Jonathan M. Wong

Depression and Cardiovascular Disorders

During the past two decades, research in the field of depression and cardiovascular disorders has exploded. Multiple studies have demonstrated that depression is more prevalent in populations with cardiovascular disease, is a robust risk factor for the development of cardiovascular disease in healthy populations, and is predictive of adverse outcomes (such as myocardial infarction and death) among populations with preexisting cardiovascular disease. Mechanistic studies have shown that poor health behaviors, such as physical inactivity, medication nonadherence, and smoking, strongly contribute to this association. Small randomized trials have found that antidepressant therapies may improve cardiac outcomes. Based on this accumulating evidence, the American Heart Association has recommended routine screening for depression in all patients with coronary heart disease. This review examines the key epidemiological literature on depression and cardiovascular disorders and discusses our current understanding of the mechanisms responsible for this association. We also examine current recommendations for screening, diagnosis, and management of depression. We conclude by highlighting new research areas and discussing therapeutic management of depression in patients with cardiovascular disorders.

Relation of Left Atrial Dysfunction to Ischemic Stroke in Patients With Coronary Heart Disease (from the Heart and Soul Study)

This study sought to determine whether left atrial (LA) dysfunction independently predicts ischemic stroke. Atrial fibrillation (AF) impairs LA function and is associated with ischemic stroke. However, ischemic stroke frequently occurs in patients without known AF. The direct relation between LA function and risk of ischemic stroke is unknown. We performed transthoracic echocardiography at rest in 983 subjects with stable coronary heart disease. To quantify LA dysfunction, we used the left atrial function index (LAFI), a validated formula incorporating LA volumes at end-atrial systole and diastole. Cox proportional hazards models were used to evaluate the association between LAFI and ischemic stroke or transient ischemic attack (TIA). Over a mean follow-up of 7.1 years, 58 study participants (5.9%) experienced an ischemic stroke or TIA. In patients without known baseline AF or warfarin therapy (n = 893), participants in the lowest quintile of LAFI had >3 times the risk of ischemic stroke or TIA (hazard ratio 3.3, 95% confidence interval 1.1 to 9.7, p = 0.03) compared with those in the highest quintile. For each standard deviation (18.8 U) decrease in LAFI, the hazard of ischemic stroke or TIA increased by 50% (hazard ratio 1.5, 95% confidence interval 1.0 to 2.1, p = 0.04). Among measured echocardiographic indexes of LA function, including LA volume, LAFI was the strongest predictor of ischemic stroke or TIA. In conclusion, LA dysfunction is an independent risk factor for stroke or TIA, even in patients without baseline AF.

Association of CHADS2, CHA2DS2-VASc, and R2CHADS2 Scores With Left Atrial Dysfunction in Patients With Coronary Heart Disease (from the Heart and Soul Study)

The predictive ability of the CHADS2 index to stratify stroke risk may be mechanistically linked to severity of left atrial (LA) dysfunction. This study investigated the association between the CHADS2 score and LA function. We performed resting transthoracic echocardiography in 970 patients with stable coronary heart disease and normal ejection fraction and calculated baseline LA functional index (LAFI) using a validated formula: (LA emptying fraction×left ventricular outflow tract velocity time integral)/LA end-systolic volume indexed to body surface area. We performed regression analyses to evaluate the association between risk scores and LAFI. Among 970 subjects, mean CHADS2 was 1.7±1.2. Mean LAFI decreased across tertiles of CHADS2 (42.8±18.1, 37.8±19.1, 36.7±19.4, p<0.001). After adjustment for age, sex, race, systolic blood pressure, hyperlipidemia, myocardial infarction, revascularization, body mass index, smoking, and alcohol use, high CHADS2 remained associated with the lowest quartile of LAFI (odds ratio 2.34, p=0.001). In multivariable analysis of component co-morbidities, heart failure, age, and creatinine clearance<60 ml/min were strongly associated with LA dysfunction. For every point increase in CHADS2, the LAFI decreased by 4.0%. Secondary analyses using CHA2DS2-VASc and R2CHADS2 scores replicated these results. Findings were consistent when excluding patients with baseline atrial fibrillation. In conclusion, CHADS2, CHA2DS2-VASc, and R2CHADS2 scores are associated with LA dysfunction, even in patients without baseline atrial fibrillation. These findings merit further study to determine the role of LA dysfunction in cardioembolic stroke and the value of LAFI for risk stratification.

Cryptogenic stroke and the left atrial septal pouch: a case report.

The left atrial septal pouch (LASP) is an anatomic variant of the interatrial septum and may be a nidus for thromboembolism. We present the case of a 49 year-old man without known vascular risk factors who experienced bi-hemispheric strokes over the course of 10 days, suggestive of multiple emboli. Transesophageal echocardiography revealed a prominent LASP. We suggest that presence of LASP was a likely cause of stroke in this patient and that further study of a possible association between LASP and ischemic stroke in younger individuals may be warranted.

Left atrial septal pouch in cryptogenic stroke.

