Acute effects of exercise on cerebrovascular response and cognitive performance in individuals with stable coronary heart disease.

BACKGROUND: Individuals with coronary heart disease (CHD) exhibit cognitive deficits and cerebrovascular dysfunctions, and are at higher risk of developing dementia. Cognitive function in individuals with CHD has never been studied during acute aerobic exercise. Given the increasing popularity of training at high peak power output (PPO), its impact on cerebrovascular and cognitive functions in individuals with CHD should be further studied. METHOD: Thirty-eight individuals with CHD and 16 healthy controls completed two exercise bouts at 30% and 70% of their individualized PPO on an ergocycle while performing a cognitive task including non-executive and executive conditions. Variations of oxy- deoxy-hemoglobin, and total hemoglobin concentrations were measured on left prefrontal cortex at both PPO using near-infrared spectroscopy. RESULTS: Cognitive task performances were equivalent between groups at all intensity levels. Individuals with CHD exhibited larger variation of deoxyhemoglobin in the executive condition and larger variation in total hemoglobin concentration in all task conditions compared to healthy controls at 70% of PPO. CONCLUSION: Exercising at high intensity seems to have a larger impact on cerebral blood volume in CHD patients compared to healthy age-matched controls. Higher exercise intensity has negative impacts on cerebral blood volume variations during a cognitive task in CHD patients and could potentially lead to other neurocognitive dysfunctions. Other studies are needed to determine if a cognitive task administered during an exercise test could help identify individuals with CHD at higher risk of developing cognitive decline.

Barriers to physical activity in coronary artery disease patients: Development and validation of a new scale.

OBJECTIVE: To develop and validate a self-report questionnaire to measure barriers to regular physical activity (PA) in patients with stable coronary artery disease (CAD). METHODS: Phase 1: 17 patients completed a semi-structured interview. After grouping and reformulating the reported barriers, their pertinence was reevaluated by the patients. Then, a decision algorithm was used to select items. A principal component analysis was performed to determine content validity. Phase 2: 49 patients completed the questionnaire resulting from phase 1 twice, 7 days apart, and questionnaires to evaluate depression, anxiety, and the level of physical activity. Construct validity was evaluated by analysis of Spearman's correlation coefficient between the total score for the questionnaire and a convergent dimension (anxiety), as well as a divergent dimension (Dijon physical activity score). Internal consistency was evaluated by Cronbach's alpha coefficient. Test-retest reliability was evaluated by the intraclass coefficient (ICC). RESULTS: Eleven items were selected after phase 1. The questionnaire presented good face validity and the content validity seemed satisfactory after analysis of the literature by the experts. Construct validity was moderate. Internal consistency was very good (Cronbach's α>0.81). Reproducibility was excellent with an ICC at 0.95. Feasibility was good with less than 3minutes to complete the questionnaire. CONCLUSION: This questionnaire presents good psychometric properties. A further prospective study should evaluate sensitivity to change and help determine a threshold value indicating the need for a specific behavioral strategy to alleviate barriers to physical activity in these patients.

Social support, depression, and mortality during the first year after myocardial infarction.

BACKGROUND: We previously reported that depression after myocardial infarction (MI) increases the long-term risk of cardiac mortality. Other research suggests that social support may also influence prognosis. This article examines the interrelationships between baseline depression and social support in terms of cardiac prognosis and changes in depression symptoms over the first post-MI year. METHODS AND RESULTS: For this study, 887 patients completed the Beck Depression Inventory (BDI) and the Perceived Social Support Scale (PSSS) at about 7 days after MI. Some 32% had BDIs > or =10, indicating mild to moderate depression. One-year survival status was determined for all patients. Follow-up interviews, including the BDI, were conducted with 89% of survivors. There were 39 deaths (35 cardiac). Elevated BDI scores were related to cardiac mortality (P=0.0006), but PSSS scores and other measures of social support were not. There was a significant interaction between depression and the PSSS (P=0. 016). The relationship between depression and cardiac mortality decreased with increasing support. Furthermore, residual change score analysis revealed that among 1-year survivors who had been depressed at baseline, higher baseline social support was related to more improvement in depression symptoms than expected. CONCLUSIONS: Post-MI depression is a predictor of 1-year cardiac mortality, but social support is not directly related to survival. However, very high levels of support appear to buffer the impact of depression on mortality. Furthermore, high levels of support predict improvements in depression symptoms over the first post-MI year in depressed patients. High levels of support may protect patients from the negative prognostic consequences of depression because of improvements in depression symptoms.

