Erin D. Michos, MD, MHS; Lisa M. Wilson, ScM; Hsin-Chieh Yeh, PhD; Zackary Berger, MD, PhDs; Catalina Suarez-Cuervo, MD; Sylvie R. Stacy, MD; Eric B. Bass, MD, MPH
Disclaimer: This article is based on research conducted by the Johns Hopkins University Evidence-based Practice Center under a contract with AHRQ. The authors of this article are responsible for its contents, including any clinical or treatment recommendations. No statement in this article should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Elisabeth Nannes, Brijesh Patel, Sunil Agrawal, Allen Zhang, Sylvia Wang, and Oluwaseun Shogbesan for their help in reviewing articles and abstracting data.
Financial Support: This article is based on research conducted by the Johns Hopkins University Evidence-based Practice Center under contract with AHRQ (contract 290-2012-00007-I).
Disclosures: Dr. Michos worked under a contract from AHRQ during the conduct of the study and received a grant from the National Institutes of Health outside of the submitted work. Ms. Wilson reports that she worked under a contract from AHRQ during the conduct of the study. Dr. Stacy reports that she worked under a contract from AHRQ during the conduct of the study. Dr. Bass reports receiving a contract from AHRQ for performance of the systematic review. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0743.
Requests for Single Reprints: Erin D. Michos, MD, MHS, Associate Professor of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, MD 21287; e-mail, email@example.com.
Current Author Addresses: Dr. Michos: Division of Cardiology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 568, Baltimore, MD 21287.
Ms. Wilson and Dr. Suarez-Cuervo: Johns Hopkins University, Evidence-based Practice Center, 624 North Broadway, Suite 680, Baltimore, MD 21205.
Dr. Yeh: Johns Hopkins University, 2024 East Monument Street, Suite 2-500, Baltimore, MD 21287.
Dr. Berger: Johns Hopkins Outpatient Center, 601 North Caroline Street, Suite 7143, Baltimore, MD 21287.
Dr. Stacy: Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room WB602, Baltimore, MD 21205.
Dr. Bass: Johns Hopkins University School of Medicine, 624 North Broadway, Room 680A, Baltimore, MD 21205.
Author Contributions: Conception and design: E.D. Michos, L.M. Wilson, H.C. Yeh, Z. Berger, C. Suarez-Cuervo, E.B. Bass.
Analysis and interpretation of the data: E.D. Michos, L.M. Wilson, Z. Berger, C. Suarez-Cuervo, S.R. Stacy, E.B. Bass.
Drafting of the article: E.D. Michos, H.C. Yeh, Z. Berger, C. Suarez-Cuervo.
Critical revision of the article for important intellectual content: E.D. Michos, L.M. Wilson, Z. Berger, C. Suarez-Cuervo, E.B. Bass.
Final approval of the article: E.D. Michos, L.M. Wilson, Z. Berger, C. Suarez-Cuervo, E.B. Bass.
Provision of study materials or patients: L.M. Wilson, E.B. Bass.
Statistical expertise: L.M. Wilson, H.C. Yeh.
Obtaining of funding: E.B. Bass.
Administrative, technical, or logistic support: E.D. Michos, L.M. Wilson, E.B. Bass.
Collection and assembly of data: E.D. Michos, L.M. Wilson, H.C. Yeh, Z. Berger, C. Suarez-Cuervo, S.R. Stacy.
Clinicians face uncertainty about the prognostic value of troponin testing in patients with chronic kidney disease (CKD) without suspected acute coronary syndrome (ACS).
To systematically review the literature on troponin testing in patients with CKD without ACS.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014.
Studies examining elevated versus normal troponin levels in patients with CKD without ACS.
Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE). Meta-analyses were conducted when studies had sufficient homogeneity of key variables.
Ninety-eight studies met inclusion criteria. Elevated troponin levels were associated with all-cause and cardiovascular mortality among patients receiving dialysis (moderate SOE). Pooled hazard ratios (HRs) for all-cause mortality from studies that adjusted for age and coronary artery disease or a risk equivalent were 3.0 (95% CI, 2.4 to 4.3) for troponin T and 2.7 (CI, 1.9 to 4.6) for troponin I. The pooled adjusted HRs for cardiovascular mortality were 3.3 (CI, 1.8 to 5.4) for troponin T and 4.2 (CI, 2.0 to 9.2) for troponin I. Findings were similar for patients with CKD who were not receiving dialysis, but there were fewer studies. No study tested treatment strategies by troponin cut points.
