A Better Test for Detecting MI in Women?

By Mara L. Morr, PhD
Reviewed by Vrunda Bhavsar Desai, MD, FACOG, Assistant Professor of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 

Take Note

• When it comes to heart disease, women are generally underdiagnosed, undertreated, and understudied.
• A high-sensitivity troponin I assay with sex-specific diagnostic thresholds has been shown to double the diagnosis of myocardial infarction in women.
• More research is urgently needed to establish firm conclusions.

A middle-aged woman enters the emergency department doubled over with chest pain, shortness of breath, and nausea. Two doctors approach her, both suspecting a heart attack. The first physician wants to confirm it by standard diagnostic blood testing, the second by using a blood test that he says is much more specific in women. 

The second doctor made the wiser choice. Recent data have demonstrated that a new high-sensitivity assay, with sex-specific diagnostic thresholds, could potentially double the number of heart attack diagnoses in women.1

As we’re all aware, coronary heart disease is the leading cause of death in women worldwide, with women dying at higher rates than men. In fact, coronary disease is responsible for more deaths in women than all forms of cancer combined. Women remain underdiagnosed, undertreated, and are underrepresented in clinical trials. 2

Shah and colleagues recently published a study that may help move this field forward. The authors are the first to report on sex-specific diagnostic thresholds for myocardial infarction (MI). They prospectively studied, at a single center, 1126 consecutive patients (45% of whom were women) with suspected acute coronary syndrome. Two cardiologists independently assessed each patient. One cardiologist used a contemporary troponin I assay (50 ng/L, single threshold) for diagnosis, while the other used a high-sensitivity troponin I assay with sex-specific diagnostic thresholds (34 ng/L for men, 16 ng/L for women). 1

With the standard blood test, 11% of women and 19% of men were classified as having type 1 MI. When the high-sensitivity assay was used, however, the percentage of women diagnosed with a heart attack doubled, to 22%. (The rate for the men increased slightly, to 21%.) These data illuminate that sex-specific thresholds result in a similar proportion of women and men being diagnosed, as opposed to the fairly wide gap that exists with standard blood testing. Additionally, the study showed that there was no instance where a patient was identified as having an MI with the contemporary assay, but not with the high-sensitivity assay. 1

The study also highlighted clinical management disparities by gender. Specifically, women with a diagnosis of MI were less likely than men with the same diagnosis to be referred to a cardiologist (80% versus 95%, P=.004); undergo coronary angiography (47% versus 74%, P=.001); have percutaneous coronary revascularization (29% versus 64%, P<.001); be prescribed a statin at discharge (60% versus 85%, P=.001) 

These differences persisted in sensitivity analyses where patients were stratified by age and restricted to those with non–ST-segment elevation MI. 1

Furthermore, clinical outcome follow-ups revealed that the women who were diagnosed using the high-sensitivity assay with sex-specific thresholds had the highest risk of death or recurrent MI at 12 months. 1

The authors concluded that “although having little effect in men, a high-sensitivity troponin assay with sex-specific diagnostic thresholds may double the diagnosis of myocardial infarction in women and identify those at high risk of reinfarction and death. Whether use of sex-specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention.” 

To test the authors’ theories, a much larger, randomized, multicenter clinical trial is now underway. It’s expected to enroll a total of about 24,000 patients. 3

The use of high-sensitivity troponin testing could potentially have a significant impact on the practice of cardiology. Late last year, the National Institute for Health and Care Excellence recommended 2 high-sensitivity troponin tests. 4 And as the body of evidence increases, physicians may begin to more routinely use sex-specific thresholds when interpreting troponin testing. That said, while it’s a helpful addition to the clinician’s diagnostic toolbox, troponin testing alone wouldn’t necessarily be relied upon to diagnose MI. 4,5 Clinical fundamentals, such as the patient’s medical history, a physical examination, and electrocardiogram testing, will continue to accompany troponin testing as well.5

In a classic from the late editorial cartoonist Etta Hulme, a woman is sitting across from a male physician. He says to her, “We have studies of fruit flies, mice, hamsters, frogs, monkeys, and men with this condition—but medical research using women as subjects just never occurred to anybody.” 

While Hulme was clearly joking, and things aren’t nearly as bad as her cartoon makes it out to be, it remains unclear why women are underdiagnosed and are treated less aggressively than men. It’s also unclear whether outcomes will improve simply because diagnostics improve. With more research come more answers. 

A Note About Funding: Shah and colleagues’ research was funded by a special project grant from the British Heart Foundation. Abbott Laboratories provided the high-sensitivity troponin I assay reagents, calibrators, and controls without charge. The study sponsors, however, had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the manuscript for publication. 

Published: 05/29/2015

References:

1. Shah AS, Griffiths M, Lee KK, et al. High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study. BMJ. 2015;350:g7873
2. Wenger NK. Women and coronary heart disease: a century after Herrick: understudied, underdiagnosed, and undertreated. Circulation. 2012;126:604-611
3. ClinicalTrials.gov. NCT01852123. High-sensitivity troponin in the evaluation of patients with acute coronary syndrome (High-STEACS). 
4. National Institute for Health and Care Excellence. Myocardial infarction (acute): Early rule out using high-sensitivity troponin tests (Elecsys Troponin T high-sensitive, ARCHITECT STAT High Sensitive Troponin-I and AccuTnI+3 assays). Diagnostics guidance. October 2014
5. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Eur Heart J.