Depression and heart disease: What do we know, and where are we headed?

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ABSTRACTDepression and heart disease have an intricate association and perhaps a causal relationship. We review the current status of depression and heart disease and provide an algorithm for diagnosing and treating depression in cardiac patients that internists and cardiologists can use in their daily patient encounters.


  • Depression is a risk factor for new cardiac disease and has a detrimental impact in established cardiac disease.
  • Numerous mechanistic pathways have been implicated.
  • In clinical trials, drug therapy and psychotherapy have not clearly decreased the rate of cardiac death in depressed cardiac patients, but they did improve depression, adherence to drug therapy, and quality of life.
  • Clinicians should routinely screen for depression in cardiac patients and should not hesitate to treat it.
  • Eligible patients should routinely be referred to cardiac rehabilitation programs.



Depression is a risk factor for heart disease, and in patients with heart disease, it is a risk factor for complications and death. Unfortunately, in the trials performed to date, treating depression in cardiac patients did not lead to lower rates of recurrent cardiovascular events or death. Nevertheless, we recommend that clinicians systematically screen for it in their heart patients, in view of the benefits of antidepressant therapy.

In this article we review key epidemiologic and psychosocial studies, the mechanistic links between depression and heart disease, and recent intervention trials. We also offer practical management advice and address the continued need for guidelines and risk stratification in the treatment of depressed cardiac patients.

After we submitted our review article, the American Heart Association (AHA)1 released a consensus document recommending that health care providers screen for and treat depression in patients with coronary heart disease. We will discuss the same screening tests that have been recommended by the AHA.


Depression and heart disease are very common and often coexist: the prevalence of depression in various heart conditions ranges from 15% to 20%.1–3 According to data from the World Health Organization, by the year 2020 depression will be the second-leading cause of disability in developed countries (after heart disease).4

The World Health Survey5 showed that depression worsens health more than angina, arthritis, asthma, or diabetes. Furthermore, patients with severe mental illness have a higher risk of dying from heart disease and stroke.6


In the 1980s, the “type A” personality (ambitious, aggressive, hostile, and competitive, with a chronic sense of urgency) was linked to heart disease.7 Later studies differed as to whether the entire set of features is valid as a collective risk factor for progressive heart disease,8 but hostility remains a validated risk factor and a focus of behavior modification.9,10

Other psychosocial risk factors have been implicated,11,12 one of which is social isolation.9,13 Another is the “type D” personality, which includes a tendency to experience negative emotions across time and situations coupled with social inhibition and which is believed to be more valid than the type A personality as a risk factor for cardiac disease.14,15

The INTERHEART study16 gathered data about attributable risk in the development of myocardial infarction (MI) in 52 countries in a case-control fashion. Psychosocial factors including stress, low generalized locus of control (ie, the perceived inability to control one’s life), and depression accounted for 32.5% of the attributable risk for an MI.17 This would mean that they account for slightly less attributable risk than that of lifetime smoking but more than that of hypertension and obesity.

Job stress increases the risk of initial coronary heart disease18 and also the risk of recurrent cardiac events after a first MI.19 Even though numerous psychosocial risk factors have been associated with coronary heart disease, including anxiety,20,21 depression is perhaps the best studied.


To examine the impact of depression in coronary heart disease, prospective studies have been done in healthy people and in patients with established cardiovascular disease who develop depression.22

In healthy people, depression increases the risk of coronary disease

The 1996 Epidemiologic Catchment Area study23 found that people with major depression had a risk of MI four times higher than the norm, and people with 2 weeks of sadness or dysphoria had a risk two times higher.

A subsequent meta-analysis of 11 studies,24 which included 36,000 patients, found that the overall relative risk of developing heart disease in depressed but healthy people was 1.64.

A meta-analysis by Van der Kooy et al25 of 28 epidemiologic studies with nearly 80,000 patients showed depression to be an independent risk factor for cardiovascular disease.

Wulsin and Singal26 performed a systematic review to see if depression increases the risk of coronary disease. In 10 studies with a follow-up of more than 4 years, the relative risk in people with depression was 1.64, which was less than that in active smokers (2.5) but more than that in passive smokers (1.25).

Depression can also exacerbate the classic risk factors for coronary disease, such as smoking, diabetes, obesity, and physical inactivity. 27

A 2007 study from Sweden28 prospectively followed patients who were hospitalized for depression. The odds ratio of developing an acute MI was 2.9, and the risk persisted for decades after the initial hospitalization.

A prospective United Kingdom cohort study of people initially free of heart disease revealed major depression to be associated with a higher rate of death from ischemic heart disease.29 Specifically, patients who had depression currently or in the past 12 months had a 2.7 times higher risk of dying than those who had never had depression or who had had it more than 12 months previously.

In existing heart disease, depression predicts recurrent events, death

Carney et el30 found that patients with major depressive disorder had a higher incidence of new cardiac events in the 12 months after undergoing cardiac catheterization than those without major depressive disorder.

Frasure-Smith et al,31 in a landmark study, showed that patients who were depressed at 1 week after an MI were three to four times more likely to die in the next 6 months than nondepressed post-MI patients. Even after 18 months, depression remained an independent risk factor for cardiac-related death.32

In longer studies (with up to 19.4 years of follow-up), depression was associated with higher rates of death from cardiac and all causes in patients with coronary artery disease.33 Lespérance et al34 found that in MI patients, the higher the Beck Depression Inventory score at the time of hospital admission, the higher the 5-year death rate.

Using meta-analysis, Barth et al35 found the risk of dying in the first 2 years after initial assessment to be twice as high in depressed cardiac patients as in nondepressed cardiac patients (odds ratio 2.24).

Van Melle et al36 reviewed 22 studies and found that in the 2 years after an MI, depressed patients had a 2 to 2.5 times higher risk of dying of a cardiac or any other cause than did nondepressed patients.

Depression also predicts higher morbidity and mortality rates in patients undergoing coronary artery bypass grafting,37,38 patients with congestive heart failure,39 and heart transplant recipients.40


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