Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome

Abstract

Background: Major disparities between women and men in the diagnosis, management, and outcomes of acute coronary syndrome are well recognized.

Objectives: The aim of this study was to evaluate the impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds for myocardial infarction in women and men with suspected acute coronary syndrome.

Methods: Consecutive patients with suspected acute coronary syndrome were enrolled in a stepped-wedge, cluster-randomized controlled trial across 10 hospitals. Myocardial injury was defined as high-sensitivity cardiac troponin I concentration >99th centile of 16 ng/l in women and 34 ng/l in men. The primary outcome was recurrent myocardial infarction or cardiovascular death at 1 year.

Results: A total of 48,282 patients (47% women) were included. Use of the high-sensitivity cardiac troponin I assay with sex-specific thresholds increased myocardial injury in women by 42% and in men by 6%. Following implementation, women with myocardial injury remained less likely than men to undergo coronary revascularization (15% vs. 34%) and to receive dual antiplatelet (26% vs. 43%), statin (16% vs. 26%), or other preventive therapies (p < 0.001 for all). The primary outcome occurred in 18% (369 of 2,072) and 17% (488 of 2,919) of women with myocardial injury before and after implementation, respectively (adjusted hazard ratio: 1.11; 95% confidence interval: 0.92 to 1.33), compared with 18% (370 of 2,044) and 15% (513 of 3,325) of men (adjusted hazard ratio: 0.85; 95% confidence interval: 0.71 to 1.01).

Conclusions: Use of sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this increase, women received approximately one-half the number of treatments for coronary artery disease as men, and outcomes were not improved. (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]; NCT01852123).

Keywords: acute coronary syndrome; high-sensitivity cardiac troponin; myocardial infarction; sex-specific threshold.

Graphical abstract

Figure 1

Flow Diagram of Adjudication Process in Women and Men With Suspected Acute Coronary Syndrome Adjudicated diagnoses are presented for patients with troponin concentration above the contemporary cardiac troponin I assay threshold of 50 ng/l and those with troponin concentration above the sex-specific 99th centile threshold of 16 ng/l in women and 34 ng/l in men. *Where there was consensus among the adjudication panel that there was insufficient clinical information to make a definitive diagnosis, because of missing admission or discharge letters, we did not attempt to adjudicate the diagnosis (1,245 of 10,360 [12%]). As we had access to all other information, including medical history, clinical investigations, management, and outcomes, these patients were not excluded from our primary or secondary analyses.

Figure 2

Patient Management During Index Hospitalization and Adjusted Odds Ratio of Myocardial Infarction or Cardiovascular Death at 1 Year Stratified by Treatment Received During Index Hospitalization and Sex (Top) Odds ratio of myocardial infarction and cardiovascular death at 1 year in patients receiving each treatment modality compared with those not receiving treatment for all patients and stratified by sex. Odds ratios were adjusted for hospital site (fitted as a random effect), season, time of presentation from the start date of the trial, age, sex and study phase as an interaction term, history of diabetes mellitus, ischemic heart disease or cerebrovascular disease, high sensitivity cardiac troponin I, creatinine concentration, and social deprivation. (Middle) Treatment commenced during index hospitalization in all patients and stratified by sex. (Bottom) Pre-existing treatment prior to index presentation in all patients and stratified by sex. ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; CI = confidence interval; DAPT = dual-antiplatelet therapy.

Figure 3

Incidence of Myocardial Infarction or Cardiovascular Death at 1 Year in Women and Men, Stratified by Troponin Concentration and Study Phase (Left) Cumulative incidence time-to-event curves for the primary outcome of myocardial infarction or cardiovascular death at 1 year for men admitted during the validation phase (dashed line) and implementation phase (solid line). Patients are grouped according to whether myocardial injury was present (blue) or absent (gray). Paired log-rank test results are p = 0.01 for men with myocardial injury and p = 0.06 for men without myocardial injury. (Right) Cumulative incidence time-to-event curves for the primary outcome of myocardial infarction or cardiovascular death at 1 year for women admitted during the validation phase (dashed line) and implementation phase (solid line). Patients are grouped according to whether myocardial injury was present (red) or absent (gray). Paired log-rank test results are p = 0.40 for women with myocardial injury and p = 0.08 for women without myocardial injury.

Central Illustration

Implementation of High-Sensitivity Troponin and Sex-Specific Thresholds Sex-specific thresholds identified 5 times more additional women than men with myocardial injury. Despite this, women received fewer treatments for coronary artery disease than men, and their outcomes were not improved. CI = confidence interval; MI = myocardial infarction.