"£5 blood test will save thousands of women," shouts the front page of the Daily Mail in very large print.
This headline is based on a study recently presented at the European Society of Cardiology conference in Amsterdam.
The research looked at the effects of changing the diagnostic threshold levels of a blood test used to help diagnose heart attacks.
When someone with symptoms of a heart attack turns up at A&E, doctors will carry out an electrocardiogram (ECG) and a blood test to measure levels of an enzyme called troponin. Troponin levels are raised when heart muscle is damaged.
Only limited information is available on this study's methods and the patients included, but preliminary results suggest that lowering the diagnostic threshold for troponin in women (rather than using the same threshold for men and women) may improve our ability to correctly diagnose women who have symptoms of heart attack.
The main effect of doing so may be to increase the proportion of women diagnosed with non-ST elevation MI, where troponin levels are raised but the ECG changes are not compatible with a heart attack. These women would previously have been classed as having unstable angina.
The current recommended diagnostic and treatment approach for non-ST elevation MI and unstable angina are broadly similar, so it is unclear whether this would lead to the major improvements in patient care and outcomes that the media has suggested.
The conference presentation involves an analysis of the results of a study that is not scheduled for completion until 2016. Until more information is available, the possible implications of this study are unknown.
Where did the story come from?
The study was carried out by researchers from the University of Edinburgh. Funding sources were not reported, but a press release states that the diagnostic test in question is made by Abbott Diagnostics.
The study was published online as a conference abstract from the European Society of Cardiology Congress in Amsterdam. This means that it has not been peer reviewed.
Coverage of the research by the media failed to disclose some of its major limitations, including that these are preliminary results of a trial not scheduled for completion until 2016. The study did not look at the impact of this test on mortality, meaning that any conclusions about whether the test will "save thousands of lives" – as the Mail and Telegraph suggest – is an assumption not backed by the evidence.
The media also failed to report that the test is already in use, and it is unclear why the Mail has suggested it might be in use "in casualty departments by Christmas". The origin of the £5 claim is also unclear from the media coverage, the press release or the conference abstract.
What kind of research was this?
This study examined the predictive accuracy of a blood test used in the diagnosis of heart attack by measuring troponin levels. When a person presents to hospital with symptoms of a heart attack, the main initial tests used in their diagnosis are an electrocardiogram (ECG) and a blood test that measures troponin levels.
Troponin is an enzyme released by the heart muscle. Levels of troponin are raised when the heart muscle has been damaged, as would happen when its blood supply has been interrupted and it has been starved of oxygen.
People who have symptoms of a heart attack may be classed as having one of the three acute coronary syndromes (ACS) depending on the results of their ECG and blood tests. All of these conditions are caused by fatty build-up in the arteries (atherosclerosis).
Even if a person hasn't had a heart attack but has unstable angina (symptoms of a heart attack but without raised troponin and ECG changes), they are still at very high risk of a full heart attack. This is because their symptoms suggest there is a large blockage in the artery supplying the heart, which could block off the heart's blood supply completely and cause a full heart attack.
Currently there is a single "threshold" for troponin levels to indicate whether a person is having a heart attack. However, the researchers believe there may be gender differences in troponin values among men and women having heart attacks. They suggest that the current diagnostic thresholds may lead to underdiagnosis of heart attacks in women, which could lead to differences in treatment and health outcomes.
This study sought to determine the diagnostic accuracy of using different troponin levels as the diagnostic threshold for men and women with suspected acute coronary syndrome (ACS).
What did the research involve?
The researchers recruited 1,126 patients (46% women) with suspected acute coronary syndrome from a UK regional cardiac centre. Two cardiologists independently diagnosed patients' heart attacks using lower diagnostic thresholds for the high-sensitivity troponin I assay.
The current test threshold used for both men and women is 50 nanograms per litre (ng/l). In this research, lower thresholds of 34ng/l for men and 16ng/l women were used.
