Changes In N-terminal Pro-brain Natriuretic Peptide Research Articles

Reproducibility of cardiac biomarkers response to prolonged treadmill exercise

We examined the reproducibility of alterations in cardiac biomarkers after two identical bouts of prolonged exercise in young athletes. Serum high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were assessed before and after exercise. Significant rises in median hs-cTnT and NT-proBNP occurred in both trials. While the absolute changes in hs-cTnT were smaller after trial 2, the pattern of change was similar and the delta scores were significantly related. However, the change in NT-proBNP was not correlated between trials. The hs-cTnT release demonstrates some consistency after exercise although the blunted hc-cTnT response requires further study.

NT-proBNP Changes in Patients with Ascites during Large Volume Paracentesis.

Background. N-terminal probrain natriuretic peptide (NT-proBNP) is a hormone involved in the regulation of cardiovascular homeostasis. Changes in serum NT-proBNP during large volume paracentesis (LVP) in patients with ascites have never before been examined. Aims. To determine if significant changes in serum NT-proBNP occur in patients undergoing LVP and the associated clinical correlates in patients with cirrhosis. Method. A total of 45 patients with ascites were prospectively recruited. Serum NT-proBNP, biochemistry, and haemodynamics were determined at baseline and at key time points during and after paracentesis. Results. 34 patients were analysed; 19 had ascites due to cirrhosis and 15 from malignancy. In those with cirrhosis, NT-proBNP decreased by 77.3 pg/mL at 2 L of drainage and 94.3 pg/mL at the end of paracentesis, compared with an increase of 10.5 pg/mL and 77.2 pg/mL in cancer patients at the same time points (P = 0.05 and P = 0.03). Only congestive cardiac failure (CCF) was an independent predictor of significant NT-proBNP changes at the end of drainage in cirrhotic patients (P < 0.01). There were no significant changes in haemodynamics or renal biochemistry for either group. Conclusion. Significant reductions in serum NT-proBNP during LVP occur in patients with cirrhosis but not malignancy, and only comorbid CCF appeared to predict such changes.

Exercise capacity and N-terminal pro-brain natriuretic peptide levels with biventricular vs. right ventricular pacing for atrioventricular block: results from the PREVENT-HF German Substudy

Previous studies showed unfavourable effects of right ventricular (RV) pacing. Ventricular pacing (VP), however, is required in many patients with atrioventricular (AV) block. The PREVENT-HF study explored left ventricular (LV) remodelling during RV vs. biventricular (BIV) pacing in AV block without advanced heart failure. The pre-specified PREVENT-HF German Substudy examined exercise capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP). Patients with expected VP ≥80% were randomized to RV or BIV pacing. Endpoints were peak oxygen uptake (pVO2), oxygen uptake at the anaerobic threshold (VO2AT), ventilatory efficiency (VE/VCO2), and logNT-proBNP. Considering crossover, intention to treat (ITT), and on-treatment (OT) analyses of covariance (ANCOVA) were performed. For exercise testing 44 (RV: 25, BIV: 19), and for NT-proBNP 53 patients (RV: 29, BIV: 24) were included. The ITT analysis revealed significant differences in pVO2 [ANCOVA effect 2.83 mL/kg/min, confidence interval (CI) 0.83-4.91, P = 0.007], VO2AT (ANCOVA effect 2.14 mL/min/k, CI 0.14-4.15, P = 0.03), and VE/VCO2 (ANCOVA effect -5.46, CI -10.79 to -0.13, P = 0.04) favouring BIV randomization. The significant advantage in pVO2 persisted in OT analysis, while VO2AT and VE/VCO2 showed trends favouring BIV pacing. LogNT-proBNP did not differ between groups. (ITT: ANCOVA effect 0.008, CI -0.40 to +0.41, P = 0.97; OT: ANCOVA effect -0.03, CI -0.44 to 0.30, P = 0.90). Our study suggests that BIV pacing produces better exercise capacity over 1 year compared with RV pacing in patients without advanced heart failure and AV block. In contrast, we observed no significant changes of NT-proBNP. Larger trials will allow appraising the clinical usefulness of BIV pacing in AV block. ClinicalTrials.gov Identifier: NCT00170326.

