Systematic Review of Sex-specific High Sensitivity Cardiac Troponin I and T Thresholds
Mengchen Cao1, Ava E Pierce1, Marquita S Norman1
1Department of Emergency Medicine, UT Southwestern Medical Center, Dallas, Texas.
Insights
High-sensitivity cardiac troponin assays show lower 99th percentiles in females. Adopting these sex-specific thresholds can improve acute myocardial infarction diagnosis in women.
Area of Science:
- Cardiology
- Biomarkers
- Sex-Specific Medicine
Background:
- High-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays have established 99th percentiles, but lower female thresholds are often overlooked.
- Clinical underdiagnosis of acute myocardial infarction (AMI) in females may result from the non-adoption of sex-specific troponin cut-offs.
- This systematic review investigates sex-specific 99th percentiles for hs-cTnI and hs-cTnT in healthy populations.
Approach:
- A systematic review adhering to PRISMA guidelines was conducted.
- Searches of PubMed and OVID EMBASE identified studies published between November 2017 and November 2021.
- Inclusion criteria specified healthy adult reference populations (>300 participants) using high-sensitivity troponin assays with independently derived, sex-specific 99th percentiles.
Key Points:
- Nineteen studies met the inclusion criteria, analyzing 11 hs-cTnI and 9 hs-cTnT assays.
- Over 90% of hs-cTnI assays and 88.9% of hs-cTnT assays revealed lower 99th percentiles in females compared to males and overall populations.
- One study with multiple hs-cTnI assays found only one assay with higher female 99th percentiles.
Conclusions:
- The findings confirm significantly lower 99th percentiles for hs-cTn in females across various assays.
- Implementing sex-specific 99th percentile cut-offs in clinical practice is crucial for accurate AMI diagnosis in women.
- Adoption of these thresholds may lead to improved diagnostic accuracy and patient outcomes for females experiencing AMI.
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.
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