Robert A. Waugh

Exercise and Pharmacotherapy in the Treatment of Major Depressive Disorder

Objective: To assess whether patients receiving aerobic exercise training performed either at home or in a supervised group setting achieve reductions in depression comparable to standard antidepressant medication (sertraline) and greater reductions in depression compared to placebo controls. Methods: Between October 2000 and November 2005, we performed a prospective, randomized controlled trial (SMILE study) with allocation concealment and blinded outcome assessment in a tertiary care teaching hospital. A total of 202 adults (153 women; 49 men) diagnosed with major depression were assigned randomly to one of four conditions: supervised exercise in a group setting; home-based exercise; antidepressant medication (sertraline, 50–200 mg daily); or placebo pill for 16 weeks. Patients underwent the structured clinical interview for depression and completed the Hamilton Depression Rating Scale (HAM-D). Results: After 4 months of treatment, 41% of the participants achieved remission, defined as no longer meeting the criteria for major depressive disorder (MDD) and a HAM-D score of <8. Patients receiving active treatments tended to have higher remission rates than the placebo controls: supervised exercise = 45%; home-based exercise = 40%; medication = 47%; placebo = 31% (p = .057). All treatment groups had lower HAM-D scores after treatment; scores for the active treatment groups were not significantly different from the placebo group (p = .23). Conclusions: The efficacy of exercise in patients seems generally comparable with patients receiving antidepressant medication and both tend to be better than the placebo in patients with MDD. Placebo response rates were high, suggesting that a considerable portion of the therapeutic response is determined by patient expectations, ongoing symptom monitoring, attention, and other nonspecific factors. BDI = Beck Depression Inventory; CI = confidence interval; HAM-D = Hamilton Depression Rating Scale; ITT = intention-to-treat; MDD = major depressive disorder; SD = standard deviation; SSRIs = selective serotonin reuptake inhibitors; TSH = thyroid stimulating hormone.

Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study.

BACKGROUND Although the DASH (Dietary Approaches to Stop Hypertension) diet has been shown to lower blood pressure (BP) in short-term feeding studies, it has not been shown to lower BP among free-living individuals, nor has it been shown to alter cardiovascular biomarkers of risk. OBJECTIVE To compare the DASH diet alone or combined with a weight management program with usual diet controls among participants with prehypertension or stage 1 hypertension (systolic BP, 130-159 mm Hg; or diastolic BP, 85-99 mm Hg). DESIGN AND SETTING Randomized, controlled trial in a tertiary care medical center with assessments at baseline and 4 months. Enrollment began October 29, 2003, and ended July 28, 2008. PARTICIPANTS Overweight or obese, unmedicated outpatients with high BP (N = 144). INTERVENTIONS Usual diet controls, DASH diet alone, and DASH diet plus weight management. OUTCOME MEASURES The main outcome measure is BP measured in the clinic and by ambulatory BP monitoring. Secondary outcomes included pulse wave velocity, flow-mediated dilation of the brachial artery, baroreflex sensitivity, and left ventricular mass. RESULTS Clinic-measured BP was reduced by 16.1/9.9 mm Hg (DASH plus weight management); 11.2/7.5 mm (DASH alone); and 3.4/3.8 mm (usual diet controls) (P < .001). A similar pattern was observed for ambulatory BP (P < .05). Greater improvement was noted for DASH plus weight management compared with DASH alone for pulse wave velocity, baroreflex sensitivity, and left ventricular mass (all P < .05). CONCLUSION For overweight or obese persons with above-normal BP, the addition of exercise and weight loss to the DASH diet resulted in even larger BP reductions, greater improvements in vascular and autonomic function, and reduced left ventricular mass. CLINICAL TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00571844.

Effects of spouse-assisted coping skills training and exercise training in patients with osteoarthritic knee pain: a randomized controlled study

&NA; This study tested the separate and combined effects of spouse‐assisted pain coping skills training (SA‐CST) and exercise training (ET) in a sample of patients having persistent osteoarthritic knee pain. Seventy‐two married osteoarthritis (OA) patients with persistent knee pain and their spouses were randomly assigned to: SA‐CST alone, SA‐CST plus ET, ET alone, or standard care (SC). Patients in SA‐CST alone, together with their spouses, attended 12 weekly, 2‐h group sessions for training in pain coping and couples skills. Patients in SA‐CST+ET received spouse‐assisted coping skills training and attended 12‐weeks supervised ET. Patients in the ET alone condition received just an exercise program. Data analyses revealed: (1) physical fitness and strength: the SA‐CST+ET and ET alone groups had significant improvements in physical fitness compared to SA‐CST alone and patients in SA‐CST+ET and ET alone had significant improvements in leg flexion and extension compared to SA‐CST alone and SC, (2) pain coping: patients in SA‐CST+ET and SA‐CST alone groups had significant improvements in coping attempts compared to ET alone or SC and spouses in SA‐CST+ET rated their partners as showing significant improvements in coping attempts compared to ET alone or SC, and (3) self‐efficacy: patients in SA‐CST+ET reported significant improvements in self‐efficacy and their spouses rated them as showing significant improvements in self‐efficacy compared to ET alone or SC. Patients receiving SA‐CST+ET who showed increased self‐efficacy were more likely to have improvements in psychological disability. An intervention that combines spouse‐assisted coping skills training and exercise training can improve physical fitness, strength, pain coping, and self‐efficacy in patients suffering from pain due to osteoarthritis.

