Long-term prognostic value of exercise testing in men and women from the Coronary Artery Surgery Study (CASS) registry.

Many prior studies involving a predominantly male population have demonstrated the importance of exercise test results in determining the outcome of patients with coronary artery disease. The prognostic significance of exercise testing in women is unknown. In our study, a total of 3,086 men and 747 women underwent maximal treadmill exercise testing, coronary angiography, and were prospectively followed for up to 16 years. They were divided into 3 groups (high, intermediate, and low risk) on the basis of exercise testing. Sixteen-year survival based on exercise test groups ranged from 38% to 61% in men and from 44% to 79% in women (p < 0.001). Among men, 12-year survival was enhanced by coronary artery bypass surgery versus medical therapy in the high-risk subgroup (69% vs 55%, respectively, p = 0.0025), but the 2 therapies were similar in the intermediate- and low-risk subgroups. Among women, neither medical nor surgical therapy resulted in improved 12-year survival rates in any of the 3 subgroups. These results suggest that exercise testing is helpful in assessing long-term survival in men and women. However, only exercise testing in men could identify a high-risk subset whose survival was enhanced by coronary artery bypass graft surgery.

Significance of silent myocardial ischemia during exercise testing in women: report from the Coronary Artery Surgery Study.

To evaluate the significance of silent myocardial ischemia during exercise testing in women compared to men, we analyzed the data on 1087 women and 3834 men who underwent exercise testing and coronary angiography from the Coronary Artery Surgery Study (CASS) registry. The patients were divided into three groups on the basis of the results of exercise testing: group 1, silent ischemia (253 women, 853 men); group 2, symptomatic ischemia (156 women, 1250 men); and group 3, no ischemia (678 women, 1731 men). The survival rate at 12 years for women was 80% for group 1, 75% for group 2, and 86% for group 3 (p = 0.0022); the survival rate for men was 69% for group 1, 69% for group 2, and 76% for group 3 (p < 0.001). In both men and women with silent ischemia, the 12-year survival rate was related to the severity of coronary artery disease (CAD) and ranged from 79% for women with one-vessel CAD to 46% for men with three-vessel CAD. Survival at 12 years was enhanced by coronary artery bypass graft surgery as compared to medical treatment in patients with silent ischemia and three-vessel CAD for men (61% vs 46%, respectively, p = 0.0014) but not for women (45% vs 50%, respectively, p = 0.98). These data suggest that silent ischemia in women and men adversely affects survival rate and that men may gain more benefit from coronary artery bypass graft surgery than women when three-vessel CAD is present.

Quality of life among 5,025 patients with left ventricular dysfunction randomized between placebo and enalapril: the Studies of Left Ventricular Dysfunction. The SOLVD Investigators.

OBJECTIVES: This study was performed to assess the quality of life of patients with left ventricular dysfunction for up to 2 years after randomization to enalapril or placebo. BACKGROUND: Previous reports have documented that survival of patients with congestive heart failure can be extended by the angiotensin-converting enzyme inhibitor enalapril. However, it is unknown whether enalapril has a long-term favorable impact on the quality of life in patients with heart failure. METHODS: A brief quality of life questionnaire assessing the quality of life was administered at baseline and at 6 weeks, 1 year and 2 years of follow-up to patients randomized to placebo or enalapril in the Studies of Left Ventricular Dysfunction (SOLVD). Participants had an ejection fraction < or = 0.35, no other serious illnesses and either symptomatic heart failure (treatment trial, n = 2,465) or asymptomatic left ventricular dysfunction (prevention trial, n = 2,560). RESULTS: Among the 14 scales of quality of life, better scores at one or more follow-up intervals were noted in 6 scales in the treatment trial and in 1 scale in the prevention trial among patients assigned to enalapril. Consistent superiority with enalapril at two consecutive follow-up intervals was noted in the treatment trial for social functioning and dyspnea but for no scale in the prevention trial. However, an average of 40% of quality of life responses were missing at 2 years of follow-up because of death or failure to complete the questionnaire. In the treatment trial, survivors with more severe heart failure were less likely to complete the questionnaire. CONCLUSIONS: Modest benefits in quality of life for > or = 1 year occurred when patients with left ventricular dysfunction and symptomatic heart failure were treated with enalapril. No apparent beneficial or adverse effect on quality of life was observed with enalapril in asymptomatic patients with left ventricular dysfunction.

