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AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.
High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.
The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.
He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.
Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.
The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.
Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.
"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.
In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.
The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.
"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.
Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.
"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.
High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.
The under-recognition of heart disease and differences in clinical presentation in women lead to less aggressive treatment strategies and a lower representation of women in clinical trials. Thus, as seen in this study, an improvement in the diagnosis of MI in women using the more sensitive cardiac troponin assay and different gender-based cutoffs can have a meaningful impact in outcomes in our female patients.
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| Dr. Hiren Shah |
In a recent large meta-analysis of 11 randomized ACS trials it was shown that sex-based differences in 30-day mortality among patients with various manifestations of ACS are largely explained by clinical differences at presentation and the severity of angiographically documented disease (JAMA. 2009;302:874-82.). Thus, new assays that account for gender-based differences may lead to an earlier identification of heart disease in women to address some component of this mortality disparity.
The second phase of this study using these new thresholds will shed light on if this increased capture rate of MI for women leads to improved long term cardiac outcomes, as one hopes that the increased sensitivity seen in the first phase of the study is also balanced with an improvement in specificity. If the results of this and future studies are conclusive, gender-based interpretation of diagnostic tests will lead to earlier diagnosis and improved therapeutic strategies in women.
Dr. Hiren Shah is an assistant professor of medicine in the Feinberg School of Medicine, Northwestern University, Chicago, and a medical director of the Medicine and Cardiac Telemetry Hospitalist Unit at Northwestern Memorial Hospital in Chicago. He is on the advisory board of Hospitalist News.
The under-recognition of heart disease and differences in clinical presentation in women lead to less aggressive treatment strategies and a lower representation of women in clinical trials. Thus, as seen in this study, an improvement in the diagnosis of MI in women using the more sensitive cardiac troponin assay and different gender-based cutoffs can have a meaningful impact in outcomes in our female patients.
|
| Dr. Hiren Shah |
In a recent large meta-analysis of 11 randomized ACS trials it was shown that sex-based differences in 30-day mortality among patients with various manifestations of ACS are largely explained by clinical differences at presentation and the severity of angiographically documented disease (JAMA. 2009;302:874-82.). Thus, new assays that account for gender-based differences may lead to an earlier identification of heart disease in women to address some component of this mortality disparity.
The second phase of this study using these new thresholds will shed light on if this increased capture rate of MI for women leads to improved long term cardiac outcomes, as one hopes that the increased sensitivity seen in the first phase of the study is also balanced with an improvement in specificity. If the results of this and future studies are conclusive, gender-based interpretation of diagnostic tests will lead to earlier diagnosis and improved therapeutic strategies in women.
Dr. Hiren Shah is an assistant professor of medicine in the Feinberg School of Medicine, Northwestern University, Chicago, and a medical director of the Medicine and Cardiac Telemetry Hospitalist Unit at Northwestern Memorial Hospital in Chicago. He is on the advisory board of Hospitalist News.
The under-recognition of heart disease and differences in clinical presentation in women lead to less aggressive treatment strategies and a lower representation of women in clinical trials. Thus, as seen in this study, an improvement in the diagnosis of MI in women using the more sensitive cardiac troponin assay and different gender-based cutoffs can have a meaningful impact in outcomes in our female patients.
|
| Dr. Hiren Shah |
In a recent large meta-analysis of 11 randomized ACS trials it was shown that sex-based differences in 30-day mortality among patients with various manifestations of ACS are largely explained by clinical differences at presentation and the severity of angiographically documented disease (JAMA. 2009;302:874-82.). Thus, new assays that account for gender-based differences may lead to an earlier identification of heart disease in women to address some component of this mortality disparity.
The second phase of this study using these new thresholds will shed light on if this increased capture rate of MI for women leads to improved long term cardiac outcomes, as one hopes that the increased sensitivity seen in the first phase of the study is also balanced with an improvement in specificity. If the results of this and future studies are conclusive, gender-based interpretation of diagnostic tests will lead to earlier diagnosis and improved therapeutic strategies in women.
Dr. Hiren Shah is an assistant professor of medicine in the Feinberg School of Medicine, Northwestern University, Chicago, and a medical director of the Medicine and Cardiac Telemetry Hospitalist Unit at Northwestern Memorial Hospital in Chicago. He is on the advisory board of Hospitalist News.
AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.
High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.
The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.
He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.
Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.
The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.
Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.
"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.
In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.
The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.
"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.
Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.
"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.
High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.
AMSTERDAM – The use of a high-sensitivity cardiac troponin I assay and gender-specific cutoffs to define acute myocardial infarction nearly doubled the diagnosis of MI in women in an early subanalysis from the High-STEACS trial.
High-sensitivity troponin assays have identified gender differences in the normal reference range. This becomes relevant in light of the third universal definition of acute MI, released last year, which defines the biomarker threshold for the diagnosis of MI as a cardiac troponin at the 99th percentile of a healthy reference population (Eur. Heart J. 2012;33:2551-67). The conventional cardiac troponin assays in widespread use today aren’t sufficiently sensitive to detect gender differences in the normal reference range, so they rely upon a single diagnostic threshold that sets the bar so high it appears to lead to underdiagnosis of MI in women. This likely contributes to gender inequalities in treatment and outcome, Dr. Nicholas L. Mills asserted at the annual congress of the European Society of Cardiology.
