Systematic Review of Sex-specific High Sensitivity Cardiac Troponin I and T Thresholds

Abstract

Purpose

High-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) have been demonstrated to have lower sex-specific 99th percentiles in healthy females. However, these sex-specific thresholds are not widely adopted in clinical practice which could lead to underdiagnosis of acute myocardial infarction in females. We conducted a systematic review to explore sex-specific 99th percentiles for hs-cTnI and hs-cTnT from healthy reference populations.

Methods

The principles of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to complete this systematic review. We used PubMed and OVID EMBASE to search for original studies published between November 2017 and November 2021 that included reference populations used to establish the 99th percentiles of hs-cTnI and hs-cTnT with the following inclusion criteria: adults; English language; samples taken as part of a healthy, reference population; studies using high-sensitivity troponin assay; and sample size > 300. Studies were excluded if the reference population sample size was < 300, if a conventional troponin assay was used, or if they did not include independently derived, sex-specific 99th percentiles. Data was extracted from the studies through Covidence to perform a qualitative data synthesis. Female-specific, male-specific, and overall 99th percentiles for hs-cTn were compared.

Findings

We reviewed 131 articles of which 19 met inclusion criteria. These 19 studies derived sex-specific 99th percentiles for 11 different hs-cTnI assays and 9 different hs-cTnT assays. More than 90% (13 of 14 studies) of hs-cTnI assays found lower female 99th percentiles compared to male and to overall 99th percentiles. One study included nine different hs-cTnI assays, of which only one assay resulted in a higher female 99th percentile compared to male and to overall 99th percentiles. Eight of nine hs-cTnT studies (88.9%) found lower female 99th percentiles compared to male and to overall 99th percentiles.

Implications

The data shows significantly lower 99th percentiles in females compared to 99th percentiles in males and overall. Incorporating these sex-specific 99th percentile cut-offs into clinical practice could lead to increased diagnosis and potentially better outcomes for females presenting with acute myocardial infarction.