Sex-Specific Thresholds of High-Sensitivity Troponin in Patients With Suspected Acute Coronary Syndrome
Key result
Sex-specific hs-cTnI identifies more myocardial injury in women but fails to improve 1-year outcomes.
- HR 1.11
- 95% CI 0.92-1.33
- P=0.289
- n=48,282
Why the study?
Disparities exist between women and men in the diagnosis, management, and outcomes of acute coronary syndrome, prompting evaluation of a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds.
Does implementing a high-sensitivity cardiac troponin I assay with sex-specific thresholds improve recurrent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome?
Key Points
- To assess the clinical impact of implementing a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds in women and men evaluated for suspected acute coronary syndrome.
- Stepped-wedge, cluster-randomized controlled trial across 10 hospitals enrolling 48,282 consecutive patients (47% women) with suspected acute coronary syndrome (NCT01852123).
- Defined myocardial injury as high-sensitivity cardiac troponin I concentrations above sex-specific 99th centile thresholds (16 ng/l in women, 34 ng/l in men).
- Evaluated a primary composite outcome of recurrent myocardial infarction (type 1 or type 4b) or cardiovascular death at 1 year.
- Sex-specific thresholds increased diagnoses of myocardial injury by 42% in women and 6% in men, identifying 5 times more additional women than men.
- Following implementation, women with myocardial injury remained significantly less likely than men to undergo coronary revascularization (15% vs. 34%) or receive dual antiplatelet therapy (26% vs. 43%) and statins (16% vs. 26%; p < 0.001 for all).
- The primary outcome occurred in 18% (369 of 2,072) versus 17% (488 of 2,919) of women before and after implementation (adjusted HR: 1.11; 95% CI: 0.92 to 1.33), compared with 18% (370 of 2,044) versus 15% (513 of 3,325) of men (adjusted HR: 0.85; 95% CI: 0.71 to 1.01).
Study Design
Type
RCT (n=48,282)
Blinding
Open-label clinical care, adjudicators blinded
Randomization
stepped-wedge, cluster-randomized
Multicenter
Yes
Structured PICO
Does implementing a high-sensitivity cardiac troponin I assay with sex-specific thresholds improve recurrent myocardial infarction or cardiovascular death in patients with suspected acute coronary syndrome?
P
Population
48,282 consecutive patients with suspected acute coronary syndrome across 10 hospitals in Scotland, with 47% women, followed for 1 year.
I
Intervention
High-sensitivity cardiac troponin I (hs-cTnI) assay with sex-specific 99th centile diagnostic thresholds (16 ng/l for women, 34 ng/l for men) to guide clinical care.
C
Comparator
Contemporary cardiac troponin I (cTnI) assay with a single diagnostic threshold (40 or 50 ng/l) to guide clinical care (validation phase).
O
Outcome
Composite of type 1 or type 4b myocardial infarction or cardiovascular death at 1 year.hard clinical
Main Result
Hazard Ratio: 1.11 (95% CI 0.92–1.33)
Absolute Event Rate: 17% vs 18%
p-value: p=0.289
Using sex-specific troponin thresholds identifies more women with myocardial injury, but without equitable treatment, clinical outcomes do not improve.
Limitations
- Adjudication panel may have underdiagnosed type 1 myocardial infarction in women
- Estimates of treatment efficacy are subject to confounding by indication
- Impact will differ at hospitals that use lower uniform thresholds
- Impact will differ for assays where the difference between women and men is modest
- Did not directly compare whether sex-specific thresholds were superior to a uniform threshold using a hs-cTnI assay
- Adjudication panel may have underdiagnosed type 1 MI in women
- Confounding by indication for treatment efficacy
- Single healthcare system (Scotland)
- Did not directly compare sex-specific vs uniform threshold using the same hs-cTnI assay
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
ASAllan S. JaffeCardiologist, Mayo Clinic, Rochester
“It is clear from this study that simply improving diagnostic accuracy cannot remedy deeply embedded gender disparities in attitudes, practice, and outcomes. Simply put, if one does not act on the data, no diagnostic test will ever have additional worth.”
“We need to continue to educate clinicians about the importance of high-sensitivity troponin as a diagnostic test and to continue to promote the investigation of coronary artery disease, particularly in women, to try and close the gap between men and women.”
SHSharonne HayesCardiologist, Mayo Clinic, Rochester
“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.”
Implication
Sex-specific troponin thresholds do not improve women's outcomes; challenges the premise that enhanced detection alone closes gender gaps in ACS care.
Cite This Study
Lee et al. (2019) conducted an RCT in Suspected acute coronary syndrome (n=48,282). High-sensitivity cardiac troponin I assay with sex-specific thresholds vs. Contemporary cardiac troponin I assay with a single diagnostic threshold was evaluated on Recurrent myocardial infarction or cardiovascular death at 1 year in women with myocardial injury (HR 1.11, 95% CI 0.92-1.33, p=0.289). Implementation of a high-sensitivity cardiac troponin I assay with sex-specific thresholds identified 5 times more additional women with myocardial injury but did not improve their 1-year outcomes (HR 1.11, 95% CI 0.92-1.33).