Faculty Opinions recommendation of Impact of Body Mass Index on the Accuracy of N-Terminal Pro-Brain Natriuretic Peptide and Brain Natriuretic Peptide for Predicting Outcomes in Patients With Chronic Heart Failure and Reduced Ejection Fraction: Insights From the PARADIGM-HF Study (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial).

Author(s):  
Lars H Lund
Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ryuji Okamoto ◽  
Ryotaro Hashizume ◽  
Noboru Suzuki ◽  
Hiroshi Kiyonari ◽  
Kaoru Dohi

Introduction: Brain natriuretic peptide (BNP) levels are relatively higher in patients with heart failure with preserved ejection fraction (HFpEF) than heart failure with reduced ejection fraction (HFrEF); however, the mechanism remains unclear. BNP is induced by undetermined stretch-activated receptors including mechanically gated channels, which can be activated by a mechanical stimulus alone, and mechanically modulated channels, which require nonmechanical stimuli such as agonists. Thus it is possible that serum-induced expression of BNP may contribute to the increase of BNP in patients. Purpose: Our purpose is to examine whether serum-induced BNP expression (iBNP) partly contributes to the increase in BNP in patients with HFpEF. Methods: We generated the BNP reporter mice by knocking luciferase cDNA in the initiation site of NPPB . Neonatal cardiomyocytes were isolated and cultured from 2-day-old neonates. These cardiomyocytes were stimulated for 24 hours with 20% serum from patients with HFpEF or HFrEF (n=114 and 82, respectively) and the luciferase activity was examined as iBNP and the ratio of iBNP to BNP was measured. The patients’ characteristics and clinical parameters were compared and multivariate regression analysis was performed using SPSS version 25. Results: The mean ages were 71 yrs in HFpEF and 67 yrs in HFrEF. The female gender was higher in HFpEF (46% vs 32%). The prevalence of atrial fibrillation and hypertension and the use of calcium channel blocker (CCB) were higher in HFpEF than in HFrEF (31 vs 17%, 66 vs 43%, 28 vs 18%). The prevalence of coronary artery disease, chronic kidney disease and diabetes mellitus were lower in HFpEF than HFrEF (21 vs 42%, 44 vs 74%, 25 vs 44%). The ratio of iBNP to BNP was significantly higher in HFpEF than in HFrEF (26.9 vs 16.1, P<0.001). Multivariate regression analysis showed the existence of HFpEF was an independent predictor for the ratio of iBNP to BNP after adjusting all other measurements (β=0.154, P=0.032). Age, hemoglobin, the use of CCB and the deceleration time were also independent predictors (β=0.167, P=0.025; β=0.203, P=0.006; β=0.138, P=0.049; β=0.143, P=0.049, respectively). Conclusions: These results indicate the elevation of BNP in patients with HFpEF is partly due to the iBNP from heart.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Gianluigi Savarese ◽  
Camilla Hage ◽  
Ulf Dahlström ◽  
Pasquale Perrone-Filardi ◽  
Lars H Lund

Introduction: Changes in N-terminal pro brain natriuretic peptide (NT-proBNP) have been demonstrated to correlate with outcomes in patients with heart failure (HF) and reduced ejection fraction (EF). However the prognostic value of a change in NT-proBNP in patients with heart failure and preserved ejection fraction (HFPEF) is unknown. Hypothesis: To assess the impact of changes in NT-proBNP on all-cause mortality, HF hospitalization and their composite in an unselected population of patients with HFPEF. Methods: 643 outpatients (age 72+12 years; 41% females) with HFPEF (ejection fraction ≥40%) enrolled in the Swedish Heart Failure Registry between 2005 and 2012 and reporting NT-proBNP levels assessment at initial registration and at follow-up were prospectively studied. Patients were divided into 2 groups according the median value of NT-proBNP absolute change that was 0 pg/ml. Median follow-up from first measurement was 2.25 years (IQR: 1.43 to 3.81). Adjusted Cox’s regression models were performed using total mortality, HF hospitalization (with censoring at death) and their composite as outcomes. Results: After adjustments for 19 baseline variables including baseline NT-proBNP, as compared with an increase in NT-proBNP levels at 6 months (NT-proBNP change>0 pg/ml), a reduction in NT-proBNP levels (NT-proBNP change<0 pg/ml) was associated with a 45.2% reduction in risk of all-cause death (HR: 0.548; 95% CI: 0.378 to 0.796; p:0.002), a 50.1% reduction in risk of HF hospitalization (HR: 0.49; 95% CI: 0.362 to 0.689; p<0.001) and a 42.6% reduction in risk of the composite outcome (HR: 0.574; 95% CI: 0.435 to 0.758; p<0.001)(Figure). Conclusions: Reductions in NT-proBNP levels over time are independently associated with an improved prognosis in HFPEF patients. Changes in NT-proBNP could represent a surrogate outcome in phase 2 HFPEF trials.


