Dataset Information

Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.

ABSTRACT: BACKGROUND:Among persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized. METHODS:Patients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels between PHIV with HF and uninfected controls with HF. RESULTS:Among 2578 patients with HF, there were 434 PHIV; 90% were prescribed antiretroviral therapy and 62% were virally suppressed. As compared to controls, PHIV had higher admission (3822 [IQR, 2413-7784] pg/ml vs 5546 [IQR, 3257-8792] pg/ml, respectively; P < .001), higher discharge (1922 [IQR, 1045-4652] pg/ml vs 3372 [IQR, 1553-5452] pg/ml, respectively; P < .001), and lower admission-to-discharge changes in NT-proBNP levels (32 vs 48%, respectively; P = .007). Similar findings were noted after stratifying based on left ventricular ejection fraction (LVEF). In a multivariate analysis, cocaine use, a lower LVEF, a higher NYHA class, a higher viral load (VL), and a lower CD4 count were associated with higher NT-proBNP concentrations. In follow-up, among PHIV, a higher admission NT-proBNP concentration was associated with increased cardiovascular mortality (first tertile, 11.5; second tertile, 20; third tertile, 44%; P < .001). Among PHIV, each doubling of NT-proBNP was associated with a 19% increased risk of death. However, among patients living without HIV, each doubling was associated with a 27% increased risk; this difference was attenuated among PHIV with lower VLs and higher CD4 counts. CONCLUSIONS:PHIV with HF had higher admission and discharge NT-proBNP levels, and less change in NT-proBNP concentrations. Among PHIV, VLs and CD4 counts were associated with NT-proBNP concentrations; in follow-up, higher NT-proBNP levels among PHIV were associated with cardiovascular mortality.

SUBMITTER: Alvi RM

PROVIDER: S-EPMC7442853 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.

Alvi Raza M RM Zanni Markella V MV Neilan Anne M AM Hassan Malek Z O MZO Tariq Noor N Zhang Lili L Afshar Maryam M Banerji Dahlia D Mulligan Connor P CP Rokicki Adam A Awadalla Magid M Januzzi James L JL Neilan Tomas G TG

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20200801 5

<h4>Background</h4>Among persons living with human immunodeficiency virus (PHIV), incident heart failure (HF) rates are increased and outcomes are worse; however, the role of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations among PHIV with HF has not been characterized.<h4>Methods</h4>Patients were derived from a registry of those hospitalized with HF at an academic center in a calender year. We compared the NT-proBNP concentrations and the changes in NT-proBNP levels bet ...[more]

PMID: 31740919

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Project description:AimsHypertension is the leading cause for the development of heart failure (HF). Here, we aimed to identify cardiomyocyte stretch-induced circulating biomarkers for predicting hypertension-associated HF.Methods and resultsCirculating levels of 149 proteins were measured by proximity extension assay at baseline examination in 4742 individuals from the Malmö Diet and Cancer study. Protein levels were compared with stretch-activated gene expression changes in cultured neonatal rat ventricular myocytes (NRVMs) in response to 1-48 h of mechanical stretch. We also studied the association between protein levels and hypertension and HF incidence using respectively binary logistic and Cox regressions. Levels of 35 proteins were differentially expressed after Bonferroni correction in incident HF vs. control (P < 3.4E-4). Growth differentiation factor-15 (GDF-15), interleukin-6 (IL-6), IL-1 receptor type 1, and urokinase plasminogen activator surface receptor had corresponding mRNA levels up-regulated by stretch in NRVMs at all time points (P < 0.05). These four proteins were individually associated with increased risk of HF after age and sex adjustment [hazard ratio (HR) per standard deviation: 1.19 ≤ HR ≤ 1.49, P ≤ 4.90E-3]. GDF-15 and IL-6 were associated with HF independently of each other (1.22 ≤ HR ≤ 1.33, P ≤ 0.001). In subjects with hypertension, these associations remained significant after further adjustment for N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (1.23 ≤ HR ≤ 1.45, P ≤ 0.001). A higher fasting value of a GDF-15, IL-6 score aggregate was associated with increased risk of hypertensive HF after adjustment for all traditional risk factors for HF and NT-proBNP (HR = 1.31, P = 2.19E-4).ConclusionsCardiomyocyte mRNA levels of GDF-15 and IL-6 are consistently up-regulated by stretch, and their circulating protein levels predict HF in hypertensive subjects independently of NT-proBNP during long-term follow-up. Our results encourage further studies on lower blood pressure goals in hypertensive subjects with high GDF-15 and IL-6, and interventions targeted at stretch-induced cardiomyocyte expressed biomarkers.

