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(Circulation. 1995;92:1209-1216.)
© 1995 American Heart Association, Inc.

Articles

Gender-Specific Criteria and Performance of the Exercise Electrocardiogram

Peter M. Okin, MD; Paul Kligfield, MD

From the Division of Cardiology, Department of Medicine, the New York Hospital-Cornell Medical Center, New York, NY.

Correspondence to Peter M. Okin, MD, The New York Hospital-Cornell Medical Center, 525 E 68th St, New York, NY 10021.

	Abstract

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Background Significant gender differences have been found in performance of the exercise ECG for the identification of coronary artery disease. However, identical exercise ECG ST segment criteria have been used in men and women, which might contribute to the lower accuracy of these methods in women than in men.

Methods and Results To assess the effect of gender-specific test partitions on relative performance of standard and heart rate–adjusted ST segment depression criteria in men and women, the exercise ECGs of 143 women and 477 men were examined. Non–gender-specific test partitions, selected to have matched specificities of 96% for each test method, were determined in all 283 normal subjects, and gender-specific test partitions with identical specificity were determined separately in the 52 normal women and 231 normal men; sensitivity of these criteria was then examined in the 91 women and 246 men with coronary disease. Standard ST segment depression criteria (0.1 mV of additional horizontal or downsloping ST segment depression at end exercise) with identical 96% specificity in the entire group of normal subjects and separately in women and men had a significantly lower sensitivity of 51% in women compared with 67% in men (P<.01). Among women, performance of the ST segment/heart rate (ST/HR) slope was more improved than that of the ST/HR index by the use of gender-specific criteria. Compared with the performance of non–gender-specific criteria, application of gender-specific ST/HR slope partitions with matched specificity of 96% resulted in a significant increase in sensitivity in women from 84% to 91% (P<.01), with no significant change in sensitivity in men (89% to 88%) and with no residual difference in sensitivity between men and women. Although the use of gender-specific ST/HR slope criteria significantly improved sensitivity in both men and women with respect to standard criteria (each P<.0001), the relative increase in sensitivity provided by heart rate adjustment was significantly greater in women than in men (40% versus 21%, P<.001). Similar gender differences in improvement in performance using gender-specific criteria for the ST/HR slope were observed when analysis of test performance was restricted to the detection of three-vessel coronary disease (50% versus 9%, P=.002).

Conclusions At high specificity, gender-specific test partitions improve sensitivity of the ST/HR slope for the identification of coronary disease in women, with no decrease in sensitivity in men. In contrast, gender-specific partitions do not change performance of standard test criteria, which is lower in women than in men. Accordingly, the relative benefit of heart rate adjustment by the ST/HR slope method is greater in women than in men. These findings support use of the ST/HR slope with use of gender-specific partitions for the identification and quantification of coronary artery disease in both men and women.

Key Words: electrocardiography • heart rate • exercise

	Introduction

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Among the problems with standard exercise electrocardiography is its lower overall test accuracy for the identification of coronary artery disease in women than in men.^{1 2 3 4 5 6 7 8 9 10} The basis for decreased test performance in women remains unclear. Early studies suggested lower specificity of standard exercise test criteria in women,^{1 2 3} but other studies demonstrate similar specificities in men and women,^{4 5 6 7 8 9 10} with trends toward lower sensitivity in women^{6 7 8 9 10} or even high specificities in normal women.^{4 5 11 12} Although heart rate adjustment of the magnitude of ST depression using the simple ST segment/heart rate (ST/HR) index and the computationally more complex ST/HR slope can increase the accuracy of the exercise ECG for the identification of coronary disease in women,^{6 10 13} sensitivity of the ST/HR index has remained lower in women than in men.^{6 14 15} In all of these comparative studies, however, identical criteria for the detection of coronary disease were used in both men and women.^{1 2 3 4 5 6 7 8 9 10} Therefore, the present study was performed to examine gender differences in the distribution of ST depression responses to exercise and to determine whether the use of gender-specific criteria can improve the exercise ECG identification of coronary artery disease in women by standard and heart rate–adjusted ST depression criteria.

