Advertisement

Change in Cardiac Biomarkers and Risk of Incident Heart Failure and Atrial Fibrillation in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Published:December 09, 2020DOI:https://doi.org/10.1053/j.ajkd.2020.09.021

      Rationale & Objective

      Circulating cardiac biomarkers may signal potential mechanistic pathways involved in heart failure (HF) and atrial fibrillation (AF). Single measures of circulating cardiac biomarkers are strongly associated with incident HF and AF in chronic kidney disease (CKD). We tested the associations of longitudinal changes in the N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor 15 (GDF-15), and soluble ST-2 (sST-2) with incident HF and AF in patients with CKD.

      Study Design

      Observational, case-cohort study design.

      Setting & Participants

      Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort study.

      Exposures

      Biomarkers were measured at baseline and 2 years later among those without kidney failure. We created 3 categories of absolute change in each biomarker: the lowest quartile, the middle 2 quartiles, and the top quartile.

      Outcomes

      The primary outcomes were incident HF and AF.

      Analytical Approach

      Cox proportional hazards regression models were used to test the associations of the change categories of each cardiac biomarker with each outcome (with the middle 2 quartiles of change as the referent group), adjusting for potential confounders and baseline concentrations of each biomarker.

      Results

      The incident HF analysis included 789 participants (which included 138 incident HF cases), and the incident AF analysis included 774 participants (123 incident AF cases). In multivariable models, the top quartile of NT-proBNP change (>232 pg/mL over 2 years) was associated with increased risk of incident HF (HR, 1.79 [95% CI, 1.06-3.04]) and AF (HR, 2.32 [95% CI, 1.37-3.93]) compared with the referent group. Participants in the top quartile of sST2 change (>3.37 ng/mL over 2 years) had significantly greater risk of incident HF (HR, 1.89 [95% CI, 1.13-3.16]), whereas those in the bottom quartile (≤−3.78 ng/mL over 2 years) had greater risk of incident AF (HR, 2.43 [95% CI, 1.39-4.22]) compared with the 2 middle quartiles. There was no association of changes in hsTnT, galectin-3, or GDF-15 with incident HF or AF.

      Limitations

      Observational study.

      Conclusions

      In CKD, increases in NT-proBNP were significantly associated with greater risk of incident HF and AF, and increases in sST2 were associated with HF. Further studies should investigate whether these markers of subclinical cardiovascular disease can be modified to reduce the risk of cardiovascular disease in CKD.

