B-type natriuretic peptides for the prediction of cardiovascular events in patients with stable coronary heart disease: the Heart and Soul Study.

Brain-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are known predictors of cardiovascular outcomes in patients with coronary heart disease; however, the relative prognostic value of these 2 biomarkers for secondary events remains unclear. In 983 participants with stable coronary heart disease, we evaluated the association of BNP and NT-proBNP with time to hospitalization for heart failure, nonfatal myocardial infarction, stroke or transient ischemic attack, cardiovascular death, and combined major adverse cardiovascular events (MACE). During an average follow-up of 6.5±3.3 years, both BNP and NT-proBNP were associated with increased risk of MACE in a multivariable-adjusted model (hazard ratio per standard deviation of log BNP: 1.58; 95% CI: 1.32 to 1.89; hazard ratio per standard deviation of log NT-proBNP: 1.84; 95% CI: 1.52 to 2.24). When added to traditional risk factors, NT-proBNP predicted MACE better than BNP (C statistic: 0.76 versus 0.72, P<0.001). Similarly, the addition of NT-proBNP resulted in a greater net reclassification improvement for predicting MACE than the addition of BNP (65% for NT-proBNP, 56% for BNP). Both BNP and NT-proBNP were significant predictors of MACE in stable coronary heart disease; however, NT-proBNP was superior to BNP for net risk reclassification for MACE.

Mishra RK ，Beatty AL ，Jaganath R ，Regan M ，Wu AH ，Whooley MA ... -  《Journal of the American Heart Association》

Role of B-Type Natriuretic Peptide and N-Terminal Prohormone BNP as Predictors of Cardiovascular Morbidity and Mortality in Patients With a Recent Coronary Event and Type 2 Diabetes Mellitus.

Natriuretic peptides are recognized as important predictors of cardiovascular events in patients with heart failure, but less is known about their prognostic importance in patients with acute coronary syndrome. We sought to determine whether B-type natriuretic peptide (BNP) and N-terminal prohormone B-type natriuretic peptide (NT-proBNP) could enhance risk prediction of a broad range of cardiovascular outcomes in patients with acute coronary syndrome and type 2 diabetes mellitus. Patients with a recent acute coronary syndrome and type 2 diabetes mellitus were prospectively enrolled in the ELIXA trial (n=5525, follow-up time 26 months). Best risk models were constructed from relevant baseline variables with and without BNP/NT-proBNP. C statistics, Net Reclassification Index, and Integrated Discrimination Index were analyzed to estimate the value of adding BNP or NT-proBNP to best risk models. Overall, BNP and NT-proBNP were the most important predictors of all outcomes examined, irrespective of history of heart failure or any prior cardiovascular disease. BNP significantly improved C statistics when added to risk models for each outcome examined, the strongest increments being in death (0.77-0.82, P<0.001), cardiovascular death (0.77-0.83, P<0.001), and heart failure (0.84-0.87, P<0.001). BNP or NT-proBNP alone predicted death as well as all other variables combined (0.77 versus 0.77). In patients with a recent acute coronary syndrome and type 2 diabetes mellitus, BNP and NT-proBNP were powerful predictors of cardiovascular outcomes beyond heart failure and death, ie, were also predictive of MI and stroke. Natriuretic peptides added as much predictive information about death as all other conventional variables combined. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01147250.

Wolsk E ，Claggett B ，Pfeffer MA ，Diaz R ，Dickstein K ，Gerstein HC ，Lawson FC ，Lewis EF ，Maggioni AP ，McMurray JJV ，Probstfield JL ，Riddle MC ，Solomon SD ，Tardif JC ，Køber L ... -  《Journal of the American Heart Association》

N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP), cardiovascular events, and mortality in patients with stable coronary heart disease.

Bibbins-Domingo K ，Gupta R ，Na B ，Wu AH ，Schiller NB ，Whooley MA ... -  《-》

Combining the use of amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide in the prognosis of hospitalized heart failure patients.

