Joost P. van Melle

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.

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.

Treatment of post-myocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine.

Objective: To examine the antidepressant efficacy of a dual-acting antidepressant (mirtazapine) in patients with post-myocardial infarction (MI) depressive disorder. Antidepressants used in post MI trials with a randomized, double-blind, placebo-controlled design have been restricted to selective serotonin reuptake inhibitors (SSRIs). Antidepressant effects have been limited. Methods: In a prospective multicenter study, 2177 patients with MI were evaluated for depressive disorder during the first year post MI. Ninety-one patients who met the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for major or minor depressive disorder were randomized to a 24-week, double-blind, placebo-controlled trial. Antidepressant efficacy was tested using last-observation-carried-forward procedure and repeated measurements analysis using the SPPS mixed models approach, with as primary outcome reduction in depressive symptomatology on the 17-item Hamilton-Depression Rating Scale (Ham-D), and secondary outcomes the Beck Depression Inventory (BDI) and depression subscale of the Symptom Check List 90 items (dSCL-90) as well as the Clinical Global Impression (CGI) scale. Results: Using the “last observation carried forward” (LOCF) method, mirtazapine did not show to be superior to placebo on the Ham-D, but did on the BDI, dSCL-90, and CGI scale over the acute treatment phase of 8 weeks (n = 91). Using mixed models analysis over the entire 24 weeks of treatment (n = 40), we did find a significant difference favoring mirtazapine to placebo on the Ham-D, BDI, and CGI, but on the dSCL-90, this difference was not significant. Conclusions: This trial shows efficacy of mirtazapine on primary and secondary depression measures. Mirtazapine seems to be safe in the treatment of post-MI depression. MI = myocardial infarction; RCT = randomized controlled trial; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders; CAD = coronary artery disease; SSRI = selective serotonin reuptake inhibitors; TCA = tricyclic antidepressant; Ham-D = Hamilton-Depression Rating Scale; BDI = Beck Depression Inventory; CGI = Clinical Global Impression; dSCL-90 = Symptom Check List 90 items, depression subscale; SES = standardized effect size.

Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure.

Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg(-1)·day(-1)). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

Differential associations between specific depressive symptoms and cardiovascular prognosis in patients with stable coronary heart disease.

OBJECTIVES The purpose of this research was to evaluate the relationship between cognitive and somatic depressive symptoms and cardiovascular prognosis. BACKGROUND Depression in patients with stable coronary heart disease (CHD) is associated with poor cardiac prognosis. Whether certain depressive symptoms are more cardiotoxic than others is unknown. METHODS In the Heart and Soul Study, 1,019 patients with stable CHD were assessed using the Patient Health Questionnaire to determine the presence of the 9 depressive symptoms included in the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. The mean age of the patients was 67 years, and 82% were men. A comparison was made on a new cardiovascular event (myocardial infarction, stroke, transient ischemic attack, or congestive heart failure) or death (mean follow-up duration 6.1 +/- 2.0 years) on the basis of cognitive and somatic sum scores and for patients with or without each of those specific depressive symptoms. Demographic characteristics, cardiac risk factors, and cardiac medications were controlled for. RESULTS After adjustment for demographic data and cardiac risk factors, each somatic symptom was associated with 14% greater risk for events (hazard ratio [HR]: 1.14; 95% confidence interval [CI]: 1.05 to 1.24; p = 0.002). Fatigue (HR: 1.34; 95% CI: 1.07 to 1.67; p = 0.01), appetite problems (HR: 1.46; 95% CI: 1.12 to 1.91; p = 0.005), and sleeping difficulties (HR: 1.26; 95% CI: 1.00 to 1.58; p = 0.05) were most strongly predictive of cardiovascular events. In contrast, cognitive symptoms (HR: 1.08; 95% CI: 0.99 to 1.17; p = 0.09) were not significantly associated with cardiovascular events. CONCLUSIONS In patients with stable CHD, somatic symptoms of depression were more strongly predictive of cardiovascular events than cognitive symptoms, although the CIs surrounding these estimates had substantial overlap. These findings are highly consistent with those of previous studies. Further research is needed to understand the pathophysiological processes by which somatic depressive symptoms contribute to prognosis in patients with CHD.

Psychophysiological biomarkers explaining the association between depression and prognosis in coronary artery patients: a critical review of the literature.

This paper aims to provide an overview of the current state of affairs on psychophysiological factors that may explain the link between depression and adverse outcome in coronary artery disease (CAD) patients. Factors discussed include heart rate variability, inflammation, platelet function, hypothalamus-pituitary-adrenal axis activity, serotonin metabolism and polyunsaturated fatty acids. Evidence suggests the involvement of each of these factors in both depression and CAD, together contributing to the prospective association between depression and cardiac outcome. Unfortunately, the involvement of above factors has been evaluated mostly in isolation, despite their functional interrelations and associations with behavioral factors. Moreover, there may be specific relations between individual symptoms of depression and certain psychophysiological mechanisms, rather than with general depression, further complicating the notion of depression as a cardiotoxic factor. The relatively understudied complexity of the relation between depression and CAD may serve as an explanation for the finding that depression treatment does not or barely affect cardiac outcome. Future studies should focus on the network of psychophysiological (and behavioral) factors to elucidate their precise role and timing in depressed cardiac patients.

