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Depression is a risk factor for cardiac morbidity and mortality in patients with coronary heart disease, especially in those with a recent history of acute coronary syndrome. To improve risk stratification and treatment planning, it would be useful to identify the characteristics or subtypes of depression that are associated with the highest risk of cardiac events. This paper reviews the evidence concerning several putative depression subtypes and symptom patterns that may be associated with a high risk of morbidity and mortality in cardiac patients, including single-episode major depressive disorder, depression that emerges after a cardiac event, somatic symptoms of depression, and treatment-resistant depression.

Background: Depression is a known risk factor for mortality after an acute myocardial infarction. Patients with treatment-responsive depression may have a better prognosis than those with treatment-resistant depression., Aims: We sought to determine whether mortality following acute myocardial infarction was associated with treatment-resistant depression., Method: Follow-up began after myocardial infarction and continued until death or censorship. Depression was counted as present if diagnosed any time during the study period. Treatment for depression was defined as receipt of 12 or more weeks of continuous antidepressant therapy at a therapeutic dose during follow-up. Treatment-resistant depression was defined as use of two or more antidepressants plus augmentation therapy, receipt of electroconvulsive therapy or use of monoamine oxidase inhibitors. Mean duration of follow-up was 39 months., Results: During follow-up of 4037 patients with major depressive disorder who had had a myocardial infarction, 6.9% of those with insufficiently treated depression, 2.4% of those with treated depression and 5.0% of those with treatment-resistant depression died. A multivariable survival model that adjusted for sociodemographics, anxiety disorders, beta-blocker use, mortality risk factors and health service utilisation indicated that compared with treated patients, insufficiently treated patients were 3.04 (95% CI 2.12-4.35) times more likely and patients with treatment-resistant depression were 1.71 (95% CI 1.05-2.79) times more likely to die., Conclusions: All-cause mortality following an acute myocardial infarction is greatest in patients with depression who are insufficiently treated and is a risk in patients with treatment-resistant depression. However, the risk of mortality associated with treatment-resistant depression is partly explained by comorbid disorders. Further studies are warranted to determine whether changes in depression independently predict all-cause mortality.

Archaeopteryx has been regarded as an icon of evolution ever since its discovery from the Late Jurassic limestone deposits of Solnhofen, Germany in 1861. Here we report the first evidence of colour from Archaeopteryx based on fossilized colour-imparting melanosomes discovered in this isolated feather specimen. Using a phylogenetically diverse database of extant bird feathers, statistical analysis of melanosome morphology predicts that the original colour of this Archaeopteryx feather was black, with 95% probability. Furthermore, reexamination of the feather's morphology leads us to interpret it as an upper major primary covert, contrary to previous interpretations. Additional findings reveal that the specimen is preserved as an organosulphur residue, and that barbule microstructure identical to that of modern bird feathers had evolved as early as the Jurassic. As in extant birds, the extensive melanization would have provided structural advantages to the Archaeopteryx wing feather during this early evolutionary stage of dinosaur flight.

Objective: Evidence from several clinical trials in patients with coronary heart disease suggests that depression that does not respond to treatment is associated with a particularly high risk of adverse cardiac outcomes. The purpose of this study was to determine whether obstructive sleep apnea/hypopnea syndrome (OSAHS) is associated with a poor response to antidepressant medication in patients with coronary heart disease., Method: This was a secondary analysis of data from a randomized, double-blind, placebo-controlled clinical trial of omega-3 fatty-acid augmentation of sertraline for depression in patients with coronary heart disease. Patients with documented coronary heart disease were recruited between May 2005 and December 2008 from cardiology practices in St Louis, Missouri, and through cardiac diagnostic laboratories affiliated with Washington University School of Medicine, St Louis, Missouri. One hundred five patients (mean age = 58 years) with coronary heart disease and current major depressive disorder (DSM-IV) were randomized to receive sertraline plus either omega-3 or placebo for 10 weeks. Cyclical heart-rate patterns associated with OSAHS were detected via ambulatory electrocardiography prior to treatment. Symptoms of depression were measured at baseline and follow-up with the Beck Depression Inventory-II (BDI-II) and the 17-item Hamilton Depression Rating Scale (HDRS-17). The primary endpoint was the BDI-II score at 10 weeks., Results: Thirty of the 105 patients (29%) were classified as having probable moderate to severe OSAHS on the basis of nighttime heart-rate patterns. These OSAHS patients had significantly higher scores on both the BDI-II (t = -2.78, P = .01) and the HDRS-17 (t = -2.33, P = .02) at follow-up as compared to the reference group. Adjustment for baseline depression score, treatment arm (omega-3 vs placebo), body mass index, and inflammatory markers did not change the results. Patients with OSAHS reported higher item scores at follow-up on all depressive symptoms measured with the BDI-II compared to those without OSAHS., Conclusions: Obstructive sleep apnea/hypopnea syndrome is associated with a relatively poor response to sertraline treatment for depression. Future research should determine the contribution of OSAHS to the increased risk of adverse cardiac outcome associated with treatment-resistant depression., (© Copyright 2012 Physicians Postgraduate Press, Inc.)