	Methods

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Study Population
There were 620 consecutively studied subjects and patients who met previously defined criteria¹⁵ and who were entered into one of three clinical groups: one with a low likelihood of coronary disease and two with a high (or certain) likelihood of disease as outlined below.

Normal Subjects
There were 283 normal subjects (231 men and 52 women; mean age, 48±10 years). These subjects were selected to represent clinically normal ambulatory populations rather than normal volunteer groups or patients with normal coronary arteries found at catheterization. All subjects were free of chest pain, had no history of cardiac disease, no history of hypercholesterolemia, no family history of premature death due to coronary artery disease, and no diabetes mellitus; they had normal cardiac physical examinations, normal blood pressure, normal resting ECGs, and were not taking any cardioactive medications. Based on the data of Diamond et al¹⁶ and Diamond and Forrester,¹⁷ the age- and sex-adjusted likelihood of coronary disease in these asymptomatic subjects can be estimated as no more than .05.

Patients With Clinical Angina
There were 153 patients with stable exertional angina (94 men and 59 women; mean age, 61±9 years). These subjects were selected to represent ambulatory coronary disease populations not selected for angiography and thus free of accelerating symptoms and posttest referral bias. Patients with left bundle branch block or myocardial infarction within 8 weeks were not included. Thirteen patients had resting ECG evidence of previous Q-wave myocardial infarction and 13 patients had ECG evidence of left ventricular hypertrophy. There were 95 patients who were not taking medications; among the remaining 58 patients, 38 were taking ß-blocking drugs, 25 were taking long-acting nitrates, and 25 were taking calcium channel blockers at the time of exercise testing. No patient was taking an angiotensin-converting enzyme inhibitor at the time of exercise testing. The age- and sex-adjusted likelihood of coronary disease in this group can be estimated at no less than .93.^{16 17}

Patients With Catheterization-Proven Coronary Disease
There were 184 patients with coronary disease proved by catheterization (152 men and 32 women; mean age, 64±11 years). Patients with left bundle branch block or recent myocardial infarction were also excluded. There were 27 patients with ECG evidence of Q-wave myocardial infarction and 18 with evidence of left ventricular hypertrophy. There were 36 patients who were unmedicated; among the remaining 148 patients, 114 were taking ß-blocking drugs, 92 were taking nitrates, and 93 were taking calcium channel blockers at the time of exercise evaluation. No patient was taking an angiotensin-converting enzyme inhibitor at the time of exercise testing.

Exercise ECG
Exercise ECGs were performed on a treadmill with a computerized exercise system modified by the addition of a bipolar lead CM₅. All patients exercised according to the Cornell protocol,¹⁸ our more gently graded modification of the Bruce protocol that produces the small heart rate increments between stages necessary for accurate determination of the ST/HR slope.¹⁹ The protocol divides each stage of the modified Bruce protocol into half-stages and consists of 2-minute stages, beginning with stage 0 at 1.7 mph and 0% grade and gradually increasing in a stepwise fashion to stage 5 and 5.0 mph at an 18% grade.¹⁸ Age-adjusted target heart rates were sought as the exercise end point for all studies, but tests were terminated when necessary because of limiting chest pain, dyspnea, or fatigue. Exercise tests were not terminated for the presence of ST segment depression in the absence of limiting symptoms, but only 2% of patients (13 of 620) had 0.4 mV or more ST depression at peak exercise. Computer-calculated ST segment amplitudes, measured to the nearest 10 µV at a point 60 ms after the J-point with the end of the PR segment as reference, were obtained in each lead after each minute of exercise and at peak exercise; accuracy of this measurement has been validated in our laboratory.^{19 20}

Exercise tests were evaluated using standard ECG criteria based on the measured amount of ST segment depression on the peak exercise ECG.^{15 21} The test was considered positive in the presence of 0.1 mV (100 µV) of additional horizontal or downsloping ST segment depression. For determination of both standard and heart rate–adjusted criteria, only additional ST segment depression below the isoelectric baseline was used; all resting ST segment elevation was normalized to the zero baseline as previously described.^{22 23}

