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1.  Influence of preoperative serum N-terminal pro-brain type natriuretic peptide on the postoperative outcome and survival rates of coronary artery bypass patients 
Clinics  2010;65(12):1239-1245.
BACKGROUND:
The N-terminal fragment of pro-brain type natriuretic peptide (NT-proBNP) is an established biomarker for cardiac failure.
OBJECTIVE:
To determine the influence of preoperative serum NT-proBNP on postoperative outcome and mid-term survival in patients undergoing coronary artery bypass grafting (CABG).
METHODS:
In 819 patients undergoing isolated CABG surgery preoperative serum NT-proBNP levels were measured. NT-proBNP was correlated with various postoperative outcome parameters and survival rate after a median follow-up time of 18 (0.5–44) months. Risk factors of mortality were identified using χ2, Mann–Whitney test, and Cox regression.
RESULTS:
NT-proBNP levels >430 ng/ml and >502 ng/ml predicted hospital and overall mortality (p<0.05), with an incidence of 1.6% and 4%, respectively. Kaplan–Meier analysis revealed decreased survival rates in patients with NT-proBNP >502 ng/ml (p = 0.001). Age, preoperative serum creatinine, diabetes, chronic obstructive pulmonary disease, low left ventricular ejection fraction and BNP levels >502 ng/ml were isolated as risk factors for overall mortality. Multivariate Cox regression analysis, including the known factors influencing NT-proBNP levels, identified NT-proBNP as an independent risk factor for mortality (OR = 3.079 (CI = 1.149-8.247), p = 0.025). Preoperative NT-proBNP levels >502 ng/ml were associated with increased ventilation time (p = 0.005), longer intensive care unit stay (p = 0.001), higher incidence of postoperative hemofiltration (p = 0.001), use of intra-aortic balloon pump (p<0.001), and postoperative atrial fibrillation (p = 0.031)
CONCLUSION:
Preoperative NT-proBNP levels >502 ng/ml predict mid-term mortality after isolated CABG and are associated with significantly higher hospital mortality and perioperative complications.
doi:10.1590/S1807-59322010001200004
PMCID: PMC3020332  PMID: 21340210
Brain type natriuretic peptide; BNP; NT-proBNP; CABG; Coronary artery disease
2.  Association of 25-hydroxyvitamin D deficiency with NT-pro BNP levels in patients with acute myocardial infarction: a cross-sectional analysis 
BMC Research Notes  2011;4:542.
Background
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.
Methods
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).
Results
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.
Conclusions
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.
doi:10.1186/1756-0500-4-542
PMCID: PMC3266347  PMID: 22171582
Vitamin D; N-terminal proBNP; Acute myocardial infarction
3.  Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease 
Gut  2003;52(10):1511-1517.
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.
PMCID: PMC1773816  PMID: 12970147
brain natriuretic peptide; cardiac dysfunction; cirrhotic cardiomyopathy; pro-brain natriuretic peptide; QT interval; cardiac ventricular peptides
4.  Natriuretic peptide testing for the evaluation of critically ill patients with shock in the intensive care unit: a prospective cohort study 
Critical Care  2006;10(1):R37.
Introduction
Amino-terminal pro-brain natriuretic peptide (NT-proBNP) is useful in evaluating heart failure, but its role in evaluating patients with shock in the intensive care unit (ICU) is not clear.
Method
Forty-nine consecutive patients in four different ICUs with shock of various types and with an indication for pulmonary artery catheter placement were evaluated. Analyses for NT-proBNP were performed on blood obtained at the time of catheter placement and results were correlated with pulmonary artery catheter findings. Logistic regression identified independent predictors of mortality.
Results
A wide range of NT-proBNP levels were observed (106 to >35,000 pg/ml). There was no difference in median NT-proBNP levels between patients with a cardiac and those with a noncardiac origin to their shock (3,046 pg/ml versus 2,959 pg/ml; P = 0.80), but an NT-proBNP value below 1,200 pg/ml had a negative predictive value of 92% for cardiogenic shock. NT-proBNP levels did not correlate with filling pressures or hemodynamics (findings not significant). NT-proBNP concentrations were higher in patients who died in the ICU (11,859 versus 2,534 pg/ml; P = 0.03), and the mortality rate of patients in the highest log-quartile of NT-proBNP (66.7%) was significantly higher than those in other log-quartiles (P < 0.001); NT-proBNP independently predicted ICU mortality (odds ratio 14.8, 95% confidence interval 1.8–125.2; P = 0.013), and was superior to Acute Physiology and Chronic Health Evaluation II score and brain natriuretic peptide in this regard.
Conclusion
Elevated levels of NT-proBNP do not necessarily correlate with high filling pressures among patients with ICU shock, but marked elevation in NT-proBNP is strongly associated with ICU death. Low NT-proBNP values in patients with ICU shock identifed those at lower risk for death, and may be useful in excluding the need for pulmonary artery catheter placement in such patients.
doi:10.1186/cc4839
PMCID: PMC1550815  PMID: 16507171
5.  Log-transformation improves the prognostic value of serial NT-proBNP levels in apparently stable pulmonary arterial hypertension 
Pulmonary Circulation  2011;1(2):244-249.
