Short- and long-term efficacy of nicardipine, assessed by placebo-controlled single- and double-blind crossover trials in patients with chronic stable angina.

The efficacy of nicardipine, a new calcium ion antagonist, was studied in 39 patients aged 42 to 70 years with chronic stable angina in two different placebo-controlled single- and double-blind crossover trials and with long-term follow-up, using serial quantitated exercise testing and ambulatory ST segment monitoring. In the first study the minimal effective dose was determined, and in the repeat study the effects of three different dose levels were evaluated. Treadmill exercise testing was performed at the end of each 2 week treatment period with on-line computer analysis of the electrocardiogram. The mean (+/- standard error of the mean) exercise time was 6.8 +/- 0.7 minutes on placebo and 7.0 +/- 0.8 minutes during treatment with nicardipine, 60 mg/day (p = NS). This increased to 8.7 +/- 0.8 (p less than 0.001) and 9.2 +/- 0.9 minutes (p less than 0.001) with 90 and 120 mg/day, respectively. The mean heart rate at rest during placebo administration was 75 +/- 2 beats/min and increased to 85 +/- 3, 84 +/- 2 and 88 +/- 3 beats/min (p less than 0.02, p less than 0.01, p less than 0.01, respectively) at each dose level. The time taken to develop 1 mm of ST segment depression was prolonged from 4.8 +/- 0.6 minutes during placebo administration to 5.3 +/- 0.7 (p = NS), 6.4 +/- 0.7 (p less than 0.01) and 6.7 +/- 0.8 minutes (p less than 0.001), respectively, at each dose level. The improvement achieved after 2 weeks of nicardipine, 120 mg daily, was maintained over a period of 6 months of follow-up. Three patients were withdrawn, one taking 60 mg of nicardipine, one taking 90 mg of nicardipine and one taking placebo, but the overall incidence of side effects was low. Nicardipine is an effective antianginal agent with an optimal dose of 90 to 120 mg/day.

Sustained release verapamil, a once daily preparation: objective evaluation using exercise testing, ambulatory monitoring and blood levels in patients with stable angina.

The efficacy of a once daily, sustained release formulation of verapamil (Verapamil SR, 360 mg) was evaluated in 19 patients with chronic angina pectoris using a double-blind placebo-controlled crossover protocol. Evaluation by exercise testing, 24 hour electrocardiographic ambulatory monitoring and blood drug level assays was performed at the end of each 2 week phase, 21 to 23 hours after the last dose. After the crossover protocol, all patients were given sustained release verapamil for 4 weeks and the evaluation was repeated. Exercise time (mean +/- SEM) increased from 7.4 +/- 0.6 minutes with placebo to 9.6 +/- 0.8 minutes with verapamil (p less than 0.001) and to 9.5 +/- 0.7 minutes (p less than 0.001) after 4 weeks of therapy. The mean time to 1 mm ST depression also increased significantly, from 4.5 +/- 0.4 and 4.8 +/- 0.5 minutes in bipolar leads CM5 and CC5, respectively, with placebo, to 5.5 +/- 0.6 (p less than 0.05) and 6.2 +/- 0.5 minutes (p less than 0.01) with verapamil. Maximal ST depression and rest and peak heart rates were not altered significantly. The mean rate-pressure product was 208 +/- 9.9 with placebo and decreased to 189 +/- 7.7 (p less than 0.05) with verapamil but rose to 200.6 +/- 10.4 (p = NS) after 4 weeks of therapy. The mean hourly heart rates were lower with the drug than with placebo throughout the 24 hour period but there was no significant bradycardia, arrhythmia or heart block.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective evaluation of three dose levels of diltiazem in patients with chronic stable angina.

Twenty-one patients with chronic stable angina were treated with the calcium antagonist diltiazem. Dose titration studies involving 180, 270 and 360 mg/day were conducted using a blinded objective protocol. Improvement in exercise tolerance was observed at all dose levels, but the best reduction of anginal attacks and glyceryl trinitrate consumption, enhancement of exercise capacity and improvement of objective ischemic variables were observed with the 360 mg/day dose. The mean exercise time to produce grade II angina on treadmill walking increased from 5.6 +/- 0.7 minutes on placebo to 7.9 +/- 0.8 minutes on diltiazem 180 mg/day (probability [p] less than 0.001), 8.0 +/- 0.8 minutes on 270 mg/day and 9.5 +/- 0.9 minutes on 360 mg/day (p less than 0.001 as compared with 270 mg/day). One patient was withdrawn at the 360 mg/day dosage because of pedal edema. The 24 hour Holter monitoring data confirmed the findings on exercise testing, and left ventricular function was not altered with any dose level. Diltiazem in doses ranging from 180 to 360 mg/day is another powerful antianginal agent in the calcium antagonist group producing excellent therapeutic benefit in chronic stable angina with no adverse effects on left ventricular function.

