May 2015 Product Focus -BIOMARKERS

May 24, 2015

When patients complaining of chest pain present to the emergency department, they get attended to right away. If they are suspected of having a heart attack, they are quickly triaged into the chest pain procedure in these acute settings. Additionally, patients are clinically evaluated by the attending physician, and diagnostic testing, electrocardiogram (ECG), and blood testing are performed as soon as possible. All of these steps are taken to determine whether patients are having a heart attack. If they are, they need to be sent for invasive management to prevent as much damage to the heart muscle as possible. If not, then they can be evaluated for other causes of the chest pain, such as skeletal muscle, gastric reflux, or other etiologies. So, are high-sensitivity troponin blood tests really needed, when the healthcare system responds quickly and treats as soon as possible? If we are trying to diagnose heart attacks, it would seem that the only need is for a highly specific test result.

However, the discussion above may be an overly simple and misleading representation of the situation. Each year five to eight million patients with chest pain present to emergency departments in the United States, and of these patients only 20 percent to 25 percent are diagnosed as having some type of heart attack, according to the American Heart Association. The rest of this patient population has to be determined as not having a heart attack. This requires the same process as mentioned above to rule out heart attacks, but also needs a bit more time for evaluation.

Thus, most of the patients walking in with chest pain are actually not having a heart attack, but they need to wait a long time for a decision because repeat testing is sometimes needed and, per the guidelines, this may require six to twelve hours of observation time between the serial tests.1 Additionally, two percent to five percent of heart attacks may be missed from this population.2,3 Among the patients frequently missed are ones that present with gastric reflux or women under the age of 55.2 This clearly shows us that sensitivity is important, particularly if the test is highly sensitive and the test result is negative so that we can be nearly certain that they don’t have the disease or condition.

High-sensitivity troponin tests address a clinical need among the larger proportion of the chest pain population for which heart attacks need to be ruled out. These tests have the capability of detecting very low levels of troponin and the change in the troponin level over a shorter period of time, which helps reduce the observation period for patients who are not overtly having a heart attack.1 It is also well known that women present with lower circulating levels of troponin than men. The “definitive normal range study” by Apple et al. clearly showed in the same normal cohort that there was a gender difference in troponin values and that it was not specific to a single troponin method.4

A study published in the British Medical Journal this year by Shah et al. evaluated 1,126 patients presenting to the emergency department with chest pain. In this well-distributed gender cohort, women presenting to the emergency department with chest pain could be potentially missed 50 percent of the time for a heart attack in comparison to men presenting to the emergency department with chest pain, if a high-sensitivity troponin-I biomarker with gender-specific cutoffs is not used.5 This level of discrepancy between the genders has consequences for patient management in the acute setting, as well as in short- and long-term outcomes.

Another study, recently published by Omland et al. in Clinical Chemistry, shows that sensitivity of the troponin assay is important in risk stratification for cardiovascular disease among the genders in a seemingly normal general population. They studied 9,712 subjects—4,431 women and 5,281 men—from a general population cohort where the concentrations of high-sensitivity troponin I and relationship of cardiovascular death between men and women were also different.6 This suggests that the differences early in the process of cardiac damage may explain some of the differences in long-term cardiovascular disease outcomes between men and women.

However, even with research reflecting the value of high-sensitivity troponin in both the acute and general setting, there is still concern related to the issue of too much sensitivity. It is safe to say that high-sensitivity troponins are needed to elevate the standard of care in the emergency setting and to help clinicians diagnose heart attacks. This is the next stage of improvement for this area in healthcare that needs to be known and understood prior to implementation so the full benefit of its capabilities can be achieved. As with any new approach or method, the healthcare community is in a transition phase with regard to high-sensitivity troponin.


  1. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Euro Heart J. 2012;33:2551-2567.
  2. Pope JH, Aufderheide TP, Ruthazer R, et. al. Missed diagnoses of acute cardiac ischemia in the emergency department. NEJM. 2000;342:1163-1170.
  3. Wilson M, Welch J, Schuur J, et. al. Hospital and emergency department factors associated with variations in missed diagnosis and costs for patients age 65 years and older with acute myocardial infarction who present to emergency departments. Academic Emer Med. October 2014; 21:10.
  4. Apple FS, Ler R, Murakami MM. Determination of 19 cardiac troponin I and T assay 99th percentile values from a common presumably healthy population. Clin Chem. 2012;58 (11):1574–1581.
  5. Shah A, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction women: Prospective cohort study. BMJ. 2015;350: g7873 doi: 10.1136/bmj.g7873.
  6. Omland T, de Lemos JA, Holmen OL, et. al. Impact of sex on the prognostic value of high sensitivity troponin I in the general population: Hunt study. Clin Chem. 2015;61(4): 646-656.

Agim Beshiri, MD, serves as Senior Medical Director of Medical Affairs, Diagnostics for Abbott Laboratories.