Sex-Specific Troponin Threshold Identifies Higher Proportion of Women With Myocardial Injury

Use of a high-sensitivity cardiac troponin I (hs-cTnI) assay with sex-specific thresholds detects myocardial injury in 5 times more additional women than men, according to study results published in the Journal of the American College of Cardiology.

A previous randomized controlled trial called the High-Sensitivity Troponin in the Evaluation of Patients With Suspected Acute Coronary Syndrome was the first trial (High-STEACS; ClinicalTrials.gov identifier: NCT01852123) to evaluate the use of an hs-cTnI assay with sex-specific thresholds in clinical practice. However, women with suspected acute coronary syndrome remain less likely to undergo evidence-based investigations and treatment and tend to experience poorer outcomes than those observed in men. The objective of this prespecified secondary analysis was to evaluate the impact of using an hs-cTnI assay with sex-specific diagnostic thresholds to investigate and treat coronary heart disease in both men and women separately.

Researchers evaluated consecutive patients with suspected acute coronary syndrome (N=48,282) presenting across 10 secondary and tertiary hospitals in Scotland, 47% of whom were women (n=22,562) and 53% of whom were men (n=25,720). 

Participants underwent cardiac troponin testing at presentation and at 6 or 12 hours after the onset of symptoms. Myocardial injury was defined as hs-cTnI concentration above the sex-specific 99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction following initial presentation or cardiovascular death within 1 year.

Results revealed that a higher number of women than men were reclassified by the hs-cTnI assay and sex-specific thresholds (1470 of 1771 women [83%] vs 301 of 1771 men [17%]). The total number of patients with myocardial injury increased from 16% to 22% in women and from 20% to 21% in men.

Overall, the use of an hs-cTnI assay and sex-specific thresholds led to an increase in the diagnosis of type 1 myocardial infarction (by 25% in women and by 6% in men), an increase in the diagnosis of type 2 myocardial infarction (by 39% in women and by 9% in men), and an increase in the diagnosis of nonischemic myocardial injury (by 67% in women and by 12% in men).

Additionally, compared with men, women with type 1 myocardial infarction were less likely to undergo coronary angiography (43% vs 66% during validation and 53% vs 73% during implementation; P <.001 for both) and coronary revascularization (26% vs 48% and 35% vs 57%; P <.001 for both).

Compared with men, women were also less likely to receive secondary prevention prescriptions, such as dual-antiplatelet therapy (48% vs 61% during validation and 54% vs 67% during implementation; P <.001 for both), statins (24% vs 37% and 31% vs 41%; P <.001 for both), and beta-blockers (26% vs 42% and 33% vs 42%; P <.001 for both).

The primary outcome occurred in 18% of women during validation and in 17% during implementation (adjusted hazard ratio [HR], 1.11; 95% CI, 0.92-1.33; P =.289), compared with 18% of men during validation and 15% during implementation (adjusted HR 0.85; 95% CI, 0.71-1.01; P =.071).

This study had 6 limitations. First, type 1 myocardial infarction may have been underdiagnosed in women. Second, estimates of treatment efficacy were subject to confounding by indication. Third, hospitals that use lower uniform thresholds for cardiac troponin may observe fewer women being reclassified following clinical implementation of hs-cTnI. Fourth, there are many other high-sensitivity assays being used in clinics worldwide, which could lead to different diagnostic thresholds. Fifth, the impact of implementing hs-cTnI testing may differ at hospitals that use higher or lower cardiac troponin thresholds. Lastly, researchers did not directly compare whether sex-specific thresholds were superior to a uniform threshold using a hs-cTnI assay.

The study researchers concluded that the use of an hs-cTnI assay with sex-specific thresholds can identify myocardial injury in 5 times more additional women than men, and that women remain less likely than men to receive treatment and do not experience outcome improvements following implementation of hs-cTnI testing.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Lee KK, Ferry AV, Anand A, et al; High-STEACS Investigators. Sex-specific thresholds of high-sensitivity troponin in patients with suspected acute coronary syndrome. J Am Coll Cardiol. 2019;74(16):2032-2043.