New Perspectives on Treatment of Depression in Coronary Heart Disease.

ABSTRACT: It has been 35 years since we published a study in Psychosomatic Medicine showing that patients with coronary heart disease (CHD) and major depression were at twice the risk of having a cardiac event as were nondepressed patients (Carney et al. Psychosom Med. 1988;50:627-33). This small study was followed a few years later by a larger, more convincing report from Frasure-Smith et al. (JAMA. 1993;270:1819-25) showing that depression increased the rate of mortality in patients with a recent acute myocardial infarction. Since the 1990s, there have been many more studies of depression as a risk factor for cardiac events and cardiac-related mortality from all over the world, and many clinical trials designed to determine whether treating depression improves medical outcomes in these patients. Unfortunately, the effects of depression treatment in patients with CHD remain unclear. This article considers why it has been difficult to determine whether treatment of depression improves survival in these patients. It also proposes several lines of research to address this question, with the goal of definitively establishing whether treating depression can extend cardiac event-free survival and enhance quality of life in patients with CHD.

The Promise of Polygenic Risk Prediction in Smoking Cessation: Evidence From Two Treatment Trials.

INTRODUCTION: Tobacco use disorder is a complex behavior with a strong genetic component. Genome-wide association studies (GWAS) on smoking behaviors allow for the creation of polygenic risk scores (PRSs) to approximate genetic vulnerability. However, the utility of smoking-related PRSs in predicting smoking cessation in clinical trials remains unknown. AIMS AND METHODS: We evaluated the association between polygenic risk scores and bioverified smoking abstinence in a meta-analysis of two randomized, placebo-controlled smoking cessation trials. PRSs of smoking behaviors were created using the GWAS and Sequencing Consortium of Alcohol and Nicotine use (GSCAN) consortium summary statistics. We evaluated the utility of using individual PRS of specific smoking behavior versus a combined genetic risk that combines PRS of all four smoking behaviors. Study participants came from the Transdisciplinary Tobacco Use Research Centers (TTURCs) Study (1091 smokers of European descent), and the Genetically Informed Smoking Cessation Trial (GISC) Study (501 smokers of European descent). RESULTS: PRS of later age of smoking initiation (OR [95% CI]: 1.20, [1.04-1.37], p = .0097) was significantly associated with bioverified smoking abstinence at end of treatment. In addition, the combined PRS of smoking behaviors also significantly predicted bioverified smoking abstinence (OR [95% CI] 0.71 [0.51-0.99], p = .045). CONCLUSIONS: PRS of later age at smoking initiation may be useful in predicting smoking cessation at the end of treatment. A combined PRS may be a useful predictor for smoking abstinence by capturing the genetic propensity for multiple smoking behaviors. IMPLICATIONS: There is a potential for polygenic risk scores to inform future clinical medicine, and a great need for evidence on whether these scores predict clinically meaningful outcomes. Our meta-analysis provides early evidence for potential utility of using polygenic risk scores to predict smoking cessation amongst smokers undergoing quit attempts, informing further work to optimize the use of polygenic risk scores in clinical care.

Effects of Depression on Heart Failure Self-Care.

BACKGROUND: Depression has been identified as a barrier to effective heart failure self-care, but recent studies suggest that the relationship between depression and self-care is more complex than was previously believed. This study was designed to clarify the relationship between depression and self-care in hospitalized patients with HF. METHODS AND RESULTS: During hospitalization with a confirmed clinical diagnosis of HF, 400 patients completed a structured interview to diagnose Diagnostic and Statistical Manual, 5th edition (DSM-5) depressive disorders, the Patient Health Questionnaire (PHQ-9) depression questionnaire, the Self-Care of Heart Failure Index (SCHFI), and several psychosocial questionnaires. Multivariable models were fitted to each SCHFI scale; separate models were run with DSM-5 disorders and PHQ-9 depression scores. Higher PHQ-9 depression scores were independently associated with lower (worse) scores on the SCHFI Maintenance (P < .05), Management (P < .01), and Confidence (P < .01) scales. No independent associations with DSM-5 depressive disorders were detected. Measures of perceived stress, anxiety, and low perceived social support were also significantly associated with poor HF self-care. CONCLUSIONS: Patients with a combination of psychosocial problems, including symptoms of depression, stress, anxiety, and inadequate social support, may be more likely than other patients to display difficulties with HF self-care that can increase their risk for hospitalization. Research is needed on "broad-spectrum" psychosocial interventions for patients with HF self-care deficits.