N-terminal pro B-type natriuretic peptide (NT-proBNP) is a product of cleavage of the cardiac prohormone pro B-type natriuretic peptide into its active form. It has proven to be a useful biomarker in left heart failure. However, studies examining the utility of serial measurements of NT-proBNP in pulmonary arterial hypertension (PAH) patients have shown mixed results. We compared three methods of predicting adverse clinical outcomes in PAH patients: the change in 6 minute walk distance (6MWD), the change in absolute levels of NT-proBNP and the change in log-transformed levels of NT-proBNP. All PAH patients presenting from March-June 2007 were screened. Patients who were clinically unstable, had abnormal renal function or hemoglobin levels or lacked a prior NT-proBNP were excluded. 63 patients were followed up for adverse clinical outcomes (defined as death, transplantation, hospitalisation for right heart failure, or need for increased therapy). Three methods were used to predict adverse events, i.e.: (a) comparing a 6MWD performed in March-June 2007 and a previous 6MWD. A decrease in 6MWD of ≥30m was used to predict clinical deterioration; (b) comparing a NT-proBNP value measured in March-June 2007 and a previous NT-proBNP. An increase in NT-proBNP of ≥250pg/ml was used to predict clinical deterioration (250pg/ml represented approximately 30% change from the baseline median value of NT-proBNP for this cohort); and (c) comparing the loge equivalents of two consecutive NT-proBNP values. We used the formula: loge(current NT-proBNP) - loge(previous NT-proBNP)=x. A value of x≥+0.26 was used to predict adverse events. This is equivalent to a 30% change from baseline, and hence is comparable to the chosen cut-off for absolute levels of NT-proBNP. A loge difference of ≥+0.26 identifies patients at risk of adverse events with a specificity of 98%, a sensitivity of 60%, a positive predictive value of 89%, and a negative predictive value of 90%. A drop in 6MWD of ≥30m has a specificity of 29%, a sensitivity of 73%, a positive predictive value of 24% and a negative predictive value of 24%. It seems possible to risk-stratify apparently stable PAH patients by following the changes in their serial log-transformed NT-proBNP values. In this small pilot study, this method was better than relying on changes in the actual levels of NT-proBNP or changes in 6MWD. This needs to be validated prospectively in a larger cohort.
doi:10.4103/2045-8932.83450
PMCID: PMC3198650  PMID: 22034610
N-terminal pro B-type natriuretic peptide; 6-minute walk distance; biomarker
6.  Analysis of N-terminal pro-B-type natriuretic peptide and cardiac index in multiple injured patients: a prospective cohort study 
Critical Care  2008;12(5):R118.
Introduction
Increased serum B-type natriuretic peptide (BNP) has been identified for diagnosis and prognosis of impaired cardiac function in patients suffering from congestive heart failure, ischemic heart disease, and sepsis. However, the prognostic value of BNP in multiple injured patients developing multiple organ dysfunction syndrome (MODS) remains undetermined. Therefore, the aims of this study were to assess N-terminal pro-BNP (NT-proBNP) in multiple injured patients and to correlate the results with invasively assessed cardiac output and clinical signs of MODS.
Methods
Twenty-six multiple injured patients presenting a New Injury Severity Score of greater than 16 points were included. The MODS score was calculated on admission as well as 24, 48, and 72 hours after injury. Patients were subdivided into groups: group A showed minor signs of organ dysfunction (MODS score less than or equal to 4 points) and group B suffered from major organ dysfunction (MODS score of greater than 4 points). Venous blood (5 mL) was collected after admission and 6, 12, 24, 48, and 72 hours after injury. NT-proBNP was determined using the Elecsys proBNP® assay. The hemodynamic monitoring of cardiac index (CI) was performed using transpulmonary thermodilution.
Results
Serum NT-proBNP levels were elevated in all 26 patients. At admission, the serum NT-proBNP values were 116 ± 21 pg/mL in group A versus 209 ± 93 pg/mL in group B. NT-proBNP was significantly lower at all subsequent time points in group A in comparison with group B (P < 0.001). In contrast, the CI in group A was significantly higher than in group B at all time points (P < 0.001). Concerning MODS score and CI at 24, 48, and 72 hours after injury, an inverse correlation was found (r = -0.664, P < 0.001). Furthermore, a correlation was found comparing MODS score and serum NT-proBNP levels (r = 0.75, P < 0.0001).
Conclusions
Serum NT-proBNP levels significantly correlate with clinical signs of MODS 24 hours after multiple injury. Furthermore, a distinct correlation of serum NT-proBNP and decreased CI was found. The data of this pilot study may indicate a potential value of NT-proBNP in the diagnosis of post-traumatic cardiac impairment. However, further studies are needed to elucidate this issue.
doi:10.1186/cc7013
PMCID: PMC2592747  PMID: 18789145
7.  Usefulness of N-terminal pro-brain natriuretic peptide and C-reactive protein to predict ICU mortality in unselected medical ICU patients: a prospective, observational study 
Critical Care  2011;15(1):R42.
