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The concept and use of the 99th percentile for interpre- tation of cardiac troponin was introduced with the re- definition of myocardial infarction in 2000, a time when few assays could detect cardiac troponin at the 99th percentile and none could meet the criteria of an assay CV of 10% at this concentration. There have been many reports of the 99th percentile providing useful information toward defining a population at high risk of future myocardial injury (1 ).
However, as we increase our knowledge regarding cardiac troponin, it is apparent that the 99th percentile has limitations. Cardiac troponin may be released in response to minor noncardiac illness, and this can cause confusion. Further, with the new high-sensitivity (hs)6 assays becoming available, it is apparent that most healthy persons have low concentrations of car- diac troponin present in their blood. Thus we have to come to terms with the concept that cardiac troponin may be released by physiological mechanisms as well as pathological ones. As assay quality has improved, the use of cardiac troponin in a clinical setting has become more complex and confusing.
We list below some of the ways in which 99th per- centile has problems and how we may be better served by other criteria when using cardiac troponin for the assessment of individual patients.
Cardiac Troponin below the 99th Percentile May Also Identify Persons at Risk of a Major Coronary Event
Many studies that use conventional and hs cardiac tro- ponin assays have demonstrated that there is a progres- sive rise in risk from the assay limit of detection (2, 3 ). This is logical when one considers the nature of the acute coronary syndrome, where in the vast majority of cases there is rupture of a plaque, leading to emboli causing cardiac myocyte ischemia and death. The number of cells affected might range from very few to very many, and this will be reflected in the relative car- diac troponin concentration. There is no magic thresh- old at which a person suddenly becomes at risk of a cardiac event. Putting an arbitrary cutpoint into a con- tinuum of disease is not ideal.
Variability between Assays
Cardiac troponin I (cTnI) assays are not standardized. Results with early assays could vary greatly in...