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Depression and Cardiovascular Disease PROGRESS IN CARDIOVASCULAR DISEASES 55 (2013) 511– 523 Available online at www.sciencedirect.com www.onlinepcd.com Depression and Cardiovascular Disease Larkin Elderona, Mary A. Whooleyb,⁎ aUCSF School of Medicine, San Francisco, CA bDepartments of Medicine, Epidemiology & Biostatistics, UCSF School of Medicine and San Francisco Veterans Affairs Medical Center, San Francisco, CA ARTICLE INFO ABSTRACT Keywords: Approximately one out of every five patients with cardiovascular disease (CVD) suffers from Cardiovascular disease major depressive disorder (MDD). Both MDD and depressive symptoms are risk factors for Major depressive disorder CVD incidence, severity and outcomes. Great progress has been made in understanding Health-related behaviors potential mediators between MDD and CVD, particularly focusing on health behaviors. Diagnosis Investigators have also made considerable strides in the diagnosis and treatment of Treatment depression among patients with CVD. At the same time, many research questions remain. In what settings is depression screening most effective for patients with CVD? What is the optimal screening frequency? Which therapies are safe and effective? How can we better integrate the care of mental health conditions with that of CVD? How do we motivate depressed patients to change health behaviors? What technological tools can we use to improve care for depression? Gaining a more thorough understanding of the links between MDD and heart disease, and how best to diagnose and treat depression among these patients, has the potential to substantially reduce morbidity and mortality from CVD. Published by Elsevier Inc. Major depressive disorder (MDD) is present in approximately link MDD and CVD, but also on how to best screen and treat 1 1 out of every 5 patients with cardiovascular disease (CVD). patients with both conditions. This manuscript reviews some Beyond its frequent co-occurrence with CVD, MDD has been of these important discoveries and highlights future direc- associated with both increased incidence and worse out- tions that we hope will lead to new treatment strategies for comes of coronary heart disease (CHD), even after controlling these diseases. for traditional CVD risk factors. The presence of depressive symptoms (with or without a clinical diagnosis of MDD) predicts incident CHD in healthy individuals,2 secondary Is depression an independent risk factor of CVD? – events in patients with known CHD,3 6 and adverse outcomes among individuals who have undergone coronary artery Historically, age, gender, family history of CVD, smoking, bypass grafting.7 MDD was the 4th leading cause of worldwide hypertension, diabetes, cholesterol levels, obesity and physi- disability in 2002 and is expected to become the 2nd leading cal inactivity have been recognized as “traditional risk factors” cause of worldwide disability by 2030.8 In recent years, for CVD. In recent decades, studies have demonstrated that researchers have shed light not only on what mechanisms psychosocial factors play an equal role in predicting CVD Statement of Conflict of Interest: see page 519. ⁎ Address reprint requests to Mary A. Whooley MD, FACP, FAHA, FACC, University of California, San Francisco, Department of Veterans Affairs Medical Center, 4150 Clement Street (111A1), San Francisco, CA 94121. E-mail address: [email protected] (M.A. Whooley). 0033-0620/$ – see front matter. Published by Elsevier Inc. http://dx.doi.org/10.1016/j.pcad.2013.03.010 Downloaded for Anonymous User (n/a) at SAN FRANCISCO VA MEDICAL CENTER from ClinicalKey.com by Elsevier on June 14, 2019. For personal use only. No other uses without permission. Copyright ©2019. Elsevier Inc. All rights reserved. 512 PROGRESS IN CARDIOVASCULAR DISEASES 55 (2013) 511– 523 Abbreviations and Acronyms morbidity and mortali- Many studies have sought to determine how depression ty. The INTERHEART interacts with other CVD risk factors. A study published by AHA = American Heart study, a case–control Rutledge and colleagues followed 620 women for a median of Association study which examined 5.9 years of follow-up, and found that the relationship BDI = Beck Depression Inventory modifiable risk factors between modifiable CVD risk factors and CVD outcomes CBT = Cognitive-Behavioral for acute myocardial varied with depression status. The authors concluded that, Therapy infarction (MI) in over in addition to influencing CVD as an independent risk factor, 25,000 patients from depression also intensifies the influence of other risk factors CHD = Coronary Heart Disease 52 different counties, on cardiac outcomes. This finding points to the need for COPES = Coronary Psychosocial found that psychoso- further research to understand the complex interactions 18 