Introduction
The performance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and C-reactive protein (CRP) to predict clinical outcomes in ICU patients is unimpressive. We aimed to assess the prognostic value of NT-proBNP, CRP or the combination of both in unselected medical ICU patients.
Methods
A total of 576 consecutive patients were screened for eligibility and followed up during the ICU stay. We collected each patient's baseline characteristics including the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, NT-proBNP and CRP levels. The primary outcome was ICU mortality. Potential predictors were analyzed for possible association with outcomes. We also evaluated the ability of NT-proBNP and CRP additive to APACHE-II score to predict ICU mortality by calculation of C-index, net reclassification improvement (NRI) and integrated discrimination improvement (IDI) indices.
Results
Multiple regression revealed that CRP, NT-proBNP, APACHE-II score and fasting plasma glucose independently predicted ICU mortality (all P < 0.01). The C-index with respect to prediction of ICU mortality of APACHE II score (0.82 ± 0.02; P < 0.01) was greater than that of NT-proBNP (0.71 ± 0.03; P < 0.01) or CRP (0.65 ± 0.03; P < 0.01) (all P < 0.01). As compared with APACHE-II score (0.82 ± 0.02; P < 0.01), combination of CRP (0.83 ± 0.02; P < 0.01) or NT-proBNP (0.83 ± 0.02; P < 0.01) or both (0.84 ± 0.02; P < 0.01) with APACHE-II score did not significantly increase C-index for predicting ICU mortality (all P > 0.05). However, addition of NT-proBNP to APACHE-II score gave IDI of 6.6% (P = 0.003) and NRI of 16.6% (P = 0.007), addition of CRP to APACHE-II score provided IDI of 5.6% (P = 0.026) and NRI of 12.1% (P = 0.023), and addition of both markers to APACHE-II score yielded IDI of 7.5% (P = 0.002) and NRI of 17.9% (P = 0.002). In the cardiac subgroup (N = 213), NT-proBNP but not CRP independently predicted ICU mortality and addition of NT-proBNP to APACHE-II score obviously increased predictive ability (IDI = 10.2%, P = 0.018; NRI = 18.5%, P = 0.028). In the non-cardiac group (N = 363), CRP rather than NT-proBNP was an independent predictor of ICU mortality.
Conclusions
In unselected medical ICU patients, NT-proBNP and CRP can serve as independent predictors of ICU mortality and addition of NT-proBNP or CRP or both to APACHE-II score significantly improves the ability to predict ICU mortality. NT-proBNP appears to be useful for predicting ICU outcomes in cardiac patients.
doi:10.1186/cc10004
PMCID: PMC3221971  PMID: 21272380
8.  N-Terminal Pro-B-type Natriuretic Peptide Levels in the Korean General Population 
Korean Circulation Journal  2010;40(12):645-650.
Background and Objectives
B-type natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) levels may serve as a useful marker of cardiovascular risk for screening of the general population. We evaluated reference levels and distribution of NT-proBNP in the Korean general population based on a large cohort study.
Subjects and Methods
We included 1,518 adult subjects (ages 40-69) of a community-based cohort from the Korea Rural Genomic Cohort (KRGC) Study. Thorough biochemical and clinical data were recorded for all subjects. Levels of NT-proBNP from all participants were determined. In order to determine normal reference levels, subjects with factors known to influence NT-proBNP levels were excluded.
Results
The characteristics of the cohort are described below; subjects were 41.2% male, and the mean age was 54.8±8.4 years. The distribution of risk factors for cardiovascular disease in the cohort included hypertension (25%), left ventricular hypertrophy by electrocardiography (ECG-LVH) (15%), hypercholestolemia (4.5%), smoking (32%), diabetes (10.9%), history of coronary heart disease (4.9%), history of heart failure (0.9%), symptoms of heart failure (6.1%), elevated serum creatinine (≥1.5, 3.7%), and severe obesity (body mass index >30 kg/m2, 4.6%). The levels of NT-proBNP of all subjects are shown below; the mean was 60.1±42.1, and the median was 36.5 pg/mL. In addition, the levels of NT-proBNP of normal subjects (which did not have any risk factors, n=224) are shown below; the mean was 40.8, and the median was 32.1 pg/mL. In normal subjects, the NT-proBNP level was slightly higher in females (25.7±24.8 vs. 46.9±35.4, p<0.001). NT-proBNP level increased with age in both the normal population and the total population. There were no significant differences in NT-proBNP levels in subjects who smoked, or had diabetes mellitus, hypertension or ECG-LVH. However, in subjects with a history of congestive heart failure (CHF) (58.5±103.29 vs. 213.8±258.8, p<0.005), elevated serum creatinine levels (≥1.5 mg/dL, 146.2±98.2 vs. 54.3±38.1, p<0.001), or who were older (≥60, 48.4 vs. 84.2±139.5 pg/mL, p<0.05), the BNP level was higher. In addition, patients with more than 3 risk factors for CHF had higher BNP levels (risk 0: 40.8±34.0, 1-2: 57.4±93.2, ≥3: 85.0±152.9 pg/mL). NT-proBNP levels were also related with age, sex, urine albumin, serum Cr, and high sensitivity C-reactive protein (p<0.05).
