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Background: At present, 4 prescription therapies have been approved by the US Food and Drug Administration for the treatment of chronic idiopathic constipation (CIC) in adults., Objectives: To compare persistence with and adherence to prucalopride vs 3 other prescription medications for CIC in a US population., Methods: This retrospective, observational cohort study used data from the IBM MarketScan Commercial Claims and Encounters and Medicare Supplemental Databases (January 2015-June 2020). Inclusion criteria were patients (aged ≥18 years) with at least 1 prescription fill for prucalopride, lubiprostone, linaclotide, or plecanatide on or after April 2, 2019 (commercial availability of prucalopride), and at least 1 constipation-related diagnosis code. Persistence was assessed by time to discontinuation, and adherence was assessed by the proportion of days covered (PDC) and the proportion of patients who achieved PDC of at least 80%. Adjusted hazard ratios (HRs) for discontinuation and odds ratios for adherence were calculated., Results: A total of 14,700 patients (mean age = 48.3 years; female = 81.9%) were included (prucalopride, n = 675; lubiprostone, n = 1,591; linaclotide, n = 11,105; plecanatide, n = 1,329). After adjusting for confounding factors, the HRs for discontinuation were significantly higher for all comparator medications compared with prucalopride after 2 months (HR [95% CI]: lubiprostone, 1.70 [1.48-1.95]; linaclotide, 1.25 [1.10-1.41]; plecanatide, 1.31 [1.13-1.51], all P < 0.001). The unadjusted mean (SD) PDC was 0.53 (0.32) with prucalopride compared with 0.41 (0.31); P less than 0.001 with lubiprostone, 0.48 (0.31), P less than 0.05 with linaclotide, and 0.48 (0.29), P = 0.98 with plecanatide. The comparator medications were all associated with lower odds of achieving PDC of at least 80% relative to prucalopride (odds ratio [95% CI]: lubiprostone, 0.52 [0.40-0.69], P < 0.001; linaclotide, 0.73 [0.58-0.93], P = 0.009; plecanatide, 0.70 [0.53-0.93], P = 0.015)., Conclusions: The findings of this study indicate that prucalopride has higher treatment persistence and adherence compared with other CIC prescription medications. This research represents the first instance of a real-world claims study showcasing such outcomes.

Background: Natriuretic peptides (NPs) are hormones with a range of key functions vital for cardiometabolic health. However, the reference ranges of NPs and the prevalence of NP deficiency in the healthy United States population remains poorly defined., Objectives: This study aims to establish the reference range for N-terminal pro-B-type natriuretic peptide (NT-proBNP) values and to assess the prevalence of NP deficiency in a nationally representative healthy United States population., Methods: Healthy participants with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey were included. Weighted multivariable-adjusted linear regression models were used to assess the adjusted percentage difference of NT-proBNP concentrations by sex and race and ethnicity. NP deficiency was defined as concentrations <2.5th percentile in the study cohort., Results: Among 18,145 individuals (median age: 33.9 years [IQR: 17.1-49.0 years], 49.8% males, and 68.5% non-Hispanic White individuals), females had similar NT-proBNP concentrations in the 1-10 years group (4.2% [95% CI: -3.3% to 12.2%]), and highest differences in the 20-30 years group (150.5% [95% CI: 123.5%-180.8%]) compared with males in their respective age groups. Compared with non-Hispanic White individuals, non-Hispanic Black individuals had lower NT-proBNP concentrations in the 1- to 10-years group (19.6% [95% CI: 10.7%-27.6%]), and these differences were most pronounced in the 30-40 years group (40.2% [95% CI: 33.7%-46.0%]). An estimated 9.1 million United States individuals had NP deficiency. NP deficiency was associated with a higher risk of cardiometabolic diseases such as hypertension, dyslipidemia, obesity, and insulin resistance., Conclusions: This study establishes the normative NP concentrations across the lifespan of a healthy United States population., Competing Interests: Funding Support and Author Disclosures Dr Arora is supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health awards R01HL160982, R01HL163852, R01HL163081, and K23HL146887; and has received grant support from Merck Sharp & Dohme LLC and Bristol-Myers Squibb and consulting income from Bristol-Myers Squibb, which are all unrelated to this work. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Plasma concentrations of B-type natriuretic peptide (BNP) and troponin are often measured for diagnostic purposes when patients are admitted with heart failure, but their prognostic value when measured soon after admission is uncertain. We aimed to investigate the added prognostic value of admission measurements of BNP and troponins in patients with acute heart failure.Methods and Results: Multivariable prognostic models for death or any worsening heart failure (WHF) or rehospitalization for WHF by 30 days, 30-day death or rehospitalization for WHF, and 90-day mortality were constructed using baseline data from the Value of Endothelin Receptor Inhibition with Tezosentan in Acute heart failure Studies (VERITAS) including BNP and troponin I. Of 1347 patients, the median (interquartile range) value of BNP was 422 (156-945) pg/mL and 855 (63%) had measurable troponin I. By 30 days, 432 patients had died or experienced WHF. Clinical variables had only moderate predictive performance that was not substantially improved by BNP or troponin I (c-indices 0.6528 and 0.6595, respectively). By 30 days, 150 patients died or were rehospitalized for WHF. The c-index using clinical variables (0.6855) was not improved by adding biomarkers. By 90 days, 135 patients had died. The c-index for mortality was somewhat better than for composite outcomes (0.7394) but improved little with biomarkers (0.7461).Conclusion: Routine clinical data recorded at the time of admission in patients with acute heart failure are poor at predicting recurrent admissions but somewhat better at predicting mortality. Neither BNP nor troponin measured at admission improved predictions; measurement closer to discharge, or of other novel biomarkers, might perform differently. [ABSTRACT FROM AUTHOR]

