Conference Coverage
AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.
High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.
Dr. Nicholas L. Mills
The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.
He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.
Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.
The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.
Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.
"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.
In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.
The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.