Analysis of novel troponin T cut off values that improve early risk stratification of patients with suspected myocardial ischemia

ABSTRACT

TroponinT [TnT] is accepted as a sensitive and specific marker of myocyte necrosis. A consensus recommendation developed by a joint committee of the European Society of Cardiology/American College of Cardiology [JESC/ ACC] that a TnT level above the 99[th] percentile of a reference control population [i.e., TnT >0.01 micro g/1] at a coefficient of variation [cv] of myocyte necrosis. However, the cv of the latest available version of the TnT assay can only achieve this precision at 0.03 micro g/1. A clinical problem arises when an arbitrary cut off point is selected for determination of myocardial infarction [MI] [i.e., TnT >/= 0.1 micro g/1], which the manufacturer continues to recommend, as minor elevations of troponin are associated with increased cardiovascular risk in selected patients with acute coronary syndromes [ACSs]. Therefore, the accepted cut off level of TnT as a sensitive evidence of ischemic cardiac damage is currently under debate. This level is likely to be between 0.03 and 0.1 micro g/1. We evaluated TnT as a risk stratification tool in 235 unselected patients presenting with symptoms of myocardial ischemia [MIS]. We compared a 99[th] percentile MI cut off limit for TnT [at 0.06 micro g/1] determined by constructing a receiver operator curve [ROC] for the patient cohort, in whom ST segment elevation ACS was excluded, to the standard MI cut off value of 0.1 micro g/1 in assessing cardiovascular risk. We also assessed the prognostic significance of detectable TnT values below this 99[th] percentile MI cut off, but above the upper reference limit of healthy controls [i.e., TnT >0.01-<0.03 micro g/1] and of CKMB/total CK ratio [MB%]. TnT was estimated by An electrochemiluminescence immunoassay, CK was assayed by a trichromatic rate technique, and CKMB was measured by mass immunoassay. The diagnosis of ACS was more frequent in groups with higher TnT concentrations 3.3% with normal TnT [TnT<0.03 micro g/1], 16.7% [p<0.01] with TnT values between 0.03 micro g/1 and the 99[th] percentile MI cut off, 70.6% [p<0.001] with detectable TnT between the 99[th] percentile MI cut off and the standard MI cut off [0.06 and 0.099 micro g/1], and 81.6% [p<0.001] with TnT values >/= 0. 1 micro g/1. The 30 day cardiovascular event rate, likewise, increased progressively with increasing TnT values 0.8% with normal TnT. 3.3% with detectable TnT below the 99[th] percentile MI limit, 11.8% [p<0.01] with TnT concentrations between 0.06 and 0.099 micro g/1, and 13.2% [p <0.01] with TnT detectable above the standard MI cut off value [>/= 0. 1 micro g/1]. In conclusion: using a MI cut off value for TnT from a reference cohort with suspected MIS including patients with non-ST segment elevation ACS [NSTE-ACS] improves risk stratification but further studies are required to ascertain the exact cut off