[Show abstract][Hide abstract] ABSTRACT: Objectives: To combine individual patient data (IPD) from prospective studies on the association between depression after myocardial infarction (post-MI) and all-cause mortality (ACM) and cardiovascular events (CVE) into one single database. To investigate to what extent disease severity and other medical risk factors explain the association, and to what extent post-MI depression independently predicts prognosis.
Design: IPD meta-analysis using multilevel, multivariable Cox regression analyses.
Data sources: PubMed, Embase, and PsychINFO were searched from inception to January 5th, 2011.
Eligibility criteria for selecting studies: Studies investigating the impact of post-MI depression on cardiovascular outcome, defined as all-cause mortality and cardiac events, were identified. Authors were contacted and invited to contribute their data to a combined database of individual patient data.
Results: Sixteen research groups contributed data, resulting in a combined database of 10,175 post-MI patients. This yielded an HR (adjusted for age and sex) of 1.32 (95%CI 1.26 to 1.38, p<0.001) for ACM, and 1.19 (95%CI 1.14 to 1.24, p<0.001) for CVE. HRs adjusted for disease severity and other medical risk factors were attenuated by 28% (ACM) and 25% (CVE).
Conclusion: The association between post-MI depression and ACM or CVE is substantially attenuated after adjustment for cardiac disease severity and other medical risk factors. Still, depression remains independently and significantly associated with (cardiac) prognosis, with a 22% higher risk of ACM and a 13% higher risk of CVE for each SD increase in depression severity.
The British Journal of Psychiatry 08/2013; 203:90-102. · 6.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Determining the prognosis of patients with heart failure is essential for patient management and clinical trial conduct. The relative value of traditional prognostic criteria remains unclear and the assessment of long-term prognosis for individual patients is problematic.
To determine the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of patients with idiopathic dilated cardiomyopathy.
We investigated the ability of clinical, hemodynamic and echocardiographic parameters to predict the long-term prognosis of individual patients in a large, representative, contemporary cohort of idiopathic dilated cardiomyopathy (IDCM) patients referred to Johns Hopkins from 1997 to 2004 for evaluation of cardiomyopathy. In all patients a baseline history was taken, and physical examination, laboratory studies, echocardiogram, right heart catheterization and endomyocardial biopsy were performed.
In 171 IDCM patients followed for a median 3.5 years, there were 50 long-term event-free survivors (LTS) (median survival 6.4 years) and 34 patients died or underwent ventricular assist device placement or transplantation within 5 years (NLTS; non-long-term survivors) (median time to event 1.83 years. Established risk factors (gender, race, presence of diabetes, serum creatinine, sodium) and the use of accepted heart failure medications (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta blockers) were similar between the two groups. Although LTS had younger age, higher ejection fraction (EF) and lower New York Heart Association (NYHA) class at presentation, the positive predictive value of an EF < 25% was 64% (95% CI 41%-79%) and that of NYHA class > 2 was 53% (95% CI 36-69%). A logistic model incorporating these three variables incorrectly classified 29% of patients.
IDCM exhibits a highly variable natural history and standard clinical predictors have limited ability to classify IDCM patients into broad prognostic categories. These findings suggest that there are important host-environmental factors still unappreciated in the biology of IDCM.
The Israel Medical Association journal: IMAJ 11/2012; 14(11):666-71. · 0.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depressed older individuals have a higher mortality than older persons without depression. Depression is associated with physical inactivity, and low levels of physical activity have been shown in some cohorts to be a partial mediator of the relationship between depression and cardiovascular events and mortality.
A cohort of 5888 individuals (mean 72.8 ± 5.6 years, 58% female, 16% African-American) from four US communities was followed for an average of 10.3 years. Self-reported depressive symptoms (10-item Center for Epidemiological Studies Depression Scale) were assessed annually and self-reported physical activity was assessed at baseline and at 3 and 7 years. To estimate how much of the increased risk of cardiovascular mortality associated with depressive symptoms was due to physical inactivity, Cox regression with time-varying covariates was used to determine the percentage change in the log HR of depressive symptoms for cardiovascular mortality after adding physical activity variables.