An effective conscious animal model of atrial fibrillation.

In 11 fully conscious dogs with chronically implanted spicardial electrodes, 50 Hz sine-wave electrical stimulation of the left atrium reliably and repeatedly produced an arrhythmia which was indistinguishable from atrial fibrillation in terms of its ECG appearance, the statistical properties of the ventricular response and responses to a number of pharmacological agents. In five of the 11 preparations this arrhythmia consistently persisted for periods in excess of 10 min following the cessation of stimulation, indicating an intrinsic cardiac basis for the arrhythmia and suggesting that it is true atrial fibrillation. A close correlation between the ventricular response to this arrhythmia and the degree of atrioventricular conductivity, together with the observation that dramatic changes can occur in ventricular responses without corresponding changes in atrial activity, suggest that the ventricular response is mainly a function of the atrio-ventricular conducting system. The experimental model described is useful for the study of both short and long term drug action no atrial fibrillation and for the evaluation of methods used therapeutically in attempts to terminate episodes of paroxysmal atrial fibrillation.

An evaluation of self-recorded blood pressure during drug trials.

To our knowledge, there have been no published comparisons of different techniques for measuring blood pressure during clinical trials. We undertook a comparison during clinical trials with verapamil and prazosin. During an open trial of verapamil we compared the treatment-induced blood pressure reductions as measured by clinic, intra-arterial, and self-recorded methods. The mean reduction in blood pressure was 38 +/- 13.6/20 +/- 10.1 mm Hg for clinic blood pressure, 24 +/- 17.9/16 +/- 7.3 mm Hg for self-recorded blood pressure, and 23 +/- 12.3/19 +/- 10.1 mm Hg for mean daytime intra-arterial blood pressure. During prazosin treatment the mean reduction in blood pressure was 28 +/- 21.5/18 +/- 8.5 mm Hg for clinic blood pressure, 21 +/- 20.5/6 +/- 13.7 mm Hg for self-recorded blood pressure, and 18 +/- 19.2/5 +/- 9.6 mm Hg for mean daytime intra-arterial blood pressure. There was little agreement between methods within individual patients and for group comparisons of intra-arterial or clinic methods. There was, however, good agreement between intra-arterial and self-recorded methods. This study suggests that self-recorded blood pressure recording is suitable for monitoring efficacy of antihypertensive agents in a group of patients, although caution must be exercised when interpreting the effects of therapy when measured by indirect methods in an individual patient.

Is there a relationship between ambulatory intra-arterial blood pressure and left ventricular function?

The relationship between ambulatory intra-arterial blood pressure and left ventricular ejection fraction was examined in a group of 23 untreated hypertensive subjects who underwent concurrent radionuclide ventriculography. All patients had a normal ejection fraction at rest (range, 50-80%), and no significant correlation was found between blood pressure and resting ejection fraction. Sixty-one percent of patients failed to increase their ejection fraction by 5% on exercise; the mean daytime systolic pressure (168 +/- 15 mm Hg) was lower in this group than in those who had a normal exercise response (188 +/- 17 mm Hg; p less than 0.005). Thirty percent of patients had left ventricular hypertrophy based on electrocardiographic criteria; this group had a higher mean blood pressure (189 +/- 20 mm Hg) than the remainder (170 +/- 15 mm Hg; p less than 0.05). A closer correlation was demonstrated between blood pressure and ejection fraction response to exercise in the group with left ventricular hypertrophy (r = 0.8) than in the group without hypertrophy (r = 0.3). These results failed to demonstrate a linear relationship between blood pressure and ejection fraction. However, a relationship between the height of blood pressure and the development of left ventricular hypertrophy was shown, and myocardial response to exercise was increased in patients with left ventricular hypertrophy.

