Sylvie R. Stacy, MD, MPH (*); Catalina Suarez-Cuervo, MD (*); Zackary Berger, MD, PhD; Lisa M. Wilson, ScM; Hsin-Chieh Yeh, PhD; Eric B. Bass, MD, MPH; Erin D. Michos, MD, MHS
Disclaimer: 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. Stacy reports that she worked under a contract from AHRQ during the conduct of the study. Ms. Wilson reports that she worked under a contract from AHRQ during the conduct of the study. Dr. Bass reports receiving a contract from AHRQ for the conduct of the study. Dr. Michos worked under a contract from AHRQ during the conduct of the study and a grant from the National Institutes of Health outside of the submitted work. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M14-0746.
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, Carnegie 568, Baltimore, MD 21287; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Stacy: Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Room WB602, Baltimore, MD 21205.
Dr. Suarez-Cuervo and Ms. Wilson: Johns Hopkins University, Evidence-based Practice Center, 624 North Broadway, Suite 680, Baltimore, MD 21205.
Dr. Berger: Johns Hopkins Outpatient Center, 601 North Caroline Street, Suite 7143, Baltimore, MD 21287.
Dr. Yeh: Johns Hopkins University, 2024 East Monument Street, Suite 2-500, Baltimore, MD 21287.
Dr. Bass: Johns Hopkins University School of Medicine, 624 North Broadway, Room 680A, Baltimore, MD 21205.
Dr. Michos: Johns Hopkins University School of Medicine, 600 North Wolfe Street, Carnegie 568, Baltimore, MD 21287.
Author Contributions: Conception and design: C. Suarez-Cuervo, Z. Berger, L.M. Wilson, H.C. Yeh, E.B. Bass, E.D. Michos.
Analysis and interpretation of the data: S.R. Stacy, C. Suarez-Cuervo, Z. Berger, L.M. Wilson, H.C. Yeh, E.B. Bass, E.D. Michos.
Drafting of the article: S.R. Stacy, C. Suarez-Cuervo, Z. Berger, E.D. Michos.
Critical revision of the article for important intellectual content: C. Suarez-Cuervo, Z. Berger, L.M. Wilson, H.C. Yeh, E.B. Bass, E.D. Michos.
Final approval of the article: S.R. Stacy, C. Suarez-Cuervo, Z. Berger, L.M. Wilson, E.B. Bass, E.D. Michos.
Provision of study materials or patients: L.M. Wilson, E.B. Bass.
Statistical expertise: H.C. Yeh.
Obtaining of funding: E.B. Bass.
Administrative, technical, or logistic support: L.M. Wilson, E.B. Bass, E.D. Michos.
Collection and assembly of data: S.R. Stacy, C. Suarez-Cuervo, Z. Berger, L.M. Wilson, E.D. Michos.
Stacy SR, Suarez-Cuervo C, Berger Z, Wilson LM, Yeh H, Bass EB, et al. Role of Troponin in Patients With Chronic Kidney Disease and Suspected Acute Coronary Syndrome: A Systematic Review. Ann Intern Med. 2014;161:502-512. doi: 10.7326/M14-0746
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Published: Ann Intern Med. 2014;161(7):502-512.
Patients with chronic kidney disease (CKD) have high prevalence of elevated serum troponin levels, which makes diagnosis of acute coronary syndrome (ACS) challenging.
To evaluate the utility of troponin in ACS diagnosis, treatment, and prognosis among patients with CKD.
MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials through May 2014.
Studies examining elevated versus normal troponin levels in terms of their diagnostic performance in detection of ACS, effect on ACS management strategies, and prognostic value for mortality or cardiovascular events after ACS among patients with CKD.
Paired reviewers selected articles for inclusion, extracted data, and graded strength of evidence (SOE).