Clinical, Echocardiographic, and Neurohormonal Response to Cardiac Resynchronization Therapy: Are They Interchangeable?

The relationship between changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic or clinical definitions of response to cardiac resynchronization therapy (CRT) has not been evaluated. The aims of the present evaluation were to assess: (1) the relationship between changes in NT-proBNP after 6 months of CRT and clinical and echocardiographic responses; (2) the association between NT-proBNP changes and long-term outcome. In 170 patients treated with CRT (age 61 ± 11 years, 75% male), clinical and echocardiographic parameters and circulating NT-proBNP levels were assessed at baseline and 6 months after CRT. At 6 months follow-up, improvement in New York Heart Association class ≥ 1 point, decrease in left ventricular end-systolic volume ≥ 15%, and decrease in NT-proBNP ≥ 15% defined clinical, echocardiographic, and neurohormonal CRT response, respectively. All-cause mortality data were collected and related to neurohormonal response. Neurohormonal, echocardiographic, and clinical response rates were 54%, 58%, and 66%, respectively. The majority of patients (71%) showing echocardiographic response had NT-proBNP reduction ≥ 15%. In contrast, only 58% of patients who showed clinical response also had NT-proBNP reduction ≥ 15%. During a median follow-up of 32 months, 40 patients died. Patients with neurohormonal response demonstrated a superior long-term outcome compared to patients without neurohormonal response (log-rank P = 0.02). NT-proBNP reduction ≥ 15% showed better agreement with echocardiographic response compared to clinical response. Neurohormonal response was associated with superior long-term outcome compared to insufficient reduction in NT-proBNP levels.

FRI0119 Improvement in some, but not all, surrogate measures of cardiovascular disease following intensive treatment of early rheumatoid arthritis

BackgroundPatients with rheumatoid arthritis (RA) have an elevated risk of cardiovascular disease (CVD), predominantly ischaemic heart disease (IHD). Systemic inflammation is thought to be a key contributor to this risk...

NT-proBNP levels may be influenced by inflammation in active ankylosing spondylitis receiving TNF blockers: a pilot study

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a strong marker of cardiovascular disease with recent evidence that inflammation may also influence its levels; discrimination of this confounding variable is of particular interest in rheumatic diseases. Therefore, we evaluated NT-proBNP in ankylosing spondylitis (AS) patients pre- and post-TNF blocker to determine the possible association between NT-proBNP levels and inflammatory parameters. Forty-five consecutive AS patients without previous/current cardiovascular disease or systolic myocardial dysfunction, who were eligible to anti-TNF therapy, were prospectively enrolled. All patients received TNF blockers and they were evaluated for circulating NT-proBNP levels, clinical and laboratory parameters of disease activity, traditional cardiovascular risk factors, and conventional and tissue Doppler imaging echocardiography at baseline (BL) and 6 months after (6M) treatment. At BL, all patients had active AS, NT-proBNP levels had a median of 36 (20-72) pg/mL and 11 % were high in spite of no systolic alteration. Multiple linear regression analysis revealed that this peptide, at BL, was independently correlated with erythrocyte sedimentation rate (ESR) (p < 0.001), age (p = 0.01), and pulse pressure (p = 0.01). After 6M, all disease parameters improved and NT-proBNP levels were significantly reduced [24 (16-47) pg/mL, p = 0.037] compared to BL. Changes in NT-proBNP were positively correlated with ESR changes (r = 0.41, p = 0.006). Cardiovascular risk factors remained stable during follow-up. In conclusion, our data suggest that elevations of NT-proBNP should be interpreted with caution in active AS patients with no other evidence of cardiovascular disease. The short-term reduction of NT-proBNP levels in these patients receiving anti-TNF therapy appears to reflect an improvement in inflammatory status.

