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Determinants of a positive exercise test in patients admitted with acute non-infarct chest pain
International Journal of Cardiology 66 (1998) 147–151
Determinants of a positive exercise test in patients admitted with acute non-infarct chest pain ´ Moreno*, Jose-Luis ´ ´ ´ Ana Ortega, Javier Fernandez ´ Raul Cantalapiedra, Esteban Lopez de Sa, ´ ´ ´ ´ Juan-Luis Delcan ´ Portales, Jaime Fernandez-Bobadilla, Jose-Luis Lopez-Sendon, ˜ ´ , Doctor Esquerdo, 46, 28007 Madrid, Spain Cardiology Department, Hospital Gregorio Maranon Received 21 April 1998; accepted 30 June 1998
Abstract Background and objectives. Some patients with suspected unstable angina show ischemia at the exercise treadmill test despite having been medically stabilized. The objective of this study was to determine clinical characteristics predicting a positive exercise treadmill test in patients with suspected unstable angina after medical stabilization. Methods. In 885 hospitalized patients with medically stabilized unstable angina, the relationship between the result of the pre-discharge exercise treadmill test and clinical characteristics was studied. Results. Mean age was 6269 years and 668 (75%) were male. Exercise test was positive (chest pain and / or ST depression $1 mm) in 288 patients (33%). Univariate analysis showed the following associated with ischemia at the exercise test: male gender (56% vs. 20%, P,0.001), diabetes mellitus (41% vs. 31%, P50.009), previous unstable angina (41% vs. 24%, P50.001), previous stable angina (44% vs. 30%, P,0.001), previous coronary artery bypass grafting (43% vs. 31%, P50.043), peripheral artery disease (45% vs. 31%) and progressive angina (55% vs. 31%, P,0.001). Multivariate analysis showed the following as independent predictors of ischemia: male gender (OR52.25), diabetes (OR54.12), previous unstable angina (OR53.89), previous stable angina (OR53.74) and progressive angina (OR54.05). Conclusions. In patients with suspected unstable angina, after medical stabilization: (1) the exercise treadmill test is positive in one-third of cases; (2) male gender, diabetes, previous angina (unstable and stable) and progressive angina are independent predictors of ischemia. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Chest pain; Exercise test; Myocardial ischaemia; Unstable angina
1. Introduction The first aim in patients with suspected unstable angina is to achieve stabilization with medical treatment [1]. Usually, in stabilized patients, the next objective is to identify those with a higher future risk of myocardial infarction and death. The exercise treadmill test has been demonstrated to be safe [2] and of diagnostic and prognostic value not only in *Corresponding author.
myocardial infarction, but also in non-infarct acute chest pain, with those having a positive exercise test a higher frequency of multivessel disease [3,4] and a worse prognosis [6–10]. About 20–40% of patients with non-infarct acute chest pain perform a positive exercise test [2,3], and these are frequently referred to cardiac catheterization and coronary revascularization [1], while those with a negative exercise test are usually discharged on medical treatment. However, it has not been studied what patients with suspected unstable angina are
0167-5273 / 98 / $19.00 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00202-2
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R. Moreno et al. / International Journal of Cardiology 66 (1998) 147 – 151
more likely to show ischemia at the exercise test despite having been medically stabilized. The aim of this study was to determine the clinical variables predicting a positive exercise test in patients with non-infarct acute chest pain.
and / or ST depression of at least 1 mm in two or more adjacent electrocardiographic leads.
2.5. Left ventricular ejection fraction
2. Material and methods
It was measured by transthoracic echocardiography (M-mode, paraesternal long axis view), and considered to be depressed if lower than 0.50.
2.1. Patients
2.6. Statistical analysis
Between January 1991 and April 1996, a symptom-limited pre-discharge exercise treadmill test was performed after medical stabilization in 885 hospitalized patients with suspected unstable angina, 48–72 h after the last episode of chest pain. These patients constitute the study population.