Randomized trial comparing intravenous nitroglycerin and heparin for treatment of unstable angina secondary to restenosis after coronary artery angioplasty.

BACKGROUND: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina. METHODS AND RESULTS: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction. CONCLUSIONS: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Effect of a standardized meal on the threshold of exercise-induced myocardial ischemia in patients with stable angina.

OBJECTIVES: This study was undertaken to determine the effect of a standardized meal on the ischemic threshold and exercise capacity in a series of 20 patients with stable angina, exercise-induced ischemia and reversible exercise-induced perfusion defects. BACKGROUND: It is generally accepted that exercise tolerance in patients with angina is reduced after a meal. However, studies that have addressed this phenomenon have yielded results that are contradictory and inconclusive. METHODS: Two exercise tests using the Bruce protocol with technetium-99m (99mTc)-sestamibi were performed on consecutive days in a randomized order. One test was performed in the fasting state and the other 30 min after a 1,000-calorie meal. RESULTS: In the postprandial state, exercise time to ischemia was reduced by 20% from 248 +/- 93 s to 197 +/- 87 s (p = 0.0007), time to angina by 15% from 340 +/- 82 s to 287 +/- 94 s (p = 0.002) and exercise tolerance by 9% from 376 +/- 65 s to 344 +/- 86 s (p = 0.002). Rate-pressure products at these exercise test end points were not significantly different in the fasting and postprandial tests, and the quantitative 99mTc-sestamibi ischemia score was unchanged. CONCLUSIONS: In patients with stable angina, a 1,000-calorie meal significantly reduced time to ischemia, time to angina and exercise tolerance because of a more rapid increase in myocardial oxygen demand with exercise. The extent and severity of exercise-induced ischemia were unchanged.

Limited usefulness of intermittent nitroglycerin patches in stable angina.

The efficacy of continuous and intermittent nitroglycerin patches (10 mg/day) was compared in a randomized, placebo-controlled trial in 36 patients with stable angina and reproducible, exercise-induced ST depression. Intermittent treatment was administered either 18 or 14 h/day with an intermission of 6 h or 10 h, respectively. Exercise tests were performed during the last 2 h of patch application. Compared with placebo, neither continuous nitroglycerin nor the two intermittent regimens prolonged total treadmill time or time to 1 mm ST depression. No treatment eliminated exercise-induced ST depression in greater than 1 of the 36 patients. Time to angina was prolonged (by 40 +/- 66 s) only during the "10 h off" treatment (p = 0.001); time to angina increased by greater than or equal to 20% in 13 patients. Responders to treatment could be predicted by a short history of angina (p less than 0.05) and a time to angina less than or equal to 250 s during the placebo test. For each treatment, greater than or equal to 25 of the patients reported headache; 4 additional patients dropped out because of severe headache and 2 others because of a coronary event in a washout period. Thus, in most patients with stable angina, side effects outweight any benefit demonstrable with this therapy.

Intravenous diltiazem in acute myocardial infarction. Diltiazem as adjunctive therapy to activase (DATA) trial.

OBJECTIVES: This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks. BACKGROUND: Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans. METHODS: In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function. RESULTS: Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo. CONCLUSIONS: A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.

Symptom-limited versus low level exercise testing before hospital discharge after myocardial infarction.