Background: Elevated scores on depression symptom questionnaires predict rehospitalization after acute myocardial infarction (AMI). Whether the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, depressive disorders predict rehospitalization after AMI is unknown., Methods and Results: Participants (n=766) in an Enhancing Recovery and Coronary Heart Disease ancillary study were classified by diagnostic interview as having no depression, minor depression, or major depression after AMI. Cardiac rehospitalizations were tracked for up to 42 months. Cox proportional hazards regression was used to model the effect of depressive disorder on time to first cardiac rehospitalization, controlling for mortality risk factors. Logistic regression was used to compare the accuracy with which rehospitalization could be predicted by depression diagnosis or by the Beck Depression Inventory (BDI). Secondary analyses examined the effects of depression on the cumulative number of all-cause rehospitalizations, length of stay, and emergency department visits. Compared with patients without depression, patients with either minor or major depression were hospitalized sooner (minor depression adjusted hazard ratio, 2.22; 95% CI, 1.59-3.08; P<0.001; major depression adjusted hazard ratio, 2.54; 95% CI, 1.84-3.53; P<0.001), had more hospitalizations (minor, P<0.001; major, P<0.001) and emergency department visits (minor, P=0.003; major, P<0.001), and spent more days in the hospital (minor, P<0.001; major, P<0.001). The interview and questionnaire methods of assessing depression did not significantly differ in their overall accuracy of predicting rehospitalization., Conclusions: Depressive disorders increase the risk of rehospitalization after AMI. Future work should focus on developing multivariable models to predict risk of rehospitalization after AMI, and depression should be included in these.

Introduction: This article discusses agomelatine (Valdoxan(™)/Thymanax(™); Servier/Novartis), which is a melatonin (MT1/MT2) agonist and serotonin (5-HT2c) receptor antagonist. Agomelatine has been approved for the treatment of adults with major depression by several regulatory agencies and is now on the market in 41 countries., Areas Covered: Literature related to agomelatine was reviewed on PubMed using the search terms 'agomelatine OR S-20098' and 204 articles were found. Twelve published, randomized, double-blind studies were included in this review., Expert Opinion: Agomelatine produces strong effects on circadian sleep phase disturbances, improving time to sleep onset and quality of sleep. It has been shown to be superior to placebo and similar to existing antidepressants, as demonstrated by short-term clinical trials and one relapse prevention trial. However, 0 - 0.6% and 3 - 4.5% of patients treated with 25 and 50 mg, respectively, showed elevated transaminases. Although none of these reactions so far seem to have been serious, the adverse effects in the liver may present a regulatory and marketing challenge. Given equivalence or modest superiority to existing, generic alternatives, the acceptability in a third-party reimbursement environment is questionable. Future clinical trials are needed to establish an appropriate market niche.

Non-Gaussianity index (λ) is a new index of heart rate variability (HRV) that characterizes increased probability of the large heart rate deviations from its trend. A previous study has reported that increased λ is an independent mortality predictor among patients with chronic heart failure. The present study examined predictive value of λ in patients after acute myocardial infarction (AMI). Among 670 post-AMI patients, we performed 24-h Holter monitoring to assess λ and other HRV predictors, including SD of normal-to-normal interval, very-low frequency power, scaling exponent α(1) of detrended fluctuation analysis, deceleration capacity, and heart rate turbulence (HRT). At baseline, λ was not correlated substantially with other HRV indices (|r| < 0.4 with either indices) and was decreased in patients taking β-blockers (P = 0.04). During a median follow-up period of 25 months, 45 (6.7%) patients died (32 cardiac and 13 non-cardiac) and 39 recurrent non-fatal AMI occurred among survivors. While all of these HRV indices but λ were significant predictors of both cardiac and non-cardiac deaths, increased λ predicted exclusively cardiac death (RR [95% CI], 1.6 [1.3-2.0] per 1 SD increment, P < 0.0001). The predictive power of increased λ was significant even after adjustments for clinical risk factors, such as age, diabetes, left ventricular function, renal function, prior AMI, heart failure, and stroke, Killip class, and treatment ([95% CI], 1.4 [1.1-2.0] per 1 SD increment, P = 0.01). The prognostic power of increased λfor cardiac death was also independent of all other HRV indices and the combination of increased λ and abnormal HRT provided the best predictive model for cardiac death. Neither λ nor other HRV indices was an independent predictor of AMI recurrence. Among post-AMI patients, increased λ is associated exclusively with increased cardiac mortality risk and its predictive power is independent of clinical risk factors and of other HRV predictors.

Objective: To investigate major depressive disorder (MDD), which complicates the course of type 2 diabetes and is associated with an increased risk of cardiovascular disease and death. This risk may be due to a greater susceptibility for myocardial infarction (MI) in depressed patients with type 2 diabetes compared with nondepressed patients with type 2 diabetes., Research Design and Methods: Veterans Administration electronic medical records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25 to 80 years. ICD-9-CM codes were used to create a four-level risk group indicating 1) neither diabetes nor MDD (n = 214,749), 2) MDD alone (n = 77,568), 3) type 2 diabetes alone (n = 40,953), and 4) comorbid MDD and type 2 diabetes (n = 12,679). Age-adjusted Cox proportional hazards models were computed before and after adjusting for baseline sociodemographic and time-dependent covariates., Results: After adjusting for covariates, patients with type 2 diabetes alone and patients with MDD alone were at ∼30% increased risk for MI, and patients with type 2 diabetes and MDD were at 82% increased risk for MI (hazard ratio 1.82 [95% CI 1.69-1.97]) compared with patients without either condition., Conclusions: Compared with patients with only diabetes or only MDD, individuals with type 2 diabetes and MDD are at increased risk for new-onset MI. Monitoring cardiovascular health in depressed patients with type 2 diabetes may reduce the risk of MI in this especially high-risk group.

The Dynamic Continuous-Area Space-Time (DYCAST) system is a biologically based spatiotemporal model that uses public reports of dead birds to identify areas at high risk for West Nile virus (WNV) transmission to humans. In 2005, during a statewide epidemic of WNV (880 cases), the California Department of Public Health prospectively implemented DYCAST over 32,517 km2 in California. Daily risk maps were made available online and used by local agencies to target public education campaigns, surveillance, and mosquito control. DYCAST had 80.8% sensitivity and 90.6% specificity for predicting human cases, and k analysis indicated moderate strength of chance-adjusted agreement for >4 weeks. High-risk grid cells (populations) were identified an average of 37.2 days before onset of human illness; relative risk for disease was >39× higher than for low-risk cells. Although prediction rates declined in subsequent years, results indicate DYCAST was a timely and effective early warning system during the severe 2005 epidemic.

