By Nicolas Mills
Other authors: Dr Anoop SV Shah, UK; Ms Megan Griffiths, UK; Dr Ken Kuan Lee, UK; Dr David A McAllister, UK; Dr Amanda L Hunter, UK; Dr Anne Cruikshank, UK; Dr Alan Reid, UK; Mrs Mary Stoddart, UK; Dr Fiona Strachan, UK; Dr Simon Walker, UK; Dr Paul O Collinson, UK ; Dr Fred S Apple, US; Professor Keith AA Fox, UK; Professor David E Newby, UK; Dr Nicholas L Mills, UK
High-sensitivity cardiac troponin assays have identified differences in the normal reference range for cardiac troponin between men and women. Current diagnostic thresholds may lead to under diagnosis of myocardial infarction in women and contribute to sex inequalities in treatments and outcomes.
Consecutive patients with suspected acute coronary syndrome (n=1,126, 46% women) were prospectively identified over a three-month period from August 2012 in a United Kingdom regional cardiac center. The diagnosis of myocardial infarction was adjudicated by two independent cardiologists using a high-sensitivity troponin I assay with sex-specific diagnostic thresholds (men 34 ng/L and women 16 ng/L) and compared to current practice where a contemporary sensitive assay (50 ng/L; single cutoff) was used to guide patient care.
Use of a high-sensitivity cardiac troponin assay markedly increased the diagnosis of myocardial infarction in women (from 13% to 23%; P<0.001) but had a minimal effect in men (from 23% to 24%, P=0. 021). Diagnostic accuracy was greater with the high-sensitivity assay compared to the contemporary assay in women (area under the curve [AUC] 0.91, 95% confidence intervals [CI] 0.88-0.94 versus 0.70, 95%CI 0.64-0. 77) with smaller improvements in men (0.93, 95%CI 0.91-0.96 versus 0.86, 95%CI 0.82-0.91). Women with an adjudicated diagnosis of myocardial infarction were less likely to be referred to a cardiologist (52% versus 87%), or to undergo coronary angiography (28% versus 67%) or revascularisation (18% versus 58%) compared to men (P<0.001 for all).
In comparison to men, women with suspected acute coronary syndrome are more likely to be misdiagnosed and under treated for myocardial infarction. Whilst having little effect in men, a high-sensitivity troponin assay doubles the diagnosis of myocardial infarction in women. Whether implementation of high-sensitivity assays will improve clinical outcomes and address persisting discrepancies in the management of women with suspected acute coronary syndrome requires urgent attention.
The current study aims at evaluating the diagnosis of myocardial infarction using a high-sensitivity cardiac troponin I assay, comparing sex specific diagnostic thresholds in consecutive men and women presenting with suspected ACS.
The results are interesting, revealing what the authors claim are novel and important observations.
The diagnosis of MI in women was doubled using the sex-specific diagnostic threshold, which the authors say improves sensitivity in women but not in men. The authors further speculate that this under diagnosis of MI in women could explain why women are not managed equally to men and thus have a worse prognosis.
If this report holds, the implications could be great and favor the future management of women with suspected ACS. Anyhow there are some thoughts regarding this study. As is so nicely formulated in the paper by Thygesen et al last year in EHJ,(1) it is important to note that an increased hs-cTn concentration alone is not sufficient to make the diagnosis of MI. Mills et al have not sufficiently explained how they could with such certainty declare that the increased hs-cTnI-level is indeed caused by an MI.
Patients with stable angina, heart failure, renal failure, left ventricular hypertrophy, diabetes etc. may have elevations in hs-cTn . Women with suspected ACS are older, have more diabetes, renal insufficiency and heart failure. (2-5) All these co-morbidities must be considered in ruling in AMI.
However, regardless of the cause, elevations of hs-cTn values are associated with worse prognosis regarding cardiac events and should thus be taken seriously but must not necessarily be managed as an MI. In the present study only two blood samples were taken, at admission and either at 6 or 12 hours later which is diverting from the guidelines where it is recommended for early rule-in/rule-out MI to sample at admission and at 3 hours when using the hs-cTn assays. The detection of myocardial necrosis includes also detection of a rise and/or fall of the biomarkers, this is not given in the data. To be able to judge the scientific value of the data it is also essential that the basic characteristics of the 3 hs-TnI groups are given.
The clinical challenge today is to identify individual patients with the highest risk for worse outcome without unreasonably elevated early risk for complications with treatment. To meet this challenge it is absolutely necessary to reach a correct diagnose as the outcome and thus management differs depending on this.
Last, but not least, it has to be taken into account that current evidence assessing long-term outcome in MI-patients have found no difference between the genders, or even better outcome in women, at least after adjustment.(6-8)
1. Thygesen K, Mair J, Giannitsis E, Mueller C, Lindahl B, Blankenberg S, Huber K, Plebani M, Biasucci LM, Tubaro M, Collinson P, Venge P, Hasin Y, Galvani M, Koenig W, Hamm C, Alpert JS, Katus H, Jaffe AS. How to use high-sensitivity cardiac troponins in acute cardiac care. Eur Heart J 2012; 33(18):2252-2257.
2. Alexander KP, Newby LK, Armstrong PW, Cannon CP, Gibler WB, Rich MW, Van de Werf F, White HD, Weaver WD, Naylor MD, Gore JM, Krumholz HM, Ohman EM. Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007; 115(19):2570-2589.
3. Alexander KP, Newby LK, Cannon CP, Armstrong PW, Gibler WB, Rich MW, Van de Werf F, White HD, Weaver WD, Naylor MD, Gore JM, Krumholz HM, Ohman EM. Acute coronary care in the elderly, part I: Non-ST-segment-elevation acute coronary syndromes: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology. Circulation 2007; 115(19):2549-2569.
4. Langer A, Freeman MR, Josse RG, Steiner G, Armstrong PW. Detection of silent myocardial ischemia in diabetes mellitus. Am J Cardiol 1991; 67(13):1073-1078.
5. Sederholm Lawesson S, Todt T, Alfredsson J, Janzon M, Stenestrand U, Swahn E. Gender difference in prevalence and prognostic impact of renal insufficiency in patients with ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Heart 2011; 97(4):308-314.
6. Lawesson SS, Alfredsson J, Fredrikson M, Swahn E. A gender perspective on short- and long term mortality in ST-elevation myocardial infarction - A report from the SWEDEHEART register. Int J Cardiol 2012.
7. Lawesson SS, Alfredsson J, Fredrikson M, Swahn E. Time trends in STEMI--improved treatment and outcome but still a gender gap: a prospective observational cohort study from the SWEDEHEART register. BMJ Open 2012; 2(2):e000726.
8. Alfredsson J, Swahn E. Management of acute coronary syndromes from a gender perspective. Fundam Clin Pharmacol 2010; 24(6):719-728.