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• W3084095986 abstract "HomeCirculationVol. 142, No. 10Racial Differences in Serial NT-proBNP Levels in Heart Failure Management Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBRacial Differences in Serial NT-proBNP Levels in Heart Failure ManagementInsights From the GUIDE-IT Trial Vibhu Parcha, MD Nirav Patel, MD Rajat Kalra, MBChB Garima Arora, MD James L. Januzzi Jr, MD G. Michael Felker, MD Thomas J. Wang, MD Pankaj AroraMD Vibhu ParchaVibhu Parcha Division of Cardiovascular Disease (V.P, G.A., P.A.), University of Alabama at Birmingham. Search for more papers by this author , Nirav PatelNirav Patel Department of Medicine (N.P.), University of Alabama at Birmingham. Search for more papers by this author , Rajat KalraRajat Kalra https://orcid.org/0000-0002-8982-0595 Cardiovascular Division, University of Minnesota, Minneapolis (R.K.). Search for more papers by this author , Garima AroraGarima Arora Division of Cardiovascular Disease (V.P, G.A., P.A.), University of Alabama at Birmingham. Search for more papers by this author , James L. Januzzi JrJames L. Januzzi Jr https://orcid.org/0000-0002-8338-1798 Cardiology Division, Massachusetts General Hospital, Baim Institute for Clinical Research, Boston (J.L.J.). Search for more papers by this author , G. Michael FelkerG. Michael Felker Duke Clinical Research Institute, Durham, NC (G.M.F.). Search for more papers by this author , Thomas J. WangThomas J. Wang Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (T.J.W.). Search for more papers by this author , Pankaj AroraPankaj Arora Pankaj Arora, MD, Division of Cardiovascular Disease, 1670 University Boulevard, Volker Hall B140, University of Alabama at Birmingham, Birmingham, AL 35294. Email E-mail Address: [email protected] https://orcid.org/0000-0003-2420-3550 Division of Cardiovascular Disease (V.P, G.A., P.A.), University of Alabama at Birmingham. Section of Cardiology, Birmingham Veterans Affairs Medical Center, AL (P.A.). Search for more papers by this author Originally published8 Sep 2020https://doi.org/10.1161/CIRCULATIONAHA.120.046374Circulation. 2020;142:1018–1020Racial differences exist in the circulating natriuretic peptides (NPs)1 and they manifest starting in early adulthood.2 N-terminal pro-B-type NP (NT-proBNP) levels have a weaker predictive ability for heart failure (HF) in Black individuals with obesity and kidney dysfunction.3 Use of serial NT-proBNP levels was tested in the multicenter, randomized GUIDE-IT trial (Guiding Evidence-Based Therapy Using Biomarker-Intensified Treatment in HF), the results of which were neutral.4 An analysis from GUIDE-IT indicates that treatment to a therapeutic NT-proBNP target of ≤1000 pg/mL is an important component of optimal HF management.5 However, the prognostic value of achieving the threshold of NT-proBNP ≤1000 pg/mL has not been examined in Black individuals. We aimed to evaluate the racial differences in the prognostic implications of guiding HF management to a target NT-proBNP level of ≤1000 pg/mL among the GUIDE-IT trial participants.Anonymized study data are publically available at the US National Heart, Lung, and Blood Institute BioLINCC data repository. All patients provided written informed consent, and the institutional review boards at each site approved the study. Individuals who self-identified as Black or White, and who did not experience adverse cardiovascular outcomes (HF hospitalization or death caused by cardiovascular causes) in the first 6 weeks were included in the study. The achievement of target NT-proBNP cutoff was defined using the NT-proBNP levels at the 6-week visit. Baseline characteristics were compared using descriptive statistics, with the continuous data compared using a Wilcoxon rank-sum test and the categorical variables compared using a χ2 test. Survival analyses were conducted for the risk of adverse cardiovascular outcomes using multivariable-adjusted Cox proportional hazard models. The rate of adverse cardiovascular outcomes was estimated using Poisson regression. Multivariable-adjusted incidence rate ratio was computed for the racial groups using 6-week NT-proBNP levels. The models were adjusted for age, sex, body-mass index, baseline NT-proBNP, baseline left ventricular ejection fraction, blood pressure, atrial fibrillation, heart