Objective: Treatment-resistant depression has recently emerged as a marker of increased risk for morbidity and mortality in patients with coronary heart disease (CHD). Studies in depressed patients without CHD suggest that elevated markers of inflammation predict poor response to treatment. This may help to explain the increased risk of cardiac events associated with depression. We therefore studied the relationship between pretreatment markers of inflammation and treatment response in patients with CHD and major depression., Methods: This was a planned, secondary analysis of a clinical trial in which 122 patients with CHD and comorbid major depression were randomly assigned to 50 mg of sertraline plus 2 g/day omega-3 fatty acids or to 50 mg of sertraline plus 2 g/day corn oil placebo capsules for ten weeks. Depressive symptoms were assessed with the Beck Depression Inventory-II (BDI-II). Blood samples were collected at baseline to determine levels of high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). The primary outcome was the post-treatment BDI-II depression score., Results: Baseline levels of hs-CRP, IL-6, and TNF-α were not associated with the 10-week post-treatment depression score (P=.89, P=.88, and P=.31, respectively). Treatment responders (>50% reduction from baseline BDI-II score) did not differ from non-responders in either baseline hs-CRP, IL-6, or TNF-α (P=.83, P=.93, and P=.24, respectively). Similarly, depression remitters (BDI-II ≤8 at post-treatment) did not differ from non-remitters on the three baseline inflammation markers., Conclusion: These findings do not support the hypothesis that elevated baseline inflammatory markers predict poor response to sertraline in patients with CHD and major depression. The explanation for the increased risk of cardiac events associated with poor response to depression treatment remains unclear., (Copyright © 2010 Elsevier Inc. All rights reserved.)

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

Background: The long-term risk of myocardial infarction (MI) associated with use of antidepressants is uncertain, especially for nontricyclic antidepressants. The present study uses a national Veterans Affairs cohort to test whether antidepressants increase or decrease risk of MI and all-cause mortality., Methods: US Department of Veterans Affairs patient records were analyzed to identify a cohort free of cardiovascular disease in fiscal years 1999 and 2000, aged 25-80 years, who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating an episode of depression (n=93,653). Incident MI and all-cause mortality were modeled in patients who received 12 weeks or more of antidepressant pharmacotherapy as compared with 0-11 weeks during follow-up. Age-adjusted Cox proportional hazard models were computed before and after adjusting for baseline sociodemographics and time-dependent covariates., Results: Receipt of 12 or more weeks of continuous antidepressant therapy was associated with significantly reduced rates of incident MI across classes of antidepressants: selective serotonin reuptake inhibitor (SSRIs) (hazard ratio [HR] 0.48; 95% confidence interval [CI], 0.44-0.52), serotonin-norepinephrine reuptake inhibitors (SNRIs) (HR 0.35; 95% CI, 0.32-0.40), tricyclic antidepressants (TCAs) (HR 0.39; 95% CI, 0.34-0.44), and "Other" (HR 0.41; 95% CI, 0.37-0.45). Risk of all-cause mortality also was decreased with receipt of 12 weeks of pharmacotherapy with all classes of antidepressants (SSRI, SNRI, TCA, Other), with HRs ranging from 0.50 to 0.66., Conclusions: Across classes of antidepressants, 12 weeks of pharmacotherapy appears to be safe in terms of MI risk. Although the mechanism for this association remains uncertain, it is possible that compliance with pharmacotherapy for depression reflects compliance with cardiovascular medications. It also is possible that a direct drug effect or improved depressed mood may attenuate the risk of MI in depressed patients., (Published by Elsevier Inc.)

Background: Chronic low-grade systemic inflammation is a key component in atherogenesis. Decreased heart rate variability (HRV), a strong predictor of cardiovascular events, has been associated with elevations in circulating levels of C-reactive protein (CRP), interleukin (IL)-6, and fibrinogen in apparently healthy individuals. We investigated whether decreased HRV is associated with inflammatory markers in patients with coronary heart disease (CHD)., Methods: We studied the relationship between HRV and CRP, IL-6, and fibrinogen in 862 outpatients with CHD. All participants provided fasting blood samples and underwent 24-h ambulatory monitoring to assess time-domain measures of HRV (MeanNN, SDNN, SDANN, and RMSSD). Regression analyses were adjusted for age, sex, ethnicity, body mass index, smoking, diabetes, beta blocker use, and cardiopulmonary history., Results: MeanNN, SDNN, and SDANN were significantly and inversely associated with CRP and IL-6 levels in age-adjusted models and after adjustment for all covariates (p ≤ 0.02). MeanNN, SDNN, and SDANN were also inversely associated with fibrinogen levels in age-adjusted models (p < 0.03), but not significantly so in multivariable-adjusted models. Reduced vagal modulation of heart rate (RMSSD) was not significantly associated with any inflammatory measures., Conclusions: Reduced cardiac autonomic control is associated with increased systemic inflammation in patients with stable CHD. This relationship was largely independent of important covariates.

