HIV infection is associated with left ventricular (LV) dysfunction and accelerated atherosclerosis. These conditions result in elevation of plasma natriuretic peptide (NP) levels. The present study compares N-terminal-pro-BNP (NT-pro-BNP) levels in HIV-infected and -uninfected women and identifies factors influencingNT-pro-BNP levels in HIV-infected women. A total of 454 HIV-infected and 200 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had NT-pro-BNP determination. Elevated NT-pro-BNP level was defined using previously determined age stratified cut-off values of >164 ng/liter (age <60 years) and >225 (age ≥ 60 years). HIV-infected women were older (41.6 ± 8.9 vs. 38.9 ± 10.5 years, p < 0.01) and were more likely to have anemia, hepatitis C virus (HCV) antibodies, and kidney dysfunction than HIV-uninfected women. HIV-infected women had significantly higher NT-pro-BNP levels (142.4 ± 524.8 vs. 73.6 ± 115.1 ng/liter, p = 0.01) and a higher prevalence of elevated NT-pro-BNP (12.1% vs. 7.5%; p = 0.08). In univariate analyses, elevated NT-pro-BNP was significantly associated with age, systolic BP, hypertension, anemia, triglyceride levels, kidney disease, and HCV seropositivity, but not HIV infection. In multivariate analysis, elevated NT-pro-BNP levels were significantly associated with anemia and kidney function, and had a borderline association with the presence of HCV antibodies. Among HIV-infected women, NT-pro-BNP levels were not independently associated with measures of severity of infection or with HAART use. Although HIV-infected women have higher NT-pro-BNP levels than HIV-uninfected women, the differences are due to non-HIV factors such as anemia, kidney disease, and HCV coinfection. These findings suggest that natriuretic peptide levels are a global marker of comorbidity in the setting of HIV infection.
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.
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.
Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma.
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.
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.
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.
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.
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.
Determine whether assessment of left ventricular ejection fraction (LVEF) enhances prediction of new onset heart failure (HF) and cardiovascular mortality over and above N-terminal pro–B-type natriuretic peptide (NT-proBNP) level in older adults.
Elevated NT-proBNP levels are common in older adults and associated with increased risk of HF.
NT-proBNP and LVEF were measured in 4,137 older adults free of HF. Repeat measures of NT-proBNP were performed 2–3 years later and echocardiography was repeated 5 years later (n=2,375) with a median follow-up of 10.7 years. The addition of an abnormal (<55%) LVEF (n=317 [7.7%]) to initially elevated or rising NT-proBNP levels was evaluated to determine risk of HF or cardiovascular mortality. Change in NT-proBNP levels were also assessed for estimating the risk of conversion from a normal to abnormal LVEF.
For participants with a low baseline NT-proBNP level (<190 pg/mL) (n=2,918), addition of an abnormal LVEF didn’t improve the estimation of risk of HF and identified a moderate increase in adjusted risk for cardiovascular mortality (HR 1.69; 95%CI: 1.22 to 2.31). Among those whose NT-proBNP subsequently increased ≥ 25% to ≥190 pg/mL, an abnormal LVEF was likewise associated with an increased risk of cardiovascular mortality but not HF. Participants with an initially high NT-proBNP (≥190 pg/mL) were at greater risk overall for both outcomes, and those with an abnormal LVEF were at the highest risk. However, an abnormal LVEF did not improve model classification or risk stratification for either endpoint when added to demographic factors and change in NT-proBNP. An initially elevated NT-proBNP or rising level was associated with an increased risk of developing an abnormal LVEF.
Assessment of LVEF in HF free older adults based on NT-proBNP levels should be considered on an individual basis, as such assessments do not routinely improve prognostication.
Elderly; heart failure; echocardiography; natriuretic peptides; outcomes
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.
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.
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).
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.
AIDS; antiretroviral therapy; cardiovascular disease events; HIV; NT-proBNP; SMART
In patients with symptoms of heart failure, elevations in B-type natriuretic peptide (BNP) accurately identify ventricular dysfunction. However, BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevations in BNP.