Significance of silent myocardial ischemia during exercise testing in patients with diabetes mellitus: a report from the Coronary Artery Surgery Study (CASS) Registry.

To evaluate the significance of ischemic ST depression without anginal chest pain during exercise testing among patients with diabetes mellitus, the data on 45 such patients from the Coronary Artery Surgery Study registry were analyzed. These patients (group 1, silent ischemia) were compared with 37 diabetic patients with both ischemic ST depression and chest pain (group 2, symptomatic ischemia), with 31 diabetic patients without ischemic ST depression or chest pain (group 3, no ischemia), and with 429 patients without diabetes who had silent ischemia during exercise testing. All patients had documented coronary artery disease (CAD) (greater than 70% diameter narrowing). The 6-year survival among patients with silent ischemia was worse in diabetic than nondiabetic patients (59 vs 82%, respectively, p less than 0.001). By contrast, the 6-year survival among patients without ischemia was similar among diabetic and nondiabetic patients (93 vs 85%, respectively, p = 0.476). Among diabetic patients, survival at 6 years with medical treatment was 59% for group 1, 66% for group 2 and 93% for group 3 (p = 0.008). Survival among subsets of patients with diabetes and silent ischemia (group 1) based on the extent of CAD and left ventricular function ranged from 100 to 32% (p = 0.093). The survival of the 45 patients with diabetes mellitus and silent ischemia (group 1) treated medically was compared with that of 28 patients receiving coronary artery graft bypass surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevalence and prognostic significance of silent and symptomatic ischemia after coronary bypass surgery: a report from the Coronary Artery Surgery Study (CASS) randomized population.

The prevalence and prognostic significance of postoperative myocardial ischemia, as detected by exercise testing, were prospectively assessed in 174 patients from the Coronary Artery Surgery Study (CASS) randomized surgical population who had exercise testing before and 6 months after coronary artery bypass graft surgery. Whereas the prevalence of symptomatic ischemia significantly decreased postoperatively (52% vs. 6%, p less than 0.001), the frequency of silent myocardial ischemia did not change (30% vs. 29%). Survival at 12 years after bypass surgery based on the 6-month postoperative exercise test results was significantly better for the 112 patients with no ischemia (80%) than for the 51 patients with silent ischemia (68%) or the 11 patients with symptomatic ischemia (45%). These data show that coronary artery bypass graft surgery diminishes the overall prevalence of symptomatic but not silent ischemia and that both silent and symptomatic ischemia adversely affect the postoperative prognosis of these patients.

Ten-year follow-up of quality of life in patients randomized to receive medical therapy or coronary artery bypass graft surgery. The Coronary Artery Surgery Study (CASS)

Quality of life indexes were assessed in 780 patients 10 years after randomization to medical therapy (n = 390) or coronary artery bypass graft surgery (n = 390) in the Coronary Artery Surgery Study. At 10 years, mortality was 21.8% in the medical group and 19.2% in the surgical group (p = NS), and 144 (37%) of the medical group had undergone surgery because of increasing chest pain. At study entry, 22% of medical and surgical patients were angina free; at 1 and 5 years after entry, the frequency of asymptomatic patients was 66% and 63% in the surgical group and 30% and 38% in the medical group. However, by 10 years after entry, the proportion of patients free of angina had fallen to 47% in the surgical group and to 42% in the medical group. Activity limitation and use of beta-blockers and long-acting nitrates were less in the surgical than the medical group at 1 and 5 years after entry but little different from the medical group at 10 years after entry. Throughout follow-up, recreational status, employment status, frequency of heart failure, use of other medications, and hospitalization frequency were similar between the two groups. Thus, indexes of quality of life such as angina relief, increased activity, and reduction in use of antianginal medications initially appear superior in patients with stable manifestations of ischemic heart disease assigned to surgery, but by 10 years after entry, these advantages are much less apparent. Although the observed similarities of the medically and surgically assigned groups at 10 years reflect return of symptoms in the surgical group to some extent, a more important explanation is the performance of late surgery in a large proportion of the medically assigned patients, rendering them asymptomatic.