      Index Words

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to American Journal of Kidney Diseases
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kottgen A.
        • Russell S.D.
        • Loehr L.R.
        • et al.
        Reduced kidney function as a risk factor for incident heart failure: the atherosclerosis risk in communities (ARIC) study.
        J Am Soc Nephrol. 2007; 18: 1307-1315
        • Go A.S.
        • Chertow G.M.
        • Fan D.
        • McCulloch C.E.
        • Hsu C.Y.
        Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.
        N Engl J Med. 2004; 351: 1296-1305
        • Bansal N.
        • Katz R.
        • Robinson-Cohen C.
        • et al.
        Absolute rates of heart failure, coronary heart disease, and stroke in chronic kidney disease: an analysis of 3 community-based cohort studies.
        JAMA Cardiol. 2017; 2: 314-318
        • Saran R.
        • Robinson B.
        • Abbott K.C.
        • et al.
        US Renal Data System 2016 annual data report: epidemiology of kidney disease in the United States.
        Am J Kidney Dis. 2017; 69: S1-S434
        • Porter A.C.
        • Lash J.P.
        • Xie D.
        • et al.
        Predictors and outcomes of health-related quality of life in adults with CKD.
        Clin J Am Soc Nephrol. 2016; 11: 1154-1162
        • Harel Z.
        • Wald R.
        • McArthur E.
        • et al.
        Rehospitalizations and emergency department visits after hospital discharge in patients receiving maintenance hemodialysis.
        J Am Soc Nephrol. 2015; 26: 3141-3150
        • Bansal N.
        • Fan D.
        • Hsu C.Y.
        • Ordonez J.D.
        • Go A.S.
        Incident atrial fibrillation and risk of death in adults with chronic kidney disease.
        J Am Heart Assoc. 2014; 3e001303
        • Bansal N.
        • Fan D.
        • Hsu C.Y.
        • Ordonez J.D.
        • Marcus G.M.
        • Go A.S.
        Incident atrial fibrillation and risk of end-stage renal disease in adults with chronic kidney disease.
        Circulation. 2013; 127: 569-574
        • Bansal N.
        • Xie D.
        • Tao K.
        • et al.
        Atrial fibrillation and risk of ESRD in adults with CKD.
        Clin J Am Soc Nephrol. 2016; 11: 1189-1196
        • Wang T.J.
        • Wollert K.C.
        • Larson M.G.
        • et al.
        Prognostic utility of novel biomarkers of cardiovascular stress: the Framingham Heart Study.
        Circulation. 2012; 126: 1596-1604
        • Rohatgi A.
        • Patel P.
        • Das S.R.
        • et al.
        Association of growth differentiation factor-15 with coronary atherosclerosis and mortality in a young, multiethnic population: observations from the Dallas Heart Study.
        Clin Chem. 2012; 58: 172-182
        • Kempf T.
        • Horn-Wichmann R.
        • Brabant G.
        • et al.
        Circulating concentrations of growth-differentiation factor 15 in apparently healthy elderly individuals and patients with chronic heart failure as assessed by a new immunoradiometric sandwich assay.
        Clin Chem. 2007; 53: 284-291
        • Bonaca M.P.
        • Morrow D.A.
        • Braunwald E.
        • et al.
        Growth differentiation factor-15 and risk of recurrent events in patients stabilized after acute coronary syndrome: observations from PROVE IT-TIMI 22.
        Arterioscler Thromb Vasc Biol. 2011; 31: 203-210
        • Kempf T.
        • von Haehling S.
        • Peter T.
        • et al.
        Prognostic utility of growth differentiation factor-15 in patients with chronic heart failure.
        J Am Coll Cardiol. 2007; 50: 1054-1060
        • Anand I.S.
        • Kempf T.
        • Rector T.S.
        • et al.
        Serial measurement of growth-differentiation factor-15 in heart failure: relation to disease severity and prognosis in the Valsartan Heart Failure Trial.
        Circulation. 2010; 122: 1387-1395
        • Xanthakis V.
        • Larson M.G.
        • Wollert K.C.
        • et al.
        Association of novel biomarkers of cardiovascular stress with left ventricular hypertrophy and dysfunction: implications for screening.
        J Am Heart Assoc. 2013; 2e000399
        • Lind L.
        • Wallentin L.
        • Kempf T.
        • et al.
        Growth-differentiation factor-15 is an independent marker of cardiovascular dysfunction and disease in the elderly: results from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) Study.