Impact of the Look AHEAD Intervention on NT‐pro Brain Natriuretic Peptide in Overweight and Obese Adults With Diabetes

Look AHEAD (Action for Health in Diabetes) is a randomized trial determining whether intensive lifestyle intervention (ILI) aimed at long-term weight loss and increased physical fitness reduces cardiovascular morbidity and mortality in overweight and obese individuals with type 2 diabetes compared to control (diabetes support and education, DSE). We investigated the correlates of N-terminal pro-brain natriuretic peptide (NT-proBNP), a biomarker associated with heart failure (HF) risk, in a subsample from 15 of 16 participating centers and tested the hypothesis that ILI decreased NT-proBNP levels. Baseline and 1-year blood samples were assayed for NT-proBNP in a random sample of 1,500 without, and all 628 with, self-reported baseline CVD (cardiovascular disease) (N = 2,128). Linear models were used to assess relationships that log-transformed NT-proBNP had with CVD risk factors at baseline and that 1-year changes in NT-proBNP had with intervention assignment. At baseline, the mean (s.d.) age, BMI, and hemoglobin A(1c) (HbA(1c)) were 59.6 (6.8) years, 36.0kg/m(2) (5.8), and 7.2% (1.1), respectively. Baseline geometric mean NT-proBNP was not different by condition (ILI 53.3 vs. DSE 51.5, P = 0.45), was not associated with BMI, and was inversely associated with HbA(1c). At 1 year, ILI participants achieved an average weight loss of 8.3% compared to 0.7% in DSE. At 1 year, NT-proBNP levels increased to a greater extent in the intervention arm (ILI +21.3% vs. DSE +14.2%, P = 0.046). The increased NT-proBNP associated with ILI was correlated with changes in HbA(1c), BMI, and body composition. In conclusion, among overweight and obese persons with diabetes, an ILI that reduced weight was associated with an increased NT-proBNP.

Serum A-FABP Is Increased and Closely Associated with Elevated NT-proBNP Levels in Type 2 Diabetic Patients Treated with Rosiglitazone

BackgroundAdipocyte fatty acid-binding protein (A-FABP) has been shown to play important roles in the development of metabolic syndrome, diabetes, and cardiovascular diseases. In this study we investigated the possible role of A-FABP in the development of cardiac dysfunction related to rosiglitazone treatment.Methodology/Principal FindingsA total of 84 patients with newly diagnosed type 2 diabetes were treated with rosiglitazone for 48 weeks. Circulating A-FABP and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were determined at baseline and repeated at 24 and 48 weeks. After the 48-week rosiglitazone treatment period, serum levels of both A-FABP and NT-proBNP increased progressively and significantly (P<0.01). Serum levels of A-FABP were demonstrated to be positively correlated with gender and waist circumference both at baseline and the end of the study, and with age, body mass index (BMI), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and NT-proBNP at 48 weeks (all P<0.05). In addition, changes in A-FABP were significantly and positively correlated with changes in NT-proBNP (r = 0.239, P = 0.039). Furthermore, multiple stepwise regression analysis showed that the changes in A-FABP were independently and positively associated with changes in NT-proBNP after adjusting for confounding factors (β = 0.320, P = 0.007).Conclusions/SignificanceRosiglitazone-mediated increase of A-FABP is closely associated with the elevation of NT-proBNP, a well-established marker of cardiac dysfunction. The findings of our study imply that A-FABP may mediate the cross-talk between heart and adipose tissue.

Prognostic Utility of Changes in N-Terminal Pro-Brain Natriuretic Peptide Combined with Sequential Organ Failure Assessment Scores in Patients with Acute Lung Injury/Acute Respiratory Distress Syndrome Concomitant with Septic Shock

