Depression, Anxiety, and Stress

American Heart Association

In 2008, the American Heart Association (AHA) issued a science advisory endorsed by the American Psychiatric Association (APA) that recommended administering a depression screening questionnaire to ACS patients and referring those who screen positive to a professional qualified to diagnose and manage depression according to the algorithm in Fig. 26.1 . Boxes 26.1 and 26.2 detail the recommended screening questionnaires. The United States Preventative Services Task Force (USPSTF) and AHA/APA guidelines recommend the Patient Health Questionnaire-2 (PHQ-2) yes/no version as the initial screen, as it has been validated as more sensitive and easier to administer than the PHQ-2 multiple choice screening questionnaire. This advisory effectively expanded the scope of the previous year’s release of evidence-based guidelines for cardiovascular disease prevention in women, which suggested that screening women at risk of CHD for depression and referring/treating when indicated was a class IIa (weight of evidence/opinion is in favor of usefulness/efficacy), level B (limited evidence from single randomized trial or other randomized studies) recommendation. The 2008 AHA advisory did specifically note that, at the time of its issuance, there was no direct evidence linking the treatment of depression with improved cardiac outcomes.

The AHA/American College of Cardiology (ACC) released secondary prevention guidelines for CHD patients in 2011 that provide a class IIa, level B recommendation that patients with recent myocardial infarction (MI) or coronary artery bypass graft (CABG) be screened for depression. These guidelines acknowledged that treating depression has not been shown to improve CHD outcomes but issued a class IIb, level C recommendation for treating depression with the logic that it may have clinical benefits other than improved CHD outcomes.

In 2014, the AHA issued a scientific statement formally recognizing depression as a risk factor for poor post-ACS outcomes, including all-cause mortality, cardiac mortality, and composite endpoints (cardiac or all-cause mortality and nonfatal cardiac events). This conclusion was based on a systematic review that identified prospective studies showing a strong and consistent observational association between depression and CHD outcomes, a lack of other explanations for this association, and the existence of a plausible biologic mechanism to account for this association.

American Academy of Family Practitioners

In 2009, the American Academy of Family Practitioners (AAFP) published guidelines for the detection and management of post-MI depression. It issued four specific guidelines based on review of published evidence. First, it recommended using any standardized symptom checklist to screen post-MI patients for depression during the index hospitalization and at regular intervals thereafter. Second, it recommended treating post-MI depression in order to improve symptoms. These recommendations were issued as level A with the specific note that they were based on RCTs showing improvement in depression outcomes but not cardiac outcomes, “though the evidence does not yet exclude the possibility of a small benefit.” The third and fourth recommendations suggested selective serotonin reuptake inhibitors (SSRIs) (level A) and/or psychotherapy (level B) for treating depression.

European Societies

The European Guidelines on Cardiovascular Disease Prevention in Clinical Practice are issued by a task force of the European Society of Cardiology and other societies. In 2012, the guidelines stated that depression contributes to both incident CHD and poor CHD outcomes. The guidelines made class IIa, level B recommendations that depression be assessed by a clinical interview or standardized questionnaire, and that tailored clinical management for depression be considered with the goal of improving CHD outcomes and enhancing quality of life.

The British healthcare system, via the National Institute of Health and Care Excellence (NICE), endorses depression screening in CHD patients and referral for treatment if depression is detected.

European Societies

The 2012 European prevention guidelines also state that anxiety contributes to both incident CHD and poor CHD outcomes. The guidelines included anxiety in the class IIa, level B recommendations, suggesting that anxiety be screened for via clinical interview or standardized questionnaire and tailored clinical management should be given, with the goal of improving CHD outcomes and enhancing quality of life.

European Societies

The 2012 guidelines also state that stress at work and in family life increases the risk of both incident CHD and poor CHD outcomes. The guidelines provide a class IIa, level B recommendation to screen and provide tailored clinical management for stress, with the goal of improving CHD outcomes and enhancing quality of life.

Both stress and anxiety have not been the focus of guidelines or consensus statements; however, interest in this topic seems to be increasing.

Depression and Incident Coronary Heart Disease

In many studies with varied cohorts, depressive symptoms were associated with an increased risk of developing CHD. Depressive symptoms confer a relative risk of CHD ranging from 0.98 to 3.5 in different studies and a combined overall risk ranging from 1.6 to 5.4 compared with nondepressed patients in systematic reviews. MDD is associated with an even greater risk of incident MI with an odds ratio of approximately 4.5. The risk associated with depressive symptoms or clinical depression is perhaps even greater than that associated with traditional cardiovascular risk factors, as seen in Fig. 26.2 .