Methods and Results
To determine whether BNP elevations are associated with myocardial ischemia, we measured plasma BNP levels before performing exercise treadmill testing with stress echocardiography in outpatients with stable coronary disease. Of the 355 participants, 113 (32%) had inducible ischemia. Compared with participants in the lowest BNP quartile (0 to 16.4 pg/mL), those in the highest quartile of BNP (≥105 pg/mL) had double the risk of inducible ischemia (adjusted relative risk, 2.0; 95% CI, 1.2 to 2.6; P=0.008). The relation between elevated BNP levels and inducible ischemia was especially evident in the 206 participants who had a history of myocardial infarction (adjusted relative risk, 2.6; 95% CI, 1.5 to 3.7, P=0.002) and was absent in those without a history of myocardial infarction (adjusted relative risk, 1.0; 95% CI, 0.3 to 2.2; P=0.9). This association between BNP levels and inducible ischemia remained strong after adjustment for measures of systolic and diastolic dysfunction.
Elevated levels of BNP are independently associated with inducible ischemia among outpatients with stable coronary disease, particularly among those with a history of myocardial infarction. The observed association between BNP levels and ischemia may explain why tests for BNP are not specific for ventricular dysfunction among patients with coronary disease.
natriuretic peptides; ischemia; myocardial infarction; heart failure; coronary 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.
Acute coronary syndromes; B-type natriuretic peptide; Coronary artery disease; Ischemic heart disease; Myocardial infarction; N-terminal B-type natriuretic peptide
Background and aims: Cardiac dysfunction may be present in patients with cirrhosis. This study was undertaken to relate plasma concentrations of cardiac peptides reflecting early ventricular dysfunction (pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP)) to markers of severity of liver disease, cardiac dysfunction, and hyperdynamic circulation in patients with cirrhosis.
Patients and methods: Circulating levels of proBNP and BNP were determined in 51 cirrhotic patients during a haemodynamic investigation.
Results: Plasma proBNP and BNP were significantly increased in cirrhotic patients (19 and 12 pmol/l, respectively) compared with age matched controls (14 and 6 pmol/l; p<0.02) and healthy subjects (<15 and <5.3 pmol/l; p<0.002). Circulating proBNP and BNP were closely correlated (r = 0.89, p<0.001), and the concentration ratio proBNP/BNP was similar to that of control subjects (1.8 v 2.3; NS). Circulating proBNP and BNP were related to severity of liver disease (Child score, serum albumin, coagulation factors 2, 7, and 10, and hepatic venous pressure gradient) and to markers of cardiac dysfunction (QT interval, heart rate, plasma volume) but not to indicators of the hyperdynamic circulation. Moreover, in multiple regression analysis, proBNP and BNP were also related to arterial carbon dioxide and oxygen tensions. The rate of hepatic disposal of proBNP and BNP was not significantly different in cirrhotic patients and controls.
Conclusion: Elevated circulating levels of proBNP and BNP in patients with cirrhosis most likely reflects increased cardiac ventricular generation of these peptides and thus indicates the presence of cardiac dysfunction, rather than being caused by the hyperdynamic circulatory changes found in these patients.
brain natriuretic peptide; cardiac dysfunction; cirrhotic cardiomyopathy; pro-brain natriuretic peptide; QT interval; cardiac ventricular peptides
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.
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.
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).
Natriuretic peptides correlate weakly with IVC size and do not predict changes in response to intrathoracic pressure.
heart failure; inferior vena cava; natriuretic peptides
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.
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.
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.
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.
Heart failure; Left heart catheterization; Left ventricular hemodynamics; N-terminal pro-brain natriuretic peptide
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.
Single ventricle; congenital heart defect; heart failure; B-type natriuretic peptide; N-terminal pro-BNP; hypoplastic left heart; atrioventricular canal defect; double-outlet right ventricle
Plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are elevated in patients with secondary pulmonary hypertension and chronic lung disease with right ventricular overload. The aim of the present study was to investigate the use of plasma NT-proBNP levels as a prognostic marker of severe COPD with chronic respiratory failure and latent pulmonary hypertension.
Plasma NT-proBNP levels were measured in 61 patients with stable COPD. Plasma NT-proBNP levels, pulmonary function, PaO2, and PaCO2 levels and systolic pulmonary artery pressure were compared according to COPD severity. In addition, we examined correlations between plasma NT-proBNP levels and pulmonary function, PaO2, PaCO2, and systolic pulmonary artery pressure.