Twenty-three studies met inclusion criteria. The sensitivity of troponin T for ACS diagnosis ranged from 71% to 100%, and specificity ranged from 31% to 86% (6 studies; low SOE). The sensitivity and specificity of troponin I ranged from 43% to 94% and from 48% to 100%, respectively (8 studies; low SOE). No studies examined how troponin levels affect management strategies. Twelve studies analyzed prognostic value. Elevated levels of troponin I or troponin T were associated with higher risk for short-term death and cardiac events (low SOE). A similar trend was observed for long-term mortality with troponin I (low SOE), but less evidence was found for long-term cardiac events for troponin I and long-term outcomes for troponin T (insufficient SOE). Patients with advanced CKD tended to have worse prognoses with elevated troponin I levels than those without them (moderate SOE).
Studies were heterogeneous in design and in ACS definitions and adjudication methods.
In patients with CKD and suspected ACS, troponin levels can aid in identifying those with a poor prognosis, but the diagnostic utility is limited by varying estimates of sensitivity and specificity.
Agency for Healthcare Research and Quality.
Appendix Table 1. Detailed Search Strategies
Summary of evidence search and selection.
ACS = acute coronary syndrome; CKD = chronic kidney disease.
* Articles could be excluded for >1 reason.
Table 1. SOE for Diagnostic Accuracy and Prognostic Value of Elevated Troponin Level in Patients With CKD and Suspected ACS
Table 2. Operating Characteristics of Elevated Troponin Level in Diagnosis of ACS Among Patients With CKD
Appendix Table 2. Characteristics of Studies Analyzing Operating Characteristics of Elevated Troponin Level in Diagnosis of ACS Among Patients With CKD
Sensitivity and specificity of elevated troponin T level in the diagnosis of ACS among patients with CKD.
Solid symbols represent studies that adjudicated ACS, and open symbols represent studies that did not adjudicate or did not report adjudicating ACS. Diamonds indicate studies that used a troponin T cutoff <0.1 µg/L. Circles indicate studies that used a troponin T cutoff ≥0.1 µg/L. ACS = acute coronary syndrome; CKD = chronic kidney disease; hsTnT = high-sensitivity troponin T.
* Did not specify whether patients were receiving dialysis.
† Included patients receiving dialysis.
Sensitivity and specificity of elevated troponin I level in the diagnosis of ACS among patients with CKD.
Solid symbols represent studies that adjudicated ACS, and open symbols represent studies that did not adjudicate or did not report adjudicating ACS. Diamonds indicate studies that used a troponin I cutoff <0.1 µg/L. Circles indicate studies that used a troponin I cutoff of 0.1 to <0.5 µg/L. Squares indicate studies that used a troponin I cutoff of 0.5 to <1.0 µg/L. Triangles indicate studies that used a troponin I cutoff ≥1.0 µg/L. ACS = acute coronary syndrome; CKD = chronic kidney disease.
* Included both patients who were and were not receiving dialysis.
‡ Did not specify whether patients were receiving dialysis.
§ Included patients not receiving dialysis.
Appendix Table 3. Characteristics of Studies Evaluating Short- or Long-Term Prognosis of Patients With CKD After Presentation With ACS
Appendix Table 4. Association of Elevated Troponin T Level With Adverse Outcomes Among Patients With CKD Presenting With ACS Symptoms
Appendix Table 5. Association of Elevated Troponin I Level With Adverse Outcomes Among Patients With CKD Presenting With ACS Symptoms
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Neelesh Gupta, Nayan Gupta
Kastuba Hospital,Bhopal,India ; Mu Sigma Business Solutions Pvt.Ltd.,Bengaluru,India
November 4, 2014
True Significance of Elevated 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)).May be, 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, AppleFS 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.Conflict of Interest: NoneReferences: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/M14-07462.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; 106:2941-5Neelesh Gupta,Medical student (Intern), Kastuba Hospital,Bhopal,IndiaNayan Gupta,B.Tech, Data analyst,Mu Sigma Business Solutions Pvt.Ltd.,Bangaluru,India
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