Original article
Review article
Comorbid depression and health-related quality of life in patients with coronary artery disease

https://doi.org/10.1016/j.jpsychores.2006.12.009Get rights and content

Abstract

Objective

This article reviews recent studies relating to the impact of depression and its treatment on the health-related quality of life (HRQOL) of patients with coronary artery disease (CAD).

Methods

Articles for the primary review were identified via MEDLINE and PsycINFO (1995–2006).

Results

Evidence suggests that depression has an aversive impact on the HRQOL of patients with stable CAD as well as on patients hospitalized for acute myocardial infarction and coronary artery bypass graft surgery. Unfortunately, there are few depression treatment studies in patients with CAD that make use of standardized HRQOL measures, but the limited evidence suggests that successful treatment has positive implications for HRQOL in these patients. The mechanisms through which depression impacts on HRQOL require further study but are likely to be behavioral.

Conclusions

Depressive symptoms significantly undermine HRQOL in patients with CAD despite successful medical and surgical management. Although successful treatment of depression has not been shown to reduce mortality rates in patients with CAD, further study may find that the HRQOL benefits of such treatment are equally valuable.

Introduction

Coronary artery disease (CAD) is the major cause of disability in many developed countries and, by 2020, is forecast to be the major cause of disease burden worldwide [1]. Depression is disproportionately common in patients with CAD: 17% to 27% evidence major depression [2], [3], [4], [5], [6], [7], [8], [9], [10], [11] and 20% to 45% report depressive symptoms [5], [10], [11], [12], [13], [14], [15]. Patients with comorbid depression and CAD have a two- to threefold increased risk for future cardiac events [3], [4], [5], [10], [12], [16], [17]. However, despite the availability of effective therapies for depression, there is little evidence that these interventions improve cardiac or all-cause mortality for depressed CAD patients [11], [18], [19], [20]. Regardless of mortality benefit, the recognition and treatment of depression in patients with CAD are important. Depression results in substantial disability for both depressed individuals and their families [21], [22], and the treatment thereof has significant potential benefits for health-related quality of life (HRQOL) [23], [24].

In this article, we review the results of recent studies of the impact of depression and its treatment on the HRQOL of patients with CAD. A brief introduction to the concept of quality of life is also provided. Articles for the primary review were identified by searching the PsycINFO and MEDLINE (1995–2006) databases using the terms ‘quality of life and depression and coronary disease’ and ‘health status and depression and coronary disease.’ Reference sections of these articles were also used to identify additional studies that had not been identified by the database searches.

HRQOL has been defined as ‘the functional effect of an illness and its consequent therapy upon a patient, as perceived by the patient’ [25]. This subjective focus means that HRQOL is concerned with illness experience rather than the disease itself [26]. Most conceptualizations of HRQOL are multidimensional and include domains of physical functioning, social functioning, role functioning, and mental health and general health perceptions [27]. HRQOL instruments can be generic, allowing for comparisons between groups of patients with different conditions and characteristics, or disease specific, which tend to be more responsive to changes in HRQOL [28], [29]. Examples of measures of HRQOL in patients with CAD are provided in Table 1.

Unfortunately, a unified approach to the measurement and definition of the concept of quality of life is lacking [37]. These methodological issues are reviewed elsewhere [27], [38], [39], [40], but it should be noted that the lack of standardization in the reporting of effects on HRQOL and the use of diverse HRQOL measures may result in findings that are difficult to interpret. A large multisite study is currently underway to develop a core heart disease HRQOL questionnaire that will allow for meaningful comparisons between studies [41].

In terms of interpretation, HRQOL measurements are limited in several ways. HRQOL may change over time, perhaps being at its best soon after an intervention and deteriorating in the long term [42]. Alternatively, how patients evaluate their HRQOL may change over time [39]. Evidence suggests that as an individual comes to terms with the fact of long-term illness, psychological adaptations occur, which preserve life satisfaction [43]. Thus, changes in HRQOL over time need not necessarily derive from actual changes in health or symptoms.

