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Heart Disease

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Can Mental Stress Lead to Heart Disease?


The Tale of Mind & Heart: Psychiatric Disorders & Coronary Heart Disease

Missouri Medicine - Missouri State Medical Association Logo

Published in Missouri Medicine, the journal of the Missouri State Medical Association, June/July 2012



The mind-body interaction has always intrigued humans.  Most people, on the basis of either intuition or personal experience, believe that emotional stress can cause or alter the course of even major physical diseases.  Sir William Osler described his typical patient with angina pectoris as ‘a man whose engine is always set full speed ahead’ and described his patients with cardiac disease as ‘worriers’.  In recent years there has been tangible evidence for the existence of this interaction however modern medicine is still trying to unravel its intricacies.

In this article we review the current knowledge regarding the effect of depression, anxiety disorders and the detrimental effect it has on coronary heart disease. In addition we discuss some of the proven acute psychological triggers for acute coronary syndrome.



Heart disease has considerable impact on individual’s overall health, well-being and perception of mortality.  Therefore, it is not surprising that depression is the most prevalent psychiatric disease in patients with coronary heart disease (CHD).  About 20% of patients with chronic CHD and 16-23% of those with acute coronary syndrome meet diagnostic criteria for major depression, while an even larger percentage has depressed mood but don’t meet diagnostic threshold of major depression.1, 2  The exact mechanisms underlying the interplay between depression and ischemic heart disease remain poorly understood and the same is true for the most effective depression treatment for cardiac patients.

There is evidence that patients with depression are more likely to develop CHD.  However, whether depression is an independent risk factor for CHD is still a matter of debate.  Several studies suggest an interaction between depression and the development of CHD after adjustment for traditional cardiovascular risk factors.3,4,5,6 Such studies however have been criticized for being based on registries and for incomplete adjustments for the multiple known risk factors for CHD.

In one study a cohort of 2,832 subjects who participated in the National Health Examination Follow-up Study (mean follow-up=12.4 years) and who had no history of CHD or serious illness at baseline, 11% had depressed affect; 10.8% reported moderate hopelessness, and 2.9% reported severe hopelessness.  After adjustment for demographics and CHD risk factors, patients with depressed affect were at higher risk to suffer fatal CHD, relative risk 1.5 (95% CI 1.0–2.3). Moderate as well as severe levels of hopelessness also increased risk of fatal CHD, relative risk 1.6 (95% CI=1.0–2.5) and 2.1 (95% CI=1.1–3.9), respectively.  Depressed affect and hopelessness were found to be associated with an increased risk of non-fatal CHD.  The authors concluded that depressed affect and hopelessness may play a causal role in the occurrence of both fatal and nonfatal CHD.3

The notion that depression increases the risk of CHD has been often explained by the hypothesis that persons with psychiatric disorders generally have other risk factors for the development of CHD.  A large meta-analysis which included 21 etiologic studies and 34 prognostic studies concluded that depression has yet to be established as an independent risk factor for CHD due to wide range of measurements tools, variability in outcome measures and incomplete adjustment for conventional risk factors.7

The detrimental effect depression has on outcomes in patients with existing CHD is better established.   In post-myocardial infarction (MI) patients, Frasure-Smith and colleagues demonstrated that the risk of death in the first six months after MI for patients with major depression was five times that of the nondepressed patients, with an odds ratio of 4.29.8  Lesperance and colleagues followed 896 post-MI patients for five years, evaluating depression during admission and again one year after MI, and found a significant dose-response relationship between initial in-hospital depressive symptoms and cardiac mortality.9  Depression also worsens outcomes in patients undergoing coronary artery bypass surgery (CABG).  In a prospective study, which included 966 patients undergoing CABG, higher levels of depression symptoms at the time of CABG are a strong risk factor for lack of functional benefits six months after CABG.10

The effect depression has on CHD is likely secondary to combination of physiologic and behavioral factors.  Multiple physiologic derangements have been described in patients with depression include high sympathetic tone and catecholamine levels, hypercortisolemia, abnormal platelet activation, increased inflammatory markers and endothelial dysfunction.11, 12,13,14  Rumsfield and Ho proposed a unifying stress-response hypothesis, which proposes that patients with depression are in essence in a constant state of perceived stress.  This results in continuous upregulation of hypothalamus-pituitary-adrenal axis (HPA) and sympathetic adrenomedullary (SA) system.  Stress results in serotonin dysregulation and state of depression.15,16  Persistent HPA and SA activation leads to observed abnormalities in platelet function, inflammation, and endothelial function.  This hypothesis can potentially explain how depression could be a risk factor for CHD and the increase morbidity and mortality in patients with preexisting CHD.17

Behavioral factors linking depression with morbidity and mortality in CHD patients, such as poor self-care and compliance with cardiac treatment regimens, continued smoking, low motivation to change lifestyle, and low participation in cardiac rehabilitation are also important to recognize.

In patients with CHD, several small clinical trials suggest that treatment of depression successfully reduced anxiety and depression, and thus facilitated the modification of cardiac risk factors.18,19,20  Serotonine reuptake inhibitors (SSRI) are considered safe and antidepressant class of choice in patients with CHD.

Swenson and colleagues demonstrated that sertraline treatment is associated with clinically meaningful improvement in multiple quality-of-life domains in patients with acute coronary syndrome and recurrent depression.21  It is possible that SSRIs benefit in patients with CHD is primarily through modification of depression-mediated mechanisms, such as compliance with medication, diet and exercise.22  Along with their effect on depression, SSRIs have an inhibitory effect on platelet activation and, therefore, may theoretically be another mechanism for benefit seen in CHD patients.

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