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

Shah, Anoop; Griffiths, Megan; Lee, Kuan Ken; McAllister, David A; Hunter, Amanda; Ferry, Amy V.; Cruikshank, Anne; Reid, Alan; Stoddart, Mary; Strachan, Fiona; Walker, Simon; Collinson, Paul; Apple, Fred S.; Gray, Alasdair; Fox, Keith A.A.; Newby, David E.; Mills, Nicholas L

doi:10.1136/bmj.g7873

Cited by 377 publications

(351 citation statements)

References 35 publications

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“…Furthermore, we observed only subtle and nonsignificant sex‐based differences in the strength of the relationships between the individual HEART score components—history, ECG, age, risk factors, and admission troponin level—and the occurrence of MACE within 6 weeks. Interestingly, previous studies suggest that women with ACS present more frequently with atypical chest pain complaints, and less frequently with elevations of troponins as compared with men with ACS,5, 6, 26 though we observed no significant sex differences in the predictive value of the HEART score components H istory and T roponin for the occurrence of MACE.…”

Section: Discussioncontrasting

confidence: 68%

Sex‐Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

Bank

Hoog

Kleijn

et al. 2017

JAHA

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BackgroundSex‐based differences in clinical presentation, pathophysiology, and outcomes of patients with acute chest pain are increasingly being recognized, but are not implemented in guidelines and clinical prediction tools. We evaluated the performance of the HEART score in women versus men, because sex‐based differences may exist among the algorithm's components: history, electrocardiogram, age, risk factors, and admission troponin level.Methods and ResultsThe HEART score was retrospectively assessed in 831 women and 1084 men presenting to the emergency department with acute chest pain, assigning patients to the low‐, intermediate‐, or high‐risk category for the occurrence of major adverse cardiac events (MACE) within 6 weeks. MACE, consisting of myocardial infarction, coronary revascularization, and all‐cause death, also included events during index visit. Six‐week MACE rates were 2 times lower in women than men (10.0% versus 20.8%; P<0.01). Despite similar discriminatory accuracy of the HEART score among women and men (c‐statistic, 0.80 [0.75–0.84] versus 0.77 [0.74–0.81]; P=0.43), 6‐week MACE rates were significantly lower in women than men across all HEART risk categories: 2.1% versus 6.5% (P<0.01) in the low‐risk category, 12.7% versus 21.3% (P<0.01) in intermediate‐risk category, and 53.1% versus 77.0% (P=0.02) in the high‐risk category. The HEART score‐adjusted risk ratio for men was 1.6 (1.3–2.0; P<0.01).ConclusionsThe markedly higher 6‐week MACE risk in men across all HEART risk categories should be taken into account when using the HEART score to guide clinical decision making; early discharge with a low‐risk HEART score appears less safe for men than women with acute chest pain.

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Section: Discussioncontrasting

confidence: 68%

Sex‐Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

Bank

Hoog

Kleijn

et al. 2017

JAHA

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“…The results reported by Shah et al [116] and MuellerHennessen et al [118] are contradictory concerning the usefulness of using gender-specific cut-off values with highly sensitive methods for cTnI and cTnT. The discrepancies between the results of these two studies may be related to some biological differences between cTnI and cTnT.…”

Section: Are Gender-specific Cut-offs Useful For Diagnosis Of Ami?contrasting

confidence: 43%

“…However, the most recent 2015 ESC guidelines on the management of ACS in patients without persistent ST-segment elevation do not discuss this important issue [32]. Shah et al [116] recently evaluated the diagnostic accuracy for AMI of the highly sensitive cTnI ARCHITECT assay using gender-specific diagnostic thresholds, as suggested by the manufacturer (M 34 ng/L, F 16 ng/L), in 1126 patients (46% women) with suspected ACS. The highly sensitive cTnI assay actually doubled the diagnoses of type 1 AMI [3] in women (from 11 to 22%; p < 0.001) with respect to the less sensitive contemporary cTnI assay, but had a lesser effect in men (from 19 to 21%; p = 0.002).…”

Section: Are Gender-specific Cut-offs Useful For Diagnosis Of Ami?mentioning

confidence: 99%

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Clerico

Zaninotto

Ripoli

et al. 2017

Clinical Chemistry and Laboratory Medicine (CCLM)