Left Ventricular Dysfunction and Depression in Hospitalized Patients with Heart Failure.

OBJECTIVE: This study examined whether the severity of left ventricular systolic dysfunction is associated with depression in patients with heart failure (HF). Other factors were also studied to identify independent correlates of depression in HF. METHODS: The sample consisted of 400 hospitalized patients with HF. Left ventricular ejection fraction and other medical data were obtained from medical records. Depression and other psychosocial characteristics were assessed by an interview and questionnaires. Proportional odds models were used to test the relationships of these characteristics to Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) depressive disorders, and analysis of covariance was used to test relationships with continuous measures of depression in secondary models. RESULTS: The models produced no evidence of an association between left ventricular ejection fraction and depression. The adjusted odds ratio (95% confidence interval) was 1.00 (0.98-1.01; p = .87) for depression diagnosis. Analysis of covariance estimates (standard errors) were -0.01 (0.02; p = .54) for the Hamilton Rating Scale for Depression and -0.01 (0.01; p = .59) for the Patient Health Questionnaire. The odds of depression were higher in African American patients and in those with high levels of anxiety or stress. Other characteristics that have been associated with depression in previous studies, including sex and age, were not consistently associated with depression in this study. CONCLUSIONS: There is no relationship between the severity of left ventricular systolic dysfunction and depression in hospitalized patients with HF. In contrast, African American patients and those with a high level of anxiety or perceived stress are more likely than other patients to have a comorbid depressive disorder.

Hybrid Systematic Review and Network Meta-Analysis of Randomized Controlled Trials of Interventions for Depressive Symptoms in Patients With Coronary Artery Disease.

OBJECTIVE: Depression is common in patients with coronary artery disease (CAD) and is associated with poor outcomes. Although different treatments are available, it is unclear which are best or most acceptable to patients, so we conducted a network meta-analysis of evidence from randomized controlled trials (RCTs) of different depression treatments to ascertain relative efficacy. METHODS: We searched for systematic reviews of RCTs of depression treatments in CAD and updated these with a comprehensive search for recent individual RCTs. RCTs comparing depression treatments (pharmacological, psychotherapeutic, combined pharmacological/psychotherapeutic, exercise, collaborative care) were included. Primary outcomes were acceptability (dropout rate) and change in depressive symptoms 8 week after treatment commencement. Change in 26-week depression and mortality were secondary outcomes. Frequentist, random-effects network meta-analysis was used to synthesize the evidence, and evidence quality was evaluated following Grading of Recommendations, Assessment, Development and Evaluations recommendations. RESULTS: Thirty-three RCTs (7240 participants) provided analyzable data. All treatments were equally acceptable. At 8 weeks, combination therapy (1 study), exercise (1 study), and antidepressants (10 studies) yielded the strongest effects versus comparators. At 26 weeks, antidepressants were consistently effective, but psychotherapy was only effective versus usual care. There were no differences in treatment groups for mortality. Grading of Recommendations, Assessment, Development and Evaluations ratings ranged from very low to low. CONCLUSIONS: Overall, the evidence was limited and biased. Although all treatments for post-CAD depression were equally acceptable, antidepressants have the most robust evidence base and should be the first-line treatment. Combinations of antidepressants and psychotherapy, along with exercise, could be more effective than antidepressants alone but require further rigorous, multiarm intervention trials.Systematic Review Registration: CRD42018108293 (International Prospective Register of Systematic Reviews).

