Lana L. Watkins

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.

Anxiety and vagal control of heart rate.

Objective Prospective studies have demonstrated that anxiety predicts sudden cardiac death, but the mechanism underlying this increased risk is unclear. This study examined whether anxiety is associated with reductions in vagal control of heart rate in healthy volunteers. Method Trait anxiety (T-ANX) was measured, using the Spielberger State-Trait Anxiety Inventory (STAI), in 93 healthy men and women 25 to 44 years of age. Power spectral analysis was used to measure two indices of vagal control: baroreflex control of heart rate (BRC) and respiratory sinus arrhythmia (RSA). Results High trait anxiety (T-ANX > 41, N = 23) was associated with significantly reduced vagal control of the heart, compared with low trait anxiety (T-ANX < 31, N = 22), as indicated by a 36% reduction in BRC (p < .001) and an 8% reduction in RSA (p < .05). Furthermore, T-ANX scores were negatively correlated with levels of BRC (r = -.30, p < .005), and levels of RSA (r = -.26, p < .05). Conclusions These findings provide evidence that trait anxiety is associated with reductions in vagal control of the heart. Additional studies are needed to examine whether low vagal control is involved in the increased risk of sudden cardiac death associated with anxiety.

Posttraumatic Stress Disorder, Cardiovascular, and Metabolic Disease: A Review of the Evidence

BackgroundPosttraumatic stress disorder (PTSD) is a significant risk factor for cardiovascular and metabolic disease.PurposeThe purpose of the current review is to evaluate the evidence suggesting that PTSD increases cardiovascular and metabolic risk factors, and to identify possible biomarkers and psychosocial characteristics and behavioral variables that are associated with these outcomes.MethodsA systematic literature search in the period of 2002–2009 for PTSD, cardiovascular disease, and metabolic disease was conducted.ResultsThe literature search yielded 78 studies on PTSD and cardiovascular/metabolic disease and biomarkers.ConclusionsAlthough the available literature suggests an association of PTSD with cardiovascular disease and biomarkers, further research must consider potential confounds, incorporate longitudinal designs, and conduct careful PTSD assessments in diverse samples to address gaps in the research literature. Research on metabolic disease and biomarkers suggests an association with PTSD, but has not progressed as far as the cardiovascular research.

Noninvasive Assessment of Baroreflex Control in Borderline Hypertension: Comparison With the Phenylephrine Method

In this study, we examined the sensitivity of two recently developed noninvasive baroreflex measurement techniques to assess baroreflex control in hypertension. We assessed baroreflex sensitivity noninvasively from covariations of systolic pressure and RR interval using spectral analysis and sequence detection. The noninvasive estimates of baroreflex control were compared with estimates derived from phenylephrine-induced increases in systolic pressure and RR interval in normotensive subjects (n = 27) and borderline hypertensive subjects (n = 15). Baroreflex sensitivity was significantly reduced in the borderline hypertensive group relative to the normotensive group when assessed with the use of either the noninvasive or invasive methods to index baroreflex control. In addition, estimates obtained from the noninvasive methods were significantly correlated with baroreflex sensitivity assessed with the phenylephrine method (spectral: r = .48, P < .001; sequence: r = .50, P < .001). These findings suggest that spectral analysis and the sequence method provide viable alternatives to the pharmacological approach for estimation of baroreflex sensitivity in hypertension.

Association of depressive symptoms with reduced baroreflex cardiac control in coronary artery disease.

BACKGROUND Although depression has been associated with cardiac death in coronary artery disease (CAD), little is known about the effects of depression on autonomic nervous system control of heart rate. This study evaluated whether depressive symptomatology is associated with impaired baroreflex sensitivity (BRS) in patients with CAD. METHODS AND RESULTS BRS was assessed in 66 patients with stable CAD by using cross-spectral analysis to measure baroreceptor-mediated R-R interval oscillations. Depressive symptomatology was determined with the Beck Depression Inventory, with lower (scores <3, n = 14) and upper (scores >9, n = 16) quartiles of scores used to define groups with low and high depressive symptomatology, respectively. Comparison of the two groups showed that age-adjusted BRS was reduced in the patients with high depressive symptomatology when compared with patients with low depressive symptomatology (4.5 +/- 2.7 vs 6.5 +/- 2.8 ms/mm Hg; P <. 05). CONCLUSIONS The current findings show that patients with CAD and depressive symptomatology have reduced BRS. Future studies are needed to examine whether reduced baroreflex cardiac control predicts cardiac risk in patients with CAD and depressive symptomatology.