Background: The left atrial septal pouch (LASP), an anatomic variant of the interatrial septum, has uncertain clinical significance. We examined the association between LASP and ischemic stroke subtypes in patients undergoing transesophageal echocardiography (TEE). Methods: We determined the prevalence of LASP among consecutive patients who underwent TEE at our institution. Patients identified with ischemic strokes were further evaluated for stroke subtype using standard and modified criteria from the Trial of Org 10172 in Acute Stroke Treatment (TOAST). We compared the prevalence of LASP in ischemic stroke, cryptogenic stroke, and non-stroke patients using prevalence ratios (PR). Results: The mean age of all 212 patients (including stroke and non-stroke patients) was 57 years. The overall prevalence of LASP was 17% (n = 35). Of the 75 patients who were worked-up for stroke at our institution during study period, we classified 31 as cryptogenic using standard TOAST criteria. The prevalence of LASP among cryptogenic stroke patients (using standard and modified TOAST criteria) was increased compared to the prevalence among other ischemic stroke patients (26 vs. 9%, p = 0.06; PR = 1.8, 95% CI = 1.1–3.1, and 30 vs. 10%, p = 0.04; PR = 2.2, 95% CI = 1.2–4.1, respectively). Conclusion: In this population of relatively young patients, prevalence of LASP was increased in cryptogenic stroke compared to stroke patients of other subtypes. These findings suggest LASP is associated with cryptogenic stroke, which should be verified by future large-scale studies.

Hostility, health behaviors, and risk of recurrent events in patients with stable coronary heart disease: findings from the Heart and Soul Study.

Background Hostility is a significant predictor of mortality and cardiovascular events in patients with coronary heart disease (CHD), but the mechanisms that explain this association are not well understood. The purpose of this study was to evaluate potential mechanisms of association between hostility and adverse cardiovascular outcomes. Methods and Results We prospectively examined the association between self‐reported hostility and secondary events (myocardial infarction, heart failure, stroke, transient ischemic attack, and death) in 1022 outpatients with stable CHD from the Heart and Soul Study. Baseline hostility was assessed using the 8‐item Cynical Distrust scale. Cox proportional hazard models were used to determine the extent to which candidate biological and behavioral mediators changed the strength of association between hostility and secondary events. During an average follow‐up time of 7.4±2.7 years, the age‐adjusted annual rate of secondary events was 9.5% among subjects in the highest quartile of hostility and 5.7% among subjects in the lowest quartile (age‐adjusted hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.30 to 2.17; P<0.0001). After adjustment for cardiovascular risk factors, participants with hostility scores in the highest quartile had a 58% greater risk of secondary events than those in the lowest quartile (HR: 1.58, 95% CI: 1.19 to 2.09; P=0.001). This association was mildly attenuated after adjustment for C‐reactive protein (HR: 1.41, 95% CI, 1.06 to 1.87; P=0.02) and no longer significant after further adjustment for smoking and physical inactivity (HR: 1.25, 95% CI: 0.94 to 1.67; P=0.13). Conclusions Hostility was a significant predictor of secondary events in this sample of outpatients with baseline stable CHD. Much of this association was moderated by poor health behaviors, specifically physical inactivity and smoking.

A Comparison of Cook-Medley Hostility Subscales and Mortality in Patients With Coronary Heart Disease: Data From the Heart and Soul Study

Objective Hostility is associated with adverse outcomes in patients with coronary heart disease (CHD). However, assessment tools used to evaluate hostility in epidemiological studies vary widely. Methods We administered nine subscales of the Cook-Medley Hostility Scale (CMHS) to 656 outpatients with stable CHD between 2005 and 2007. We used Cox proportional hazards models to determine the association between each hostility subscales and all-cause mortality. We also performed an item analysis using logistic regression to determine the association between each CMHS item and all-cause mortality. Results There were 136 deaths during 1364 person-years of follow-up. Four of nine CMHS subscales were predictive of mortality in age-adjusted analyses, but only one subscale (the seven-item Williams subscale) was predictive of mortality in multivariable analyses. After adjustment for age, sex, education, smoking, history of heart failure, diabetes, and high-density lipoprotein, each standard deviation increase in the Williams subscale was associated with a 20% increased mortality rate (hazard ratio = 1.20, 95% confidence interval = 1.00–1.43, p = .046), and participants with hostility scores in the highest quartile were twice as likely to die as those in the lowest quartile (hazard ratio = 2.00, 95% confidence interval = 1.10–3.65, p = .023). Conclusions Among nine variations of the CMHS that we evaluated, a seven-item version of the Williams subscale was the most strongly associated with mortality. Standardizing the assessment of hostility in future epidemiological studies may improve our understanding of the relationship between hostility and mortality in patients with CHD.

Hostility and cardiovascular disease.

An association between hostility and coronary heart disease (CHD) was initially described one-half century ago. Two cardiologists, Friedman and Rosenman ([1,2][1]), identified a “coronary prone behavior pattern” that they called “type A,” which was primarily composed of competitiveness,