The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure.
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ABSTRACT:
SUBMITTER: Santema BT
PROVIDER: S-EPMC7042190 | biostudies-literature | 2020 Mar
REPOSITORIES: biostudies-literature
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The influence of atrial fibrillation on the levels of NT-proBNP versus GDF-15 in patients with heart failure.
Santema Bernadet T BT Chan Michelle M Y MMY Tromp Jasper J Dokter Martin M van der Wal Haye H HH Emmens Johanna E JE Takens Janny J Samani Nilesh J NJ Ng Leong L LL Lang Chim C CC van der Meer Peter P Ter Maaten Jozine M JM Damman Kevin K Dickstein Kenneth K Cleland John G JG Zannad Faiez F Anker Stefan D SD Metra Marco M van der Harst Pim P de Boer Rudolf A RA van Veldhuisen Dirk J DJ Rienstra Michiel M Lam Carolyn S P CSP Voors Adriaan A AA
Clinical research in cardiology : official journal of the German Cardiac Society 20190701 3
<h4>Background</h4>In heart failure (HF), levels of NT-proBNP are influenced by the presence of concomitant atrial fibrillation (AF), making it difficult to distinguish between HF versus AF in patients with raised NT-proBNP. It is unknown whether levels of GDF-15 are also influenced by AF in patients with HF. In this study we compared the plasma levels of NT-proBNP versus GDF-15 in patients with HF in AF versus sinus rhythm (SR).<h4>Methods</h4>In a post hoc analysis of the index cohort of BIOST ...[more]
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Project description:We investigated whether growth differentiation factor-15 (GDF-15), also known as macrophage inhibitory cytokine-1 (MIC-1), levels are associated with a prothrombotic state in atrial fibrillation (AF) as compared to N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (cTnI-hs). In 103 patients with AF assessed off anticoagulation (age: 71.0 [65.0-76.0] years; CHA2DS2-VASc score: 4.6 ± 1.7), we measured endogenous thrombin potential (ETP), plasma fibrin clot permeability (Ks, a measure of clot density) and clot lysis time (CLT) and other hemostatic parameters, along with GDF-15, NT-proBNP, and cTnI-hs. GDF-15 positively correlated with ETP and CLT (r = 0.25, P = 0.01 and R = 0.56, P < 0.0001, respectively) but not with Ks, von Willebrand factor, thrombin-activatable fibrinolysis inhibitor, plasminogen, antiplasmin or tissue-type plasminogen activator antigen. NT-proBNP showed a stronger association with ETP (r = 0.60, P < 0.0001) and a similar correlation with CLT (R = 0.53, P < 0.0001), while cTnI-hs correlated solely with CLT (R = 0.25, P = 0.01). After adjustment for clinical and laboratory parameters, GDF-15 was a better independent predictor of CLT (unstandardized coefficient B 0.009; 95% confidence interval [CI] 0.006-0.012) than NT-proBNP (B 0.007; 95% CI 0.004-0.010, R (2) = 0.51; P < 0.0001); while among the three biomarkers, only NT-proBNP was an independent predictor of ETP. Elevated GDF-15 and NT-proBNP independently predict impaired fibrin clot lysability, while NT-proBNP is a key predictor of heightened thrombin formation in AF. Our findings suggest that a predictive value of NT-proBNP and GDF-15 in AF could be in part attributed to their association with prothrombotic blood alterations.