ST/HR Slope and ST/HR Index Calculation
Calculation of the maximal ST/HR slope was performed using linear regression analysis to relate the magnitude of ST segment depression in each lead (except aV_R, aV_L, and V₁, which were excluded from all analyses) to heart rate at the end of each stage of exercise and at peak exercise, according to methods previously reported in detail.^{6 15 18 19 20} The highest ST/HR slope with a significant coefficient of correlation among all the leads was taken as the test result. The ST/HR index was calculated by dividing the maximal additional ST segment depression at end exercise (corrected for any ST segment depression in that lead on the upright preexercise resting ECG) by the exercise-induced change in heart rate.^{6 15}

Coronary Angiography
In the patients who underwent catheterization, selective coronary cineangiography was performed as previously reported.^{6 15 18 19 20} Degree of obstruction was defined as the greatest percent reduction of luminal diameter in any view compared with the nearest normal segment. According to 50% luminal diameter obstruction criteria, there were 41 patients with one-vessel disease, 61 with two-vessel disease, and 82 with three-vessel coronary artery disease. Seventeen patients had left main coronary disease, including 4 with additional two-vessel disease and 13 with additional three-vessel disease.

Data Analysis and Statistical Methods
Mean values and standard deviations are reported for each variable by group. Comparison of mean demographic and exercise ECG values between men and women in each group were performed using the Student's t test; simple proportions were compared using ² analysis. Mean values of ST segment depression, the ST/HR index, and the ST/HR slope in men and women in each group were also compared using ANCOVA to adjust for baseline differences in age and exercise duration. Gender differences in the distribution of ST segment depression, the ST/HR index, and the ST/HR slope were assessed separately in patients with and without coronary disease using the Kolmogorov-Smirnov test.²⁴

Definitions of test sensitivity and specificity conform to standard use.²⁵ Test specificity of each method for the identification of coronary disease was assessed in all 283 normal subjects and separately in the 231 clinically normal men and 52 normal women to produce gender-specific test criteria. Test sensitivity of each method using both gender-specific and non–gender-specific criteria was assessed in the 246 men and 91 women with known or suspected coronary disease. Sensitivity of standard criteria, the simple magnitude of ST depression at end exercise, the ST/HR index, and ST/HR slope were compared between men and women using test partitions with matched specificity of 96% found for standard criteria using a two-tailed Fisher's exact test. Comparisons of test sensitivities of the different criteria in men and in women were performed using McNemar's modification of the ² method for paired proportions. Because test sensitivity and specificity are dependent on the partition value chosen for test positivity, test accuracy was also compared using receiver operating characteristic (ROC) curve analysis. ROC curves compare test accuracy over a wide range of possible partition values and can be used to compare differences in test performance in separate populations and to compare differences between methods independent of empirically derived criteria.²⁶ ROC curves were compared statistically by means of a univariate z test of the difference between the areas under two ROC curves.²⁷ For all comparisons, a value of P<.05 was required for rejection of the null hypothesis.

	Results

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Gender Differences in Group Characteristics and Exercise Performance
Group clinical characteristics according to gender are shown in Table 1. Of the clinically normal subjects, the women were significantly older than the men, but by group definition both men and women had no ECG evidence of Q-wave myocardial infarction or left ventricular hypertrophy and were not taking any cardioactive medications. Of the patients with clinical angina and with catheterization-proven coronary artery disease, the men and women were similar with respect to rest ECG findings and drug use, but the women with proven coronary disease were older than the men. There was no difference in the prevalence of multivessel disease (78% [118 of 152] versus 78% [25 of 32], P=NS) or three-vessel disease (46% [70 of 152] versus 38% [12 of 32], P=NS) between men and women who underwent coronary arteriography.

View this table: [in this window] [in a new window]   Table 1. Group Clinical Characteristics According to Gender

Group exercise test performance according to gender is examined in Table 2. Of the normal subjects, the women exercised for a shorter period of time and had lower exercise systolic blood pressures and smaller changes in heart rate with exercise than did the men. Of patients with clinical angina or known coronary disease, women exercised for a shorter period of time, developed significantly less ST segment depression, and had lower mean ST/HR index and ST/HR slope values than did the men in each group. Differences in mean values of ST segment depression, the ST/HR index, and the ST/HR slope between men and women with known or suspected coronary disease persisted after adjusting for baseline gender differences in age and exercise duration using ANCOVA.

