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.
Nutritional vitamin D deficiency is an emerging risk factor for acute myocardial infarction (AMI) and heart failure. The association of 25-hydroxyvitamin D levels with N-terminal pro B-type natriuretic peptide (NT-proBNP), a robust prognostic marker for post-AMI mortality and heart failure, is unknown and could illuminate a potential pathway for adverse outcomes among post-AMI patients with 25-hydroxyvitamin D deficiency.
In a cross-sectional analysis, we studied 238 AMI patients from 21 U.S. centers to test the association of nutritional vitamin D (25-hydroxyvitamin D [25(OH)D]) deficiency with NT-proBNP levels. Levels of 25(OH)D levels were categorized as normal (≥30 ng/mL), insufficient (>20 - <30 ng/mL), deficient (>10 - ≤20 ng/mL), or severely deficient (≤10 ng/mL).
Low 25(OH)D levels were found in 95.7% of AMI patients. No significant trends for higher mean baseline log NT-proBNP levels in severely deficient (6.9 ± 1.3 pg/mL), deficient (6.9 ± 1.2 pg/mL), and insufficient (6.9 ± 0.9 pg/ml) groups were observed as compared with patients having normal (6.1 ± 1.7 pg/mL) levels, P = 0.17. Findings were similar in the subset of patients who had follow-up NT-proBNP levels drawn at one month. In multivariate regression modeling, after adjusting for multiple covariates, 25(OH)D was not associated with NT-proBNP.
Potential associations between nutritional vitamin D deficiency and prognosis in the setting of AMI are unlikely to be mediated through NT-proBNP pathways. Future studies should examine other mechanisms, such as inflammation and vascular calcification, by which 25(OH)D deficiency could mediate adverse outcomes post-AMI.
Vitamin D; N-terminal proBNP; Acute myocardial infarction
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
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
A disturbed vitamin D–parathyroid hormone (PTH)–calcium axis may play a role in the pathogenesis of heart failure. Therefore, we investigated whether lower 25-hydroxyvitamin D (25(OH)D) and higher PTH are cross sectionally and after 8 years of follow-up associated with higher B-type natriuretic peptide (BNP) levels in older men and women.
Design and methods
We measured baseline 25(OH)D, PTH, and BNP in 502 subjects in 2000–2001 in the Hoorn Study, a population-based cohort. Follow-up BNP was available in 2007–2009 in 278 subjects. Subjects were categorized according to season- and sex-specific quartiles of 25(OH)D and PTH at baseline. We studied the association of 25(OH)D and PTH quartiles with BNP using linear regression analyses adjusting for confounders. Analyses were stratified by kidney function estimated glomerular filtration rate (eGFR; ≤60 ml/min per 1.73 m2) because of significant interaction.
At baseline, subjects had a mean age of 69.9±6.6 years, mean 25(OH)D level was 52.2±19.5 nmol/l and mean PTH 6.1±2.4 pmol/l. Cross sectionally, 25(OH)D was associated with BNP in subjects with impaired kidney function (eGFR ≤60 ml/min) only. The association attenuated after adjustment for PTH. PTH was cross sectionally associated with BNP, also in subjects with impaired kidney function only: regression coefficient of highest quartile 9.9 pmol/l (95% confidence interval 2.5, 17.4) with a significant trend across quartiles. Neither 25(OH)D nor PTH was associated with BNP in longitudinal analyses.
This study showed overall no strong association between 25(OH)D and BNP. However, PTH was associated with BNP in subjects with impaired kidney function and may point to a potential role in myocardial function.
vitamin D; parathyroid hormone; B-type natriuretic peptide; epidemiology
The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP) is an established biomarker for cardiac failure.
To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG).
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.
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)
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.
Brain type natriuretic peptide; BNP; NT-proBNP; CABG; Coronary artery disease
Sudden cardiac death (SCD), the cause of 250,000-450,000 deaths per year, is a major public health problem. The majority of those affected do not have a prior cardiovascular diagnosis. Elevated B-type natriuretic peptide levels have been associated with the risk of heart failure and mortality, as well as sudden death in women.
To examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.
