Age-Related Cutoffs for Troponin I
The 99th percentile upper reference limit for high-sensitivity cardiac troponin I increases with age and is higher in men than women, but current major guidelines recommend using the assay-specific 99th percentile (typically 14-53 ng/L depending on manufacturer and sex) rather than age-stratified cutoffs for diagnosing myocardial infarction. 1
Standard Diagnostic Thresholds
The American College of Cardiology/American Heart Association endorses the 99th percentile upper reference limit as the diagnostic threshold for myocardial injury and, in the appropriate clinical context, myocardial infarction. 1 This threshold must be combined with evidence of dynamic change (rising and/or falling pattern) to diagnose acute MI. 1
Assay-Specific 99th Percentile Values
The 99th percentile varies substantially by manufacturer: 2
- hs-cTnT (Elecsys; Roche): 14 ng/L
- hs-cTnI (Architect; Abbott): 16-20 ng/L
- hs-cTnI (Centaur; Siemens): 40-50 ng/L (34 ng/L women, 53 ng/L men) 3
- hs-cTnI (Access; Beckman Coulter): 17-19 ng/L
Age-Related Variation in Troponin Values
Evidence for Age-Dependent Increases
Multiple large population studies demonstrate that the 99th percentile upper reference limit increases significantly with age: 4
- In the Dallas Heart Study, ARIC Study, and Cardiovascular Health Study, the 99th percentile for hs-cTnT ranged from 18 ng/L in younger cohorts to 36 ng/L in elderly cohorts 4
- More than 10% of men aged 65-74 years with no cardiovascular disease had cardiac troponin T values above the current 14 ng/L threshold 4
- For hs-cTnI, both men and women aged ≥55 years had significantly higher 99th percentile values than those <55 years 5, 6
Sex-Specific Differences
The 99th percentile is consistently higher in men than women across all age groups: 1
- For hs-cTnI (Architect), sex-specific thresholds are approximately two-fold higher in men than women 1
- In healthy Chinese adults, the 99th percentile was 12.5 ng/L in men versus 9.6 ng/L in women 5
- In Korean populations, values were 20 ng/L for males and 19 ng/L for females 6
Clinical Implementation Challenges
Why Age-Specific Cutoffs Are Not Routinely Used
Despite clear age-related increases in troponin values, current guidelines do not recommend age-stratified diagnostic thresholds for several reasons: 1
Lack of standardization: The 99th percentile varies based on how "healthy" populations are defined—stringent screening criteria (excluding subclinical disease with biomarkers like NT-proBNP) yield lower thresholds, while less stringent criteria yield higher thresholds 1
Risk of under-diagnosis: Using higher age-specific cutoffs in elderly patients could miss acute MI in a population at highest risk for adverse outcomes 4
Need for dynamic change: The diagnosis of acute MI requires demonstration of rising/falling troponin patterns, not just a single elevated value, which mitigates concerns about static age-related elevations 1, 2
Critical Pitfalls to Avoid
Do not diagnose MI based solely on an elevated troponin value: Clinical context (ischemic symptoms, ECG changes) and dynamic change (≥20% relative change or assay-specific absolute change) are mandatory 1, 2
Recognize that 40% of patients undergoing clinical troponin testing may have values above the 99th percentile: This reflects the high prevalence of chronic myocardial injury in symptomatic populations, not acute MI 1
Be aware that massive troponin elevations (>5× the 99th percentile) can occur with non-ischemic conditions: Myocarditis, Takotsubo syndrome, and pulmonary embolism can all cause marked elevations 2
Practical Approach
Use the assay-specific 99th percentile provided by your laboratory (which should be sex-specific if available) as the diagnostic threshold, but always interpret troponin values in the context of:
- Serial measurements demonstrating dynamic change (0 and 2-3 hours minimum) 1
- Compatible clinical presentation with ischemic symptoms 2
- ECG findings 1
- Exclusion of alternative diagnoses causing myocardial injury 2
For rapid rule-out protocols, the 2020 ESC 0/1-hour algorithm uses lower thresholds (hs-cTnT <5 ng/L, hs-cTnI <3-4 ng/L at presentation) that safely identify low-risk patients regardless of age. 2