View this table: [in this window] [in a new window]   Table 2. Group Exercise Test Characteristics According to Gender

Because comparison of mean values may not necessarily reflect differences in the overall distribution of the same values,²⁴ gender differences in the distribution of ST segment depression, the ST/HR index, and the ST/HR slope were compared separately in the clinically normal subjects and in the combined patients with known or suspected coronary artery disease. Among normal subjects, there were no significant gender differences in the frequency distribution of ST segment depression, the ST/HR index, or the ST/HR slope. In contrast, among patients with known or suspected coronary artery disease, there were significant differences between men and women in the distributions of all three ST segment variables (each P<.0001). Gender differences in frequency distribution for ST segment depression are shown in Fig 1; similar patterns were observed for the ST/HR index and ST/HR slope.

View larger version (12K): [in this window] [in a new window]   Figure 1. Curves show frequency distribution of ST segment depression responses to exercise according to gender in normal subjects (left) and patients with known or suspected coronary artery disease (CHD, right).

Standard Test Criteria and Identification of Coronary Artery Disease in Men and Women
The relationship of test performance of standard ST segment depression criteria and the simple magnitude of ST segment depression for the detection of coronary obstruction to gender is examined in Table 3 and Fig 2. When specificity was defined in all 283 normal subjects using a single, non–gender-specific test partition, standard ST segment depression criteria (100 µV additional horizontal or downsloping ST segment depression at end exercise) with a specificity of 96% identified coronary disease with a sensitivity of 67% in men but only 51% in women (P<.01). Using a non–gender-specific test partition with a matched specificity of 96%, the simple magnitude of ST depression >160 µV identified coronary disease with a sensitivity of 60% in men but only 30% in women (P<.001).

View this table: [in this window] [in a new window]   Table 3. Test Sensitivity for Identification of Coronary Artery Disease According to Gender Using Gender-Specific and Non4 Gender-Specific Partitions With Matched Specificities of 96%

View larger version (12K): [in this window] [in a new window]   Figure 2. Receiver operating characteristic curves comparing overall performance of the simple magnitude of ST depression for the identification of coronary artery disease assessed in the entire population and assessed separately in men and women (*P<.05 vs men).

Because standard ST depression criteria had identical 96% specificity in men and women, use of gender-specific partitions for standard test criteria resulted in the same 67% and 51% sensitivities in men and women as when a non–gender-specific test partition was used. In contrast, when criteria with 96% specificity for the simple magnitude of ST depression were defined separately in the 231 normal men and 52 normal women, there were parallel changes of an opposing direction in sensitivity in men and in women compared with the sensitivity of non–gender-specific partitions, reducing the difference in sensitivity between men and women. In men, an ST depression partition of >170 µV with 96% specificity had a sensitivity of 55%, significantly lower than the 60% sensitivity found when non–gender-specific test partitions were used (P<.001), while in women, an ST depression partition of 150 µV with matched 96% specificity had a sensitivity of 35%, slightly but significantly greater than the 30% sensitivity found for the non–gender-specific partition. Comparison of ROC curves further illustrates that the increased overall performance of gender-specific simple ST depression criteria in men compared with women was independent of the test specificity chosen to compare sensitivities and that overall performance of criteria derived and tested in the total population of men and women does not accurately reflect performance in either sex, underestimating performance of gender-specific criteria in men and overestimating performance of gender-specific criteria in women (Fig 2).