The article discusses the use of B-type natriuretic peptide (BNP) and N-terminal-proBNP (NT-proBNP) in heart failure (HF) management. It states that alternative medicine is necessary in HF since it is the most lethal condition in modern medicine that affects millions of patients in the U.S. It adds that HF patients are often hospitalized, causing a financial burden on the healthcare system.

The discrimination of a risk prediction model measures that model's ability to distinguish between subjects with and without events. The area under the receiver operating characteristic curve (AUC) is a popular measure of discrimination. However, the AUC has recently been criticized for its insensitivity in model comparisons in which the baseline model has performed well. Thus, 2 other measures have been proposed to capture improvement in discrimination for nested models: the integrated discrimination improvement and the continuous net reclassification improvement. In the present study, the authors use mathematical relations and numerical simulations to quantify the improvement in discrimination offered by candidate markers of different strengths as measured by their effect sizes. They demonstrate that the increase in the AUC depends on the strength of the baseline model, which is true to a lesser degree for the integrated discrimination improvement. On the other hand, the continuous net reclassification improvement depends only on the effect size of the candidate variable and its correlation with other predictors. These measures are illustrated using the Framingham model for incident atrial fibrillation. The authors conclude that the increase in the AUC, integrated discrimination improvement, and net reclassification improvement offer complementary information and thus recommend reporting all 3 alongside measures characterizing the performance of the final model. [ABSTRACT FROM AUTHOR]

Crotalus oreganus abyssus is a rattlesnake that is usually found in the Grand Canyon, United States of America. Knowledge regarding the composition of C. o. abyssus venom is scarce. New natriuretic peptides (NPs) have been isolated and characterized from the venoms of members of the Crotalinae family. The NP family comprises three members, ANP (atrial natriuretic peptide), BNP (b-type natriuretic peptide) and CNP (c-type natriuretic peptide), and has an important role in blood pressure regulation and electrolyte homeostasis. The aim of the present study was to characterize a novel natriuretic-like peptide (Coa_NP2), isolated from C. o. abyssus venom. The Coa_NP2 presents an average molecular mass of 3419.88Da (theoretical average molecular mass 3418.94Da, monoisotopic molecular mass 3416.66Da and theoretical PI 7.78) and its amino acid sequence presents the loop region that is characteristic of natriuretic peptides. The peptide has 32 amino acids and its complete sequence is SYGISSGCFGLKLDRIGTMSGLGCWRLLQDSP. Coa_NP2 is a natriuretic peptide of the ANP/BNP-like family, since the carboxyterminal region of CNP has its own NP domain. We demonstrate, herein, that Coa_NP2 produces a dose-dependent decrease in mean arterial pressure in rats, followed by significant increases in concentrations of markers of nitric oxide formation measured in the plasma and vasorelaxation in a thoracic aortic ring bath. The structural and biological aspects confirm Coa_NP2 as a new natriuretic peptide, isolated from snake venom. [ABSTRACT FROM AUTHOR]

The article discusses the study which investigates the association of corin 1555 (P568) Allele with impaired brain natriuretic peptide processing and adverse outcomes for Blacks with systolic heart failure in the U.S. It notes that the study analyzes the significance of interaction between the corin 1555 allele and treatment assignment. It discovers that corin is associated with an increase of death and heart failure hospitalization in patients after receiving standard neurohormonal blockade.

