Letter Regarding Article by Khan et al, “Prognostic Value of Troponin T and I Among Asymptomatic Patients With End-Stage Renal Disease: A Meta-Analysis”
To the Editor:
We read with interest the article by Khan et al1 and agree that cardiac troponin T (cTnT) is a promising biomarker in end-stage renal disease (ESRD), but we are concerned about the following issues.
First, the authors state, “overall prognostic usefulness of the troponins remains unclear” and “previous studies, based on retrospective study designs and multiple insensitive assays that cross-react with skeletal troponin, have produced conflicting results” (p 3089).1 To the contrary, the evidence-based literature was clear to the Food and Drug Administration, which approved cTnT for stratification of cardiac risk in dialysis patients a year before the meta-analysis by Khan et al was submitted, as well as to the National Kidney Foundation Kidney Disease Outcomes Quality Initiative on Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients, which endorsed cTn for risk stratification in dialysis patients,2 also before the submission of this article.
Second, the decision of Khan et al to use a >5-fold increment over the lower limit of detection is unsupported. This is not part of the European Society of Cardiology/American College of Cardiology guidelines.3 This skews the data toward higher values. Imprecision around a 99th percentile cutoff does not lead to false-positive results,4 and there is overwhelming evidence of the power of risk stratification using the 99th percentile.5–7
Third, the 99th percentile identifies a greater number of ESRD patients at risk. In our 733-patient–based study,5 an additional 453 patients with ESRD were identified by using this cutoff. The adjusted relative risk of death at ≥0.01 ng/mL was 4.7 compared with 1.8 at >0.1 ng/mL at 1 year. Our follow-up study6 confirmed these findings, and the results of the meta-analysis by Khan et al might have been different had our study been included.
Fourth, the difference between cTnI and cTnT is not their ability to predict risk; cTnT identifies more patients at risk.6,7
Finally, in their Table 2, the 90th percentile should be designated as the 99th percentile.
Randomized clinical trials in patients with ESRD with cTnT or cTnI are needed but should use cutoff concentrations below those advocated by Khan et al.1
Dr Apple has received research grants from Roche, Beckman, and Dade and honoraria from companies that manufacture cardiac troponin assays; has ownership interest in Sensera; and has served as a consultant to or on the advisory boards of Abbott, Ortho-Clinical Diagnostics, Biosite, and Senera. Dr Jaffe has received research grants from Dade-Behring and other research support from Roche and Beckman-Coulter, and has served as a consultant to or on the advisory board of Dade-Behring, Roche, Beckman-Coulter, and Ortho Diagnostics. Dr Herzog reports no conflicts.
Khan NA, Hemmelgarn BR, Tonelli M, Thompson CR, Levin A. Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis. Circulation. 2005; 112: 3088–3096.
Alpert JS, Thygesen K. Myocardial infarction redefined. J Am Coll Cardiol. 2000; 21: 1502–1513.
Apple FS, Parvin CA, Buechler KF, Christenson RH, Wu AHB, Jaffe AS. Validation of the 99th percentile cutoff independent of assay imprecision (%CV) for cardiac troponin monitoring for ruling out myocardial infarction. Clin Chem. 2005; 51: 1198–2200.
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.
Apple FS, Murakami MM, Pearce LA, Herzog CA. Prognostic value of high sensitivity C-reactive protein, N-terminal proBNP, and cardiac troponin T and I in end-stage renal disease for subsequent death over two years. Clin Chem. 2004; 50: 2279–2285.