The researchers then assessed how well these lower thresholds performed by comparing a statistic called area under the curve (AUC). This is a common method of assessing the predictive ability of a diagnostic test. The method takes into account both the sensitivity of a test (in this case, the percentage of patients having a heart attack who had test values above the selected threshold) to its specificity (the percentage of patients who were not having a heart attack who had test values below the selected threshold).
In most diagnostic tests there is a trade-off between sensitivity and specificity. As you lower the threshold for diagnosis, you can expect to increase the number of positive tests. This will likely increase both the number of true positives (improved sensitivity), but also the number of false positives (reduced specificity). Area under the curve values are used to select the optimal test threshold by taking this trade-off into account. The values range from 0 to 1, with higher scores indicating greater predictive ability.
What were the basic results?
When the researchers lowered the diagnostic threshold of the cardiac troponin assay from 50ng/l to 16ng/l, the diagnosis of heart attack in women increased from 13% to 23% (a statistically significant difference). Presumably this would mean that a larger proportion of women would be considered to have non-ST elevation MI who previously would have been classed as having unstable angina. The increase in diagnosis among men was also statistically significant but small in absolute terms (diagnosis increase from 23% to 24%).
The predictive ability of the new test threshold was greater when compared with the current threshold used for diagnosis in women, with an AUC value of 0.91 (95% confidence intervals [CI] 0.88 to 0.94) when using the 16ng/l threshold, compared with 0.70 (95% CI 0.64 to 0.77) at the current threshold.
Similarly, the improvements in diagnostic accuracy in men were small, with an AUC of 0.93 (95% CI 0.91 to 0.96) at the new threshold compared with 0.86 (95% CI 0.82 to 0.91). This difference borders on being statistically significant.
Finally, the researchers report that there were significant differences in treatment patterns between men and women, with women being significantly less likely to be referred to a cardiologist (52% women versus 87% men), undergo coronary angiography (28% women versus 67% men), or undergo revascularisation (18% women versus 58% men).
How did the researchers interpret the results?
The researchers conclude that the use of lower thresholds of the cardiac troponin assay, which varies between men and women, led to little effect on the diagnosis of heart attack in men, but a near doubling of the diagnosis in women.
This conference abstract suggests that lowering the troponin threshold may improve the predictive accuracy of this blood test to diagnose heart attacks. If someone attends hospital with symptoms of a heart attack, using a lower troponin threshold would presumably increase the proportion of women considered to have non-ST elevation MI who previously would have been classed as having unstable angina.
As the study has been reported from a conference presentation and only an abstract has been made available, we cannot draw any conclusions yet based on this information. It has not yet gone through the peer review process necessary before publication in scientific and medical journals. Without details about the methods used and more thorough data on patient characteristics and results, critical appraisal and an assessment of the quality of the study and validity of the results is not possible.
Despite the Daily Mail headline claiming that this test will save thousands of women, the study does not appear to have looked at clinical outcomes (what happened to the women following the test), including whether or not the improved diagnostic accuracy had any impact on mortality among the individuals included in the study. It is not possible to say that lowering the troponin threshold would lead to increased survival, and this assumption requires further investigation to be backed up by evidence.
If a person has symptoms of acute coronary syndrome (even if their troponin levels are below the diagnostic threshold and they do not have the ECG changes of heart attack), these still suggest that there is a significant blockage in a coronary artery and that they could be at high risk of having a full heart attack.
For this reason, the recommended diagnostic and treatment approach for people with non-ST elevation MI and unstable angina (for example, angiography, revascularisation and drug therapy) is fairly similar. Therefore, it would not be expected to make a great difference to treatment outcomes if a person is classed as having non-ST elevation MI who would otherwise have been classed as having unstable angina.
In fact, the researchers themselves say that as outcomes are not known, further attention should be paid to whether lowering the troponin threshold will improve clinical outcomes and help reduce the inequalities between men and women in terms of the diagnosis and management of ACS.
Overall, the limited information available suggests that lowering the diagnostic threshold of this blood test may primarily influence whether a person with symptoms of ACS is diagnosed as having heart attack (without ST elevation) or unstable angina. Whether this leads to improvements in outcomes, including mortality, remains to be seen.