Evaluation Study cial factors were stron- among the numerous pathways leading to CVD. While ger risk factors for most researchers recognize that depression is an independent CVD = Cardiovascular Disease incident MI than were risk factor for CVD, an aim in future years will be to ENRICHD = Enhancing Recovery diabetes, smoking, hy- understand the interrelationship of various behavioral and 9 in Coronary Heart Disease pertension and obesity. biological pathways that contribute to cardiac risk. The psychosocial fac- HF = Heart Failure tors examined in this IPT = Interpersonal Therapy study included depres- sion, locus of control, How does depression contribute to CVD? MDD = Major depressive disorder perceived stress, and PHQ-2 = 2-Item Patient Health life events. Based on The finding that depression predicts CVD incidence and Questionnaire the findings of this and severity has prompted the question of precisely how depres- other studies, depres- sion causes or exacerbates CVD. Multiple potential biological PHQ-9 = 9-Item Patient Health sion was officially rec- and behavioral mediators have been identified, including Questionnaire ognized as a CHD risk smoking, physical inactivity,19 medication nonadherence,20,21 PST = Problem-Solving Therapy factorinthe2010Global lower heart rate variability,22 toxicity from antidepressants,23 Burden of Disease enhanced activity of the hypothalamo-pituitary-adrenal PAD = Peripheral Arterial Disease Study.10 (HPA) axis,24 greater catecholamine levels,25 poor diet, low SSRI = Selective Serotonin Reup- In addition to CHD, omega-3 fatty acid levels,26 platelet activation,27 and inflam- take Inhibitor depression (defined matory processes.28,29 However, most of these factors have here as either MDD or been identified based on separate linkages with both depres- significant depressive symptoms with substantial functional sion and CVD. Health behaviors, inflammatory processes and impairment) is associated with an increased risk of—and heart rate variability are the only candidate mechanisms that adverse outcomes among patients with—heart failure (HF), have actually been shown to mediate the association. – stroke,11 and peripheral artery disease (PAD).11 13 One study The bulk of evidence suggests that poor health behav- of 4500 patients with HF found that the relative risk of HF in iors, particularly physical inactivity, are largely responsible – depressed patients as compared to non-depressed patients for the excess risk of CVD associated with depression.30 38 In was 2.6, even after adjustment for traditional CVD risk the Heart and Soul Study, a prospective cohort study of 1024 factors.14 Depression has also been shown to be an indepen- subjects with stable coronary heart disease, patients with dent predictor of mortality and re-hospitalization among depressive symptoms had a 50% greater rate of adverse patients with established HF.15 cardiovascular events than those without depressive symp- Similarly, depression increases risk of recurrent total toms. The increase in risk was attenuated, but still stroke, fatal stroke and ischemic stroke in patients with significant, following adjustment for comorbid conditions existing cerebrovascular disease.11 In the reverse direction, and left ventricular ejection fraction. However, the differ- stroke survivors have a 33% greater pooled frequency of ence in outcomes was no longer significant following depressive symptoms compared to that of the general adjustment for smoking, medication adherence, and espe- population, with higher rates found when more formal cially physical activity.32 Several other cohort studies have – depression scales were used.16,17 As one might expect, worse reported similar findings.30,31,33 36 functional status and inability to work following stroke were Inflammation is another potential mediator of interest. associated with an even higher risk of depression in these Certain inflammatory biomarkers such as C-reactive protein, patients.16 As compared with other forms of CVD, cerebro- interleukin 1, and interleukin 6 have been associated with vascular disease is unique in that depression may be directly atherosclerosis and depression alike, both in healthy subjects – linked to cerebral ischemia through patterns of blood flow in and in cardiac patients.29,39 45 However, previous studies have the central nervous system. This contrasts to MI or HF, which suggested both that inflammation increases risk of are thought to be related to depression more indirectly depression42,46 and that depression causes inflammation in through symptom burden, emotional distress and functional patients with CHD.47 Thus, it is difficult to determine whether impairment. The mechanisms relating depression to cerebral such markers serve as triggers of both depression and CVD,
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