Risk stratification after acute myocardial infarction by amplitude-frequency mapping of cyclic variation of heart rate.

BACKGROUND: Blunted cyclic variation of heart rate (CVHR), measured as a decrease in CVHR amplitude (Acv), predicts mortality risk after acute myocardial infarction (AMI). However, Acv also can be reduced in mild sleep apnea with mild O2 desaturation. We investigated whether Acv's predictive power for post-AMI mortality could be improved by considering the effect of sleep apnea severity. METHODS: In 24-hr ECG in 265,291 participants of the Allostatic State Mapping by Ambulatory ECG Repository project, sleep apnea severity was estimated by the frequency of CVHR (Fcv) measured by an automated algorithm for auto-correlated wave detection by adaptive threshold (ACAT). The distribution of Acv on the Acv-Fcv relation map was modeled by percentile regression, and a function converting Acv into percentile value was developed. In the retrospective cohort of the Enhancing Recovery in Coronary Heart Disease (ENRICHD) study, consisting of 673 survivors and 44 non-survivors after AMI, the mortality predictive power of percentile Acv calculated by the function was compared with that of unadjusted Acv. RESULTS: Among the ALLSTAR ECG data, low Acv values appeared more likely when Fcv was low. The logistic regression analysis for mortality in the ENRICHD cohort showed c-statistics of 0.667 (SE, 0.041), 0.817 (0.035), and 0.843 (0.030) for Fcv, unadjusted Acv, and the percentile Acv, respectively. Compared with unadjusted Acv, the percentile Acv showed a significant net reclassification improvement of 0.90 (95% CI, 0.51-1.42). CONCLUSIONS: The predictive power of Acv for post-AMI mortality is improved by considering its relation to sleep apnea severity estimated by Fcv.

Improving Quality of Life in Heart Failure.

PURPOSE OF REVIEW: Heart failure has substantial effects on health-related quality of life. Maintaining or improving quality of life is an important goal of heart failure therapy, and many patients value better quality of life over greater longevity. RECENT FINDINGS: The symptoms and functional severity of heart failure, medical comorbidities, and depression are the strongest predictors of poor quality of life. Guideline-recommended medical and behavioral interventions for HF, including exercise training and cardiac rehabilitation, self-care interventions, and treatment of depression, can help to improve quality of life. Heart failure is, in most cases, a progressive condition with a poor prognosis. However, poor quality of life is not inevitable, and a variety of medical, surgical, and nonpharmacological interventions can help to maintain or improve quality of life in patients with heart failure.

Moderators of Response to Cognitive Behavior Therapy for Major Depression in Patients With Heart Failure.

OBJECTIVE: Although cognitive behavior therapy (CBT) is efficacious for major depression in patients with heart failure (HF), approximately half of patients do not remit after CBT. To identify treatment moderators that may help guide treatment allocation strategies and serve as new treatment targets, we performed a secondary analysis of a randomized clinical trial. Based on evidence of their prognostic relevance, we evaluated whether clinical and activity characteristics moderate the effects of CBT. METHODS: Participants were randomized to enhanced usual care (UC) alone or CBT plus enhanced UC. The single-blinded outcomes were 6-month changes in Beck Depression Inventory total scores and remission (defined as a Beck Depression Inventory ≤ 9). Actigraphy was used to assess daily physical activity patterns. We performed analyses to identify the specific activity and clinical moderators of the effects of CBT in 94 adults (mean age = 58, 49% female) with HF and major depressive disorder. RESULTS: Patients benefited more from CBT (versus UC) if they had the following: more medically severe HF (i.e., a higher New York Heart Association class or a lower left ventricular ejection fraction), more stable activity patterns, wider active periods, and later evening settling times. These individual moderator effects were small (|r| = 0.10-0.21), but combining the moderators yielded a medium moderator effect size (r = 0.38; 95% CI = 0.20-0.52). CONCLUSIONS: These findings suggest that increasing the cross-daily stability of activity patterns, and prolonging the daily active period, might help increase the efficacy of CBT. Given moderating effects of HF severity measures, research is also needed to clarify and address factors in patients with less severe HF that diminish the efficacy of CBT. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01028625.

