Key result
Specificity- and likelihood-ratio-derived troponin thresholds provide more consistent MI risk prediction than 99th percentiles.
Why the study?
The two methods used to determine cardiac troponin thresholds for high-risk stratification of MI—healthy population 99th percentiles and thresholds targeting a 70% positive predictive value—were hypothesized to produce inconsistent prediction of MI risk.
Do cardiac troponin thresholds derived using positive likelihood ratio or specificity provide more consistent prediction of myocardial infarction risk than 99th percentile or 70% PPV thresholds in patients presenting to the emergency department with chest pain?
Observational (n=2,584)
Do cardiac troponin thresholds derived using positive likelihood ratio or specificity provide more consistent prediction of myocardial infarction risk than 99th percentile or 70% PPV thresholds in patients presenting to the emergency department with chest pain?
In emergency department chest pain patients, deriving high-sensitivity cardiac troponin thresholds using specificity or positive likelihood ratio provides more consistent myocardial infarction risk prediction across sexes and varying disease prevalence than using 99th percentiles or positive predictive value.
Answers are grounded in this paper and cite their sources.
May support more consistent troponin-based MI risk stratification across sexes; leaves open prospective validation before practice change.
BACKGROUND: Two methods are used to determine cardiac troponin (cTn) thresholds for high-risk stratification for myocardial infarction (MI), namely the assay's healthy population 99th percentiles and a threshold that has a positive predictive value (PPV) of about 70%. We hypothesized that these methods may produce inconsistent prediction of MI risk. METHODS: We compared the positive likelihood ratio (LR+), sensitivity, and specificity at 99th percentiles and published high-risk thresholds for a high-sensitivity (hs) cTnI (Abbott) and cTnT (Roche) assay. We simulated the high-risk threshold derivation methodology that derives thresholds with 70% PPV as a function of prevalence and sample size. We derived and validated thresholds based on LR+ = 20 and specificity = 95%. RESULTS: In 2584 patients there was an almost 2-fold difference in LR+ between males and females at the sex-specific 99th percentiles, and a 2- to 3-fold difference between assays. Thresholds giving 70% PPV were much higher in lower-prevalence cohorts for both assays, being 3- to 10-fold lower at 5% than 20% prevalence. Thresholds derived using a LR+ or specificity had similar performance in a validation cohort between sexes but had a 2-fold difference in LR+ in a validation cohort between assays. CONCLUSIONS: In patients presenting to the emergency department with possible MI, sex-specific 99th percentile thresholds convey lower risk of MI for females than males. Risks also differed between assays. Risk thresholds derived using the PPV vary considerably with the prevalence and size of cohort. Thresholds derived with specificity or positive likelihood ratio had more consistent risk-prediction.
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Pickering et al. (2026) conducted an observational in Possible myocardial infarction / chest pain (n=2,584). Troponin thresholds based on LR+ = 20 or specificity = 95% (hs-cTnI Abbott and hs-cTnT Roche) vs. Healthy population 99th percentile and 70% PPV thresholds was evaluated on Positive likelihood ratio (LR+), sensitivity, and specificity for myocardial infarction risk stratification. Troponin thresholds derived using LR+=20 or 95% specificity showed more consistent MI risk prediction than 99th percentiles (nearly 2-fold sex difference in LR+) or 70% PPV thresholds.
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