The role of exercise-induced silent myocardial ischemia in patients with abnormal left ventricular function. A report from the Coronary Artery Surgery Study (CASS) registry.

To evaluate the significance of ischemic ST depression without anginal chest pain (silent ischemia) during exercise testing among patients with abnormal left ventricular function, the data on 121 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients with silent ischemia (group 1) were compared to: 124 CAD patients with both ST depression and angina (symptomatic ischemia, group 2); 159 CAD patients with neither ST depression nor angina (no ischemia, group 3); and 37 patients without CAD (controls). Survival at 7 years with medical therapy was similar for groups 1 (55%) and 2 (60%), but was substantially better for group 3 (73%, p = 0.001). Among group 1 patients with silent ischemia, survival was related to the severity of CAD (p = 0.001). Patients with silent ischemia and three-vessel CAD had a poor 7-year survival rate (37%) when treated medically. A comparable but non-randomized group of patients with silent ischemia and three-vessel CAD who underwent coronary artery bypass surgery had a much better 7-year survival rate (83%, p less than 0.0001). These results suggest that among patients with CAD and abnormal left ventricular function, silent ischemia adversely affects survival and can identify a higher risk subset of patients whose survival might be improved after coronary bypass surgery.

Risk of developing an acute myocardial infarction or sudden coronary death in patients with exercise-induced silent myocardial ischemia. A report from the Coronary Artery Surgery Study (CASS) registry.

To evaluate whether patients with silent myocardial ischemia during exercise testing are at increased risk for developing a subsequent acute myocardial infarction or sudden death, the data on 424 such patients with proven coronary artery disease (CAD) from the Coronary Artery Surgery Study (CASS) registry were analyzed. These patients (group 1) were compared with 456 other patients with CAD (group 2) who had both ischemic ST depression and angina pectoris during exercise testing and with 1,019 control patients without CAD. The probability of remaining free of a subsequent acute myocardial infarction or sudden death at 7 years was 80 and 91%, respectively, for group 1, 82 and 93%, respectively, for group 2 (difference not significant, compared with group 1), and 98 and 99%, respectively, for the control patients (p less than 0.001), compared with group 1 or 2). Among patients in group 1, the probability of remaining free of myocardial infarction and sudden death at 7 years was related to the severity of CAD and presence of left ventricular (LV) dysfunction, and ranged from 90% for patients with 1-vessel CAD and preserved LV function to 38% for patients with 3-vessel CAD and abnormal LV function (p less than 0.001). Thus, patients with either silent or symptomatic ischemia during exercise testing have a similar risk of developing an acute myocardial infarction or sudden death--except in the 3-vessel CAD subgroup, where the risk is greater in silent ischemia. The risk of patients with silent myocardial ischemia is based primarily on angiographic variables.

Comparison of coronary artery bypass surgery and medical therapy in patients with exercised-induced silent myocardial ischemia: a report from the Coronary Artery Surgery Study (CASS) registry.

To determine whether coronary artery bypass surgery would prolong survival in patients with silent myocardial ischemia during exercise testing, the data on 692 such patients from the Coronary Artery Surgery Study (CASS) registry were analyzed. The patients were followed up for up to 7 years after medical (n = 424) or surgical (n = 268) therapy. Stratification of patients into subsets was based on the results of cardiac catheterization. Surgical benefit was greatest in the patients with three vessel coronary artery disease or abnormal left ventricular function. Among the 75 patients with three vessel coronary disease and left ventricular dysfunction, the 7 year survival rate was 37% for the medical group and 90% for the surgical group (p less than 0.0001). Thus, among patients with silent myocardial ischemia during exercise testing in this nonrandomized study, survival appeared to be enhanced by coronary artery bypass surgery in subsets of patients with severe coronary artery disease and abnormal left ventricular function.

The role of computerized ECG interpretation in clinical trials.