OBJECTIVE: This study was undertaken to compare a low level and a symptom-limited test performed before hospital discharge after an uncomplicated myocardial infarction. BACKGROUND: Exercise testing after myocardial infarction provides useful prognostic information. Usually either a low level test is performed before hospital discharge or a symptom-limited test is performed at 3 weeks. METHODS: The study group comprised 202 patients with an uncomplicated myocardial infarction; 58 patients had a non-Q wave infarction and 115 patients had received thrombolytic therapy. Both a low level and a symptom-limited exercise test were performed in 200 of the 202 study patients in randomized order on consecutive days, a mean of 7.4 +/- 2.3 days after infarction. RESULTS: The symptom-limited test required a considerably greater effort than the low level test: exercise duration was 554 +/- 209 versus 389 +/- 125 s (p less than 0.0001), and peak work load was 5.7 +/- 1.8 versus 4.2 +/- 1.1 METs (p less than 0.0001). The peak heart rate was higher during the symptom-limited test (121 +/- 20 vs. 108 +/- 14 beats/min, p less than 0.0001), as was the rate-pressure product. The number of patients who developed ST segment depression greater than or equal to 1 mm increased from 56 during the low level test to 89 during the symptom-limited test (p less than 0.0001). ST segment depression greater than or equal to 2 mm occurred in 22 patients during the low level test and in 41 patients during the symptom-limited test, an 86% increase (p less than 0.0001). The number of patients with either angina or ST depression greater than or equal to 1 mm increased from 66 to 105 (p less than 0.0001) with the symptom-limited test. Exercise test results were similar for patients with a Q wave or a non-Q wave infarction. Exercise duration was longer and exercise-induced ST depression less frequent in patients who had received thrombolytic therapy. CONCLUSIONS: A symptom-limited exercise test performed before hospital discharge after uncomplicated myocardial infarction provides a significantly greater cardiovascular stress than does a low level test and is associated with an ischemic response nearly twice as frequently. The prognostic significance of a positive response at higher work loads has not been defined.

Depression and 1-year prognosis in unstable angina.

BACKGROUND: Depression is common after acute myocardial infarction and is associated with an increased risk of mortality for at least 18 months. The prevalence and prognostic impact of depression in patients with unstable angina, who account for a substantial portion of acute coronary syndrome admissions, have not been examined. METHODS: Interviews were carried out in hospital with 430 patients with unstable angina who did not require coronary artery bypass surgery before hospital discharge. Depression was assessed using the 21-item self-report Beck Depression Inventory and was defined as a score of 10 or higher. The primary outcome was 1-year cardiac death or nonfatal myocardial infarction. RESULTS: The Beck Depression Inventory identified depression in 41.4% of patients. Depressed patients were more likely to experience cardiac death or nonfatal myocardial infarction than other patients (odds ratio, 4.68; 95% confidence interval, 1.94-11.27; P<.001). The impact of depression remained after controlling for other significant prognostic factors, including baseline electrocardiographic evidence of ischemia, left ventricular ejection fraction, and the number of diseased coronary vessels (adjusted odds ratio, 6.73; 95% confidence interval, 2.43-18.64; P<.001). CONCLUSIONS: Depression is common following an episode of unstable angina and is associated with an increased risk of major cardiac events during the following year.

Sauna-induced myocardial ischemia in patients with coronary artery disease.

PURPOSE: Sauna bathing is a popular recreational activity that is generally considered to be safe. However, there have been case reports of adverse cardiac events. We sought to determine whether sauna use caused myocardial ischemia in patients with coronary artery disease. METHODS: Sixteen patients with proven coronary artery disease were submitted to three conditions (rest, exercise, and sauna bathing) with continuous electrocardiographic (ECG) monitoring and regular blood pressure measurements. During each condition, patients were injected with Tc-99 sestamibi followed by nuclear scintigraphic imaging. Perfusion defect scores were calculated in 15 patients. RESULTS: Sauna bathing was well tolerated. There was a mean (+/- SD) increase in heart rate of 32% +/- 20% in the sauna (resting mean heart rate = 60 +/- 9 beats per minute vs sauna mean heart rate = 79 +/- 11 beats per minute, P <0.001) and a 13% +/- 6% drop in systolic blood pressure (resting mean systolic blood pressure = 142 +/- 14 mm Hg vs sauna mean systolic blood pressure = 123 +/- 15 mm Hg, P <0.001). There were no arrhythmias or ECG changes in the sauna. Compared with rest, there was significant ischemia during sauna bathing (average perfusion defect score at rest = -0.44 vs average sauna score = -0.93, P <0.001). The perfusion defect score in the sauna was worse than the resting score in 14 of the 15 patients. Sauna-associated perfusion defect scores were highly correlated with exercise-induced scores (R2 = 0.65, P <0.001). CONCLUSION: In patients with stable coronary artery disease, sauna use is clinically well tolerated but is associated with scintigraphically demonstrated myocardial ischemia.