We investigated the prognostic utility of changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) in combination with Sequential Organ Failure Assessment (SOFA) score in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) concomitant with septic shock. Forty-nine mechanically ventilated patients with ALI/ARDS concomitant with septic shock were studied. N-terminal pro-brain natriuretic peptide levels were measured on the first 3 days (days 0, 1, and 2) in the intensive care unit. The median NT-proBNP levels in survivors and nonsurvivors were 3,999 vs. 2,819 pg/mL on day 0 (P = 0.719); 4,495 vs. 5,397 pg/mL on day 1 (P = 0.543); and 2,325 vs. 14,173 pg/mL on day 2 (P = 0.028). N-terminal pro-brain natriuretic peptide levels increased significantly from baseline values in nonsurvivors only. We observed a monotonic increase in 28-day mortality associated with increasing quartiles of percent change in NT-proBNP on day 2 (P < 0.0001). Kaplan-Meier survival analysis revealed that mortality was significantly higher in patients with a change in NT-proBNP of 30% or more (log-rank P < 0.0001). On day 2, areas under the receiver operating characteristic curves for predicting 28-day mortality were 0.74 for SOFA alone and 0.85 (P = 0.028) for SOFA combined with percent change in NT-proBNP. In conclusion, in patients with ALI/ARDS concomitant with septic shock, a rising trend (high percent change) in NT-proBNP levels had better prognostic utility than absolute levels. The combination of percent change in NT-proBNP with SOFA may provide superior prognostic accuracy to SOFA alone.

Effect of heart rate reduction by ivabradine on left ventricular remodeling in the echocardiographic substudy of BEAUTIFUL

Occlusive coronary artery disease (CAD) is associated with left ventricular (LV) remodeling, LV systolic dysfunction, and heart failure. The BEAUTIFUL Echo substudy aimed to evaluate the effects of heart rate reduction with ivabradine on LV size (primary end-point: change in LV end-systolic volume index [LVESVI]) and function and the cardiac biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP). The substudy was carried out in 86 centers participating in the BEAUTIFUL study. 2D echocardiography was performed at baseline, and after 3 and 12 months in patients with stable CAD and LV systolic dysfunction receiving ivabradine or placebo at the same time-points. All data were read and analyzed centrally. Of 525 patients completing the study, 426 had adequate echocardiographic readings (n = 220 ivabradine; n = 206 placebo). Treatment with ivabradine was associated with a decrease in the primary end-point LVESVI (change from baseline to last value, -1.48 ± 13.00 mL/m(2)) versus an increase with placebo (1.85 ± 10.54 mL/m(2)) (P=0.018). There was an increase in LV ejection fraction with ivabradine (2.00 ± 7.02%) versus no change with placebo (0.01 ± 6.20%) (P=0.009). Reduction in LVESVI was related to the degree of heart rate reduction with ivabradine. There were no differences in any other echocardiographic parameters or NT-proBNP. Change in LVESVI was related to the log change in NT-proBNP in the ivabradine group only (r = 0.18, P = 0.006). Our observations suggest that ivabradine may reverse detrimental LV remodeling in patients with CAD and LV systolic dysfunction.

N-terminal pro–brain natriuretic peptide as a marker of right ventricular dysfunction after open-lung approach in patients with acute lung injury/acute respiratory distress syndrome

PurposeThe purpose of the study was to evaluate the utility of N-terminal pro–brain natriuretic peptide (NT-proBNP) as a marker of right ventricular (RV) dysfunction after open-lung approach (OLA) in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Materials and MethodsTwenty-seven patients with ALI/ARDS underwent OLA (2-minute steps of fixed pressure-controlled ventilation with progressive positive end-expiratory pressure levels up to 30 cm H2O, followed by stepwise decrement of positive end-expiratory pressure level by 2 cm H2O). Patients who showed a PaO2/FiO2 increase of more than 50% from baseline were defined as responders. Plasma NT-proBNP levels were taken immediately before OLA and 2 and 6 hours later. A minimum 30% increase in NT-proBNP level from baseline was considered significant. ResultsRight-over-left ventricular stroke work ratio and its percentage change did not differ between responders and nonresponders, whereas these values were higher in patients showing NT-proBNP increase (P < .05). The NT-proBNP percentage change correlated with right-over-left ventricular stroke work ratio percentage change (r = 0.83), pulmonary vascular resistance (r = 0.81), and RV ejection fraction (r = -0.79) and correlated with plateau pressure in nonresponders only (r = 0.82). ConclusionsIn patients with ALI/ARDS, intraindividual NT-proBNP changes correlated with RV afterload following OLA, thereby serving as a potential marker for RV dysfunction after OLA.

