Christopher M. Celano, MD

Depression and anxiety disorders are common and persistent-and they have a lasting impact on quality of life, functioning, and cardiac health. In this article, we review the associations between negative psychological states and cardiovascular health, the physiologic and health behavior mechanisms that may mediate these relationships, ways to diagnose depression and anxiety disorders, and safe and effective treatments for these disorders.

Among patients with heart disease, such as coronary artery disease or heart failure, depression and anxiety disorders are extremely common. In these populations, 20% to 40% have elevated depressive symptoms, and 15% to 20% suffer from MDD.

 Anxiety may be even more common than depression. A recent meta-analysis suggests that over 50% of patients with heart failure have elevated rates of anxiety, and 13% meet criteria for an anxiety disorder.

 These prevalence rates are significantly higher than those in the general population and highlight the high-risk status of cardiac patients for these disorders.

In contrast to being a transient response to cardiac symptoms or a cardiac event, depression and anxiety may persist in many cases. After a myocardial infarction, depression tends to persist over the next year.

 Similarly, among individuals who have significantly elevated anxiety following an episode of acute coronary syndrome, only 50% have a resolution of their anxiety in the year after the event, which suggests that for many patients anxiety can remain a chronic problem.

Associations between psychiatric illness and cardiac health

Depression, anxiety, and anxiety disorders may play a significant role in heart health and have been implicated in the development and progression of both coronary artery disease and heart failure. Of these, depression has been studied most extensively. In patients without heart disease, depression is prospectively associated with the development of atherosclerosis and heart failure.

 Similarly, in patients with established heart disease, depression is associated with poor outcomes. Depression confers a 2-fold increased risk of mortality and adverse cardiac events after myocardial infarction or heart failure and has been linked to poor outcomes after cardiac surgery.

 The evidence for depression’s links to cardiac health is so strong that the American Heart Association (AHA) labeled depression a risk factor for poor medical outcomes following acute coronary syndrome.

Anxiety also appears to be associated with cardiac health, although less strongly than depression. In patients with coronary artery disease, anxiety is associated with an increased risk of adverse cardiac events; however, when adjusted for potential confounding variables, this relationship is significantly weakened, which suggests that other factors may be driving this relationship.

 In patients with heart failure, anxiety has been associated with poor outcomes in some analyses but not others, and this relationship typically disappears when controlling for covariates.

The links between anxiety disorders and cardiac health are significantly stronger. Anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, and PTSD, have been associated with an increased risk of coronary artery disease or heart failure.

 Among patients with established cardiovascular disease, anxiety disorders also are associated with poor cardiac outcomes. For example, following myocardial infarction, GAD has been prospectively linked to increased rates of subsequent mortality.

Mediators of the relationship between depression/anxiety and cardiac health

The links between depression, anxiety, and cardiovascular disease are complex and involve psychological, biological, and behavioral mechanisms.

 Depression, arrhythmias, and coronary artery disease frequently co-occur because they share common behavioral and pathophysiological drivers-unhealthy lifestyle, autonomic dysregulation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, endothelial dysfunction, and inflammation-that are intricately related to one another.

. There are numerous unhealthy behaviors that are common in depression, anxiety, and heart disease. Patients with depression and anxiety are more likely to smoke and drink alcohol, which are known risk factors for cardiovascular disease.

 Depressed persons are also less likely to exercise regularly, which may contribute to the development of cardiovascular disease and limit participation in cardiac rehabilitation.

 Furthermore, studies have shown that people with depression have a higher daily caloric intake while being deficient in vitamins D and B12 and folate, which may contribute to the metabolic dysregulation seen in depression and cardiovascular disease.

. Autonomic dysregulation, HPA axis dysregulation, inflammation, and endothelial dysfunction all may mediate the relationship between psychiatric illness and heart health. In depression, anxiety, and cardiovascular disease, an autonomic imbalance with sympathetic predominance is common; these disease states potentiate each other through the autonomic nervous system.

 Chronic stress can lead to inflammation, as well as alterations in cortisol levels via the HPA axis, which in turn leads to lasting, deleterious changes in the limbic system.

Inflammation also promotes depression and anxiety by reducing monoamine neurotransmitters in the brain, by activating anxiety-related neurocircuitry, and by decreasing antidepressant response; moreover, it has been implicated in the development of cardiovascular plaque formation.