Conclusion
We determined the reference value and distribution of NT-proBNP in the Korean adult general population. We also found that adjustments for the independent effects of age, sex and renal function appear necessary when determining cardiac risk based on proBNP levels.
doi:10.4070/kcj.2010.40.12.645
PMCID: PMC3025338  PMID: 21267387
Natriuretic peptides; Cohort studies; Population surveillance; Reference values
9.  Reference Limits for N-terminal-pro-B-type Natriuretic Peptide in Healthy Individuals (From the Framingham Heart Study) 
The American journal of cardiology  2011;108(9):1341-1345.
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.
doi:10.1016/j.amjcard.2011.06.057
PMCID: PMC3209520  PMID: 21864812
Natriuretic peptides; Cardiac Biomarkers; Heart Failure
10.  Direct Immunochemiluminescent Assay for proBNP and Total BNP in Human Plasma proBNP and Total BNP Levels in Normal and Heart Failure 
PLoS ONE  2013;8(1):e53233.
Background
Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure.
Methodology/Principal Findings
We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%–8.0% in proBNP assay and from 7.0%–8.4% in total BNP assay, and between-run CVs ranged from 5.3–7.4% in proBNP assay and from 2.9%–9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998–1.00), and analytical recovery was 90–101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects.
Conclusions/Significance
Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma.
doi:10.1371/journal.pone.0053233
PMCID: PMC3554706  PMID: 23365636
11.  Carbohydrate Antigen-125 and N-Terminal Pro-Brain Natriuretic Peptide Levels 
Texas Heart Institute Journal  2012;39(1):30-35.
Carbohydrate antigen-125 (CA-125) is emerging as a prognostic biomarker of risk in heart failure. In a prospective study, we compared the prognostic values of CA-125 and amino-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with stable heart failure.
We enrolled 102 consecutive chronic, stable, systolic-heart-failure patients (68 men and 34 women; median age, 71 yr) from November 2008 through February 2010. We measured baseline NT-proBNP and CA-125 levels and compared their prognostic values. The primary endpoint was all-cause death and other major adverse events, defined as hospitalization for decompensated heart failure or acute coronary syndrome.
During a mean follow-up period of 14 ± 2 months, 12 patients died and 35 others sustained major adverse events. We found that CA-125 level significantly correlated with New York Heart Association functional class, pulmonary artery pressure, microalbuminuria, creatine kinase–MB fraction, and hemoglobin, albumin, and NT-proBNP levels. Upon receiver operating characteristic curve analysis, CA-125 and NT-proBNP had similar accuracy in predicting major adverse events and death: for major adverse events, area under the curve (AUC) was 0.699 for CA-125 (P=0.002) and 0.696 for NT-proBNP (P=0.002); for death, AUC was 0.784 for CA-125 (P=0.003) and 0.824 for NT-proBNP (P=0.001). Multivariate Cox regression analysis showed that CA-125 levels greater than 32 U/mL and NT-proBNP levels greater than 5,300 pg/mL had independent prognostic value for major adverse events and death.
We conclude that baseline CA-125 and NT-proBNP levels are comparably reliable as heart-failure markers, and that CA-125 can be used for prognosis prediction in heart failure.
PMCID: PMC3298903  PMID: 22412224
Biological markers/blood; CA-125 antigen/blood; diagnostic tests, routine/utilization; health status indicators; heart failure/physiopathology; natriuretic peptide, brain/blood; predictive value of tests; sensitivity and specificity
12.  Secretion of Glycosylated Pro-B-Type Natriuretic Peptide from Normal Cardiomyocytes 
Clinical chemistry  2011;57(6):864-873.
Background
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.
Methods
We expressed pre-proBNP in cardiomyocytes, and determined the subcellular localization, dominant intracellular and extracellular forms of BNP.
Results
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.
Conclusions
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.
doi:10.1373/clinchem.2010.157438
PMCID: PMC3634583  PMID: 21482747
13.  B-type natriuretic peptide versus amino terminal pro-B type natriuretic peptide: selecting the optimal heart failure marker in patients with impaired kidney function 
BMC Nephrology  2013;14:117.
Background
The effect of impaired kidney function on B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) is vague. This study was performed to examine the effect of kidney dysfunction on the afore-mentioned markers and determine appropriate cutoffs for systolic heart failure (SHF).
Methods
In this cross sectional study adults with estimated glomerular filtration rate (eGFR) <60 ml/min for ≥3 months were identified in consulting clinics from June 2009 to March 2010. SHF was defined as documented by a cardiologist with ejection fraction of < 40% and assessed by New York Heart Association classification (NYHA). Plasma was assayed for creatinine (Cr), BNP and NT-proBNP.