This article describes the physiologic background for the use of nesiritide, a human B-type natriuretic peptides (BNP), and reviews the clinical experience with the use of nesiritide in the treatment of decompensated heart failure. Nesiritide has been recently approved by the U.S. Food and Drug Administration for the intravenous treatment of patients with decompensated congestive heart failure. The natriuretic peptide family consists of three peptides, amino-acid peptide, BNP, and C-type natriuretic peptide and plays an important role in the prevention of plasma volume expansion and hypertension.

Document Reviewers: Rudolf A. de Boer (CPG Review Coordinator) (Netherlands), P. Christian Schulze (CPG Review Coordinator) (Germany), Magdy Abdelhamid (Egypt), Victor Aboyans (France), Stamatis Adamopoulos (Greece), Stefan D. Anker (Germany), Elena Arbelo (Spain), Riccardo Asteggiano (Italy), Johann Bauersachs (Germany), Antoni Bayes-Genis (Spain), Michael A. Borger (Germany), Werner Budts (Belgium), Maja Cikes (Croatia), Kevin Damman (Netherlands), Victoria Delgado (Netherlands), Paul Dendale (Belgium), Polychronis Dilaveris (Greece), Heinz Drexel (Austria), Justin Ezekowitz (Canada), Volkmar Falk (Germany), Laurent Fauchier (France), Gerasimos Filippatos (Greece), Alan Fraser (United Kingdom), Norbert Frey (Germany), Chris P. Gale (United Kingdom), Finn Gustafsson (Denmark), Julie Harris (United Kingdom), Bernard Iung (France), Stefan Janssens (Belgium), Mariell Jessup (United States of America), Aleksandra Konradi (Russia), Dipak Kotecha (United Kingdom), Ekaterini Lambrinou (Cyprus), Patrizio Lancellotti (Belgium), Ulf Landmesser (Germany), Christophe Leclercq (France), Basil S. Lewis (Israel), Francisco Leyva (United Kingdom), AleVs Linhart (Czech Republic), Maja-Lisa Løchen (Norway), Lars H. Lund (Sweden), Donna Mancini (United States of America), Josep Masip (Spain), Davor Milicic (Croatia), Christian Mueller (Switzerland), Holger Nef (Germany), Jens-Cosedis Nielsen (Denmark), Lis Neubeck (United Kingdom), Michel Noutsias (Germany), Steffen E. Petersen (United Kingdom), Anna Sonia Petronio (Italy), Piotr Ponikowski (Poland), Eva Prescott (Denmark), Amina Rakisheva (Kazakhstan), Dimitrios J. Richter (Greece), Evgeny Schlyakhto (Russia), Petar Seferovic (Serbia), Michele Senni (Italy), Marta Sitges (Spain), Miguel Sousa-Uva (Portugal), Carlo G. Tocchetti (Italy), Rhian M. Touyz (United Kingdom), Carsten Tschoepe (Germany), Johannes Waltenberger (Germany/Switzerland) All experts involved in the development of these guidelines have submitted declarations of interest. These have been compiled in a report and published in a supplementary document simultaneously to the guidelines. The report is also available on the ESC website www.escardio.org/guidelines For the Supplementary Data which include background information and detailed discussion of the data that have provided the basis for the guidelines see European Heart Journal online., (© 2022 European Society of Cardiology This article has been co-published with permission in European Heart Journal (published by Oxford University Press on behalf of European Society of Cardiology) and European Journal of Heart Failure (published by John Wiley & Sons Ltd on behalf of European Society of Cardiology).)

