Peter de Jonge

Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: A meta-analysis

Objective: To assess the association of depression following myocardial infarction (MI) and cardiovascular prognosis. Methods: The authors performed a meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975–2003) combined with crossreferencing without language restrictions. The authors selected prospective studies that determined the association of depression with the cardiovascular outcome of MI patients, defined as mortality and cardiovascular events within 2 years from index MI. Depression had to be assessed within 3 months after MI using established psychiatric instruments. A quality assessment was performed. Results: Twenty-two papers met the selection criteria. These studies described follow up (on average, 13.7 months) of 6367 MI patients (16 cohorts). Post-MI depression was significantly associated with all-cause mortality (odds ratio [OR], fixed 2.38; 95% confidence interval [CI], 1.76–3.22; p <.00001) and cardiac mortality (OR fixed, 2.59; 95% CI, 1.77–3.77; p <.00001). Depressive MI patients were also at risk for new cardiovascular events (OR random, 1.95; 95% CI, 1.33–2.85; p = .0006). Secondary analyses showed no significant effects of follow-up duration (0–6 months or longer) or assessment of depression (self-report questionnaire vs. interview). However, the year of data collection (before or after 1992) tended to influence the effect of depression on mortality (p = .08), with stronger associations found in the earlier studies (OR, 3.22; 95% CI, 2.14–4.86) compared with the later studies (OR, 2.01; 95% CI, 1.45–2.78). Conclusions: Post-MI depression is associated with a 2- to 2.5-fold increased risk of impaired cardiovascular outcome. The association of depression with cardiac mortality or all-cause mortality was more pronounced in the older studies (OR, 3.22 before 1992) than in the more recent studies (OR, 2.01 after 1992). CI = confidence interval; CA = cardiac arrest; CABG = coronary artery bypass graft; CAD = coronary artery disease; DIS = modified version of the National Institute of Mental Health Diagnostic Interview Schedule; DM = diabetes mellitus; DSM = Diagnostic and Statistical Manual of Mental Disorders; DISH = Depression Interview and Structured Hamilton; ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients Randomized Trial; FU = follow up; HADS = hospital anxiety and depression scale; IHD = ischemic heart disease; KSb-S = Klinische Selbstbeurteilungsskalen aus dem Münchner psychiatrische Informations-System; LVEF = left ventricular ejection fraction; MADRS = Montgomery Asberg Depression Rating Scale; MI = myocardial infarction; MIND-IT = Myocardial INfarction and Depression–Intervention Trial; NA = not available; OR = odds ratio; PVC = premature ventricular contraction; SCID = Structured Clinical Interview for DSM; SCL-90 = 90-item Symptom Check List; SSRI = selective serotonin re-uptake inhibitor.

Depressive Symptoms, Health Behaviors, and Risk of Cardiovascular Events in Patients With Coronary Heart Disease

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.

Anxiety and Risk of Incident Coronary Heart Disease: A Meta-Analysis

OBJECTIVES The purpose of this study was to assess the association between anxiety and risk of coronary heart disease (CHD). BACKGROUND Less research has focused on the association of anxiety with incident CHD in contrast to other negative emotions, such as depression. METHODS A meta-analysis of references derived from PubMed, EMBASE, and PsycINFO (1980 to May 2009) was performed without language restrictions. End points were cardiac death, myocardial infarction (MI), and cardiac events. The authors selected prospective studies of (nonpsychiatric) cohorts of initially healthy persons in which anxiety was assessed at baseline. RESULTS Twenty studies reporting on incident CHD comprised 249,846 persons with a mean follow-up period of 11.2 years. Anxious persons were at risk of CHD (hazard ratio [HR] random: 1.26; 95% confidence interval [CI]: 1.15 to 1.38; p < 0.0001) and cardiac death (HR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003), independent of demographic variables, biological risk factors, and health behaviors. There was a nonsignificant trend for an association between anxiety and nonfatal MI (HR: 1.43; 95% CI: 0.85 to 2.40; p = 0.180). Subgroup analyses did not show any significant differences regarding study characteristics, with significant associations for different types of anxiety, short- and long-term follow-up, and both men and women. CONCLUSIONS Anxiety seemed to be an independent risk factor for incident CHD and cardiac mortality. Future research should examine the association between anxiety and CHD with valid and reliable anxiety measures and focus on the mechanisms through which anxiety might affect CHD.

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.

