High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study

Abstract

Objective: To evaluate the diagnosis of myocardial infarction using a high sensitivity troponin I assay and sex specific diagnostic thresholds in men and women with suspected acute coronary syndrome.

Design: Prospective cohort study.

Setting: Regional cardiac centre, United Kingdom.

Participants: Consecutive patients with suspected acute coronary syndrome (n=1126, 46% women). Two cardiologists independently adjudicated the diagnosis of myocardial infarction by using a high sensitivity troponin I assay with sex specific diagnostic thresholds (men 34 ng/L, women 16 ng/L) and compared with current practice where a contemporary assay (50 ng/L, single threshold) was used to guide care.

Main outcome measure: Diagnosis of myocardial infarction.

Results: The high sensitivity troponin I assay noticeably increased the diagnosis of myocardial infarction in women (from 11% to 22%; P<0.001) but had a minimal effect in men (from 19% to 21%, P=0.002). Women were less likely than men to be referred to a cardiologist or undergo coronary revascularisation (P<0.05 for both). At 12 months, women with undisclosed increases in troponin concentration (17-49 ng/L) and those with myocardial infarction (≥50 ng/L) had the highest rate of death or reinfarction compared with women without (≤16 ng/L) myocardial infarction (25%, 24%, and 4%, respectively; P<0.001).

Conclusions: Although having little effect in men, a high sensitivity troponin assay with sex specific diagnostic thresholds may double the diagnosis of myocardial infarction in women and identify those at high risk of reinfarction and death. Whether use of sex specific diagnostic thresholds will improve outcomes and tackle inequalities in the treatment of women with suspected acute coronary syndrome requires urgent attention.

Fig 1 Steps involved in adjudication and classification of patients with suspected acute coronary syndrome. Patients were adjudicated using the contemporary troponin I assay with a single threshold (50 ng/L) and then reclassified using the high sensitivity troponin I assay, with both single (26 ng/L) and sex specific (men 34 ng/L and women 16 ng/L) thresholds

Fig 2 Proportion of men and women with diagnosis of type 1 myocardial infarction and type 2 myocardial infarction or myocardial injury using the contemporary troponin I assay (single threshold 50 ng/L) and high sensitivity troponin I assay (single threshold 26 ng/L, and sex specific threshold 34 ng/L for men and 16 ng/L for women)

Fig 3 Density plots of predicted probabilities of myocardial infarction in women. Women were stratified into three groups using both assays: those with no myocardial infarction (group 1; solid blue line) and myocardial infarction (group 3; dashed green line) where the assays were concordant and those reclassified as having myocardial infarction using the high sensitivity assay with sex specific thresholds (group 2; dashed red line). Rug plot indicates the probability of myocardial infarction for individual patients in group 2 (red lines) and group 3 (green lines)

Fig 4 Survival free from death or recurrent myocardial infarction in women and men with suspected acute coronary syndrome. Outcomes are shown for women and men with no myocardial infarction (group 1, solid blue line) and with myocardial infarction (group 3, dashed green line) where both assays were concordant, and for those reclassified as having myocardial infarction using the high sensitivity assay with sex specific thresholds (group 2, dashed red line)