Background: Hypertension is a common condition that increases risk for future cardiovascular disease. N-terminal B-type natriuretic peptide (NT-proBNP) is higher in individuals with hypertension, but studies of its association with hypertension risk have been mixed., Methods: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study enrolled 30,239 U.S. Black or White adults aged ≥45 years from 2003 to 2007. A subcohort included 4,400 participants who completed a second assessment in 2013-2016. NT-proBNP was measured by immunoassay in 1,323 participants without baseline hypertension, defined as blood pressure ≥140/90 or self-reported antihypertensive prescriptions. Two robust Poisson regression models assessed hypertension risk, yielding incidence rate ratios (IRRs): Model 1 included behavioral and demographic covariates and Model 2 added risk factors. A sensitivity analysis using a less conservative definition of hypertension (blood pressure ≥130/80 or self-reported antihypertensive prescriptions) was conducted., Results: Four hundred and sixty-six participants developed hypertension after mean follow-up of 9.4 years. NT-proBNP was not associated with hypertension (Model 2 IRR per SD log NT-proBNP 1.01, 95% confidence interval 0.92-1.12), with no differences by sex, body mass index, age, or race. Similar findings were seen in lower-threshold sensitivity analysis., Conclusions: NT-proBNP was not associated with incident hypertension in REGARDS; this did not differ by race or sex., (© American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background Elevated natriuretic peptides (NP) are associated with adverse cerebrovascular conditions including stroke, cerebral small vessel disease, and dementia. However, the mechanisms underlying these associations remain unclear. In this study, we examined the relationship of NT-proBNP (N-terminal pro brain NP) and NT-proANP (N-terminal pro atrial NP) with cerebrovascular function, measured by cerebral autoregulation. Methods and Results We included 154 participants (mean age 56±4 years old) from the CARDIA (Coronary Artery Risk Development in Young Adults) cohort. NT-proBNP and NT-proANP were measured in blood samples from the year 25 examination using electrochemiluminescence Immunoassay and enzyme-linked immunoassay, respectively. Dynamic cerebral autoregulation (dCA) was assessed at the year 30 examination by transcranial Doppler ultrasound, using transfer function analysis (phase and gain) of spontaneous blood pressure and flow velocity oscillations, where lower phase and higher gain reflect less efficient cerebral autoregulation. We used multivariable linear regression models adjusted for demographics, vascular risk factors, and history of kidney and cardiac diseases. Higher NT-proBNP levels at year 25 were associated with lower phase (β [95% CI]=-5.30 lower degrees of phase [-10.05 to -0.54]) and higher gain (β [95% CI]=0.06 higher cm/s per mm Hg of gain [0.004-0.12]) at year 30. Similarly, higher NT-proANP levels were associated with lower phase (β [95% CI]=-9.08 lower degrees of phase [-16.46 to -1.70]). Conclusions Higher circulating levels of NT-proBNP and NT-proANP are associated with less efficient dCA 5 years later. These findings link circulating NP to cerebral autoregulation and may be one mechanism tying NP to adverse cerebrovascular outcomes.

An introduction is presented in which the authors discuss a report in the issue which deals with the prognostic factors such as natriuretic peptide levels which are associated with short and long term mortality in older heart failure patients in America, and it mentions a Brain Natriuretic Peptide.

Background: Most heart failure (HF) risk scores have been derived from cohorts of stable HF patients and may not incorporate up to date treatment regimens or deep phenotype characterization that change baseline risk over the short- and long-term follow-up period. We undertook the current analysis of participants in the GUIDE-IT (Guiding Evidence-Based Therapy Using Biomarker Intensified Treatment) trial to address these limitations., Methods and Results: The GUIDE-IT study randomized 894 high-risk patients with HF and reduced ejection fraction (≤ 40%) to biomarker-guided treatment strategy vs. usual care. We performed risk modelling using Cox proportional hazards models and analysed the relationship between 35 baseline clinical factors and the primary composite endpoint of cardiovascular (CV) death or HF hospitalization, the secondary endpoint of all-cause mortality, and the exploratory endpoint of 90-day HF hospitalization or death. Prognostic relationships for continuous variables were examined and key predictors were identified using a backward variable selection process. Predictive models and risk scores were developed. Over a median follow-up of 15 months, the cumulative number of HF hospitalizations and CV deaths was 328 out of 894 patients (Kaplan-Meier event rate 34.5% at 12 months). Frequency of all-cause deaths was 143 out of 894 patients (Kaplan-Meier event rate 12.2% at 12 months). Outcomes for the primary and secondary endpoints between strategy arms of the study were similar. The most important predictor that was present in all three models was the baseline natriuretic peptide level. Hispanic ethnicity, low sodium and high heart rate were present in two of the three models. Other important predictors included the presence or absence of a device, New York Heart Association class, HF duration, black race, co-morbidities (sleep apnoea, elevated creatinine, ischaemic heart disease), low blood pressure, and a high congestion score., Conclusion: Risk models using readily available clinical information are able to accurately predict short- and long-term CV events and may be useful in optimizing care and enriching patients for clinical trials., Clinical Trial Registration: ClinicalTrials.gov ID number NCT01685840., (© 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology.)