The Lipid Research Clinics project consisted of the Prevalence Study and the Coronary Primary Prevention Study. The first study characterized the levels of blood lipids in the population studied, and related these to the presence of coronary artery disease as detected by medical history, symptom analysis, resting ECG and treadmill exercise ECG tests. The prevention trial tested whether a reduction of elevated serum cholesterol would reduce the incidence of coronary events (Table I). Both projects collected resting 12-lead ECGs and treadmill exercise test data on the participants. Instrumentation and methodology were standardized. Rest and exercise electrocardiographic data were recorded on analog magnetic tape. Tapes were sent to the ECG Center where they were digitized, analyzed and also reproduced for visual analysis according to the Minnesota Code of Blackburn. There were two reasons for using both visual coding and computer analyses in these projects. It was thought that computer methodology would enhance the accuracy of the electrocardiographic data, but on the other hand its accuracy had not been adequately documented and its output statements were not in the language of the Minnesota Code, which is traditionally accepted by epidemiologists. The other and more pressing reason for using the Minnesota Code is that the computer programming had not been completed at the start of the project, and visual coding was required in order to provide the ECG data necessary for the randomization of the Prevention Trial participants.

Computer-aided electrocardiography.

The three principal forms of medical electrocardiography are the standard 12 lead electrocardiogram (ECG), the exercise ECG and the long-term ambulatory ECG. The volume of use of the 12 lead ECG is 10 to 20 times greater than that of the exercise test or the ambulatory test, and it has received correspondingly more developmental and marketing attention. A great increase in the rate of adoption of computerized electrocardiography was brought about when large scale integration of computer hardware made it possible to place the entire computational package within a standard-sized ECG cart. Exercise ECG testing involves processing a data sample minutes in duration. Only a very few diagnostic possibilities are examined; emphasis is on measurements of the ST segment and on non-ECG observations. Ambulatory electrocardiography currently involves only one or two ECG leads and these are tested for only a few diagnostic possibilities; however, duration of the data sample is relatively long, usually 24 hours. Computer processing involves examination of about 100,000 cardiac cycles for RR interval, QRS shape and ST segment deviation.

Value of exercise testing in determining the risk classification and the response to coronary artery bypass grafting in three-vessel coronary artery disease: a report from the Coronary Artery Surgery Study (CASS) registry.

To determine whether exercise testing can identify higher risk patients with 3-vessel coronary artery disease (CAD) whose survival might be prolonged by coronary artery bypass grafting (CABG), the results of CABG were compared with those of medical therapy in 1,249 nonrandomized patients with 3-vessel CAD from the Coronary Artery Surgery Study (CASS) registry who underwent exercise testing. Analysis of 28 variables by Cox's regression model for survival revealed an independent effect of the left ventricular (LV) score, the final exercise stage, and treatment received on survival. Seven-year survival rates between medical and surgical therapy were compared among subsets of patients according to the LV function and the results of exercise testing. Among patients with normal LV function, those with at least 1 mm of ischemic ST-segment depression or low exercise capacity had better 7-year survival if treated by surgical rather than medical therapy (p less than 0.05). Survival was not different between the medical and surgical groups in patients without ischemic ST depression or with good exercise capacity. Among patients with impaired LV function, surgery improved survival in most subsets of patients with the exception of patients with a preserved exercise capacity. These results support the use of exercise testing in the risk stratification of patients with 3-vessel CAD.

Bundle branch block in patients with chronic coronary artery disease: angiographic correlates and prognostic significance.

