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

Abstract

Objectives To determine the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) in three large independent cohorts. Background The presently recommended 14 ng/L cutpoint 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 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 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 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 aged 65–74 with no cardiovascular disease in our study had cTnT 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.

High-Sensitivity Troponin T and N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and Risk of Incident Heart Failure in Patients with CKD

“…Furthermore, we did not observe any differences in the associations or thresholds of each cardiac biomarker with risk of incident HF in important subgroups. Prior investigations have suggested that thresholds for troponin, for example, may be higher in men (versus women) 32,33 and blacks (versus whites). 33 Interestingly, it has been suggested that NT-proBNP levels may be higher in women (versus men) 34 and blacks (versus whites).…”

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

“…Regarding the highly sensitive cTnT ECLIA method, variability among the 99th URL values reported in different studies and by manufacturers is very similar (Table 5) [9,12,26,41,124,[126][127][128]. Considering as a whole the clinical studies including a total of 10,078 individuals [9,12,26,47,124,[126][127][128], median (25th-75th percentiles) values of 99th URL results of highly sensitive cTnT ECLIA method are for the overall population 14.6 (13.2-18.0) ng/L, for men 16.0 (15.0-19.5) ng/L, and for women 12.0 (9.6-12.5) ng/L, respectively.…”

“…Data reported by Franzini et al [26], for example, show that the calculated 99th URL values for cTnT ECLIA method in apparently healthy elderly men and women (>65 years) were 36.8 ng/L and 28.6 ng/L, respectively, whereas the 99th URL value advocated by the manufacturer is 14 ng/L. Furthermore, Gore et al [41] reported that the use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of AMI, particularly in men and the elderly.…”

What are normal high-sensitivity troponin-T values in a large multi-ethnic Asian population?

“…Troponin elevations with age, contributed in part by age-related co-morbidities, have been emphasized [23][24][25]. Sandoval [9] and Collinson [26] underscore the vital role of population selection and pre-screening on the 99P decision limit.…”