Results
A total of 190 subjects were enrolled in the study, 95 with and 95 without SHF. The mean age of patients was 58 (±15) years, 67.4% being males. Mean BNP levels showed a 2.5 fold and 1.5 fold increase from chronic kidney disease (CKD) stage 3 to stage 5 in patients with and without SHF respectively. NT-proBNP levels in non-heart failure group were 3 fold higher in CKD stage 5 compared to stage 3. Mean NT-proBNP levels were 4 fold higher in CKD stage 5 compared to stage 3 in patients with SHF. Optimal BNP and NT-proBNP cutoffs of SHF diagnosis for the entire CKD group were 300 pg/ml and 4502 pg/ml respectively.
Conclusion
BNP and NT-proBNP were elevated in kidney dysfunction even in the absence of SHF; however the magnitude of increase in NT-proBNP was greater than that of BNP. BNP and NT-proBNP can be useful in diagnosing SHF, nonetheless, by using higher cutoffs stratified according to kidney dysfunction. NT-proBNP appears to predict heart failure better than BNP.
doi:10.1186/1471-2369-14-117
PMCID: PMC3680180  PMID: 23725445
B-Type natriuretic peptide; Heart failure; NT-proBNP; Kidney
14.  The Relationship between Serum NT– Pro-BNP Levels and Prognosis in Patients with Systolic Heart Failure 
Introduction
Most studies reported using N-terminal pro-brain natriuretic peptide (NT-proBNP) in diagnosis of heart failure but there is controversy about use of these tests in determining prognosis and classification of severity of heart failure. The objective of this study was to determine the value of plasma NT-proBNP levels assessment in evaluation of mortality and morbidity of patients with systolic left ventricular dysfunction.
Methods
A cohort study was performed in 150 patients with heart failure since September 2009 until February 2010. The patients were followed for 6 months to assess their prognosis. Patients were divided into two good and bad prognosis groups according to severity of heart failure in New York Heart Association (NYHA) class and frequency of hospital admission and mortality due to cardiac causes. Patients with good prognosis had ≥1 admission or no mortality or NYHA class ≥2 and patients that had one of this criteria considered as bad prognosis groups. Pro-BNP levels were measured at baseline and left ventricular ejection fraction (LVEF) was estimated with echocardiography. Data was analyzed with using Chi-square, t-test, ANOVA, Kruskal-Wallis tests.
Results
In patients with heart failure that enrolled in this clinical study, ten patients were lost during follow-up. The mean of NT-proBNP is significantly correlated with ejection fraction (p=0.003) and NYHA class (p<0.001). In our study among 140 patients who were follow-up for 6 months, 11(9.7%) of individuals died with mean NT-proBNP of 8994.8±8375 pg/ml, in survived patients mean NT-proBNP was 3756.8±5645.6 pg/ml that was statistically significant (P=0.02). Mean NT-proBNP in the group with good prognosis was 2723.8±4845.2 pg/ml and in the group with bad prognosis was 5420.3±6681 pg/ml, difference was statistically significant (P=0.0001).
Conclusion
Our study in consistent with other studies confirms that NT-proBNP is significantly correlated with mortality and morbidity. This could be predicting adverse out come and stratification in patients with heart failure. It is recommended that more research be performed in Iran.
doi:10.5681/jcvtr.2011.012
PMCID: PMC3825328  PMID: 24250954
Heart failure; Pro-BNP; Prognosis; Mortality; Morbidity
15.  Relation of Vitamin D and Parathyroid Hormone to Cardiac Biomarkers and to Left Ventricular Mass (From the Cardiovascular Health Study) 
The American journal of cardiology  2012;111(3):418-424.
Vitamin D and parathyroid hormone (PTH) may impact cardiovascular health among individuals with kidney disease and in the general population. We investigated associations of serum 25-hydroxyvitamin D (25OHD) and PTH concentrations with a comprehensive set of biochemical, electrocardiographic and echocardiographic measurements of cardiac structure and function in the Cardiovascular Health Study. A total of 2,312 subjects who were free of cardiovascular disease at baseline were studied. Serum 25OHD and intact PTH concentrations were measured using mass-spectrometry and a 2-site immunoassay. Outcomes were N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T, electrocardiographic measures of conduction, and echocardiographic measures of left ventricular mass and diastolic dysfunction. At baseline, subjects had a mean age of 73.9±4.9 years, 69.7% were female and 21% had chronic kidney disease (CKD; glomerular filtration rate <60ml/min). Mean (SD) 25OHD was 25.2 (10.2) ng/ml and median PTH was 51 pg/ml (range 39–65 pg/ml). After adjustment, 25OHD was not associated with any of the biochemical, conduction, or echocardiographic outcomes. Serum PTH levels ≥ 65 pg/ml were associated with greater NT-proBNP, cardiac troponin T and left ventricular mass in subjects with CKD. The regression coefficients were: 120 (36.1, 204 pg/ml), 5.2 (3.0, 7.4 pg/ml) and 17 (6.2, 27.8 g) (p-value <0.001). In subjects with normal kidney function, PTH was not associated with the outcomes. Among older adults with CKD, PTH excess is associated with higher NT-pro-BNP, cardiac troponin T, and left ventricular mass. In conclusion, these findings suggest a role for PTH in cardiovascular health and the prevention of cardiac diseases.
doi:10.1016/j.amjcard.2012.10.021
PMCID: PMC3546140  PMID: 23168286
Vitamin D; parathyroid hormone; cardiac biomarkers; left ventricular mass; epi-demiology
16.  Serial measurements of NT-proBNP are predictive of not-high-dose anthracycline cardiotoxicity in breast cancer patients 
British Journal of Cancer  2011;105(11):1663-1668.