Nifedipine or verapamil as sole treatment of hypertension. An intraarterial study.

Intraarterial ambulatory blood pressures were recorded prior to and during therapy with two different calcium ion antagonists, nifedipine and verapamil, in two separate groups of patients. In the first group, nine patients were studied off therapy and following a minimum of 6 weeks of nifedipine treatment (dose range, 20 to 60 mg twice daily). A second group of 16 patients followed the identical protocol but were prescribed verapamil (120 to 160 mg, three times daily). During both studies, patients underwent standardized physiological tests including tilt, isometric handgrip, and dynamic bicycle exercise. Both verapamil and nifedipine caused a reduction in blood pressure over most of the 24 hours studied. Nifedipine did not affect heart rate whereas verapamil caused a reduction of approximately 10 bpm. Nifedipine and verapamil did not induce postural hypotension, and the absolute responses to dynamic and isometric exercise were reduced. These results show the efficacy of slow channel inhibitors in the management of essential hypertension.

Evaluation of the Remler M2000 blood pressure recorder. Comparison with intraarterial blood pressure recordings both at hospital and at home.

The Remler M2000 is a semiautomated device that has been used to collect epidemiological data and assess blood pressure variability. It has been subjected to limited evaluation in operation, however, and no studies of its accuracy away from the hospital or office environment have been undertaken. We recruited a group of 28 patients with essential hypertension who were undergoing intraarterial ambulatory blood pressure monitoring and compared the intraarterial recordings with those made with the Remler instrument both at home and in the hospital. The Remler recordings were also compared with simultaneous indirect blood pressure measurements made with the random zero sphygmomanometer. The mean difference between the Remler and intraarterial blood pressure recordings was -3/7 in the hospital and 7/0 at home. All standard deviations were greater than 10 mm Hg, indicating large between-subject variability. Overall, the relationship of the Remler M2000 readings to intraarterial pressures was as close if not closer than standard indirect sphygmomanometry and thus might provide useful data for epidemiological surveys or drug trials. It would appear that for accurate measurement of short-term blood pressure variation and 24-hour recording, intraarterial recording is the method of choice.

An intra-arterial profile of methyldopa.

The "Oxford" system for intra-arterial ambulatory blood pressure monitoring was used to monitor the blood pressure profile in 24 patients with essential hypertension who had received no therapy for 4 wk. The responses to tilt and isometric and dynamic bicycle exercise were recorded. Following the baseline study patients received methyldopa 125 mg t.i.d., which was titrated to a maximum of 500 mg t.i.d. according to blood pressure responses. The mean daily dosage was 1359 mg. Six weeks after the last dosage increment the experiment was repeated. Each patient was asked to take the total daily dosage once a day and the intra-arterial monitoring program was repeated after another 6 wk. Mean daytime intra-arterial blood pressure during three-times-daily dosing was reduced by 27/15 mm Hg; circadian curves were clearly separated during the day but not at night. Once-daily dosing did not control blood pressure as well. There was no evidence of postural hypotension and the absolute pressure response was lowered during both isometric and dynamic exercise. These results are comparable to those from similar studies with alpha- and beta-adrenoreceptor--blocking drugs.

Relationship between plasma cholesterol and coronary artery disease in Asians.

Cholesterol, high density lipoprotein (HDL) cholesterol and triglyceride concentrations were measured in 150 male survivors of first myocardial infarction and in 115 age and ethnic matched healthy controls. The total cholesterol concentration was higher in whites than in respective Asian groups and higher in patients than in controls (P less than 0.001). The ratio of cholesterol to HDL cholesterol was significantly higher in patients (P less than 0.001) and in both ethnic groups was a powerful independent predictor of cases. In Asians, the extent of coronary atheroma assessed by arteriography 2-12 weeks after infarction correlated independently with the total cholesterol concentration (P = 0.03). Thus, in Asian men, the lower level of total cholesterol compared to whites may be misleading. In Asian men the extent of atheroma correlated with the total cholesterol concentration and the relative risk of infarction increased with the ratio of total to HDL cholesterol. At a given level of cholesterol different ethnic groups may be at differing levels of cardiac risk and the cholesterol ratio may be a more appropriate means of inter-ethnic comparison.

Fibrinogen, factor VII clotting activity and coronary artery disease severity.

