Evidence Alert : Heart attack claims and cardiac biomarkers above the 99th percentile

Caution should be used when claims assessors assess heart attack critical illness claims given the findings of a recent study (Mariathas et al., 2019). The study measured high sensitivity troponin I (hs-trop I) in 20,000 consecutive in-patients and out-patients seen at a UK hospital, regardless of why they presented to hospital (most presented without any clinical suspicion of myocardial infarction). Other studies have also found similar results, but this is the largest study population by far (Harvell et al., 2016).

The researchers (Mariathas et al) found that over 5% of the 20,000 patients seen had elevations above the manufacturers 99th percentile upper reference limit (99% URL). The manufacturers 99% URL was set at 40ng/L, and in the study group it was 296ng/L. 39% of patients in critical care had levels above the manufacturers 99% URL.

What is the 99th percentile upper reference limit? For many cardiac biomarkers, the level is can set by the manufacturer, and should be confirmed by the testing laboratory as relevant for the local population. The level is recommended to be set by taking at least 300 ‘healthy’ men and 300 ‘healthy’ women and measuring the level of the biomarker in these subjects, a range of results will be produced, and the highest 1% will be considered above the 99th percentile upper reference limit. The study by Mariathas et al was a study on 20,000 ‘unhealthy’ subjects and obviously produced significantly different results compared to the manufacturer.

Many conditions are associated with elevated cardiac biomarkers other than myocardial infarction, including advanced age, cardiac injury, renal impairment, and heart failure. It is important for the clinician to take the clinical context into account when assessing the result of any test, including cardiac biomarkers. If there is a low likelihood (pre-test probability) of a myocardial infarction and the result is above the reference range there may be other explanations for the abnormal result.

This study should get clinicians and claims assessors thinking about whether the reference range supplied is appropriate for their patient or claimant prior to making a diagnosis of myocardial infarction or heart attack.

Most Australian heart attack critical illness definitions reference the 3rd universal definition of myocardial infarction (updated to the 4th universal definition of myocardial infarction in 2018). The standard definition of heart attack contained within the Life Insurance Code of Practice defines a heart attack as “meaning the death of a portion of the heart muscle as a result of inadequate blood supply, where the diagnosis is supported but the detection of a rise and/or fall of cardiac biomarker values with at least one value above the 99th percentile upper reference limit (URL)”.

As a result of this study and the fact most definitions reference the 3rd universal definition of myocardial infarction, claims assessors need to pay close attention to the clinical context in which the cardiac biomarker test was taken, before assuming an abnormal result represents a myocardial infarction. I would suggest routine involvement of medical staff when assessing cardiac biomarkers in heart attack claims.

Harvell, B., Henrie, N., Ernst, A. A., Weiss, S. J., Oglesbee, S., Sarangarm, D., & Hernandez, L. (2016). The meaning of elevated troponin I levels: not always acute coronary syndromes. Am J Emerg Med, 34(2), 145-148. doi:10.1016/j.ajem.2015.09.037

Mariathas, M., Allan, R., Ramamoorthy, S., Olechowski, B., Hinton, J., Azor, M., . . . Curzen, N. (2019). True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study. BMJ, 364, l729. doi:10.1136/bmj.l729