Analytical Characteristics of High-Sensitivity Cardiac Troponin Assays

Results:

The following are 10 points to remember about this review article:

1. Cardiac troponins I (cTnI) and T (cTnT) have been endorsed internationally as the standard biomarkers for the detection of myocardial injury, risk stratification in patients with suspected acute coronary syndrome, and the diagnosis of myocardial infarction.

2. The use of an antibody pair specific to adult cTnT found no evidence of cTnT isoforms corresponding to adult cTnT in skeletal muscle from patients with renal disease. However, a recent analysis has reported that a protein found in skeletal muscle of patients with primary skeletal muscle disease is captured by all of these antibodies, again raising the possibility that the specificity of cTnT for cardiac muscle may not be absolute.

3. Current generations of commercially available TnI assays have an analytical sensitivity almost 100-fold higher (1 vs. 100 ng/L) than that of the first available commercial assays.

4. cTnI measurements are influenced by multiple factors, among which include post-translational modifications (proteolytic degradation and phosphorylation), and complexing with other molecules such as TnC, heparin, heterophile or human antimouse antibodies, and cTnI-specific autoantibodies circulating in patients’ blood, which affect current available assays variably.

5. A working group of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) is cooperating with manufacturers to address the question of whether cTnI standardization or harmonization can be achieved.

6. Multiple different terms have been used to identify newer cTn assays. These include “high-performance,” “highly sensitive,” “high-sensitive,” “ultrasensitive,” “novel highly sensitive,” “sensitive,” and “high sensitivity.”

7. The term “high-sensitivity (hs)” has been proposed to be uniformly used for publication in Clinical Chemistry and throughout the scientific literature.

8. A recommendation on defining an hs assay includes meeting two basic criteria: 1) the total imprecision (cardiovascular) at the 99th percentile value should be <10%, and 2) measurable concentrations below the 99th percentile should be attainable at a concentration value above the assay’s limit of detection for at least 50% (and ideally 95%) of healthy individuals.

9. Concentrations for hs assays should be expressed as ng/L (pg/ml) instead of the commonly published units of µg/L to avoid confusion. For example, a concentration of 0.0015 µg/L would be reported as 1.5 ng/L.

10. Defining what constitutes a healthy reference individual is currently a topic of debate, an important point given the ability of newer generation assays to be able to detect concentrations in “normal” individuals.

Perspective:

This is an updated and readable review on the analytic characteristics of cTn assays with information that will be important for understanding hs assays as well.

Clinical Topics: Acute Coronary Syndromes, Anticoagulation Management, ACS and Cardiac Biomarkers, Anticoagulation Management and ACS

Keywords: Autoantibodies, Myocardial Infarction, Acute Coronary Syndrome, Diterpenes, Protein Isoforms, Biological Markers, Troponin I, Cardiology, Heparin, Troponin T, Myocardium, Phosphorylation


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