At baseline, 20% of participants scored above the cut-off for depressive symptoms. There were 2915 deaths (49.8%), of which 1176 (20.1%) were from cardiovascular causes. Depressive symptoms and physical inactivity each independently increased the risk of cardiovascular mortality and were strongly associated with each other (all p < 0.001). Individuals with both depressive symptoms and physical inactivity had greater cardiovascular mortality than those with either individually (p < 0.001, log rank test). Physical inactivity reduced the log HR of depressive symptoms for cardiovascular mortality by 26% after adjustment. This was similar for persons with (25%) and without (23%) established coronary heart disease.
Physical inactivity accounted for a significant proportion of the risk of cardiovascular mortality due to depressive symptoms in older adults, regardless of coronary heart disease status.
[Show abstract][Hide abstract] ABSTRACT: Self-report measures of health status predict mortality in several groups of patients with cardiovascular disease, although overlap with symptoms of depression may reduce or eliminate this relationship. The association between self-reported health status and mortality has not been examined in patients hospitalized for acute coronary syndrome (ACS). The objective was to investigate whether the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores of the SF-12 predicted 12-month all-cause mortality after controlling for cardiac risk factors and symptoms of depression.
The SF-12 and Beck Depression Inventory were administered 2-5 days after admission to 800 ACS patients from 12 coronary care units. Logistic regression was used to assess the relationship of the PCS and MCS with mortality 12 months later, controlling for age, sex, cardiac diagnosis (acute myocardial infarction vs. unstable angina), Killip class, history of myocardial infarction, and in-hospital depressive symptoms.
Lower scores on the SF-12 PCS (worse health) were associated with a significantly higher risk of mortality [odds ratio (OR)=0.94, 95% confidence interval (CI)=0.92-0.97, P<.001]. MCS scores failed to reach significance (OR=0.98, CI=0.95-1.00, P=.053). The PCS significantly predicted mortality even after controlling for other cardiac risk factors and depressive symptoms (OR=0.96, CI=0.93-0.99, P=.008), equivalent to a 34% increase in risk per 10-point (1 SD) decrement in PCS scores.
The brief SF-12 PCS presents an attractive option for improving risk stratification among hospitalized ACS patients.
Journal of Psychosomatic Research 01/2009; 65(6):587-93. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Killip classification is an independent predictor of early mortality after myocardial infarction, and the presence of left ventricular systolic dysfunction (left ventricular ejection fraction <50%) and high Killip class predicts poor short-term prognosis. The long-term prognostic significance of Killip class and left ventricular systolic dysfunction, however, is unknown.
We studied the impact of Killip class and left ventricular systolic dysfunction on all-cause mortality (assessed in May 2007 using the Social Security Death Index) in myocardial infarction patients admitted from July 1995 to December 1996.
Of 282 patients, 60% (n=168) were Killip class 1, 23% (n=64) were Killip class 2, and 17% (n=50) were Killip class 3 or 4. Patients with higher Killip class were older and more likely to have diabetes, a non-Q-wave myocardial infarction, renal insufficiency, chronic obstructive pulmonary disease, and left ventricular systolic dysfunction. There were 152 deaths at 10 years after myocardial infarction, and patients with Killip class 2, 3, or 4 had higher mortality compared with Killip class 1 in unadjusted analyses. Patients with left ventricular systolic dysfunction and Killip class of 2 or more had significantly higher 10-year mortality (70 deaths or 76.9%) compared with Killip class 1 patients without left ventricular systolic dysfunction (29 deaths or 34.5%, P <.001). This risk persisted after adjusting for demographics, cardiovascular risk factors, and co-morbidities. Much of the risk was explained by deaths in the first 5 years after myocardial infarction.
Killip class is a strong predictor of long-term mortality, and patients with high Killip class and left ventricular systolic dysfunction are at highest risk.