Statistical analysis was performed with the help of the computer program JMP 3.0.1 (SAS Institute). Quantitative variables are expressed as mean6standard deviation, and qualitative variables as percentages (proportions). Comparison between two or more than two media was performed with the Student T-test and ANOVA test, respectively, and the association between qualitative variables was studied 2 with the x test. Intervals are expressed with a confidence level of 95%. Associations were considered as statistically significant with a value of less than 0.05. Multivariate analysis was performed with a stepwise logistic regression method.
2.2. Variables studied The following characteristics were studied: gender, coronary risk factors, previous coronary disease (myocardial infarction, admission due to unstable angina, stable angina, coronary bypass grafting and coronary angioplasty), presence of peripheral artery disease, type of angina (rest, recent onset, progressive or postinfarction), left ventricular systolic function and type of antianginous treatment.
2.3. Diagnosis of unstable angina All patients had been admitted with acute chest pain indicative of unstable angina. Recent onset angina: angina since less than 1 month. Rest angina: angina occurring in the absence of physical or psychological stress. Postinfarction angina: angina occurring during the first month after a myocardial infarction. Progressive angina: stable angina with worsening of symptoms during the last 2 weeks. The patient was considered to be medically stabilized 48 h after the last episode of chest pain.
2.4. Exercise treadmill ( ET) test The ET test was performed following the Bruce protocol [11], and was limited by symptoms. It was considered as positive in the presence of chest pain
3. Results
3.1. Baseline characteristics Baseline characteristics are shown in Table 1. Twenty-three percent of the patients were on nitrates, 74% on calcium channel blockers and 55% on betablockers. One hundred and seventy-four (19.7%) referred chest pain during the exercise test, and ST depression appeared in 213 (24.1%). Two hundred and eighty-eight (32.5%) performed a positive exercise test (chest pain and / or ST depression).
3.2. Predictors of ischemia at the exercise test Patients with a positive exercise test, compared with those with a negative exercise test, had a lower functional capacity (8.262.9 vs. 8.965.1 METS, P5 0.0373) and a lower percentage of the maximum heart rate reached (76.8613.0 vs. 81.2614.2, P5 0.0001), but there was no difference regarding the duration of exercise. The univariate analysis showed
R. Moreno et al. / International Journal of Cardiology 66 (1998) 147 – 151 Table 1 Baseline characteristics Age (years) Male gender (%) Smoking (%) Diabetes mellitus (%) Hypercholesterolemia (%) Hypertension (%) Previous AMI (%) Previous unstable angina (%) Previous SA (%) Previous CABG (%) Previous PTCA (%) Peripheral artery disease (%) Type of UA Rest UA (%) Recent UA (%) Progressive UA (%) Postinfarction UA (%) Left ventricular dysfunction (%) Functional capacity (METS) Exercise duration (min) Percent of MHR
149
Table 2 Prevalence of positivity in exercise test in different subgroups of patients 62.169.7 76 61 20 38 47 33 27 18 8 11 10 73 15 10 2 15 8.764.6 7.764.5 80614
AMI, acute myocardial infarction; UA, unstable angina; SA, stable angina; CABG, coronary artery bypass grafting; PTCA, percutaneous coronary angioplasty; left ventricular dysfunction, left ventricular ejection fraction less than 0.50; MHR, maximum heart rate.
