Depression, Stress and the Risk of Heart Disease

Psychiatric Times

October 2005

Vol. XXII

Issue 11

In recent years, depression has emerged in the discussion of the impact of psychological aspects on risk of heart disease. Several prognostic studies have shown that depression is a predictor for mortality after acute myocardial infarction (AMI) (Frasure-Smith et al., 1995a, 1993) and the risk is directly related to the severity of mood symptoms: a one- to twofold increase in coronary heart disease (CHD) for minor depression and a three- to fivefold increase for major depression (Bunker et al., 2003).

Extensive longitudinal data suggest that depression may also precede the development of CHD; however, whether depression has an impact on such development in initially healthy individuals is less clear and drawing conclusions from studies investigating the association between depressive symptomatology and CHD has been limited by the various criteria and methods used to define both clinical and subsyndromal depression. These diverse methods include self-report, clinical diagnosis and symptom checklist (Littman, 1998).

One aspect of depression, hopelessness, has received particular attention. Prospective epidemiological studies have also reported a relationship between symptoms of hopelessness and the development of CHD through carotid atherosclerosis (Everson et al., 1997, 1996). A related phenomenon is vital exhaustion: Appels and Mulder (1988) found that this state--characterized by unusual fatigue, increased irritability and demoralized feelings--is associated with an increased risk of AMI.

Moreover, a large number of investigations have suggested a role for stressful life events in uncovering an individual's vulnerability to acute CHD (Mayou, 1979; Reich, 1983). A life event represents a discrete change in an individual's social or personal environment, which should be external and verifiable rather than internal or psychological. The use of structured methods of data collection has indicated that stressful life events were significantly more frequent in patients with AMI compared to control groups (Magni et al., 1983). While the link between stressful life events and the onset of depression has been well documented, the relationship between recent life events (evaluated by observer interview), clinical and subsyndromal depression (observer rated and clearly defined by diagnostic criteria), and the onset of a first episode of AMI has been less investigated.

Rafanelli and colleagues (2005), in a case-controlled study, evaluated the presence of major and minor depression, recurrent depression, demoralization and stressful life events in the year preceding the first occurrence of AMI and/or a first episode of instable angina and compared stressful life events also related with mood disorders in 97 patients and 97 healthy participants. The following measures were used: 1) Structured Clinical Interview for DSM-IV Axis I Diagnosis (SCID-I) for determining major and minor depression diagnoses; 2) semi-structured interview for new Diagnostic Criteria in Psychosomatic Research (DCPR) (Rafanelli et al., 2003), which identifies the subclinical psychological syndrome of demoralization (Table 1) (Due to copyright concerns this Table cannot be reproduced online. Please see p37 of the print edition--Ed.); and 3) Paykel's (1997) Interview for Recent Life Events (IRLE) to detect 64 life events clustered in 10 areas: employment, education, financial status, somatic health, loss/bereavement, relocation, courtship/relationships, legal, family and social problems, and marital conflicts. The IRLE also identifies the quality of events such as the objective negative impact (i.e., the judgment of the expected stressfulness of the event when its full nature and particular circumstances are taken into account, ignoring the subjective reaction of the patient) and independence (i.e., the likelihood that the event is not a consequence of the psychological or physical states of the patient). It considers three categories of events: 1) entrances (involving introduction of new people, such as marriage) and exits (involving departure of a person from the social field of the patient, such as the death of a close family member); 2) socially desirable (e.g., promotion) or undesirable (e.g., major financial problems) events; and 3) controlled events (when the initiation of the event was likely to be under the individual's control or choice) or uncontrolled events (not likely to be under individual's control or against one's wish).

In this study, 30% of patients were suffering from one or more episodes of major depression (Rafanelli et al., 2005). Within this group, less than half of the patients (n=13) suffered from recurrent depression. Nine percent of the total sample were suffering from minor depression and 20% from demoralization. In 12% of patients there was an overlap between major depression and demoralization (Table 2). Moreover, patients reported significantly more life events (129 versus 21), independent and with negative impact, than controls (p(Due to copyright concerns this Table cannot be reproduced online. Please see p37 of the print edition--Ed.). All categories of events, except entrances, were more frequent in patients than in healthy controls (Table 4) (Due to copyright concerns this Table cannot be reproduced online. Please see p37 of the print edition--Ed.). The most frequent events in the CHD group occurred in the following areas: loss/bereavement (25%), somatic health (19%), employment (16%), family problems (12%), legal problems (10%) and financial problems (9%). See Table 5 for more detailed events.