Exercise and Pharmacological Treatment of Depressive Symptoms in Patients With Coronary Heart Disease: Results From the UPBEAT (Understanding the Prognostic Benefits of Exercise and Antidepressant Therapy) Study

OBJECTIVES The aim of this study was to assess the efficacy of exercise and antidepressant medication in reducing depressive symptoms and improving cardiovascular biomarkers in depressed patients with coronary heart disease. BACKGROUND Although there is good evidence that clinical depression is associated with poor prognosis, optimal therapeutic strategies are currently not well defined. METHODS One hundred one outpatients with coronary heart disease and elevated depressive symptoms underwent assessment of depression, including a psychiatric interview and the Hamilton Rating Scale for Depression. Participants were randomized to 4 months of aerobic exercise (3 times/week), sertraline (50-200 mg/day), or placebo. Additional assessments of cardiovascular biomarkers included measures of heart rate variability, endothelial function, baroreflex sensitivity, inflammation, and platelet function. RESULTS After 16 weeks, all groups showed improvement on Hamilton Rating Scale for Depression scores. Participants in both the aerobic exercise (mean -7.5; 95% confidence interval: -9.8 to -5.0) and sertraline (mean -6.1; 95% confidence interval: -8.4 to -3.9) groups achieved larger reductions in depressive symptoms compared with those receiving placebo (mean -4.5; 95% confidence interval: -7.6 to -1.5; p = 0.034); exercise and sertraline were equally effective at reducing depressive symptoms (p = 0.607). Exercise and medication tended to result in greater improvements in heart rate variability compared with placebo (p = 0.052); exercise tended to result in greater improvements in heart rate variability compared with sertraline (p = 0.093). CONCLUSIONS Both exercise and sertraline resulted in greater reductions in depressive symptoms compared to placebo in patients with coronary heart disease. Evidence that active treatments may also improve cardiovascular biomarkers suggests that they may have a beneficial effect on clinical outcomes as well as on quality of life. (Exercise to Treat Depression in Individuals With Coronary Heart Disease; NCT00302068).

Association of Anxiety and Depression With All-Cause Mortality in Individuals With Coronary Heart Disease

Background Depression has been related to mortality in coronary heart disease (CHD) patients, but few studies have evaluated the role of anxiety or the role of the co‐occurrence of depression and anxiety. We examined whether anxiety is associated with increased risk of mortality after accounting for depression in individuals with established CHD. Methods and Results The cohort was composed of 934 men and women with confirmed CHD (mean age, 62±11 years) who completed the Hospital Anxiety and Depression scale (HADS) during hospitalization for coronary angiography. Over the 3‐year follow‐up period, there were 133 deaths. Elevated scores on the HADS anxiety subscale (HADS‐A≥8) were associated with increased risk of mortality after accounting for established risk factors including age, congestive heart failure, left ventricular ejection fraction, 3‐vessel disease, and renal disease (hazard ratio [HR], 2.27; 95% CI, 1.55 to 3.33; P<0.001). Elevated scores on the HADS depression subscale (HADS‐D≥8) were also associated with increased risk of mortality (HR, 2.18; 95% CI, 1.47 to 3.22; P<0.001). When both psychosocial factors were included in the model, each maintained an association with mortality (anxiety, HR, 1.83; 95% CI, 1.18 to 2.83; P=0.006; depression, HR, 1.66; 95% CI, 1.06 to 2.58; P=0.025). Estimation of the HR for patients with both anxiety and depression versus those with neither revealed a larger HR than for patients with either factor alone (HR, 3.10; 95% CI, 1.95 to 4.94; P<0.001). Conclusions Anxiety is associated with increased risk of mortality in CHD patients, particularly when comorbid with depression. Future studies should focus on the co‐occurrence of these psychosocial factors as markers of increased mortality risk.