The high-sensitivity cardiac troponin I assay utilized in the ongoing High-STEACS (High-Sensitivity Troponin in the Evolution of Patients with Acute Coronary Syndrome) trial uses an MI diagnostic threshold of 16 ng/L in women and 34 ng/L in men. These levels were derived by identifying the 99th percentiles in a healthy reference population composed of nearly 4,600 individuals. In contrast, the conventional troponin I assay utilized for purposes of comparison in High-STEACS employs a threshold of 50 ng/L for both men and women, explained Dr. Mills of the University of Edinburgh.
He reported on 1,126 patients with suspected acute coronary syndrome (ACS), 46% of them women, who presented to the Royal Infirmary of Edinburgh, one of the 10 Scottish medical centers participating in High-STEACS. Subjects’ plasma samples were analyzed using both the Abbott conventional sensitive cardiac troponin I assay and Abbott’s newer high-sensitivity assay, but clinicians received only the results of the conventional assay. The aim of this High-STEACS substudy was to evaluate the effect of gender-specific biomarker thresholds. The final diagnosis of acute MI was determined independently by two cardiologists on the basis of all clinical studies and 30-day outcomes.
Using the conventional assay with a requirement of a troponin level of 50 ng/L or more in both men and women, acute MI was diagnosed in 13% of women and 23% of men. Utilization of the high-sensitivity assay with sex-specific thresholds boosted the rate of diagnosis of MI from 13% to 23% in the women while having little effect in men, where the rate inched up from 23% to 24%.
The diagnostic sensitivity of the conventional assay was 77% in men and 47% in women, while the high-sensitivity assay with gender-specific thresholds had a sensitivity of 86% in men and 95% in women, according to Dr. Mills.
Women with an adjudicated diagnosis of MI were less likely than men to undergo coronary angiography, by a margin of 28% compared with 67%, and they were far less likely to undergo coronary revascularization, by a margin of 18% to 58%. That’s largely because 55 women in the study had a high-sensitivity troponin I level of 17-49 ng/L, above the level required for diagnosis of MI using the sex-specific threshold but below the 50 ng/L requirement with the conventional assay that clinicians used in their patient management decisions.
"The critical question is whether reclassification of these patients as having MI would lead to better treatment and change clinical outcomes. At 6 months, one in four of these patients had a recurrent MI or died, compared with less than 2% of women with a high-sensitivity troponin I of 16 ng/L or less. Those outcomes were similar to or worse than those in women with much larger MIs, who were treated based upon the results of the contemporary assay requiring a level of 50 ng/L or more," the cardiologist noted.
In a previous study, Dr. Mills and his coworkers demonstrated that lowering the diagnostic threshold for acute MI using a previous-generation sensitive cardiac troponin assay in patients with suspected ACS led to a 50% reduction in recurrent MI or death (JAMA 2011;305:1210-5). This was accomplished simply by reclassifying patients as having MI provided their peak troponin exceeded the new, lower threshold.
The hypothesis being tested in High-STEACS is that lowering the biomarker diagnostic threshold for MI still further while utilizing gender-specific cutoffs will result in even better clinical outcomes. High-STEACS is an ongoing randomized trial involving a planned 26,000 Scottish patients with suspected ACS who will be followed for 30 months.
"If improved sensitivity does not impinge on specificity in diagnosis, then clinical outcomes will improve through better targeting of therapies for coronary heart disease. But if increased sensitivity leads to poorer specificity, then misdiagnosis and use of inappropriate therapies may lead to detrimental clinical outcomes," Dr. Mills explained.
Discussant Dr. Eva Swahn of Linkoping (Sweden) University commented that if the results of this High-STEACS substudy showing the value of gender-specific biomarker thresholds hold up, the implications regarding diagnosis and management of MI in women could be great. But elevations in cardiac troponins can be caused by other conditions besides acute MI, including stable angina, renal failure, diabetes, and heart failure, and the substudy design leaves her unconvinced that troponin I elevations in the 17- to 49-ng/L range were necessarily due to MI.
"If you don’t have an MI you shouldn’t be treated as though you do. The management will be completely wrong, and maybe the outcome will be worse," she cautioned.
High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.
AT THE ESC CONGRESS 2013
Major finding: The use of a high-sensitivity cardiac troponin I assay with novel gender-specific diagnostic thresholds boosted the MI diagnosis rate in women with suspected ACS from 13% to 23%.
Data source: A substudy of the ongoing prospective High-STEACS trial in 1,126 consecutive men and women who presented with suspected ACS.
Disclosures: High-STEACS is funded by the British Heart Foundation. Abbott Diagnostics is supplying the cardiac troponin assay materials. Dr. Mills and Dr. Swahn reported having no financial conflicts.
