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J Am Coll Cardiol, 1998; 32:1657-1664 © 1998 by the American College of Cardiology Foundation |

a Outcomes Research and Assessment Group, Duke Clinical Research Institute, the Division of Cardiology, Duke University Medical Center, Durham, North Carolina, USA
* Department of Medicine, and the Division of Biometry, Duke University Medical Center, Durham, North Carolina, USA
Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA
Manuscript received May 13, 1998; revised manuscript received July 7, 1998, accepted July 24, 1998.
Address for correspondence: Dr. Karen P. Alexander, Box 3411, Duke University Medical Center, Durham, North Carolina 27710
alexa019{at}mc.duke.edu
| Abstract |
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Background. Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown.
Methods. We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994.
Results. Women and men differed significantly in DTS (1.6 vs. 0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (
1 vessel with
75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or
75% left main stenosis) (3.5% vs. 11.4%, p < 0.001).
Conclusions. By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.
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Although the interpretation of the exercise test as "positive" or "negative" has traditionally been based on the presence of ST segment depression, the exercise test provides a variety of other diagnostic and prognostic indicators, including exercise capacity and symptoms, which are useful in test interpretation (12). By interpreting all the information as a composite score, the diagnostic ability of treadmill testing in women may increase. The Duke Treadmill Score (DTS), a weighted index combining ST segment deviation, treadmill time and exercise-induced angina, was developed and validated as a risk-prediction instrument in a predominately male population (13,14). Recently, it has also been shown in a predominately male population to stratify risk of significant and severe coronary disease (15). Because of its demonstrated prognostic ability, the DTS has been included in the recommended screening algorithms of the Agency for Health Care Policy and Research (AHCPR) Unstable Angina Guidelines and the newly revised ACC/AHA (American College of Cardiology/American Heart Association) Guidelines for Exercise Testing (9,16). To date, however, the diagnostic and prognostic accuracy of the DTS in women has not been fully evaluated. The purpose of the present study was to assess the diagnostic and prognostic performance of the DTS in almost 1,000 women undergoing treadmill testing and cardiac catheterization.
| Methods |
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Clinical, catheterization and follow-up data. Baseline clinical, exercise stress test and catheterization results were collected prospectively and entered into a computerized data base. Follow-up data were obtained by mailed questionnaire or telephone interview at 6 months and 1 year postcatheterization, and yearly thereafter as previously described (13,14). All cardiac deaths were confirmed with clinical data or death certificate by reviewers unaware of the clinical, angiographic or exercise stress data. Two-year follow-up for survival was 97% complete.
Exercise treadmill testing. All patients underwent symptom-limited treadmill testing using the standard Bruce protocol (13,14). A 12-lead ECG was recorded before exercise, at the end of each exercise stage, at peak exercise and at 2-min intervals during recovery. Three standard ECG leads were continuously monitored during exercise. The test was discontinued for limiting symptoms (angina, dyspnea, fatigue), abnormalities of rhythm or blood pressure, or marked and progressive ST segment deviation (>0.2 mV in the presence of typical angina or in the first stage of exercise). The ECG criterion for a positive test was 1 mm or more of exercise-induced ST segment deviation at 0.06 after the J point, relative to the PR segment.
Duke Treadmill Score.
The Duke Treadmill Score (DTS) was calculated by inserting a patients test results into the following formula:
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5), moderate risk (DTS score between 5 and 11) and high risk (DTS score
11) (13).
Statistical analyses.
For descriptive purposes, continuous variables were presented as medians (25th and 75th quartiles) and discrete variables as percentages. Statistical comparisons were made between men and women. The Wilcoxon rank-sum test was used to assess differences in continuous variables, and chi-square tests were used for discrete variables. Outcomes evaluated were significant coronary artery disease, severe coronary artery disease and survival. Significant coronary artery disease was defined as
75% diameter stenosis in one or more vessels, and severe disease, a subset of significant disease, was defined as
75% stenosis in three vessels or
75% left main stenosis.
The prognostic value of the DTS was examined in three ways. First, to examine the empirical risk stratification provided by the DTS, Kaplan-Meier survival curves were generated separately for women and men stratified by the three DTS risk categories (17). In this analysis, patients who subsequently underwent coronary revascularization were censored at the time of their procedure. Second, to test whether the DTS performed differently in women and men, we introduced an interaction term (gender by DTS) into the Cox model with DTS and gender and tested for its significance (18). Finally, we added independent clinical history and physical examination prognostic factors to the Cox model, and we tested for the predictive contribution of the DTS by comparing the model containing only clinical data to the model containing both clinical data and the DTS (Appendix) (19). The difference in the overall likelihood ratio chi-squares between the models was used to quantitate the incremental contribution of the DTS to the overall model of prognosis in women and men.