In physically healthy individuals, both cross-sectional [44], [45] and longitudinal [46] studies have shown that the effect of depression on HRQOL is equal to or greater than that of most common chronic medical conditions. Moreover, functional limitations due to depression are additive to the limitations from the medical conditions [45]. These findings have been confirmed in another large primary care sample [47] and a community sample [48], and similar effects have been reported for health care service utilization [49] and days off from work [50]. Studies of primary care outpatients have shown that HRQOL status changes in accordance with changes in depressive symptoms [51], [52], [53], a phenomenon described as ‘synchrony of change’ [53].

In patients with CAD, both cross-sectional and prospective studies have examined the effect of depression on HRQOL. Few of these studies made use of structured clinical interviews for diagnosing depression, and most refer to depressive symptoms as measured by self-report instruments. An overview of these studies is provided in Table 2.

Ruo et al. [54] compared the effects of cardiac disease severity and depressive symptoms on the HRQOL in a cross-sectional study of 1204 patients with stable CAD. Depressive symptoms were strongly associated with greater symptom burden, worse HRQOL on the Seattle Angina Questionnaire (SAQ), greater physical limitation, and poorer overall health, whereas measures of cardiac severity (ejection fraction and presence of ischemia) did not show a significant association.

Cross-sectional studies of patients with acute myocardial infarction (AMI) and unstable angina have yielded similar results: in a substudy [55] of the Sertraline Antidepressant Heart Attack Randomized Trial (SADHART) [56], a randomized controlled trial of sertraline pharmacotherapy in 369 patients hospitalized with acute coronary syndrome (ACS) and major depression, multivariate analysis showed that depression on the Hamilton Depression Scale (HAM-D) was the strongest predictor of impaired baseline HRQOL. Disease variables such as ejection fraction and Killip class had little effect on HRQOL scores. Another study of 1957 patients hospitalized with ACS found that a history of depression was a significant predictor of HRQOL 7 months after hospitalization for ACS [57]. Although active depressive symptoms were not investigated, the presence of depression at index hospitalization was a significant predictor of angina burden, physical limitation, and HRQOL on the SAQ, even after adjusting for a range of cardiac, demographic, and comorbid disease variables. Similar findings were reported in a study of the HRQOL of 1660 patients hospitalized with ACS, which was also assessed 7 months following discharge [58]. Using the Medical Outcomes Study Short-Form 36 Health Status Questionnaire (SF-36), this study found that a history of depression (documented in medical record or self-reported) was the dominant predictor of 7-month mental health status, alone accounting for 80% of the explanatory power of the multivariate risk model. History of depression was also an independent predictor of physical health status, together with other comorbid medical conditions. A recent study of 181 patients with ACS showed that 16 months after hospitalization, gender and depressive symptoms were independent predictors of the mental component summary (MCS) score of the SF-36, and the physical component summary (PCS) score of the SF-36 was independently predicted by gender, baseline PCS, level of education, and prior cardiovascular events [59].

Several prospective studies have also shown that symptoms of depression and anxiety predict diminished HRQOL in CAD patients.

Among patients with stable CAD, depression and anxiety are significant predictors of a variety of HRQOL indices. One study of 198 patients who underwent elective catheterization [60] found that depression and anxiety independently predicted diminished self-reported physical function and activity interference at 6- and 12-month follow-up. This effect persisted despite changes in anxiety and depression that would be expected over the time period of the study and after adjusting for demographic, cardiac, and comorbid conditions. In contrast, no significant correlation between number of coronary arteries stenosed >70% at catheterization and self-reported physical function at 12 months was observed. Spertus et al. [61] reported on the HRQOL of 1282 patients with stable CAD and found a significant dose–response relationship between depressive symptoms and HRQOL, such that the more frequently participants endorsed the item ‘down-hearted and blue,’ the worse their outcome on the SAQ. In another prospective study, a 5-year follow-up of 111 patients with stable CAD showed that the impact of depression on perceived physical health (PCS score of the SF-36) was significantly mediated by physical symptoms of angina and fatigue and was both mediated and moderated by personality states and traits (positive affect and novelty seeking) [62]. Positive affect and novelty seeking had more marked effects on physical health in the presence of more depression. Thus, a broad range of psychological and physical factors beyond the severity of the ischemia itself would need to be considered in assessing indices of HRQOL.

