Age and Sex Dependent Upper Reference Limits for the High Sensitivity Cardiac Troponin T Assay

Study Questions:

What is the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) stratified by age, sex, and race?


Data were included from three well characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) study, and the Cardiovascular Health Study (CHS). 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 analyzed and stratified by age, sex, and race.


The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/L, respectively (subcohort 1) and 14, 21, and 28 ng/L, respectively (subcohort 2). These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men ages 65-74 with no cardiovascular disease in this study had cTnT values above the current myocardial infarction (MI) threshold.


The authors concluded that use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to overdiagnosis of MI, particularly in men and the elderly.


The primary finding from this study is that a uniform upper reference limit for the hs-cTnT assay of 14 ng/L, as currently recommended for MI diagnosis, does not reflect the 99th percentile value of a reference population with diverse demographic characteristics. This study demonstrates that 99th percentile values for the hs-cTnT assay are greater in men and rise notably with increasing age in both men and women. New sex- and age-specific cutoff values for the hs-cTnT assay will need to be developed and validated. Use of more accurate, sex- and age-specific 99th percentile values for the hs-cTnT assay may be expected to decrease false-positive MI diagnosis with the hs-cTnT assay, a problem with major clinical and financial implications.

Keywords: Myocardial Infarction, Cardiovascular Diseases, Troponin T

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