The onset of bundle branch block during acute myocardial infarction is indicative of ischemia in the distribution of the left anterior descending coronary artery. However, whether patients with chronic coronary artery disease and bundle branch block have a predominance of left anterior descending artery lesions is not known. Similarly, the prognostic implications of bundle branch block have been studied primarily in the setting of acute myocardial infarction, and the independent prognostic implications of bundle branch block in patients with chronic coronary artery disease are not known. The electrocardiograms (ECGs) of 15,609 patients with chronic coronary artery disease who underwent coronary and left ventricular angiography as part of the Coronary Artery Surgery Study (CASS) were reviewed, and 522 patients with bundle branch block were identified. Patients with bundle branch block had both more extensive coronary artery disease and worse left ventricular function than did patients without bundle branch block. However, no particular location of coronary artery stenosis or left ventricular wall motion abnormality predominated in patients with bundle branch block. During a follow-up period of 4.9 +/- 1.3 years, 2,386 patients died. Actuarial probability of mortality at 2 years in patients with left bundle branch block was more than five times that in patients without bundle branch block (p less than 0.0001), and in patients with right bundle branch block the mortality rate was approximately twice that in patients without bundle branch block (p less than 0.0001). Stepwise Cox regression analysis showed that left bundle branch block, but not right bundle branch block, was a strong predictor of mortality, independent of degree of heart failure, extent of coronary disease and other variables (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Significance of silent myocardial ischemia during exercise testing in patients with coronary artery disease.

To evaluate the significance of ischemic ST-segment depression without associated chest pain during exercise testing, data were analyzed from 2,982 patients from the Coronary Artery Surgery Study (CASS) registry who underwent coronary arteriography and exercise testing and were followed up for 7 years. Patients with proved coronary artery disease (CAD) (at least 70% diameter narrowing) were grouped according to whether they had at least 1 mm of ST-segment depression or anginal chest pain during exercise testing. Four hundred twenty-four had ischemic ST depression without angina (group 1); 232 had angina but no ischemic ST depression (group 2); 456 had both ischemic ST depression and angina (group 3); and 471 had neither ischemic ST depression nor angina (group 4). Sixty-three percent of patients in group 1 and 55% in group 2 had multivessel CAD (difference not significant). The 7-year survival rates were similar for patients in groups 1 (76%), 2 (77%), and 3 (78%), but were significantly better for patients in group 4 (88%, p less than 0.001). Among group 1 patients, survival was related to severity of CAD (p less than 0.001). The 7-year survival rate in group 1 was significantly worse than that in a separate group of 282 patients with ischemic ST depression without angina during exercise testing who had no CAD (95% survival, p less than 0.001). Thus, in patients with silent myocardial ischemia during exercise testing, the extent of CAD and the 7-year survival rate are similar to those of patients with angina during exercise testing. Prognosis is determined primarily by the severity of CAD. In patients without CAD, the survival rate is excellent.

Smoking, physical activity, and other predictors of endurance and heart rate response to exercise in asymptomatic hypercholesterolemic men. The Lipid Research Clinics Coronary Primary Prevention Trial.

The association of known coronary risk factors with progressive submaximal treadmill exercise tolerance test performance was studied in 6,238 asymptomatic white 34-60-year-old hypercholesterolemic men screened between 1973 and 1976 for the Lipid Research Clinics Coronary Primary Prevention Trial. Cigarette smoking and habitual physical inactivity were each associated with a doubling of the rate of symptom-related discontinuation of the exercise test; the tests of sedentary smokers were discontinued at four times the rate observed for active nonsmokers. Smaller increases in heart rate were observed during exercise testing in physically active men and in smokers than in their sedentary and nonsmoking counterparts. Thus, smoking, like habitual physical activity, reduced the heart rate required to sustain a given external workload. However, the heart rates of smokers tended to remain elevated after exercise, while those of physically active men returned more rapidly toward resting levels. Age, Quetelet index, and low plasma levels of high density lipoprotein cholesterol were also strong predictors of decreased endurance, while resting heart rate and blood pressure levels were significant predictors of heart rate response. Comparison of these results with those previously reported for ischemic electrocardiographic changes in this cohort suggests that coronary risk factors may selectively influence specific aspects of exercise tolerance test performance.

The role of exercise testing in identifying patients with improved survival after coronary artery bypass surgery.