Mental Stress–Induced Ischemia in the Laboratory and Ambulatory Ischemia During Daily Life Association and Hemodynamic Features

BACKGROUND The purpose of this study was to determine the correspondence of mental stress-induced ischemia in the laboratory with ambulatory ischemia and to assess the relationship between hemodynamic responses to mental stress and the occurrence of ischemia. Although exercise testing is usually used to elicit myocardial ischemia, ischemia during daily life usually occurs at relatively low heart rates and in the absence of strenuous physical exercise. Mental stress has been shown to trigger ischemic events in the laboratory at lower heart rates but at blood pressures comparable to exercise. We therefore compared the extent to which mental stress and exercise testing identify patients who develop ischemia out of hospital. METHODS AND RESULTS One hundred thirty-two patients with documented coronary disease and recent evidence of exercise-induced myocardial ischemia underwent 48-hour ambulatory monitoring and radionuclide ventriculography during exercise and mental stress testing. Patients who displayed mental stress-induced ischemia in the laboratory were more likely to exhibit ischemia during daily life (P < .021). Furthermore, patients who exhibited ischemia during ambulatory monitoring displayed larger diastolic blood pressure (P < .006), heart rate (P < .039), and rate-pressure product responses (P < .018) during mental stress. CONCLUSIONS Among patients with prior positive exercise stress tests, mental stress-induced ischemia, defined by new wall motion abnormalities, predicts daily ischemia independent of exercise-induced ischemia. Exaggerated hemodynamic responses during mental stress testing also identify individuals who are more likely to exhibit myocardial ischemia during daily life and mental stress.

Prognostic value of ventricular arrhythmias associated with treadmill exercise testing in patients studied with cardiac catheterization for suspected ischemic heart disease

The prognostic information provided by ventricular arrhythmias associated with treadmill exercise testing was evaluated in 1,293 consecutive nonsurgically treated patients undergoing an exercise test within 6 weeks of cardiac catheterization. The 236 patients with simple ventricular arrhythmias (at least one premature ventricular complex, but without paired complexes or ventricular tachycardia) had a higher prevalence of significant coronary artery disease (57 versus 44%), three vessel disease (31 versus 17%) and abnormal left ventricular function (43 versus 24%) than did patients without ventricular arrhythmias. Patients with paired complexes or ventricular tachycardia had an even higher prevalence of significant coronary artery disease (75%), three vessel disease (39%) and abnormal left ventricular function (54%). In the 620 patients with significant coronary artery disease, patients with paired complexes or ventricular tachycardia had a lower 3 year survival rate (75%) than did patients with simple ventricular arrhythmias (83%) and patients with no ventricular arrhythmias (90%). Ventricular arrhythmias were found to add independent prognostic information to the noninvasive evaluation, including history, physical examination, chest roentgenogram, electrocardiogram and other exercise test variables (p = 0.03). Ventricular arrhythmias made no independent contribution once the cardiac catheterization data were known. In patients without significant coronary artery disease, no relation between ventricular arrhythmias and survival was found.

Test of a cardiology patient simulator with students in fourth-year electives

A total of 208 fourth-year students at five medical schools participated in an evaluation of a cardiology patient simulator (CPS). One group (116 students) used the CPS during a fourth-year cardiology elective, while another group (92 students) completed a cardiology elective that did not include use of the CPS. There were no differences between the two groups on a multiple-choice test on cardiology and a skills test on the CPS at the beginning of the clerkship. After the clerkship, the students in the CPS group achieved significantly higher scores on a multiple-choice test, a skills test on the CPS, and a skills test on cardiology patients. Both the students and faculty members expressed very favorable attitudes toward the CPS, but the patients perceived no differences between the two student groups. These data demonstrate that the CPS enhances learning both the knowledge and the skills necessary to perform a bedside cardiovascular evaluation and that the skills obtained from use of the simulator are transferable to use with patients.

Usefulness of psychosocial treatment of mental stress-induced myocardial ischemia in men.

