Mood disturbances and coronary heart disease: progress in the past decade

Anxiety
Studies of patients with pre-existing CHD show that anxiety, independently of conventional risk factors, can be predictive of recurrent acute CHD events.⁴ Moreover, prospective studies of anxiety in normal populations show that there is an association between anxiety assessed at enlistment and subsequent CHD mortality over many years, even when conventional risk factors are controlled for -- the relative risks are significant, being of the order of 5-6 for sudden death and 2-3 for fatal acute myocardial infarction (AMI).⁵ Impressive data also come from prospective studies of panic disorder, which show that CHD mortality risk may be doubled in people with the disorder.^6,7 There has been strong supportive psychophysiological evidence -- for example, in patients with pre-existing CHD undergoing ventriculography and exposed to trivial experimental stressful tasks, a significant but transient reduction (of up to 50%) in coronary muscle perfusion can occur.^2,8 At the other end of the evidence hierarchy are the clinical case reports of patients with panic disorder, found to be free of CHD at angiography, who have had an acute AMI or ongoing angina following panic attacks.⁹ It has furthermore been shown that patients with panic disorder, while lacking any demonstrable peripheral elevation in serum catecholamine levels, nonetheless have significant release of adrenaline from the coronary sinus during panic attacks.¹⁰ This may in turn adversely affect coronary perfusion, cardiac rhythm, shear forces on atheromatous plaques, and platelet function.¹¹

States of severe emotional arousal can also affect underlying pathophysiological risk factors for CHD, including platelet function and haemostasis.^12,13 Longer-term effects of anxiety on cardiovascular pathophysiology are also possible; it has been shown that subjects with an exaggerated blood pressure response to mental stress may experience more rapid progression of carotid atherosclerosis.¹⁴

Depressed mood
Depressed mood is emerging as an important risk factor for CHD. Depressed mood in CHD patients is associated with increased mortality.¹⁵ The increased risk is not trivial (relative risk > 3), being of the same order as other risk factors such as prior AMI and impaired left ventricular function after infarction. Even in long-term studies of normal CHD-free populations, depression at enlistment doubles the risk of subsequent acute coronary events¹⁶ and increases mortality risk.¹⁷

States resembling depression, such as "vital exhaustion" (characterised by fatigue, irritability and demoralisation),¹⁸ have been shown to be associated with acute myocardial events in normal populations even when conventional risk factors are controlled.

Unlike the more acute effects of anxiety, the effects of depression are not immediate. Indeed, in one prospective study, mortality rates in women with depression did not begin to increase until after 16 months of follow-up.¹⁹ Thus, depression may well have a prolonged mode of action on CHD risk. One study found that one component of depression (ie, hopelessness) was associated with more rapid progression of atherosclerosis.²⁰ The CHD risk of a person with chronic depression or dysphoric mood, either as an induced state or an enduring trait of "depressive" personality, needs further study.

Personality
Recently the "type D ('distressed') personality" has been described by Denollet et al as a result of finding significant differences in CHD outcome in those with certain personality traits. The type D personality is identified by two components: the continual experience of negative emotions, including depression, and the inhibition of social expression of these emotions. In a sample of patients undergoing cardiac rehabilitation, deaths from cardiac causes were increased fourfold in those with type D personality even after controlling for conventional risk factors.²¹ This suggests that type D personality (whether as a biological construct of temperament or a constellation of habitual behaviours) is a risk factor at least equivalent in importance to the other, "conventional" coronary heart disease prognostic factors.

Implications
It is possible that the association between mood and CHD risk is not causal, but that the two are linked by some common underlying genetic factor, perhaps associated with vascular disease in general. Weighted against this interpretation are the experimental findings showing the effect of emotions on cardiovascular pathophysiology. To explore the possibility of covariance, prospective aetiological and interventional studies are necessary to examine both mood state (which is episodic) and the personality-based predisposition (trait) to depression. Intervention studies are now in progress to assess whether antidepressants may reduce CHD events in those with depression following AMI.²² In the meantime, in patients with pre-existing CHD or those at increased risk of CHD, the identification and treatment of mood disorders, including anxiety and depression, is important for improving quality of life and for reducing the risk of CHD events and mortality.

Christopher C Tennant
Professor, Department of Academic Psychiatry

Loyola McLean
Lilly Psychiatry Research Training Fellow
Department of Academic Psychiatry
Royal North Shore Hospital, St Leonards, NSW
tennantATmed.usyd.edu.au

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