To determine whether exercise testing can identify patients whose survival might be prolonged by coronary artery bypass surgery, the results of bypass surgery were compared with those of medical therapy alone in 5,303 nonrandomized patients from the Coronary Artery Surgery Study registry who underwent exercise testing. Patients in the two treatment groups differed substantially with regard to important baseline variables. Analysis of 32 variables by Cox's regression model for survival revealed an independent beneficial effect of bypass surgery on survival (p less than 0.00001). Patients were then stratified into subsets according to the results of exercise testing. Surgical benefit was greatest in the 789 patients who exhibited at least 1 mm of ST segment depression and who could exercise only into stage 1 or less. Among the 398 patients with three vessel coronary disease showing these characteristics, 7 year survival was 58% for the medical group and 81% for the surgical group (p less than 0.001). There was no difference in survival between the surgical and medical groups among the 1,545 patients without ischemic ST segment depression who were able to exercise into stage 3 or greater. Thus, in patients who demonstrate ischemia on exercise testing and whose exercise capacity is limited, coronary bypass surgery appears to improve survival in comparison with medical therapy alone.

Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study.

More than 3600 white men, from 30 to 79 years old and without a history of myocardial infarction, underwent submaximal treadmill exercise tolerance tests as part of their baseline evaluation for the Lipid Research Clinics Mortality Follow-up Study. The exercise test was conducted according to a common protocol and coded centrally; depression of the ST segment by at least 1 mm (visual coding) and/or 10 microV-sec (ST integral, computer coding) signified a positive test. Concurrent measurements of age, blood pressure, history of cigarette smoking, and plasma levels of lipids, lipoproteins, and glucose, as well as other coronary risk factors, were obtained. Cumulative mortality from cardiovascular disease was 11.9% (22/185) over 8.1 years mean follow-up among men with a positive exercise test vs 1.2% (36/2993) over 8.6 years mean follow-up among men with a negative test. Three-quarters (43) of these deaths were due to coronary heart disease. The relative risk for cardiovascular mortality associated with a positive exercise test was 9.3 before and 4.6 after age adjustment. Cardiovascular mortality rates were especially elevated (relative risk 15.6 before and 5.1 after age adjustment) among the 82 men whose exercise tests were adjusted "strongly" positive based on degree and timing of the ischemic electrocardiographic response. A positive exercise test was also moderately associated with noncardiovascular mortality; the relative risk for all-cause mortality was 7.2 before and 3.4 after age adjustment. The relative risk for cardiovascular mortality associated with a positive exercise test was not appreciably altered by covariance adjustment for known coronary risk factors other than age. A positive exercise test was a stronger predictor of cardiovascular death than were high plasma levels of low-density lipoprotein cholesterol, low plasma levels of high-density lipoprotein cholesterol, smoking, hyperglycemia, or hypertension. Its impact on risk of cardiovascular death was equivalent to that of a 17.4 year increment in age.

Dyslipoproteinemias and manifestations of coronary heart disease. The Lipid Research Clinics Program Prevalence Study.

The Lipid Research Clinics Prevalence Study population underwent a noninvasive evaluation to assess the odds of coronary heart disease (CHD) among individuals with various types of dyslipoproteinemia (DLP) relative to the odds for individuals free of DLP in a nonselected population. The noninvasive evaluation included the Rose questionnaire for angina, a resting electrocardiogram, and a graded treadmill exercise test. The presence of manifestations of CHD was assessed by a combination of these findings. Multiple linear regression and multiple logistic regression analyses were used to evaluate associations between CHD and DLP, with adjustments for the following covariates: age, body mass, systolic blood pressure, alcohol consumption, and cigarette use. There were no consistent associations in women or in men 30 to 49 years old. In men 50 to 69 years old, the mean high-density lipoprotein cholesterol (HDL-C) values and HDL-C/cholesterol ratio were significantly lower in the definite CHD and angina categories, compared with the negative (no evidence of CHD) group. Higher odds ratios for CHD were present in those classified as having type IIa, type IV, and hypoHDL DLPs, relative to those classified as normal by the phenotyping algorithm. These associations were consistent across the several categories of CHD manifestations, but did not reach statistical significance after adjustment for multiple testing. A statistically significant lower odds ratio for CHD was observed in men 50 to 69 classified as having hyperHDL when compared with those without DLPs. The associations between CHD and the various forms of DLP were consistent with those observed between CHD and the plasma lipid and lipoprotein-cholesterol concentrations. The Lipid Research Clinics Prevalence Study confirmed the relationship between elevated low-density lipoprotein cholesterol, decreased HDL-C, and noninvasively determined CHD in a free-living asymptomatic population of older men.