Impact of bosentan on exercise capacity in adults after the Fontan procedure : a randomized controlled trial

An endothelin‐1 receptor blocker, shown to be effective in patients with pulmonary arterial hypertension, might decrease pulmonary vascular resistance to increase cardiac filling and consequently improve exercise capacity in Fontan patients.

Illness perceptions of adults with congenital heart disease and their predictive value for quality of life two years later

Background: To improve patients’ quality of life (QoL) we need to identify modifiable determinants, such as illness perceptions. Patients’ illness perceptions are known to regulate emotional responses and health-behaviour. Illness perceptions comprise several components: consequences, control, coherence, changeability and emotional representations. Aims: To examine (a) the relation between patient characteristics and illness perceptions, and (b) the independent predictive value of illness perceptions for future QoL. Methods: A longitudinal study in 845 patients with congenital heart disease was conducted. Patients completed three questionnaires: the IPQ-R (illness perceptions) and two years later the SF-36 and TAAQOL-CHD (QoL). Linear regression analyses were performed relating illness perceptions to patient characteristics (sex, age, disease complexity and functional status) and QoL. Results: Patients with a complex defect or poor functional status reported poor illness perceptions. Independent of patient characteristics, poor illness perceptions (i.e. a strong belief that the illness has severe consequences; a weak belief that you have a coherent illness understanding and that the illness can be controlled by treatment; and a strong belief that the illness is changeable and causes negative emotions) were predictive of future QoL. Conclusion: Illness perceptions independently predict QoL, suggesting that QoL may be improved by altering patients’ beliefs about their illness. For example, increasing patients’ knowledge regarding their disease and informing them about treatment opportunities may enhance their QoL.

Diabetes, Glycemic Control, and New-Onset Heart Failure in Patients With Stable Coronary Artery Disease: Data from the Heart and Soul Study

OBJECTIVE Diabetes is a predictor of both coronary artery disease (CAD) and heart failure. It is unknown to what extent the association between diabetes and heart failure is influenced by other risk factors for heart failure. RESEARCH DESIGN AND METHODS We evaluated the association of diabetes and A1C with incident heart failure in outpatients with stable CAD and no history of heart failure (average follow-up 4.1 years). RESULTS Of 839 participants, 200 had diabetes (23.8%). Compared with patients who did not have diabetes, those with diabetes had an increased risk of heart failure (hazard ratio [HR] 2.17 [95% CI 1.37–3.44]). Adjustment for risk factors for CAD (age, sex, race, smoking, physical inactivity, obesity, blood pressure, and LDL cholesterol), interim myocardial infarction, and myocardial ischemia did not alter the strength of the association between diabetes and heart failure. After inclusion also of other risk factors for heart failure (left ventricular ejection fraction, diastolic dysfunction, and C-reactive protein) and medication use, diabetes remained an independent predictor of heart failure (HR 3.34 [95% CI 1.65–6.76]; P = 0.001). Each 1% increase in A1C concentration was associated with a 36% increased HR of heart failure hospitalization (HR 1.36 [95% CI 1.17–1.58]). CONCLUSIONS In patients with stable CAD who are free from heart failure at baseline, diabetes and glycemic control are independent risk factors for new-onset heart failure. The mechanisms by which diabetes and hyperglycemia lead to heart failure deserve further study, as the association is independent of baseline functional assessment of ischemia, systolic and diastolic function, and interim myocardial infarction.

Left ventricular outflow tract obstruction: should cardiac screening be offered to first-degree relatives?

Objectives To determine whether offering cardiac screening to relatives of patients with left ventricular outflow tract obstructions (LVOTOs) would be justified. Background LVOTOs have been recognised as a group of congenital heart diseases with ‘high heritability’. One of the LVOTOs, the bicuspid aortic valve, is often asymptomatic, but has become known to be associated with sudden, unexpected cardiac death. However, the need for cardiac screening of first-degree relatives of patients with LVOTO has not been determined owing to the lack of studies in well-defined cohorts of consecutive patients. Methods The families of a cohort of 249 consecutive paediatric patients with LVOTO were offered genetic counselling. Of 182 consenting index patients, 40 patients (22%) appeared to have associated non-cardiac congenital anomalies (LVOTO-NCA). In the other 142 patients with LVOTO, cardiac screening of 449 first-degree relatives was performed. Results Cardiac screening disclosed a cardiac anomaly in 34 first-degree relatives (8%). In 23 (68%) of these the cardiac anomaly was a bicuspid aortic valve. Twenty-four of these anomalies were newly detected by our screening programme (71%). These 34 cardiac anomalies were found in the families of 28 index cases (20%). Conclusions This study shows that of the patients with LVOTO without NCA, 20% had (an) affected first-degree relative(s), frequently with undetected bicuspid aortic valves. These data suggest that cardiac screening of relatives of patients with LVOTO without NCA is justified. This may help prevent sudden, unexpected, cardiac death or life-threatening complications in relatives with undetected bicuspid aortic valves.