The risk of SCD associated with baseline NT-proBNP was examined in 5447 participants. Covariate-adjusted Cox model regressions were used to estimate the hazard ratios of developing SCD as a function of baseline NT-proBNP
Over a median follow-up of 12.5 years (maximum of 16), there were 289 cases of SCD. Higher NT-proBNP levels were strongly associated with SCD, with an unadjusted hazard ratio of 4.2 (95% CI: 2.9, 6.1, p<0.001) in the highest quintile compared to the lowest. NT-proBNP remained associated with SCD even after adjustment for numerous clinical characteristics and risk-factors (age, sex, race, and other associated conditions), with an adjusted hazard ratio for the 5th versus the 1st quintile of 2.5 (95% CI: 1.6, 3.8, p<0.001).
NT-proBNP provides information regarding the risk of sudden cardiac death in a community based population of older adults, beyond other traditional risk factors. This biomarker may ultimately prove useful in targeting the population at risk with aggressive medical management of comorbid conditions.
Sudden cardiac death; B-type natriuretic peptide; BNP; NT-proBNP
The aim of this study was to assess the value of N-terminal pro-brain natriuretic peptide (NT-proBNP) in predicting late cardiotoxicity in patients treated with not-high-dose chemotherapy (NHDC), and to compare the predictive value of NT-proBNP and cardiac troponin I (cTnI).
In 71 patients undergoing NHDC with anthracyclines, NT-proBNP and cTnI levels were measured before and 24 h after each NHDC cycle. Left ventricular (LV) function was assessed by echocardiography at baseline, every two NHDC cycles, at the end of chemotherapy, and at 3-, 6- and 12-month follow-up.
During NHDC, only NT-proBNP showed abnormal values. According to NT-proBNP behaviour, patients were divided into two groups: group A (n=50) with normal (n=23) or transiently elevated NT-proBNP levels (n=27), and group B (n=21) with persistently elevated NT-proBNP levels. At follow-up, LV impairment was significantly worse in group B than in group A. %Δ (baseline–peak) NT-proBNP was predictive of LV impairment at 3-, 6- and 12-month follow-up, with a cutoff of 36%.
Serial measurements of NT-proBNP may be a useful tool for the early detection of patients treated with NHDC at high risk of developing cardiotoxicity.
anthracyclines; brain natriuretic peptide; cardiac biomarkers; cardiotoxicity; N-terminal pro-brain natriuretic peptide
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.
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
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.
To assess the long‐term prognostic value of plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) after major vascular surgery.
A single‐centre prospective cohort study.
335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery.
Prior to surgery, baseline NT‐proBNP level was measured. Patients were also evaluated for cardiac risk factors according to the Revised Cardiac Risk Index. Dobutamine stress echocardiography (DSE) was performed to detect stress‐induced myocardial ischaemia.
Main outcome measures
The prognostic value of NT‐proBNP was evaluated for the endpoints all‐cause mortality and major adverse cardiac events (MACE) during long‐term follow‐up.
In this patient cohort (mean age: 62 years, 76% male), median NT‐proBNP level was 186 ng/l (interquartile range: 65–444 ng/l). During a mean follow‐up of 14 (SD 6) months, 49 patients (15%) died and 50 (15%) experienced a MACE. Using receiver operating characteristic curve analysis for 6‐month mortality and MACE, NT‐proBNP had the greatest area under the curve compared with cardiac risk score and DSE. In addition, an NT‐proBNP level of 319 ng/l was identified as the optimal cut‐off value to predict 6‐month mortality and MACE. After adjustment for age, cardiac risk score, DSE results and cardioprotective medication, NT‐proBNP ⩾319 ng/l was associated with a hazard ratio of 4.0 for all‐cause mortality (95% CI: 1.8 to 8.9) and with a hazard ratio of 10.9 for MACE (95% CI: 4.1 to 27.9).
Preoperative NT‐proBNP level is a strong predictor of long‐term mortality and major adverse cardiac events after major non‐cardiac vascular surgery.
dobutamine stress echocardiography; natriuretic peptides; prognosis; vascular surgery
Several epidemiologic studies have reported an inverse association between serum levels of carotenoids and cardiovascular disease risk. However, no studies have reported an association between serum carotenoids and N-terminal pro-brain-type natriuretic peptide (NT-proBNP) in the general population.
In this cross-sectional study, we investigated whether serum carotenoids were associated with serum NT-proBNP in 1056 Japanese subjects (390 men, 666 women) who attended a health examination. Serum levels of carotenoids were separately determined by high-performance liquid chromatography. Serum NT-proBNP level was measured by electrochemiluminescence immunoassay.
