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Received on December 5, 2007
Accepted on August 19, 2008
General Clinical Chemistry |
1 Department of Medical Sciences, Uppsala University Hospital, Sweden
2 Department of Mayo Medical School, Rochester, MN
3 Department of Medicine, Uppsala University Hospital, Sweden
4 Department of Clinical Chemistry, Uppsala University Hospital, Sweden
5 Department of Medical Sciences, Cardiology, Uppsala University Hospital, Sweden
* To whom correspondence should be addressed. E-mail: kai.eggers{at}ucr.uu.se.
BACKGROUND: The aim of this study was to evaluate factors influencing measurement of the 99th percentile for cardiac troponin I (cTnI) when this cutoff value is established on a highly sensitive assay, and to compare the value of this cutoff to that of lower cutoffs in the prognostic assessment of patients with coronary artery disease.
METHODS: We used the recently refined Access AccuTnI assay (Beckman-Coulter) to assess the distribution of cTnI results in a community population of elderly individuals [PIVUS (Prospective Study of the Vasculature in Uppsala Seniors) study; n = 1005]. The utility of predefined cTnI cutoffs for risk stratification was then evaluated in 952 patients from the FRISC II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease) study at 6 months after these patients had suffered acute coronary syndrome.
RESULTS: Selection of assay results from a subcohort of PIVUS participants without cardiovascular disease resulted in a decrease of the 99th percentile from 0.044 µg/L to 0.028 µg/L. Men had higher rates of cTnI elevation with respect to the tested thresholds. Although the 99th percentile cutoff was not found to be a useful prognostic indicator for 5-year mortality, both the 90th percentile (hazard ratio 3.1; 95% CI 1.9–5.1) and the 75th percentile (hazard ratio 2.8; 95% CI 1.7–4.7) provided useful prognostic information. Sex-specific cutoffs did not improve risk prediction.
CONCLUSIONS: The 99th percentile of cTnI depends highly on the characteristics of the reference population from which it is determined. This dependence on the reference population may affect the appropriateness of clinical conclusions based on this threshold. However, cTnI cutoffs below the 99th percentile seem to provide better prognostic discrimination in stabilized acute–coronary-syndrome patients and therefore may be preferable for risk stratification.
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