Much ado is made regarding potential differences in symptoms between men and women presenting with acute coronary symptoms. Little is mentioned, however, about potential differences in laboratory thresholds between the sexes. Considering women, on average, have decreased myocardial mass than men, any ischemic insult simply damages a smaller absolute quantity of myocardium. Less damaged tissue, then, ought to lead to lower circulating biomarkers.
Why haven’t we tried this before? Because the limit of detection of conventional troponin assays are above the clinically important thresholds for delineating such small quantities of circulating molecules. However, with the advent of highly-sensitive troponins with reasonable precision below the conventional troponin cut-off of 50 ng/L, it’s now a reasonable concept for investigation.
These authors conducted a yearlong prospective evaluation of all patients with suspected acute coronary syndrome, collecting conventional and highly-sensitive troponins on each. Treating clinicians and initial adjudication of myocardial infarction were blinded to the results of the hsTnI. Following conclusion of the study, records and unmasked hsTnI values were provided for independent adjudication and diagnosis changes accordingly.
Initially, 19% of men were diagnosed with Type 1 MI based on conventional troponin testing. After using a gender-specific cut-off for men of 34 ng/L, only a handful of additional cases were re-classified – rising to 21%. For women, 11% were initially diagnosed with Type 1 MI. Using a gender-specific cut-off for hsTnI of 16 ng/L, however, doubled the diagnosis cohort to 22%.
Of course, simply lowering the threshold for any assay increases the rate of diagnosis. In order to answer the question of whether the re-classified cases were clinically appropriate, all patients were also followed for survival free from death or MI. While women not diagnosed with MI at initial presentation did well throughout the follow-up period, the women reclassified as MI using the hsTnI threshold suffered the same dismal outcomes as those initially diagnosed with MI.
I like this concept, and this is promising preliminary data. It remains to be seen whether treatment, including increased treatment intensity for women, based on the gender-specific cut-offs changes clinical outcomes – or whether splitting these little nanograms worth of hairs is just overdiagnosis. The good news: a clinical trial is ongoing. I look forward to their results.
“High sensitivity cardiac troponin and the under-diagnosis of myocardial infarction in women: prospective cohort study”
http://www.bmj.com/content/350/bmj.g7873 (free fulltext)
Cheers from Stockholm, great blog! I don't quite get the pathophysiology here. Isn't it reasonable to think that the smaller blood volume in women would lead to the concentration of troponins being equal to that in men? Or am I missing something? (will blame that on having influenza).