Effect of diltiazem slow-release formulation on silent myocardial ischemia in stable coronary artery disease. The Canadian Multicenter Diltiazem Study Group.

Silent myocardial ischemia is associated with adverse outcome in several subsets of coronary artery disease patients. This article presents results of a placebo-controlled, randomized, double-blind study of the effects of sustained-release diltiazem (180 mg twice daily) on ischemic episodes in 60 patients with documented coronary artery disease. The mean age of the study population was 60 years and 93% were male. The mean number of episodes of silent ischemia per patient was 5.6 (placebo) and 2.8 (diltiazem), a 50% reduction (p less than 0.0001). Duration of ST-segment depression was 119 minutes (placebo) and 67 minutes (diltiazem), a 44% reduction (p less than 0.001). This study demonstrates that sustained-release diltiazem can significantly reduce the frequency and total duration of silent ischemic episodes.

Differential long-term impact of in-hospital symptoms of psychological stress after non-Q-wave and Q-wave acute myocardial infarction.

Because of their unstable pathophysiology, it was hypothesized that patients with non-Q-wave acute myocardial infarctions (AMI) would be more vulnerable to the negative effects of psychological stress than patients with Q-wave AMI, and thus would be more likely to benefit from programs aimed at relieving stress. This hypothesis was tested through secondary analysis of data from a 1-year randomized clinical trial of psychological stress monitoring and intervention after AMI. After discharge, treatment group patients were telephoned each month and asked to respond to an index of psychological stress symptoms (General Health Questionnaire GHQ-20). Those with high stress symptoms (GHQ greater than or equal to 5) received home nursing visits. Control group patients received usual care. The sample consisted of 461 men, aged 31 to 86 years, who responded to the GHQ-20 before hospital discharge. Patients were followed for 5 years using record data. There were 321 Q-wave AMIs, 112 non-Q-wave AMIs and 28 indeterminate electrocardiograms. Life-table analyses showed that among patients with non-Q-wave AMIs receiving usual care, high stress in the hospital (GHQ greater than or equal to 5) was associated with a 1-year relative risk (RR) of cardiac mortality of 5.49 +/- 1.39 (p = 0.01). In comparison, control patients with Q-wave MIs had no stress-related increase in risk (RR = 0.41 +/- 2.08, p = 0.40). In the treatment group, the patients with non-Q-wave AMIs did not experience an increase in risk associated with high stress (RR = 1.80 +/- 1.79, p = 0.52).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of fibrinolysis and percutaneous transluminal coronary angioplasty on the frequency of ventricular premature complexes.

This study evaluated the aggressive management of acute myocardial infarction to determine how it modifies the incidence of ventricular arrhythmias and of other determinants of prognosis during recovery. The population consisted of 344 consecutive survivors of acute myocardial infarction admitted to the hospital with chest pain and ST-segment elevation on the electrocardiogram. Three groups constituted the study population: 168 control patients treated conservatively or in whom fibrinolysis was unsuccessful, 73 patients successfully reperfused with intravenous streptokinase and 103 patients with both successful fibrinolysis and successful percutaneous transluminal coronary angioplasty (PTCA) of the artery responsible for the infarct. Early spontaneous angina occurred in 47 control patients (28%), 25 streptokinase patients, (34%) and, in significantly fewer number, 20 PTCA patients (19%, p less than 0.05). Similarly, exercise-induced ST-segment depression on the predischarge exercise treadmill test was less frequent with PTCA (p less than 0.05). The number of ventricular premature complexes (VPCs) on a 24-hour Holter recording was 40 +/- 123/hr in the control group and significantly less in the streptokinase (21 +/- 64, p less than 0.05) and PTCA groups (17 +/- 61, p less than 0.05). Three or more VPCs/hr were observed in 50% of the control patients, compared with 29% of the streptokinase and 27% of the PTCA patients (p less than 0.005). Mean radionuclide ejection fraction was greater than 40% and similar in the 3 study groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Value of exercise electrocardiography in the detection of restenosis after coronary angioplasty in patients with one-vessel disease.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Effectiveness of self-monitored, home-based, moderate-intensity exercise training in middle-aged men and women.