Depression is a common comorbid condition in heart failure, and there is growing evidence that it increases the risks of mortality and other adverse outcomes, including rehospitalization and functional decline. The prognostic value of depression depends, in part, on how it is defined and measured. The few studies that have compared different subsets of patients with depression suggest that major (or severe) depression is a stronger predictor of mortality than is minor (or mild) depression. Whether depression is a causal risk factor for heart failure mortality, or simply a risk marker, has not yet been established, but mechanistic research has identified several plausible behavioral and biologic pathways. Further research is needed to clarify the relationships among depression, heart failure, and adverse outcomes, as well as to develop efficacious interventions for depressive disorders in patients with heart failure., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Depression is a risk factor for incident myocardial infarction (MI), but little is known about the independent or additive risk from anxiety disorders., Methods: In a 7-year retrospective cohort design, we identified a cohort free of cardiovascular disease in fiscal years 1999 and 2000 that contained 96,612 patients between 25 and 80 years of age who had an International Classification of Diseases, Ninth Revision, Clinical Modification code indicating a diagnosis of depression in 2000 (baseline) and 259,387 patients without depression. Cox proportional hazards models stratified by depression were computed to test for a main effect of anxiety disorder unspecified, generalized anxiety disorder, panic disorder, social phobia, obsessive-compulsive disorder, and posttraumatic stress disorder (PTSD) on risk of incident MI. The models were adjusted for multiple MI risk factors and sociodemographics., Results: Depressed as compared to nondepressed Veterans Administration patients were at increased risk for incident MI (HR 1.39; 95% CI 1.34-1.45). In nondepressed patients those with anxiety disorder unspecified (HR 1.34; 95% CI 1.21-1.47), panic disorder (HR 1.43; 95% CI 1.11-1.83), and PTSD (HR 1.25; 95% CI 1.16-1.36) were at increased risk for incident MI. The independent risk associated with anxiety disorders was reduced in patients comorbid for depression., Conclusions: In Veterans Administration patients free of heart disease in 1999 and 2000, those with depression, anxiety disorder unspecified, panic disorder, and PTSD were at increased risk of incident MI. Anxiety disorders are independent risk factors for MI. Depression partially accounts for the effect of anxiety disorders on risk of MI in patients with both conditions., (Published by Mosby, Inc.)

Objective: This study evaluates whether depression is a risk factor for incident myocardial infarction (MI) in Department of Veterans Affairs (VA) patients with rheumatoid arthritis (RA) between 30 and 79 years of age., Methods: We used a retrospective cohort study of 15,634 patients with RA. Diagnoses and sociodemographic data were obtained from VA administrative and pharmacy databases between fiscal years 1999 and 2006. Entry into the cohort required 2 years of patient time with no evidence of cardiovascular disease. Cox proportional hazard models with time-dependent covariates were computed to determine whether RA patients with depression as compared to RA patients without depression were at increased risk for MI during the maximum 6-year follow-up period., Results: Unadjusted analyses indicated depressed RA patients were 1.4 times more likely than nondepressed RA patients to have an MI during follow-up. These results remained significant (HR=1.4; 95% CI: 1.1-1.8) in the adjusted Cox proportional hazards model which included the effects of sociodemographics and known physical risks (e.g., diabetes) for MI., Conclusions: Depressed RA patients, without a history of cardiovascular disease, are 40% more likely to have a heart attack as compared to those without depression. These data demonstrate a rapid (within 6 years) transition to MI following onset of depression in RA patients. Increased monitoring of depression and heart disease status in this patient population may be warranted which in turn may result in longer duration of life.

Depression is common in patients with coronary heart disease (CHD) and is a risk factor for cardiac morbidity and mortality in these patients. Depression is associated with autonomic nervous system dysfunction, which may at least partially explain this increased risk. Low heart rate variability (HRV), which reflects excessive sympathetic and/or inadequate parasympathetic modulation of heart rate, is a strong predictor of mortality in patients with CHD. Most studies-both in patients with stable CHD and in patients with a recent acute coronary event-have found HRV to be lower in depressed patients than in their nondepressed counterparts. This manuscript provides an overview of this literature and concludes that HRV may account for a substantial part of the risk associated with depression in CHD.

Depression is a risk factor for morbidity and mortality in patients with coronary heart disease, especially following acute coronary syndrome. Evidence from recent clinical trials suggests that treatment-resistant depression may be associated with a particularly high risk of mortality or cardiac morbidity in patients following acute coronary syndrome. This article reviews this evidence and considers possible explanations for this relationship. Directions for future research are also considered, with particular emphasis on efforts to elucidate the underlying mechanisms and to develop more efficacious treatments for depression in patients with coronary heart disease.

Context: There has been little research on the treatment of depression after coronary artery bypass surgery., Objective: To test the efficacy of 2 nonpharmacological interventions for depression after coronary artery bypass surgery compared with usual care., Design: A 12-week, randomized, single-blind clinical trial with outcome evaluations at 3, 6, and 9 months., Setting: Outpatient research clinic at Washington University School of Medicine, St Louis, Missouri., Patients: One hundred twenty-three patients who met the DSM-IV criteria for major or minor depression within 1 year after surgery., Intervention: Twelve weeks of cognitive behavior therapy or supportive stress management. Approximately half of the participants were taking nonstudy antidepressant medications., Main Outcome Measure: Remission of depression, defined as a score of less than 7 on the 17-item Hamilton Rating Scale for Depression., Results: Remission of depression occurred by 3 months in a higher proportion of patients in the cognitive behavior therapy (71%) and supportive stress-management (57%) arms than in the usual care group (33%) (chi(2)(2) = 12.22, P = .002). Covariate-adjusted Hamilton scores were lower in the cognitive behavior therapy (mean [standard error], 5.5 [1.0]) and the supportive stress-management (7.8 [1.0]) arms than in the usual care arm (10.7 [1.0]) at 3 months. The differences narrowed at 6 months, but the remission rates differed again at 9 months (73%, 57%, and 35%, respectively; chi(2)(2) = 12.02, P = .003). Cognitive behavior therapy was superior to usual care at most points on secondary measures of depression, anxiety, hopelessness, stress, and quality of life. Supportive stress management was superior to usual care only on some of the measures., Conclusions: Both cognitive behavior therapy and supportive stress management are efficacious for treating depression after coronary artery bypass surgery, relative to usual care. Cognitive behavior therapy had greater and more durable effects than supportive stress management on depression and several secondary psychological outcomes., Trial Registration: clinicaltrials.gov Identifier: NCT00042198.