the following variables associated with a positive exercise test: male gender (36.5 vs. 20.2%, P, 0.0001), diabetes mellitus (41.4 vs. 31.4%, P5 0.0149), previous admissions due to unstable angina (41.0 vs. 29.8%, P50.0020), previous stable angina (44.0 vs. 30.4%, P50.0013), previous coronary bypass grafting (44.3 vs. 31.8%, P50.0368), peripheral artery disease (45.2 vs. 31.6%, P50.0131) and progressive angina (56.2 vs. 29.8%, P,0.0001) (Table 2). Other characteristics, such as previous myocardial infarction, left ventricular function and type of antianginous treatment (betablockers, calcium antagonists or nitrates), were not statistically associated with the presence of ischemia at the exercise test. Male gender (OR52.46; 95% CI: 1.68–3.67), diabetes mellitus (OR51.61; 95% CI: 1.10–2.35), previous unstable angina (OR51.57; 95% CI: 1.10– 2.23), previous stable angina (OR51.56; 95% CI: 1.04–2.33) and progressive angina (OR52.77: 95% CI: 1.69–4.58) were independent risk factors for a positive exercise test in the multivariate analysis. In patients with none of these characteristics, the prevalence of positivity at the exercise test was 6%. The exercise test was positive in 41–56%, 43–67% and
Age .65 years Male gender Smoking Hypercholesterolemia Diabetes mellitus Hypertension Previous AMI Previous UA Previous SA Previous CABG Previous PTCA Peripheral artery disease Progressive UA Left ventricular dysfunction
Yes (%)
No (%)
P
31 37 34 33 41 32 35 41 44 44 38 45 56 29
34 20 31 33 31 34 32 30 30 32 32 32 30 34
NS ,0.0001 NS NS 0.0149 NS NS 0.0020 0.0013 0.0368 NS 0.0131 ,0.0001 NS
Yes, prevalence of positivity in patients with the characteristic; No, prevalence of positivity in patients without the characteristic; AMI, acute myocardial infarction; UA, unstable angina; SA, stable angina; CABG, coronary artery bypass grafting; PTCA, percutaneous coronary angioplasty; left ventricular dysfunction, left ventricular ejection fraction less than 0.50.
49–80% of the patients in the presence of one, two or more than two of these independent risk factors.
3.3. Predictors of chest pain during the exercise test The univariate analysis showed the following associated with the presence of chest pain at the exercise test: male gender (22.3 vs. 11.5%, P5 0.0003), previous unstable angina (28.2 vs. 16.8%, P50.0003), previous stable angina (28.0 vs. 18.0%, P50.0059), previous coronary bypass (34.3 vs. 18.6%, P50.0030) and progressive angina (43.8 vs. 17%, P,0.0001). Male gender (OR52.23; 95% CI: 1.49–3.84), previous unstable angina (OR51.80; 95% CI: 1.17–2.58) and progressive angina (OR5 3.68; 95% CI: 2.21–6.12) were independent risk factors for the appearance of chest pain in the multivariate analysis.
3.4. Predictors of ST depression at the exercise test Variables associated with ST depression were: male gender (27.4 vs. 13.8%, P,0.0001), diabetes mellitus (31.4 vs. 23.1%, P50.0288), previous stable angina (31.2 vs. 22.7%, P50.0283), peripheral artery disease (34.5 vs. 23.2%, P50.0268) and progressive
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angina (39.3 vs. 22.3%, P50.0004). Male gender (OR52.52; 95% CI: 1.65–3.97), diabetes mellitus (OR51.61; 95% CI: 1.08–2.38) and progressive angina (OR52.09; 95% CI: 1.26–3.45) were independent risk factors for ST depression in the multivariate analysis.
Finally, some studies have demonstrated that patients with recent onset and rest angina have a worse prognosis than patients with progressive effort angina [23]. All the patients of our study had been medically stabilized, and constitute a subgroup of patients that do not represent all the patients with unstable angina. Therefore, our results do not contradict the fact that patients with rest angina have a worse prognosis.
4. Discussion
4.1. Prevalence of ischemia at the exercise test In the present series of patients with suspected unstable angina, the prevalence of positivity at the exercise test after medical stabilization was 32.5%, which is in agreement with previous studies [2,3].
4.2. Predictors of a positive exercise test Some variables were associated with a positive exercise treadmill test: previous angina (unstable and stable), progressive angina, male gender and diabetes mellitus. Probably, patients with previous angina have significant coronary stenosis and even multivessel disease more frequently [4,5]. Male gender is associated with a more extended coronary disease compared with women, who have a higher prevalence of microvascular disease and single vessel disease [13–16]. Diabetes is associated with a more rapidly progressive and more extended coronary artery disease [17–19]. Finally, in patients with rest or recent onset angina, as compared with progressive angina, coronary lesions contain more thrombi [20,21], and perhaps this may explain why after stabilization on antianginous and antiplatelet therapy significant coronary lesions underly more frequently in progressive angina, and therefore ischemia at the exercise test is more probably. Some characteristics associated with a worse prognosis in patients with coronary artery disease, such as previous myocardial infarction and left ventricular function [12,22], were not associated with the presence of ischemia at the exercise test. The reason for this may be that the poorer prognosis in patients with previous myocardial infarction or in those with left ventricular dysfunction is due not to residual ischemia, but mainly to heart failure and arrhythmic sudden death.
