not differ significantly (area under the curve 0.916 v 0.903, p  =  0.277, statistical power 94%). Cut off concentrations with the highest diagnostic accuracy were 295 ng/l for BNP (sensitivity 80%, specificity 86%, diagnostic accuracy 83%) and 825 ng/l for NT-proBNP (sensitivity 87%, specificity 81%, diagnostic accuracy 84%). Evaluation of discordant false classifications at these cut off concentrations showed no advantage for either BNP nor NT-proBNP in the biochemical diagnosis of CHF (17 misclassifications by BNP and 14 by NT-proBNP, p  =  0.720). In the population studied, age, sex, and renal function had no impact on the diagnostic utility of both tests when compared by logistic regression models.

Conclusions: BNP and NT-proBNP may be equally useful as an aid in the diagnosis of CHF in short of breath patients presenting to the emergency department.

Background

B-type natriuretic peptide (BNP) is predictive of inducible ischemia in patients with coronary heart disease (CHD). Whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) has a comparable strength of association with ischemia is uncertain.

Hypothesis

Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD.

Methods

We performed a cross-sectional study of 901 outpatients with stable CHD. NT-proBNP was measured in all patients prior to exercise treadmill testing and stress echocardiography. In addition, plasma BNP was measured in a subset of 355 participants. Logistic regression was used to examine the association of NT-proBNP and BNP quartiles with inducible ischemia.

Results

Inducible ischemia was found in 216 (24%) patients. The proportion with inducible ischemia ranged from 42% (95/225) in the highest quartile of NT-proBNP levels (>410 pg/ml) to 9% (21/226) in the lowest quartile (0–72 pg/ml). The highest quartile had a 7-fold greater odds of inducible ischemia than the lowest quartile (odds ratio [OR]: 7.1, 95% confidence interval [CI]: 4.2–12; P<0.0001). This association remained robust after adjustment for traditional cardiovascular risk factors, left ventricular ejection fraction, and diastolic dysfunction (OR: 3.6, 95% CI: 1.4–9.1; P = 0.009). In the subgroup with measurements of both NT-proBNP and BNP, both natriuretic peptides were predictive of ischemia. The multivariable-adjusted c-statistics for inducible ischemia were 0.71 for NT-proBNP and 0.62 for BNP (entered as continuous variables).

Conclusions

Resting NT-proBNP levels are independently associated with inducible ischemia in outpatients with stable CHD. Baseline elevations of natriuretic peptide may indicate subclinical inducible ischemia in high risk patients with CHD.

Congestive heart failure (CHF) is the main cause of acute dyspnea in patients presented to an emergency department (ED), and it is associated with high morbidity and mortality. B-type natriuretic peptide (BNP) is a polypeptide, released by ventricular myocytes directly proportional to wall tension, for lowering renin-angiotensin-aldosterone activation. For diagnosing CHF, both BNP and the biologically inactive NT-proBNP have similar accuracy. Threshold values are higher in elderly population, and in patients with renal dysfunction. They might have also a prognostic value. Studies demonstrated that the use of BNP or NT-proBNP in dyspneic patients early in the ED reduced the time to discharge, total treatment cost. BNP and NT-proBNP should be available in every ED 24 hours a day, because literature strongly suggests the beneficial impact of an early appropriate diagnosis and treatment in dyspneic patients.

Etiologic diagnosis of febrile patients who present to an ED is complex and sometimes difficult. However, new evidence showed that there are interventions (including early appropriate antibiotics), which could reduce mortality rate in patients with sepsis. For diagnosing sepsis, procalcitonin (PCT) is more accurate than C-reactive protein. Thus, because of its excellent specificity and positive predictive value, an elevated PCT concentration (higher than 0.5 ng/mL) indicates ongoing and potentially severe systemic infection, which needs early antibiotics (e.g. meningitis). In lower respiratory tract infections, CAP or COPD exacerbation, PCT guidance reduced total antibiotic exposure and/or antibiotic treatment duration.

Background

Cardiovascular disease (CVD) is increasing in HIV-infected patients. N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a significant predictor of CVD in the general population. We aimed to quantify the risk of CVD events associated with NT-proBNP at baseline in the Strategies for Management of Anti-Retroviral Therapy study.