Residual Symptoms After Treatment for Depression in Patients With Coronary Heart Disease.

OBJECTIVE: Depression is associated with an increased risk of mortality in patients with coronary heart disease (CHD). The risk may be reduced in patients who remit with adequate treatment, but few patients achieve complete remission. The purpose of this study was to identify the symptoms that persist despite aggressive treatment for depression in patients with CHD. METHODS: One hundred twenty-five patients with stable CHD who met the DSM-IV criteria for a moderate-to-severe major depressive episode completed treatment with cognitive behavior therapy, either alone or combined with an antidepressant, for up to 16 weeks. Depression symptoms were assessed at baseline and after 16 weeks of treatment. RESULTS: The M (SD) Beck Depression Inventory scores were 30.0 (8.6) at baseline and 8.3 (7.5) at 16 weeks. Seventy seven (61%) of the participants who completed treatment met remission criteria (Hamilton Rating Scale for Depression ≤7) at 16 weeks. Loss of energy and fatigue were the most common posttreatment symptoms both in remitters (n = 44, 57%; n = 34, 44.2%) and nonremitters (n = 42, 87.5%; n = 35, 72.9%). These symptoms were not predicted by baseline depression severity, anxiety, demographic, or medical variables including inflammatory markers or cardiac functioning or by medical events during depression treatment. CONCLUSIONS: Fatigue and loss of energy often persist in patients with CHD even after otherwise successful treatment for major depression. These residual symptoms may increase the risks of relapse and mortality. Development of effective interventions for these persistent symptoms is a priority for future research.

Blunted cyclic variation of heart rate predicts mortality risk in post-myocardial infarction, end-stage renal disease, and chronic heart failure patients.

AIMS: Cyclic variation of heart rate (CVHR) associated with sleep-disordered breathing is thought to reflect cardiac autonomic responses to apnoeic/hypoxic stress. We examined whether blunted CVHR observed in ambulatory ECG could predict the mortality risk. METHODS AND RESULTS: CVHR in night-time Holter ECG was detected by an automated algorithm, and the prognostic relationships of the frequency (FCV) and amplitude (ACV) of CVHR were examined in 717 patients after myocardial infarction (post-MI 1, 6% mortality, median follow-up 25 months). The predictive power was prospectively validated in three independent cohorts: a second group of 220 post-MI patients (post-MI 2, 25.5% mortality, follow-up 45 months); 299 patients with end-stage renal disease on chronic haemodialysis (ESRD, 28.1% mortality, follow-up 85 months); and 100 patients with chronic heart failure (CHF, 35% mortality, follow-up 38 months). Although CVHR was observed in ≥96% of the patients in all cohorts, FCV did not predict mortality in any cohort. In contrast, decreased ACV was a powerful predictor of mortality in the post-MI 1 cohort (hazard ratio [95% CI] per 1 ln [ms] decrement, 2.9 [2.2-3.7], P < 0.001). This prognostic relationship was validated in the post-MI 2 (1.8 [1.4-2.2], P < 0.001), ESRD (1.5 [1.3-1.8], P < 0.001), and CHF (1.4 [1.1-1.8], P = 0.02) cohorts. The prognostic value of ACV was independent of age, gender, diabetes, ß-blocker therapy, left ventricular ejection fraction, sleep-time mean R-R interval, and FCV. CONCLUSION: Blunted CVHR detected by decreased ACV in a night-time Holter ECG predicts increased mortality risk in post-MI, ESRD, and CHF patients.

Smoking Cessation and Electronic Cigarettes in Community Mental Health Centers: Patient and Provider Perspectives.