4.3. Is a pre-discharge exercise test mandatory for all patients with suspected unstable angina? Although a negative exercise test is not a guarantee for a good long-term outcome [24], the test has been demonstrated to be of prognostic value in patients with suspected unstable angina, with those having a positive test having a higher incidence of acute myocardial infarction and death [6–10]. A predischarge exercise test in these patients has a similar diagnostic value as compared with an exercise test 1 month after discharge [25,26]. However, since half of the 1-year new coronary events in patients with unstable angina occur during the first months of evolution, a predischarge exercise test is usually recommended [25]. Nevertheless, since patients with a negative exercise test are usually discharged on medical treatment, in centers in which the exercise test produces a long delay in discharge, those not presenting characteristics predicting a positive exercise test could be referred to a post-discharge exercise test. Only 6% of the patients with none of the independent risk factors showed ischemia at the exercise test, and therefore women without previous coronary artery disease or effort angina could perhaps be referred to a post-discharge exercise test.
References [1] Braunwald E, Jones RH, Mark D, et al. Unstable angina: diagnosis and management of unstable angina. Circulation 1994;90:613–22. [2] Swahn E, Areskog M, Wallentin L. Early exercise testing after coronary care for suspected unstable coronary artery disease – safety and diagnostic value. Eur Heart J 1986;7(7):594–601. [3] Butman SM, Olson HG, Butman LK. Early exercise testing after stabilization of unstable angina: correlation with coronary angiographic findings and subsequent cardiac events. Am Heart J 1986;111(1):11–8.
R. Moreno et al. / International Journal of Cardiology 66 (1998) 147 – 151 [4] Freeman MR, Chisholm RJ, Armstrong PW. Usefulness of exercise electrocardiography and thallium scintigraphy in unstable angina pectoris in predicting the extent and severity of coronary artery disease. Am J Cardiol 1988;62(17):1164–70. [5] Swahn E, Areskog M, Berglund U, Walfridsson H, Wallentin L. Predictive importance of clinical findings and a predischarge exercise test in patients with suspected unstable coronary artery disease. Am J Cardiol 1987;59(4):208–14. [6] Nyman I, Larsson H, Areskog M, Areskog NH, Wallentin L. The predictive value of silent ischemia at an exercise test before discharge after an episode of unstable coronary artery disease. RISC Study Group. Am Heart J 1992;123(2):324–31. [7] Wilcox I, Freedman SB, Allman KC, et al. Prognostic significance of a predischarge exercise test in risk stratification after unstable angina pectoris. J Am Coll Cardiol 1991;18:677–83. [8] Swahn E, Areskog M, Wallentin L. Prognostic importance of early exercise testing in men with suspected unstable coronary artery disease. Eur Heart J 1987;8(8):861–9. [9] Nyman I, Wallentin L, Areskog M, Areskog NH, Swahn E. Risk stratification by early exercise testing after an episode of unstable coronary artery disease. The RISC Study Group. Int J Cardiol 1993;39(2):131–42. [10] Bogaty P, Dagenais GR, Cantin B, Alain P, Rouleau JR. Prognosis in patients with a strongly positive exercise electrocardiogram. Am J Cardiol 1989;64(19):1284–8. [11] Bruce RA, Kusumi F, Hosmer D. Maximal oxygen intake and nomographic assessment of functional aerobic impairment in cardiovascular disease. Am Heart J 1973;85:546–62. [12] Mock MB, Ringkvist I, Fisher LD, Davis KB, Chaitman BR, Kouchoukos NT. Survival of medically treated patients in the Coronary Artery Surgery Study (CASS) registry. Circulation 1982;66:562–8. [13] Chaitman BR, Bourassa MG, Davis K, et al. Angiographic prevalence of high coronary artery disease in patients subsets (CASS). Circulation 1981;64:360–7. [14] Proudfit WL, Welch CCH, Siqueira C, Morcerf FP, Sheldon WC. Prognosis of 1,000 young women studied by coronary angiography. Circulation 1981;64:1185–90. [15] Swahn E, Areskog M, Berglund V, Walfridsson H, Wallentin L. Predictive importance of clinical findings and a predischarge exercise test in patients with suspected unstable coronary artery disease. Am J Cardiol 1987;59:208–14.