Background:
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).
Methods:
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.
Results:
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%.
Conclusion:
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.
doi:10.1038/bjc.2011.439
PMCID: PMC3242597  PMID: 22068815
anthracyclines; brain natriuretic peptide; cardiac biomarkers; cardiotoxicity; N-terminal pro-brain natriuretic peptide
17.  Relationships of N-terminal pro-B-natriuretic peptide and cardiac troponin T to left ventricular mass and function and mortality in asymptomatic hemodialysis patients 
Background:
Although the cardiac biomarker troponin T (cTnT) is strongly related to mortality in end-stage renal disease, the independent association of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cTnT in predicting outcomes is unknown.
Objective:
To determine factors associated with NT-proBNP and cTnT, and to determine whether these levels are associated with mortality.
Study Design:
Cohort Study
Settings and Participants:
Asymptomatic hemodialysis patients (n=150) in 4 university-affiliated hemodialysis units.
Exposure and Outcomes:
For cross-sectional analysis, echocardiographic variables as exposures and N-terminal proBNP and cardiac troponin T as outcomes; for longitudinal analysis, association of N-terminal proBNP and cardiac troponin T as exposures to all-cause and cardiovascular disease mortality as outcomes.
Results:
In a multivariate regression analysis, low midwall fractional shortening a measure of poor systolic function was an independent correlate of log NT-proBNP (p<0.01), while left ventricular mass index was an independent correlate of cTnT (p<0.01). Over a median follow-up of 24 months, 46 patients died of which, 26 died due to cardiovascular causes. NT-ProBNP had a strong graded relationship with all-cause (Hazard Ratio (HR) 1.54, 4.78 and 4.03 for increasing quartiles, Chi2 32.2, p<0.001) and cardiovascular mortality (HR 2.99, 10.95, 8.54 Chi2 23.66, p<0.01), while cTnT had a weaker relationship with all-cause (HR 1.57, 2.32, 3.39, Chi2 23.09, p<0.01) and cardiovascular mortality (HR 1, 0.81, 2.12, 2.14, Chi2 15.05, p=0.1). The combination of the two biomarkers did not improve the association with all-cause or cardiovascular mortality compared to NT-proBNP alone. NT-proBNP was a marker of mortality even after adjusting for left ventricular mass index and midwall fractional shortening.
Limitations:
Our cohort was predominantly black and of limited sample size.
Conclusion:
NT-proBNP strongly correlates with left ventricular systolic dysfunction and is more strongly associated with mortality than cTnT in asymptomatic hemodialysis patients.
doi:10.1053/j.ajkd.2007.08.017
PMCID: PMC2408379  PMID: 18037101
NT-proBNP; Troponin T; left ventricular mass; left ventricular function; mortality; hemodialysis
18.  N-Terminal Pro-B-Type Natriuretic Peptide in Overweight and Obese Patients With and Without Diabetes: An Analysis Based on Body Mass Index and Left Ventricular Geometry 
Korean Circulation Journal  2009;39(12):538-544.
Background and Objectives
Several recent studies have shown that there is an inverse relationship between plasma B-type natriuretic peptide (BNP) and body mass index (BMI) in subjects with and without heart failure. Obesity frequently coexists with diabetes, so it is important to consider the relationship between diabetes and natriuretic peptide levels. We evaluated the influence of diabetes on the correlation of BNP and BMI.
Subjects and Methods
We examined 933 patients with chest pain and/or dyspnea undergoing cardiac catheterization between Feb. 2006 and Nov. 2007 in the Maryknoll cardiac center who had creatinine levels <2.0 mg/dL and normal systolic heart function. BMI was checked, transthoracic echocardiography was performed, and aminoterminal pro-brain natriuretic peptide (NT-proBNP) was sampled at the start of each case.
Results
In 733 non-diabetic patients, mean plasma NT-proBNP levels of non obese individuals (BMI <23 kg/m2), overweight individuals (23≤ BMI <25 kg/m2), and obese individuals (BMI ≥25 kg/m2) showed a significant negative correlation with increasing BMI (856.39±237.3 pg/mL, 601.69±159.6 pg/mL, 289.62±164.9 pg/mL, respectively, p<0.0001). However, in 200 diabetic patients, the correlation between BMI and NT-proBNP was not significant (r=-0.21, p=0.19), and NT-proBNP did not correlate with mitral E/Ea in obese diabetic patients (r=0.14, p=0.56). NT-proBNP was significantly correlated with mitral E/Ea in the non-obese (r=0.24, p=0.008) and non diabetic (r=0.32, p=0.003) groups. Left ventricular (LV) mass index was significantly correlated with NT-proBNP in all BMI groups (r=0.61, p<0.001), and patients with concentric cardiac hypertrophy showed the highest NT-proBNP levels.
