Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay

J Am Coll Cardiol. 2014 Apr 15;63(14):1441-8. doi: 10.1016/j.jacc.2013.12.032. Epub 2014 Feb 12.


Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts.

Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization.

Methods: Data were included from 3 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 stratified by age, sex, and race.

Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. 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 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold.

Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.

Keywords: diagnosis; myocardial infarction; population; troponin.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Biological Assay / methods
  • Biomarkers / analysis
  • Biomarkers / blood
  • Blood Chemical Analysis
  • Cohort Studies
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / blood*
  • Myocardial Infarction / diagnosis*
  • Reference Values
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Sex Factors
  • Troponin T / analysis
  • Troponin T / blood*


  • Biomarkers
  • Troponin T