Investigations of the impact of depression on HRQOL in coronary artery bypass graft (CABG) patients have yielded similar results to studies of other CAD patients. Presurgical depression has been found to be an independent predictor of HRQOL indices such as self-reported functional status [63], symptom burden [64], and return to work [65]. In a study of 89 CABG patients followed up 6 months after surgery, Burg et al. [66] reported that presurgical depression on the Beck Depression Inventory (BDI) independently predicted cardiac hospitalization, continued surgical pain, failure to return to previous activity levels, and depressed affect. Similarly, a study of 963 CABG patients assessed at baseline and, again, at 6 months after surgery found that baseline depression scores on the Geriatric Depression Scale were a significant independent predictor of lack of functional improvement (PCS score of the SF-36) after adjustment for CAD severity, angina class, baseline PCS, and medical history [67]. The authors concluded that depression was a stronger predictor of poor functional improvement after CABG than traditional measures of cardiovascular disease severity.

A recent prospective study evaluated the impact of the severity and course of depressive symptoms using the BDI on 2 and 6 months postsurgical HRQOL measured with the SF-36 (n=90) [68]. Higher levels of preoperative depressive symptoms predicted poorer 6-month physical functioning independently of and more powerfully than all other preoperative variables. Postoperative increases in depression from baseline assessment to 2-month follow-up significantly predicted both poorer physical and psychosocial functioning at 6 months, even after adjusting for presurgical depression and other traditional predictors. However, in contrast to other findings [63], [69], this study did not find a significant relationship between preoperative depression and postoperative psychological and social functioning.

A prospective study of 288 patients hospitalized for AMI found that depressive symptoms on the BDI provided the best independent prediction of HRQOL on the Dartmouth COOP Scales during a 12-month follow-up [70]. Other predictive factors included living alone, state anxiety at index hospitalization, and the severity of infarction. Similarly, clinically significant levels of anxiety and depressive symptoms predicted poorer HRQOL on all dimensions of the SF-36, as well as more impairment on measures of daily activity and frequency of chest pain at 3 and 12 months after infarct (n=347) [71]. Beck et al. [72] reported that the presence of baseline depression on the BDI predicted poorer HRQOL of 587 AMI patients followed up 6 and 12 months after infarct. Other important predictors were baseline HRQOL, age, and previous bypass surgery.

One study has specifically examined the particular functional domains of HRQOL that are negatively impacted by the presence of depression as well as the issue of whether poor HRQOL prior to infarct accounts for this relationship [73]. One hundred ninety-six patients hospitalized for AMI were assessed at baseline using the Structured Clinical Interview for DSM-IV (SCID) to evaluate depression before hospitalization and both the BDI and Beck Anxiety Inventory to measure post-AMI depression and anxiety, respectively, which were present since admission. HRQOL was measured using the SF-36 at baseline by asking patients to rate their HRQOL prior to infarct, and the SF-36 was administered again at 4-month follow-up. Baseline assessment was used to assign subjects to a depressed or nondepressed group. After adjusting for preinfarct HRQOL, in-hospital anxiety, and demographic variables, depression was prospectively and independently related to reduced general health at 4 months as well as reduced overall mental health—including vitality, psychological health and social function, and increased role interference from psychological problems. Aggregated MCS scores of both groups improved significantly over the follow-up period, and while significant changes in the aggregated PCS scores were not evident, physical function tended to decline for the depressed group and improve slightly for the nondepressed group. This study extends on previous work by detecting the same pattern of poorer perceived general health and psychological and social outcomes but at an earlier time point and with baseline anxiety and preinfarct HRQOL controlled.