The American journal of medicine 11/2008; 121(11):1015-8. · 5.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A single-item general self-rated health (GSRH) question consistently predicts mortality in community cohort studies, but has not been examined in patients with acute coronary syndrome (ACS). We investigated whether a single-item GSRH question predicted mortality 12 months post-discharge in 800 ACS patients.
Logistic regression was used to assess the relationship of the single-item GSRH question with mortality, controlling for cardiac risk factors, including depressive symptoms.
The single-item GSHR question was associated with mortality on a bivariable basis (odds ratio=0.50, 95% confidence interval=0.28-0.92, P=0.027), but was not significant after controlling for other risk factors (odds ratio=0.80, 95% confidence interval=0.40-1.60, P=0.522).
European Journal of Cardiovascular Prevention and Rehabilitation 09/2008; 15(4):479-81. · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Reported links between depression and post-acute myocardial infarction (AMI) mortality may be due to confounding between somatic symptoms of depression and symptoms related to the AMI. The objective of this study was to assess the relationship between depressive symptoms and 12-month post-AMI mortality after removing potential bias from somatic symptoms of depression.
Four hundred seventy-seven hospitalized AMI patients from 12 cardiac care units. The relationship of a General Depression factor with mortality was assessed using a probit structural equation regression model, controlling for an uncorrelated somatic symptom factor, age, Killip class, previous AMI, and other potential confounders.
Mortality was significantly predicted by the General Depression factor (P=0.009), controlling for age (P=0.128), Killip class (P=0.210), history of AMI (P=0.001), and other predictors in a structural equation model that removed variance related to somatic factors, but unrelated to the General Depression factor.
This study demonstrated that the use of structural equation modeling presents a viable mechanism to test links between symptoms of depression and health outcomes among patients with AMI after explicitly removing variance due to somatic symptoms that is unrelated to the General Depression factor.
Journal of Clinical Epidemiology 09/2008; 61(8):832-9. · 5.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression, ischaemic heart disease and cerebrovascular disease are important causes of morbidity and are among the leading contributors to global health burden. These conditions often occur in the same patient, resulting in considerably greater effect on health than combinations of chronic diseases without depression. The frequent occurrence of these conditions in the same patient raises the possibility of a common genetic predisposition, similar risk factors or a pathophysiological link. Serotoninergic and adrenergic signalling play important roles in causing major depression and also in platelet activation and aggregation, which underlies vascular disease. This review discusses the potential pathophysiological link between major depression and conditions in which platelet activation plays an important role and also provides evidence linking the use of the most commonly used antidepressant drugs (i.e. the selective serotonin re-uptake inhibitors) to increased risk of bleeding.
[Show abstract][Hide abstract] ABSTRACT: Depression accelerates the development and progression of cardiovascular disease and confers an increased risk of mortality. Platelets share biochemical similarity with the central nervous system, particularly in the uptake, storage, and metabolism of serotonin. Given this similarity, and considering the central role of platelets in the biology of cardiovascular disease, it is highly plausible that platelets play an important role in the increased cardiovascular risk of patients with depression. This article provides a comprehensive review of the evidence in this area and shows that the relationship between depression and platelet function is hardly straightforward. Whereas many studies have found that patients with depression have exaggerated platelet activation, quite a number of others show no such relationship or even lower levels of platelet activation in patients with depression. Larger, carefully designed, adequately powered studies with standardized methods of assessing platelet function are needed to address this issue.
