NT-proBNP: is it a more significant risk factor for mortality than troponin T in incident hemodialysis patients?

Hyung Jung Oh, Mi Jung Lee, Hye Sun Lee, Jung Tak Park, Seung Hyeok Han, Tae-Hyun Yoo, Yong-Lim Kim, Yon Su Kim, Chul Woo Yang, Nam-Ho Kim, Shin-Wook Kang, Hyung Jung Oh, Mi Jung Lee, Hye Sun Lee, Jung Tak Park, Seung Hyeok Han, Tae-Hyun Yoo, Yong-Lim Kim, Yon Su Kim, Chul Woo Yang, Nam-Ho Kim, Shin-Wook Kang

Abstract

Numerous studies have demonstrated that cardiac biomarkers are significant predictors of cardiovascular (CV) and all-cause mortality in ESRD patients, but most of the studies were retrospective or included small numbers of patients, only prevalent dialysis patients, or measured 1 or 2 biomarkers. This study was to analyze the association between 3 cardiac biomarkers and mortality in incident HD patients. A prospective cohort of 864 incident HD patients was followed for 30 months. Based on the median values of baseline NT-proBNP, cTnT, and hsCRP, the patients were divided into "high" and "low" groups, and CV and all-cause mortality were compared between each group. Additionally, time-dependent ROC curves were constructed, and the NRI and IDI of the models with various biomarkers were calculated. The CV survival rates were significantly lower in the "high" NT-proBNP and cTnT groups compared to the corresponding "low" groups, while there was no significant difference in CV survival rate between the 2 hsCRP groups. However, all-cause mortality rates were significantly higher in all 3 "high" groups compared to each lower group. In multivariate analyses, only Ln NT-proBNP was found to be an independent predictor of mortality. Moreover, NT-proBNP was a more prognostic marker for mortality compared to cTnT. In conclusion, NT-proBNP is the biomarker that results in the most added prognostic value on top of traditional risk factors for CV and all-cause mortality in incident HD patients.

Trial registration: ClinicalTrials.gov NCT00931970.

Conflict of interest statement

The authors have no funding and conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Kaplan–Meier survival curves for cardiovascular and all-cause mortality based on the median baseline values of NT-proBNP (A/D), cTnT (B/E), and hsCRP (C/F). The CV survival rates were significantly lower in the “high” NT-proBNP and cTnT groups compared to the corresponding “low” groups, while there was no significant difference in CV survival rates between the “high” and “low” hsCRP groups (A, B, and C). However, the all-cause mortality rates were significantly higher in all 3 “high” groups (D, E, and F). cTnT = cardiac troponin T, CV = cardiovascular, hsCRP = high-sensitivity C-reactive protein, NT-proBNP = N-terminal proB-type natriuretic peptide.
FIGURE 2
FIGURE 2
Time-dependent ROC curve analyses for cardiovascular (A) and all-cause mortality (B). iAUC values for CV mortality were 0.815 (95% CI, 0.701–0.937) for traditional risk factors, and 0.897 (95% CI, 0.794–0.984) for traditional risk factors with Ln NT-proBNP. The ESD in iAUC was 0.083 (95% CI, 0.015–0.171). In addition, iAUC values for all-cause mortality were 0.748 (95% CI, 0.655–0.828) for traditional risk factors, and 0.778 (95% CI, 0.684–0.862) for traditional risk factors with Ln NT-proBNP, and the ESD in iAUC value for all-cause mortality was 0.031 (95% CI, 0.001–0.088). Regarding cTnT, the ESDs in iAUC for CV and all-cause mortality were 0.054 (95% CI, 0.008–0.113) and 0.026 (95% CI, 0.001–0.079), respectively. However, the ESDs of hsCRP for CV and all-cause mortality were 0.017 (95% CI, −0.003 to 0.077) and 0.006 (95% CI, −0.003 to 0.034), respectively. ∗Null model; including traditional risk factors, such as age, gender, hypertension, and DM. ∗∗Model 1; Null model plus Ln NT-proBNP. ∗∗∗Model 2; Null model plus Ln cTnT. ∗∗∗Model 3; Null model plus Ln hsCRP. CI = confidence interval, cTnT = cardiac troponin T, CV = cardiovascular, hsCRP = high-sensitivity C-reactive protein, iAUC = integrated area under curve, NT-proBNP = N-terminal proB-type natriuretic peptide, ROC = receiver operating curve.