| S-EPMC7098929 | biostudies-literature
Project description:AimsHeart failure (HF) and atrial fibrillation (AF) frequently coexist and are both associated with increased levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP). It is known that AF impairs the diagnostic accuracy of NT-proBNP for HF. The aim of the present study was to compare the diagnostic and predictive accuracy of NT-proBNP for HF and AF in stable outpatients with cardiovascular risk factors.Methods and resultsData were obtained from the DIAST-CHF trial, a prospective cohort study that recruited individuals with cardiovascular risk factors and followed them up for 12 years. Data were validated in three independent population-based cohorts using the same inclusion/exclusion criteria: LIFE-Adult (n = 2869), SHIP (n = 2013), and SHIP-TREND (n = 2408). Serum levels of NT-proBNP were taken once at baseline. The DIAST-CHF study enrolled 1727 study participants (47.7% female, mean age 66.9 ± 8.1 years). At baseline, patients without AF or HF (n = 1375) had a median NT-proBNP of 94 pg/mL (interquartile range 51;181). In patients with AF (n = 93), NT-proBNP amounted to 667 (215;1130) pg/mL. It was significantly higher than in the first group (P < 0.001) and compared with those with only HF [n = 201; 158 (66;363) pg/mL; P < 0.001]. The highest levels of NT-proBNP [868 (213;1397) pg/mL] were measured in patients with concomitant HF and AF (n = 58; P < 0.001 vs. control and vs. HF, P = 1.0 vs. AF). In patients with AF, NT-proBNP levels did not differ between those with HF and preserved ejection fraction (EF) > 50% [n = 38; 603 (175;1070) pg/mL] and those without HF (P = 1.0). Receiver-operating characteristic curves of NT-proBNP showed a similar area under the curve (AUC) for the detection of AF at baseline (0.84, 95% CI [0.79-0.88]) and for HF with EF < 50% (0.78 [0.72-0.85]; P = 0.18). The AUC for HF with EF > 50% was significantly lower (0.61 [0.56-0.65]) than for AF (P = 0.001). During follow-up, AF was newly diagnosed in 157 (9.1%) and HF in 141 (9.6%) study participants. NT-proBNP was a better predictor of incident AF during the first 2 years (AUC: 0.79 [0.75-0.83]) than of newly diagnosed HF (0.59 [0.55-0.63]; P < 0.001). Data were validated in three independent population-based cohorts (LIFE-Adult, n = 2869; SHIP, n = 2013; and SHIP-TREND, n = 2408).ConclusionsIn stable outpatients, NT-proBNP is a better marker for prevalent and incident AF than for HF. In AF patients, the diagnostic value of NT-proBNP for HF with EF > 50% is very limited.
| S-EPMC8788004 | biostudies-literature
Project description:ObjectiveTo evaluate effects of atrial fibrillation (AF) on cardiac biomarkers and outcomes in a trial population of patients with heart failure (HF) with reduced ejection fraction treated with optimal guideline-directed medical therapy.MethodsWe performed a secondary analysis of 894 patients in the Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in Heart Failure (GUIDE-IT) trial (January 2013-July 2016). Patients were stratified by AF status and compared with regard to guideline-directed medical therapy use, longitudinal levels of N-terminal pro-B type natriuretic peptide (NT-proBNP), and outcomes including HF hospitalization and mortality.ResultsAfter adjustment, AF was associated with a significant increase in the risk of HF hospitalization or cardiovascular death (hazard ratio, 1.28; 95% CI, 1.02 to 1.61; P=0.04) and HF hospitalization (hazard ratio, 1.31; 95% CI, 1.02 to 1.68; P=.03) but with no difference in mortality during a median 15 months of follow-up. There were no significant differences in medication treatment between those with and those without AF. At 90 days, a higher proportion of patients with AF (89.4% vs 81.5%; P=.002) had an NT-proBNP level above 1000 pg/mL (to convert NT-proBNP values to pmol/L, multiply by 0.1182), and AF patients had higher NT-proBNP levels at all time points through 2 years of follow-up.ConclusionAmong patients with HF with reduced ejection fraction, prevalent AF was associated with higher NT-proBNP concentrations through 2 years of follow-up and higher risk for HF hospitalization despite no substantial differences in medical therapy.
| S-EPMC8105522 | biostudies-literature
