How does the sensitivity, specificity, and precision of cardiac troponin assays vary?

Updated: Jul 30, 2021
  • Author: Kamal (Komo) Gursahani, MD, MBA; Chief Editor: Barry E Brenner, MD, PhD, FACEP  more...
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The sensitivity, specificity, and precision of the different commercially available troponin assays vary considerably. These differences are related to a lack of standardization, the use of different monoclonal antibodies, the presence of modified TnI and TnT in the serum, and variations in antibody cross-reactivity to the myriad detectable forms of TnI that result from its degradation.

At present, the 99th upper reference limit of cardiac troponin is still the best-established criterion for the diagnosis of acute MI. [18, 19] Only one manufacturer produces the TnT assay, and its 99th percentile cutoffs and the 10% CV are well established. However, up to 20-fold variation has occurred in results obtained with the multitude of commercial TnI assays currently available, each with their own 99th percentile upper reference limits and 10% CV levels.

In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) IV study, a relatively insensitive point-of-care TnI assay was used to screen patients for study eligibility. In a subsequent study, the blood samples were reanalyzed using the 99th percentile cutoff of a far more sensitive central laboratory TnT assay. [20] The more sensitive 99th percentile cutoff of this TnT assay identified an additional 96 (28%) of 337 patients with a positive TnT result but negative point-of-care TnI; these patients had higher rates of death or MI at 30 days. [20]

In a similar reanalysis of the TACTICS-TIMI 18 trial, three different TnI cutoffs were compared on 1821 patients to evaluate the 30-day risk of death or MI: the 99th percentile, 10% CV, and the World Health Organization (WHO) acute MI cutoffs. [21, 22] (The WHO cutoffs define acute MI using creatine kinase-MB [CK-MB] and report troponin levels as either a higher “acute MI level” or a lower “intermediate level” that is correlated with “leak” or “minor myocardial injury.”)

Using the 10% CV cutoff identified, an additional 12% more cases were identified relative to the WHO acute MI cutoff. The 99th percentile cutoff identified an additional 10% of cases relative to the 10% CV cutoff, as well as a 22% increase in the number of cases over the WHO acute MI cutoff. Nevertheless, the odds ratios for the adverse cardiac event rates of death or MI at 30 days were similar for all three cutoffs, suggesting that the lower cutoffs detected more patients with cardiovascular risk without sacrificing specificity. [21, 22]

The American Association for Clinical Chemistry Academy (AACC) (formerly the National Academy of Clinical Biochemistry [NACB]) working with the ACC/ESC guidelines has recommended adoption of the 99th percentile upper reference limit as the recommended cutoff for a positive troponin result. [19, 23, 24] Ideally, the precision of the assay at this cutoff level should be measured by a CV that is less than 10%.

However, most TnI assays are imprecise at the 99th percentile reference limit. [25] Some have therefore recommended that the cutoff level be raised to the slightly higher 10% CV level instead of the 99th percentile reference limit to ensure adequate assay precision.

In addition, studies have shown that populations within the 99th percentile reference limit include patients with low troponin levels who nevertheless have an elevated cardiac risk, and that the true 99th percentile cutoff for a healthy patient population is actually a factor of 10-50 lower. Accordingly, these investigations suggest that higher sensitivity or ultrasensitive troponin assays are necessary. [22] A high-sensitivity cardiac troponin (hs-cTn) can quantify lower cardiac troponin concentrations by up to 10 fold lower than conventional assays while also detecting measurable cardiac troponin values in over 50% of healthy subjects. These tests are very precise in that their CV is below 10% at the 99th percentile upper reference limit. Therefore, the advantage of ultrasensitive troponins is based on the premise that lower cutoff levels achieve higher sensitivity that will allow earlier diagnosis, often within 90 minutes of presentation. High-sensitivity troponins confer additional clinical benefits in that they help detect myocardial injury due to acute ischemia earlier, sometimes before a larger infarct occurs. [26]

Cardiac Markers. This graph describes the improved Cardiac Markers. This graph describes the improved sensitivity of the cardiac troponin assay. Whereas conventional cardiac troponin assays could detect the red region in patients with myocardial necrosis, the newer high-sensitivity assays can detect people with myocardial injury, early onset myocardial infarction, and baseline cardiac troponin levels in 50% of healthy patients. Courtesy of Oxford University Press [Park KC, Gaze DC, Collinson PO, Marber MS. Cardiac troponins: from myocardial infarction to chronic disease. Cardiovasc Res. 2017 Dec 1;113(14):1708-18. Online at]

Additionally, the introduction of hs-cTn assays into practice necessitates serial measurements to differentiate a number of previously mentioned disease states that cause myocardial injury. [27]

Of note, the 99th percentile upper reference limit has been shown to differ between men and women when measured with high-sensitivity assays. [19, 23, 24, 28]

To optimize use of the assay in the emergency department (ED), it is important to be familiar with the particular troponin assay available in the individual laboratory and to know whether the cutoff is set at the 10% CV level or at the 99th percentile upper reference limit.

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