Quarterly Focus Issue: Prevention/OutcomesClinical Research: Cardiovascular RiskAnxiety and Risk of Incident Coronary Heart Disease: A Meta-Analysis

OBJECTIVES The purpose of this study was to assess the association between anxiety and risk of coronary heart disease (CHD). BACKGROUND Less research has focused on the association of anxiety with incident CHD in contrast to other negative emotions, such as depression. METHODS A meta-analysis of references derived from PubMed, EMBASE, and PsycINFO (1980 to May 2009) was performed without language restrictions. End points were cardiac death, myocardial infarction (MI), and cardiac events. The authors selected prospective studies of (nonpsychiatric) cohorts of initially healthy persons in which anxiety was assessed at baseline. RESULTS Twenty studies reporting on incident CHD comprised 249,846 persons with a mean follow-up period of 11.2 years. Anxious persons were at risk of CHD (hazard ratio [HR] random: 1.26; 95% confidence interval [CI]: 1.15 to 1.38; p < 0.0001) and cardiac death (HR: 1.48; 95% CI: 1.14 to 1.92; p = 0.003), independent of demographic variables, biological risk factors, and health behaviors. There was a nonsignificant trend for an association between anxiety and nonfatal MI (HR: 1.43; 95% CI: 0.85 to 2.40; p = 0.180). Subgroup analyses did not show any significant differences regarding study characteristics, with significant associations for different types of anxiety, short- and long-term follow-up, and both men and women. CONCLUSIONS Anxiety seemed to be an independent risk factor for incident CHD and cardiac mortality. Future research should examine the association between anxiety and CHD with valid and reliable anxiety measures and focus on the mechanisms through which anxiety might affect CHD.

Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis of 25 years of research

OBJECTIVE A meta-analysis of over 25 years of research into the relationship between post-myocardial infarction (MI) depression and cardiac prognosis was conducted to investigate changes in this association over time and to investigate subgroup effects. METHOD A systematic literature search was performed (Medline, Embase and PsycINFO; 1975–2011) without language restrictions. Studies investigating the impact of post-MI depression on cardiovascular outcome, defined as all-cause mortality, cardiac mortality and cardiac events within 24 months after the index MI, were identified. Depression had to be assessed within 3 months after MI using established instruments. Pooled odds ratios (ORs) were calculated using a random effects model. RESULTS A total of 29 studies were identified, resulting in 41 comparisons. Follow-up (on average 16 months) was described for 16,889 MI patients. Post-MI depression was associated with an increased risk of all-cause mortality [(OR), 2.25; 95% confidence interval [CI], 1.73-2.93; P<.001], cardiac mortality (OR, 2.71; 95% CI, 1.68–4.36; P<.001) and cardiac events (OR, 1.59; 95% CI, 1.37-1.85; P<.001). ORs proved robust in subgroup analyses but declined over the years for cardiac events. CONCLUSIONS Post-MI depression is associated with a 1.6- to 2.7-fold increased risk of impaired outcomes within 24 months. This association has been relatively stable over the past 25 years.

Prognostic Association of Anxiety Post Myocardial Infarction With Mortality and New Cardiac Events: A Meta-Analysis

Objective: To assess the association of anxiety after myocardial infarction (MI) with cardiac prognosis. Methods: A meta-analysis of references derived from MEDLINE, EMBASE, and PSYCINFO (1975–March 2009) was performed without language restrictions. End point was cardiac outcome defined as all-cause mortality, cardiac mortality, and cardiac events. The authors selected prospective studies with at least 6 months follow-up, and anxiety had to be assessed within 3 months after MI with reliable and valid instruments. Results: Twelve papers met selection criteria. These studies described follow-up (on average, 2.6 years) of 5750 patients with MI. Anxious patients were at risk of adverse events (odds ratio (OR) fixed, 1.36; 95% confidence interval (CI), 1.18–1.56; p < .001). Anxiety was also specifically associated with all-cause mortality (OR fixed, 1.47; 95% CI, 1.02–2.13; p = .04), cardiac mortality (OR fixed, 1.23; 95% CI, 1.03–1.47; p = .02), and new cardiac events (OR fixed, 1.71; 95% CI, 1.31–2.23; p < .001). Conclusions: Post-MI anxiety is associated with a 36% increased risk of adverse cardiac outcomes in bivariate analyses. Because the existing literature is small and contains several limitations, more research is needed to evaluate the association of anxiety and prognosis in patients with MI and to assess the extent to which this association is independent of clinical variables, such as disease severity, and other psychological variables, especially depression. BMI = body mass index; CABG = coronary artery bypass graft; CHD = coronary heart disease; CI = confidence interval; CBAHF = Cognitive Behavioral Assessment Hospital Form; ENRICHD = Enhancing Recovery in Coronary Heart Disease Patients; FEM = fixed effects model; GAD = generalized anxiety disorder; HADS = Hospital Anxiety and Depression Scale; HR = hazard ratio; LVEF = left ventricular ejection fraction; MI = myocardial infarction; MIND-IT = Myocardial Infarction and Depression Intervention Trial; NA = not available; OR = odds ratio; REM = random effects model; STAI = State Trait Anxiety Inventory; STPI = State Trait Personality Inventory; UA = unstable angina.