Project description:Background Novel circulating biomarkers may help in understanding the underlying mechanisms of atrial fibrillation (AF), a challenge for AF management and prevention of cardiovascular (CV) events. Whether glycosylation affects the prognostic value of N-terminal pro-B type natriuretic peptide (NT-proBNP) in AF is still unknown. Objectives To test how deglycosylated total NT-proBNP, NT-proBNP and a panel of biomarkers are associated with: (1) recurrent AF, (2) first hospitalization for CV reasons. Methods A total of 382 patients of the GISSI-AF trial in sinus rhythm with a history of AF, echocardiographic variables, total NT-proBNP, NT-proBNP and nine additional biomarkers [Total N-terminal pro-B type natriuretic peptide (Total NT proBNP), N-terminal pro-B type natriuretic peptide (NTproBNP), Angiopoietin 2 (Ang2), Bone morphogenic protein-10 (BMP10), Dickkopf-related protein-3 (DKK3), Endothelial cell specific molecule-1 (ESM1), Fatty acid-binding protein 3 (FABP3), Fibroblast growth factor 23 (FGF23), Growth differentiation factor-15 (GDF15), Insulin-like growth factor-binding protein-7 (IGFBP7) and Myosin binding protein C3 (MYPBC3)]. were assayed at baseline, 6 and 12 months under blind conditions in a laboratory at Roche Diagnostics, Penzberg, Germany. The associations between circulating biomarkers and AF at the 6- and 12-month visits, and their predictive value, were assessed in multivariable models with logistic regression analysis and Cox proportional hazards regression analysis. Biomarkers associations were modelled for 1SD increase in their level. Results Over a median follow-up of 365 days, 203/382 patients (53.1%) had at least one recurrence of AF and 16.3% were hospitalized for CV reasons. Total NT-proBNP, NT-proBNP, Ang2 and BMP10 showed the strongest associations with ongoing AF. Natriuretic peptides also predicted recurrent AF (total NT-proBNP: HR:1.19[1.04–1.36], p = 0.026; NT-proBNP: HR:1.19[1.06–1.35], p = 0.016; Ang2: HR:1.07[0.95–1.20], p = 0.283; BMP10: HR:1.09[0.96–1.25], p = 0.249) and CV hospitalization (total NT-proBNP: HR:1.57[1.29–1.90], p < 0.001 1.63], p = 0.097). Conclusions The association of total NT-proBNP with the risk of AF first recurrence was similar to that of NT-proBNP, suggesting no influence of glycosylation. Analogous results were obtained for the risk of first hospitalization for CV reasons. Natriuretic peptides, Ang2 and BMP10 were associated with ongoing AF. Findings from the last two biomarkers point to a pathogenic role of cardiac extracellular matrix and cardiomyocyte growth in the myocardium of the right atrium and ventricle. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-021-02358-y.
| S-EPMC8603582 | biostudies-literature
Project description:BackgroundDialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis.Methods and resultsWe compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (n = 80) and with HF (n = 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL, p < 0.001), GDF-15 (7512 [7084] vs. 6005 [4892] pg/mL, p = 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL, p = 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min, p < 0.001). In ROC analyses, a multi-marker model combining clinical covariates, NT-proBNP, GDF-15, and cNEP activity demonstrated best discrimination of HF from controls (AUC = 0.902, 95% CI 0.857-0.947, p < 0.001 vs. base model AUC = 0.785).ConclusionWe present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients.
| S-EPMC7376515 | biostudies-literature
Project description:This study aimed to investigate the association of circulating biomarkers with echocardiographic parameters of atrial remodelling and their potential for predicting atrial fibrillation (AF). In patients with and without AF (n = 21 and n = 60) the following serum biomarkers were determined: soluble ST2 (sST2), Galectin-3 (Gal-3), N-terminal pro-brain natriuretic peptide (NT-proBNP), microRNA (miR)-21, -29a, -133a, -146b and -328. Comprehensive transthoracic echocardiography was performed in all participants. Biomarkers were significantly altered in patients with AF. The echocardiographic parameter septal PA-TDI, indicating left atrial (LA) remodelling, correlated with concentrations of sST2 (r = 0.249, p = 0.048), miR-21 (r = -0.277, p = 0.012), miR-29a (r = -0.269, p = 0.015), miR-146b (r = -0.319, p = 0.004) and miR-328 (r = -0.296, p = 0.008). In particular, NT-proBNP showed a strong correlation with echocardiographic markers of LA remodelling and dysfunction (septal PA-TDI: r = 0.444, p < 0.001, LAVI/a': r = 0.457, p = 0.001, SRa: r = 0.581, p < 0.001). Multivariate Cox regressions analysis highlighted miR-21 and NT-proBNP as predictive markers for AF (miR-21: hazard ratio (HR) 0.16; 95% confidence interval (CI) 0.04-0.7, p = 0.009; NT-proBNP: HR 1.002 95%CI 1.001-1.004, p = 0.006). Combination of NT-proBNP and miR-21 had the best accuracy to discriminate patients with AF from those without AF (area under the curve (AUC)= 0.843). Our findings indicate that miR-21 and NT-proBNP correlate with echocardiographic parameters of atrial remodeling and predict AF, in particular if combined.
