High sensitivity cardiac troponin T assay may lead to over diagnosis of myocardial infarction

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A study published ahead of print in the Journal of the American College of Cardiology has found that the 99th percentile values for the high sensitivity cardiac troponin T (hs-cTnT) assay that is used to aid diagnosis of myocardial infarction are significantly higher in healthy men aged ≥50 years and healthy women aged ≥65 than the currently recommended cutoff value of 14ng/L—suggesting that using a universal cutoff value may lead to an over diagnosis of myocardial infarction.

Study authors M Odette Gore (Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA) and others write that the hs-cTnT assay has been implemented in many countries for the diagnosis of myocardial infarction, adding “By convention, the upper reference limit for high sensitivity troponin assays is defined as the 99th percentile value from a normal reference population.”


The presently accepted upper reference limit for the hs-cTnT assay is 14ng/L. However, the authors comment that this is based on a study of “apparently healthy” participants “with little information regarding subject selection” and that the current cutoff does not “take into account patient sex, age, and race”. Therefore, Gore et al analysed cardiac troponin T values (measured with the hs-cTnT assay) of patients in three large independent community-based studies, looking at two subcohorts: individuals free from recent hospitalisation of any cause with no clinical cardiovascular disease or stage III or greater chronic kidney disease (subcohort one); and subcohort one patients without subclinical heart disease (subcohort two).


A total of 12,618 adults were analysed in the study, and the 99th percentile values were significantly higher than 14ng/L in subcohort one patients from all three studies and in subcohort two patients from two studies. The authors note: “Moreover, the 99th percentile values were significantly higher than 14ng/L in all strata of men aged ≥50 years and women aged ≥65 years. Importantly, 99th percentile values were consistent across cohorts within age and sex strata.”


Gore et al also found that 99th percentile values were higher in men compared with women, in black individuals compared with non-black individuals, and in subgroups of increasing age among both men and women (≥65 years). They note: “More than 10% of men older than 65 years in our study who were free from clinical or subclinical cardiovascular disease had cTnT values above the current myocardial infarction threshold. This suggests that clinical use of hs-cTnT assay with the currently recommended cutpoint may result in over diagnosis of myocardial infarction, particularly in elderly men.”


Based on their findings, they propose that the cutoff values for the assay are increased to 17ng/L for men aged 50–64 and for women aged 65 or older and to 31ng/L for men aged 65 or older (provided that further studies show that these cutoffs improve diagnostic performance in myocardial infarction). They claim that the current cutoff point should only be used for men younger than 50 years and women younger than 65 years. “Of note, the true 99th percentile cTnT value for women younger than 50 may be lower than 14ng/L but validating a lower cutoff is not feasible with the current assay because the coefficient of variation of the assay exceeds 10% at values of 13ng/L and lower”, Gore et al comment.


The authors conclude: “Use of more accurate, sex- and age-specific 99th percentile values for the hs-cTnT assay would be expected to decrease false positive myocardial infarction diagnosis with the hs-cTnT assay, a problem with major clinical and public health ramifications.”


Study author James de Lemos (Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, USA) told Cardiovascular News: “False positive myocardial infraction diagnoses have important implications as patients may be exposed to treatments, including invasive therapies, that expose them to risks without benefit. Also, false positive myocardial infarction tests contribute to the growing problem of ‘troponin fatigue’ where clinicians become sceptical of the value of the diagnostic test. For these reasons, it is important that normal ranges be accurately determined so troponin tests can be appropriately used.”