Methods

In a nested case–control study, NT-proBNP was measured at baseline in 186 patients who experienced a CVD event over an average of 2.8 years of follow-up and in 329 matched controls. Odds ratios (ORs) associated with baseline levels of NT-proBNP for CVD were estimated using conditional logistic regression.

Results

At baseline median NT-proBNP [interquartile range (IQR)] was 48.1 (18.5, 112.9) pg/ml in patients who developed a CVD event and 25.7 (12.4, 50.2) pg/ml in controls. The unadjusted OR for the highest versus the lowest quartile was 3.7 [95% confidence interval (CI) 2.1–6.5, P < 0.0001]. After adjustment for baseline covariates and CVD risk factors, OR was 2.8 (95% CI 1.4–5.6, P = 0.003); with additional adjustment for IL-6, high-sensitivity C-reactive protein and D-dimer, OR was 2.3 (95% CI 1.1–4.9, P = 0.02).

Conclusions

Higher levels of NT-proBNP are associated with increased risk of CVD in HIV patients after considering established CVD risk factors and markers for inflammation and thrombosis.

Background/Aims

Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are often increased in patients with impaired renal function. The objective of this study was to investigate whether the increase in NT-proBNP is predominantly due to a reduced renal clearance or an increased cardiac secretion.

Methods

A series of 697 outpatients (age: 57.5 ± 16.4 years) referred for evaluation of dyspnea were assigned to 4 groups according to their estimated glomerular filtration rate [eGFR (ml/min per 1.73 m2)]: group 1, eGFR <60 (n = 77); group 2, eGFR ≥60 to <75 (n = 139); group 3, eGFR ≥75 to <90 (n = 191), and group 4, eGFR ≥90 (n = 289). The patients were also grouped into 2 categories based on the presence (n = 176) or absence (n = 521) of heart disease.

Results

In patients with heart disease, the adjusted values for NT-proBNP were higher in eGFR group 1 than in eGFR groups 2–4 (p ≤ 0.01). In patients without heart disease, eGFR group 1 membership had no effect on NT-proBNP.

Conclusion

A reduced renal clearance does not explain increased NT-proBNP levels in patients with moderate renal impairment and dyspnea. Our data suggest that a moderate reduction in renal function places additional stress on the heart in patients with established cardiac disease.

Natriuretic peptides (NPs) are hormones which are mainly secreted from heart and have important natriuretic and kaliuretic properties. There are four different groups NPs identified till date [atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), C-type natriuretic peptide (CNP) and dendroaspis natriuretic peptide, a D-type natriuretic peptide (DNP)], each with its own characteristic functions. The N-terminal part of the prohormone of BNP, NT-proBNP, is secreted alongside BNP and has been documented to have important diagnostic value in heart failure. NPs or their fragments have been subjected to scientific observation for their diagnostic value and this has yielded important epidemiological data for interpretation. However, little progress has been made in harnessing the therapeutic potential of these cardiac hormones.

Aims

N-terminal-pro-B-type-natriuretic-peptide (NT-pro-BNP) concentrations are altered in renal failure. This study examined the effect of baseline and change from baseline NT-pro-BNP on cardiovascular outcome and mortality in haemodialysis patients.

Methods and results

On the basis of the German Diabetes and Dialysis Study, which evaluated atorvastatin in 1255 type 2 diabetes mellitus (T2DM) haemodialysis patients (median follow-up 4 years), the impact of NT-pro-BNP on pre-specified, adjudicated endpoints was investigated: sudden death (SD; n = 160), stroke (n = 99), myocardial infarction (MI; n = 200), cardiovascular events (CVEs: cardiac death, MI, stroke; n = 465), all-cause mortality (n = 612). Patients with baseline NT-pro-BNP ≥9252 pg/mL (fourth quartile) exhibited a more than four-fold risk of stroke [hazard ratio (HR) 4.1; 95% confidence interval (CI) 2.0–8.4] and a more than two-fold risk of SD (HR 2.0; 95% CI 1.2–3.3), CVE (HR 2.0; 95% CI 1.5–2.7), and mortality (HR 2.1; 95% CI 1.6–2.7) compared with patients with baseline NT-pro-BNP ≤ 1433 pg/mL (first quartile). Change in NT-pro-BNP was strongly associated with SD, CVE, and mortality. Doubling of NT-pro-BNP increased the risk of death by 46% (95% CI 1.1–2.0). Neither baseline nor change in NT-pro-BNP was significantly associated with MI.