Heart Rate–Adjusted ST Depression Criteria and Identification of Coronary Artery Disease in Men and Women
The relationship of the performance of the ST/HR index and ST/HR slope for the identification of coronary disease to gender is examined in Table 3 and Figs 3 and 4. Using non–gender-specific test partitions with 96% specificity in the entire group of clinically normal subjects, trends toward lower sensitivity of both the ST/HR index and the ST/HR slope in women were evident. Compared with non–gender-specific criteria, the use of separate gender-specific partitions for men and women resulted in a significant increase in sensitivity of the ST/HR slope in women from 84% to 91% (P<.01) but with no significant decrease in sensitivity in men and with no resulting difference in sensitivity between men and women. Comparison of ROC curves confirmed that overall performance of the ST/HR slope was comparable in men and women but at different gender-specific partition values (Fig 3). Furthermore, gender-specific performance at very high specificities was greater in both men and women than performance that was based on criteria derived and tested in the entire population (Fig 3). In contrast, the use of gender-specific test partitions had no significant effect on the separate sensitivities of the ST/HR index at 96% specificity in either men or women compared with non–gender-specific test performance. However, there remained a small but statistically significant increase in overall performance of the gender-specific ST/HR index in men than in women when ROC curves were compared (Fig 4).

View larger version (11K): [in this window] [in a new window]   Figure 3. Receiver operating characteristic curves comparing overall performance of the ST segment/heart rate (ST/HR) slope for the identification of coronary artery disease assessed in the entire population and assessed separately in men and women.

View larger version (11K): [in this window] [in a new window]   Figure 4. Receiver operating characteristic curves comparing overall performance of the ST segment/heart rate (ST/HR) index for the identification of coronary artery disease assessed in the entire population and assessed separately in men and women (*P<.05 vs men).

The relative improvement in sensitivity over standard criteria provided by each method of gender-specific heart rate adjustment is illustrated in Fig 5. Use of the heart rate–adjusted methods improved sensitivity to a greater degree in women than in men when gender-specific criteria were used: compared with standard criteria, the 35% increase in sensitivity for the ST/HR index and 40% increase in sensitivity for the ST/HR slope in women were significantly greater than the 24% and 21% increases attributable to heart rate adjustment in men. Of note, sensitivity of gender-specific criteria at a matched specificity of 96% and overall test performance as measured by ROC curve area was significantly greater for both the ST/HR index and ST/HR slope than for either standard test criteria or the simple magnitude of ST depression in both men and women (Table 3), but there were no significant differences in gender-specific test performance between the ST/HR index and the ST/HR slope in either men or women for the identification of coronary disease in this population.

View larger version (23K): [in this window] [in a new window]   Figure 5. Bar graphs show gender differences in the improvement in sensitivity obtained using the ST segment/heart rate (ST/HR) index and ST/HR slope compared with standard test criteria for the identification of coronary artery disease (top) and for the identification of three-vessel coronary disease (bottom). Solid bars represent men; hatched bars, women.

Because the requirement of matching test specificity to the 96% specificity of standard test criteria in the current population produced different and higher test partitions for both the ST/HR index and ST/HR slope than the test partitions of 1.60 µV/beat per minute (bpm) and 2.40 µV/bpm that were originally derived to have 95% specificity in a subset of the present study group,¹⁵ alternative analyses were performed using these partitions for the calculation of test sensitivities and specificities for the identification of coronary disease in this enlarged, gender-stratified population (Table 4). In the total group of men and women, specificity of original criteria for the ST/HR slope was 93% and for the ST/HR index was 94%, while sensitivity of each heart rate–adjusted measure was 94%. When test performance of these test partitions was examined separately according to sex, there were trends toward lower sensitivities and higher specificities in women than in men. These findings represent a small decline in the overall specificity of these measures with time compared with the 95% specificity of these partitions in the first 100 of the 283 clinically normal subjects in the present population in which these partitions had been derived.¹⁵

View this table: [in this window] [in a new window]   Table 4. Test Sensitivity and Specificity for Identification of Coronary Artery Disease of Previously Established ST/HR Index and ST/HR Slope Partitions in the Overall Population and Separately According to Gender