 Finally, endothelial dysfunction is directly related to inflammation and is associated with depression, anxiety, and cardiovascular disease.

 Ultimately, it is likely that a combination of these shared physiologic processes and lifestyle choices may help explain the observed relationships between depression, anxiety, and cardiovascular health.

Diagnosing and screening for depression and anxiety disorders in cardiac disease

Prospective research studies have identified the negative effects of depression and anxiety on morbidity and mortality in patients with cardiac disease. Given the impact on patient prognosis, it is important to be vigilant in identifying these disorders and recommending treatment when indicated.

The overlap of symptoms in psychiatric disorders and cardiac disease may cause diagnostic confusion. When faced with somatic symptoms that overlap depression or anxiety and cardiac disease, clinicians may have difficulty determining which symptoms are related to cardiac disease and which to psychiatric illness. In these cases, it is important to determine whether any depression- or anxiety-specific symptoms are present. For example, among cardiac patients, sadness and loss of pleasure have been found mainly in those who meet criteria for major depression, whereas symptoms such as poor sleep and loss of appetite may occur in both depressed and non-depressed cardiac patients.

 When evaluating patients with overlapping cardiac and psychiatric symptoms, it is critical to evaluate patients both medically and psychiatrically (using DSM-5 diagnostic criteria) to ensure that there is a true psychiatric disorder diagnosis, and that underlying medical disorders are not misdiagnosed.

The association between depression and poor cardiac outcomes prompted the AHA to develop guidelines that outline a screening pathway for depression in patients with cardiac disease.

 It is important to keep in mind, however, that the benefits of screening are largely determined by the availability of mental health resources to assess and treat patients with positive screening results. The AHA recommends initial screening with the Patient Health Questionnaire (PHQ-2), which consists of 2 questions (inquiring about the presence of depressed mood or anhedonia over the past 2 weeks) and is quick and easy to administer.

Patients who have a positive response to either of the 2 questions should be screened with the 9-question Patient Health Questionnaire (PHQ-9).

 The PHQ-9 has the advantage of being a brief screening tool that can be completed and scored quickly, and it has reasonable sensitivity and specificity for depression in patients with cardiac disease.

 It is recommended that patients with screening scores that indicate a high probability of depression (PHQ-9 score of 10 or higher) should be referred for a more comprehensive clinical evaluation.

Anxiety disorders are prevalent among patients with cardiac disease and have been associated with adverse outcomes; however, in contrast to depression, no organization has developed guidelines for anxiety screening in this patient population. One study that examined a screening procedure for patients who were in inpatient cardiac units supported a 2-step screening for depression and GAD.

 Initial screening is based on a 4-item scale (GAD-2 plus PHQ-2). In patients whose scores are of concern, follow-up with the PHQ-9 and the GAD-728 is recommended.

 An emphasis was placed on screening linked with a treatment program to ensure a positive impact on individual patient outcomes. Bunevicius and colleagues

 compared several longer anxiety self-rating scales and found that the Hospital Anxiety and Depression Scale–Anxiety subscale (HADS-A) had greater specificity and positive predictive value in cardiac patients undergoing rehabilitation. False-positive scores were high and necessitated that patients with positive screening results undergo a psychiatric interview, thereby reducing the cost-effectiveness and clinical usefulness of routine screening with this scale.

Briefer validated screening tools that involve a step-wise escalation of the level of evaluation may be the most productive care pathway for patients with cardiac disease. It ensures that depression and anxiety disorders in cardiac patients who need treatment and counseling are identified in an expedient manner, and it optimizes the use of mental health resources.

Management of depression and anxiety disorders in cardiac disease

Once depression or an anxiety disorder is diagnosed, we recommend treatment because this may affect both psychiatric and cardiac health. Fortunately, safe and effective pharmacologic and psychotherapeutic interventions are available.

. Antidepressant medications-especially the SSRIs-are mainstays of treatment for depression and anxiety disorders. In contrast to TCAs, which can have significant cardiovascular adverse effects, SSRIs are better tolerated and have similar degrees of efficacy as older antidepressants.

 Sertraline, citalopram, and fluoxetine have been studied in patients with coronary artery disease, and in this patient population these medications ameliorate depression and have few adverse effects.