Dynamic changes in N-terminal pro-brain natriuretic peptide in acute coronary syndromes treated with percutaneous coronary intervention: a marker of ischemic burden, reperfusion and outcome

Whereas N-terminal pro-brain natriuretic peptide (NT-proBNP) is approved for risk stratification of patients with acute coronary syndromes (ACS), short-term temporal changes in NT-proBNP concentrations and the optimal time points for sampling are not clear. The purpose of this study was to better define the short-term changes in NT-proBNP in relation to clinical presentation, reperfusion and prognostic value in patients with ACS, as well as to identify the optimum time points for sampling. We studied daily plasma concentrations of NT-proBNP in 133 unselected patients with myocardial infarction (n=65), stable coronary artery disease (CAD, n=46) and no CAD (n=22) who underwent coronary angiography. Patients with non-ST-elevation myocardial infarction (NSTEMI) presented with markedly higher NT-proBNP than patients with ST-elevation myocardial infarction (STEMI) [1305 (741-3208) ng/L vs. 170 (70-424) ng/L, p<0.001]. Also, time to presentation from onset of pain was much longer in NSTEMI as compared to STEMI (>48 h vs. <6 h, p<0.001). Patients with NSTEMI also presented with higher NT-proBNP as compared with CAD [224 (98-732) ng/L] and no CAD [47 (26-102) ng/L; p<0.001, NSTEMI vs. both]. Following successful percutaneous coronary intervention [thrombolysis in myocardial infarction (TIMI) 3-flow established], NT-proBNP increased markedly within 24 h in patients with STEMI [718 (379-1338) ng/L, p<0.01 vs. 0 h], whereas no change in NT-proBNP was noted in patients with NSTEMI [1190 (1010-2024) ng/L, p=0.88 vs. 0 h]. In both STEMI and NSTEMI, NT-proBNP decreased significantly 96 h after successful reperfusion [STEMI -52%, 372 (189-610) ng/L, p<0.05; NSTEMI -52%, 613 (365-724) ng/L, p<0.05]. Unsuccessful reperfusion (TIMI<3) was associated with unchanged or increased NT-proBNP. NT-proBNP at 96 h and peak NT-proBNP further displayed a strong correlation with cardiac troponin T (r=0.64 and r=0.54, p<0.001), a marker of infarct size, and NT-proBNP at 96 h was a strong predictor of long-term prognosis (hazard ratio 7.29, p=0.025). In patients with NSTEMI, NT-proBNP may be increased as high as concentrations usually associated with acute congestive heart failure despite the absence of clinical signs. In contrast, patients with STEMI and short time to presentation may present with completely normal NT-proBNP, but dramatic short-term increases following reperfusion. NT-proBNP reflects ischemic burden, reperfusion success and prognosis, and the current data support repetitive sampling in patients with ACS.

Evaluation of Pimobendan and N‐Terminal Probrain Natriuretic Peptide in the Treatment of Pulmonary Hypertension Secondary to Degenerative Mitral Valve Disease in Dogs