The CHD group was then analyzed, separating patients with depression (major and minor) and/or demoralization from those without. Each subgroup was then compared with its own subgroup of healthy controls regarding life events. The same significant difference (p

In view of the methods used (i.e., detailed investigation from the onset of mood symptoms, rigorous definition of the event, and delay of the interview until acute phase of the disease has passed), the results suggest a role for life events in the pathogenesis of CHD, apart from mood symptoms. On the other hand, there are subgroups of patients with life events and mood disorders who could be at a greater risk of cardiac morbidity. There is evidence in previous studies that several factors may contribute to the risk of CHD. Although psychosocial stresses have been reviewed as individual entities, generally these stresses tend to cluster together. As outlined by Rosengren and colleagues (1993), among healthy individuals, there is a synergy between high levels of life stress and social isolation in an increased rate of subsequent cardiovascular events. These data indicate that psychological factors resulting in cardiac risk elevation are comparable to those associated with hypercholesterolemia, hypertension and other major risk factors for CHD. Further, psychosocial factors also interact synergistically with conventional CHD risk factors to heighten the risk for cardiac events (Rozanski et al., 1999).

In several studies, behavioral and physiological mechanisms have been proposed for the association between depression and cardiovascular illness. Individuals with depression certainly are more likely to engage in risk-related behaviors such as smoking and lack of physical activity. However, after control of traditional risk factors and risk-related behaviors, depression is still associated with poor cardiac outcomes, suggesting that other factors are involved, such as a hyperactive hypothalamic-pituitary-adrenal (HPA) axis, high levels of norepinephrine, reduced heart rate variability and changes in blood platelet function (Krantz and McCeney, 2002).

A review by Bunker and colleagues (2003) concluded that acute life event stressors, such as bereavement, can trigger CHD events. It could be that life events could precipitate a CHD event meeting a predisposal field suggesting previous psychological vulnerability such as recurrent depression. In the study by Rafanelli et al. (2005), patients revealed that they had not taken any antidepressant drugs or they had not requested psychological treatment during major depressive episodes. This is likely to expose the individual to recurrent depression and major vulnerability to stress, involving residual symptoms of depression that may then predispose the relapse (Fava, 1999). Since the available observations indicate that previous depression is a risk factor for depression during hospitalization following AMI (Frasure-Smith et al., 1995b), the prognostic impact of recurrent depression on the course of the disease might be even larger. The interaction between life events and residual symptoms of depression should thus be considered by the physician in detecting the risk of CHD. Hammen et al. (1986) found that non-symptomatic individuals were relatively resistant to the onset of depression even when exposed to high impact stressful events, whereas those who were symptomatic continued to have both more depression and more high-impact events over time. The results of the study by Rafanelli et al. (2005) lend support to the importance of assessing both clinical and subclinical symptoms: Demoralization could not be considered a cardiac risk factor per se, but the addition of this subsyndromal state to major depression could individuate a subgroup of patients at a greater risk of a cardiac morbidity. In this case, the stressful event could serve as a signal for a considerably increased period of risk, when psychological intervention aimed at preventing the evolution of understandable distress into a pathological disorder can be targeted (Paykel, 1994).

The retrospective nature of the investigation by Rafanelli et al. (2005) and the pathophysiological process of CHD--potentially extending over many years--cannot ascertain whether stressful life events alone or in association with depressive symptomatology may be related to the onset of illness or its clinical manifestations (such as myocardial infarction or instable angina). Nonetheless, within the complexity of phenomena implicated in the pathogenesis of CHD, the results of the study may alert physicians to inquire about the relevance of stress and depressive symptomatology in the patient's life as an integrated part of risk stratification for heart disease, both for primary and secondary care.

In the case of secondary care, several recent studies have assessed the extent to which depression can be successfully treated in cardiac populations. In the Sertraline Antidepressant Heart Attack Randomized Trial (SADHEART) study, sertraline (Zoloft) was significantly superior to placebo only in subsets of patients who had a previous episode of depression and those with more severe depression; the incidence of severe cardiovascular adverse events was numerically, but not significantly, greater in the placebo group compared to the sertraline group (Glassman et al., 2002). Moreover, although the only randomized behavioral intervention trial attempting to reduce morbidity and mortality in depressed patients with existing coronary disease showed that changes in depression did not translate into improved survival (Berkman et al., 2003), the need remains to further investigate if treating depression can reduce the risk of morbidity and mortality in these patients.

Dr. Rafanelli is a medical doctor, psychiatrist and psychotherapist. She is also researcher at the Faculty of Psychology, University of Bologna in Bologna, Italy.

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