Roy C. Ziegelstein

Even minimal symptoms of Depression increase mortality risk after acute myocardial infarction

Mild to moderate levels of depressive symptoms as characterized by Beck Depression Inventory (BDI) scores of > or =10 are associated with decreased survival after acute myocardial infarction (AMI). We investigated whether lower levels of depressive symptoms are also associated with increased mortality risk after AMI. We prospectively studied 285 patients with AMI who survived to discharge for evidence, at the time of hospitalization, of a DSM-IIIR mood disorder (using a structured clinical interview) and for symptoms of depression (using the BDI). The overall mortality rate at 4 months was 6.7%. Multiple logistic regression (chi-square 35.79, p < or =0.001) revealed that the independent predictors of mortality were: age > or =65 years, left ventricular ejection fraction <35%, diabetes mellitus, and any depression (DSM-IIIR mood disorder or BDI > or =10) present at the time of AMI. Among patients > or =65 years old with left ventricular ejection fraction <35%, the 4-month mortality was 12%. However, in this same group, those with any depression at the time of AMI had a 4-month mortality of 50% (relative risk 4.1, p = 0.01). Among patients aged > or =65 years, the mortality according to BDI scale grouping 0 to 3, 4 to 9, and 10+ was 2.6%, 17.1%, and 23.3%, respectively (p <0.002). Highest mortality rates were observed in patients with most severe depressive symptoms. However, compared with those without depression, higher mortality was also observed at very low levels of depressive symptoms (BDI 4 to 9) not generally considered clinically significant and below the level usually considered predictive of increased post-AMI mortality.

Prevalence of depression in survivors of acute myocardial infarction.

OBJECTIVES: To assess the prevalence and persistence of depression in patients with acute myocardial infarction (AMI) and the relationship between assessment modality and prevalence.DATA SOURCES: MEDLINE®, Cochrane, CINAHL®, PsycINFO®, and EMBASE®.REVIEW METHODS: A comprehensive search was conducted in March 2004 to identify original research studies published since 1980 that used a standardized interview or validated questionnaire to assess depression. The search was augmented by hand searching of selected journals from October 2003 through April 2004 and references of identified articles and reviews. Studies were excluded if only an abstract was provided, if not in English, or if depression was not measured by a validated method.RESULTS: Major depression was identified in 19.8% (95% confidence interval [CI] 19.1% to 20.6%) of patients using structured interviews (N=10,785, 8 studies). The prevalence of significant depressive symptoms based on a Beck Depression Inventory score ≥10 was 31.1% (CI 29.2% to 33.0%; N=2,273, 6 studies), using a Hospital Anxiety and Depression Scale (HADS) score ≥8%, 15.5% (CI 13.2% to 18.0%; N=863, 4 studies), and with a HADS score ≥11%, 7.3% (CI 5.5% to 9.3%; N=830, 4 studies). Although a significant proportion of patients continued to be depressed in the year after discharge, the limited number of studies and variable follow-up times precluded specification of prevalence rates at given time points.CONCLUSIONS: Depression is common and persistent in AMI survivors. Prevalence varies depending on assessment method, likely reflecting treatment of somatic symptoms.

Depression screening and patient outcomes in cardiovascular care: a systematic review

CONTEXT Several practice guidelines recommend that depression be evaluated and treated in patients with cardiovascular disease, but the potential benefits of this are unclear. OBJECTIVE To evaluate the potential benefits of depression screening in patients with cardiovascular disease by assessing (1) the accuracy of depression screening instruments; (2) the effect of depression treatment on depression and cardiac outcomes; and (3) the effect of screening on depression and cardiac outcomes in patients in cardiovascular care settings. DATA SOURCES MEDLINE, PsycINFO, CINAHL, EMBASE, ISI, SCOPUS, and Cochrane databases from inception to May 1, 2008; manual journal searches; reference list reviews; and citation tracking of included articles. STUDY SELECTION We included articles in any language about patients in cardiovascular care settings that (1) compared a screening instrument to a valid major depressive disorder criterion standard; (2) compared depression treatment with placebo or usual care in a randomized controlled trial; or (3) assessed the effect of screening on depression identification and treatment rates, depression, or cardiac outcomes. DATA EXTRACTION Methodological characteristics and outcomes were extracted by 2 investigators. RESULTS We identified 11 studies about screening accuracy, 6 depression treatment trials, but no studies that evaluated the effects of screening on depression or cardiovascular outcomes. In studies that tested depression screening instruments using a priori-defined cutoff scores, sensitivity ranged from 39% to 100% (median, 84%) and specificity ranged from 58% to 94% (median, 79%). Depression treatment with medication or cognitive behavioral therapy resulted in modest reductions in depressive symptoms (effect size, 0.20-0.38; r(2), 1%-4%). There was no evidence that depression treatment improved cardiac outcomes. Among patients with depression and history of myocardial infarction in the ENRICHD trial, there was no difference in event-free survival between participants treated with cognitive behavioral therapy supplemented by an antidepressant vs usual care (75.5% vs 74.7%, respectively). CONCLUSIONS Depression treatment with medication or cognitive behavioral therapy in patients with cardiovascular disease is associated with modest improvement in depressive symptoms but no improvement in cardiac outcomes. No clinical trials have assessed whether screening for depression improves depressive symptoms or cardiac outcomes in patients with cardiovascular disease.