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[16] Kannel WB, Feinleib M. Natural history of angina pectoris in the Framingham study. Prognosis and survival. Am J Cardiol 1971;29:154–63. [17] van Miltenburg-van Zijl AJ, Simoons ML, Veerhoek RJ, Bossuyt PM. Incidence and follow-up of Braunwald subgroups in unstable angina pectoris. J Am Coll Cardiol 1995;25:1286–92. [18] Moreno R, Rey JR, Cantalapiedra JL et al. Predictors of multivessel disease in cases of acute chest pain. Int J Cardiol (in press). [19] Stone PH, Muller JE, Hartwell T, et al. The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. J Am Coll Cardiol 1989;14:49–57. [20] Wilensky RL, Bourdillon PDV, Vix VA, Zeller JA. Intracoronary thrombus formation in unstable angina: a clinical, biochemical and angiographic correlation. J Am Coll Cardiol 1993;21:692–9. [21] Dangas G, Mehran R, Wallenstein S, et al. Correlation of angiographic morphology and clinical presentation in unstable angina. J Am Coll Cardiol 1997;29:519–25. [22] Gottlieb SO, Weisfeldt ML, Ouyang P, Mellits ED, Gerstemblith G. Silent ischemia predicts infarction and death during 2 years of follow-up of unstable angina. J Am Coll Cardiol 1987;10:756–60. [23] Rizik DG, Healy SH, Margulis A, et al. A new clinical classification for hospital prognosis of unstable angina pectoris. Am J Cardiol 1995;75:993–7. ´ ´ ´ JL et al. Prognosis of [24] Moreno R, Lopez de Sa´ E, Lopez-Sendon medically stabilized unstable angina pectoris and a negative exercise test. Am J Cardiol (in press). [25] Larsson H, Areskog M, Areskog NH, et al. Should the exercise test (ET) be performed at discharge or one month later after an episode of unstable angina or non-Q-wave myocardial infarction? Int J Card Imaging 1991;7(1):7–14. [26] Karlsson JE, Bjorkholm A, Blomstrand P, Ohlsson J, Wallentin L. Ambulatory ST-recording has no additional value to exercise test for identification of severe coronary lesions after an episode of unstable coronary artery disease in men. Int J Card Imaging 1993;9(4):281– 9.
Determinants of a positive exercise test in patients admitted with acute non-infarct chest pain ´ Moreno*, Jose-Luis ´ ´ ´ Ana Ortega, Javier Fernandez ´ Raul Cantalapiedra, Esteban Lopez de Sa, ´ ´ ´ ´ Juan-Luis Delcan ´ Portales, Jaime Fernandez-Bobadilla, Jose-Luis Lopez-Sendon, ˜ ´ , Doctor Esquerdo, 46, 28007 Madrid, Spain Cardiology Department, Hospital Gregorio Maranon Received 21 April 1998; accepted 30 June 1998
Abstract Background and objectives. Some patients with suspected unstable angina show ischemia at the exercise treadmill test despite having been medically stabilized. The objective of this study was to determine clinical characteristics predicting a positive exercise treadmill test in patients with suspected unstable angina after medical stabilization. Methods. In 885 hospitalized patients with medically stabilized unstable angina, the relationship between the result of the pre-discharge exercise treadmill test and clinical characteristics was studied. Results. Mean age was 6269 years and 668 (75%) were male. Exercise test was positive (chest pain and / or ST depression $1 mm) in 288 patients (33%). Univariate analysis showed the following associated with ischemia at the exercise test: male gender (56% vs. 20%, P,0.001), diabetes mellitus (41% vs. 31%, P50.009), previous unstable angina (41% vs. 24%, P50.001), previous stable angina (44% vs. 30%, P,0.001), previous coronary artery bypass grafting (43% vs. 31%, P50.043), peripheral artery disease (45% vs. 31%) and progressive angina (55% vs. 31%, P,0.001). Multivariate analysis showed the following as independent predictors of ischemia: male gender (OR52.25), diabetes (OR54.12), previous unstable angina (OR53.89), previous stable angina (OR53.74) and progressive angina (OR54.05). Conclusions. In patients with suspected unstable angina, after medical stabilization: (1) the exercise treadmill test is positive in one-third of cases; (2) male gender, diabetes, previous angina (unstable and stable) and progressive angina are independent predictors of ischemia. 1998 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Chest pain; Exercise test; Myocardial ischaemia; Unstable angina
1. Introduction The first aim in patients with suspected unstable angina is to achieve stabilization with medical treatment [1]. Usually, in stabilized patients, the next objective is to identify those with a higher future risk of myocardial infarction and death. The exercise treadmill test has been demonstrated to be safe [2] and of diagnostic and prognostic value not only in *Corresponding author.
