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Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy

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Abstract

Objective

A recently developed immunoassay for high-sensitivity measurement of cardiac troponin T (hsTnT) allows measurement at the 99th percentile for a normal population with an assay imprecision <10%. It is unclear whether such a low cutpoint (14 ng/L) is helpful for long-term risk stratification of patients with an acute coronary syndrome (ACS) undergoing routine early invasive strategy.

Patients and main outcome measures

Consecutive patients with ACS admitted to a chest pain unit were studied. The usefulness of hsTnT for early diagnosis of myocardial infarction (MI) and prediction of all-cause death or death/MI over a median of 271 days following presentation was compared against the fourth generation cTnT at the 99th percentile cutpoint.

Results

Of 1,384 patients with ACS enrolled, 47.8% had non-ST-segment elevation MI (NSTEMI), 26.4% unstable angina, 21.8% STEMI and 4% had non-ACS. Adjusted risk for all-cause death [adjusted HR 8.26 (95%CI: 1.13–66.33), p = 0.038] and death/MI [adjusted HR 2.71 (95% CI: 1.15–6.38), p = 0.023] were significantly higher with hsTnT above the 99th percentile. In particular, among patients with a standard fourth generation cTnT result below the 99th percentile cutoff (0.01 ng/mL), hsTnT improved risk assessment. Mortality risk associated with an elevated hsTnT was present across the spectrum of ACS, as well as in conditions with hsTnT elevations not related to ACS.

Conclusion

hsTnT at the 99th percentile cutoff is useful for the diagnostic evaluation of patients with ACS, and provides strong and independent predictive power for adverse long-term outcomes even after early invasive strategy.

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Acknowledgments

We thank Mr. Oliver Hartmann, a biostatistician from BRAHMS Biomarkers (clinical diagnostics division of Thermo Fisher Scientific) for support regarding statistical analyses. EG has received financial support for clinical trials from Roche Diagnostics, Germany. He is consultant to Roche Diagnostics and receives honoraria for lectures from Roche Diagnostics. JLJ has received grant support from Roche Diagnostics, and has received honoraria for lectures from Roche Diagnostics. HAK has developed the cTnT assay and holds a patent jointly with Roche Diagnostics. He has received grants and research support from several companies, and has received honoraria for lectures from Roche Diagnostics. DZ and GH are employees of Roche Diagnostics responsible for the preclinical testing of hsTnT. The investigations were supported by Roche Diagnostics, Germany providing assays for hsTnT assay.

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Authors and Affiliations

  1. Medizinische Klinik, Abteilung für Innere Medizin III, Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Germany

    S. Celik, E. Giannitsis, K. Schwöbel, D. Lossnitzer, T. Hilbel, S. Lehrke & H. A. Katus

  2. Roche Diagnostics GmbH, Nonnenwald 2, Penzberg, Germany

    D. Zdunek & A. Hess

  3. Klinik für Kardiologie und Angiologie, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Germany

    K. C. Wollert

  4. Cardiology Division, Massachusetts General Hospital, Boston, MA, 02114, USA

    J. L. Januzzi

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Correspondence to E. Giannitsis.

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392_2011_344_MOESM4_ESM.ppt

Supplemental Fig. 1. Kaplan–Meier survival (A) and event-free survival (B, death/MI) according to four ranges of cTnT (< 0.01 ng/mL, 0.01 ng/mL - < 0.03 ng/mL, ≥ 0.03 ng/mL - < 0.1 ng/mL, and ≥ 0.1 ng/mL). The concentration of 0.01 ng/mL corresponds to the 99th percentile value, 0.03 ng/mL corresponds to the cutoff that can be measured with ≤ 10% CV, and 0.1 ng/mL corresponds to ROC determined cutoff. (PPT 364 kb)

392_2011_344_MOESM5_ESM.ppt

Supplemental Fig. 4. The absolute risk of death and the composite of death/MI in the reference category was 0.2% and 1.4%, respectively. Unadjusted HRs and 95% CIs for all-cause death and the composite of all-cause death or MI by deciles of hsTnT at baseline. The concentration range for hsTnT, rate of death [triangles], or death/MI [circles]) are reported for each decile of hsTnT. HRs and 95% CIs are reported on a logarithmic scale. The HRs (95% CI) for all-cause death (OR 12.94 (1.66-100.98), p = 0.015) and the composite of all-cause death or MI (OR 12.79 (2.94-55.53), p = 0.0007) were significantly higher at decile 4 (median 34.6 ng/L; concentration range 22.5-46.2 ng/L) and higher deciles than for the reference category (decile 1; Fig. 4). Number of patients per decile = 138 to 139. (PPT 119 kb)

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Celik, S., Giannitsis, E., Wollert, K.C. et al. Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy. Clin Res Cardiol 100, 1077–1085 (2011). https://doi.org/10.1007/s00392-011-0344-x

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