Improving the diagnosis of heart attack in women

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3 February 2015

Muscle damage releases proteins called troponins into the bloodstream. Measurements of serum heart-specific troponin concentrations are widely used in patients with the acute coronary syndrome (ACS) to help diagnose or rule out a heart attack.

Standard heart-specific troponin blood tests are rapidly being replaced by new, more reproducible high-sensitivity troponin tests. In October 2014 the National Institute for Health and Care Excellence (NICE) published recommendations on the use of either of two manufacturers’ high-sensitivity assays along with standard clinical tests for the early ruling out of heart attack in patients with chest pain and suspected acute coronary syndrome. NICE recognised that the upper limit of normal of these tests may be lower in women than men.

The first evaluation of the use of sex specific diagnostic thresholds of troponin for myocardial infarction was published online as an open access paper in the British Medical Journal on 21 January 2015. The investigators compared a standard troponin test and a high-sensitivity troponin test both with and without a lower diagnostic value for women to find out if the diagnosis of heart attack and the prediction of future heart attack could be improved. The 1126 patients, 622 men and 504 women, had presented consecutively to the Royal Infirmary of Edinburgh between 1 August and 31 October 2012 with suspected acute coronary syndrome. The doctors who managed the patients were aware of the patients’ standard troponin blood test results but not of the high-sensitivity troponin result, and assessed symptoms and the results of other tests such as an electrocardiogram (ECG) in the standard way.

Subsequently two heart specialists in the research team independently reviewed each patient’s clinical information including their standard troponin result from admission to 30 days to classify the cause of the suspected acute coronary syndrome. They then reclassified the patients, first using the highly-sensitive troponin result with a single (mean) diagnostic value and again with a lower value for women and a higher value for men. In addition, they judged whether the results could predict what happened to the patients during the 12 month follow-up period.

Of the 622 men, a heart attack was diagnosed in 19% with the standard test and in 21% with the high-sensitivity test using the male upper limit of normal. Of the 504 women, a heart attack was diagnosed in 11% with the standard test and in 22% with the high-sensitivity test using the female upper limit of normal. Thus, while nearly twice as high a proportion of men as women were diagnosed using the standard test, the proportions became equal with the high-sensitivity sex specific diagnostic value because the proportion in women had doubled.

During the 12 month follow-up period, the additional 11% of women diagnosed with the sensitive test were found to have a very similar risk of having another heart attack or of dying as the 11% diagnosed with the standard test. No individuals diagnosed using the standard troponin test result were missed with the sensitive test.

An unexpected finding during this investigation was that women with a diagnostic standard troponin test and a positive ECG were less likely than men to have been referred to a heart specialist, to have had angioplasty or to have been prescribed statins. The lead author, consultant cardiologist Dr Nicholas Mills, commented that women in the study were about seven years older than men and may have had more comorbid conditions which might have influenced decision-making, particularly about invasive treatment of acute coronary syndrome.

The authors of the study concluded that, "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 (another heart attack) and death."

Professor Peter Weissberg of the British Heart Foundation which funded the study said "If these results are confirmed in the much larger clinical trial we are funding, using a high sensitivity troponin test, with a threshold specific to each gender, we could save many more women's lives by identifying them earlier to take steps to prevent them dying or having another, bigger heart attack."