Pimobendan is a positive inotrope and vasodilator that may be useful in the treatment of pulmonary hypertension (PHT) secondary to degenerative mitral valve disease. Pimobendan decreases the severity of PHT measured echocardiographically and improves quality-of-life scores. Changes in N-terminal probrain natriuretic peptide (NT-proBNP) concentrations will reflect improvement in severity of PHT. Ten client-owned dogs with peak tricuspid regurgitant flow velocity (TRFV) > or =3.5 m/s. Prospective short-term, double-blinded, crossover design, with a long-term, open-label component. Short term, dogs were randomly allocated to receive either placebo or pimobendan (0.18-0.3 mg/kg PO q12 h) for 14 days. After a 1-week washout, they received the alternative treatment for 14 days, followed by pimobendan open-label for 8 weeks. Short-term comparison: peak TRFV decreased in all dogs on pimobendan compared with placebo from a median of 4.40 (range, 3.2-5.6) to 3.75 (range, 2.4-4.8) m/s (P < .0001). NT-proBNP concentration decreased after treatment with pimobendan from a median of 2,143 (range, 450-3,981) to 1,329 (range, 123-2,411) pmol/L (P= .0009). All dogs improved their quality-of-life score (P= .006). In the long-term comparisons, peak TRFV decreased in all dogs from a median of 4.28 (range, 3.5-5.7) to 3.52 (range, 2.4-5.0) m/s (P < .0001). No significant changes in NT-proBNP or quality-of-life scores were detected. Pimobendan lowered severity of measurable PHT, improved quality-of-life scores, and decreased NT-proBNP concentrations short-term. Long term, only the reduction in TRFV was maintained.

Effects Of Training On Blood NT-proBNP In Cardiac Patients Classified According To Ejection Fraction

Blood N-terminal pro-brain natriuretic peptide (NT-proBNP), a known marker for heart failure, is released from ventricles in response to stretch of cardiomyocytes. PURPOSE: Cardiac patients (68 women, 296 men, aged 63 ± 11 yr) were categorized by echo-derived ejection fraction (EF) into 4 groups (EF >55%, 45 - 55%, 30 - 44%, <30%), then studied for changes in NT-proBNP and training effects before and after 25 ± 4 days of residential cardiac rehabilitation. METHODS: Exercise training consisted of 6 x wk cycle ergometry for 14 - 22 min (mean 17 ± 4 min), and daily walking for 45 min at 60 - 70% maximal heart rate (HRmax). Nutrition, diet, and pharmacologic prescriptions where initiated when indicated. RESULTS: see table. In addition to changes with training, NT-proBNP was significantly greater before rehab training in patients with EF <30% and EF 30-44% than those with higher EF. This remained true after training in spite of significant NT-proBNP reductions in all EF groups.Table: No caption providedCONCLUSIONS: These significant findings in only 25 days suggest a relatively powerful effect of short-term exercise training to improve myocardial function in cardiac patients regardless of initial EF, and to at least partially ameliorate the symptoms of ventricular systolic and diastolic insufficiency. Partial support: Sydney and J.L. Huffines Institute for Sports Medicine and Human Performance

Growth Differentiation Factor-15 in Idiopathic Pulmonary Arterial Hypertension

Growth-differentiation factor (GDF)-15 is a stress-responsive, transforming growth factor-beta-related cytokine. Circulating levels of GDF-15 provide independent prognostic information in patients with acute pulmonary embolism and chronic left-sided heart failure. To assess the prognostic value of GDF-15 in idiopathic pulmonary arterial hypertension. GDF-15 levels were determined in 76 treatment-naive patients at the time of baseline right heart catheterization. Patients were monitored for a median (range) of 48 (0-101) months (first cohort). Twenty-two additional patients were studied at baseline and 3 to 6 months after initiation of therapy (second cohort). Fifty-five percent of the patients in the first cohort presented with GDF-15 levels above 1,200 ng/L, the previously defined upper reference limit. The risk of death or transplantation at 3 years was 15 and 44% in patients with GDF-15 levels below or above 1,200 ng/L, respectively (P = 0.006). Elevated levels of GDF-15 were associated with increased mean right atrial and pulmonary capillary wedge pressures, a lower mixed venous oxygen saturation (Sv(O(2))), and higher levels of uric acid and N-terminal pro-brain natriuretic peptide (NT-proBNP). After adjustment for hemodynamic and biochemical variables, GDF-15 remained an independent predictor of adverse outcomes (P = 0.002). GDF-15 provided prognostic information in clinically relevant patient subgroups, and added prognostic information to hemodynamic variables and NT-proBNP. Changes in GDF-15 over time in the second cohort were related to changes in NT-proBNP (P = 0.031) and inversely related to changes in Sv(O(2)) (P < 0.001). GDF-15 is a promising new biomarker in idiopathic pulmonary arterial hypertension.