Background: There is considerable evidence that depression and low social support are associated with increased morbidity and mortality for patients with coronary heart disease (CHD). However, there is a lack of consensus regarding the measurement of social support and its relation to depression., Purpose: The primary purpose of the present study was to identify key dimensions of existing social support and depression measures for patients with CHD using factor analysis., Method: Seven hundred-five patients with a recent acute myocardial infarction and either depression, low social support, or both, completed measures of several types of social support and depression. Exploratory and confirmatory factor analysis were used to examine the underlying dimensions of the existing social support and depression measures, and to compare theoretically plausible models specifying the relation between the social support and depression factors., Results: Confirmatory factor analysis indicated that an approach in which smaller facets of depression are measured (somatic, cognitive/affective, anxious) and social support (perceived emotional support from intimate relationships; perceived tangible support from peripheral contacts; and the number of children, relatives, and friends in a patient's support network), may be the most optimal way to measure social support and depression in this population RMSEA = 0.05; CFI = 0.81; TLI = 0.88)., Conclusion: Efforts to identify patients at increased psychosocial risk may be improved by screening for these subcomponents of social support and depression.

Context: Depressive symptoms predict adverse cardiovascular outcomes in patients with coronary heart disease, but the mechanisms responsible for this association are unknown., Objective: To determine why depressive symptoms are associated with an increased risk of cardiovascular events., Design and Participants: The Heart and Soul Study is a prospective cohort study of 1017 outpatients with stable coronary heart disease followed up for a mean (SD) of 4.8 (1.4) years., Setting: Participants were recruited between September 11, 2000, and December 20, 2002, from 12 outpatient clinics in the San Francisco Bay Area and were followed up to January 12, 2008., Main Outcome Measures: Baseline depressive symptoms were assessed using the Patient Health Questionnaire (PHQ). We used proportional hazards models to evaluate the extent to which the association of depressive symptoms with subsequent cardiovascular events (heart failure, myocardial infarction, stroke, transient ischemic attack, or death) was explained by baseline disease severity and potential biological or behavioral mediators., Results: A total of 341 cardiovascular events occurred during 4876 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 10.0% among the 199 participants with depressive symptoms (PHQ score > or = 10) and 6.7% among the 818 participants without depressive symptoms (hazard ratio [HR], 1.50; 95% confidence interval, [CI], 1.16-1.95; P = .002). After adjustment for comorbid conditions and disease severity, depressive symptoms were associated with a 31% higher rate of cardiovascular events (HR, 1.31; 95% CI, 1.00-1.71; P = .04). Additional adjustment for potential biological mediators attenuated this association (HR, 1.24; 95% CI, 0.94-1.63; P = .12). After further adjustment for potential behavioral mediators, including physical inactivity, there was no significant association (HR, 1.05; 95% CI, 0.79-1.40; P = .75)., Conclusion: In this sample of outpatients with coronary heart disease, the association between depressive symptoms and adverse cardiovascular events was largely explained by behavioral factors, particularly physical inactivity.

Approximately 20% of patients with coronary heart disease (CHD) have major depression and 20% have minor depression at any given point in the course of their illness. Depression causes significant psychological and social morbidity, and is a risk factor for further cardiac morbidity and mortality. Although there are many possible biological and behavioral mechanisms, the causal pathways through which depression increases the risk for cardiac events and death are not well understood. Despite the morbidity associated with depression, and the devastating impact it has on the quality of life of patients with CHD, it is underdiagnosed and often left untreated. This article describes screening techniques for use in primary care and cardiology settings, and discusses the safety and efficacy of available treatments for depression in patients with CHD.

Historically, data for genetic studies are collected at one time point. However, for diseases with late onset or with complex phenotypes, such as Alzheimer disease (AD), restricting diagnosis to a single ascertainment contact may not be sufficient. Affection status may change over time and some initial diagnoses may be inconclusive. Follow-up provides the opportunity to resolve these complications. However, to date, previous studies have not formally demonstrated that longitudinally re-contacting families is practical or productive. To update data initially collected for linkage analysis of late-onset Alzheimer disease (LOAD), we successfully re-contacted 63 of 81 (78%) multiplex families (two to 17 years after ascertainment). Clinical status changed for 73 of the 230 (32%) non-affected participants. Additionally, expanded family history identified 20 additional affected individuals to supplement the data set. Furthermore, fostering ongoing relationships with participating families helped recruit 101 affected participants into an autopsy and tissue donation program. Despite similar presentations, discordance between clinical diagnosis and neuropathologic diagnosis was observed in 28% of those with tissue diagnoses. Most of the families were successfully re-contacted, and significant refinement and supplementation of the data was achieved. We concluded that serial contact with longitudinal evaluation of families has significant implications for genetic analyses., (Copyright 2008 Wiley-Liss, Inc.)

In a large, prospectively followed, two-center cohort of patients listed for lung transplantation (n = 376), we used Cox proportional hazards models to determine the importance of baseline 6-min walk distance (6MWD) in predicting patient survival. 6MWD used as a continuous variable was a significant predictor of survival after adjusting for other important covariates when transplant was considered as a time-varying covariate (HR for each 500 ft increase in 6MWD = 0.57, 95% CI: 0.43-0.77, p = 0.0002). 6MWD remained an important predictor of survival in models that considered only survival to transplant (HR for each 500 ft increase in 6MWD = 0.41, 95% CI: 0.27-0.62, p < 0.0001) or survival only after transplant (HR for each 500 ft increase in 6MWD = 0.40, 95% CI: 0.22-0.72, p = 0.002). Unadjusted Kaplan-Meier analysis demonstrates significantly different survival by 6MWD tertiles (<900, 900-1200, or >1200 ft, p-value = 0.0001). In the overall model, 6MWD prediction of survival was relatively homogeneous across disease category (6MWD by disease interaction term, p-value = 0.63). Our results demonstrate a significant relationship between baseline 6MWD and survival among patients listed for lung transplantation that exists across all native disease categories and extends through transplantation. The 6MWD is thus a useful measure of both urgency and utility among patients awaiting lung transplantation.