Background & Aims: Patients with non-alcoholic fatty liver disease (NAFLD) are thought to be at increased risk of cardiovascular morbidity and mortality. However, the relationships between NAFLD and subclinical myocardial injury or structural heart disease are unknown., Methods: We conducted a cross-sectional analysis of 8668 participants from the Atherosclerosis Risk in Communities (ARIC) Study, who showed no clinical evidence of cardiovascular disease. We used levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST] and gamma-glutamyl transpeptidase [GGT]), in the context of no history of elevated alcohol consumption as non-invasive surrogates of NAFLD. We used highly sensitive cardiac troponin T (hs-cTnT) and N-terminal pro-Brain natriuretic peptide (NT-proBNP) as biomarkers of myocardial damage and function., Results: In this population-based study (mean age 63 years, 60% women, 78% white), higher levels of ALT, AST, and GGT, even within the normal range, were significantly and independently associated with detectable (hs-cTnT >3 ng/L) and elevated (hs-cTnT ⩾14 ng/L) concentrations of hs-cTnT. The adjusted odds ratios (95% confidence interval) for elevated liver enzymes (vs. normal levels) with elevated hs-cTnT were: 1.65 (1.28-2.14) for ALT, 1.90 (1.36-2.68) for AST, and 1.55 (1.13-2.12) for GGT. Furthermore, there was evidence for inverse associations of ALT and AST with NT-proBNP., Conclusions: Our results suggest that elevated liver enzyme levels in the absence of elevated alcohol consumption may be associated with subclinical myocardial injury. The inverse association between NT-proBNP and both ALT and AST supports the recently described metabolic role of natriuretic peptides., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

We sought to investigate the role of aldosterone as a mediator of disease and its relationship with the counter-regulatory natriuretic peptide (NP) system. We measured plasma aldosterone (n=1674; aged≥45 years old) in a random sample of the general population from Olmsted County, MN. In a multivariate logistic regression model, aldosterone analyzed as a continuous variable was associated with hypertension (odds ratio [OR]=1.75; 95% confidence interval [CI]=1.57-1.96; P<0.0001), obesity (OR=1.34; 95% CI=1.21-1.48; P<0.0001), chronic kidney disease (OR=1.39; 95% CI=1.22-1.60; P<0.0001), central obesity (OR=1.47; 95% CI=1.32-1.63; P<0.0001), metabolic syndrome (OR=1.41; 95% CI=1.26-1.58; P<0.0001), high triglycerides (OR=1.23; 95% CI=1.11-1.36; P<0.0001), concentric left ventricular hypertrophy (OR=1.22; 95% CI=1.09-1.38; P=0.0007), and atrial fibrillation (OR=1.24; 95% CI=1.01-1.53; P=0.04), after adjusting for age and sex. The associations with hypertension, central obesity, metabolic syndrome, triglycerides, and concentric left ventricular hypertrophy remained significant after further adjustment for body mass index, NPs, and renal function. Furthermore, aldosterone in the highest tertile correlated with lower NP levels and increased mortality. Importantly, most of these associations remained significant even after excluding subjects with aldosterone levels above the normal range. In conclusion, we report that aldosterone is associated with hypertension, chronic kidney disease, obesity, metabolic syndrome, concentric left ventricular hypertrophy, and lower NPs in the general community. Our data suggest that aldosterone, even within the normal range, may be a biomarker of cardiorenal and metabolic disease. Further studies are warranted to evaluate a therapeutic and preventive strategy to delay the onset and progression of disease, using mineralocorticoid antagonists or chronic NP administration in high-risk subjects identified by plasma aldosterone., (© 2014 American Heart Association, Inc.)

Background: B-type natriuretic peptide (BNP) is a marker for heart failure (HF) severity, but its association with hospital readmission is not well defined., Methods and Results: We identified all hospital discharges (n=109 875) with a primary diagnosis of HF in the Veterans Affairs Health Care System from 2006 to 2009. We examined the association between admission (n=53 585), discharge (n=24 326), and change in BNP (n=7187) and 30-day readmission for HF or other causes. Thirty-day HF readmission was associated with elevated admission BNP, elevated discharge BNP, and smaller percent change in BNP from admission to discharge. Patients with a discharge BNP ≥ 1000 ng/L had an unadjusted 30-day HF readmission rate over 3 times as high as patients whose discharge BNP was ≤ 200 ng/L (15% vs. 4.1%). BNP improved discrimination and risk classification for 30-day HF readmission when added to a base clinical model, with discharge BNP having the greatest effect (C-statistic, 0.639 to 0.664 [P<0.0001]; net reclassification improvement, 9% [P<0.0001]). In contrast, 30-day readmission for non-HF causes was not associated with BNP levels during index HF hospitalization., Conclusions: In this study of over 50 000 veterans hospitalized with a primary diagnosis of HF, BNP levels measured during hospitalization were associated with 30-day HF readmission, but not readmissions for other causes. These data may help guide future study aimed at identifying the optimal timing for hospital discharge and help allocate high-intensity, HF-specific transitional care interventions to the patients most likely to benefit., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)