Effects of the Dietary Approaches to Stop Hypertension Diet Alone and in Combination With Exercise and Caloric Restriction on Insulin Sensitivity and Lipids

This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on insulin sensitivity and lipids. In a randomized control trial, 144 overweight (body mass index: 25 to 40) men (n=47) and women (n=97) with high blood pressure (130 to 159/85 to 99 mm Hg) were randomly assigned to one of the following groups: (1) DASH diet alone; (2) DASH diet with aerobic exercise and caloric restriction; or (3) usual diet controls (UC). Body composition, fitness, insulin sensitivity, and fasting lipids were measured before and after 4 months of treatment. Insulin sensitivity was estimated on the basis of glucose and insulin levels in the fasting state and after an oral glucose load. Participants in the DASH diet with aerobic exercise and caloric restriction condition lost weight (−8.7 kg [95% CI: −2.0 to −9.7 kg]) and exhibited a significant increase in aerobic capacity, whereas the DASH diet alone and UC participants maintained their weight (−0.3 kg [95% CI: −1.2 to 0.5 kg] and +0.9 kg [95% CI: 0.0 to 1.7 kg], respectively) and had no improvement in exercise capacity. DASH diet with aerobic exercise and caloric restriction demonstrated lower glucose levels after the oral glucose load, improved insulin sensitivity, and lower total cholesterol and triglycerides compared with both DASH diet alone and UC, as well as lower fasting glucose and low-density lipoprotein cholesterol compared with UC. DASH diet alone participants generally did not differ from UC in these measures. Combining the DASH diet with exercise and weight loss resulted in significant improvements in insulin sensitivity and lipids. Despite clinically significant reductions in blood pressure, the DASH diet alone, without caloric restriction or exercise, resulted in minimal improvements in insulin sensitivity or lipids.

Phobic anxiety, depression, and risk of ventricular arrhythmias in patients with coronary heart disease.

Objective: Findings of an association between phobic anxiety and elevated risks of sudden cardiac death suggest that phobic anxiety may be related to increased risk of ventricular arrhythmias. The purpose of this study was to examine whether phobic anxiety is associated with ventricular arrhythmias in patients with documented coronary artery disease (CAD). Methods: Phobic anxiety level was measured using the Crown-Crisp phobic anxiety scale in 940 patients (660 men, 280 women) hospitalized for diagnostic cardiac catheterization between April 1999 and June 2002. Depressive symptomatology was assessed using the Beck Depression Inventory. Patients were followed for a median follow-up period of 3 years, and the occurrence of ventricular arrhythmias was determined through review of medical records. Results: Ventricular arrhythmias occurred in 97 patients and were significantly related to higher phobic anxiety after statistical adjustment for established medical and demographic determinants of arrhythmias (odds ratio = 1.40; p = .012). Depressive symptomatology was significantly correlated with phobic anxiety (r = 0.44, p < .001) and was also related to ventricular arrhythmias (odds ratio = 1.40; p = .006). The composite of depression and phobic anxiety predicted ventricular arrhythmias with a larger effect size than either depression or phobic anxiety score alone (odds ratio = 1.6, 95% confidence interval, 1.2–2.1, p = .002). Conclusions: Both phobic anxiety and depressive symptomatology predict ventricular arrhythmias in patients with CAD and may share a common factor predictive of ventricular arrhythmias. CAD = coronary artery disease; SCD = sudden cardiac death; MI = myocardial infarction; LVEF = left ventricular ejection fraction; BDI = Beck Depression Inventory; NSVT = nonsustained ventricular tachycardia; susVT = sustained ventricular tachycardia; V-fib = ventricular fibrillation; BMI = body mass index; ICD = internal cardiodefibrillator device.