The levels of plasma NT-proBNP significantly increased in patients with stage IV and stage III COPD compared to individuals with stage II COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The area under the receiver-operating characteristic curve of plasma NT-proBNP for severe to very severe COPD (FEV1 < 50%) was 0.707 (95% confidence interval [CI] 0.566–0.847, P = 0.008). Plasma NT-proBNP levels significantly correlated with %FEV1 (r = −0.557; P < 0.001), arterial blood gas parameters such as PaCO2 (r = 0.476; P < 0.001) and PaO2 (r = −0.347; P = 0.031), and systolic pulmonary artery pressure (r = 0.435; P = 0.001).
Plasma NT-proBNP levels increased significantly with disease severity, progression of chronic respiratory failure, and secondary pulmonary hypertension in patients with stable COPD. These results suggest that plasma NT-proBNP can be a useful prognostic marker to monitor COPD progression and identify cases of secondary pulmonary hypertension in patients with stable COPD.
Chronic obstructive pulmonary disease; NT-proBNP; Prognosis; Medicine & Public Health; Pneumology/Respiratory System
Objective: To determine the performance of a new NT-proBNP assay in comparison with brain natriuretic peptide (BNP) in identifying left ventricular systolic dysfunction (LVSD) in randomly selected community populations.
Methods: Blood samples were taken prospectively in the community from 591 randomly sampled individuals over the age of 45 years, stratified for age and socioeconomic status and divided into four cohorts (general population; clinically diagnosed heart failure; patients on diuretics; and patients deemed at high risk of heart failure). Definite heart failure (left ventricular ejection fraction (LVEF) < 40%) was identified in 33 people. Samples were handled as though in routine clinical practice. The laboratories undertaking the assays were blinded.
Results: Using NT-proBNP to diagnose LVEF < 40% in the general population, a level of > 40 pmol/l had 80% sensitivity, 73% specificity, 5% positive predictive value (PPV), 100% negative predictive value (NPV), and an area under the receiver-operator characteristic curve (AUC) of 76% (95% confidence interval (CI) 46% to 100%). For BNP to diagnose LVSD, a cut off level of > 33 pmol/l had 80% sensitivity, 88% specificity, 10% PPV, 100% NPV, and AUC of 88% (95% CI 75% to 100%). Similar NPVs were found for patients randomly screened from the three other populations.
Conclusions: Both NT-proBNP and BNP have value in diagnosing LVSD in a community setting, with similar sensitivities and specificities. Using a high cut off for positivity will confirm the diagnosis of LVSD but will miss cases. At lower cut off values, positive results will require cardiac imaging to confirm LVSD.
natriuretic peptides; left ventricular systolic dysfunction; heart failure
The identification of patients at highest risk for adverse outcome who are presenting with acute dyspnea to the emergency department remains a challenge. This study investigates the prognostic value of the newly described midregional fragment of the pro-Adrenomedullin molecule (MR-proADM) alone and combined to B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in patients with acute dyspnea.
We conducted a prospective, observational cohort study in the emergency department of a University Hospital and enrolled 287 unselected, consecutive patients (48% women, median age 77 (range 68 to 83) years) with acute dyspnea.
MR-proADM levels were elevated in non-survivors (n = 77) compared to survivors (median 1.9 (1.2 to 3.2) nmol/L vs. 1.1 (0.8 to 1.6) nmol/L; P < 0.001). The areas under the receiver operating characteristic curve (AUC) to predict 30-day mortality were 0.81 (95% CI 0.73 to 0.90), 0.76 (95% CI 0.67 to 0.84) and 0.63 (95% CI 0.53 to 0.74) for MR-proADM, NT-proBNP and BNP, respectively (MRproADM vs. NTproBNP P = 0.38; MRproADM vs. BNP P = 0.009). For one-year mortality the AUC were 0.75 (95% CI 0.69 to 0.81), 0.75 (95% CI 0.68 to 0.81), 0.69 (95% CI 0.62 to 0.76) for MR-proADM, NT-proBNP and BNP, respectively without any significant difference. Using multivariate linear regression analysis, MR-proADM strongly predicted one-year all-cause mortality independently of NT-proBNP and BNP levels (OR = 10.46 (1.36 to 80.50), P = 0.02 and OR = 24.86 (3.87 to 159.80) P = 0.001, respectively). Using quartile approaches, Kaplan-Meier curve analyses demonstrated a stepwise increase in one-year all-cause mortality with increasing plasma levels (P < 0.0001). Combined levels of MR-proADM and NT-proBNP did risk stratify acute dyspneic patients into a low (90% one-year survival rate), intermediate (72 to 82% one-year survival rate) or high risk group (52% one-year survival rate).