Serum NT-proBNP was elevated (≥55 pg/ml) in 31.8% of men and 48.2% of women. Multivariate logistic regression analyses adjusted for confounding factors showed a significant association between the highest quartile of serum α-carotene and elevated NT-proBNP in men (odds ratio [OR] = 0.40, 95% CI = 0.19–0.82, P for trend = 0.005) and women (OR = 0.62, 95% CI = 0.39–0.99, P for trend = 0.047). In women, moreover, elevated serum NT-proBNP was significantly associated with serum canthaxanthin (OR = 0.57, 95% CI = 0.36–0.90 for highest quartile, P for trend = 0.026) and β-cryptoxanthin (OR = 0.53, 95% CI = 0.32–0.85 for highest quartile, P for trend = 0.026), after adjusting for potential confounders.
Higher levels of serum carotenoids were associated with lower risk of elevated serum NT-proBNP levels after adjusting for possible confounders, which suggests that a diet rich in carotenoids could help prevent cardiac overload in the Japanese population.
carotenoids; N-terminal pro-brain-type natriuretic peptide; cross-sectional study
This study investigated the prognostic value of detectable cardiac troponin T (TnT) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in a population of community-dwelling older adults.
Minimally elevated levels of TnT, a marker of cardiomyocyte injury, have been found in small subsets of the general population, with uncertain implications. A marker of ventricular stretch, NT-proBNP has clinical utility in many venues, but its long-term prognostic value in apparently healthy older adults and in conjunction with TnT is unknown.
Participants were 957 older adults from the Rancho Bernardo Study with plasma NT-proBNP and TnT measured at baseline (1997 to 1999) and followed up for mortality through July 2006.
Participants with detectable TnT (≥0.01 ng/ml, n = 39) had an increased risk of all-cause and cardiovascular death (adjusted hazard ratio [HR] by Cox proportional hazards analysis: 2.06; 95% confidence interval [CI]: 1.29 to 3.28, p = 0.003 for all-cause mortality; HR: 2.06, 95% CI: 1.03 to 4.12, p = 0.040 for cardiovascular mortality); elevated NT-proBNP also predicted an increased risk of all-cause and cardiovascular mortality (adjusted HR per unit-log increase in NT-proBNP: 1.85, 95% CI: 1.36 to 2.52, p < 0.001 for all-cause mortality; HR: 2.51, 95% CI: 1.55 to 4.08, p < 0.001 for cardiovascular mortality). Those with both elevated NT-proBNP and detectable TnT had poorer survival (HR for high NT-proBNP and detectable TnT vs. low NT-proBNP and any TnT: 3.20, 95% CI: 1.91 to 5.38, p < 0.001). Exclusion of the 152 participants with heart disease at baseline did not materially change the TnT mortality or NT-proBNP mortality associations.
Apparently healthy adults with detectable TnT or elevated NT-proBNP levels are at increased risk of death. Those with both TnT and NT-proBNP elevations are at even higher risk, and the increased risk persists for years.
aging; cardiovascular diseases; epidemiology; natriuretic peptides; prognosis; risk factors; survival
B-type natriuretic peptide (BNP), a key cardiac hormone in cardiorenal homeostasis, is produced as a 108 amino acid pro-hormone proBNP1-108. proBNP1-108 is converted to a biologically active peptide BNP1-32 and an inactive NT-proBNP1-76. The widely accepted model is that the normal heart releases a proteolytically processed BNP1-32 and NT-proBNP, while the diseased heart secretes high amounts of unprocessed/glycosylated proBNP1-108 or inappropriately processed BNPs. In contrast, circulating proBNP1-108 has recently been identified in normal subjects, indicating that the normal heart also secretes unprocessed proBNP1-108. However, the mechanism of proBNP1-108 secretion from normal heart remains elusive. Our goal is to determine the molecular mechanisms underlying proBNP1-108 intracellular trafficking and secretion from normal heart.
We expressed pre-proBNP in cardiomyocytes, and determined the subcellular localization, dominant intracellular and extracellular forms of BNP.
Intracellular immunoreactive BNPs accumulated in the Golgi apparatus, which were distributed throughout the cytoplasm as secretory vesicles. The predominant intracellular form of BNP was non-glycosylated proBNP1-108, rather than BNP1-32. Glycosylated proBNP1-108, but not non-glycosylated proBNP1-108, was detected as the major extracellular form in the culture supernatants of pre-proBNP-expressing cell lines or primary human cardiomyocytes. Ablation of O-glycosylation of proBNP1-108 at T71 residue, near the convertase recognition site, reduced the extracellular proBNP1-108 and increased extracellular BNP1-32.