 In patients with heart failure, sertraline, escitalopram, citalopram, and paroxetine have been studied. While well-tolerated in this group, antidepressants unfortunately have been relatively ineffective at improving depressive symptoms.

 This may be because of the significantly greater burden of physical symptoms associated with heart failure compared with coronary artery disease.

If an SSRI is prescribed, several important factors should be considered. First, SSRIs have been shown to inhibit platelet aggregation in patients with cardiovascular disease, which can increase the risk of bleeding.

 Therefore, care should be taken when prescribing these medications to individuals who are taking antiplatelet agents or anticoagulants. Second, several SSRIs, especially citalopram and escitalopram, lead to prolongation of the QT interval, although not to the same degree as TCAs.

 Finally, certain SSRIs (eg, fluvoxamine, fluoxetine) can interact with medications for cardiovascular disease; care should be taken to identify potential interactions before prescribing these medications.

Other antidepressants also have been studied in patients with cardiovascular disease. Bupropion has been examined as a smoking cessation medication in patients with cardiovascular disease and appears safe in this population.

 The safety of venlafaxine and duloxetine is less clear. Case reports have linked these medications to exacerbations of heart failure, although a recent retrospective cohort study found that venlafaxine was associated with a lower risk of heart failure in adults older than age 66.

 Given the mixed evidence, we would recommend using SNRI medications only when alternative treatments (eg, SSRIs, bupropion) have failed and with significant caution because of their potential effect on cardiac function. Finally, given the effects of TCAs on intraventricular conduction, QTc prolongation, orthostatic hypotension, and tachycardia, we generally avoid using these medications in individuals with established heart disease, who are at higher risk for these adverse effects.

. Given its lack of adverse effects and medication interactions, psychotherapy is a very appealing option for the management of depression and anxiety disorders in patients with cardiac disease. Cognitive behavioral therapy (CBT) is the best-studied form of psychotherapy in patients with coronary artery disease or heart failure, and in these settings it is effective at reducing depressive symptoms.

 However, CBT has not been shown to reduce hospitalizations or mortality, and evidence for its use for the management of anxiety in cardiac populations has been extremely limited. Finally, CBT is not available in all areas, and patients with greater physical impairments may have difficulty attending sessions regularly. Therefore, its use should be reserved for patients who are able to commit to attending psychotherapy sessions.

In patients with cardiovascular disease, depression and anxiety disorders are common, persistent, and associated with poor functional and cardiac outcomes. As such, making a timely and accurate clinical diagnosis using DSM-5 criteria is critical. Safe and effective treatments are available for the management of these disorders in patients with cardiac disease, and it is hoped that such treatment can improve psychiatric health, quality of life, and medical outcomes.

The preparation of this manuscript was supported by the National Heart, Lung, and Blood Institute grant K23HL123607 to Dr. Celano. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health.

The authors acknowledge Christina Wichman, DO, FAPM, and Catherine C. Crone, MD, of the Academy of Psychosomatic Medicine (APM) for helping bring this article to fruition. The APM is the professional home for psychiatrists providing collaborative care bridging physical and mental health. Over 1200 members offer psychiatric treatment in general medical hospitals, primary care, and outpatient medical settings for patients with comorbid medical conditions.

Dr. Celano is Instructor in Psychiatry, Harvard Medical School, Boston, MA, and Assistant Psychiatrist, Department of Psychiatry, Massachusetts General Hospital, Boston, MA. Dr. Shapter is a third-year resident in psychiatry, Institute of Living/Hartford Hospital, Hartford, CT. Dr. Styra is Associate Professor, Department of Psychiatry, University of Toronto, Toronto, Canada, and staff psychiatrist, Centre for Mental Health, University Health Network, Toronto, Canada. Dr. Czick is attending anesthesiologist, Hartford Hospital, Hartford, CT, and Assistant Clinical Professor, University of Connecticut School of Medicine, Farmington, CT. The authors report no conflicts of interest concerning the subject matter of this article.

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Articles

Here: a look at the associations between negative psychological states and CV health, physiologic and health behavior mechanisms, and ways to diagnose and treat depression and anxiety disorders. 

Christopher M. Celano, MD

Articles

Depression and Anxiety in Cardiac Disease