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

Shah AS, Griffiths M, Lee KK, et al.
BMJ. 2015 Jan 21;350:g7873. doi: 10.1136/bmj.g7873
 Women with suspected acute coronary syndrome (ACS) are less likely to be diagnosed with myocardial infarction (MI) than men, which used to be explained by atypical symptoms and less reliable findings on electrocardiography (ECG) [1,2].
The universal definition of MI uses an increase of cardiac troponin above the 99^th centile of a normal reference population as a diagnostic criterion [3]. A minority of the clinical laboratories currently uses this diagnostic threshold, due to the analytical imprecision of established troponin assays [4].
High sensitivity assays allow quantification of troponin concentrations in most healthy people. These assays have identified potentially important differences between the sexes, in that the 99^th centile (upper reference limit) was twofold higher in men than in women [5,6].
It is unknown whether the use of a single diagnostic threshold with contemporary assays has been associated with under-diagnosis of MI in women. This study evaluated the effect of the use of sex specific diagnostic thresholds with a high sensitivity assay for cardiac troponin I, on the incidence of MI. 1126 Consecutive patients with suspected ACS were included, of whom 45% were female.

Main results

• Women and men were equally likely to present with chest pain (82% vs. 86%, P=0.441) and to show ST segment depression and T wave inversion on ECGs. Women did present less often with ST segment elevation (19% vs. 31%, P=0.024).
• At admission, women had lower serum troponin concentration than men (29 ng/L (IQR: 17-102) vs. 69 ng/L (IQR: 22-480), P0.025), and lower peak troponin concentrations (50 ng/L (IQR: 24-2630) vs. 1230 ng/L (IQR: 82-14700), P<0.001).
• As compared with a contemporary troponin I assay (threshold 50 ng/L), using a high sensitivity assay with a sex specific threshold (women: 16 ng/L) classified more women as having type 1 MI (22% vs. 11%). In men, the incidence of diagnosis of type I MI increased to a lesser extent with a male-specific threshold (34 ng/L, 21% vs. 19%).
• A small increase in the number of women with a diagnosis of type 2 MI were seen when high sensitivity assay and sex specific thresholds were used.
• Women diagnosed with MI were managed differently from men with diagnosis of MI, in that they were less often referred to a cardiologist (80% vs. 95%), less likely to undergo coronary angiography (47% vs. 74%) or PCI (29% vs. 64%), or to be prescribed statin treatment on discharge (60% vs. 85%).
• The event rate in women with troponin concentrations of between the sex-specific (16 ng/L) and the generic (26 ng/L) threshold was sixfold higher (23%) than in those with concentrations of 16 ng/L or less (4%) and similar to those with troponin concentrations of 27-49 ng/L (25%).

Conclusion

Diagnosis, treatment and outcomes differ greatly between men and women presenting with suspected ACS. Using a high sensitivity troponin assay with a generic threshold value appears to contribute to the underdiagnosis of MI in women, and differences in clinical management.
Using a sex specific threshold appeared to correctly identify more women at increased risk of recurrent MI or death than a generic threshold. 

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