References

    1. United States Renal Data S. The USRDS 1999 Annual Data Report. Bethesda, MD: National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases Division of Kidney, Urologic, and Hematologic Diseases; 1999.
    1. Levin A, Djurdjev O, Thompson C, et al. Canadian randomized trial of hemoglobin maintenance to prevent or delay left ventricular mass growth in patients with CKD. Am J Kidney Dis 2005; 46:799–811.
    1. Middleton RJ, Parfrey PS, Foley RN. Left ventricular hypertrophy in the renal patient. J Am Soc Nephrol 2001; 12:1079–1084.
    1. Levin A, Thompson CR, Ethier J, et al. Left ventricular mass index increase in early renal disease: impact of decline in hemoglobin. Am J Kidney Dis. 1999; 34:125–134.
    1. Foley RN, Parfrey PS, Harnett JD, et al. Clinical and echocardiographic disease in patients starting end-stage renal disease therapy. Kidney Int 1995; 47:186–192.
    1. Hickman PE. Biomarkers and cardiac disease in patients with end-stage renal disease on dialysis. Clin Biochem Rev 2011; 32:115–119.
    1. Longenecker JC, Coresh J, Powe NR, et al. Traditional cardiovascular disease risk factors in dialysis patients compared with the general population: the CHOICE Study. J Am Soc Nephrol 2002; 13:1918–1927.
    1. Wang AY, Lai KN. Use of cardiac biomarkers in end-stage renal disease. J Am Soc Nephrol 2008; 19:1643–1652.
    1. Rosner MH. Measuring risk in end-stage renal disease: is N-terminal pro brain natriuretic peptide a useful marker? Kidney Int 2007; 71:481–483.
    1. Satyan S, Light RP, Agarwal R. Relationships of N-terminal pro-B-natriuretic peptide and cardiac troponin T to left ventricular mass and function and mortality in asymptomatic hemodialysis patients. Am J Kidney Dis 2007; 50:1009–1019.
    1. Apple FS, Murakami MM, Pearce LA, Herzog CA. Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all-cause death. Clin Chem 2004; 50:2279–2285.
    1. Apple FS, Murakami MM, Pearce LA, Herzog CA. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease. Circulation 2002; 106:2941–2945.
    1. Mallamaci F, Zoccali C, Parlongo S, et al. Troponin is related to left ventricular mass and predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2002; 40:68–75.
    1. Yeun JY, Levine RA, Mantadilok V, Kaysen GA. C-Reactive protein predicts all-cause and cardiovascular mortality in hemodialysis patients. Am J Kidney Dis 2000; 35:469–476.
    1. de Lemos JA, McGuire DK, Drazner MH. B-type natriuretic peptide in cardiovascular disease. Lancet 2003; 362:316–322.
    1. Baughman KL. B-type natriuretic peptide: a window to the heart. N Engl J Med 2002; 347:158–159.
    1. Kinnunen P, Vuolteenaho O, Ruskoaho H. Mechanisms of atrial and brain natriuretic peptide release from rat ventricular myocardium: effect of stretching. Endocrinology 1993; 132:1961–1970.
    1. McDonagh TA, Robb SD, Murdoch DR, et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet 1998; 351:9–13.
    1. Yamamoto K, Burnett JC, Jr, Jougasaki M, et al. Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. Hypertension 1996; 28:988–994.
    1. Alpert JS, Thygesen K, Antman E, Bassand JP. Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol 2000; 36:959–969.
    1. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol 2000; 36:970–1062.
    1. Hickman PE, McGill DA, Talaulikar G, et al. Prognostic efficacy of cardiac biomarkers for mortality in dialysis patients. Intern Med J 2009; 39:812–818.
    1. Madsen LH, Ladefoged S, Corell P, et al. N-terminal pro brain natriuretic peptide predicts mortality in patients with end-stage renal disease in hemodialysis. Kidney Int 2007; 71:548–554.
    1. Rao M, Jaber BL, Balakrishnan VS. Inflammatory biomarkers and cardiovascular risk: association or cause and effect? Semin Dial 2006; 19:129–135.
    1. Pearson TA, Mensah GA, Alexander RW, et al. Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003; 107:499–511.
    1. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 2003; 107:363–369.
    1. Arici M, Walls J. End-stage renal disease, atherosclerosis, and cardiovascular mortality: is C-reactive protein the missing link? Kidney Int 2001; 59:407–414.