The impact of the severity and duration of depressive symptoms on a range of health status variables including HRQOL, cardiac symptoms, and disability was prospectively investigated in 468 patients 3 and 12 months postinfarct [74]. ICD-10 diagnostic criteria were used to assess the presence and duration of depression, and severity of symptoms was measured using the BDI. In multivariate analyses adjusting for baseline cardiac condition, history of depression, health status at 3 months, age, and sex, post-AMI depression remained a strong predictor of poorer health status including HRQOL on the SF-36. Thus, post-AMI depression had a greater impact on health status than pre-AMI depression. Furthermore, severity, but not duration of depressive symptoms, contributed to a further reduction in HRQOL, more disability, and increased reporting of angina. These findings suggest that depression not only is associated with poor health status but also predicts changes in aspects of health status: while the addition of 3-month health status reduced the effects of post-AMI depression on most 12-month health status indicators, the effect remained for HRQOL and disability outcomes. Since the effects of post-AMI depression were attenuated by depressive symptoms still present at follow-up, the authors conclude that previous reports that did not adjust for baseline health status (e.g., Refs. [54], [70]) may have overestimated the prospective effects of depression on HRQOL because participants were suffering from a concurrent depression that affected health status and/or the assessment thereof.

Therapeutic options for the treatment of depression include depression-focused psychotherapies, antidepressant drugs, and a combination of these. Although the data are limited and are primarily from open or comparator trials, the tricyclic (TCAs) and selective serotonin reuptake inhibitors have been shown to be effective for the treatment of depression in patients with CAD, with response rates comparable to those reported in depressed patients without CAD [75]. As a point of reference, treatment with sertraline [76] and venlafaxine [77] has been associated with improvement in multiple domains of HRQOL in large samples of depressed general practice patients and outpatients.

In terms of psychotherapeutic treatment of depression, cognitive behavior therapy (CBT) and interpersonal therapy are effective as both acute and maintenance treatments [78], [79]. However, the efficacy of these evidence-based psychotherapies in depressed patients with CAD has only been investigated in a small number of studies, and none have included HRQOL as an outcome. The Enhancing Recovery in Coronary Heart Disease (ENRICHD) trial enrolled 2481 patients with AMI and depression and/or low perceived social support in 6 to 12 sessions of individual CBT, group therapy (if feasible), and antidepressant medication, if indicated, versus usual care [20]. Results of the ENRICHD trial were mixed: the findings showed small, statistically significant improvements in depressive symptoms and small, significant increases in perceived social support—the two main outcomes other than mortality and recurrent infarct. Psychological outcomes for the intervention group were better than the control group at the 6-month mark, but these effects did not persist to the 30-month evaluation. There was no difference in event-free survival between the two groups.

Unfortunately, there is a paucity of depression treatment studies in the CAD population that make use of standardized HRQOL measures beyond the usual depressive symptom scales [80]. One such study is the SADHART in which 369 patients hospitalized with ACS, who also met criteria for major depressive disorder, were randomized to 24 weeks of double-blind treatment with sertraline or placebo [56]. In a substudy of SADHART, HRQOL was assessed using the SF-36 and the Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q) [55]. Two groups were analyzed: the full intent-to-treat sample and a subgroup of patients with recurrent depression (defined as a history of two or more major depressive episodes before the current hospitalization). At 24 weeks, the SF-36 PCS and MCS scores showed clinically meaningful improvement with sertraline and placebo in the total randomized group, but there was no significant drug–placebo difference. However, in the recurrent depression subgroup, sertraline showed greater improvement on the SF-36 MCS score than did placebo and was more effective in producing clinically meaningful changes on the emotional role limitations and mental health subscales.

Another recent study that investigated the clinical and functional outcomes of depression treatment in patients with (n=235) and without (n=204) chronic medical illness included a cohort with CAD (n=68) [81]. Depression (measured with the SCID and Hopkins Symptom Checklist), disability, and functional outcome (using the SF-36 subscales assessing functional impairment) were assessed at baseline and at 2 and 6 months after index prescription. Significant improvements in clinical outcomes of depression were found, which, in turn, were associated with robust improvements in disability measures and those SF-36 subscales that were responsive to limitations in social and emotional functioning. There was minimal improvement in those SF-36 scales that were more responsive to limitations in physical functioning. Thus, despite indications that physical limitations remain unchanged, disability improved as depression improved, which implies that depression may be a stronger determinant of disability than a comorbid medical condition.