2019 ◽  
Vol 74 (9) ◽  
pp. 1205-1217 ◽  
Author(s):  
James L. Januzzi ◽  
Tariq Ahmad ◽  
Hillary Mulder ◽  
Adrian Coles ◽  
Kevin J. Anstrom ◽  
...  

2022 ◽  
Vol 9 (1) ◽  
pp. 23
Author(s):  
Alexander A. Berezin ◽  
Ivan M. Fushtey ◽  
Alexander E. Berezin

Background: Apelin is a regulatory vasoactive peptide, which plays a pivotal role in adverse cardiac remodeling and heart failure (HF) with reduced ejection fraction. The purpose of the study was to investigate whether serum levels of apelin is associated with HF with preserved election fraction (HFpEF) in patients with T2DM. Methods: The study retrospectively involved 101 T2DM patients aged 41 to 62 years (48 patients with HFpEF and 28 non-HFpEF patients). The healthy control group consisted of 25 individuals with matched age and sex. Data collection included demographic and anthropometric information, hemodynamic performances and biomarkers of the disease. Transthoracic B-mode echocardiography, Doppler and TDI were performed at baseline. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and apelin were measured by ELISA in all patients at the study entry. Results: Unadjusted multivariate logistic model yielded the only apelin to NT-proBNP ratio (OR = 1.44; p = 0.001), BMI > 34 кг/м2 (OR = 1.07; p = 0.036), NT-proBNP > 458 pmol/mL (OR = 1.17; p = 0.042), LAVI > 34 mL/m2 (OR = 1.06; p = 0.042) and E/e’ > 11 (OR = 1.04; p = 0.044) remained to be strong predictors for HFpEF. After obesity adjustment, multivariate logistic regression showed that the apelin to NT-proBNP ratio < 0.82 × 10−2 units remained sole independent predictor for HFpEF (OR = 1.44; 95% CI: 1.18–2.77; p = 0.001) HFpEF in T2DM patients. In conclusion, we found that apelin to NT-proBNP ratio < 0.82 × 10−2 units better predicted HFpEF in T2DM patients than apelin and NT-proBNP alone. This finding could open new approach for CV risk stratification of T2DM at higher risk of HF.


2007 ◽  
Vol 53 (11) ◽  
pp. 1928-1935 ◽  
Author(s):  
Morten Schou ◽  
Finn Gustafsson ◽  
Caroline N Kistorp ◽  
Pernille Corell ◽  
Andreas Kjaer ◽  
...  

Abstract Background: Obesity is a state characterized by glomerular hyperfiltration and age-related decreases in glomerular filtration rate (GFR). Body mass index (BMI), age, and GFR are associated with plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in chronic heart failure (CHF) patients. We hypothesized that the effects of BMI and age on plasma concentrations of NT-proBNP are associated with GFR. Methods: We obtained clinical data and laboratory test results from 345 CHF patients at the baseline visit in our heart failure clinic and examined the hypothesis using multiple linear regression models. Results: Age (P = 0.0184), BMI (P = 0.0098), hemoglobin (P = 0.0043), heart rhythm (P &lt;0.0001), and left ventricular ejection fraction (P &lt;0.0001) were associated with log(NT-proBNP). After adjustment for GFR estimated by the Cockcroft and Gault equation, the parameter estimates for BMI (P = 0.3807) and age (P = 0.7238) changed markedly and became insignificant. In another model, after adjustment for GFR estimated by the 4-component Modification of Diet in Renal Disease formula (eGFRMDRD), the parameter estimates for age (P = 0.0674) changed markedly and became insignificant, but BMI (P = 0.0067) remained significant and unchanged. The eGFRMDRD is adjusted for body surface area, which may explain the difference. Conclusions: In CHF patients, the effect of age on NT-proBNP is associated with estimates for GFR derived from serum creatinine, and the significance of the effects of BMI on NT-proBNP depends on the method by which GFR is estimated.


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