Calcium signaling and oxidant stress in the vasculature

Recent evidence suggests that oxidant stress plays a major role in several aspects of vascular biology. Oxygen free radicals are implicated as important factors in signaling mechanisms leading to vascular pathologies such as postischemic reperfusion injury and atherosclerosis. The role of intracellular Ca(2+) in these signaling events is an emerging area of vascular research that is providing insights into the mechanisms mediating these complex physiological processes. This review explores sources of free radicals in the vasculature, as well as effects of free radicals on Ca(2+) signaling in vascular endothelial and smooth muscle cells. In the endothelium, superoxides enhance and peroxides attenuate agonist-stimulated Ca(2+) responses, suggesting differential signaling mechanisms depending on radical species. In smooth muscle cells, both superoxides and peroxides disrupt the sarcoplasmic reticulum Ca(2+)-ATPase, leading to both short- and long-term effects on smooth muscle Ca(2+) handling. Because vascular Ca(2+) signaling is altered by oxidant stress in ischemia-related disease states, understanding these pathways may lead to new strategies for preventing or treating arterial disease.

The prevalence of anxiety and depression in adults with implantable cardioverter defibrillators: A systematic review

OBJECTIVE The implantable cardioverter defibrillator (ICD) is used to treat life-threatening ventricular arrhythmias and in the prevention of sudden cardiac death. A significant proportion of ICD patients experience psychological symptoms including anxiety, depression or both, which in turn can impact adjustment to the device. The objective of this systematic review was to assess the prevalence of anxiety and depression or symptoms of anxiety and depression among adults with ICDs. METHODS Search of MEDLINE®, CINAHL®, PsycINFO®, EMBASE® and Cochrane® for English-language articles published through 2009 that used validated diagnostic interviews to diagnose anxiety or depression or self-report questionnaires to assess symptoms of anxiety or depression in adults with an ICD. RESULTS Forty-five studies that assessed over 5000 patients were included. Between 11% and 28% of patients had a depressive disorder and 11-26% had an anxiety disorder in 3 small studies (Ns=35-90) that used validated diagnostic interviews. Rates of elevated symptoms of anxiety (8-63%) and depression (5-41%) based on self-report questionnaires ranged widely across studies and times of assessment. Evidence was inconsistent on rates pre- versus post-implantation, rates over time, rates for primary versus secondary prevention, and for shocked versus non-shocked patients. CONCLUSION Larger studies utilizing structured interviews are needed to determine the prevalence of anxiety and depression among ICD patients and factors that may influence rates of anxiety and depressive disorders. Based on existing data, it may be appropriate to assume a 20% prevalence rate for both depressive and anxiety disorders post-ICD implant, a rate similar to that in other cardiac populations.

The Significance of Depression in Older Patients After Myocardial Infarction

OBJECTIVES: Depression is common in patients recovering from a myocardial infarction (MI) and is an independent risk factor for early mortality. Although most patients with MI are aged 65 and older, there is little information about post‐MI depression in this age group. This study was performed to determine the significance of post‐MI depression in individuals aged 65 and older.

[Ca2+] i Oscillation Frequency Regulates Agonist-stimulated NF-κB Transcriptional Activity

In nonexcitable cells, stimulation by high agonist concentrations typically produces a biphasic increase in cytosolic Ca2+ ([Ca2+] i ). This response is characterized by a transient initial increase because of intracellular Ca2+ release followed by a sustained elevation which varies in amplitude depending on the nature of the stimulus. In contrast, low-level stimulation often evokes oscillatory changes in [Ca2+] i . The specific information provided by repetitive [Ca2+] i spikes appears to be encoded in the frequency rather than in the amplitude of [Ca2+] i oscillations. The specific, membrane-permeable inositol 1,4,5-trisphosphate (Ins-1,4,5-P3) receptor blocker Xestospongin C (XeC, 2–20 μm) was used to affect [Ca2+] i signaling in human aortic endothelial cells (HAEC) during an established response to low-level (1 μm) histamine stimulation. XeC produced a dose-dependent decrease in the frequency of [Ca2+] i oscillations during histamine stimulation without affecting oscillation amplitude. Histamine stimulated a 14-fold increase in NF-κB-chloramphenicol acetyltransferase reporter gene activity that was dose-dependently decreased by XeC. Thus, during low-level agonist stimulation, [Ca2+] i oscillation frequency regulates nuclear transcription in HAEC.

