Ian M. Kronish

Enhanced Depression Care for Patients With Acute Coronary Syndrome and Persistent Depressive Symptoms: Coronary Psychosocial Evaluation Studies Randomized Controlled Trial

BACKGROUND Depressive symptoms are an established predictor of mortality and major adverse cardiac events (defined as nonfatal myocardial infarction or hospitalization for unstable angina or urgent/emergency revascularizations) in patients with acute coronary syndrome (ACS). This study was conducted to determine the acceptability and efficacy of enhanced depression treatment in patients with ACS. METHODS A 3-month observation period to identify patients with ACS and persistent depressive symptoms was followed by a 6-month randomized controlled trial. From January 1, 2005, through February 29, 2008, 237 patients with ACS from 5 hospitals were enrolled, including 157 persistently depressed patients randomized to intervention (initial patient preference for problem-solving therapy and/or pharmacotherapy, then a stepped-care approach; 80 patients) or usual care (77 patients) and 80 nondepressed patients who underwent observational evaluation. The primary outcome was patient satisfaction with depression care. Secondary outcomes were depressive symptom changes (assessed with the Beck Depression Inventory), major adverse cardiac events, and death. RESULTS At the end of the trial, the proportion of patients who were satisfied with their depression care was higher in the intervention group (54% of 80) than in the usual care group (19% of 77) (odds ratio, 5.4; 95% confidence interval [CI], 2.2-12.9 [P < .001]). The Beck Depression Inventory score decreased significantly more (t(155) = 2.85 [P = .005]) for intervention patients (change, -5.7; 95% CI, -7.6 to -3.8; df = 155) than for usual care patients (change, -1.9; 95% CI, -3.8 to -0.1; df = 155); the depression effect size was 0.59 of the standard deviation. At the end of the trial, 3 intervention patients and 10 usual care patients had experienced major adverse cardiac events (4% and 13%, respectively; log-rank test, chi(2)(1) = 3.93 [P = .047]), as well as 5 nondepressed patients (6%) (for the intervention vs nondepressed cohort, chi(2)(1) = 0.48 [P = .49]). CONCLUSION Enhanced depression care for patients with ACS was associated with greater satisfaction, a greater reduction in depressive symptoms, and a promising improvement in prognosis. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00158054.

Predictors of Nonadherence to Statins: A Systematic Review and Meta-Analysis

Background: Nonadherence to statins limits the benefits of this common drug class. Individual studies assessing predictors of nonadherence haue produced inconsistent results. Objective: To identify reliable predictors of nonadherence to statins through systematic review and meta-analysis. Methods: Multiple databases, including MEDLINE, EMBASE, and PsycINFO, were searched (from inception through February 2009) to identify studies that evaluated predictors of nonadherence to statins. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics and outcomes. Relative risks were then pooled, using an inverse-variance weighted random-effects model. Results: Twenty-two cohort studies met inclusion criteria. Age had a U-shaped association with adherence; the oldest (≥70 years) and youngest (<50 years) subjects had lower adherence than the middle-aged (50-69 years) subjects. Women and patients with lower incomes were more likely to be nonadherent than were men (odds of nonadherence 1.07; 95% CI 1.04 to 1.11) and those with higher incomes (odds of nonadherence 1.18:95% CI 1.10 to 1.28), respectively. A history of cardiovascular disease predicted better adherence to statins (odds of nonadherence 0.68; 95% CI 0.66 to 0.78). Similarly, a diagnosis of hypertension or diabetes was associated with better adherence. Although there were too few studies for quantitative pooling, increased testing of lipid levels and lower out-of-pocket costs appeared to be associated with better adherence. There was substantial (l2 range 68.7-96.3%) heterogeneity between studies across factors. Conclusions: Several sociodemographic, medical, and health-care utilization characteristics are associated with statin nonadherence. These factors may be useful guides for targeting statin adherence interventions.

Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes.