The effects of 6 months of self-monitored, home-based exercise training on maximal oxygen uptake (VO2 max), body composition and plasma lipid levels of healthy, sedentary, middle-aged persons were evaluated in 60 men, aged 49 +/- 6 years, and 60 women, aged 47 +/- 5 years. Moderate-intensity training was performed 5 times per week in sessions of 47 +/- 7 minutes and 54 +/- 8 minutes for men and women, respectively. The individually prescribed range of heart rate corresponded to 65 to 77% of the peak value during symptom-limited treadmill testing (mean of 72% for men and 69% for women). Caloric expenditure per training session was approximately 345 kcal for men and 235 kcal for women. VO2 max increased 15% in men and 9% in women (both p less than 0.01). The greater increase in VO2 max in men than in women primarily reflected greater adherence to training in men (greater than or equal to 90% vs greater than or equal to 75%). The increase in VO2 max in women who showed very high adherence was comparable to that of men. Body weight decreased, by 1.5 +/- 10 kg, in men (p less than 0.05) but not in women undergoing training. No significant training-induced changes in plasma lipid levels were noted in either men or women. Baseline orientation and follow-up telephone calls required less than 1 hour of staff time per participant. Self-monitored, moderate-intensity, home-based exercise training significantly increases functional capacity in healthy, middle-aged men and women. Such training provides an alternative to group-based exercise training.

Assessment by a microprocessor of adherence to home-based moderate-intensity exercise training in healthy, sedentary middle-aged men and women.

Research in exercise training of healthy persons, which has been conducted almost exclusively in supervised group programs, is relatively expensive for the investigator and inconvenient for the participant. To overcome these obstacles, self-monitored moderate-intensity home-based exercise training was prescribed for 28 middle-aged men and 26 middle-aged women. The median energy expenditure prescribed for each of 5 weekly exercise sessions was 4 cal/kg body weight, or 317 kcal for men and 265 kcal for women, corresponding to a median duration of 45 and 60 minutes, respectively. In the next 24 weeks, peak oxygen uptake increased 13.7% in men who exercised, from 31 +/- 4 to 37 +/- 4 ml/kg/min, and 10% in women who exercised, from 26 +/- 4 to 29 +/- 5 ml/kg/min (p less than 0.001 for both comparisons). The proportion of prescribed caloric expenditure per session, which was documented by a solid-state heart rate recorder, was 108% in men and 90% in women. The duration of training at heart rates above the prescribed range approximated 10 minutes per session for both men and women; the proportion of total caloric expenditure represented by exercise at heart rates exceeding the prescribed limit was 9% for men and 4% for women. The proportion of time spent within the prescribed heart rate range during training sessions was 76% for men and 84% for women. Training-induced musculoskeletal problems were reported by 6 men and no women. No subject sought medical attention and all resumed training within 1 week.(ABSTRACT TRUNCATED AT 250 WORDS)

Usefulness of sustained-release diltiazem for stable angina pectoris.

Sustained-release diltiazem, 120 and 180 mg twice daily, was assessed in a multicenter, double-blind, randomized, placebo-controlled trial in 65 stable angina patients with exercise-induced ST depression. Exercise testing was performed 12 +/- 1 hours after the last dose at the end of each of the 3 treatment weeks. Both dose levels of drug reduced spontaneous angina (p less than 0.001) and increased exercise duration (p less than 0.01) and time to 1-mm ST depression (p less than 0.001). No differences were noted between the 2 dose levels. Rate-pressure product at maximal exercise was similar for the 3 groups. Only 1 patient terminated the study because of adverse drug effects; severe adverse effects occurred in 1 placebo and 1 low-dose period. Sustained-release diltiazem is safe and efficacious monotherapy for patients with stable angina.

Efficacy and Safety of Evening Administration of Controlled-Delivery Diltiazem Capsules in Chronic Stable Angina Patients.