Project description:AimsThe N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a commonly used biomarker in heart failure for diagnosis and prognostication. We aimed to determine the prevalence of NT-proBNP testing, distribution of NT-proBNP concentrations, and factors associated with receiving an NT-proBNP test in patients with heart failure with reduced ejection fraction (HFrEF), including the subset with a worsening heart failure event (WHFE).Methods and resultsThis was a retrospective cohort study using two US databases: (i) the de-identified Humana Research Database between January 2015 and December 2018 and (ii) the Veradigm PINNACLE Registry® between July 2013 and September 2017. We included adult patients with a confirmed diagnosis of HFrEF. In each data source, a subgroup of patients with a WHFE was identified, where a WHFE was defined as a heart failure-related hospitalization or receipt of intravenous diuretics. Bivariate and multivariate analyses were conducted to assess factors associated with receiving NT-proBNP testing. In Cohort 1 (n = 249 238), 9.2% of patients with HFrEF and 10.8% of patients with a WHFE received NT-proBNP testing. When restricted to patients with at least one laboratory claim, 11.3% of patients with HFrEF and 13.2% of those with a WHFE received NT-proBNP testing. In Cohort 2 (n = 91 444), 2.3% of patients with HFrEF were tested. Median (inter-quartile range) NT-proBNP concentrations among patients with HFrEF were 1399 (423-4087) pg/mL in Cohort 1 and 394 (142-688) pg/mL in Cohort 2. Median (inter-quartile range) NT-proBNP concentrations in the subset of patients with a WHFE in each cohort were 2209 (740-5894) and 464 (174-783) pg/mL, respectively. In Cohort 1, 13.4% of all HFrEF patients receiving NT-proBNP testing and 18.9% of patients with a WHFE had NT-proBNP values >8000 pg/mL; in Cohort 2, these percentages were 1.0% and 2.5%, respectively.ConclusionsIn US clinical practice, NT-proBNP testing was not frequently performed in patients with HFrEF. NT-proBNP concentrations varied across data sources and subpopulations within HFrEF.

Project description:BACKGROUND:Elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with clinically overt heart failure (HF). However, whether it provides additive prognostic information for incident HF beyond traditional risk factors and left ventricular (LV) mass index among multi-ethnic asymptomatic individuals has not yet been determined. We studied the associations of plasma NT-proBNP and magnetic resonance imaging defined LV mass index with incident HF in an asymptomatic multi-ethnic population. METHODS AND RESULTS:A total of 5597 multi-ethnic participants without clinically apparent cardiovascular disease underwent baseline measurement of NT-proBNP and were followed for 5.5±1.1 years. Among them, 4163 also underwent baseline cardiac magnetic resonance imaging. During follow-up, 111 participants experienced incident HF. Higher NT-proBNP was significantly associated with incident HF, independent of baseline age, sex, ethnicity, systolic blood pressure, diabetes mellitus, smoking, estimated glomerular filtration rate, medications (anti-hypertensive and statin), LV mass index, and interim myocardial infarction (hazard ratio: 1.95 per 1U log NT-proBNP increment, 95% CI 1.54-2.46, P<0.001). This relationship held among different ethnic groups, non-Hispanic whites, African-Americans, and Hispanics. Most importantly, NT-proBNP provided additive prognostic value beyond both traditional risk factors and LV mass index for predicting incident HF (integrated discrimination index=0.046, P<0.001; net reclassification index; 6-year risk probability categorized by <3%, 3-10%, >10% =0.175, P=0.019; category-less net reclassification index=0.561, P<0.001). CONCLUSIONS:Plasma NT-proBNP provides incremental prognostic information beyond traditional risk factors and the magnetic resonance imaging-determined LV mass index for incident symptomatic HF in an asymptomatic multi-ethnic population. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT00005487.

Project description:BackgroundNT-proBNP (N-terminal pro-B-type natriuretic peptide) levels are variably elevated in heart failure with preserved ejection fraction (HFpEF), even in the presence of increased left ventricular filling pressures. NT-proBNP levels are prognostic in HFpEF and have been used as an inclusion criterion for several recent randomized clinical trials. However, the underlying biologic differences between HFpEF participants with high and low NT-proBNP levels remain to be fully understood.MethodsWe measured 4928 proteins using an aptamer-based proteomic assay (SOMAScan) in available plasma samples from 2 cohorts: (1) Participants with HFpEF enrolled in the PHFS (Penn Heart Failure Study; n=253); (2) TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) participants in the Americas (n=218). We assessed the relationship between SOMAScan-derived plasma NT-proBNP and levels of other proteins available in the SOMAScan assay version 4 using robust linear regression, with correction for multiple comparisons, followed by pathway analysis.ResultsNT-proBNP levels exhibited prominent proteome-wide associations in PHFS and TOPCAT cohorts. Proteins most strongly associated with NT-proBNP in both cohorts included SVEP1 (sushi, von Willebrand factor type-A, epidermal growth factor, and pentraxin domain containing 1; βTOPCAT=0.539; P<0.0001; βPHFS=0.516; P<0.0001) and ANGPT2 (angiopoietin 2; βTOPCAT=0.571; P<0.0001; βPHFS=0.459; P<0.0001). Canonical pathway analysis demonstrated consistent associations with multiple pathways related to fibrosis and inflammation. These included hepatic fibrosis and inhibition of matrix metalloproteases. Analyses using cut points corresponding to estimated quantitative concentrations of 360 pg/mL (and 480 pg/mL in atrial fibrillation) revealed similar proteomic associations.ConclusionsCirculating NT-proBNP levels exhibit prominent proteomic associations in HFpEF. Our findings suggest that higher NT-proBNP levels in HFpEF are a marker of fibrosis and inflammation. These findings will aid the interpretation of NT-proBNP levels in HFpEF and may guide the selection of participants in future HFpEF clinical trials.

Dataset Information

Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.

Publications

Amino-terminal Pro-B-Type Natriuretic Peptide Among Patients Living With Both Human Immunodeficiency Virus and Heart Failure.

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