Chronic depression symptoms and salivary NOx are associated with retinal vascular dysregulation: The SABPA study.

BACKGROUND: Depression has been associated with impaired nitric oxide (NO)-mediated vasodilation and vascular dysregulation (VD). Whether depression and NO levels will disturb retinal haemodynamics is not clear. OBJECTIVES AND METHODS: Associations between the retinal vasculature, diastolic ocular perfusion pressure (DOPP) as measure of hypoperfusion, NO metabolites (NOx) and depression symptoms were assessed. Chronic VD risk markers [depression symptoms (Patient Health Questionnaire/PHQ-9 ≥ 10) and 24 h pulse pressure] were determined in a bi-ethnic cohort (n = 313; 48.6 ± 9 years; 53.9% men). At 3 year follow-up, retinal vessel calibre and retinopathy signs were quantified from digital images. Salivary NOx was obtained pre- and post-flicker light-induced provocation (FLIP). DOPP was defined as diastolic blood pressure minus intraocular pressure. RESULTS: Chronic VD risk was evident in Blacks opposed to acute risk in Whites (P < 0.05). At follow-up, retinopathy (Blacks 60.4%/Whites 39.6%), lower pre-FLIP (µM) and higher post-FLIP NOx (changes from baseline, %), arteriolar narrowing and wider venular calibre values were evident in Blacks compared to Whites, independent of confounders. A wider venular calibre, an index of stroke risk, was associated with chronic depression symptoms [cut point 248 MU: Area under the curve 0.61 (95% CI: 0.51, 0.72); 71% sensitivity; 55% specificity] as well as with hypoperfusion in the Blacks. In this group, arteriolar narrowing was associated with hypoperfusion; and attenuated arteriolar dilation with increased post-FLIP NOx responses. CONCLUSIONS: Chronic depression symptoms may alter NO regulation and facilitate VD. NO-mediated vasoconstriction presumably impeded perfusion, retinal haemodynamics and -remodelling; potentiating stroke risk in Blacks.

Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: systematic review and recommendations: a scientific statement from the American Heart Association.

BACKGROUND: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome. METHODS AND RESULTS: Writing group members were approved by the American Heart Association's Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes. CONCLUSIONS: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.

Cardiac resynchronization therapy in patients with heart failure and a QRS complex <120 milliseconds: the Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial.

BACKGROUND: Although the benefits of cardiac resynchronization therapy are well established in selected patients with heart failure and a prolonged QRS duration, salutary effects in patients with narrow QRS complexes remain to be demonstrated. METHODS AND RESULTS: The Evaluation of Resynchronization Therapy for Heart Failure (LESSER-EARTH) trial is a randomized, double-blind, 12-center study that was designed to compare the effects of active and inactive cardiac resynchronization therapy in patients with severe left ventricular dysfunction and a QRS duration <120 milliseconds. The trial was interrupted prematurely by the Data Safety and Monitoring Board because of futility and safety concerns after 85 patients were randomized. Changes in exercise duration after 12 months were no different in patients with and without active cardiac resynchronization therapy (-0.7 minutes [95% confidence interval (CI), -2.9 to 1.5] versus 0.8 minutes [95% CI, -1.2 to 2.9]; P=0.31]. Similarly, no significant differences were observed in left ventricular end-systolic volumes (-6.4 mL [95% CI, -18.8 to 5.9] versus 3.1 mL [95% CI, -9.2 to 15.5]; P=0.28) and ejection fraction (3.3% [95% CI, 0.7-6.0] versus 2.1% [95% CI, -0.5 to 4.8]; P=0.52). Moreover, cardiac resynchronization therapy was associated with a significant reduction in the 6-minute walk distance (-11.3 m [95% CI, -31.7 to 9.7] versus 25.3 m [95% CI, 6.1-44.5]; P=0.01), an increase in QRS duration (40.2 milliseconds [95% CI, 34.2-46.2] versus 3.4 milliseconds [95% CI, 0.6-6.2]; P<0.0001), and a nonsignificant trend toward an increase in heart failure-related hospitalizations (15 hospitalizations in 5 patients versus 4 hospitalizations in 4 patients). CONCLUSIONS: In patients with a left ventricular ejection fraction ≤35%, symptoms of heart failure, and a QRS duration <120 milliseconds, cardiac resynchronization therapy did not improve clinical outcomes or left ventricular remodeling and was associated with potential harm. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00900549.