AbstractBACKGROUND: The persistence of depressive symptoms after hospitalization is a strong risk factor for mortality after acute coronary syndromes (ACS). Poor adherence to secondary prevention behaviors may be a mediator of the relationship between depression and increased mortality. OBJECTIVE: To determine whether rates of adherence to risk reducing behaviors were affected by depressive status during hospitalization and 3 months later. DESIGN: Prospective observational cohort study. SETTING: Three university hospitals. PARTICIPANTS: Five hundred and sixty patients were enrolled within 7 days after ACS. Of these, 492 (88%) patients completed 3-month follow-up. MEASUREMENTS: We used the Beck Depression Inventory (BDI) to assess depressive symptoms in the hospital and 3 months after discharge. We assessed adherence to 5 risk-reducing behaviors by patient self-report at 3 months. We used χ2 analysis to compare differences in adherence among 3 groups: persistently nondepressed (BDI<10 at hospitalization and 3 months); remittent depressed (BDI ≥10 at hospitalization; <10 at 3 months); and persistently depressed patients (BDI ≥10 at hospitalization and 3 months). RESULTS: Compared with persistently nondepressed, persistently depressed patients reported lower rates of adherence to quitting smoking (adjusted odds ratio [OR] 0.23, 95% confidence interval [95% CI] 0.05 to 0.97), taking medications (adjusted OR 0.50, 95% CI 0.27 to 0.95), exercising (adjusted OR 0.57, 95% CI 0.34 to 0.95), and attending cardiac rehabilitation (adjusted OR 0.5, 95% CI 0.27 to 0.91). There were no significant differences between remittent depressed and persistently nondepressed patients. CONCLUSIONS: Persistently depressed patients were less likely to adhere to behaviors that reduce the risk of recurrent ACS. Differences in adherence to these behaviors may explain in part why depression predicts mortality after ACS.

Association of Anhedonia With Recurrent Major Adverse Cardiac Events and Mortality 1 Year After Acute Coronary Syndrome

CONTEXT Depression consistently predicts recurrent events and mortality in patients with acute coronary syndrome (ACS), but it has 2 core diagnostic criteria with distinct biological correlates-depressed mood and anhedonia (loss of pleasure or interest). OBJECTIVE To determine if depressed mood and/or anhedonia predict 1-year medical outcomes for patients with ACS. DESIGN Observational cohort study of post-ACS patients hospitalized between May 2003 and June 2005. Within 1 week of admission, patients underwent a structured psychiatric interview assessing clinically impairing depressed mood, anhedonia, and major depressive episode (MDE). Also assessed were the Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, antidepressant use, and depressive symptom severity using the Beck Depression Inventory. SETTING Cardiac units of 3 university hospitals in New York and Connecticut. PARTICIPANTS Consecutive sample of 453 patients with ACS (age, 25-93 years; 42% women). MAIN OUTCOMES MEASURES All-cause mortality (ACM) and documented major adverse cardiac events (MACEs)-myocardial infarction, hospitalization for unstable angina, or urgent/emergency coronary revascularization)-actively surveyed for 1 year after admission. RESULTS There were 67 events (16 deaths and 51 MACEs; 14.8%): 108 (24%) and 77 (17%) patients had anhedonia and depressed mood, respectively. Controlling for sex, age, and medical covariates, anhedonia (adjusted hazard ratio, 1.58; 95% confidence interval, 1.16-2.14; P < .01) was a significant predictor of combined MACE and ACM, but depressed mood was not. Anhedonia continued to significantly predict outcomes (P < .05) when additionally controlling for MDE diagnosis or depressive symptom severity. Findings were confirmed using depressed mood and anhedonia subscores from the Beck Depression Inventory in place of clinician interview ratings. CONCLUSIONS Anhedonia identifies risk of MACE and ACM beyond that of established medical prognostic indicators, including MDE and depressive symptom severity. Correlates of anhedonia may add to the understanding of the link between depression and heart disease.

Posttraumatic stress disorder and risk for coronary heart disease: A meta-analytic review

OBJECTIVE The aim of this study was to estimate the association of posttraumatic stress disorder (PTSD) with risk for incident coronary heart disease (CHD). DESIGN A systematic review and meta-analysis were used as study designs. DATA SOURCES Articles were identified by searching Ovid MEDLINE, PsycINFO, Scopus, Cochrane Library, PILOTS database, and PubMed Related Articles and through a manual search of reference lists (1948-present). STUDY SELECTION All studies that assessed PTSD in participants initially free of CHD and subsequently assessed CHD/cardiac-specific mortality were included. DATA EXTRACTION Two investigators independently extracted estimates of the association of PTSD with CHD, as well as study characteristics. Odds ratios were converted to hazard ratios (HRs), and a random-effects model was used to pool results. A secondary analysis including only studies that reported estimates adjusted for depression was conducted. RESULTS Six studies met our inclusion criteria (N = 402,274); 5 of these included depression as a covariate. The pooled HR for the magnitude of the relationship between PTSD and CHD was 1.55 (95% CI 1.34-1.79) before adjustment for depression. The pooled HR estimate for the 5 depression-adjusted estimates (N = 362,950) was 1.27 (95% CI 1.08-1.49). CONCLUSION Posttraumatic stress disorder is independently associated with increased risk for incident CHD, even after adjusting for depression and other covariates. It is common in both military veterans and civilian trauma survivors, and these results suggest that it may be a modifiable risk factor for CHD. Future research should identify the mechanisms of this association and determine whether PTSD treatment offsets CHD risk.