MR-proADM alone or combined to NT-proBNP has a potential to assist clinicians in risk stratifying patients presenting with acute dyspnea regardless of the underlying disease.
To determine the optimal cut‐off values of B‐type natriuretic peptide (BNP) for the diagnosis of congestive heart failure (CHF) in 1040 Korean patients with dyspnoea visiting emergency departments.
BNP values were measured for 662 patients without CHF to examine whether significant relationships existed between the BNP values and age, gender or underlying disease. In 378 patients with CHF, a similar analysis was performed in addition to the examination of the relationship between the mean BNP values and CHF severity.
The optimal threshold for the detection of heart failure was a BNP concentration of 296.5 pg/mL, regardless of age, sex and underlying disease among the Korean study population. In the non‐CHF patients, women showed significantly higher mean BNP values than did men. Further, in these patients, the mean BNP values of men with underlying disease (hypertension, angina pectoris, chronic renal failure, chronic obstructive pulmonary disease) and those with at least two underlying diseases, one of which was hypertension, was higher than those without underlying disease, whereas no difference was observed between women with and without underlying disease. Based on the New York Heart Association classification, echocardiography findings and mortality rate of the CHF patients, the BNP value was found to be related to both the severity of heart failure and its prognosis.
The BNP concentration used for the diagnosis of CHF in Korean people is considerably higher than the normal cut‐off value of 100 pg/mL. In the non‐CHF patients, the BNP values of women were influenced less by underlying disease. This suggests that the factors that influence BNP values in women are different from those in men.
natriuretic peptide; brain; heart failure; congestive; gender identity; Korea; prognosis
To assess the long term prognostic value of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) on admission and its prognostic interaction with both admission troponin T (TnT) concentrations and resolution of ST segment elevation in fibrinolytic treated ST elevation myocardial infarction (STEMI).
Design and setting
Substudy of the ASSENT (assessment of the safety and efficacy of a new thrombolytic) ‐2 and ASSENT‐PLUS trials.
NT‐proBNP and TnT concentrations were determined on admission in 782 patients. According to NT‐proBNP concentrations, patients were divided into three groups: normal concentration (for patients ⩽ 65 years, ⩽ 184 ng/l and ⩽ 268 ng/l and for those > 65 years, ⩽ 269 ng/l and ⩽ 391 ng/l in men and women, respectively); higher than normal but less than the median concentration (742 ng/l); and above the median concentration. For TnT, a cut off of 0.1 μg/l was used. Of the 782 patients, 456 had ST segment resolution (< 50% or ⩾ 50%) at 60 minutes calculated from ST monitoring.
Main outcome measures
All cause one year mortality.
One year mortality increased stepwise according to increasing concentrations of NT‐proBNP (3.4%, 6.5%, and 23.5%, respectively, p < 0.001). In receiver operating characteristic analysis, NT‐proBNP strongly trended to be associated more with mortality than TnT and time to 50% ST resolution (area under the curve 0.81, 95% confidence interval (CI) 0.72 to 0.9, 0.67, 95% CI 0.56 to 0.79, and 0.66, 95% CI 0.56 to 0.77, respectively). In a multivariable analysis adjusted for baseline risk factors and TnT, both raised NT‐proBNP and ST resolution < 50% were independently associated with higher one year mortality, whereas raised TnT contributed independently only before information on ST resolution was added to the model.
Admission NT‐proBNP is a strong independent predictor of mortality and gives, together with 50% ST resolution at 60 minutes, important prognostic information even after adjustment for TnT and baseline characteristics in STEMI.
acute myocardial infarction; brain natriuretic peptide; prognosis; electrocardiography
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.
Accurate cardiovascular risk stratification is challenging in the elderly.
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.
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.
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.