| S-EPMC7230176 | biostudies-literature
Project description:BackgroundWe aimed to compare absolute plasma concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and growth differentiation factor 15 (GDF-15) obtained by a conventional immunoassay with the corresponding relative concentrations from a proximity extension assay (PEA) and compare the prognostic impact of the protein levels obtained from these assays.MethodsWe evaluated 437 patients with peripheral arterial disease (PAD) and a population-based cohort of 643 individuals without PAD. Correlations were calculated using Spearman's rank correlation coefficients (rho). The discriminatory accuracy of the protein levels to predict future cardiovascular events was analyzed with Cox regression and presented as time-dependent areas under the receiver-operator-characteristic curves (tdAUCs).ResultsFor NT-proBNP, the two assays correlated with rho 0.93 and 0.93 in the respective cohort. The PEA values leveled off at higher values in both cohorts. The corresponding correlations for GDF-15 were 0.91 and 0.89. At 5 years follow-up, the tdAUCs in the patient cohort were similar for NT-proBNP and GDF-15 regardless of assay used (0.65-0.66). The corresponding tdAUCs in the population-based cohort were between 0.72 and 0.77.ConclusionExcept for the highest levels of NT-proBNP, we suggest that PEA data for NT-proBNP and GDF-15 reliably reflects absolute plasma levels and contains similar prognostic information.
| S-EPMC9872369 | biostudies-literature
Project description:BACKGROUND: Circulating adipocyte fatty acid-binding protein (FABP4) levels are considered to be a link between obesity, insulin resistance, diabetes, and cardiovascular (CV) diseases. In vitro, FABP4 has exhibited cardiodepressant activity by suppressing cardiomyocyte contraction. We have explored the relationship between FABP4 and the N-terminal fragment of pro-B-type natriuretic peptide (NT-proBNP) as a clinical parameter of heart failure (HF). METHODS: We included 179 stable HF patients who were referred to a specialized HF unit, 108 of whom were prospectively followed for up to 6 months. A group of 163 non-HF patients attending a CV risk unit was used as the non-HF control group for the FABP4 comparisons. RESULTS: In the HF patients, FABP4 and NT-proBNP were assayed, along with a clinical and functional assessment of the heart at baseline and after 6 months of specialized monitoring. The FABP4 levels were higher in the patients with HF than in the non-HF high CV risk control group (p<0.001). The FABP4 levels were associated with the NT-proBNP levels in patients with HF (r=0.601, p<0.001), and this association was stronger in the diabetic patients. FABP4 was also associated with heart rate and the results of the 6-minute walk test. After the follow-up period, FABP4 decreased in parallel to NT-proBNP and to the clinical parameters of HF. CONCLUSIONS: FABP4 is associated with the clinical manifestations and biomarkers of HF. It exhibits a parallel evolution with the circulating levels of NT-proBNP in HF patients.
| S-EPMC3653725 | biostudies-literature
Project description:N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a well-established biomarker in heart failure (HF) but controversially discussed as a potential surrogate marker in HF trials. We analyzed the NT-proBNP/mortality relationship in real-world data (RWD) of 108,330 HF patients from the IBM Watson Health Explorys database and compared it with the NT-proBNP / clinical event end-point relationship in 20 clinical HF studies. With a hierarchical statistical model, we quantified the functional relationship and interstudy variability. To independently qualify the model, we predicted outcome hazard ratios in five phase III HF studies solely based on NT-proBNP measured early in the respective study. In RWD and clinical studies, the relationship between NT-proBNP and clinical outcome is well described by an Emax model. The NT-proBNP independent baseline risk (R0 , RWD/studies median (interstudy interquartile range): 5.5%/3.0% (1.7-4.9%)) is very low compared with the potential NT-proBNP-associated maximum risk (Rmax : 55.2%/79.4% (61.5-89.0%)). The NT-proBNP concentration associated with the half-maximal risk is comparable in RWD and across clinical studies (EC50 : 3,880/2,414 pg/mL (1,460-4,355 pg/mL)). Model-based predictions of phase III outcomes, relying on short-term NT-proBNP data only, match final trial results with comparable confidence intervals. Our analysis qualifies NT-proBNP as a surrogate for clinical outcome in HF trials. NT-proBNP levels after short treatment durations of less than 10 weeks quantitatively predict hazard ratios with confidence levels comparable to final trial readout. Early NT-proBNP measurement can therefore enable shorter and smaller but still reliable HF trials.
| S-EPMC8360001 | biostudies-literature
Project description:N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is a versatile biomarker, that has been extensively studied in large cohorts of individuals in the general population, in subjects at risk for developing left ventricular dysfunction and cardiovascular events, and in patients with chronic or acutely decompensated heart failure (HF). In this paper, the pros and cons of using natriuretic peptide testing to manage patients with HF are presented and discussed over 3 broad areas: (1) dyspnea triage in the emergency room, (2) natriuretic peptide-guided treatment of chronic HF, and (3) management of patients with HF in primary care and nursing homes.
| S-EPMC4975180 | biostudies-literature