Meta-Analysis Impact of Drug Class on Adherence to Antihypertensives

Background— Observational studies suggest that there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings. Methods and Results— Studies were identified through a systematic search of English-language articles published from the inception of computerized databases until February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance–weighted random-effects model was used to pool results. Hazard ratios (HRs) and odds ratios were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for &bgr;-blockers to 65% for angiotensin II receptor blockers. There was better adherence to angiotensin II receptor blockers compared with angiotensin-converting enzyme inhibitors (HR, 1.33; 95% confidence interval, 1.13 to 1.57), calcium channel blockers (HR, 1.57; 95% confidence interval, 1.38 to 1.79), diuretics (HR, 1.95; 95% confidence interval, 1.73 to 2.20), and &bgr;-blockers (HR, 2.09; 95% confidence interval, 1.14 to 3.85). Conversely, there was lower adherence to diuretics compared with the other drug classes. The same pattern was present when studies that used odds ratios were pooled. After publication bias was accounted for, there were no longer significant differences in adherence between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors or between diuretics and &bgr;-blockers. Conclusion— In clinical settings, there are important differences in adherence to antihypertensives in separate classes, with lowest adherence to diuretics and &bgr;-blockers and highest adherence to angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. However, adherence was suboptimal regardless of drug class.Background— Observational studies suggest that there are differences in adherence to antihypertensive medications in different classes. Our objective was to quantify the association between antihypertensive drug class and adherence in clinical settings. Methods and Results— Studies were identified through a systematic search of English-language articles published from the inception of computerized databases until February 1, 2009. Studies were included if they measured adherence to antihypertensives using medication refill data and contained sufficient data to calculate a measure of relative risk of adherence and its variance. An inverse-variance–weighted random-effects model was used to pool results. Hazard ratios (HRs) and odds ratios were pooled separately, and HRs were selected as the primary outcome. Seventeen studies met inclusion criteria. The pooled mean adherence by drug class ranged from 28% for β-blockers to 65% for angiotensin II receptor blockers. There was better adherence to angiotensin II receptor blockers compared with angiotensin-converting enzyme inhibitors (HR, 1.33; 95% confidence interval, 1.13 to 1.57), calcium channel blockers (HR, 1.57; 95% confidence interval, 1.38 to 1.79), diuretics (HR, 1.95; 95% confidence interval, 1.73 to 2.20), and β-blockers (HR, 2.09; 95% confidence interval, 1.14 to 3.85). Conversely, there was lower adherence to diuretics compared with the other drug classes. The same pattern was present when studies that used odds ratios were pooled. After publication bias was accounted for, there were no longer significant differences in adherence between angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors or between diuretics and β-blockers. Conclusion— In clinical settings, there are important differences in adherence to antihypertensives in separate classes, with lowest adherence to diuretics and β-blockers and highest adherence to angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors. However, adherence was suboptimal regardless of drug class. # Clinical Perspective {#article-title-43}

State of the Art Review: Depression, Stress, Anxiety, and Cardiovascular Disease

The notion that psychological states can influence physical health is hardly new, and perhaps nowhere has the mind-body connection been better studied than in cardiovascular disease (CVD). Recently, large prospective epidemiologic studies and smaller basic science studies have firmly established a connection between CVD and several psychological conditions, including depression, chronic psychological stress, posttraumatic stress disorder (PTSD), and anxiety. In addition, numerous clinical trials have been conducted to attempt to prevent or lessen the impact of these conditions on cardiovascular health. In this article, we review studies connecting depression, stress/PTSD, and anxiety to CVD, focusing on findings from the last 5 years. For each mental health condition, we first examine the epidemiologic evidence establishing a link with CVD. We then describe studies of potential underlying mechanisms and finally discuss treatment trials and directions for future research.

