JACC in a Flash | High-sensitivity assays for cardiac troponin T (hs-cTnT) have recently been implemented in several countries for the diagnosis of acute MI, but have yet to be implemented in US practice. Currently, there is no clear consensus regarding the "normal" reference population, and how to judge the upper limits for these assays—a critically important number for the use and interpretation of troponin assays.

Recently, M. Odette Gore, MD, from the University of Texas Southwestern Medical Center in Dallas, and colleagues analyzed cTnT values measured with the hs-cTnt assay in three large, independent, community-based cohorts: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS).

The presently accepted 99th percentile for these tests is 14 ng/L, which was initially derived from a study of "apparently healthy" volunteers and blood donors, with little information reported regarding selection criteria. It is also important to note, the authors write, that this cutoff does not take patient sex, age, and race into account.

The current study included 12,618 adults; within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease and kidney disease (Subcohort 1) and further excluding those with subclinical structural heart disease (Subcohort 2). Data were stratified by age, sex, and race.

The 99th percentile values for the hs-cTnT assay were:

• Subcohort 1: 18 ng/L (DHS), 22 ng/L (ARIC), and 36 ng/L (CHS)
• Subcohort 2: 14 ng/L (DHS), 21 ng/L (ARIC), and 28 ng/L (CHS)

These differences in 99th percentile values paralleled age differences across cohorts, and analyses along sex and age strata yielded similar results between cohorts. Within each cohort, increased age and male gender increased 99th percentile values: more than 10% of men aged 65-74 with no cardiovascular disease in this study had cTnT values above the current MI threshold.

Ultimately, the authors suggest that use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of MI, particularly in men and the elderly. Clinical validation, therefore, is needed of new age- and sex-specific cutoff values for this assay.

In an accompanying editorial, Christopher M. Kramer, MD, from the University of Virginia Health System, described the problems with newer hs-cTnT assays: "These new assays can detect cTnT concentrations 10-fold lower than current assays. They increase the sensitivity for acute MI but at the price of a reduction in specificity that could lead to a plague of 'troponinitis' and confusion to the clinical cardiology community regarding interpretation of these values."

While the article by Gore et al. presents "convincing" data in regards to the flaws in the presently used 99th percentile for the hs-cTnT assays, Dr. Kramer added, the retrospective study design means it is not ideal to truly test these cutoffs limits. "We, as a cardiology community, have work to do if we wish to avoid the imminent plague of troponinitis that will be upon us if we are unable to interpret the high-sensitivity cardiac troponin T assays that will undoubtedly be coming to an emergency department and intensive care unit near us very soon."

Gore MO, Seliger SL, deFillippi CR, et al. J Am Coll Cardiol. 2014 February 12. [Epub ahead of print]
Kramer CM. J Am Coll Cardiol. 2014 February 12. [Epub ahead of print]

Keywords: Risk, Intensive Care Units, Patient Selection, Plague, Emergency Service, Hospital, Consensus, Troponin, ACC Publications, CardioSource WorldNews

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