myocardial infarction, but also in non-infarct acute chest pain, with those having a positive exercise test a higher frequency of multivessel disease [3,4] and a worse prognosis [6–10]. About 20–40% of patients with non-infarct acute chest pain perform a positive exercise test [2,3], and these are frequently referred to cardiac catheterization and coronary revascularization [1], while those with a negative exercise test are usually discharged on medical treatment. However, it has not been studied what patients with suspected unstable angina are
0167-5273 / 98 / $19.00 1998 Elsevier Science Ireland Ltd. All rights reserved. PII: S0167-5273( 98 )00202-2
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R. Moreno et al. / International Journal of Cardiology 66 (1998) 147 – 151
more likely to show ischemia at the exercise test despite having been medically stabilized. The aim of this study was to determine the clinical variables predicting a positive exercise test in patients with non-infarct acute chest pain.
and / or ST depression of at least 1 mm in two or more adjacent electrocardiographic leads.
2.5. Left ventricular ejection fraction
2. Material and methods
It was measured by transthoracic echocardiography (M-mode, paraesternal long axis view), and considered to be depressed if lower than 0.50.
2.1. Patients
2.6. Statistical analysis
Between January 1991 and April 1996, a symptom-limited pre-discharge exercise treadmill test was performed after medical stabilization in 885 hospitalized patients with suspected unstable angina, 48–72 h after the last episode of chest pain. These patients constitute the study population.
Statistical analysis was performed with the help of the computer program JMP 3.0.1 (SAS Institute). Quantitative variables are expressed as mean6standard deviation, and qualitative variables as percentages (proportions). Comparison between two or more than two media was performed with the Student T-test and ANOVA test, respectively, and the association between qualitative variables was studied 2 with the x test. Intervals are expressed with a confidence level of 95%. Associations were considered as statistically significant with a value of less than 0.05. Multivariate analysis was performed with a stepwise logistic regression method.
2.2. Variables studied The following characteristics were studied: gender, coronary risk factors, previous coronary disease (myocardial infarction, admission due to unstable angina, stable angina, coronary bypass grafting and coronary angioplasty), presence of peripheral artery disease, type of angina (rest, recent onset, progressive or postinfarction), left ventricular systolic function and type of antianginous treatment.
2.3. Diagnosis of unstable angina All patients had been admitted with acute chest pain indicative of unstable angina. Recent onset angina: angina since less than 1 month. Rest angina: angina occurring in the absence of physical or psychological stress. Postinfarction angina: angina occurring during the first month after a myocardial infarction. Progressive angina: stable angina with worsening of symptoms during the last 2 weeks. The patient was considered to be medically stabilized 48 h after the last episode of chest pain.