        Eur Heart J. 2009; 30: 2346-2353
        • Kempf T.
        • Bjorklund E.
        • Olofsson S.
        • et al.
        Growth-differentiation factor-15 improves risk stratification in ST-segment elevation myocardial infarction.
        Eur Heart J. 2007; 28: 2858-2865
        • Bansal N.
        • Xie D.
        • Sha D.
        • et al.
        Cardiovascular events after new-onset atrial fibrillation in dults with CKD: results from the Chronic Renal Insufficiency Cohort (CRIC) Study.
        J Am Soc Nephrol. 2018; 29: 2859-2869
        • Wollert K.C.
        • Kempf T.
        • Lagerqvist B.
        • et al.
        Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome.
        Circulation. 2007; 116: 1540-1548
        • Wollert K.C.
        • Kempf T.
        • Peter T.
        • et al.
        Prognostic value of growth-differentiation factor-15 in patients with non-ST-elevation acute coronary syndrome.
        Circulation. 2007; 115: 962-971
        • Wollert K.C.
        • Kempf T.
        • Wallentin L.
        Growth differentiation factor 15 as a biomarker in cardiovascular disease.
        Clin Chem. 2017; 63: 140-151
        • Gleissner C.A.
        • Erbel C.
        • Linden F.
        • et al.
        Galectin-3 binding protein, coronary artery disease and cardiovascular mortality: insights from the LURIC study.
        Atherosclerosis. 2017; 260: 121-129
        • Ò Miró
        • González de la Presa B.
        • Herrero P.
        • et al.
        The GALA study: relationship between galectin-3 serum levels and short- and long-term outcomes of patients with acute heart failure.
        Biomarkers. 2017; 22: 731-739
        • Drechsler C.
        • Delgado G.
        • Wanner C.
        • et al.
        Galectin-3, renal function, and clinical outcomes: results from the LURIC and 4D studies.
        J Am Soc Nephrol. 2015; 26: 2213-2221
        • Bansal N.
        • Hyre Anderson A.
        • Yang W.
        • et al.
        High-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide (NT-proBNP) and risk of incident heart failure in patients with CKD: the Chronic Renal Insufficiency Cohort (CRIC) Study.
        J Am Soc Nephrol. 2015; 26: 946-956
        • Tuegel C.
        • Katz R.
        • Alam M.
        • et al.
        GDF-15, Galectin 3, soluble ST2, and risk of mortality and cardiovascular events in CKD.
        Am J Kidney Dis. 2018; 72: 519-528
        • Czaya B.
        • Seeherunvong W.
        • Singh S.
        • et al.
        Cardioprotective effects of paricalcitol alone and in combination with FGF23 receptor inhibition in chronic renal failure: experimental and clinical studies.
        Am J Hypertens. 2019; 32: 34-44
        • Faul C.
        Cardiac actions of fibroblast growth factor 23.
        Bone. 2017; 100: 69-79
        • Xie J.
        • Yoon J.
        • An S.W.
        • Kuro-o M.
        • Huang C.L.
        Soluble klotho protects against uremic cardiomyopathy independently of fibroblast growth factor 23 and phosphate.
        J Am Soc Nephrol. 2015; 26: 1150-1160
        • Faul C.
        • Amaral A.P.
        • Oskouei B.
        • et al.
        FGF23 induces left ventricular hypertrophy.
        J Clin Invest. 2011; 121: 4393-4408
        • Fan J.
        • Cao H.
        • Su L.
        • et al.
        NT-proBNP, but not ANP and C-reactive protein, is predictive of paroxysmal atrial fibrillation in patients undergoing pulmonary vein isolation.
        J Interv Card Electrophysiol. 2012; 33: 93-100
        • Kornej J.
        • Schmidl J.
        • Ueberham L.
        • et al.
        Galectin-3 in patients with atrial fibrillation undergoing radiofrequency catheter ablation.
        PLoS One. 2015; 10e0123574
        • Sinner M.F.
        • Stepas K.A.
        • Moser C.B.
        • et al.
        B-type natriuretic peptide and C-reactive protein in the prediction of atrial fibrillation risk: the CHARGE-AF Consortium of community-based cohort studies.
        Europace. 2014; 16: 1426-1433
        • Wallentin L.
        • Hijazi Z.
        • Andersson U.
        • et al.
        • ARISTOTLE Investigators
        Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.
        Circulation. 2014; 130: 1847-1858
        • Wu X.Y.
        • Li S.N.
        • Wen S.N.
        • et al.
        Plasma galectin-3 predicts clinical outcomes after catheter ablation in persistent atrial fibrillation patients without structural heart disease.
        Europace. 2015; 17: 1541-1547
