A synopsis based on the WPA volume “Depression and Heart Disease”
(Glassman AH, Maj M, Sartorius N, eds. – Chichester: Wiley, 2010)

• The incidence of DSM-III major depressive disorder after myocardial infarction has been found to be 16% (Schleifer et al.,
1989; Frasure-Smith et al., 1993). Studies based on selfadministered questionnaires have reported rates up to 50%.
From Jiang W, Xiong GL. Epidemiology of the comorbidity between depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N
(eds). Chichester: Wiley, 2010.

• Patients with major depression after myocardial infarction are 5 times more likely to die from cardiac events by 6 months than non-depressed patients. At 18 months, cardiac mortality reaches 20% in patients with major depression vs. 3% in nondepressed patients (Frasure-Smith et al., 1993, 1995).
• Patients with a Beck Depression Inventory score ≥10 after myocardial infarction are almost 7 times more likely to die by 18 months than those with a score <10 (Frasure-Smith et al., 1995).
From Jiang W, Xiong GL. Epidemiology of the comorbidity between depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N
(eds). Chichester: Wiley, 2010.

The cumulative mortality is significantly higher in depressed than in non-depressed patients following myocardial infarction (MI) (Lesperance at al., Circulation 2002;105:1049-1053). From
Glassman AH, Bigger JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In: Depression and Heart
Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.

• In patients with stable coronary heart disease, the DSM-IV diagnosis of major depression is the best predictor of cardiac events at 1 year. The relative risk is 2.2 times higher in patients with major depression than in non-depressed patients (Carney et al., 1988).
•
Among patients hospitalized for unstable angina, those with a Beck
Depression Inventory ≥10 had a rate of death or myocardial infarction one year after assessment 5 times higher than their non-depressed counterparts (Lesperance et al., 2000).
From Jiang W, Xiong GL. Epidemiology of the comorbidity between depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

• Clinical depression is associated with an almost 2-fold higher risk of subsequent coronary heart disease.
This association remains significant after adjustment for smoking, alcohol use and coffee consumption (Ford et al., 1998).
• A meta-analysis of 28 studies comprising almost 80,000 subjects found that depression was associated with increased risk of cardiovascular diseases, in particular for acute myocardial infarction
(RR = 1.6) (van der Kooy et al., 2003).
From Jiang W, Xiong GL. Epidemiology of the comorbidity between depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

Mechanism
Sleep disturbance
Physical inactivity
Comment
Common in depression; may be exacerbated by heart disease symptoms
Common in depression
Effect on heart disease
Leads to autonomic hyperactivity which is linked to obesity, diabetes, hypertension, and the metabolic syndrome
Increases cardiovascular morbidity and mortality
Cigarette smoking Individuals with depression are more likely to smoke, and depressed smokers are less likely to quit
Increases cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

Poor hygiene
Mechanism
Adherence to treatment
Comment Effect on heart disease
Inattentiveness to self care is more common in depression; depression is associated with decreased salivary flow and cariogenic diet. Some antidepressants cause xerostomia and gingivitis
Periodontal disease (especially gingivitis) has been associated with increased cardiovascular morbidity and mortality
Patients with depression are less likely to adhere to medical therapy and risk reducing behaviors
Poor adherence to medical therapy is associated with increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

Mechanism
Attitudes about treatment
Social isolation
Comment Effect on heart disease
Depression may be associated with negative attitudes toward treatment.
Individuals with depression may perceive more, and have greater concern about, medication side effects
Attitudes about treatment appear important to therapeutic effect; even poor adherers to placebo in cardiovascular disease trials have increased mortality
Depression is associated with less social support and greater social isolation
Decreased social support and social isolation are associated with increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

Mechanism
Cardiovascular stress response
Comment Effect on heart disease
Some studies show that depression is associated with heightened, and some with attenuated, cardiovascular reactivity to physiological stress
Autonomic hyperactivity at baseline and in response to stressors may increase cardiovascular risk
Self-efficacy Depression is often associated with low self-efficacy
Low self-efficacy is associated with greater symptom burden and physical limitation; worse quality of life; poor adherence; and possibly increased cardiovascular morbidity and mortality
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

• Autonomic nervous system dysregulation (low heart rate variability is a powerful predictor of mortality in patients with coronary heart disease; depressed patients have a decreased heart rate variability than non-depressed controls).
• Blood clotting and endothelial dysfunction (depression is associated with enhanced platelet activation, increased plasma levels of pro-thrombogenic factors and reduced endothelial dependent vasodilatation).
• Inflammation (depression is associated with increased levels of pro-inflammatory cytokines and inflammatory acute phase proteins; activation of the inflammatory system is linked to ischemic cardiovascular events in patients with coronary heart disease).
• Neuroendocrine abnormalities (depression is associated with an increased activity of the hypothalamic-pituitary-adrenal axis, with a consequent overstimulation of the sympathetic nervous system).
From Monteleone P. The association between depression and heart disease: the role of biological mechanisms. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

• Twin and family studies provide evidence for a role of genetic pleiotropy in the association between major depression and coronary heart disease (i.e., genetic variants influence risk factors that independently increase the risk for both major depression and coronary heart disease). The actual genetic variants at the base of this pleiotropy remain to be detected.
From de Geus E. The association between depression and heart disease: the role of genetic factors. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester:
Wiley, 2010.