Hydrogen peroxide induces intracellular calcium oscillations in human aortic endothelial cells

BACKGROUND Because the vascular endothelium is exposed to oxidant stress resulting from ischemia/reperfusion and from the products of polymorphonuclear leukocytes or monocytes, studies were performed to examine the effect of hydrogen peroxide (1 micromol/L to 10 mmol/L) on endothelial Ca2+ signaling. METHODS AND RESULTS At low concentrations (1 to 10 micromol/L), hydrogen peroxide did not affect intracellular Ca2+ concentration in subconfluent, indo 1-loaded human aortic endothelial monolayers. At a concentration of 100 micromol/L hydrogen peroxide, intracellular free Ca2+ gradually increased from 125.3+/-6.8 to 286.3+/-19.9 nmol/L over 4.2+/-0.9 minutes before repetitive Ca2+ oscillations were observed, consisting of an initial large, transient spike of approximately 1 micromol/L followed by several spikes of decreasing amplitudes at a frequency of 0.7+/-0.1 min-1 over 12.0+/-1.1 minutes. After these oscillations, intracellular Ca2+ reached a plateau of 543.4+/-64.0 nmol/L, which was maintained above baseline levels for >5 minutes and then partially reversible on washout of hydrogen peroxide in most monolayers. Intracellular Ca2+ oscillations were typically observed when monolayers were exposed to 100 to 500 micromol/L hydrogen peroxide. Higher concentrations of hydrogen peroxide (1 and 10 mmol/L) increased intracellular Ca2+ but only rarely (2 of 6 monolayers at 1 mmol/L) or never (at 10 mmol/L) stimulated intracellular Ca2+ oscillations. Removal of Ca2+ from the buffer either before hydrogen peroxide stimulation or during an established response did not block intracellular Ca2+ oscillations in response to 100 micromol/L hydrogen peroxide, but prior depletion of an intracellular Ca2+ store with either caffeine, histamine, or thapsigargin abolished Ca2+ oscillations. CONCLUSIONS Hydrogen peroxide induces concentration-dependent intracellular Ca2+ oscillations in human endothelial cells, which results from release of an endoplasmic reticulum Ca2+ store. Because oxidant production appears to occur in the micromolar range in the postischemic/anoxic endothelium and is associated with impaired endothelium-dependent relaxation, the effects of micromolar concentrations of hydrogen peroxide on endothelial Ca2+ signaling described in the present study may be important in the pathogenesis of postischemic endothelial dysfunction.

Rethinking recommendations for screening for depression in primary care

Screening for depression in primary care is an issue that is highly contentious and hotly debated, and recommendations have evolved over time. For example, early policy statements from the 1990s in Canada[1][1] and the United States[2][2] recommended against screening for depression in primary care[

The mirror and "the village": a new method for teaching practice-based learning and improvement and systems-based practice.

Purpose Practice-based learning and improvement (PBLI) and systems-based practice (SBP) may be conceptually difficult for both residents and faculty. Methods for introducing these concepts are needed if PBLI and SBP are to be incorporated into education and practice. Method In 2001, PBLI and SBP were introduced at Johns Hopkins Bayview Medical Center in Baltimore, Maryland, using the metaphors “the mirror” and “the village.” PBLI was likened to residents’ holding up a mirror to document, assess, and improve their practice. Specific tools for residents (e.g., weekly morbidity and mortality morning reports, continuity clinic chart self-audits, and resident learning portfolios) became the mirrors. SBP was introduced through specific training activities (e.g., multidisciplinary patient care rounds, nursing evaluations, and quality assessment-systems improvement exercises) using the metaphor of the village made famous by Hillary Clinton in the phrase: “It takes a village to raise a child.” Residents completed a questionnaire in which they rated these initiatives’ impact on their training. Results The majority of residents who participated in specific activities agreed that quality assessment-systems improvement exercises (92.9%), multidisciplinary rounds (92.1%), morbidity and mortality morning reports (86.8%), clinic chart self-audits (76.4%), and nursing evaluations (52.8%) helped to improve their proficiency in specific aspects of PBLI and SBP. Residents’ retrospective self-assessments of their PBLI abilities demonstrated significant improvement after the introduction of specific training activities. Conclusions PBLI and SBP can be introduced effectively in residency training by incorporating specific activities that use the metaphors of the mirror and the village.