Age-specific 99th percentile of high-sensitivity cardiac troponin I

Background Precise and rapid identification of myocardial infarction (MI) relies substantially on cardiac troponin measurement, with the 99th percentile upper reference limit serving as the standardised diagnostic cut-off. Increasing evidence indicates that troponin concentrations rise with age, potentially leading to over-diagnosis of MI in elderly patients when using current thresholds. Age-specific upper reference limits are currently not recommended, partly due to scarce clinical data in healthy elderly individuals and older patients with suspected MI. Purpose This study aims to determine age-specific 99th percentile troponin values in a cohort of healthy older people and assess clinical impact when applied to elderly patients presenting with suspected MI. Methods The age-specific 99th percentile of high-sensitivity cardiac troponin I (hs-cTnI, Abbott Architect) was derived from healthy people aged ≥70 years with no prior cardiovascular events recruited to a large clinical trial (ASPREE). The association with major adverse cardiac events (MACE) over up to 10 years was evaluated in Cox regression analyses. To assess its diagnostic value, this age-specific 99th percentile was applied to an independent cohort of patients (BACC) aged ≥70 years presenting with suspected MI. Patients reclassified from > the official 99th percentile to ≤ the age-specific 99th percentile were evaluated regarding their characteristics and incident MACE during follow-up. Results Hs-cTnI measurements were available in 11,889 ASPREE participants (median age 73.9 years, 46.5% male). The age-specific 99th percentile (36 ng/L) exceeded the official 99th percentile (28 ng/L). After application of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) criteria, individuals with impaired renal function, elevated NTproBNP, diabetes or hypertension were excluded. Only 1,395 individuals remained eligible and the 99th percentile was 25.3 ng/L. Individuals with hs-cTnI > 36 ng/L had a 74% increased 10-year risk of MACE (HR 1.74; 95% CI: 1.07–2.81). In the cohort of patients with suspected MI (n=1,272, median age 77 years, 58.5% male), 44 (3.5%) were reclassified from above the official 99th percentile to below the age-specific 99th percentile. Among these, 8 (18.2%) had the diagnosis of Type 1 MI. Reclassification was not independently associated with MACE (HR 1.06; 95% CI: 0.47-2.43). Conclusion Among healthy elderly people, the age-specific 99th percentile for hs-cTnI lies above the official cut-off. However, when applied to patients with suspected MI, it results in minimal reclassification, which is not independently associated with MACE. Our findings do not support routine use of age-specific cut-offs in clinical practice. Remarkably, applying strict IFCC criteria results in 99th percentile values below the official threshold, suggesting that current IFCC-based definitions may be too restrictive for elderly populations.cumulative incidence curve for MACE in ASPREE