Conclusion
The present study demonstrates that obese patients have reduced concentrations of NT-proBNP compared to non obese patients despite having higher LV filling pressures. However, NT-proBNP is not suppressed in obese patients with diabetes. This suggests that factors other than cardiac status affect NT-proBNP concentrations.
doi:10.4070/kcj.2009.39.12.538
PMCID: PMC2801462  PMID: 20049140
B-type natriuretic peptide; Body mass index; Obesity
19.  Minimally Elevated Cardiac Troponin T and Elevated N-Terminal Pro-B-Type Natriuretic Peptide Predict Mortality in Older Adults: Results From the Rancho Bernardo Study 
Objectives
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.
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1016/j.jacc.2008.04.033
PMCID: PMC2613773  PMID: 18672166
aging; cardiovascular diseases; epidemiology; natriuretic peptides; prognosis; risk factors; survival
20.  The Effect of Amlodipine and Sildenafil on the NT-ProBNP Level of Patients with COPD-Induced Pulmonary Hypertension  
Pulmonary hypertension (PH) is an important cause of heart failure in chronic obstructive pulmonary disease (COPD). The pro brain natriuretic peptide N-terminal (NT-proBNP) has been suggested as a noninvasive marker to evaluate ventricular function. However, there is no evidence to support the use of NT-proBNP in monitoring the benefits of vasodilators in COPD induced PH. Thus, we used NT-proBNP as a biomarker to evaluate the effect of oral vasodilators on cardiac function in COPD-induced PH.
Forty clinically-stable PH patients were enrolled with history of COPD, normal left ventricular ejection-fraction (LVEF), right ventricular systolic pressure (RVSP) > 45 mmHg and baseline blood NT-proBNP levels >100 pg/mL. Patients were randomized into two groups, one group received sildenafil and second group were given amlodipine for two weeks. NT-proBNP and systolic pulmonary arterial pressure (systolic PA-pressure) were measured at the beginning and the end of study.
Mean NT-proBNP level in the first group was 1297 ± 912 pg/mL before therapy and 554 ± 5 pg/mL after two weeks drug therapy, respectively. Similarly, in second group NT-proBNP level was 1657 ± 989 pg/mL and 646 ± 5 pg/mL before and after treatment. Amlodipine or sildenafil significantly reduced NT-proBNP levels in COPD-induced PH patients (p < 0.05).
Our study shows that amlodipine and sildenafil have a similar effect on NT-proBNP levels. In both groups NT- proBNP levels were significantly reduced after treatment. Therefore, our findings support the potential benefits of treatment with vasodilators in COPD induced PH.
Pulmonary hypertension, Chronic obstructive pulmonary disease, NT-proBNP, Amlodipine, Sildenafil
PMCID: PMC3977066  PMID: 24711842
21.  N-terminal pro-B-type Natriuretic Peptide is Associated with Sudden Cardiac Death Risk: the Cardiovascular Health Study 
Background
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.
Objective
To examine the relationship between N-terminal pro-B-type natriuretic peptide (NT-proBNP) and SCD in the Cardiovascular Health Study population.
Methods
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
Results
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).
Conclusion
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.
doi:10.1016/j.hrthm.2010.10.038
PMCID: PMC3826546  PMID: 21044699
Sudden cardiac death; B-type natriuretic peptide; BNP; NT-proBNP
22.  N-Terminal Pro-B-type Natriuretic Peptide Is Useful to Predict Cardiac Complications Following Lung Resection Surgery 
Background
Cardiovascular complications are major causes of morbidity and mortality following non-cardiac thoracic operations. Recent studies have demonstrated that elevation of N-Terminal Pro-B-type natriuretic peptide (NT-proBNP) levels can predict cardiac complications following non-cardiac major surgery as well as cardiac surgery. However, there is little information on the correlation between lung resection surgery and NT-proBNP levels. We evaluated the role of NT-proBNP as a potential marker for the risk stratification of cardiac complications following lung resection surgery.
Material and Methods
Prospectively collected data of 98 patients, who underwent elective lung resection from August 2007 to February 2008, were analyzed. Postoperative adverse cardiac events were categorized as myocardial injury, ECG evidence of ischemia or arrhythmia, heart failure, or cardiac death.
Results
Postoperative cardiac complications were documented in 9 patients (9/98, 9.2%): Atrial fibrillation in 3, ECG-evidenced ischemia in 2 and heart failure in 4. Preoperative median NT-proBNP levels was significantly higher in patients who developed postoperative cardiac complications than in the rest (200.2 ng/L versus 45.0 ng/L, p=0.009). NT-proBNP levels predicted adverse cardiac events with an area under the receiver operating characteristic curve of 0.76 [95% confidence interval (CI) 0.545~0.988, p=0.01]. A preoperative NT-proBNP value of 160 ng/L was found to be the best cut-off value for detecting postoperative cardiac complication with a positive predictive value of 0.857 and a negative predictive value of 0.978. Other factors related to cardiac complications by univariate analysis were a higher American Society of Anesthesiologists grade, a higher NYHA functional class and a history of hypertension. In multivariate analysis, however, high preoperative NT-proBNP level (>160 ng/L) only remained significant.