Depression has been shown to be a risk factor for mortality during the 12 months following an acute myocardial infarction (MI), but few studies have examined whether it is associated with increased risk over longer periods. Most of the existing studies utilized depression questionnaires rather than diagnostic interviews, the gold standard for clinical depression diagnosis. The purpose of this study was to determine whether interview-diagnosed clinical depression affects survival for at least 5 years after an acute MI. Vital status was determined for 163 patients with major depression, 195 with minor depression or dysthymia, and 408 nondepressed patients, during a median follow-up period of 60 months after an acute MI. Survival analysis was used to model time from the index MI to death. There were 106 deaths during the follow-up. After adjusting for other risk factors for mortality, patients with either major or minor depression (HR=1.76; 95% CI: 1.19 to 2.60), major depression alone (HR=1.87; 95% CI: 1.17 to 2.98), or minor depression alone (HR=1.67; 95% CI: 1.06 to 2.64) were at higher risk for all-cause mortality compared to the nondepressed patients. Depression is an independent risk factor for death 5 years after an acute MI. Even minor depression is associated with an increased risk. Although it is not known whether treating depression can improve survival, patients with depression should be recognized as being at increased risk long after their acute MI.

Objective: Patients with end-stage lung disease (ESLD) experience significant decrements in quality of life (QOL). Although coping strategies are related to QOL in patients with ESLD, the extent to which specific native lung disease moderates this relationship is unknown., Methods: We investigated the relationship between coping, native lung disease, and QOL among 187 patients awaiting lung transplantation, including 139 patients with chronic obstructive pulmonary disease (COPD) and 48 with cystic fibrosis (CF). Participants completed a psychosocial battery assessing psychological QOL, physical QOL, and coping strategies., Results: For both COPD and CF patients, higher levels of Active Coping (P< .0001) and lower levels of Disengagement (P< .0001) were associated with better psychological QOL. For physical QOL, we observed a Native Disease x Coping interaction (P=.01) such that Active Coping was associated with better physical QOL in patients with COPD but not in patients with CF., Conclusions: The relationship between coping and QOL may vary as a function of native lung disease. Patients' native disease may need to be considered in order to develop effective interventions to help patients cope successfully with ESLD.

Epidemic transmission of West Nile virus (WNV) in Sacramento County, California, in 2005 prompted aerial application of pyrethrin, a mosquito adulticide, over a large urban area. Statistical analyses of geographic information system datasets indicated that adulticiding reduced the number of human WNV cases within 2 treated areas compared with the untreated area of the county. When we adjusted for maximum incubation period of the virus from infection to onset of symptoms, no new cases were reported in either of the treated areas after adulticiding; 18 new cases were reported in the untreated area of Sacramento County during this time. Results indicated that the odds of infection after spraying were approximately 6x higher in the untreated area than in treated areas, and that the treatments successfully disrupted the WNV transmission cycle. Our results provide direct evidence that aerial mosquito adulticiding is effective in reducing human illness and potential death from WNV infection.

Background: Patients with obstructive sleep apnea are reported to have a peak of sudden cardiac death at night, in contrast to patients without apnea whose peak is in the morning. We hypothesized that ventricular premature contraction (VPC) frequency would correlate with measures of apnea and sympathetic activity., Methods: Electrocardiograms from a sleep study of 125 patients with coronary artery disease were evaluated. Patients were categorized by apnea-hypopnea index (AHI) into Moderate (AHI <15) or Severe (AHI>15) apnea groups. Sleep stages studied were Wake, S1, S2, S34, and rapid eye movement (REM). Parameters of a potent autonomically-based risk predictor for sudden cardiac death called heart rate turbulence were calculated., Results: There were 74 Moderate and 51 Severe obstructive sleep apnea patients. VPC frequency was affected significantly by sleep stage (Wake, S2 and REM, F=5.8, p<.005) and by AHI (F=8.7, p<.005). In Severe apnea patients, VPC frequency was higher in REM than in Wake (p=.011). In contrast, patients with Moderate apnea had fewer VPCs and exhibited no sleep stage dependence (p=.19). Oxygen desaturation duration per apnea episode correlated positively with AHI (r(2)=.71, p<.0001), and was longer in REM than in non-REM (p<.0001). The heart rate turbulence parameter TS correlated negatively with oxygen desaturation duration in REM (r(2)=.06, p=.014)., Conclusions: Higher VPC frequency coupled with higher sympathetic activity caused by longer apnea episodes in REM sleep may be one reason for increased nocturnal death in apneic patients.

SNP rs498055 in the predicted gene LOC439999 on chromosome 10 was recently identified as being strongly associated with late-onset Alzheimer disease (LOAD). This SNP falls within a chromosomal region that has engendered continued interest generated from both preliminary genetic linkage and candidate gene studies. To independently evaluate this interesting candidate SNP we examined four independent datasets, three family-based and one case-control. All the cases were late-onset AD Caucasian patients with minimum age at onset >or= 60 years. None of the three family samples or the combined family-based dataset showed association in either allelic or genotypic family-based association tests at p < 0.05. Both original and OSA two-point LOD scores were calculated. However, there was no evidence indicating linkage no matter what covariates were applied (the highest LOD score was 0.82). The case-control dataset did not demonstrate any association between this SNP and AD (all p-values > 0.52). Our results do not confirm the previous association, but are consistent with a more recent negative association result that used family-based association tests to examine the effect of this SNP in two family datasets. Thus we conclude that rs498055 is not associated with an increased risk of LOAD.