biomarkers; risk stratification; heart failure; elderly
N-terminal-pro-B-type natriuretic peptide (NT-proBNP) is a commonly measured cardiovascular biomarker in both ambulatory and hospital settings. Nonetheless, there are limited data regarding “normal” ranges for NT-proBNP in healthy individuals, despite the importance of such information for interpreting natriuretic peptide measurements. We examined a healthy reference sample free of cardiovascular disease from the Framingham Heart Study Generation 3 cohort; there were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-proBNP levels were measured using the Roche Diagnostics Elecsys 2010 assay, and reference values (2.5, 50, 97.5 quantiles) were determined using empiric and quantile regression methods. Gender, age, and body mass index accounted for approximately 33% of the inter-individual variability in NT-proBNP in the reference sample. NT-proBNP values were substantially higher in women compared with men at every age, and levels increased with increasing age for both sexes. Using quantile regression, the upper reference values (97.5 quantile) for NT-proBNP were 42.5 pg/ml to 106.4 pg/ml in men (depending on age), and 111.0 pg/ml to 215.9 pg/ml in women. Intra-individual variability was assessed in an additional 12 healthy individuals, who had serial NT-proBNP measurements over a month. Intra-class correlation was 0.85, indicating that most of the variability in NT-proBNP concentrations was among-persons rather than within-persons. However, the reference change value was 100%, suggesting that small proportional differences in NT-proBNP could be attributable to analytic variability. In conclusion, the reference limits obtained from this large, healthy community-based sample may aid in the evaluation of NT-proBNP concentrations measured for both clinical and research purposes.
Natriuretic peptides; Cardiac Biomarkers; Heart Failure
AIM: To evaluate serum levels of N-terminal pro-brain natriuretic peptide (NTproBNP) and tumor necrosis factor α (TNF-α) in a large series of patients with hepatitis C associated with mixed cryoglobulinemia (MC+HCV).
METHODS: Serum NTproBNP and TNF-α levels were assayed in 50 patients with MC+HCV, and in 50 sex- and age-matched controls.
RESULTS: Cryoglobulinemic patients showed significantly higher mean NTproBNP and TNF-α levels than controls (P < 0.001; Mann-Whitney U test). By defining high NTproBNP level as a value higher than 125 pg/mL (the single cut-off point for outpatients under 75 years of age), 30% of MC+HCV and 6% of controls had high NTproBNP (χ2, P < 0.01). With a cut-off point of 300 pg/mL (used to rule out heart failure (HF) in patients under 75 years of age), 8% of MC+HCV and 0 controls had high NTproBNP (χ2, P < 0.04). With a cut-off point of 900 pg/mL (used for ruling in HF in patients aged 50-75 years; such as the patients of our study), 6% of MC+HCV and 0 controls had high NTproBNP (χ2, P = 0.08).
CONCLUSION: The study demonstrates high levels of circulating NTproBNP and TNF-α in MC+HCV patients. The increase of NTproBNP may indicate the presence of a subclinical cardiac dysfunction.
NTProBNP; Tumor necrosis factor α; Hepatitis C; Mixed cryoglobulinemia; Heart failure
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.
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).
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.
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.
Atrial fibrillation; NT-proBNP; Doppler echocardiography
N-terminal pro brain natriuretic peptide (NT-proBNP) is a cardiac biomarker that has recently shown to be of diagnostic value in a diagnosis of decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch. We sought to study whether sepsis-induced myocardial dilation would result in an elevation of NT-proBNP.
Serum NT-proBNP measurements were made in six consecutive patients with septic shock within 6 hours of admission to the intensive care unit.
Markedly elevated levels of NT-proBNP were found in all six patients.
NT-proBNP levels can be markedly elevated in critically ill patients presenting with septic shock. An elevated NT-proBNP level in a critically ill patient is not specific for decompensated heart failure.
brain natriuretic peptide; N-terminal pro brain natriuretic peptide; septic shock
To evaluate the predictive value of N‐terminal pro B‐type natiuretic peptide (NT‐proBNP) reference cut‐off values as diagnostic markers for left ventricular systolic dysfunction (LVSD).
A retrospective study assessing the use of NT‐proBNP in the diagnostic algorithm for the investigation of patients with suspected signs and symptoms of LVSD presenting to primary care.
A generic NT‐proBNP cut‐off (150 ng/l) value has similar negative and positive predictive valves, specificity and sensitivity compared to age and sex specific cut‐off values.