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According to recent international guidelines, including the 2012 Third Universal Definiton of Myocardial Infarction by the Joint ESC/ACCF/AHA/WHF Task Force, an increase in cardiac troponin (cTn) levels over the 99th percentile upper reference limit (99th URL) should be considered clinically relevant, this cut-off being measured with an imprecision ≤10 CV%. In theory 99th URL values strongly depend not only on demographic and physiological variables (i.e. criteria for considering the reference population "healthy"), but also on the analytical performance of cTn methods and mathematical algorithms used for the calculation. The aim of the present article was therefore to review the methodological and pathophysiological factors affecting the evaluation and calculation of the 99th URL for cTn assay. The critical analysis made showed that no uniform procedure is followed, and nor have experts or regulatory bodies provided uniform guidelines for researchers or cTn assays manufacturers as an aid in "their quest to define normality". In particular, little attention has been paid to the way in which a healthy reference population is to be selected, or the criteria for calculating the 99th URL value for cTn assays, thus highlighting the need for international recommendations not only for demographic and physiological variables criteria for defining a healthy reference population, but also for calculating mathematical algorithms for establishing/ calculating clinical decision values. An expert consensus group, comprising laboratory and clinical scientists, biomedical statisticians, industrial and regulatory representatives, should be responsible for drawing up these guidelines.

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“…No classification was performed at admission to assess whether the heart failure was systolic or diastolic, but the prevalence and mortality rate were reported to be almost the same (Bhatia et al., 2006; Owan et al., 2006). The clinical importance remains to be proved of classifying more MIs in women with high sensitivity cardiac troponin with a diagnostic threshold of 16 ng/L and through these means, improving outcomes due to tailored treatment (Shah et al., 2015). …”

Section: Discussionmentioning

confidence: 99%

Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study

Eriksson

2016

Brain and Behavior

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ObjectivesTo assess long‐term prognosis after transient ischemic attack (TIA)/subtypes of stroke relative to secondary prophylactic treatment(s) given.Materials and MethodsRetro/prospective follow‐up of patients hospitalized in the Stroke Unit or in the Department of Neurology, Linköping, in 1986 and followed up to Feb. 2011.ResultsA total of 288 men were followed up for 2254 years (mean 7.8 years) and 261 women for 1984 years (mean 7.6 years). In men, the distribution to anticoagulants (AC) (warfarin treatment) was 18%, antiplatelet therapy (APT) usually ASA 75 mg/day 54%, untreated 27%, unknown 2%. In women, the distribution to AC was 15%, APT 60%, untreated 23%, unknown 2%, respectively. Mortality rates at 1 year, 10 years, and 25 years for men were 21%, 67%, and 93%, respectively, versus the rates in women of 24%, 71%, and 90%, respectively. Survival curves showed markedly increased risk of death compared to the normal population. AC treatment was more favorable for men regarding the annual risk of stroke, compared with APT (9.4% vs. 9.8%), as well as the risks of MI, (5.6% vs. 6.7%), and death (8.1% vs. 10.3%), compared to women for stroke (11.6% vs. 8.8%) and MI (5.3% vs. 3.7%) but not for death (8.3% vs. 8.4%). The risk of fatal bleeding was 0.86% annually on AC compared to 0.17% on APT. According to Cox regression analysis included patients with TIA/ischemic stroke, first‐line treatment had beneficial effects on survival: AC OR 0.67 (0.5–0.9), APT 0.67 (0.52–0.88) versus untreated.ConclusionsPatients with a history of TIA/stroke had a higher mortality rate versus controls, providing support for both primary and secondary prophylaxis regarding vascular risk factors for death. This study also provided support for secondary prophylactic treatment with either AC or ASA (75 mg once daily) to reduce the vascular risk of death unless there are contraindications.

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

Cited by 377 publications

References 35 publications

Sex‐Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

Sex‐Based Differences in the Performance of the HEART Score in Patients Presenting to the Emergency Department With Acute Chest Pain

The 99th percentile of reference population for cTnI and cTnT assay: methodology, pathophysiology and clinical implications

Secondary prophylactic treatment and long‐term prognosis after TIA and different subtypes of stroke. A 25‐year follow‐up hospital‐based observational study

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