• Selective serotonin reuptake inhibitors (SSRIs) are safe in the immediate post-MI period and are effective antidepressants.
• Although evidence suggests that antidepressants are particularly active in more severely depressed patients, it is premature to conclude that there is no treatment effect in the less severely depressed post-MI patients.
• There is strong suggestion that antidepressants in general, and SSRIs in particular, reduce morbidity and mortality in post-MI depressed patients.
From Glassman AH, Bigger JT.
Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In:
Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.

Relative risk (95% CI) for cardiovascular events: sertraline vs. placebo (adapted from Glassman et al., JAMA 2002;288:701-709). From Glassman AH, Bigger JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester:
Wiley, 2010.

Effects of antidepressant drug use on clinical events over 30 months during the ENRICHD trial
(adapted from Taylor et al., Arch. Gen. Psychiatry 2005;62:792-798). From Glassman AH, Bigger
JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In: Depression and Heart Disease. Glassman AH,
Maj M, Sartorius N (eds). Chichester: Wiley, 2010.

• In the ENRICHD trial, individual cognitive psychotherapy was superior to usual care for depression (Berkman et al., 2003).
•
In the ENRICHD trial, patients who completed the 6-month cognitive psychotherapy and whose depression improved had a lower risk of late mortality than those who remained depressed despite completing the intervention (Carney et al., 2004).
From Carney RM, Freedland KE. Psychotherapies for depression in people with heart disease. In:
Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.

• Post-MI patients should be screened for the presence of depression by a simple well-validated instrument (such as the Patient Health
Questionnaire).
• When a patient screens positive for depression, a primary care provider familiar with managing depression should follow and support him/her, with the regular supervision by a psychiatrist.
•
There is a need to educate physicians and to establish a system to identify, treat and follow up cardiac patients with depression.
From Glassman AH, Bigger JT. Depression and cardiovascular disease: the safety of antidepressant drugs and their ability to improve mood and reduce medical morbidity. In:
Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds). Chichester: Wiley, 2010.

•
Sleep. Ask your patients about their sleep habits. Ask about why patients are awakening, and see if changes in treatment or the timing of medications might decrease the need to awaken during the night to pass urine or because of breathlessness.
•
Physical activity. Strongly encourage your patients to exercise at home and to become involved (and stay involved) in structured exercise programs. Greater involvement in exercise may improve symptoms of depression.
• Cigarette smoking. Ask every patient whether he/she smokes, and counsel about smoking cessation if appropriate. Every clinician should become familiar with medications that help patients quit, and should offer specific advice on how to quit and/or set a quit date.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

• Medication adherence.
Specifically address the issue of medication adherence with every patient and try to decrease barriers to adherence.
Simplifying medication regimens, eliminating medications that are not absolutely necessary, and prescribing low-cost alternatives may be helpful in specific circumstances.
• Attitudes and beliefs about cardiac treatment regimens. Anticipate the possibility that patients with depression may have greater levels of concern and more negative attitudes and beliefs about medical treatment regimens.
Discuss the importance of each medication, what the goals of treatment are, and how the patient’s particular health goals are more likely to be achieved by adhering to a particular medical treatment.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

• Social isolation. Encourage patients to socialize with family and friends; offer to engage family and friends on behalf of the patient, encourage the patient to participate in group activities that may be appropriate and desirable (sport clubs, hobbies, religious groups).
• Self-efficacy. Inquire about your patient’s confidence that he/she can accomplish a given task or behaviour (e.g., participation in a cardiac rehabilitation program, stopping smoking, following a proper diet). If the patient’s confidence is low, consider specific counseling that might enhance self-efficacy.
From Ziegelstein RC, Elfrey MK. Behavioural and psychological mechanisms linking depression and heart disease. In: Depression and Heart Disease. Glassman AH, Maj M, Sartorius N (eds).
Chichester: Wiley, 2010.

This synopsis is part of the WPA programme aiming to raise the awareness of the prevalence and prognostic implications of depression in persons with physical diseases. The support to the programme of the
Lugli Foundation, the Italian Society of Biological Psychiatry, Eli-Lilly and
Bristol-Myers Squibb is gratefully acknowledged. The WPA is grateful to
Dr. Andrea Fiorillo, Naples, Italy for his help in the preparation of this synopsis.