Little is known about patients' electronic cigarette use, interest in and use of smoking cessation treatments, and providers' attitude towards such treatment. We assessed patients (N = 231) and providers (45 psychiatrists, 97 case workers) in four Community Mental Health Centers. Interestingly, 50% of smokers reported interest in using electronic cigarettes to quit smoking, and 22% reported current use. While 82% of smokers reported wanting to quit or reduce smoking, 91% of psychiatrists and 84% of case workers reported that patients were not interested in quitting as the lead barrier, limiting the provision of cessation interventions. Providers' assumption of low patient interest in treatment may account for the low rate of smoking cessation treatment. In contrast, patients report interest and active use of electronic cigarettes to quit smoking. This study highlights the need for interventions targeting different phases of smoking cessation in these patients suffering disproportionately from tobacco dependence.

Cardiac Risk Markers and Response to Depression Treatment in Patients With Coronary Heart Disease.

BACKGROUND: Depression is associated with an increased risk of mortality in patients with coronary heart disease. There is evidence that this risk may be reduced in patients who respond to depression treatment. The purpose of this study was to determine whether cardiac risk markers predict poor response to depression treatment and, second, whether they improve with successful treatment. METHODS: One hundred fifty-seven patients with stable coronary heart disease who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for a moderate to severe major depressive episode were treated with cognitive behavior therapy, either alone or combined with an antidepressant, for up to 16 weeks. Depression, physical activity, sleep quality, thyroid hormones (total thyroxine [T4] and free T4), and inflammatory blood markers (C-reactive protein, interleukin-6, tumor necrosis factor) were assessed at baseline and after 16 weeks of treatment. RESULTS: The mean (SD) Beck Depression Inventory scores were 30.2 (8.5) at baseline and 8.5 (7.8) at 16 weeks. More than 50% of the participants met the criteria for depression remission (17-item Hamilton Rating Scale for Depression ≤ 7) at 16 weeks. Only free T4 thyroid hormone at baseline predicted poor response to depression treatment after adjustment for potential confounders (p = .004). Improvement in sleep quality (p = .012) and physical activity level (p = .041) correlated with improvement in depression. None of the inflammatory markers predicted posttreatment depression or changed with depression. CONCLUSIONS: Thyroid hormone (T4) level predicted depression treatment outcome, and improvement in depression correlated with improvement in sleep and physical activity. More detailed studies of thyroid function and objective assessments of sleep and physical activity in relation to depression improvement and cardiac outcomes are needed.

Major Depression and Long-Term Survival of Patients With Heart Failure.

OBJECTIVES: Previous studies have found that depression predicts all-cause mortality in heart failure (HF), but little is known about its effect on long-term survival. This study examined the effects of depression on long-term survival in patients with HF. METHODS: Patients hospitalized with HF (n = 662) at an urban academic medical center were enrolled in a prospective cohort study between January 1994 and July 1999. Depression was assessed on a structured interview during the index hospitalization and on quarterly interviews for 1 year after discharge. Patients were classified at index as having Diagnostic and Statistical Manual, Fourth Edition major depressive disorder (n = 131), minor depression (n = 106), or no depression (n = 425). Clinical data and the National Death Index were used to identify date of death or last known contact through December 19, 2014, up to 20 years after the index hospitalization. The main outcome was time from enrollment to death from any cause. RESULTS: A total of 617 (94.1%) patients died during the follow-up period. Major depressive disorder was associated with higher all-cause mortality compared with no depression (adjusted hazard ratio = 1.64, 95% confidence interval = 1.27-2.11, p = .0001). This association was stronger than that of any of the established predictors of mortality that were included in the fully adjusted model. Patients with persistent or worsening depressive symptoms during the year after discharge were at greatest risk for death. The association between minor depression and survival was not significant. CONCLUSIONS: Major depression is an independent risk factor for all-cause mortality in patients with HF. Its effect persists for many years after the diagnosis of depression.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. METHODS AND RESULTS: Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. CONCLUSIONS: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

Sex dependent risk factors for mortality after myocardial infarction: individual patient data meta-analysis.