        • Yalcin M.U.
        • Gurses K.M.
        • Kocyigit D.
        • et al.
        The association of serum galectin-3 levels with atrial electrical and structural remodeling.
        J Cardiovasc Electrophysiol. 2015; 26: 635-640
        • Fashanu O.E.
        • Norby F.L.
        • Aguilar D.
        • et al.
        Galectin-3 and incidence of atrial fibrillation: the Atherosclerosis Risk in Communities (ARIC) study.
        Am Heart J. 2017; 192: 19-25
        • Nortamo S.
        • Ukkola O.
        • Lepojarvi S.
        • et al.
        Association of sST2 and hs-CRP levels with new-onset atrial fibrillation in coronary artery disease.
        Int J Cardiol. 2017; 248: 173-178
        • Yasue H.
        • Yoshimura M.
        • Sumida H.
        • et al.
        Localization and mechanism of secretion of B-type natriuretic peptide in comparison with those of A-type natriuretic peptide in normal subjects and patients with heart failure.
        Circulation. 1994; 90: 195-203
        • Vickery S.
        • Price C.P.
        • John R.I.
        • et al.
        B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy.
        Am J Kidney Dis. 2005; 46: 610-620
        • Mishra R.K.
        • Li Y.
        • Ricardo A.C.
        • et al.
        Association of N-terminal pro-B-type natriuretic peptide with left ventricular structure and function in chronic kidney disease (from the Chronic Renal Insufficiency Cohort [CRIC]).
        Am J Cardiol. 2013; 111: 432-438
        • DeFilippi C.R.
        • Fink J.C.
        • Nass C.M.
        • Chen H.
        • Christenson R.
        N-terminal pro-B-type natriuretic peptide for predicting coronary disease and left ventricular hypertrophy in asymptomatic CKD not requiring dialysis.
        Am J Kidney Dis. 2005; 46: 35-44
        • de Lemos J.A.
        • Drazner M.H.
        • Omland T.
        • et al.
        Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population.
        JAMA. 2010; 304: 2503-2512
        • Mishra R.K.
        • Li Y.
        • DeFilippi C.
        • et al.
        • CRIC Study Investigators
        Association of cardiac troponin T with left ventricular structure and function in CKD.
        Am J Kidney Dis. 2013; 61: 701-709
        • Calvier L.
        • Miana M.
        • Reboul P.
        • et al.
        Galectin-3 mediates aldosterone-induced vascular fibrosis.
        Arterioscler Thromb Vasc Biol. 2013; 33: 67-75
        • Vergaro G.
        • Prud’homme M.
        • Fazal L.
        • et al.
        Inhibition of galectin-3 pathway prevents isoproterenol-induced left ventricular dysfunction and fibrosis in mice.
        Hypertension. 2016; 67: 606-612
        • Unsicker K.
        • Spittau B.
        • Krieglstein K.
        The multiple facets of the TGF-beta family cytokine growth/differentiation factor-15/macrophage inhibitory cytokine-1.
        Cytokine Growth Factor Rev. 2013; 24: 373-384
        • Nair V.
        • Robinson-Cohen C.
        • Smith M.R.
        • et al.
        Growth differentiation factor-15 and risk of CKD progression.
        J Am Soc Nephrol. 2017; 28: 2233-2240
        • Kempf T.
        • Eden M.
        • Strelau J.
        • et al.
        The transforming growth factor-beta superfamily member growth-differentiation factor-15 protects the heart from ischemia/reperfusion injury.
        Circ Res. 2006; 98: 351-360
        • Pfisterer M.
        • Buser P.
        • Rickli H.
        • et al.
        BNP-guided vs symptom-guided heart failure therapy: the Trial of Intensified vs Standard Medical Therapy in Elderly Patients With Congestive Heart Failure (TIME-CHF) randomized trial.
        JAMA. 2009; 301: 383-392
        • Jourdain P.
        • Jondeau G.
        • Funck F.
        • et al.
        Plasma brain natriuretic peptide-guided therapy to improve outcome in heart failure: the STARS-BNP Multicenter Study.
        J Am Coll Cardiol. 2007; 49: 1733-1739
        • Ledwidge M.
        • Gallagher J.
        • Conlon C.
        • et al.
        Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial.
        JAMA. 2013; 310: 66-74
        • Felker G.M.
        • Hasselblad V.
        • Hernandez A.F.
        • O’Connor C.M.
        Biomarker-guided therapy in chronic heart failure: a meta-analysis of randomized controlled trials.
        Am Heart J. 2009; 158: 422-430
        • Hussein A.A.
        • Bartz T.M.
        • Gottdiener J.S.
        • et al.