Bridging the transition from hospital to home: effects of the VITAL telehealth program on recovery for CABG surgery patients and their caregivers.

The purpose of this randomized trial was to determine whether coronary artery bypass graft surgery patients and their caregivers who received telehealth follow-up had greater improvements in anxiety levels from pre-surgery to 3 weeks after discharge than did those who received standard care. Secondary outcomes included changes in depressive symptoms and patients' contacts with physicians. No group differences were noted in changes in patients' anxiety and depressive symptoms, but patients in the telehealth group had fewer physician contacts (p = .04). Female caregivers in the telehealth group had greater decreases in anxiety than those in standard care (p < .001), and caregivers of both genders in the telehealth group had greater decreases in depressive symptoms (p = .03).

Left ventricular versus simultaneous biventricular pacing in patients with heart failure and a QRS complex ≥120 milliseconds.

BACKGROUND: Left ventricular (LV) pacing alone may theoretically avoid deleterious effects of right ventricular pacing. METHODS AND RESULTS: In a multicenter, double-blind, crossover trial, we compared the effects of LV and biventricular (BiV) pacing on exercise tolerance and LV remodeling in patients with an LV ejection fraction ≤35%, QRS ≥120 milliseconds, and symptoms of heart failure. A total of 211 patients were recruited from 11 centers. After a run-in period of 2 to 8 weeks, 121 qualifying patients were randomized to LV followed by BiV pacing or vice versa for consecutive 6-month periods. The greatest improvement in New York Heart Association class and 6-minute walk test occurred during the run-in phase before randomization. Exercise duration at 75% of peak Vo(2) (primary outcome) increased from 9.3±6.4 to 14.0±11.9 and 14.3±12.5 minutes with LV and BiV pacing, respectively, with no difference between groups (P=0.4327). LV ejection fraction improved from 24.4±6.3% to 31.9±10.8% and 30.9±9.8% with LV and BiV pacing, respectively, with no difference between groups (P=0.4530). Reductions in LV end-systolic volume were likewise similar (P=0.6788). The proportion of clinical responders (≥20% increase in exercise duration) to LV and BiV pacing was 48.0% and 55.1% (P=0.1615). Positive remodeling responses (≥15% reduction in LV end-systolic volume) were observed in 46.7% and 55.4% (P=0.0881). Overall, 30.6% of LV nonresponders improved with BiV and 17.1% of BiV nonresponders improved with LV pacing. CONCLUSION: LV pacing is not superior to BiV pacing. However, nonresponders to BiV pacing may respond favorably to LV pacing, suggesting a potential role as tiered therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00901212.

Randomized controlled trial of tailored nursing interventions to improve cardiac rehabilitation enrollment.

BACKGROUND: Short hospital stays for patients with acute coronary syndromes (ACSs) reduce the opportunity for risk factor intervention during admission. After discharge, cardiac rehabilitation can decrease the recurrence of coronary events by up to 25%. However, it remains underused. OBJECTIVES: The aim of this study was to determine whether a nursing intervention focused on individual ACS patients' perceptions of their disease and treatment would increase rehabilitation enrollment after discharge. METHOD: A total of 242 ACS patients admitted to a specialized tertiary cardiac center were randomized to either the intervention or usual care (n = 121 in both groups). The intervention included one nurse-patient meeting before discharge with 2 additional contacts over the 10 days after discharge (mean duration = 40 minutes per contact). The primary outcome was enrollment in a free rehabilitation program offered to all participants 6 weeks after discharge. Secondary outcomes included illness perceptions; family support; anxiety level; medication adherence; and cardiac risk factors including lack of exercise, smoking, body mass index, and diet. RESULTS: The sample was composed of a majority of male, married workers who experienced a myocardial infarction or unstable angina without severe complications. The mean hospital stay in both groups was 3.6 days. There was a significantly higher rate of rehabilitation enrollment in the intervention group (45%) than in the control group (24%; p = .001). For the secondary outcomes, only the personal control dimension of illness perceptions was improved significantly with the intervention. DISCUSSION: Progressive, individualized interventions by nurses resulted in greater rehabilitation enrollment, thereby potentially improving long-term outcome.

A pilot randomized trial of a smoking cessation nursing intervention in cardiac patients after hospital discharge.