To asses the relationship between fibrinogen, factor VII coagulant (VIIc) activity and extent of coronary artery disease, we studied 43 white males shown to have greater than 50% stenosis of at least one major coronary artery. Thirty six had a definite history of myocardial infarction at least 3 months earlier and were classified as having 1, 2 or 3 vessel disease while 7 had 2 or 3 vessel disease, but no prior infarction. Groups were similar with regard to age, body mass index and blood pressure. In those with documented prior infarction, there was a significant relationship between the extent of atheroma and coagulation variables factor VIIc and fibrinogen. However, given a similar degree of atheroma, patients with prior infarction had significantly higher levels of factor VIIc activity compared with patients without such a history. These results corroborate those from prospective studies confirming a significant role for the coagulation system in the clinical manifestation of coronary artery disease.

The effect of a new calcium channel blocker nicardipine on 24-hour ambulatory blood pressure and the pressor response to isometric and dynamic exercise.

We have assessed the potential antihypertensive effect of a new slow channel blocker, nicardipine, in a group of patients with essential hypertension. Fourteen patients completed a study using the 'Oxford' system for recording blood pressure during free ambulation and physiological testing. An initial 24-h recording was performed on no treatment and repeated following chronic therapy with 40 mg b.d. of nicardipine. During each recording, the patients performed isometric and dynamic exercise according to a standardized protocol. Within-patient comparisons of consecutive mean hourly systolic and diastolic blood pressures showed a reduction throughout the 24 h during nicardipine therapy. The reduction in blood pressure was also maintained at the peaks of isometric and dynamic exercise. Side-effects were encountered frequently and led to four patient withdrawals. Nicardipine appears to be effective in reducing blood pressure although the frequency of encountered side-effects may limit its usefulness as a first-line antihypertensive agent.

Circadian variation and blood pressure: response to rapid weight loss by hypocaloric hyponatraemic diet in obesity.

Ambulatory intra-arterial blood pressure was monitored in 15 obese hypertensive and 10 obese normotensive subjects weighing more than 30% of their ideal body weight. Measurements were taken before and after 1 month in hospital on a diet of 330kCal/day designed to ensure 34 g protein and 65 mmol sodium. Mean +/- s.d. body mass index in the whole group fell from 40.8 +/- 7.6 to 37.2 +/- 7.4 kg/m2 (P less than 0.0001). Daytime intra-arterial blood pressure fell from 176 +/- 19/102 +/- 14 to 162 +/- 16/95 +/- 14 mmHg (P less than 0.0005 and P less than 0.002) in the hypertensive group and from 141 +/- 15/82 +/- 5 to 131 +/- 13/79 +/- 4 mmHg (P less than 0.005 for systolic pressure) in the normotensive group. Circadian variation of systolic intra-arterial blood pressure comparing the mean daytime with the mean night-time blood pressure recordings showed a day-night difference of 27 +/- 10 mmHg in the normotensive group compared with 12 +/- 13 mmHg in the hypertensive group (P less than 0.01). This trend was reversed after weight loss, when the normotensive group showed a day-night difference of 20 +/- 13 mmHg compared with 18 +/- 17 mmHg in the hypertensive group. Thus, circadian variation of systolic intra-arterial blood pressure in the hypertensive group was significantly (P less than 0.01) reduced compared with the normotensive group prior to, but not after, weight loss. These data show that, in obese subjects, weight loss produced a significant reduction in ambulatory intra-arterial blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Indium-111-antimyosin images compared with triphenyl tetrazolium chloride staining in a patient six days after myocardial infarction.

The results of indium-111 (111In) antimyosin imaging during life and the findings on postmortem imaging and triphenyl tetrazolium chloride (TTC) staining of the heart are reported from a patient who received 111In-antimyosin on the sixth day following myocardial infarction and died after imaging the next day. The planar images obtained during life showed abnormal 111In-antimyosin uptake in the posterior, lateral, and apical walls of the left ventricle. Autopsy revealed extensive infarction of the left ventricular lateral and posterior walls with cardiac rupture, which was the cause of sudden death. Direct imaging of the sliced specimen of heart revealed abnormal tracer uptake in the lateral and posterior walls of the left ventricle, which correlated closely with the area of necrosis outlined by TTC staining. Our results confirm the experimental findings that antimyosin antibody binds specifically to the acute irreversibly damaged myocardial cells. A high degree of tracer uptake can be seen even when 111In-antimyosin is injected six days postinfarction.