The diagnostic value of the DTS was examined in three ways. First, the probability of significant and severe coronary disease in women and men was plotted from logistic regression models including DTS and gender. The extent of coronary disease found at catheterization was correlated with DTS risk categories. Second, to compare diagnostic accuracy by gender, we used these logistic regression models, and we tested for the significance of an interaction term (gender by DTS) that would indicate differential effects of DTS on likelihood of significant or severe coronary disease due to gender. Finally, we added independent clinical history and physical exam diagnostic factors to test whether the DTS added diagnostic information to the baseline clinical data in men and women (Appendix) (20,21). We compared the models containing only clinical data to those containing both clinical data and the DTS. The difference in the overall likelihood ratio chi-squares between the models was then used to quantitate the incremental contribution of the DTS to the overall model for significant and severe disease in women and men.
| Results |
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When the DTS was added to the model with clinical predictors of coronary disease, it provided significant incremental information in both men and women. For significant disease, DTS provided 11.3% of the total information in women, and 13.9% of the total information in men. For severe disease, DTS added 18.5% of the total predictive information in women, and 26.9% in men (Table 4).
| Discussion |
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Comparison to prior studies. Because standard interpretation of exercise treadmill testing has lower specificity and positive predictive value in women, many investigators have attempted to improve the diagnostic accuracy of treadmill testing in women by creating new variables such as ST/HR (heart rate) slope, computer-generated algorithms and gender-specific guidelines for interpretation (4,2224). Because these methods have not found widespread clinical acceptance, others have suggested that initial testing strategies in women exclude standard treadmill testing in favor of exercise or stress-imaging studies (2528). In the current study, we found that the combination of several variables from treadmill testing into a single composite risk score provided equivalent risk stratification in men and women. There was no gender interaction between the DTS and the diagnosis of severe coronary disease and the prediction of survival. The borderline gender interaction between the DTS and the diagnosis of significant disease was largely explained by the weaker relationship between angina and the presence of coronary artery disease in women. Removing the angina component from the DTS did not significantly change its diagnostic ability in women because treadmill time and ST deviation substitute more of the diagnostic information in women. This emphasizes the advantage of interpreting results of treadmill testing as a composite score.
Clinical significance of treadmill scores. Our analysis showed that predictions for women should be interpreted within the context of lower pretest risk for both diagnostic and prognostic risk stratification. Because of differences in disease prevalence, women had better survival at all values of the DTS. Risk categories were essentially shifted down one level of severity in women. The three treadmill risk categories of low, moderate, and high risk in men corresponded to very low, low, and moderate risk in women. In essence, owing the lower prevalence of disease in women, a low risk DTS was actually better at excluding coronary artery disease in women than in men. Although many low risk men can be managed without additional invasive testing, this is true for both low and moderate risk women. Therefore, renewed confidence in the initial use and interpretation of treadmill testing in women should be encouraged, especially for the purpose of excluding coronary artery disease.
Study limitations. The population in our study consisted of inpatients who underwent cardiac catheterization as part of their initial cardiac evaluation. Although this is necessary to determine diagnostic accuracy of treadmill testing, it creates a potential bias toward patients with a higher likelihood of disease. The prognostic accuracy of the Duke Treadmill Score has been previously tested and validated in an outpatient population, but this latter population did not have enough women to examine this subgroup separately. Furthermore, though our population of 976 women was smaller than comparable studies in men, it still represents one of the largest assessments of treadmill accuracy in women. In addition, our findings only apply to patients who are candidates for exercise treadmill testing, who are physically able to walk on a treadmill and have no resting abnormalities on their ECG.
Conclusions. In the largest study to date of women undergoing treadmill testing, we demonstrated that the DTS can accurately stratify diagnostic and prognostic risk in women. Our results support the routine initial use of the exercise treadmill test in suitable candidates of both genders presenting with suspected coronary artery disease, as recommended by the new ACC/AHA Exercise Testing Guidelines.
| Appendix |
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: CHF = congestive heart failure; IVCD = intraventricular conduction defect; LAD = left axis deviation; LBBB = left bundle-branch block; MI = myocardial infarction; PVCs = premature ventricular contractions; RBBB = right bundle-branch block.
| Acknowledgments |
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| References |
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