BACKGROUND: One fifth of Canadians are smokers despite the availability of community-based smoking cessation programs. It was hypothesized that offering a post-discharge smoking cessation program to cardiac patients would decrease smoking rates at six months. METHOD: This pilot randomized study explored the feasibility, acceptability and preliminary efficacy of a smoking cessation intervention delivered by a smoking cessation nurse specialist (SCNS) to cardiac patients after hospital discharge. SAMPLE: Participants (N=40) were randomized to either a postdischarge telephone intervention delivered weekly for the first month and then monthly until the third month (experimental group [EG]), or referral to usual community care (control group [CG]). FINDINGS: The researchers confirmed the feasibility of recruitment and acceptability of the intervention, but dfficulty with follow-up. The intention-to-treat analysis showed similar smoking cessation rates in both groups at six months (25% EG versus 30% CG; p = 0.72). CONCLUSION: An intensifed follow-up protocol, or a more intensive, comprehensive and multidisciplinary intervention might be required, given the characteristics of the smokers.

[A pre assessment for nursing intervention to support tobacco cessation in patients hospitalized for cardiac problems: a pilot study (So-Live)]. / Evaluation préliminaire d'une intervention infirmière de soutien a la cessation tabagique chez des patients hospitalisés pour un problème cardiaque: etude pilote (So-Live).

OBJECTIVE: The aim of this study was to evaluate the effect of a smoking cessation intervention provided after discharge from a specialized cardiac hospital. DESIGN: A randomized pilot study (N = 40); after discharge, the experimental group (EG) received 6 phone calls from a nurse specialized in tobacco cessation counselling. RESULTS: Patients in the EG showed improved scores on two aspects of illness representations (perceive their illness as chronic and reported less negative emotional representations). No significant difference in smoking cessation was observed at 6 months (p = 0.72). CONCLUSION: The non-significant difference may be explained in part by the smoking characteristics within this sample exemplifying the more nicotine dependent "hard core" smokers who persist in their smoking habits despite the serious health consequences incurred by continued smoking. This population of smokers may require a more intensive, specialized intervention to achieve smoking cessation.

Elevated depression symptoms predict long-term cardiovascular mortality in patients with atrial fibrillation and heart failure.

BACKGROUND: Depression predicts prognosis in many cardiac conditions, including congestive heart failure (CHF). Despite heightened cardiac risk in patients with comorbid atrial fibrillation (AF) and CHF, depression has not been studied in this group. This substudy, from the AF-CHF Trial of rate- versus rhythm-control strategies, investigated whether depression predicts long-term cardiovascular mortality in patients with left ventricular ejection fraction or=14). Over a mean follow-up of 39 months, there were 246 cardiovascular deaths (111 presumed arrhythmic; 302 all-cause deaths). Cox proportional hazards models adjusted for other prognostic factors (including age, marital status, cause of CHF, creatinine level, left ventricular ejection fraction, paroxysmal AF, previous AF hospitalization, previous electrical conversion, and baseline medications) showed that elevated depression scores significantly predicted cardiovascular mortality (primary outcome), arrhythmic death, and all-cause mortality. The adjusted hazard ratios were 1.57 (95% confidence interval 1.20 to 2.07, P<0.001), 1.69 (95% confidence interval 1.13 to 2.53, P=0.01), and 1.38 (95% confidence interval 1.07 to 1.77, P=0.01), respectively. The risks associated with depression and marital status were additive, with the highest risk in depressed patients who were unmarried. CONCLUSIONS: Elevated depression symptoms are related to cardiovascular mortality even after adjustment for other prognostic indicators in patients with comorbid AF and CHF who receive optimized treatment. Unmarried patients are also at increased risk. Mechanisms and treatment options deserve additional study.

The efficacy of a motivational nursing intervention based on the stages of change on self-care in heart failure patients.