2.4. Exercise treadmill ( ET) test The ET test was performed following the Bruce protocol [11], and was limited by symptoms. It was considered as positive in the presence of chest pain
3. Results
3.1. Baseline characteristics Baseline characteristics are shown in Table 1. Twenty-three percent of the patients were on nitrates, 74% on calcium channel blockers and 55% on betablockers. One hundred and seventy-four (19.7%) referred chest pain during the exercise test, and ST depression appeared in 213 (24.1%). Two hundred and eighty-eight (32.5%) performed a positive exercise test (chest pain and / or ST depression).
3.2. Predictors of ischemia at the exercise test Patients with a positive exercise test, compared with those with a negative exercise test, had a lower functional capacity (8.262.9 vs. 8.965.1 METS, P5 0.0373) and a lower percentage of the maximum heart rate reached (76.8613.0 vs. 81.2614.2, P5 0.0001), but there was no difference regarding the duration of exercise. The univariate analysis showed
R. Moreno et al. / International Journal of Cardiology 66 (1998) 147 – 151 Table 1 Baseline characteristics Age (years) Male gender (%) Smoking (%) Diabetes mellitus (%) Hypercholesterolemia (%) Hypertension (%) Previous AMI (%) Previous unstable angina (%) Previous SA (%) Previous CABG (%) Previous PTCA (%) Peripheral artery disease (%) Type of UA Rest UA (%) Recent UA (%) Progressive UA (%) Postinfarction UA (%) Left ventricular dysfunction (%) Functional capacity (METS) Exercise duration (min) Percent of MHR
149
Table 2 Prevalence of positivity in exercise test in different subgroups of patients 62.169.7 76 61 20 38 47 33 27 18 8 11 10 73 15 10 2 15 8.764.6 7.764.5 80614
AMI, acute myocardial infarction; UA, unstable angina; SA, stable angina; CABG, coronary artery bypass grafting; PTCA, percutaneous coronary angioplasty; left ventricular dysfunction, left ventricular ejection fraction less than 0.50; MHR, maximum heart rate.
the following variables associated with a positive exercise test: male gender (36.5 vs. 20.2%, P, 0.0001), diabetes mellitus (41.4 vs. 31.4%, P5 0.0149), previous admissions due to unstable angina (41.0 vs. 29.8%, P50.0020), previous stable angina (44.0 vs. 30.4%, P50.0013), previous coronary bypass grafting (44.3 vs. 31.8%, P50.0368), peripheral artery disease (45.2 vs. 31.6%, P50.0131) and progressive angina (56.2 vs. 29.8%, P,0.0001) (Table 2). Other characteristics, such as previous myocardial infarction, left ventricular function and type of antianginous treatment (betablockers, calcium antagonists or nitrates), were not statistically associated with the presence of ischemia at the exercise test. Male gender (OR52.46; 95% CI: 1.68–3.67), diabetes mellitus (OR51.61; 95% CI: 1.10–2.35), previous unstable angina (OR51.57; 95% CI: 1.10– 2.23), previous stable angina (OR51.56; 95% CI: 1.04–2.33) and progressive angina (OR52.77: 95% CI: 1.69–4.58) were independent risk factors for a positive exercise test in the multivariate analysis. In patients with none of these characteristics, the prevalence of positivity at the exercise test was 6%. The exercise test was positive in 41–56%, 43–67% and
Age .65 years Male gender Smoking Hypercholesterolemia Diabetes mellitus Hypertension Previous AMI Previous UA Previous SA Previous CABG Previous PTCA Peripheral artery disease Progressive UA Left ventricular dysfunction
Yes (%)
No (%)
P
31 37 34 33 41 32 35 41 44 44 38 45 56 29
34 20 31 33 31 34 32 30 30 32 32 32 30 34
NS ,0.0001 NS NS 0.0149 NS NS 0.0020 0.0013 0.0368 NS 0.0131 ,0.0001 NS
Yes, prevalence of positivity in patients with the characteristic; No, prevalence of positivity in patients without the characteristic; AMI, acute myocardial infarction; UA, unstable angina; SA, stable angina; CABG, coronary artery bypass grafting; PTCA, percutaneous coronary angioplasty; left ventricular dysfunction, left ventricular ejection fraction less than 0.50.
49–80% of the patients in the presence of one, two or more than two of these independent risk factors.