Gender Differences in Identification of Three-Vessel Coronary Disease
The relationship of the performance of standard and heart rate–adjusted ST depression criteria for the identification of three-vessel coronary disease to gender is illustrated in Table 5. When specificity was defined in all 102 men and women with one- or two-vessel coronary disease, a markedly positive test by standard ST segment depression criteria (200 µV additional horizontal or downsloping ST segment depression) with a specificity of 65% identified three-vessel coronary disease with a sensitivity of 70% in men and only 42% in women. Using non–gender-specific test partitions with closely matched specificities, the simple magnitude of ST depression identified three-vessel disease with a sensitivity of 71% in men and only 42% in women (P<.05), but there were no significant differences in the higher sensitivities between men and women for either the ST/HR index or ST/HR slope. Use of gender-specific partitions had no effect on the sensitivity of a markedly positive standard test, the simple magnitude of ST depression, or the ST/HR index in men or women. In contrast, when gender-specific test partitions were used, sensitivity of the ST/HR slope for three-vessel disease in women increased to 92%.

View this table: [in this window] [in a new window]   Table 5. Test Sensitivity for Identification of Three-Vessel Coronary Artery Disease According to Gender Using Gender-Specific and Non–Gender-Specific Partitions With Closely Matched Specificities of 60% to 68%

The relative improvement in sensitivity for the identification of three-vessel coronary disease offered by each heart rate adjusted method compared with a markedly positive standard test in men and women is examined in Fig 5. Using gender-specific criteria, both the 33% increase in sensitivity for the ST/HR index and the 50% increase in sensitivity for the ST/HR slope in women were significantly greater than the 6% and 9% increases observed in men.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This study confirms that standard ST depression criteria are significantly less sensitive in women than in men and demonstrates that the use of gender-specific test partitions with matched specificity in men and women improves performance of both simple ST depression criteria and the ST/HR slope in women compared with non–gender-specific criteria. Furthermore, although the ST/HR index and ST/HR slope can markedly improve performance of the exercise ECG in both men and women, the benefit of heart rate adjustment is greater in women than in men. These findings support use of the ST/HR slope, with use of gender-specific test partitions, for the identification and quantification of coronary artery disease both in men and in women.

Gender Differences of the Exercise ECG
Although numerous studies have reported lower accuracy of traditional ST segment depression criteria in women than in men,^{1 2 3 4 5 6 7 8 9 10} it remains controversial whether this difference is better explained by lower test sensitivity or lower specificity in women. In a large subgroup of men and women from the Coronary Artery Surgery Study¹ matched for age, prevalence, and severity of coronary disease, there was no significant difference in test sensitivity between women and men (76% versus 78%), but specificity was significantly lower in women (64% versus 73%). Barolsky et al⁷ reported similarly lower specificities in women than in men (68% versus 89%), with no significant gender differences in sensitivity (60% versus 65%). However, when patients taking digitalis preparations were excluded from their analyses, standard ST segment depression criteria had identical 95% specificities but lower sensitivity in women than in men (50% versus 64%). Using ROC curve analyses, Morise et al⁸ found lower overall accuracy in women that appeared to be due to a combination of lower sensitivity and lower specificity in women than in men. Conversely, a number of investigators have found high test specificities in normal women.^{4 5 11 12}

Differences in the magnitude of ST depression between otherwise healthy men and women have been suggested as a possible explanation for gender differences in test specificity.^{6 28} The current study demonstrates no significant gender difference in standard test specificity and no difference in the mean values or frequency distributions of ST segment depression between clinically normal men and women. In contrast, the lower sensitivity of standard criteria and simple ST depression criteria in women in the present study can be directly attributed to the lower magnitude of ST depression among women with coronary disease. Differences in the magnitude of ST segment depression between men and women may be due in part to the effects of either estrogens or progesterones on the ST segment response to exercise in women.^{29 30} The observation that consideration of estrogen status significantly improves the overall accuracy of exercise testing in women⁸ further supports this possibility. In addition, it is possible that gender differences in the ST segment response to exercise could in part reflect variable effects of hyperventilation on the ST segment response to exercise in patients with coronary disease^{31 32} in men and women. However, gender differences in the effects of hyperventilation on the exercise ST segment have not been demonstrated.