BACKGROUND AND RESEARCH OBJECTIVE: : Heart failure (HF) patients experience frequent episodes of decompensation. While medication and behavior change play a major role in maintaining physiological stability, patient adherence to self-care recommendations is not optimal. The Theory of Heart Failure Self-care helped to understand the concepts of self-care and chose a model of intervention. Conviction and confidence are central factors in facilitating self-care. Motivational interviewing (MI), which aims to strengthen conviction and confidence, has been shown to improve self-care. In addition, the Transtheoretical Model, based on patients' readiness to change, also has proven efficacy. The MI based on the stages of change (MISC), a combination of MI and Transtheoretical Model, offers promise for improving self-care. The goal of this pilot study was to evaluate the preliminary effect of an MISC intervention on HF patients' self-care behaviors. SUBJECTS AND METHOD: : Thirty patients were recruited from an HF clinic and randomly assigned to an experimental (EG) or control group (n = 15/group). Patients from the EG received 3 interventions (1 in person, 2 on the phone). Data were collected at baseline and at 1 month after randomization. The effect of the intervention was assessed on 5 self-care outcomes using analysis-of-covariance models. RESULTS AND CONCLUSION: : Significant results were obtained regarding the confidence in performing self-care behaviors specific to HF (P =.005). Although the results of the other hypotheses were not statistically significant, for the majority, trends were in the expected direction in favor of the EG. The study suggests that an MISC intervention is useful to increase patients' confidence in HF self-care and has potential to improve self-care. Further research is needed.

Depression and coronary heart disease: recommendations for screening, referral, and treatment: a science advisory from the American Heart Association Prevention Committee of the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care and Outcomes Research: endorsed by the American Psychiatric Association.

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

The relationships among heart rate variability, inflammatory markers and depression in coronary heart disease patients.

Studies show negative correlations between heart rate variability (HRV) and inflammatory markers. In cardiac patients, depression is related to both. We investigated links between short-term HRV and inflammatory markers in relation to depression in acute coronary syndrome (ACS) patients. We measured C-reactive protein (CRP), interleukin-6 (IL-6), depression symptoms (Beck Depression Inventory, BDI-II), and SDNN, high frequency (HF) and low frequency (LF) power at rest in 682 (553 men) patients approximately two months post-ACS. There were no differences in HRV measures between those with and without elevated depressions symptoms (BDI-II >or= 14). However, all HRV measures were negatively and significantly associated with both inflammatory markers. Relationships were stronger in patients with BDI-II >or= 14. Differences were significant for CRP and not explained by covariates (including age, sex, previous MI, left ventricular ejection fraction, coronary bypass surgery at index admission, diabetes, smoking, body mass index (BMI), fasting cholesterol, fasting glucose, angiotensin-converting-enzyme inhibitors, beta-blockers, statins, and antidepressants). HRV independently accounted for at least 4% of the variance in CRP in the depressed, more than any factor except BMI. Relationships between measures of inflammation and autonomic function are stronger among depressed than non-depressed cardiac patients. Interventions targeting regulation of both autonomic control and inflammation may be of particular importance.

AHA science advisory. Depression and coronary heart disease. Recommendations for screening, referral, and treatment. A science advisory from the American Heart Association Prevention Committee to the Council on Cardiovascular Nursing, Council on Clinical Cardiology, Council on Epidemiology and Prevention, and Interdisciplinary Council on Quality of Care Outcomes Research. Endorsed by the American Psychiatric Association.

Depression is commonly present in patients with coronary heart disease (CHD) and is independently associated with increased cardiovascular morbidity and mortality. Screening tests for depressive symptoms should be applied to identify patients who may require further assessment and treatment. This multispecialty consensus document reviews the evidence linking depression with CHD and provides recommendations for healthcare providers for the assessment, referral, and treatment of depression.

Genetic predictors of depressive symptoms in cardiac patients.

Numerous studies suggest that the prevalence of depression is greater among cardiac patients than in the general population. However, little attention has been paid to the possibility of genetic contributions to depressive symptoms in cardiac patients. We conducted a candidate gene study focusing on genes related to inflammation, platelet aggregation, endothelial function and omega-3 fatty acid metabolism as predictors of depressive symptoms among 977 participants with established cardiovascular disease. Results suggested that genetic variation related to endothelial dysfunction is predictive of depressive symptoms and that endothelial dysfunction may be a novel mechanism contributing to depressive symptoms among cardiac patients.

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.

Depression, C-reactive protein and two-year major adverse cardiac events in men after acute coronary syndromes.