        Serial measures of cardiac troponin T levels by a highly sensitive assay and incident atrial fibrillation in a prospective cohort of ambulatory older adults.
        Heart Rhythm. 2015; 12: 879-885
        • van der Velde A.R.
        • Meijers W.C.
        • Ho J.E.
        • et al.
        Serial galectin-3 and future cardiovascular disease in the general population.
        Heart. 2016; 102: 1134-1141
        • Eggers K.M.
        • Kempf T.
        • Wallentin L.
        • Wollert K.C.
        • Lind L.
        Change in growth differentiation factor 15 concentrations over time independently predicts mortality in community-dwelling elderly individuals.
        Clin Chem. 2013; 59: 1091-1098
        • Boisot S.
        • Beede J.
        • Isakson S.
        • et al.
        Serial sampling of ST2 predicts 90-day mortality following destabilized heart failure.
        J Card Fail. 2008; 14: 732-738
        • Manzano-Fernandez S.
        • Januzzi J.L.
        • Pastor-Perez F.J.
        • et al.
        Serial monitoring of soluble interleukin family member ST2 in patients with acutely decompensated heart failure.
        Cardiology. 2012; 122: 158-166
        • Feldman H.I.
        • Appel L.J.
        • Chertow G.M.
        • et al.
        The Chronic Renal Insufficiency Cohort (CRIC) study: design and methods.
        J Am Soc Nephrol. 2003; 14: S148-S153
        • Lash J.P.
        • Go A.S.
        • Appel L.J.
        • et al.
        Chronic Renal Insufficiency Cohort (CRIC) study: baseline characteristics and associations with kidney function.
        Clin J Am Soc Nephrol. 2009; 4: 1302-1311
        • Giannitsis E.
        • Kurz K.
        • Hallermayer K.
        • Jarausch J.
        • Jaffe A.S.
        • Katus H.A.
        Analytical validation of a high-sensitivity cardiac troponin T assay.
        Clin Chem. 2010; 56: 254-261
        • Linnet K.
        Necessary sample size for method comparison studies based on regression analysis.
        Clin Chem. 1999; 45: 882-894
        • Ho K.K.
        • Anderson K.M.
        • Kannel W.B.
        • Grossman W.
        • Levy D.
        Survival after the onset of congestive heart failure in Framingham Heart Study subjects.
        Circulation. 1993; 88: 107-115
        • National Center for Health Statistics (NCHS)
        National Health and Nutrition Examination Survey Anthropometry Procedures Manual.
        Centers for Disease Control and Prevention [serial online], 2000 (Accessed August 15, 2020. https://www.cdc.gov/nchs/data/nhanes/nhanes_07_08/manual_an)
        • Joffe M.
        • Hsu C.Y.
        • Feldman H.I.
        • et al.
        Variability of creatinine measurements in clinical laboratories: results from the CRIC study.
        Am J Nephrol. 2010; 31: 426-434
        • Levey A.S.
        • Coresh J.
        • Greene T.
        • et al.
        Expressing the Modification of Diet in Renal Disease Study equation for estimating glomerular filtration rate with standardized serum creatinine values.
        Clin Chem. 2007; 53: 766-772
        • Levey A.S.
        • Stevens L.A.
        • Schmid C.H.
        • et al.
        A new equation to estimate glomerular filtration rate.
        Ann Intern Med. 2009; 150: 604-612
        • Therneau T.M.
        • Li H.
        Computing the Cox model for case cohort designs.
        Lifetime Data Anal. 1999; 5: 99-112
        • Barlow W.E.
        Robust variance estimation for the case-cohort design.
        Biometrics. 1994; 50: 1064-1072
        • Harrell F.E.
        • Lee K.L.
        • Mark D.B.
        Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors.
        Stat Med. 1996; 15: 361-387
        • Uno H.
        • Tian L.
        • Cai T.
        • Kohane I.S.
        • Wei L.J.
        A unified inference procedure for a class of measures to assess improvement in risk prediction systems with survival data.
        Stat Med. 2013; 32: 2430-2442
        • Rubin D.B.
        Multiple Imputation for Nonresponse in Surveys.
        Wiley, 1987
        • Bansal N.
        • Zelnick L.
        • Go A.
        • et al.
        Cardiac biomarkers and risk of incident heart failure in chronic kidney disease: the CRIC (Chronic Renal Insufficiency Cohort) study.
        J Am Heart Assoc. 2019; 8e012336
        • Miller W.L.
        • Hartman K.A.
        • Burritt M.F.
        • Grill D.E.
        • Jaffe A.S.
        Profiles of serial changes in cardiac troponin T concentrations and outcome in ambulatory patients with chronic heart failure.