Emotional valence modulates brain functional abnormalities in depression: Evidence from a meta-analysis of fMRI studies

Models describing the neural correlates of biased emotion processing in depression have focused on increased activation of anterior cingulate and amygdala and decreased activation of striatum and dorsolateral prefrontal cortex. However, neuroimaging studies investigating emotion processing in depression have reported inconsistent results. This meta-analysis integrates these findings and examines whether emotional valence modulates such abnormalities. A systematic literature search identified 26 whole-brain and 18 region-of-interest studies. Peak coordinates and effect sizes were combined in an innovative parametric meta-analysis. Opposing effects were observed in the amygdala, striatum, parahippocampal, cerebellar, fusiform and anterior cingulate cortex, with depressed subjects displaying hyperactivation for negative stimuli and hypoactivation for positive stimuli. Anterior cingulate activity was also modulated by facial versus non-facial stimuli, in addition to emotional valence. Depressed subjects also showed reduced activity in left dorsolateral prefrontal cortex for negative stimuli and increased activity in orbitofrontal cortex for positive stimuli. Emotional valence is a moderator of neural abnormalities in depression, and therefore a critical feature to consider in models of emotional dysfunction in depression.

Scared to Death? Generalized Anxiety Disorder and Cardiovascular Events in Patients With Stable Coronary Heart Disease: The Heart and Soul Study

CONTEXT Anxiety is common in patients with coronary heart disease (CHD), but studies examining the effect of anxiety on cardiovascular prognosis and the role of potential mediators have yielded inconsistent results. OBJECTIVES To evaluate the effect of generalized anxiety disorder (GAD) on subsequent cardiovascular events and the extent to which this association is explained by cardiac disease severity and potential behavioral or biological mediators. DESIGN Prospective cohort study (Heart and Soul Study). 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 until March 18, 2009. PARTICIPANTS One thousand fifteen outpatients with stable CHD followed up for a mean (SD) of 5.6 (1.8) years. MAIN OUTCOME MEASURES We determined the presence of GAD using the Diagnostic Interview Schedule. Proportional hazards models were used to evaluate the association of GAD with subsequent cardiovascular events and the extent to which this association was explained by potential confounders and mediators. RESULTS A total of 371 cardiovascular events occurred during 5711 person-years of follow-up. The age-adjusted annual rate of cardiovascular events was 9.6% in the 106 participants with GAD and 6.6% in the 909 participants without GAD (P = .03). After adjustment for demographic characteristics, comorbid conditions (including major depressive disorder), cardiac disease severity, and medication use, GAD remained associated with a 62% higher rate of cardiovascular events (hazard ratio, 1.62; 95% confidence interval, 1.11-2.37; P = .01). Additional adjustment for a variety of potential behavioral and biological mediators had little effect on this association (hazard ratio, 1.74; 95% confidence interval, 1.13-2.67; P = .01). CONCLUSIONS In outpatients with CHD, a robust association between GAD and cardiovascular events was found that could not be explained by disease severity, health behaviors, or biological mediators. How GAD leads to poor cardiovascular outcomes deserves further study.

Identifying Depressive Subtypes in a Large Cohort Study: Results From the Netherlands Study of Depression and Anxiety (NESDA)

OBJECTIVE The heterogeneity of depression in the current classification system remains a point of discussion in the psychiatric field, despite previous efforts to subclassify depressive disorders. Data-driven techniques may help to come to a more empirically based classification. This study aimed to identify depressive subtypes within a large cohort of subjects with depression. METHOD Baseline data from 818 persons with a DSM-IV diagnosis of current major depressive disorder or minor depression who participated in the Netherlands Study of Depression and Anxiety were used. Respondents were recruited in the community, in primary care, and in specialized mental health care from September 2004 through February 2007. Latent classes were derived from latent class analysis using 16 depressive symptoms from the Composite International Diagnostic Interview and the Inventory of Depressive Symptomatology. Classes were characterized using demographic, clinical psychiatric, psychosocial, and physical health descriptors. RESULTS Three classes were identified: a severe melancholic class (prevalence, 46.3%), a severe atypical class (prevalence, 24.6%), and a class of moderate severity (prevalence, 29.1%). Both severe classes were characterized by more neuroticism (melancholic OR = 1.05 [95% CI, 1.01-1.10]; atypical OR = 1.07 [95% CI, 1.03-1.12]), more disability (melancholic OR = 1.07 [95% CI, 1.05-1.09]; atypical OR = 1.06 [95% CI, 1.04-1.07]), and less extraversion (melancholic OR = 0.95 [95% CI, 0.92-0.99]; atypical OR = 0.95 [95% CI, 0.92-0.99]) than the moderate class. Comparing the melancholic class with the atypical class revealed that the melancholic class had more smokers (atypical OR = 0.57 [95% CI, 0.39-0.84]) and more childhood trauma (atypical OR = 0.86 [95% CI, 0.74-1.00]), whereas the atypical class had more women (atypical OR = 1.52 [95% CI, 0.99-2.32]), a higher body mass index (atypical OR = 1.13 [95% CI, 1.09-1.17]), and more metabolic syndrome (atypical OR = 2.17 [95% CI, 1.38-3.42]). CONCLUSIONS Both depression severity (moderate vs severe) and the nature of depressive symptoms (melancholic vs atypical) were found to be important differentiators between subtypes. Higher endorsement rates of somatic symptoms and more metabolic syndrome in the atypical class suggest the involvement of a metabolic component.