Southern medical journal 07/2008; 101(6):612-7. · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Depression during hospitalization for myocardial infarction (MI) is associated with subsequent mortality, but whether this risk persisted long term is not well studied. This study was performed to determine whether depression during hospitalization for MI, which predicted mortality at 4 months, predicted mortality 8 years later. This was a prospective observational study of 284 hospitalized patients with MI. Major depression and dysthymia were assessed using structured interview for Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition, and depressive symptoms, using the Beck Depression Inventory. Mortality was determined using the Social Security Death Index. Mean age during MI hospitalization was 64.8 years, 43.0% of patients were women, 66.7% had hypertension, and 35.7% had diabetes mellitus. Any depression (major depression, dysthymia, and/or Beck Depression Inventory score > or =10) was present in 76 patients (26.8%). The 8-year mortality rate was 47.9% (136 deaths). Any depression at the time of MI was not associated with mortality at 8 years in unadjusted (hazard ratio 1.25, 95% confidence interval 0.87 to 1.81, p = 0.22) or multivariate models (hazard ratio 0.76, 95% confidence interval 0.47 to 1.24, p = 0.27). In conclusion, depression after MI was associated with increased short-term mortality, but its relation with mortality over time appeared to wane, at least in a group of older patients who had multiple co-morbidities.
The American Journal of Cardiology 03/2008; 101(5):602-6. · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous research has focused on the relation between depression after an acute coronary syndrome (ACS) and subsequent cardiac morbidity and mortality. However, the relation between depression and quality of life during recovery remains unclear. We investigated whether symptoms of depression during hospitalization for ACS or the course of depressive symptoms after ACS predict physical health status 12 months after ACS, controlling for physical health status at the time of the ACS. This was a prospective study of 425 patients with ACS assessed with the Beck Depression Inventory (BDI) and Short Form 12 (SF-12) Health Survey during hospitalization and 12 months later. Linear regression was used to assess the relation between in-hospital BDI scores and BDI symptom trajectory after ACS with physical health status 12 months later, controlling for baseline physical health status, age, gender, Killip class, history of acute myocardial infarction, and cardiac diagnosis. Baseline BDI scores predicted 12-month physical health (p <0.001). Compared with nondepressed patients, only patients with persistent symptoms of depression were at risk for poorer physical health. Patients with newly developed depressive symptoms after ACS were at slightly increased risk for worsened physical health (p = 0.060), whereas patients with transient depressive symptoms were not at increased risk. In conclusion, these results underscore the importance of assessing depression at the time of ACS and on an ongoing basis.
The American Journal of Cardiology 02/2008; 101(1):15-9. · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eptifibatide is a glycoprotein (GP) IIb/IIIa inhibitor used globally, but there is little information on overdose. We report a case of eptifibatide overdose with no consequence to the patient.
We searched for eptifibatide overdose on PubMed, British National Formulary, Thomson Micromedex, EudraPharm, Toxbase, and the Medicines and Healthcare products Regulatory Agency and Food and Drug Administration websites.
In clinical trials, overdose occurred in 17 cases with no adverse events including bleeding. In case reports, prolonged infusions of eptifibatide were associated with gastrointestinal bleeding and thrombocytopenia. In animal studies, eptifibatide was not lethal but induced dyspnea, ptosis, cerebellar dysfunction, hypotonia and petechial hemorrhages. Eptifibatide side effects including chest pain, bradycardia, angioedema and hypotension may occur in patients with overdose. Alveolar hemorrhage should be suspected in patients with hemoptysis, dyspnea or new infiltrates on chest X-ray. Management of overdose requires discontinuation of eptifibatide, monitoring for bleeding and waiting for clearance (primarily renal). Normalization of hemostasis occurs rapidly and coronary bypass surgery performed within 2 hours of eptifibatide discontinuation did not have excess bleeding. Eptifibatide clearance is delayed in renal failure and in one report hemodialysis normalized hemostasis. Platelet transfusion is appropriate in cases of acute thrombocytopenia, a side effect of eptifibatide. If the platelet count is normal, transfusion of platelets does not help as drug molecules overwhelmingly outnumber GP IIb/IIIa receptors. Desmopressin reversed platelet dysfunction caused by eptifibatide in healthy volunteers but is untested in patients.
Available data suggest that eptifibatide overdose is rare and can be managed conservatively.
International journal of cardiology 12/2007; 131(3):430-2. · 6.18 Impact Factor