    1. Zimmermann J, Herrlinger S, Pruy A, et al. Inflammation enhances cardiovascular risk and mortality in hemodialysis patients. Kidney Int 1999; 55:648–658.
    1. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005; 18:1440–1463.
    1. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57:450–458.
    1. Okin PM, Roman MJ, Devereux RB, Kligfield P. Electrocardiographic identification of increased left ventricular mass by simple voltage-duration products. J Am Coll Cardiol 1995; 25:417–423.
    1. Heagerty PJ, Zheng Y. Survival model predictive accuracy and ROC curves. Biometrics 2005; 61:92–105.
    1. Saha-Chaudhuri P, Heagerty PJ. Non-parametric estimation of a time-dependent predictive accuracy curve. Biostatistics 2013; 14:42–59.
    1. Pencina MJ, D’Agostino RB, Sr, D’Agostino RB, Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med 2008; 27:157–172,.discussion 207-112.
    1. Shlipak MG, Fried LF, Cushman M, et al. Cardiovascular mortality risk in chronic kidney disease: comparison of traditional and novel risk factors. JAMA 2005; 293:1737–1745.
    1. Zoccali C, Benedetto FA, Mallamaci F, et al. Left ventricular mass monitoring in the follow-up of dialysis patients: prognostic value of left ventricular hypertrophy progression. Kidney Int 2004; 65:1492–1498.
    1. London GM, Pannier B, Guerin AP, et al. Alterations of left ventricular hypertrophy in and survival of patients receiving hemodialysis: follow-up of an interventional study. J Am Soc Nephrol 2001; 12:2759–2767.
    1. Silberberg JS, Barre PE, Prichard SS, Sniderman AD. Impact of left ventricular hypertrophy on survival in end-stage renal disease. Kidney Int 1989; 36:286–290.
    1. Kim SJ, Oh HJ, Yoo DE, et al. Electrocardiographic left ventricular hypertrophy and outcome in hemodialysis patients. PLoS ONE 2012; 7:e35534.
    1. Okin PM, Devereux RB, Jern S, et al. Regression of electrocardiographic left ventricular hypertrophy during antihypertensive treatment and the prediction of major cardiovascular events. JAMA 2004; 292:2343–2349.
    1. Mathew J, Sleight P, Lonn E, et al. Reduction of cardiovascular risk by regression of electrocardiographic markers of left ventricular hypertrophy by the angiotensin-converting enzyme inhibitor ramipril. Circulation 2001; 104:1615–1621.
    1. Khan NA, Hemmelgarn BR, Tonelli M, et al. Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis. Circulation 2005; 112:3088–3096.
    1. Iliou MC, Fumeron C, Benoit MO, et al. Prognostic value of cardiac markers in ESRD: Chronic Hemodialysis and New Cardiac Markers Evaluation (CHANCE) study. Am J Kidney Dis 2003; 42:513–523.
    1. Stenvinkel P, Wanner C, Metzger T, et al. Inflammation and outcome in end-stage renal failure: does female gender constitute a survival advantage? Kidney Int 2002; 62:1791–1798.
    1. Panichi V, Migliori M, De Pietro S, et al. Plasma C-reactive protein in hemodialysis patients: a cross-sectional, longitudinal clinical survey. Blood Purif 2000; 18:30–36.
    1. Schouten WE, Grooteman MP, van Houte AJ, et al. Effects of dialyser and dialysate on the acute phase reaction in clinical bicarbonate dialysis. Nephrol Dial Transplant 2000; 15:379–384.
    1. Tielemans C, Husson C, Schurmans T, et al. Effects of ultrapure and non-sterile dialysate on the inflammatory response during in vitro hemodialysis. Kidney Int 1996; 49:236–243.
    1. Koenig W, Sund M, Frohlich M, et al. Refinement of the association of serum C-reactive protein concentration and coronary heart disease risk by correction for within-subject variation over time: the MONICA Augsburg studies, 1984 and 1987. Am J Epidemiol 2003; 158:357–364.
    1. Macy EM, Hayes TE, Tracy RP. Variability in the measurement of C-reactive protein in healthy subjects: implications for reference intervals and epidemiological applications. Clin Chem 1997; 43:52–58.
    1. Goodkin DA, Bragg-Gresham JL, Koenig KG, et al. Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS). J Am Soc Nephrol 2003; 14:3270–3277.
    1. Malindretos P. The influence of hemodialysis on plasma levels of b-type natriuretic peptide in chronic hemodialysis patients. Hellen Nephrol 2007; 19:144–151.

Source: PubMed

Sponsorer og samarbejdspartnere

Medicinske tilstande

Narkotikainterventioner

3
Abonner