Depression among Patients with Coronary Heart Disease

Depression is one of the more frequently encountered chronic diseases among general medical patients, with a prevalence ranging from approximately 5% to 15%. Depression is even more prevalent among CHD patients ( Fig. 26.3 ). As many as 20% of CHD patients meet the diagnostic criteria for MDD by The Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria and 30% to 50% have significant patient-reported depressive symptoms. The increased prevalence of depression extends past the immediate post-MI period. Importantly, both clinically diagnosed depression and depressive symptoms predict increased cardiac risk. Approximately 7 million Americans living with CHD also have clinically significant depression, and half a million new such cases are added to this public health burden annually.

Prognosis Associated with Depression in Patients with Coronary Heart Disease

Compared with nondepressed post-MI patients, depressed post-MI patients have more medical comorbidities and cardiac complications and higher mortality rates. Observational studies show that ACS patients with depressive symptoms are at a two-fold higher risk of MI recurrence. As seen in Fig. 26.4 , depressive symptoms in CHD patients are at par with conventional CHD prognostic factors for predicting death and CHD recurrence.

The AHA formally recognizes depression as a risk factor for poor outcomes among ACS patients based on its systematic literature review showing depression is a risk factor for all-cause mortality, cardiac mortality, and composite endpoints (cardiac or all-cause mortality and nonfatal cardiac events) after ACS. Others have argued, however, that depression may be a risk marker rather than a risk factor because there is no trial evidence that treating depression alters the prognosis, making it more analogous to high-density lipoprotein or C-reactive protein (CRP).

Impact of Depression on Health-Related Quality of Life

Depression is more strongly associated with health-related quality of life and health status than a single health condition such as angina, arthritis, asthma, or diabetes. Depression clearly predicts impoverished health-related quality of life independent of traditional predictors of quality of life, specifically among patients with stable CHD and those with a recent ACS. In several studies of multiple predictors of quality of life in CHD patients, depression was the most important even when other predictors such as demographic and social variables, severity of disease, ejection fraction, and ischemia were assessed. Recent ACS patients with a history of depression have twice the rate of angina, triple the physical limitations, and almost triple the risk of diminished health-related quality of life. There have been calls to improve quality of life in post-ACS patients, rather than continuing to focus on extending life of diminished quality. Some suggest that treating depression could answer this call.

Costs Associated with Depression

Depression has long been associated with high costs of medical utilization, many lost days of productivity, and reduced work performance. Patients who have a chronic medical condition, such as CHD, with depression have significantly more ambulatory visits, emergency room visits, days in bed due to illness, and functional disability. Annual healthcare costs were almost 41% higher and 5-year healthcare costs were almost 53% higher in depressed post-MI patients compared with nondepressed post-MI patients.

Platelet Reactivity

Several case-controlled studies have demonstrated platelet hyperreactivity in CHD patients, and CHD patients with MDD have exhibited higher levels of platelet factor 4 and β-thromboglobulin (β-TG)—markers of platelet aggregation—and platelet/endothelial cell adhesion molecule-1 when compared with CHD patients without MDD.

Inflammation

Elevated levels of inflammatory biomarkers, including CRP, soluble intercellular adhesion molecule 1 (sICAM1), soluble vascular cell adhesion molecule-1, and tumor necrosis factor-α, are associated with an increased risk of cardiovascular events in patients with known CHD. Several cross-sectional studies have linked depression to chronic inflammation—as measured by CRP or sICAM1 levels—both in otherwise healthy participants and in post-ACS patients shortly after the index event. Proinflammatory cytokines may contribute to coronary atherosclerosis.

Autonomic Dysregulation

Autonomic dysregulation is characterized by increased activation of the sympathetic nervous system (SNS), which usually acts in concert with a reduced activation of the parasympathetic nervous system (PNS). Excess SNS activity produces many effects that contribute to CHD: high blood pressure, increased myocardial oxygen demand, platelet activation, increased myocyte apoptosis, and arrhythmias. Both elevated SNS activity and reduced PNS activity have been implicated in depression and CHD recurrence. Furthermore, CHD patients with depressive symptoms have been shown to have greater SNS activity as measured by higher norepinephrine excretion levels compared with CHD patients without depressive symptoms.

Sleep Architecture Disruption

Depression and sleep architecture disruption are closely linked, although the specific dysregulated polysomnographic parameters are unclear. Studies have shown that reduced rapid eye movement (REM) latency—the time from sleep onset to the first occurrence of REM—is the most frequently reported sleep dysregulation that distinguishes MDD patients from individuals without MDD. REM sleep is characterized by pronounced surges of SNS, which may be of sufficient magnitude to stimulate thrombotic processes, to increase hemodynamic stress on vessel walls conducive to plaque rupture, and to alter cardiac electrophysiologic properties. These autonomic surges may be responsible for cardiac events witnessed during REM sleep in humans. Importantly, this REM-induced cardiac sympathetic dominance is enhanced in individuals with a recent MI. Additionally, the total sleep time is consistently decreased in depressed patients and those prone to depressive episodes. Although there is a lack of prospective epidemiologic studies on the dimensions of sleep architecture and CHD recurrence, there is epidemiologic evidence that short sleep duration is predictive of ACS.