This study examined the effects of exercise and stress management training on clinical outcomes and medical expenditures over a 5-year follow-up period in 94 male patients with established coronary artery disease (CAD) and evidence of ambulatory or mental stress-induced myocardial ischemia. Patients were randomly assigned to 4 months of aerobic exercise 3 times per week or to a 1.5-hour weekly class on stress management; patients who lived too far from Duke to participate in the weekly treatments formed the usual care control group. Follow-up was performed at the end of treatment and annually thereafter for 5 years. Stress management was associated with a significant reduction in clinical CAD events relative to usual care over each of the first 2 years of follow-up and after 5 years. Economic analyses revealed that stress management was associated with lower medical costs than usual care and exercise in the first 2 years, and that the cumulative cost over 5 years was also lower for stress management relative to usual care. These results suggest that there may be clinical and economic benefit to offering the type of preventive stress management and exercise interventions provided to patients with myocardial ischemia. Moreover, these findings suggest that the financial benefits that accrue from an appropriately targeted intervention may be substantial and immediate.

Immediate and Remote Prognostic Significance of Fascicular Block during Acute Myocardial Infarction

The electrocardiograms of 538 patients with acute myocardial infarction were searched to identify all instances of atrioventricular (A-V) and intraventricular (I-V) conduction disturbances. Data concerning mode of therapy and clinical complications were obtained by review of the record. These variables were then analyzed for significance in relation to the development of type II A-V block acutely and syncope or sudden death during the first year of follow-up.The most accurate predictor for both these events was the status of A-V conduction in combination with the status of I-V conduction. At highest risk (50%) for type II progression were patients with acute adjacent fascicular block plus P-R prolongation, i.e., left anterior hemiblock plus right bundle-branch block (RBBB), or left bundle-branch block (LBBB), or patients with acute nonadjacent fascicular block, i.e., RBBB plus left posterior hemiblock or alternating bundle-branch block. The nonpaced survivors from this same group, plus any other patients with transient type II progression, were also at high risk (45%) for syncope or sudden death in follow-up. No syncope or sudden death has occurred in seven patients with type II progression discharged with a pacemaker. All other patients were at lower risk for these acute and chronic complications.Thus, the electrocardiogram in acute myocardial infarction can identify a high-risk group for acute type II progression in whom prophylactic pacer insertion may be beneficial. Similarly, the electrocardiogram can identify a high-risk group for syncope or sudden death in follow-up and implicates progression to higher degrees of A-V block as an important pathophysiologic mechanism.The possible role of permanent pacemaker therapy in preventing syncope or sudden death in this high-risk group is also suggested.

Effects of Exercise and Weight Loss on Mental Stress–Induced Cardiovascular Responses in Individuals With High Blood Pressure

The purpose of this study was to determine the effects of exercise and weight loss on cardiovascular responses during mental stress in mildly to moderately overweight patients with elevated blood pressure. Ninety-nine men and women with high normal or unmedicated stage 1 to stage 2 hypertension (systolic blood pressure 130 to 179 mm Hg, diastolic blood pressure 85 to 109 mm Hg) underwent a battery of mental stress tests, including simulated public speaking, anger recall interview, mirror trace, and cold pressor, before and after a 6-month treatment program. Subjects were randomly assigned to 1 of 3 treatments: (1) aerobic exercise, (2) weight management combining aerobic exercise with a behavioral weight loss program, or (3) waiting list control group. After 6 months, compared with control subjects, participants in both active treatment groups had lower levels of systolic blood pressure, diastolic blood pressure, total peripheral resistance, and heart rate at rest and during mental stress. Compared with subjects in the control group, subjects in the exercise and weight management groups also had greater resting stroke volume and cardiac output. Diastolic blood pressure was lower for the weight management group than for the exercise-only group during all mental stress tasks. These results demonstrate that exercise, particularly when combined with a weight loss program, can lower both resting and stress-induced blood pressure levels and produce a favorable hemodynamic pattern resembling that targeted for antihypertensive therapy.

Effect of phasic respiration on left ventricular dimension and performance in a normal population. An echocardiographic study.

Echocardiographic examination of the left ventricle (LV) in 30 normal subjects, 5 to 47 years of age, was performed in order to analyze the effects of phasic respiration on LV dimensions and derived LV function. Peak expiratory and peak inspiratory LV diastolic and systolic dimensions were measured and extrapolated to volume estimates using a standard formula. Although there was wide variation in the individual measurements, and particularly in systolic dimension, the mean peak inspiratory diastolic dimension, derived diastolic volume, and stroke volume all decreased significantly (P < 0.001); a smaller decrease in ejection fraction was seen (P < 0.02), while the changes in mean end-systolic dimension and end-systolic volume were not significant. While these observed changes may reflect a true physiologic variation, an artifactual component cannot be excluded. Regardless of their physiologic significance, however, these data show that the effect of phasic respiration is a factor to be considered in correlative echocardiographic studies of LV function in both normal and, possibly, pathologic cardiovascular conditions.