Objective: To compare the impact of network support and different types of perceived functional support on all-cause mortality or nonfatal reinfarction for patients with a recent acute myocardial infarction (AMI)., Design: Participants were recruited from the Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial; 2,481 AMI patients with depression or low social support were randomized to a cognitive-behavioral intervention or to a usual care control group. Data collection for certain measures of social support was limited: 2,466 participants completed the ENRICHD Social Support Inventory; 2,457 completed the Perceived Social Support Scale; 1,296 completed the Social Network Questionnaire; and 707 completed the Interpersonal Support and Evaluation List, Tangible Support subscale. Patients also completed the Beck Depression Inventory and were followed for up to 4.5 years., Main Outcome Measure: Time to death or nonfatal reinfarction., Results: Over the follow-up period, 599 patients (24%) died or had a nonfatal AMI. Survival models controlling age, sex, race, socioeconomic status, smoking, antidepressant use, and a composite measure of increased risk revealed that higher levels of perceived social support were associated with improved outcome for patients without elevated depression but not for patients with high levels of depression. Neither perceived tangible support nor network support were associated with more frequent adverse events., Conclusion: AMI patients should be assessed for multiple dimensions of perceived functional support and depression to identify those at increased psychosocial risk who may benefit from treatment., (Copyright 2007 APA.)

Both the MIND-IT and the ENRICHD studies failed to show that medical outcomes of acute myocardial infarction can be improved by treating depression. However, neither study had sufficient statistical power to convincingly test this hypothesis. More effective treatments for depression will have to be developed if this hypothesis is to be tested with sufficient power in attainable samples.

Background: Depression is associated with an increased risk for cardiac morbidity and mortality in patients with coronary heart disease (CHD). Cardiac autonomic nervous system (ANS) dysregulation, proinflammatory processes, and procoagulant processes have been suggested as possible explanations., Methods: Heart rate variability (HRV), an indicator of cardiac autonomic regulation, and markers of inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha)] and coagulation (fibrinogen) were assessed in 44 depressed patients with CHD., Results: Moderate, negative correlations were found between fibrinogen and four measures of HRV. IL-6 also negatively correlated with one measure of HRV (total power) and was marginally related to two others (very low frequency and low frequency power). Neither CRP nor TNF-alpha was significantly related to any measure of HRV., Conclusions: The finding that fibrinogen and IL-6 are moderately related to HRV suggests a link between these factors in depressed CHD patients. The relationship between ANS function and inflammatory and coagulant processes should be investigated in larger mechanistic studies of depression and cardiac morbidity and mortality.

Objective: Both behavioural and physiological factors have been proposed as mechanisms that may explain the negative effect of depression on coronary heart disease (CHD). Our aim is to review some of the most important findings since our prior review., Method: We searched MEDLINE, PsycINFO, and other sources for recent studies of candidate mechanisms, with an emphasis on publications since 2002., Results: Physiological pathways have received far greater attention than behavioural ones in the emerging literature. Recent studies have identified shared genetic determinants, inflammation, blood clotting, and vascular mechanisms as plausible explanatory mechanisms., Conclusions: Future research should focus on relations between behavioural and physiological mechanisms and on the effects of pharmacologic and psychotherapeutic treatments for depression on candidate mechanisms.

Aim: Heart rate variability (HRV) patterns reflect the changing effect of sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, there is currently no method to measure ultradian cycles of HR and HRV., Materials and Methods: HR/HRV for each 2-min interval was calculated using normal-to-normal interbeat intervals from overnight polysomnographic ECGs in 113 subjects, aged 58+/-10 years (65 male, 48 female). HR, SDNN2, high-frequency power (HF) and the LF (low-frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Results were compared for older vs. younger patients, males vs. females, with vs. without severe sleep apnea, and for the upper and lower half of sleep efficiency., Results: Ultradian patterns for different HR/HRV indices had variable correspondences with each other and none could be considered surrogates. Differences were seen for all comparison groups, but no one marker was consistently different across comparisons., Conclusion: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Quantification of ultradian patterns of HRV is feasible and could provide new insights into autonomic physiology.

Impaired quality of life is associated with increased mortality in patients with advanced lung disease. Using a randomized controlled trial with allocation concealment and blinded outcome assessment at 2 tertiary care teaching hospitals, the authors randomly assigned 328 patients with end-stage lung disease awaiting lung transplantation to 12 weeks of telephone-based coping skills training (CST) or to usual medical care (UMC). Patients completed a battery of quality of life instruments and were followed for up to 3.4 years to assess all-cause mortality. Compared with UMC, CST produced lower scores on perceived stress, anxiety, depressive symptoms, and negative affect and improved scores on mental health functioning, optimism, vitality, and perceived social support. There were 29 deaths (9%) over a mean follow-up period of 1.1 year. Survival analyses revealed that there was no difference in survival between the 2 groups. The authors conclude that a telephone-based CST intervention can be effectively delivered to patients awaiting lung transplantation. Despite the severity of pulmonary disease in this patient population, significant improvements in quality of life, but not somatic measures or survival to transplant, were achieved., (Copyright 2006 APA, all rights reserved.)

Objective: Depression is a risk factor for cardiac events in patients with coronary heart disease (CHD). Obstructive sleep apnea/hypopnea syndrome (OSAHS) is frequently comorbid with depression and is also a risk factor for cardiac events. Undetected OSAHS could help explain the increased risk associated with depression., Methods: Medically stable patients with CHD and major (MD, n = 53), minor (md, n = 36), or no depression (ND, n = 43) were evaluated for 2 nights in a sleep medicine laboratory., Results: The prevalence of OSAHS did not differ across groups (MD 66%, md 69%, ND 77%; p > .05). Patients with MD had a significantly greater frequency of apneic episodes, a significantly longer duration of apneas and hyponeas, and more oxygen desaturations per hour than those with md, but there were no differences between MD and ND in frequency of apneic episodes or oxygen desaturations. However, males with MD tended to have more obstructive episodes per hour than did ND males, whereas females with MD had fewer episodes than did ND females. Apnea duration was longer in patients with MD compared with patients with no ND. There was no difference in the mean duration of apnea per hour between the md and ND groups., Conclusions: Although OSAHS is not more common in depressed patients with CHD, MD is associated with longer obstructive sleep apneic episodes in both men and women and with a higher frequency of episodes in men.