Conclusion
An elevated preoperative NT-proBNP level is identified as an independent predictor of cardiac complications following lung resection surgery.
doi:10.5090/kjtcs.2011.44.1.44
PMCID: PMC3249272  PMID: 22263123
Cardiac; Complication; Lung surgery; Prognosis
23.  Correlation between N-Terminal Pro-Brain Natriuretic Peptide and Doppler Echocardiographic Parameters of Left Ventricular Filling Pressure in Atrial Fibrillation 
Background
Atrial fibrillation (AF) is the most common cardiac arrhythmia with a population prevalence of about 1%. Natriuretic peptide level is elevated in patients with AF with diastolic dysfunction even with a normal left ventricular (LV) ejection fraction. The N-terminal pro-brain natriuretic peptide (NT-proBNP) level and Doppler echocardiographic parameters for diastolic function have shown correlation with LV filling pressures. We aimed to evaluate the relationship between echocardiographic parameters and serum NT-proBNP in patients with AF with preserved LV ejection fraction.
Methods
We examined transthoracic echocardiography and NT-proBNP levels in the patients with AF and patients with sinus rhythm. Blood samples were taken for serum NT-proBNP measurements within 24 hours of echocardiographic examination. The group 1 was the patients with sinus rhythm (n = 30, mean age 68 ± 13 years) and the group 2 was the patients with AF (n = 33, mean age 70 ± 14 years).
Results
The group 2 patients had significantly higher mitral E, E' (lateral annulus), E/E' (septal annulus), left atrial (LA) volume index, LA size, pulmonary vein diastolic velocity, and NT-proBNP level than those of group 1 patients (p < 0.05). The area under the receiver-operating characteristic curve showed a NT-proBNP had good diagnostic power for E/E' (septal annulus) > 15 in patients with AF at cutoff value of 433 pg/mL.
Conclusion
NT-proBNP level is well correlated with Doppler echocardiographic parameters of diastolic function in patients with AF and preserved LV ejection fraction. NT-proBNP level more than 433 pg/mL may suggest elevated LV filling pressure in patients with AF.
doi:10.4250/jcu.2011.19.1.26
PMCID: PMC3079081  PMID: 21519489
Atrial fibrillation; NT-proBNP; Doppler echocardiography
24.  Plasma N‐terminal pro‐B‐type natriuretic peptide as long‐term prognostic marker after major vascular surgery 
Heart  2006;93(2):226-231.
Objective
To assess the long‐term prognostic value of plasma N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) after major vascular surgery.
Design
A single‐centre prospective cohort study.
Patients
335 patients who underwent abdominal aortic aneurysm repair or lower extremity bypass surgery.
Interventions
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.
Results
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).
Conclusion
Preoperative NT‐proBNP level is a strong predictor of long‐term mortality and major adverse cardiac events after major non‐cardiac vascular surgery.
doi:10.1136/hrt.2006.093716
PMCID: PMC1861400  PMID: 16914484
dobutamine stress echocardiography; natriuretic peptides; prognosis; vascular surgery
25.  Diagnostic Values of Plasma, Fresh and Frozen Urine NT-proBNP in Heart Failure Patients 
Introduction: The plasma N-terminal probrain natriuretic peptide (NT-proBNP) level is an important diagnostic and prognostic marker of heart failure. Recent studies have suggested urinary NT-proBNP as a new and simple test for diagnosis of heart failure. We aim to compare diagnostic value of plasma, fresh and frozen urine levels of N-terminal probrain natriuretic peptide (NT-proBNP) for detecting heart failure.
Methods: Between January 2010 and January 2012, we measured urine and plasma levels of NTproBNP in 98 patients with chronic heart failure (CHF) and 29 age- and sex-matched healthy control subjects.
Results: There were significant correlations between plasma NT-proBNP and fresh (r=0.45, p<0.001) and frozen (r=0.42, p<0.001) urine NT-proBNP concentrations in CHF patients. Due to receiver operating curve analysis, fresh and frozen urine NT-proBNP could diagnose HF with are aunder curve (AUC) of 0.73±0.04 (p<0.001) and 0.65±0.05 (p=0.01) with sensitivity and specificity of 73.97%, 58.62%, and 65.31%, 62.07%, for a cut-off of 94.2 and 96 pg/mL, respectively. Plasma NT-proBNP had greater AUC (0.94±0.02, p<0.001) and better sensitivity and specificity (94.9%, 89.66% for cut-off of 414.5 pg/mL). There was no significant correlation between LVEF and plasma, fresh and frozen urine NT-proBNP levels in CHF patients.
Conclusion: Plasma NT-proBNP is still the best diagnostic marker with high sensitivity and specificity; however, urinary especially fresh urine NT-proBNP may be a surrogate to plasma NTproBNP for diagnosing HF with acceptable accuracy.
doi:10.5681/jcvtr.2014.024
PMCID: PMC4097851  PMID: 25031827
Heart Failure; NT-proBNP; Fresh Urine; Frozen Urine; Plasma

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