To investigate whether the combination of measuring amino-terminal pro-B-type natriuretic peptide (NT-proBNP) and B-type natriuretic peptide (BNP) could provide additional prognostic value in hospitalized heart failure patients. We measured both BNP and NT-proBNP simultaneously at baseline in 1464 hospitalized heart failure patients who were admitted to our heart failure center. All patients were followed-up with the median follow-up period of 533 days. The primary endpoint is a composite of all-cause death (non-transplantation patients) or heart transplantation. The median molar ratio of NT-proBNP/BNP was 2.37, but the range of the molar ratio varied from 1.57 to 3.75 (lower quartile to higher quartile). Using the cut-off value of 1790 pg/mL for NT-proBNP and 495 pg/mL for BNP from the ROC curve analysis, univariate Cox proportional regression analysis showed that the low/high group (NT-proBNP < 1790 pg/mL and BNP ≥ 495 pg/mL), high/low group (NT-proBNP ≥ 1790 pg/mL and BNP < 495 pg/mL) and high/high group (NT-proBNP ≥ 1790 pg/mL and BNP ≥ 495 pg/mL) had significant higher risk of all-cause death or heart transplantation [HR (hazard ratio): 2.87, 95% CI (confidence interval): 1.69-4.89, p < .001; HR: 2.68, 95% CI: 1.91-3.76, p < .001; HR:5.07, 95% CI: 3.85-6.67, p < .001] than low/low group (NT-proBNP < 1790 pg/mL and BNP < 495 pg/mL). In turn, the high/high group had higher risk of all-cause death or heart transplantation than low/high (HR: 1.70, 95% CI: 1.04-2.80, p = .035) and high/low groups (HR: 1.88, 95% CI: 1.42-2.49, p < .001). The low/high and high/low groups had a similar risk of all-cause death or heart transplantation. Further multivariable Cox regression analysis also showed that both BNP and NT-proBNP above the cut-off values independently predicted the worst prognosis, while either one of the two biomarkers above the cut-off value indicated the moderate poor prognosis and both below the cut-off values indicated the best prognosis (p for trend< 0.001). The plasma levels of NT-proBNP and BNP do not always increase proportionally in heart failure patients. The combination of testing NT-proBNP and BNP may add prognostic value to predict adverse events in hospitalized heart failure patients.

Wang Y ，Zhang R ，Huang Y ，Zhai M ，Zhou Q ，An T ，Huang Y ，Zhao X ，Tian P ，Zhang Y ，Zhang J ... -  《-》

NT-proBNP and Echocardiographic Parameters for Prediction of Cardiovascular Outcomes in Patients with CKD Stages G2-G4.

Natriuretic peptides and echocardiographic parameters both predict cardiovascular events in patients with CKD. However, it is unknown whether simultaneous assessment of amino-terminal probrain natriuretic peptide (NT-proBNP) and echocardiographic parameters provides complementary or redundant predictive information; in the latter case, one of these two might be dispensable. We aimed to analyze the implications of using NT-proBNP alone, echocardiographic parameters alone, or a combination of both for prediction of adverse cardiovascular outcome. Within the longitudinal Cardiovascular and Renal Outcome in CKD 2-4 Patients-The Fourth Homburg Evaluation Study, we prospectively studied 496 patients with CKD stages G2-G4, in whom we measured NT-proBNP. Left ventricular mass index, left atrial volume index, diastolic left ventricular function, and systolic left ventricular function were assessed echocardiographically. During 4.5±2.0 years of follow-up, the occurrence of (1) decompensated heart failure or all-cause mortality and (2) atherosclerotic events or all-cause mortality was recorded. We assessed the association of NT-proBNP and echocardiographic parameters with outcome (using Cox models) and evaluated the increased discriminative value associated with the addition of echocardiographic parameters and NT-proBNP (using integrated discrimination improvement and net reclassification improvement). During follow-up, 104 patients suffered decompensated heart failure or all-cause mortality, and 127 patents had atherosclerotic events or all-cause mortality. In univariable analyses, NT-proBNP and echocardiographic parameters predicted cardiovascular events. NT-proBNP remained an independent predictor for both end points in multivariate analysis, whereas left ventricular mass index, left atrial volume index, and diastolic left ventricular function did not. The addition of NT-proBNP on top of clinical and various echocardiographic variables was associated with improvements in reclassification for decompensated heart failure or all-cause mortality (integrated discrimination improvement =6.5%-8.3%; net reclassification improvement =23.1%-27.0%; all P≤0.03). Adding echocardiographic variables on top of clinical variables and NT-proBNP was not associated with significant net reclassification improvement (all P>0.05). Our data confirm NT-proBNP is an independent predictor of adverse outcomes in patients with CKD. The additional use of echocardiography for improvement of risk stratification is not supported by our results.

Untersteller K ，Girerd N ，Duarte K ，Rogacev KS ，Seiler-Mussler S ，Fliser D ，Rossignol P ，Heine GH ... -  《-》