Haemostatic variables and the outcome of myocardial infarction.

In a study of 272 patients with myocardial infarction (MI) the 68 who died within 1 year had significantly higher levels of factor VIIIR:Ag, factor VIII:C, fibrinogen, alpha 1 antitrypsin and alpha 2 macroglobulin than those who survived. The mean white cell count (WCC) and peak creatine kinase (CK) were also significantly higher in those who died compared with the survivors. There was considerable intercorrelation between many of the haemostatic variables, WCC and CK as well as between many of the clinical predictors of outcome and the laboratory variables. The differences in haemostatic variables between those who died and those who survived may merely reflect the size of the infarct; alternatively, the haemostatic system may influence prognosis following an MI.

Lack of diurnal variation in maximal symptom-limited exercise test response in chronic stable angina.

Exercise testing is widely used to evaluate the effects of anti-ischemic drugs. Many studies have reported good reproducibility when it is performed in the morning, but little information is available regarding the diurnal variation of exercise test response in patients with chronic stable angina. With the advent of new long-acting anti-ischemic drugs, it has become necessary to perform the exercise testing at various times of the day to determine the duration of action of a given drug. To examine the diurnal variation, exercise tests were performed on 41 patients, aged 53 to 75 years, with established chronic stable angina on 2 occasions 5 days apart at 10 A.M. and 4 P.M. on each day. On day 1, the mean +/- standard error of the mean exercise time was 5.0 +/- 0.4 minutes at 10 A.M. and 5.1 +/- 0.4 minutes at 4 P.M., and on day 5, it was 5.6 +/- 0.4 minutes at 10 A.M. and 5.5 +/- 0.4 minutes at 4 P.M. These values did not differ in statistical significance. Similarly, the time to the development of 1 mm of ST-segment depression did not show any statistically significant change during either test period on either day nor did maximal ST-segment depression. Heart rate at rest was 79 +/- 3 beats/min at 10 A.M., 81 +/- 3 beats/min at 4 P.M. on day 1 and 78 +/- 2 beats/min at 10 A.M. and 80 +/- 3 beats/min at 4 P.M. on day 5 (difference not significant). Similarly, no significant changes were observed in maximal heart rate or rate-pressure product at peak exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical and prognostic significance of lung thallium uptake on rest imaging in acute myocardial infarction.

Exercise-induced pulmonary uptake of thallium-201 in patients with ischemic heart disease is probably due to transient pulmonary edema and left ventricular failure induced by exercise. The significance of increased lung uptake of thallium-201 at rest after acute myocardial infarction (AMI) has not been described. Ninety-six patients admitted with chest pain for suspected AMI or unstable angina underwent thallium-201 imaging at rest. Using conventional diagnostic criteria, 62 had AMI, 12 had unstable angina and 22 had neither. Increased lung uptake of thallium-201 was present in 24 of the total 96 (25%) patients, 20 of the 62 (32%) patients with AMI and 4 of 34 (13%) patients with no evidence of infarction. In the AMI group, those with increased lung thallium-201 uptake had a higher mean +/- standard deviation segmental thallium-201 defect score (22 +/- 7 vs 12 +/- 8, p less than 0.0001), lower ejection fraction (35 +/- 14 vs 49 +/- 14%, p less than 0.002), higher peak creatine kinase levels (2,410 +/- 1,247 vs 1,496 +/- 1,228 IU/liter, p less than 0.01), higher wall motion abnormality score (25 +/- 13 vs 13 +/- 12, p less than 0.0001), increased incidence of clinical in-hospital heart failure (15 of 20 vs 7 of 42, p less than 0.0001) and higher short-term mortality (4 of 20 vs 1 of 42, p less than 0.02) compared to those without increased lung thallium-201 uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of arrhythmias accompanying ST-segment depression on ambulatory monitoring in stable angina pectoris.