        J Am Coll Cardiol. 2009; 54: 1715-1721
        • deFilippi C.R.
        • de Lemos J.A.
        • Christenson R.H.
        • et al.
        Association of serial measures of cardiac troponin T using a sensitive assay with incident heart failure and cardiovascular mortality in older adults.
        JAMA. 2010; 304: 2494-2502
        • Eggers K.M.
        • Venge P.
        • Lind L.
        Prognostic usefulness of the change in N-terminal pro B-type natriuretic peptide levels to predict mortality in a single community cohort aged >/= 70 years.
        Am J Cardiol. 2013; 111: 131-136
        • Masson S.
        • Anand I.
        • Favero C.
        • et al.
        Serial measurement of cardiac troponin T using a highly sensitive assay in patients with chronic heart failure: data from 2 large randomized clinical trials.
        Circulation. 2012; 125: 280-288
        • Masson S.
        • Latini R.
        • Anand I.S.
        • et al.
        Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial).
        J Am Coll Cardiol. 2008; 52: 997-1003
        • Miller W.L.
        • Hartman K.A.
        • Burritt M.F.
        • et al.
        Serial biomarker measurements in ambulatory patients with chronic heart failure: the importance of change over time.
        Circulation. 2007; 116: 249-257
        • Patton K.K.
        • Ellinor P.T.
        • Heckbert S.R.
        • et al.
        N-terminal pro-B-type natriuretic peptide is a major predictor of the development of atrial fibrillation: the Cardiovascular Health Study.
        Circulation. 2009; 120: 1768-1774
        • Patton K.K.
        • Heckbert S.R.
        • Alonso A.
        • et al.
        N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis: the effects of age, sex and ethnicity.
        Heart. 2013; 99: 1832-1836
        • Lamprea-Montealegre J.A.
        • Zelnick L.R.
        • Shlipak M.G.
        • et al.
        • CRIC Study Investigators
        Cardiac biomarkers and risk of atrial fibrillation in chronic kidney disease: the CRIC study.
        J Am Heart Assoc. 2019; 8e012200
        • Miller W.L.
        • Hartman K.A.
        • Grill D.E.
        • Burnett Jr., J.C.
        • Jaffe A.S.
        Only large reductions in concentrations of natriuretic peptides (BNP and NT-proBNP) are associated with improved outcome in ambulatory patients with chronic heart failure.
        Clin Chem. 2009; 55: 78-84
        • deFilippi C.R.
        • Christenson R.H.
        • Gottdiener J.S.
        • Kop W.J.
        • Seliger S.L.
        Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing.
        J Am Coll Cardiol. 2010; 55: 441-450
        • Gaggin H.K.
        • Szymonifka J.
        • Bhardwaj A.
        • et al.
        Head-to-head comparison of serial soluble ST2, growth differentiation factor-15, and highly-sensitive troponin T measurements in patients with chronic heart failure.
        JACC Heart Fail. 2014; 2: 65-72
        • Januzzi J.L.
        • Pascual-Figal D.
        • Daniels L.B.
        ST2 testing for chronic heart failure therapy monitoring: the International ST2 Consensus Panel.
        Am J Cardiol. 2015; 115: 70b-75b
        • Sandoval Y.
        • Herzog C.A.
        • Love S.A.
        • et al.
        Prognostic value of serial changes in high-sensitivity cardiac troponin I and T over 3 months using reference change values in hemodialysis patients.
        Clin Chem. 2016; 62: 631-638
        • Anand I.S.
        • Rector T.S.
        • Kuskowski M.
        • Adourian A.
        • Muntendam P.
        • Cohn J.N.
        Baseline and serial measurements of galectin-3 in patients with heart failure: relationship to prognosis and effect of treatment with valsartan in the Val-HeFT.
        Eur J Heart Fail. 2013; 15: 511-518
        • Motiwala S.R.
        • Szymonifka J.
        • Belcher A.
        • et al.
        Serial measurement of galectin-3 in patients with chronic heart failure: results from the ProBNP Outpatient Tailored Chronic Heart Failure Therapy (PROTECT) study.
        Eur J Heart Fail. 2013; 15: 1157-1163
        • van der Velde A.R.
        • Gullestad L.
        • Ueland T.
        • et al.
        Prognostic value of changes in galectin-3 levels over time in patients with heart failure: data from CORONA and COACH.
        Circ Heart Fail. 2013; 6: 219-226
        • Felker G.M.
        • Anstrom K.J.
        • Adams K.F.
        • 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