3.3. Predictors of chest pain during the exercise test The univariate analysis showed the following associated with the presence of chest pain at the exercise test: male gender (22.3 vs. 11.5%, P5 0.0003), previous unstable angina (28.2 vs. 16.8%, P50.0003), previous stable angina (28.0 vs. 18.0%, P50.0059), previous coronary bypass (34.3 vs. 18.6%, P50.0030) and progressive angina (43.8 vs. 17%, P,0.0001). Male gender (OR52.23; 95% CI: 1.49–3.84), previous unstable angina (OR51.80; 95% CI: 1.17–2.58) and progressive angina (OR5 3.68; 95% CI: 2.21–6.12) were independent risk factors for the appearance of chest pain in the multivariate analysis.
3.4. Predictors of ST depression at the exercise test Variables associated with ST depression were: male gender (27.4 vs. 13.8%, P,0.0001), diabetes mellitus (31.4 vs. 23.1%, P50.0288), previous stable angina (31.2 vs. 22.7%, P50.0283), peripheral artery disease (34.5 vs. 23.2%, P50.0268) and progressive
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angina (39.3 vs. 22.3%, P50.0004). Male gender (OR52.52; 95% CI: 1.65–3.97), diabetes mellitus (OR51.61; 95% CI: 1.08–2.38) and progressive angina (OR52.09; 95% CI: 1.26–3.45) were independent risk factors for ST depression in the multivariate analysis.
Finally, some studies have demonstrated that patients with recent onset and rest angina have a worse prognosis than patients with progressive effort angina [23]. All the patients of our study had been medically stabilized, and constitute a subgroup of patients that do not represent all the patients with unstable angina. Therefore, our results do not contradict the fact that patients with rest angina have a worse prognosis.
4. Discussion
4.1. Prevalence of ischemia at the exercise test In the present series of patients with suspected unstable angina, the prevalence of positivity at the exercise test after medical stabilization was 32.5%, which is in agreement with previous studies [2,3].
4.2. Predictors of a positive exercise test Some variables were associated with a positive exercise treadmill test: previous angina (unstable and stable), progressive angina, male gender and diabetes mellitus. Probably, patients with previous angina have significant coronary stenosis and even multivessel disease more frequently [4,5]. Male gender is associated with a more extended coronary disease compared with women, who have a higher prevalence of microvascular disease and single vessel disease [13–16]. Diabetes is associated with a more rapidly progressive and more extended coronary artery disease [17–19]. Finally, in patients with rest or recent onset angina, as compared with progressive angina, coronary lesions contain more thrombi [20,21], and perhaps this may explain why after stabilization on antianginous and antiplatelet therapy significant coronary lesions underly more frequently in progressive angina, and therefore ischemia at the exercise test is more probably. Some characteristics associated with a worse prognosis in patients with coronary artery disease, such as previous myocardial infarction and left ventricular function [12,22], were not associated with the presence of ischemia at the exercise test. The reason for this may be that the poorer prognosis in patients with previous myocardial infarction or in those with left ventricular dysfunction is due not to residual ischemia, but mainly to heart failure and arrhythmic sudden death.
4.3. Is a pre-discharge exercise test mandatory for all patients with suspected unstable angina? Although a negative exercise test is not a guarantee for a good long-term outcome [24], the test has been demonstrated to be of prognostic value in patients with suspected unstable angina, with those having a positive test having a higher incidence of acute myocardial infarction and death [6–10]. A predischarge exercise test in these patients has a similar diagnostic value as compared with an exercise test 1 month after discharge [25,26]. However, since half of the 1-year new coronary events in patients with unstable angina occur during the first months of evolution, a predischarge exercise test is usually recommended [25]. Nevertheless, since patients with a negative exercise test are usually discharged on medical treatment, in centers in which the exercise test produces a long delay in discharge, those not presenting characteristics predicting a positive exercise test could be referred to a post-discharge exercise test. Only 6% of the patients with none of the independent risk factors showed ischemia at the exercise test, and therefore women without previous coronary artery disease or effort angina could perhaps be referred to a post-discharge exercise test.
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