When using NT‐proBNP as a triage tool for screening patients with signs and symptoms suggestive of LVSD, a simple generic cut‐off level is as effective as more complex age sex specific cut‐off values.
left ventricular systolic dysfunction; negative predictive value; NT‐proBNP; positive predictive value; sensitivity; specificity
Natriuretic peptides have important roles in the regulation of vasomotor tone, salt homeostasis, and ventricular remodeling. Lower natriuretic peptide levels observed in obese individuals may underlie the greater cardiovascular risk associated with obesity. Thus, the aim of this study was to determine whether lower natriuretic peptide levels in obesity are attributable to differences in regional fat distribution. We investigated the relationship of plasma N-terminal pro-B-type natriuretic peptide (N-BNP) with regional adiposity in 1,873 community-based individuals (46% women; mean age 45 years). Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volumes were measured by multi-detector computed tomography. In sex-specific, multivariable analyses adjusting for age and blood pressure, log N-BNP was inversely associated with VAT in both men (β −0.11, P<0.001) and women (β −0.19, P<0.001). Log N-BNP was inversely associated with SAT in women only (β −0.14, P<0.001). In models containing both VAT and SAT, only VAT was significantly associated with log N-BNP (men, β −0.137, P<0.001; women, β −0.184, P<0.001). VAT remained associated with log N-BNP even after adjustment for body mass index and waist circumference (β −0.119, P<0.001), and in analyses restricted to non-obese individuals (β −0.114; P<0.001). Adjustment for insulin resistance attenuated the associations of N-BNP with both VAT and SAT. In conclusion, this study demonstrates that circulating N-BNP is related to variation in regional and particularly visceral adiposity. These findings suggest that excess visceral adiposity and concomitant hyperinsulinemia may contribute to the natriuretic peptide “deficiency” observed in obesity.
adiposity; natriuretic peptides; cardiovascular risk
For patients presenting with acute dyspnea, an incorrect diagnosis could increase the mortality risk. When used in the evaluation of patients with acute symptoms, brain natriuretic peptide and N-terminal pro-brain natriuretic peptide (BNP and NT-proBNP, respectively) testing is highly sensitive for the diagnosis or exclusion of acute or chronic decompensated heart failure (HF). It has been demonstrated that BNP and proBNP levels can facilitate diagnosis and guide HF therapy. Natriuretic peptide (NP) levels are strictly related with HF severity; they are particularly increased in more advanced New York Heart Association (NYHA) classes and in patients with poor outcome. Therefore elevated NP levels were found to correlate with the severity of left ventricular systolic dysfunction, right ventricular dysfunction and pressures, and left ventricular filling alterations. However, the optimal use of NP determination agrees with patient history, physical examination, and all other diagnostic tools. There are some clinical conditions (ie, obesity, renal insufficiency anemia) for which the NP measurement is not diagnostic. Algorithm building taking into consideration all clinical and echocardiographic parameters, as well as NP measurements, may lead to the earlier identification and better risk stratification of patients with chronic HF, independently from etiology.
heart failure; diagnosis; echocardiography; natriuretic pepides
Increased concentrations of amino-terminal prohormone brain-type natriuretic peptide (NT-proBNP) are associated with cardiovascular morbidity and mortality, but little is known about their relationship to chronic inflammation. Patients with rheumatoid arthritis (RA) have chronic inflammation, increased arterial stiffness and accelerated coronary atherosclerosis. We tested the hypothesis that NT-proBNP concentrations are elevated in patients with RA, and are associated with coronary artery calcification and markers of inflammation.
In 159 subjects with RA (90 patients with early RA and 69 patients with longstanding RA) without heart failure and 88 control subjects, we measured serum concentrations of NT-proBNP, interleukin (IL)-6, and tumor necrosis factor-α (TNF-α), and coronary calcification.
NT-proBNP concentrations were elevated in patients with long-standing RA [median (IQR): 142.8 (54.8–270.5) pg/mL] and those with early RA [58.1 (19.4–157.6) pg/mL] compared to controls [18.1 (3.2–46.0) pg/mL, P<0.001]. In patients with RA, NT-proBNP concentrations were associated with age (ρ=0.35, P<0.001), IL-6 (ρ=0.33, P<0.001), TNF-α (ρ=0.23, P=0.003), CRP (ρ=0.21, P=0.01), coronary calcium score (ρ=0.30, P<0.001), systolic blood pressure (ρ=0.30, p<0.001), and disease activity (ρ=0.29, P<0.001). After adjustment for age, race and sex the associations between NT-proBNP concentrations and disease activity (P<0.001), TNF-α (P<0.001), IL-6 (P=0.04) and CRP concentrations (P=0.02) remained significant, but those with systolic blood pressure (P=0.10) and coronary calcium score (P=0.27) were attenuated.
NT-proBNP concentrations are increased in patients with RA without clinical heart failure and may indicate subclinical cardiovascular disease and a chronic inflammatory state.
rheumatoid arthritis; inflammation; atherosclerosis; B-type natriuretic peptide; NT-proBNP