Plasma asymmetric dimethylarginine and cardiovascular events in patients with acute decompensated heart failure

This prospective study investigated whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to cardiovascular events in patients with acute heart failure. It has been reported that increased plasma ADMA concentrations are associated with adverse cardiovascular outcome in chronic heart failure. In 118 patients with acute decompensated heart failure and impaired left ventricular function, ADMA and N-terminal pro-brain natriuretic peptide (NT-proBNP) were assessed by high-performance liquid chromatography and by an enzyme-linked immunosorbent assay, respectively. Venous blood was collected at admission and after 1 week, and clinical events were observed during follow-up. All patients (median age 73 years, 96 males) were followed up for a median of 10.7 months. A clinical endpoint (cardiac decompensation, major adverse cardiovascular event, or all-cause mortality) occurred in 66 patients. In 81 patients, changes (Delta) in ADMA or NT-proBNP between admission and a median of 7 days were available. ADMA, NT-proBNP at admission, and DeltaADMA or DeltaNT-proBNP were comparable in patients with and without a clinical endpoint. In contrast to ADMA, NT-proBNP concentrations above the median were associated with higher adjusted hazard ratio for occurrence of an endpoint (HR 2.1; 95% confidence interval 1.2-3.9; P = 0.013). An inverse relationship was observed between DeltaNT-proBNP and endpoints before (P = 0.010) and after (P = 0.015) adjustment for confounders. In patients with acute heart failure, ADMA did not detect patients at future cardiovascular risk.

Is a pattern of increasing biomarker concentrations important for long-term risk stratification in acute coronary syndrome patients presenting early after the onset of symptoms?

Guidelines for treatment of acute coronary syndrome (ACS) recommend observing a rise or fall in cardiac troponin (cTn) concentrations for assessing acute injury. It is unknown whether a rising pattern presages a more adverse long-term prognosis than elevations that do not change. The present study assessed whether a rising pattern of cardiac biomarkers was more prognostic than simple elevations. We measured N-terminal pro-brain natriuretic peptide (NT-proBNP) (Roche), cTnT (Roche) and cTnI (Beckman Coulter) in 212 ACS patients. These biomarkers were measured in coincident EDTA and heparin plasma samples available from at least 2 different time points, an early first specimen obtained a median of 2 hours after onset of symptoms, interquartile range (IQR) 2-4 hours, and a later second specimen obtained at 9 hours, IQR 9-9 hours. The cTn concentration in the second specimen was used to classify myocardial necrosis (cTnI >0.04 ug/L; cTnT >0.01 ug/L). Outcomes [death, myocardial infarction (MI), heart failure (HF)] were obtained >8 years after the initial presentation. For patients with myocardial necrosis and a cTn concentration ratio (second/first measured concentrations) > or =1.00, the concentration ratios and the absolute concentrations in the second specimen were used to assess prognosis after 4 years. In myocardial necrosis, the relative change (cTn2/cTn1) was greater for cTnI than for cTnT (P <0.01), whereas the relative change in NT-proBNP was the same regardless of which troponin was used to classify necrosis (P = 0.71). The concentration ratio for cTnI, cTnT, and NT-proBNP was not useful for risk stratification (i.e., death/MI/HF; P > or =0.15). A rise in cardiac troponin or NT-proBNP concentration in ACS patients presenting early after onset of pain is not helpful for long-term prognosis.