Gender-Specific Criteria and Identification of Coronary Artery Disease
Despite the similar magnitudes of the simple magnitude of ST segment depression, the ST/HR index, and the ST/HR slope in clinically normal men and women, gender-specific partitions were required to result in similar test specificity in men and women for these criteria. Furthermore, compared with non–gender-specific partitions, use of gender-specific partitions for the simple magnitude of ST depression and ST/HR slope increased test sensitivity in women. Interestingly, there was no difference in specificity of the traditional partition of 0.1 mV (100 µV) of horizontal or downsloping ST segment depression in our men and women, obviating the need for gender-specific partitions for this basic well-established criterion. The differential magnitude of ST segment responses in men and women with coronary disease can clearly account for the decreased accuracy of standard test criteria and of the simple magnitude of ST depression in women even when gender-specific criteria are used. In contrast, the relatively smaller differences in test performance of the ST/HR index and of the ST/HR slope between men and women reflect the smaller gender differences of these variables among patients with disease. Similar patterns of simple and heart rate–adjusted ST depression findings in relation to gender in patients with and without three-vessel coronary disease account for the lower sensitivity of simple ST depression criteria in women and absence of any significant gender differences in sensitivity for the identification of three-vessel disease by the ST/HR index and ST/HR slope.

As a consequence of the lower sensitivity of standard test criteria in women than in men and the similar performance of the ST/HR slope and ST/HR index in both sexes, increased accuracy of the heart rate–adjusted criteria relative to standard test criteria for both the detection of disease and for the identification of patients with three-vessel coronary disease was more dramatic in women than in men. The relatively greater improvement in test performance by heart rate–adjusted criteria in women than in men may in part account for the absence of any significant difference in performance between standard criteria and the ST/HR index that has been reported in a few all-male³³ or predominantly male³⁴ populations.

ST/HR Slope and ST/HR Index Test Partitions
To allow for accurate comparison of test performance between standard and heart rate–adjusted criteria in the current study, ST/HR index and ST/HR slope partitions with specificities matched to the 96% specificity of standard test criteria were used. Not unexpectedly, these values were somewhat higher than the originally derived partitions of 1.60 µV/bpm and 2.40 µV/bpm, which had been established to have 95% specificities by the method of percentile estimation in the first 100 of the 283 clinically normal subjects included in the present population.¹⁵ The slight decrease in overall specificity of these originally derived partitions in the current study is not unexpected.^{15 35 36} Specificity of a new test is often overestimated and frequently declines with time as the new method is incorporated into clinical decision making.^{35 36} The small decreases in overall specificities to 93% and 94% may additionally reflect subtle differences in patient referral patterns over time, separate from considerations of test methodology. Further study of larger numbers of clinically normal women will be necessary to establish robust, gender-specific partitions for application of these methods in women.

Clinical Implications
Increased accuracy of the exercise ECG for the detection of coronary disease in women has important implications. Because gender differences in outcome after the diagnosis of angina may be due in part to a greater misclassification of the onset of angina in women,³⁷ more accurate detection of the presence or absence of coronary disease in women presenting with symptoms consistent with typical angina would improve risk stratification. Indeed, even using non–gender-specific criteria, the ST/HR index can significantly improve prognostication in asymptomatic women when compared with standard ST depression criteria.³⁸ Moreover, recent studies have suggested that gender differences in evaluation and outcome after an abnormal exercise test³⁹ and the consequent decreased utilization of coronary angiography and coronary revascularization in women⁴⁰ argue in favor of gender-specific guidelines for diagnostic and prognostic evaluation.³⁹

At the present time, optimal accuracy of the exercise ECG in both men and women can be obtained using the linear regression–based ST/HR slope method with gender-specific criteria. The relatively low cost of exercise ECG, combined with the improved overall accuracy of the ST/HR slope relative to standard test criteria, suggests that application of heart rate–adjusted methodology should improve the clinical utility and cost effectiveness of the exercise ECG for the routine evaluation of patients with known or suspected coronary disease.

	Acknowledgments

 
This study was supported by a grant from the Michael Wolk Heart Foundation, Inc, New York, NY.

Received January 24, 1995; revision received March 3, 1995; accepted March 19, 1995.

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