rate, sodium and potassium levels, creatinine, ischemic heart disease, sleep apnea, depression, use of implantable cardioverter-defibrillator/pacemaker, and treatment arm.5 Interaction testing was done using multiplicative interaction terms (race × achievement of target NT-proBNP levels). All analyses were conducted using SAS 9.4 (Cary, NC).There were 608 patients with available data. Of them, 37.5% were Black. Similar demographic profiles and clinical characteristics were noted by race. Significantly lower NT-proBNP levels (2025.5 pg/mL [25th percentile, 75th percentile: 1155.5, 3868.5 pg/mL] vs 2447.5 pg/mL [1153.0, 4998.5 pg/mL]; adjusted P=0.002) and left ventricular ejection fraction (20.0% [15.0, 30.0%] vs 25.0% [20.0, 30.0%]; adjusted P<0.001) was present among Black patients at baseline. The event rate for adverse cardiovascular outcomes was 9.5% (8/84) and 29.1% (86/296) in White patients with HF and NT-proBNP levels ≤1000 pg/mL and >1000 pg/mL, respectively. The event rate among Black patients was 24.1% (13/54) for those who achieved the target NT-proBNP levels and 48.9% (89/174) for those who did not. Among White patients with HF, those who did not achieve the target NT-proBNP levels had a greater risk of adverse cardiovascular outcomes compared with those with NT-proBNP levels ≤1000 pg/mL (hazard ratio [HR], 3.42 [95% CI, 1.55–7.54]; P=0.002). Similarly, among Black individuals, patients who did not achieve the target NT-proBNP levels had a higher risk of developing adverse cardiovascular outcomes compared with those having NT-proBNP levels ≤1000 pg/mL (HR, 2.58 [95% CI, 1.38–4.83]; P=0.003; Figure, A). There was no significant interaction between race and achievement of target NT-proBNP levels on the outcome (P>0.10). The rates of adverse cardiovascular outcomes across different strata of NT-proBNP levels is depicted in Figure, B.Download figureDownload PowerPointFigure. Risk of adverse cardiovascular outcomes in heart failure stratified by race and NT-proBNP levels.A, Risk of heart failure hospitalization or cardiovascular death. Kaplan Meier curves depicting the probability of heart failure hospitalization or death caused by cardiovascular causes, stratified by race and N-terminal pro-B-type natriuretic peptides (NT-proBNP) levels achieved. The curves in red (NT-proBNP ≤1000 pg/mL) and blue (NT-proBNP >1000 pg/mL) represent White patients. The curves in green (NT-proBNP ≤1000 pg/mL) and yellow (NT-proBNP >1000 pg/mL) represent Black patients. B, Rates of heart failure hospitalization or cardiovascular death across NT-proBNP level categories at 6-weeks. The bars in blue represent White patients, and the bars in red represent the Black patients. The error bars represent 95% CI. HR indicates hazard ratio; and IRR, incidence rate ratio.In this study, we observed that Black patients with HF had ≈21% lower NT-proBNP levels as compared with White patients. Despite this, NT-proBNP concentrations of ≤1,000 pg/mL had prognostic significance in both Black patients and White patients, as evidenced by a better prognosis in those who achieve target NT-proBNP levels irrespective of race. Black patients with HF had a higher risk for adverse cardiovascular outcomes compared with their White counterparts, as evidenced by an upward shift of the survival curves and higher clinical event rates across various strata of NT-proBNP. We have previously shown that Black individuals have relative NP deficiency.1,2 This deficiency may be attributed to impaired NP processing and enhanced clearance of the circulating NPs.2 Racial differences in NP system response to perturbations indicate that similar NT-proBNP levels may signify different states of congestion and treatment response between racial groups. With many HF trials considering NT-proBNP levels as a surrogate therapeutic end point, our findings indicate that the achievement of NT-proBNP target ≤1,000 pg/mL is of comparable importance in both races. Our study may be underpowered because of the small population size in each stratum and fewer events, to evaluate the interaction of race with achieved target NT-proBNP levels. In summary, achieving a target NT-proBNP level of ≤1000 pg/mL has favorable prognostic implications in both Black patients and White patients with HF, but the prognosis is worse for Black patients at either level