Unlabelled: Heart rate variability (HRV) patterns reflect the changing sympathetic and parasympathetic modulation of the autonomic nervous system. While overall and circadian heart rate (HR) and HRV are well characterized by traditional measures, ultradian cycles of HR and HRV are not. We have developed a method for capturing these rhythms during sleep and have now applied it to 24-hour recordings., Methods: HR/HRV for each 2-min was calculated using normal-to-normal (NN) interbeat intervals from 24-hour Holter recordings in 10 healthy subjects, aged 26 +/- 2 yrs, 5M, 5F. HR, the standard deviation of NN intervals (SDNN2), high frequency power (HF) and the LF (low frequency power)/HF ratio were plotted. A curve-fitting algorithm, developed in MatLab, identified cyclic patterns of HR/HRV and extracted parameters to characterize them. Values were compared to those obtained in nighttime-only recordings in a set of 113 subjects, aged 58 +/- 10 yrs, 65M, 48F., Results: Cyclic ultradian cycles were observed for each HR/HRV index. They had variable correspondences with each other and none could be considered surrogates. Although the number of cycles over 24 hours was greater, the mean cycle duration/number of cycles per hour was similar in both sets of recordings., Conclusions: Each HR/HRV parameter has its own rhythm, and the correspondence between these rhythms varies greatly across subjects. Although further studies are needed, it appears that there are intrinsic rhythms of autonomic modulation of HR on an scale of about 50 mins that persist during both the day and nighttimes. Quantification of ultradian patterns of HRV from 24-hour recordings is feasible and could provide new insights into autonomic physiology.

Objective: Depressive symptoms increase the risk of morbidity and mortality in patients with coronary heart disease (CHD). Mounting evidence indicates that inflammatory processes may underlie this association. This study examined whether depressive symptoms are associated with the dysregulation of inflammatory cytokine production in response to an in vitro infectious challenge., Methods: Forty-one patients with CHD were enrolled 3 months or more after an acute myocardial infarction or revascularization procedure. Depressive symptoms were assessed through self-report and interviewer ratings. Cytokine production was measured after white blood cells were cultured in vitro with endotoxin in the presence of varying concentrations of dexamethasone., Results: Depressive symptoms were not associated with the quantity of in vitro inflammatory cytokine production. However, to the extent that they reported symptoms of depression, patients showed greater sensitivity to the anti-inflammatory properties of glucocorticoids. This was manifested by increased suppression of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) production by dexamethasone., Conclusions: Increased sensitivity to glucocorticoid inhibition could render depressed patients vulnerable to latent infections and inflammatory processes that accelerate the progression of cardiac disease.

Objective: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research., Data Sources: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors., Study Selection/data Extraction: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed., Conclusions: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Background: Depression after myocardial infarction (MI) is associated with higher morbidity and mortality. Although antidepressants are effective in reducing depression, their use in patients with cardiovascular disease remains controversial., Objective: To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study., Design: Observational secondary analysis., Setting: Eight academic sites., Patients: The Enhancing Recovery in Coronary Heart Disease clinical trial randomized 2481 depressed and/or socially isolated patients from October 1, 1996, to October 31, 1999. Depression was diagnosed using a structured clinical interview. This analysis was conducted on the 1834 patients enrolled with depression (849 women and 985 men)., Intervention: Use of antidepressant medication., Main Outcome Measures: Event-free survival was defined as the absence of death or recurrent MI. All-cause mortality was also examined. To relate exposure to antidepressants to subsequent morbidity and mortality, the data were analyzed using a time-dependent covariate model., Results: During a mean follow-up of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR, 0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% CI, 0.32-0.90), compared with patients who did not use selective serotonin reuptake inhibitors. For patients taking non-selective serotonin reuptake inhibitor antidepressants, the comparable HRs (95% CIs) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73 (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent MI, respectively, compared with nonusers., Conclusions: Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality. A controlled trial is needed to examine this important issue.

Despite mounting evidence that depressive symptoms increase the risk of morbidity and mortality in patients who have coronary artery disease, little is known about the biologic mechanisms that underlie this association. This study examined whether depressive symptoms are associated with markers of infection and inflammation that have been implicated in the pathogenesis of coronary artery disease. Sixty-five patients who were recovering from an acute coronary syndrome were enrolled (63% men; mean age 61 years, 90% white). Depressive symptoms were assessed through self-report and observer ratings; the inflammatory molecules C-reactive protein, interleukin-6, and tumor necrosis factor-alpha were measured in serum, as were antibody titers to 3 latent viruses associated with atherosclerosis. Patients who had more severe depressive symptoms exhibited higher levels of C-reactive protein (r = 0.27, p = 0.03) and higher rates of seropositivity to the latent viruses (r = 0.41, p = 0.001). These effects were large in magnitude: patients in the highest tertile of the depression distribution had C-reactive protein levels >50% higher than did patients in the middle and lowest tertiles; they also were 2 times as likely to show evidence of infection with all 3 latent viruses. Disparities in the extent, severity, or management of cardiac disease were not responsible for these associations. These findings provide evidence that depressive symptoms are associated with increases in C-reactive protein and pathogen burden in patients who have coronary artery disease. In doing so, they highlight a mechanism through which depressive symptoms might foster morbidity and mortality among patients who have cardiac disease.