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 influencing NT-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.
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
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
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
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.
The aim of this study was to investigate the modified Ross criteria score and the diagnostic cut-off level for plasmatic amino-terminal pro-brain natriuretic peptide (NT-proBNP) in the diagnosis of pediatric heart failure, by analyzing the receiver operating characteristic (ROC) curve. The plasma NT-proBNP level was measured in 80 children diagnosed with heart failure according to the modified Ross criteria, 80 children with non-cardiogenic dyspnea and 80 healthy children. The NT-proBNP levels were then compared using an F-test. The cut-off score for heart failure in the modified Ross criteria and the diagnostic cut-off level for plasmatic NT-proBNP in pediatric heart failure were determined by ROC curve analysis. The results demonstrated that the NT-proBNP level was markedly increased in 76 of the 80 children with heart failure, and the correlation with the modified Ross criteria was 95%. Based on ROC curve analysis, the diagnosis of pediatric heart failure was most accurate when the modified Ross criteria score was ≥4 and the plasmatic NT-proBNP level was ≥598 ng/l. The NT-proBNP level was normal (0–300 ng/l) in the children with non-cardiogenic dyspnea and the healthy children. Significant differences were observed in the comparison of the three groups (P<0.01). In conclusion, a NT-proBNP level of ≥598 ng/l, combined with a modified Ross criteria score ≥4, is highly diagnostic of heart failure in children.
heart failure; amino-terminal pro-B-type natriuretic peptide; diagnostic criteria; children
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
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.
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
To analyze the relationship between N-terminal pro-brain natriuretic peptide (NT-proBNP) and renal function, and compare the ability and cut-off thresholds of NT-proBNP to detect chronic heart failure (CHF) and predict mortality in elderly Chinese coronary artery disease (CAD) patients with and without chronic kidney disease (CKD).
The study included 999 CAD patients older than 60 years. The endpoint was all-cause mortality over a mean follow-up period of 417 days.
The median age was 86 years (range: 60–104 years), and the median NT-proBNP level was 409.8 pg/mL. CKD was present in 358 patients. Three hundred and six patients were positive for CHF. One hundred and ten CKD patients and 105 non-CKD patients died. Not only CKD, but also estimated glomerular filtration rate independently affected NT-proBNP. NT-proBNP detected CHF with a cut-off value of 298.4 pg/mL in non-CKD patients and a cut-off value of 435.7 pg/mL in CKD patients. NT-proBNP predicted death with a cut-off value of 369.5 pg/mL in non-CKD patients and a cut-off value of 2584.1 pg/mL in CKD patients. The NT-proBNP level was significantly related to the prevalence of CHF and all-cause mortality in CAD patients with and without CKD; this effect persisted after adjustment. The crude and multiple adjusted hazard ratios of NT-proBNP to detect CHF and predict mortality were significantly higher in patients with CKD compared with the remainder of the population. The addition of NT-proBNP to the three-variable and six-variable models generated a significant increase in the C-statistic.
Amongst elderly Chinese CAD patients, there was an independently inverse association between NT-proBNP and renal function. With the higher cutoff points, NT-proBNP better detected CHF and better predicted mortality in CKD patients than in non-CKD patients.
aged; coronary artery disease; chronic kidney disease; N-terminal pro-brain natriuretic peptide; prognosis
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
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
Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly-active antiretroviral therapy (HAART).
In the Women's Interagency HIV Study (WIHS), 127 HIV-infected women studied pre- and post-HAART were matched to HIV-uninfected controls. Six semi-annual measurements of soluble CD14, tumor necrosis factor (TNF)-alpha, soluble interleukin (IL)-2 receptor, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness (CIMT) was measured by B-mode ultrasound.
Relative to HIV-uninfected controls, HAART-naïve HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P<0.0001), TNF-alpha (6.3 vs 3.4 pg/mL, P<0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P<0.0001), IL-10 (3.3 vs 1.9 pg/mL, P<0.0001), MCP-1 (190 vs 163 pg/mL, P<0.0001) and D-dimer (0.43 vs 0.31 µg/mL, P<0.01). Elevated biomarker levels declined after HAART. While most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-alpha levels remained elevated compared to HIV-uninfected women (+0.8 pg/mL, P=0.0002). Higher post-HAART levels of soluble IL-2 receptor (P=0.02), IL-6 (P=0.05), and D-dimer (P=0.03) were associated with increased CIMT.
Untreated HIV infection is associated with abnormal hemostasis (e.g., D-dimer), and pro-atherogenic (e.g., TNF-alpha) and anti-atherogenic (e.g., IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.
antiretroviral therapy; cardiovascular diseases; cytokines; hemostasis; HIV; inflammation
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
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
To investigate the association between plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and formation of esophageal varices.
Thirty-five patients with alcoholic cirrhosis were divided into three groups according to the Child-Pugh classification: grade A (n = 11, 32%), B (n = 12, 34%), and C (n = 12, 34%). System hemodynamic parameters were measured using sphygmomanometry, electrocardiography, and echocardiography. NT-proBNP was analyzed by using an electrochemiluminiscence sandwich immunoassay.
The presence of esophageal varices was associated with a higher serum NT-proBNP level, with a cut-off value of >101 pg/mL (sensitivity, 87.60% and specificity, 72.73%; P < 0.001).
NT-proBNP was found to be a marker of the presence of esophageal varices, but not a marker of progression of liver cirrhosis. In cirrhotic patients, NT-proBNP value >101 pg/mL was shown to be a valuable noninvasive parameter in predicting the presence of varices.
Cardiac dysfunction is common in acute respiratory diseases and may influence prognosis. We hypothesised that blood levels of N-terminal B-type natriuretic peptide (NT-proBNP) and high-sensitivity Troponin T would predict mortality in adults with community-acquired pneumonia.
Methods and Findings
A prospective cohort of 474 consecutive patients admitted with community-acquired pneumonia to two New Zealand hospitals over one year. Blood taken on admission was available for 453 patients and was analysed for NT-proBNP and Troponin T. Elevated levels of NT-proBNP (>220 pmol/L) were present in 148 (33%) and 86 (19%) of these patients respectively. Among the 26 patients who died within 30 days of admission, 23 (89%) had a raised NT-proBNP and 14 (53%) had a raised Troponin T level on admission compared to 125 (29%) and 72 (17%) of the 427 who survived (p values<0.001). Both NT-proBNP and Troponin T predicted 30-day mortality in age-adjusted analysis but after mutual adjustment for the other cardiac biomarker and the Pneumonia Severity Index, a raised N-terminal pro-brain natriuretic peptide remained a predictor of 30-day mortality (OR = 5.3, 95% CI 1.4–19.8, p = 0.013) but Troponin T did not (OR = 1.3, 95% CI 0.5–3.2, p = 0.630). The areas under the receiver-operating curves to predict 30-day mortality were similar for NT-proBNP (0.88) and the Pneumonia Severity Index (0.87).
Elevated N-terminal B-type natriuretic peptide is a strong predictor of mortality from community-acquired pneumonia independent of clinical prognostic indicators. The pathophysiological basis for this is unknown but suggests that cardiac involvement may be an under-recognised determinant of outcome in pneumonia and may require a different approach to treatment. In the meantime, measurement of B-type natriuretic peptides may help to assess prognosis.
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.
type 2 diabetes; natriuretic peptides; echocardiography
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
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