Adherence to Cardiovascular Medications: Lessons Learned and Future Directions

Approximately 50% of patients with cardiovascular disease and/or its major risk factors have poor adherence to their prescribed medications. Finding novel methods to help patients improve their adherence to existing evidence-based cardiovascular drug therapies has enormous potential to improve health outcomes while potentially reducing health care costs. The goal of this report is to provide a review of the current understanding of adherence to cardiovascular medications from the point of view of prescribing clinicians and cardiovascular researchers. Key topics addressed include: (1) definitions of medication adherence; (2) prevalence and impact of non-adherence; (3) methods for assessing medication adherence; 4) reasons for poor adherence; and 5) approaches to improving adherence to cardiovascular medications. For each of these topics, the report seeks to identify important gaps in knowledge and opportunities for advancing the field of cardiovascular adherence research.

Post-traumatic stress disorder and medication adherence: Results from the mind your heart study

BACKGROUND Patients with post-traumatic stress disorder (PTSD) are at increased risk for adverse outcomes from comorbid medical conditions. Medication non-adherence is a potential mechanism explaining this increased risk. METHODS We examined the association between PTSD and medication adherence in a cross-sectional study of 724 patients recruited from two Department of Veterans Affairs Medical Centers between 2008 and 2010. PTSD was assessed using the Clinician Administered PTSD Scale. Medication adherence was assessed using a standardized questionnaire. Ordinal logistic regression models were used to calculate the odds ratios (ORs) for medication non-adherence in patients with versus without PTSD, adjusting for potential confounders. RESULTS A total of 252 patients (35%) had PTSD. Twelve percent of patients with PTSD reported not taking their medications as prescribed compared to 9% of patients without PTSD (unadjusted OR 1.85, 95% CI 1.37-2.50, P<0.001). Forty-one percent of patients with PTSD compared to 29% of patients without PTSD reported forgetting medications (unadjusted OR 1.90, 95% CI 1.44-2.52, P<0.001). Patients with PTSD were also more likely to report skipping medications (24% versus 13%; unadjusted OR 2.01, 95% CI 1.44-2.82, P<0.001). The association between PTSD and non-adherence remained significant after adjusting for demographics, depression, alcohol use, social support, and medical comorbidities (adjusted OR 1.47, 95% CI 1.03-2.10, P=0.04 for not taking medications as prescribed and 1.95, 95% CI 1.31-2.91, P=0.001 for skipping medications). CONCLUSIONS PTSD was associated with medication non-adherence independent of psychiatric and medical comorbidities. Medication non-adherence may contribute to the increased morbidity and mortality observed in patients with PTSD.

Depressive symptoms and cardiovascular health by the American Heart Association's definition in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study.

Background Depressive symptoms are associated with increased incident and recurrent cardiovascular events. In 2010, the American Heart Association published the Life’s Simple 7, a metric for assessing cardiovascular health as measured by 4 health behaviors (smoking, physical activity, body mass index, diet) and 3 biological measures (cholesterol, blood pressure, glucose). The association between depressive symptoms and the Life’s Simple 7 has not yet been explored. Methods Data from 20,093 participants ≥45 years of age who enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 and who had complete data available on Life’s Simple 7 components were used for these analyses. The prevalence of ideal, intermediate, and poor health on each Life’s Simple 7 component and total Life’s Simple 7 scores were compared between participants with and without depressive symptoms. Depressive symptoms were measured using the 4-item Centers for Epidemiologic Studies of Depression scale. Results Participants with depressive symptoms were more likely to have poor levels on each of the Life’s Simple 7 components other than cholesterol [adjusted prevalence ratios (95% CI): smoking 1.41 (1.29–1.55); physical activity 1.38 (1.31–1.46); body mass index 1.09 (1.04–1.15); diet 1.08 (1.06–1.10); blood pressure 1.11 (1.02–1.21); glucose 1.24 (1.09–1.41)]. There was a graded association between increasing depressive symptoms and lower total Life’s Simple 7 score. Conclusion Depressive symptoms are associated with worse cardiovascular health on the overall Life’s Simple 7 and on individual components representing both health behaviors and biological factors.