Studies were heterogeneous regarding assays, troponin cut points, covariate adjustment, and follow-up.
In patients with CKD without suspected ACS, elevated troponin levels were associated with worse prognosis. Future studies should focus on whether this biomarker is more appropriate than clinical models for reclassifying risk of patients with CKD and whether such classification can help guide treatment in those at highest risk for death.
Agency for Healthcare Research and Quality.
Appendix Table. MEDLINE Search Strategy
Summary of evidence search and selection.
CKD = chronic kidney disease.
* Articles could be excluded for >1 reason.
Pooled HRs from studies that examined the association of elevated troponin level with outcomes between patients who were receiving dialysis and those who were not.
HRs were adjusted for age and coronary artery disease or a risk equivalent. The SOE for outcomes not listed was graded as low or insufficient because we did not find any studies addressing them or were unable to draw conclusions from the evidence. cTnI = cardiac troponin I; cTnT = cardiac troponin T; CVD = cardiovascular disease; HR = hazard ratio; MACE = major adverse cardiovascular event; SOE = strength of evidence.
Pooled HRs, stratified by level of adjustment, for the association of elevated troponin T level with all-cause mortality among patients receiving dialysis.
Boxes indicate individual study point estimates. Horizontal lines represent the 95% CIs for each study. CAD = coronary artery disease; HR = hazard ratio; NR = not reported.
* Used a troponin assay manufactured by Roche.
† Used a troponin assay manufactured by Boehringer Mannheim.
Pooled HRs, stratified by level of adjustment, for the association of elevated troponin I level with all-cause mortality among patients receiving dialysis.
* Used a troponin assay manufactured by Dade Behring.
† Used a troponin assay manufactured by Beckman Coulter.
‡ Used a troponin assay manufactured by Siemens.
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Neelesh Gupta, Nayan Gupta
Kasturba Hospital, B.H.E.L., Bhopal, M.P., India; Mu Sigma Business Solutions Private Limited, Bengaluru, Karnataka, India
November 10, 2014
Difficult Interpretation of Troponin
We read with interest the systematic review and meta-analysis by Erin D Michos et al. published recently in Annals of Internal Medicine.(1) Despite US Food and Drug Administration approval for the measurement of Troponin T (and not Troponin I) levels for prediction of mortality in patients receiving dialysis.(2) The application of this in the day-to-day clinical practice is not homogeneous and wide. One of the reasons could be, practicing physicians and nephrologists are not fully convinced about the data and results of various studies showing the calculations of hazard or odds ratios or relative risk (as done in this meta-analysis as well (1)).
Maybe, it would have been more informative and convincing for a practicing clinician if C-statistics would have been calculated (we know the limitation of such precision in the meta-analysis). Calculating increases in the area under the curve and may be new statistical metrics of discrimination and reclassification. For example, Apple FS et al. showed an increased hazard ratios for cTnI above and below the 99th percentile cutoff while C-statistics showed an area under the curve of 0.53 to predict mortality at two years, exhibiting poor performance.
Now, as in many countries like India (still not in USA) high sensitivity cardiac troponin T(hs cTnT) assays are routinely used in many centers. This makes the true significance of the elevated troponin even more challenging, as most patients on hemodialysis have elevated levels of hs cTn T.
1.Michos Erin D, Wilson Lisa M, Yeh Hsin-chieh et al.:Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: A systematic review and meta-analysis: Ann Intern Med.2014;161(7):502-512.doi:10.7326/M14-0746
2.Roche. FDA clears new intended uses for Roche Diagnostics Troponin T test.Trade News.24 May 2004.
3.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; 106:2941-5
Michos ED, Wilson LM, Yeh H, Berger Z, Suarez-Cuervo C, Stacy SR, et al. Prognostic Value of Cardiac Troponin in Patients With Chronic Kidney Disease Without Suspected Acute Coronary Syndrome: A Systematic Review and Meta-analysis. Ann Intern Med. ;161:491–501. doi: 10.7326/M14-0743
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Published: Ann Intern Med. 2014;161(7):491-501.
Acute Coronary Syndromes, Cardiology, Chronic Kidney Disease, Coronary Heart Disease, Emergency Medicine.
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