Intracellular proBNP trafficking occurs through a conventional Golgi-ER pathway. Glycosylation of proBNP1-108 controls the stability and processing of extracellular proBNP1-108. Our data establish a new B-type natriuretic peptide secretion model where the normal cardiac cells secrete glycosylated proBNP1-108.
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.
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.
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).
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.
Pericardial effusion; Natriuretic peptide; Brain; Cardiac tamponade; Echocardiography
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).
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.
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.
Preoperative NT-proBNP levels seem to be predictive of early postoperative complications in patients with eGFR < 90 ml/min/1.73 m2 undergoing OPCAB.
NT-proBNP; OPCAB; Renal function
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.
Resting NT-proBNP levels are associated with inducible ischemia in patients with stable CHD.
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.
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).
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.
Objective and design
This cross-sectional study aimed to investigate associations between a marker of cardiac strain, the N-terminal prohormone B-type natriuretic peptide (NT-proBNP), and inflammation as reflected by either a conventional or novel inflammatory marker in a bi-ethnic South African cohort.
Methods and subjects
We measured NT-proBNP, C-reactive protein (CRP) and plasma-soluble urokinase plasminogen activator receptor (suPAR) levels along with conventional biomarkers in black (n = 117) and white (n = 116) men.
NT-proBNP, CRP and suPAR levels were higher in black compared to white men. NT-proBNP was significantly associated with both CRP (r = 0.38; p = 0.001) and suPAR (r = 0.42; p<0.001) in black men only. After full adjustment in multiple regression analyses, the above associations of NT-proBNP with CRP (β = 0.199; p = 0.018) and suPAR (β = 0.257; p<0.01) were confirmed in black men.
These results suggest that a low-grade inflammatory state as reflected by both a conventional and novel marker of inflammation may contribute to higher cardiovascular risk as reflected by the associations obtained with a marker of cardiac strain in black South African men.
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
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
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.
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.
Cognition; Cystatin C; Homocysteine; N-terminal pro-brain natriuretic peptide; Psychogeriatric patients; Vascular disease
To investigate whether testosterone administration alters natriuretic peptide levels in women.
Three-month, double-blind, randomized, placebo-controlled study.
Clinical research center.
51 women with hypoandrogenemia due to hypopituitarism.
Transdermal testosterone (300 mcg daily) or placebo patch.
Main Outcome Measure
N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels.
NT-proBNP levels decreased in the transdermal testosterone group compared with placebo over three months (p = 0.009). The difference between groups remained significant after controlling for baseline age, systolic blood pressure, body mass index, and homeostasis model of assessment-insulin resistance (p = 0.008). Change in NT-proBNP over three months was inversely associated with change in free testosterone levels (ρ = −0.41, p = 0.01).
Testosterone administration to women results in decreased natriuretic peptide levels, suggesting that testosterone may be an inverse regulator of the natriuretic peptide system.
Clinical Trials Registration Number
Testosterone; natriuretic peptides
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) is secreted from cardiomyocytes and may reflect haemodynamic abnormalities predisposing to atrial fibrillation (AF). We aimed to investigate whether N-terminal pro BNP (NT-proBNP) is associated with newly detected AF in subjects obtained from the general population.
From the PREVEND programme (n=8592), we selected all subjects with an available baseline and four-year electrocardiogram and NTproBNP levels at baseline. We excluded subjects with AF at baseline and subjects with a serum creatinine >2.0 mg/dl.
In total, 6494 subjects were eligible for the prospective analysis (aged 49±12 years, 49.7% men). At four years, AF was detected in 41 (0.6%) subjects. Median NT-proBNP levels at baseline in subjects with newly detected AF after four years was 62.2 (22.6 to 208.5) pg/ml as compared with 35.7 (15.9 to 68.7) pg/ml in those with sinus rhythm (p=0.001). Each 1 standard deviation increment in natural log transformed NT-proBNP was associated with a 54% (5% to 126%, p=0.028) increase in risk for AF after adjustment for other risk factors predisposing to AF. NT-proBNP levels above the sex-specific 80th percentile (97 pg/ml in women and 60 pg/ml in men) were associated with a multivariate odds ratio of 2.65 (1.22 to 5.76, p=0.01) for the occurrence of AF.
Plasma levels of NT-proBNP predict newly detected AF in subjects obtained from the general population independent of cardiovascular risk factors predisposing to AF. (Neth Heart J 2008;16:73-8.)
PREVEND; BNP; atrial fibrillation; epidemiology; risk factors