Left ventricular remodelling in patients with moderate systolic dysfunction after myocardial infarction: favourable effects of exercise training and predictive role of N-terminal pro-brain natriuretic peptide

To investigate the effects of exercise training (ET) on left ventricular (LV) volumes, cardiopulmonary functional capacity and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in postinfarction patients with moderate LV dysfunction. Sixty-one postinfarction patients were randomized into two groups: group T [n=30, LV ejection fraction (EF) 41.6+/-11.3%, mean+/-SD] entered a 6-month ET programme, whereas group C (n=31, EF 42.0+/-7.6%, P=NS) did not. NT-proBNP assay, Doppler-echocardiography and cardiopulmonary exercise test were performed upon enrolment and at sixth months. At sixth months, trained patients showed an improvement in workload (+26%, P<0.001), Vo2peak (+31%, P<0.001), LV end-diastolic volume index (LVEDVI; -9%, P<0.001), a reduction in NT-proBNP (-71%, P<0.001) and a significant correlation between changes in NT-proBNP and in LVEDVI (r=0.858, P<0.001). Baseline NT-proBNP correlated with changes in LVEDVI in both trained (r=0.673, P<0.001) and untrained (r=0.623, P<0.001) patients. Group C showed unfavourable LVEDVI dilation (+8%, P<0.001; T vs. C group, P<0.001) and a smaller reduction in NT-proBNP (-40%, P<0.001; T vs. C group, P<0.001). Six month ET induced a favourable LV remodelling and a marked fall in NT-proBNP that could predict LV remodelling in postinfarction patients with moderate LV dysfunction.

NT-proBNP reflects right ventricular structure and function in pulmonary hypertension

The aim of the current study was to investigate whether alterations in N-terminal pro brain natriuretic peptide (NT-proBNP) reflect changes in right ventricular structure and function in pulmonary hypertension patients during treatment. The study consisted of 30 pulmonary hypertension patients; 15 newly diagnosed and 15 on long-term treatment. NT-proBNP, right heart catheterisation and cardiac magnetic resonance imaging measurements were performed, at baseline and follow-up. There were no significant differences between newly diagnosed patients and those on treatment at baseline or follow-up with respect to NT-proBNP, haemodynamics and right ventricular parameters. Relative changes in NT-proBNP during treatment were correlated to the relative changes in right ventricular end-diastolic volume index (r = 0.59), right ventricular mass index (r = 0.62) and right ventricular ejection fraction (r = -0.81). N-terminal pro brain natriuretic peptide measurements reflect changes in magnetic resonance imaging-measured right ventricular structure and function in pulmonary hypertension patients. An increase in N-terminal pro brain natriuretic peptide over time reflects right ventricular dilatation concomitant to hypertrophy and deterioration of systolic function.

Independent elevations of N-terminal pro–brain natriuretic peptide and cardiac troponins in endurance athletes after prolonged strenuous exercise

Although elevated resting brain natriuretic peptide (BNP) concentrations reflect heart disease, the meaning of exercise-induced increases is poorly understood and has been examined in small groups only. Therefore, the present study aimed to examine the increase in N-terminal pro-brain natriuretic peptide (NT-proBNP) and relations to cardiac troponin I and T (cTnI, cTnT) elevations after prolonged strenuous exercise in a large cohort of athletes. We examined exercise-induced changes in NT-proBNP, cTnI, and cTnT in 105 obviously healthy endurance athletes (40 +/- 8 years) before and after prolonged strenuous exercise. Blood samples were taken before, 15 minutes, and 3 hours after a marathon (n = 46), a 100-km run (n = 14), and a mountain bike marathon (n = 45). Eighty-one of 105 athletes exceeded the upper reference limit of NT-proBNP (males/females 88:153 ng/L) after exercise. NT-proBNP increased in all 3 events (P < .001) with the highest increase in the 100-km runners (median increase 200 ng/L; 25th/75th percentile 115/770 ng/L), which differed from the increase in the marathon (97 ng/L; 36/254 ng/L) or the mountain bike marathon (78 ng/L; 37/196 ng/L) (P < .01). Cardiac troponin I exceeded 0.04 microg/L in 74%; cTnT exceeded 0.01 microg/L in 47% of athletes after exercise. NT-proBNP was not related to exercise-induced increases in cTnI or cTnT, but correlated with exercise time (r = 0.55, P < .001). Increases in NT-proBNP can be found in a major part of obviously healthy athletes after prolonged strenuous exercise. The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. The different nature of exercise-induced increases in BNP and cardiac troponins has to be elucidated in the future.