BACKGROUND: Although a number of risk factors are known to predict mortality within the first years after myocardial infarction, little is known about interactions between risk factors, whereas these could contribute to accurate differentiation of patients with higher and lower risk for mortality. This study explored the effect of interactions of risk factors on all-cause mortality in patients with myocardial infarction based on individual patient data meta-analysis. METHODS: Prospective data for 10,512 patients hospitalized for myocardial infarction were derived from 16 observational studies (MINDMAPS). Baseline measures included a broad set of risk factors for mortality such as age, sex, heart failure, diabetes, depression, and smoking. All two-way and three-way interactions of these risk factors were included in Lasso regression analyses to predict time-to-event related all-cause mortality. The effect of selected interactions was investigated with multilevel Cox regression models. RESULTS: Lasso regression selected five two-way interactions, of which four included sex. The addition of these interactions to multilevel Cox models suggested differential risk patterns for males and females. Younger women (age<50) had a higher risk for all-cause mortality than men in the same age group (HR 0.7 vs. 0.4), while men had a higher risk than women if they had depression (HR 1.4 vs. 1.1) or a low left ventricular ejection fraction (HR 1.7 vs. 1.3). Predictive accuracy of the Cox model was better for men than for women (area under the curves: 0.770 vs. 0.754). CONCLUSIONS: Interactions of well-known risk factors for all-cause mortality after myocardial infarction suggested important sex differences. This study gives rise to a further exploration of prediction models to improve risk assessment for men and women after myocardial infarction.

Nocturnal patterns of heart rate and the risk of mortality after acute myocardial infarction.

BACKGROUND: The purposes of this study were to identify nocturnal patterns of heart rate (HR) in depressed and nondepressed patients after an acute myocardial infarction (MI) and to determine which patterns, if any, are associated with all-cause mortality or recurrent infarction. METHODS: Functional data analysis and model-based clustering methods were used to identify nocturnal HR patterns in 245 depressed and 247 nondepressed patients with a recent MI. All-cause mortality and recurrent infarctions were ascertained over a median follow-up of 24 months. RESULTS: Three HR activity patterns were identified. In the first, HR gradually declined during the nighttime and increased the next morning. The second pattern was similar, but with a higher overall HR during the recording interval. The third showed almost no decrease in HR at night (ie, "nondipping"). All-cause mortality was higher among patients with pattern 3 than pattern 1 (P = .007), and the combined end point of recurrent MI or all-cause mortality was higher in pattern 3 than pattern 2 (P = .05). Patterns 2 and 3 were more common in the depressed than in the nondepressed patients. CONCLUSIONS: The nondipping nocturnal HR independently predicts all-cause mortality and recurrent MI. Future studies should examine the underlying causes of nondipping nocturnal HR and its association with depression and investigate the effects of treatment on survival.

The association between major depressive disorder in childhood and risk factors for cardiovascular disease in adolescence.

OBJECTIVE: Depression in adults is associated with risk factors for cardiovascular disease (CVD). It is unclear, however, when the association between clinical depression and cardiac risk factors develops or how early in life this association can be detected. METHODS: In an ongoing study of pediatric depression, we compared CVD risk factors including smoking, obesity, physical activity level, sedentary behavior, and parental history of CVD across three samples of adolescents: probands with established histories of childhood-onset major depressive disorder (n = 210), never-depressed siblings of probands (n = 195), and controls with no history of any major psychiatric disorder (n = 161). RESULTS: When assessed during adolescence, 85% of the probands were not in a major depressive episode. Nevertheless, at that assessment, probands had a higher prevalence of regular smoking (odds ratio [OR] = 12.54, 95% confidence interval [CI] = 4.36-36.12) and were less physically active than controls (OR = 0.59, CI = 0.43-0.81) and siblings (OR = 0.70, CI = 0.52-0.94) and had a higher rate of obesity than did controls (OR = 3.67, CI = 1.42-9.52). Parents of probands reported high rates of CVD (significantly higher than did parents of controls), including myocardial infarction and CVD-related hospitalization (ORs = 1.62-4.36, CIs = 1.03-15.40). Differences in CVD risk factors between probands and controls were independent of parental CVD. CONCLUSIONS: Major depression in childhood is associated with an unfavorable CVD risk profile in adolescence, and risks for pediatric depression and CVD may coincide in families. Effective prevention and treatment of childhood depression may be a means to reduce the incidence of adult CVD.