of achieved NT-proBNP.AcknowledgmentsThe authors thank the GUIDE-IT trial investigators for making the study data available for public use through the US National Heart, Lung, and Blood Institute Biological Specimen and Data Repository.Sources of FundingThis work is supported by the Minority Health and Health Disparities Research Center, National Institute of Minority Health and Health Disparities (grant no. U54MD000502), and the National Institutes of Health Mentored-Patient Oriented Research Award (5K23 HL146887-02) to Dr Pankaj Arora.DisclosuresDr Januzzi is a Trustee of the American College of Cardiology; has received grant support from Novartis Pharmaceuticals and Abbott Diagnostics; consulting income from Abbott Diagnostics, Janssen, MyoKardia, Novartis, and Roche Diagnostics; and participates in clinical end point committees/data safety monitoring boards for Abbott, AbbVie, Amgen, Bayer, CVRx, Janssen, and Takeda. Dr Felker has received research grants from NHLBI, American Heart Association, Amgen, Merck, Cytokinetics, and Roche Diagnostics. He has acted as a consultant to Novartis, Amgen, BMS, Cytokinetics, Medtronic, Cardionomic, Relypsa, V-Wave, Innolife, EBR Systems, Arena, Abbott, Sphingotec, Roche Diagnostics, Alnylam, LivaNova, Windtree Therapeutics, Rocket Pharma, and SC Pharma. Dr Wang has taken personal fees from Novartis outside of submitted work. The other authors report no conflicts.Footnoteshttps://www.ahajournals.org/journal/circAnonymized study data are publically available at the National Heart, Lung, and Blood Institute BioLINCC data repository and can be accessed at https://biolincc.nhlbi.nih.gov/home/. Arora ORCID 0000-0003-2420-3550.Guest Editor for this article was Professor Faiez Zannad, MD, PhD.Pankaj Arora, MD, Division of Cardiovascular Disease, 1670 University Boulevard, Volker Hall B140, University of Alabama at Birmingham, Birmingham, AL 35294. Email [email protected]eduReferences1. Bajaj NS, Gutiérrez OM, Arora G, Judd SE, Patel N, Bennett A, Prabhu SD, Howard G, Howard VJ, Cushman M, et al.. Racial differences in plasma levels of N-terminal pro-B-type natriuretic peptide and outcomes: the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.JAMA Cardiol. 2018; 3:11–17. doi: 10.1001/jamacardio.2017.4207CrossrefMedlineGoogle Scholar2. Patel N, Russell GK, Musunuru K, Gutierrez OM, Halade G, Kain V, Lv W, Prabhu SD, Margulies KB, Cappola TP, et al.. Race, natriuretic peptides, and high-carbohydrate challenge: a clinical trial.Circ Res. 2019; 125:957–968. doi: 10.1161/CIRCRESAHA.119.315026LinkGoogle Scholar3. Patel N, Cushman M, Gutierrez OM, Howard G, Safford MM, Muntner P, Durant RW, Prabhu SD, Arora G, Levitan EB, et al.. Racial differences in the association of NT-proBNP with risk of incident heart failure in REGARDS.JCI Insight. 2019; 4(13): e129979. doi: 10.1172/jci.insight.129979CrossrefGoogle Scholar4. Felker GM, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, Januzzi JL, Mark DB, Piña IL, Passmore G, et al.. Effect of natriuretic peptide-guided therapy on hospitalization or cardiovascular mortality in high-risk patients with heart failure and reduced ejection fraction: a randomized clinical trial.JAMA. 2017; 318:713–720. doi: 10.1001/jama.2017.10565CrossrefMedlineGoogle Scholar5. Januzzi JL, Ahmad T, Mulder H, Coles A, Anstrom KJ, Adams KF, Ezekowitz JA, Fiuzat M, Houston-Miller N, Mark DB, et al.. Natriuretic peptide response and outcomes in chronic heart failure with reduced ejection fraction.J Am Coll Cardiol. 2019; 74:1205–1217. doi: 10.1016/j.jacc.2019.06.055CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited ByParcha V, Patel N, Kalra R, Suri S, Arora G, Wang T and Arora P (2021) Obesity and Serial NT‐proBNP Levels in Guided Medical Therapy for Heart Failure With Reduced Ejection Fraction: Insights From the GUIDE‐IT Trial, Journal of the American Heart Association, 10:7, Online publication date: 6-Apr-2021. September 8, 2020Vol 142, Issue 10Article InformationMetrics Download: 961 © 2020 American Heart Association, Inc.https://doi.org/10.1161/CIRCULATIONAHA.120.046374PMID: 32897749 Originally publishedSeptember 8, 2020 Keywordsbiomarkernatriuretic peptidesheart failureracePDF download SubjectsBiomarkersRace and EthnicityHeart FailureQuality and Outcomes" @default.
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