Conclusion

Increasing NT-pro-BNP is a risk factor for SD, CVE, and mortality in haemodialysis patients with T2DM. Whether NT-pro-BNP-guided treatment improves outcome needs to be evaluated prospectively.

BACKGROUND:

Pro-brain natriuretic peptide (proBNP) is synthesized in the left ventricle. In response to transmural pressure, it is secreted into the circulation and consequently cleaved to yield the active hormone BNP and its N-terminal fragment (NT-proBNP). Determination of NT-proBNP is used as an aid in the diagnosis of left ventricular dysfunction.

METHODS:

We analyzed NT-proBNP-levels before left-heart catheterization in 115 patients. At the end of the study, we compared the NT-proBNP values to the invasively measured hemodynamic indices (left ventricular ejection fraction, maximum change in pressure over time [dP/dtmax] and left ventricular end-diastolic pressure) and the clinically observed New York Heart Association (NYHA) classifications.

RESULTS:

A significant (P=0.008) increase of the NT-proBNP values was observed in cases of low ejection fraction (less than 41%). Furthermore, a significant (P=0.03) increase of the NT-proBNP values was measured in cases of heavily reduced dP/dtmax (less than 1500 mmHg/s). The increase of NT-proBNP values in cases of high end-diastolic pressures was distinct but not significant. In the clinical observation (NYHA classification), a significant increase of NT-proBNP levels corresponded to increasing severity of heart failure. However, a large standard deviation was seen in all groups.

CONCLUSION:

Concerning low ejection fractions, a high end-diastolic pressure and strong reduced dP/dtmax in all cases an increase of pro-BNP-values was seen. However, the partly reported strong correlation of the BNP value to the left ventricular ejection fraction, dP/dtmax and left ventricular end-diastolic pressure results was not found in the cases of middle and moderate heart failure, in contrast to the clinical observation. Regarding the large standard deviation, it may be possible to discriminate an unfavourable course of heart failure in an early stage.

Background

Both N-terminal pro B-type natriuretic peptide (NT-pro BNP) and depressive symptoms independently predict cardiac events in heart failure (HF) patients. However, the relationship among NT-pro BNP, depressive symptoms, and cardiac event is unknown.

Methods and Results

Blood was drawn to measure NT-pro BNP and depressive symptoms were measured by the Patient Health Questionnaire 9 (PHQ-9) among 210 patients with HF. Data about cardiac event-free survival were collected for the average follow-up period of 397 days. Cox proportional hazards regression with survival curves were used to determine the relationship of NT-pro BNP and depressive symptoms to cardiac event-free survival. Higher NT-pro-BNP confers greater risk of cardiac events among those with depressive symptoms than those without depressive symptoms (p for the interaction = .029). Patients with NT-pro BNP > 581 pg/ml and total PHQ-9 score ≥ 10 had a 5.5 times higher risk for cardiac events, compared to patients with NT-pro BNP ≤ 581 pg/ml and total PHQ-9 score < 10 (p = .001).

Conclusions

The prognostic association of NT-pro BNP with cardiac event-free survival in patients with HF differed by the presence of depressive symptoms. Monitoring and treatment of depressive symptoms may be important for improving cardiac event-free survival in patients with HF.

B-type natriuretic peptide (BNP) and amino-terminal pro-BNP (NT-proBNP) are promising cardiac biomarkers that have recently been shown to be of diagnostic value in decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch and volume overload. In view of the high prevalence of cardiac disorders in the intensive care unit, the experience of elevated natriuretic peptide levels in the critically ill might be of enormous diagnostic and therapeutic value. BNP and NT-proBNP levels rise to different degrees in critical illness and may also serve as markers of severity and prognosis in diseases beyond acute or chronic heart failure. The diagnostic and prognostic use of natriuretic peptides in the intensive care setting for patients with various forms of shock could be an attractive alternative as noninvasive markers of cardiac dysfunction that could obviate the need for pulmonary artery catheterization in some patients.