Association of anxiety disorders and depression with incident heart failure.

OBJECTIVE: Depression has been associated with increased risk of heart failure (HF). Because anxiety is highly comorbid with depression, we sought to establish if anxiety, depression, or their co-occurrence is associated with incident HF. METHODS: A retrospective cohort (N = 236,079) including Veteran's Administration patients (age, 50-80 years) free of cardiovascular disease (CVD) at baseline was followed up between 2001 and 2007. Cox proportional hazards models were computed to estimate the association between anxiety disorders alone, major depressive disorder (MDD) alone, and the combination of anxiety and MDD, with incident HF before and after adjusting for sociodemographics, CVD risk factors (Type 2 diabetes, hypertension, hyperlipidemia, obesity), nicotine dependence/personal history of tobacco use, substance use disorders (alcohol and illicit drug abuse/dependence), and psychotropic medication. RESULTS: Compared with unaffected patients, those with anxiety only, MDD only, and both disorders were at increased risk for incident HF in age-adjusted models (hazard ratio [HR] = 1.19 [ 95% confidence interval {CI} = 1.10-1.28], HR = 1.21 [95% CI = 1.13-1.28], and HR = 1.24 [95% CI = 1.17-1.32], respectively). After controlling for psychotropics in a full model, the association between anxiety only, MDD only, and both disorders and incident HF increased (HRs = 1.46, 1.56, and 1.74, respectively). CONCLUSIONS: Anxiety disorders, MDD, and co-occurring anxiety and MDD are associated with incident HF in this large cohort of Veteran's Administration patients free of CVD at baseline. This risk of HF is greater after accounting for protective effects of psychotropic medications. Prospective studies are needed to clarify the role of depression and anxiety and their pharmacological treatment in the etiology of HF.

Impact of sleep complaints and depression outcomes among participants in the standard medical intervention and long-term exercise study of exercise and pharmacotherapy for depression.

The aim of this study was to examine the effects of exercise and sertraline on disordered sleep in patients with major depressive disorder (MDD). Methods The Standard Medical Intervention and Long-term Exercise study randomized the patients with MDD (n = 202) to one of four arms: a) supervised exercise, b) home-based exercise, c) sertraline therapy, and d) placebo pill. Sleep disturbance was assessed with three sleep-related items from the Hamilton Rating Scale for Depression (HAM-D) before and after 4 months of treatment. The patients were followed for 12 months to assess the prognostic value of sleep disturbance on MDD relapse and recovery.Results Comparison of the active treatment and placebo groups showed no treatment differences in HAM-D sleep complaints after 4 months (p = 0.758). However, residual insomnia symptoms after treatment were strongly associated with elevated depressive symptoms assessed by the HAM-D after 4 months (ß = 0.342, p < 0.0001) and MDD relapse (odds ratio, 1.55; 95% confidence interval, 1.15-2.10; p = 0.004) assessed at 1-year follow-up (16 months after randomization). Neither exercise nor sertraline was associated with greater improvements in sleep disturbance compared with the placebo controls. However, residual symptoms of insomnia after successful treatment of MDD predicted relapse, highlighting the clinical importance of addressing insomnia in patients with MDD.