BACKGROUND: We investigated the impact of depression and inflammatory markers, assessed 2 months after acute coronary syndrome (ACS), on major adverse cardiac events over 2 years (MACEs; cardiac death, survived myocardial infarction, survived cardiac arrest, and nonelective revascularization). METHODS: Depression symptoms (Beck Depression Inventory-II; BDI-II), major depression, C-reactive protein (CRP), interleukin-6, and soluble intercellular adhesion molecule were assessed in 741 ACS patients (including 602 men). RESULTS: Some 102 (78 men) experienced at least one MACE. Beck Depression Inventory-II scores of > or =14 predicted MACEs (p = .007). The increase in risk was marked in men (hazard ratio [HR] = 1.96, 95% confidence interval [CI] = 1.24-3.09, p = .004), with little evidence of a relationship in women (p = .85). Subsequent analyses were limited to men. Results were similar after covariate adjustment (HR = 1.72, 95% CI = 1.07-2.77, p = .024). C-reactive protein levels were also associated with increased MACE risk (adjusted HR for CRP > or = 2.0 mg/L = 1.67, 95% CI = 1.07-2.62, p = .025). C-reactive protein levels and BDI-II scores interacted in predicting MACEs. Men with both BDI-II scores of > or =14 and CRP of > or =2.0 mg/L experienced an increase in risk similar to those with only one of these factors. CONCLUSIONS: In men assessed 2 months after ACS, depression and CRP are overlapping prognostic risks. Patients with either risk may benefit from similar therapies.

Antiplatelet properties of escitalopram in patients with the metabolic syndrome: a dose-ranging in vitro study.

There is an increasing body of evidence suggesting that selective serotonin reuptake inhibitors exhibit clinical benefit beyond treating depression, by simultaneously inhibiting platelet activity. We recently demonstrated that escitalopram (ESC), but not its major metabolites, inhibits multiple platelet biomarkers in healthy volunteers. Considering that the metabolic syndrome represents one of the major risk factors for vascular disease, we here determined how ESC affects platelet activity in such patients. We assessed the in vitro effects of preincubation with escalating (50-200 nM/l) concentrations of ESC on platelet aggregation, expression of major surface receptors by flow cytometry, and quantitatively by platelet function analyzers. Blood samples were obtained from 20 aspirin-naïve patients with documented metabolic syndrome. Pretreatment of blood samples with medium (150 nM/l), or high (200 nM/l) doses of ESC resulted in a significant inhibition of platelet aggregation induced by ADP (p=0.007) and by collagen (p=0.004). Surface platelet expression of GPIb (CD42, p=0.03), LAMP-3 (CD63, p=0.04), and GP37 (CD165, p=0.03) was decreased in the ESC-pretreated samples. Closure time by the PFA-100 analyzer was prolonged after the 200 nM/l dose (p=0.02), indicating platelet inhibition under high shear conditions. On the other hand, the lowest tested concentration of ESC (50 nM/l) did not affect platelet activity in these patients. The in vitro antiplatelet characteristics of ESC in patients with the metabolic syndrome are similar to those in healthy volunteers. However, higher ESC doses are required to induce equally potent platelet inhibition. These data justify prospective ex vivo studies with the highest therapeutic dose to determine the potential clinical advantage of ESC in high-risk patients with vascular disease.

Effects of citalopram and interpersonal psychotherapy on depression in patients with coronary artery disease: the Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy (CREATE) trial.

CONTEXT: Few randomized controlled trials have evaluated the efficacy of treatments for major depression in patients with coronary artery disease (CAD). None have simultaneously evaluated an antidepressant and short-term psychotherapy. OBJECTIVE: To document the short-term efficacy of a selective serotonin reuptake inhibitor (citalopram) and interpersonal psychotherapy (IPT) in reducing depressive symptoms in patients with CAD and major depression. DESIGN, SETTING, AND PARTICIPANTS: The Canadian Cardiac Randomized Evaluation of Antidepressant and Psychotherapy Efficacy, a randomized, controlled, 12-week, parallel-group, 2 x 2 factorial trial conducted May 1, 2002, to March 20, 2006, among 284 patients with CAD from 9 Canadian academic centers. All patients met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for diagnosis of major depression of 4 weeks' duration or longer and had baseline 24-item Hamilton Depression Rating Scale (HAM-D) scores of 20 or higher. INTERVENTIONS: Participants underwent 2 separate randomizations: (1) to receive 12 weekly sessions of IPT plus clinical management (n = 142) or clinical management only (n = 142) and (2) to receive 12 weeks of citalopram, 20 to 40 mg/d (n = 142), or matching placebo (n = 142). MAIN OUTCOME MEASURES: The primary outcome measure was change between baseline and 12 weeks on the 24-item HAM-D, administered blindly during centralized telephone interviews (tested at alpha = .033); the secondary outcome measure was self-reported Beck Depression Inventory II (BDI-II) score (tested at alpha = .017). RESULTS: Citalopram was superior to placebo in reducing 12-week HAM-D scores (mean difference, 3.3 points; 96.7% confidence interval [CI], 0.80-5.85; P = .005), with a small to medium effect size of 0.33. Mean HAM-D response (52.8% vs 40.1%; P = .03) and remission rates (35.9% vs 22.5%; P = .01) and the reduction in BDI-II scores (difference, 3.6 points; 98.3% CI, 0.58-6.64; P = .005; effect size = 0.33) also favored citalopram. There was no evidence of a benefit of IPT over clinical management, with the mean HAM-D difference favoring clinical management (-2.26 points; 96.7% CI, -4.78 to 0.27; P = .06; effect size, 0.23). The difference on the BDI-II did not favor clinical management (1.13 points; 98.3% CI, -1.90 to 4.16; P = .37; effect size = 0.11). CONCLUSIONS: This trial documents the efficacy of citalopram administered in conjunction with weekly clinical management for major depression among patients with CAD and found no evidence of added value of IPT over clinical management. Based on these results and those of previous trials, citalopram or sertraline plus clinical management should be considered as a first-step treatment for patients with CAD and major depression. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN15858091.

Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin.

OBJECTIVE: Although it is well established that depressive symptoms are associated with recurrent cardiac events among cardiac patients and novel cardiac events among participants with no known coronary artery disease (CAD), the nature of this association remains unclear. In this regard, little attention has been paid to the possibility that common genetic vulnerability contributes to both depressive symptoms and CAD. In this paper, we review the existing evidence for common genetic contributions to depression and CAD, primarily using evidence from twin and family studies, followed by a review of two major pathophysiological mechanisms thought to underlie covariation between depressive symptoms and CAD: inflammation and serotonin. We conclude with an overview of select candidate genes within these pathways. METHODS: Literature review. RESULTS: In twin studies, both depression and CAD appear heritable. In the only twin study to consider depression and CAD jointly, the correlation across heritabilities was 0.42, suggesting that nearly 20% of variability in depressive symptoms and CAD was attributable to common genetic factors. In addition, although it is plausible that genetic variation related to inflammation and serotonin may be associated with both depression and CAD, genetic variation related to inflammation has been primary examined in relation to CAD, whereas genetic variation in the serotonin system has been primarily examined in relation to depression. CONCLUSIONS: It appears that the covariation of depressive symptoms and CAD may be attributable, in part, to a common genetic vulnerability. Although several pathways may be involved, genes within the inflammation and serotonin pathways may serve as good candidates for the first steps in identifying genetic variation important for depression, CAD or both.

Design and rationale for a randomized, controlled trial of interpersonal psychotherapy and citalopram for depression in coronary artery disease (CREATE).

OBJECTIVE: Recognition that depression is associated with increased morbidity and mortality in coronary artery disease (CAD) patients has augmented the need for evidence-based treatment guidelines. This article presents the design of a multisite, Canadian trial of the efficacy, safety, and tolerability of interpersonal psychotherapy (IPT), an empirically supported, depression-focused therapy, and the selective serotonin reuptake inhibitor citalopram, alone or in combination, in the treatment of major depression in CAD patients. METHODS: Two hundred eighty stable CAD patients with a current major depressive episode of at least 4 weeks' duration, based on the Structured Clinical Interview for Depression (SCID), and who have a baseline score >19 on a centralized, telephone-administered, 24-item Hamilton Depression Rating Scale (HAM-D) will be randomly assigned to receive 12 weekly IPT sessions or 12 weekly sessions of standardized clinical management (CM). Patients are also randomly assigned to receive 20 to 40 mg per day of citalopram or pill-placebo. This results in a 2-by-2 factorial design with four groups: IPT plus pill-placebo, IPT plus citalopram, CM plus pill-placebo, and CM plus citalopram. This permits the evaluation of both IPT and citalopram. Blinded, centralized, 24-item, HAM-D telephone ratings constitute the primary outcome variable. The self-report Beck Depression Inventory-II is the secondary outcome. Analyses will involve the intent-to-treat principle with last observation carried forward for incomplete assessments. RESULTS: Not applicable. CONCLUSIONS: The results of this trial will contribute to the development of evidence-based clinical guidelines for managing depression in the context of CAD.