The safety and efficacy of controlled-delivery (CD) once-a-day formulation of diltiazem administered in the evening, at a dose of 240 mg, was assessed in 37 patients with stable angina pectoris. A double-blind, placebo-controlled, randomized, crossover protocol was used. Following a 4-day washout period, patients entered a 5--7-day single-blind placebo run-in period during which qualification and reproducibility exercise treadmill tests (ETTs) were performed 24 h postdose. Eligible patients were randomized in a double-blind fashion, to either CD diltiazem or to placebo for a 7--10-day treatment period. They then entered a 5--7-day single-blind washout period, after which they received the alternate treatment for another 7 to 10 days. ETTs were performed at the end of each treatment period. Compared to placebo, evening administration of CD diltiazem produced a marked improvement of the time to ETT termination, time to onset of angina, and time to 1 mm ST depression. In addition, the number of angina attacks recorded in patient diaries was reduced compared to placebo. Incidence of adverse events was comparable with CD diltiazem and placebo. We conclude that evening administration of controlled-delivery diltiazem is highly effective and safe in the treatment of stable angina pectoris.

Depression and health-care costs during the first year following myocardial infarction.

OBJECTIVE: Depression in the hospital after myocardial infarction (MI) has been associated with a substantial increase in the long-term risk of cardiac mortality, but little is known about other outcomes. This study uses Quebec Medicare data to examine the relationship between post-MI depression and physician costs, including both out-patient care and hospital readmissions. METHODS: The sample consists of 848 1-year survivors of an acute MI who had completed the Beck Depression Inventory (BDI) in hospital. Two hundred sixty subjects had BDI scores of >/=10 (30.7%), indicative of mild to moderate symptoms of depression. Quebec Medicare data during the index admission for an acute MI and during the year following discharge were compared for the patients with elevated BDI scores and those with normal scores. RESULTS: Total costs, in Canadian dollars (out-patient physician charges plus physician costs during admissions plus estimates of associated direct costs), were about 41% higher (p = 0.004) for patients with elevated BDI scores. The difference was primarily related to out-patient and emergency room visits and readmission costs associated with longer stays in hospital wards, and was not accounted for by use of psychiatric services or readmissions for revascularization. CONCLUSION: Results suggest that, in addition to the survival risks associated with post-MI depression, there are increased health care costs linked to both readmissions and out-patient contacts among depressed patients who survive the first post-MI year. The extent to which the increased use of health care may have reduced depression and enhanced survival remains unclear.

Effect of a short-term primary prevention program on endothelium-dependent vasodilation in adults at risk for atherosclerosis.

BACKGROUND: Endothelium-dependent vasodilation is impaired in asymptomatic subjects with risk factors for atherosclerosis. PURPOSE: To determine whether a three-month integrative primary prevention program can improve endothelial function in asymptomatic subjects with risk factors for atherosclerosis. PATIENTS AND METHODS: Twenty-two asymptomatic middle-aged men and women (13 men and nine women) aged 55 +/- 7 years with sedentary lifestyle and dyslipidemia (low density lipoprotein [LDL] level greater than 3.4 mmol/L) underwent an exercise test, determination of fasting blood lipid levels and noninvasive measurement of brachial artery reactivity before and three months after the beginning of a prevention program. The program consisted of exercise training (three times per week) and National Cholesterol Education Program step 1 diet in all subjects. A smoking cessation program was offered when applicable (six patients). Brachial artery diameter was measured by using high resolution ultrasound at rest, during reactive hyperemia (flow-mediated dilation [FMD], which is endothelium-dependent) and after sublingual nitroglycerin (NTG) (endothelium-independent vasodilation). RESULTS: After three months, peak oxygen uptake increased significantly from 25.4 +/- 4.9 to 27.5 +/- 4.8 mL/kg/min (P < 0.005), and LDL level decreased significantly from 4.48 +/- 0.92 to 4.00 +/- 0.83 mmol/L (P < 0.005). FMD and NTG responses assessed as percentage of diameter change from baseline, however, did not change (FMD 5.4 +/- 4.3% before and 5.1 +/- 3.9% at three months, not significant; NTG 8.4 +/- 3.8% before and 7.4 +/- 4.5% at three months, not significant). CONCLUSIONS: Short-term application of the currently recommended lifestyle intervention in adults with coronary risk factors did not improve vascular endothelial function. Longer and more aggressive programs may be needed to improve vascular function in subjects with risk factors for atherosclerosis.