Sex-Specific Troponin Cutoffs Find Many More Women With Myocardial Injury

More women at risk were found, but they remained undertreated compared with men.

Sex-Specific Troponin Cutoffs Find Many More Women With Myocardial Injury

Using sex-specific thresholds with high-sensitivity troponin testing for suspected ACS leads to a disproportionately greater increase in the number of women versus men found to have some degree of myocardial injury, but it doesn’t mitigate sex-based disparities in management, a prespecified secondary analysis of the High-STEACS trial shows.

The number of women with myocardial injury jumped 42% when hospitals started using high-sensitivity cardiac troponin I assays—with the sex-specific cutoffs—instead of conventional troponin tests, with only a 6% increase in detection in men. That resulted in a similar rate of myocardial injury detected in both women (22%) and men (21%) after the switch.

The new approach also resulted in increases in coronary angiography and revascularization, as well as use of secondary preventive therapies, in both sexes, although women continued to lag behind men when it came to further evaluations and treatment. One-year outcomes remained unchanged in both women and men.

The findings were reported online ahead of the October 22, 2019, issue of the Journal of the American College of Cardiology, by lead authors Kuan Ken Lee, MD, and Amy Ferry, BSc (both University of Edinburgh, Scotland).

“This study highlights the need to improve education for both clinicians and patients to improve the treatment of women with suspected acute coronary syndrome so that hopefully in the future we can improve the outcomes following myocardial infarction,” Lee told TCTMD.

Commenting for TCTMD, Sharonne Hayes, MD (Mayo Clinic, Rochester, MN), said the findings highlight the fact that it doesn’t matter how good a test is if it doesn’t lead to appropriate follow-up actions. “You can have a test that is enhanced over a prior test, but if you don’t pay attention to the results, if you don’t use the results to improve care, you haven’t gained anything. You’ve perhaps created a more accurate test that perhaps costs more money.”

Any improvements in testing need to be coupled with a strategy for applying the results to improve patient outcomes, Hayes said. “We’ve provided a piece of information that these are people at higher risk, but then if we don’t then apply some new rubric to lower their risk or diagnose why they’re at risk, we won’t achieve the kinds of outcomes that we need.”

Sex-Based Disparities Persist

It’s well known that women with ACS tend to be underdiagnosed and undertreated and to have poorer outcomes compared with their male counterparts, Lee pointed out. The Edinburgh research group has previously shown that using a high-sensitivity troponin assay with sex-specific cutoffs—rather than the same threshold for both women and men—might double the diagnosis of MI in women.

“This raises the question as to whether the use of single diagnostic thresholds has contributed to inequalities in the diagnosis, management, and outcomes of women with acute coronary syndrome,” Lee et al write.

The High-STEACS trial presented an opportunity to explore whether improved diagnostic testing—by transitioning from a conventional to a high-sensitivity cardiac troponin I test, using sex-specific thresholds, and applying the recommendations of the universal definition of MI—had differential impacts on the evaluation, treatment, and outcomes of women versus men with suspected ACS.

Of the 48,282 patients with suspected ACS enrolled in the trial (47% women), 21.5% had some degree of myocardial injury detected using a cutoff of 16 ng/L for women and 34 ng/L for men. Most patients who were reclassified in terms of the presence of myocardial injury based on using the high-sensitivity test (83%) were women.

Looking at specific types of injury in women, use of more-sensitive testing with sex-specific thresholds increased the diagnosis of type 1 MI by 25%, of type 2 MI by 39%, and of nonischemic myocardial injury by 67%. The corresponding figures for men were 6%, 9%, and 12%.

You can have a test that is enhanced over a prior test, but if you don’t pay attention to the results, if you don’t use the results to improve care, you haven’t gained anything. Sharonne Hayes

The new testing protocol was associated with increases in the use of coronary angiography and revascularization and of preventive medical therapies in both sexes, but women consistently trailed men. Coronary angiography, for example, was used in 26% of women and 46% of men. The gap for revascularization was about the same (15% vs 34%). Women also were less likely to receive dual antiplatelet therapy (26% vs 43%), statins (16% vs 26%), and other medications.

Lee et al say it could be that part of the reason women were treated less was that they were more likely to have nonischemic myocardial injury than were men. They note, however, that analyses restricted to patients with type 1 MI yielded similar findings.

The primary outcome of High-STEACS was a composite of subsequent MI or CV death. Mirroring the main trial results, implementation of the new testing protocols did not improve this outcome in either women or men with myocardial injury, who both carried similar risk at 1 year (17% in women and 15% in men).

Education, Protocols May Help

Lee said education should go a long way toward addressing the lingering gaps in management between women and men. “The educational aspect is a huge thing that we need to do going forward, making sure that clinicians recognize that women are at risk of having myocardial infarction and that when you find women with suspected acute coronary syndrome who have been identified by this new test, that this result is not ignored and that it is acted on with appropriate investigations and also therapies for acute coronary syndrome,” he said.

Hayes, who co-wrote an editorial accompanying the study with Allan Jaffee, MD (Mayo Clinic), pointed out that prior research involving conventional troponin testing showed that women presenting with symptoms consistent with MI and elevated troponins were more likely than men in similar situations to be sent home from the emergency department.

Part of addressing the remaining sex-based disparities “is overcoming our biases and setting up protocols . . . that we can rely upon, whether that’s guidelines or clinical pathways,” Hayes said. With those in place to help guide clinicians when they see a patient with an elevated troponin level, “it isn’t an option to ignore it or explain it away,” she said. “And I think that would help us a lot. I’m not an advocate for cookbook medicine . . . but it works for pilots. And I do think that often when we follow guidelines it raises the bar for care.”

As for whether sex-specific thresholds for high-sensitivity troponin testing is the way to go, Hayes said it is. “I think that what we still don’t know is what are the things that we need to do for a woman that might be different in order to improve her outcomes,” she said. “That’s going to be the next question that needs to be answered.”

Todd Neale is the Associate News Editor for TCTMD and a Senior Medical Journalist. He got his start in journalism at …

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  • Lee KK, Ferry AV, Anand A, et al. Sex-specific thresholds of high-sensitivity troponin in patients with suspected acute coronary syndrome. J Am Coll Cardiol. 2019;74:2032-2043.

  • Jaffe AS, Hayes SN. It will take more than better diagnostics to improve the care of women with ACS. J Am Coll Cardiol. 2019;74:2044-2046.

  • The trial was funded by a Special Project Grant from the British Heart Foundation (BHF), with additional support from a BHF-Turing Cardiovascular Data Science Award and a BHF Research Excellence Award. Abbott Laboratories provided cardiac troponin assay reagents, calibrators, and controls without charge.
  • Lee and two of his co-authors report receiving support from a Clinical Research Training Fellowship, an Intermediate Clinical Research Fellowship, and the Butler Senior Clinical Research Fellowship from the BHF.
  • Jaffe reports presently or in the past consulting for Roche, Siemens, Abbott, Beckman-Coulter, Singulex, Sphingotec, Radiometer, Ortho Diagnostics, Quidel, Brava, Quanterix, and Nanosphere.
  • Hayes reports no relevant conflicts of interest.