To investigate the mechanisms of ischemic arrhythmias during daily life, 32 patients with stable angina pectoris and documented ischemic episodes were studied by 24-hour ambulatory electrocardiographic monitoring. The severity of arrhythmias observed at or before peak ST-segment depression (early arrhythmias) and arrhythmias presenting during or after resolution of the ST-segment changes (late arrhythmias) was graded according to a modified Lown classification. Eleven patients (34%) had ischemic arrhythmias and had a greater number of ischemic episodes (6.0 +/- 5.4 vs 2.3 +/- 1.5, p less than 0.001) than patients without ischemic arrhythmias. Ischemic episodes accompanied by arrhythmias had a greater ST-segment depression (2.8 +/- 1.6 mm vs 1.9 +/- 0.6 mm, p less than 0.001), and duration (18.2 +/- 14.8 minutes vs 5.7 +/- 2.6 minutes, p less than 0.001) than those without arrhythmias. Ventricular tachycardia was observed in 3 patients during the early phase of ischemia and in 2 during or after recovery. Early but not late ventricular tachycardias were preceded by prodromal ventricular ectopic activity. Late arrhythmias were more frequent and severe than early arrhythmias, with an increased incidence of R-on-T ectopic complexes. In patients with stable angina, potentially life-threatening arrhythmias are closely associated with severe repetitive episodes of ischemia, and different mechanisms produce early and late arrhythmias. Prevention or reduction of the severity of ischemic episodes occurring during daily life in patients with stable angina may be more effective than prophylactic antiarrhythmic therapy.

Effects of a new vasodilating beta-blocking drug, carvedilol, on left ventricular function in stable angina pectoris.

The effects of a new vasodilating beta-blocking drug, carvedilol, were studied in 20 patients with chronic stable angina using a single-blind, placebo-controlled protocol. Two doses of carvedilol, 25 mg twice daily and 50 mg twice daily, were compared with placebo using analysis of variance. The study design consisted of 2 weekly phases of initial placebo followed by carvedilol, 25 mg twice daily and then 50 mg twice daily, and a second placebo period. Supine rest and exercise radionuclide ventriculography was performed at the end of each phase. Carvedilol produced a significant dose-related reduction in rest and exercise heart rate and blood pressure (p less than 0.01 to less than 0.0001). Ejection fraction at rest increased significantly, from a mean (+/- standard error) of 53 +/- 3% with placebo to 58 +/- 3% with carvedilol, 50 mg twice daily, but no improvement was noted in ejection fraction on exercise. Relative, counts-based end-systolic and end-diastolic volumes were significantly reduced at rest (p less than 0.001). Rest peak filling rate index, first-third filling fraction and ejection rate index increased significantly with carvedilol. A dose-related change was observed with rest ejection fraction, peak filling rate index and ejection rate index. Exercise-induced ST-segment depression improved significantly with both doses of carvedilol compared with placebo. Carvedilol was well tolerated and produced significant hemodynamic improvement. This salutary effect on left ventricular function may confer advantages in long-term treatment of patients with chronic stable angina.

Ambulatory heart rate and ST-segment depression during painful and silent myocardial ischemia in chronic stable angina pectoris.

The relation between heart rate and ischemic ST-segment depression was studied in 70 patients with documented obstructive coronary artery disease (CAD) and reproducible effort angina. Symptom-limited treadmill exercise testing was performed before and after a 2-week placebo period and 24-hour FM ambulatory electrocardiographic monitoring at the end of the placebo period. The means (+/- standard deviation) of the basal and placebo values for exercise time, heart rate and maximal ST-segment depression were: 6.4 +/- 2.6 minutes vs 6.9 +/- 2.8 minutes (difference not significant [NS]), 125 +/- 17 beats/min vs 125 +/- 19 beats/min (NS) and 2.3 +/- 0.8 mm vs 2.1 +/- 0.8 (NS), respectively. Ambulatory monitoring revealed 205 episodes of significant ST-segment depression (J + 80 ms; 49 episodes with more than 1 mm, 83 with more than 2 mm, 39 with more than 3 mm and 34 with more than 4 mm). Of all episodes of ST-segment depression, 130 (64%) were asymptomatic. The episodes lasted for 3 to 110 minutes. The maximal 24-hour ambulatory heart rate and ST-segment depression during ischemic episodes were expressed as a percentage of those seen during exercise-induced ischemia. When all ambulatory ischemic episodes (both symptomatic and asymptomatic) were compared with exercise-induced ischemic changes in the individual patient, there was little difference in heart rate (91 +/- 15% vs 90 +/- 18%, NS) but there was a greater magnitude of ST-segment depression (122 +/- 57% vs 104 +/- 52%, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)