The mechanisms that explain the effect of depression on HRQOL in patients with CAD may be related to those behavioral factors underlying increased cardiac mortality and morbidity in this population. Cardiac rehabilitation programs that are designed to reduce mortality and morbidity by promoting adherence to medication and healthy lifestyle regimens have been shown to improve HRQOL [82], [83], [84]. Depression has a negative impact on participation in these programs [85]. Depressed patients with CAD have also been found to be less adherent to medication regimens [86], [87] and recommended lifestyle modifications intended to reduce cardiovascular risk [71], [88], [89], [90]. For instance, depression is associated with increased rates of smoking in CAD patients [91] and may lower the success rates of smoking cessation programs [92]. Depression is also associated with increased alcohol use and physical inactivity [93]. Furthermore, depression is bidirectionally associated with social isolation, a factor that contributes to poor treatment adherence [94] and which constitutes another well-established indicator of poor cardiac prognosis [95], [96], [97], [98], [99].

Finally, the cognitive–affective symptoms of depression may impact on HRQOL scores not only by impairing actual functioning but also by encouraging a negative perception of health status [27]. This raises the possibility that impaired HRQOL and depression are not necessarily distinct constructs and that the link between the two is related to negative affectivity (NA), a general disposition to experience subjective distress including aversive mood states [100], [101]. This predisposition may explain the high comorbidity of depressive and anxiety disorders. Individuals high in NA consistently report worse self-perceived health and more symptoms, although their underlying physical health is not always found to be worse [102], [103]. High-NA individuals are more likely to perceive or complain about health concerns [100], a heightened sensitivity that could lead to inflated health-related complaints and worse self-reported HRQOL. Kressin et al. [104] reported on the effect of NA on HRQOL in 1843 veterans, controlling for the effects of depression, age, and chronic medical conditions. The results showed that NA was consistently negatively associated with all SF-36 subscales, even after controlling for depression and physical illness. When adjusting for depression, the remaining variance uniquely attributable to NA ranged between 0.24% and 13.9%, suggesting that insofar as depression is correlated with NA and also has an effect on HRQOL, its removal attenuated the independent effect of NA.

Other research, however, has shown that depression is distinct from NA [106] and from HRQOL [105], [106]. One study used structural equation modeling to test a conceptual model of generic and disease-specific HRQOL in 465 CAD patients at baseline evaluation of chest pain and, again, at 1- and 3-month follow-up [105]. The model included biomedical factors as well as environmental and individual characteristics and was tested at each of the three time points. Among the individual variables, anxiety and depressive symptoms showed the greatest effect on the linked variables in the model. Although depression significantly influenced the emotional aspect of HRQOL, it had no significant direct effect on global HRQOL. However, depression had a major and constant effect on the perception of physical functioning and general health, exerting a major indirect effect on global HRQOL both at baseline and at 3 months. This depression effect had almost disappeared at 1 month after initial treatment but recurred after 3 months. This result suggests that subjective evaluation of global HRQOL shortly after treatment is influenced more by the perception of physical functioning, but later on, the indirect effects of variables such as depression regain an influence on HRQOL perception. The authors concluded that assessment of HRQOL is distinct from that of depression but that depression represents the most important indirect influence on the course of HRQOL in patients with CAD.

Section snippets

Conclusions

HRQOL, the assessment of the patient's subjective experience of disease and treatment, is now widely acknowledged as an important health care outcome. However, the wide variety of HRQOL instruments and the lack of standardization in the reporting of effects on HRQOL mean that the conceptual and methodological issues underlying this work require more attention. A core heart disease HRQOL questionnaire is being developed to allow for meaningful comparisons between studies [41]. Others [107] have

References (107)

  • JR Swenson et al.

    Influence of depression and effect of treatment with sertraline on quality of life after hospitalization for acute coronary syndrome

    Am J Cardiol

    (2003)
  • JS Rumsfeld et al.

    History of depression, angina and quality of life after acute coronary syndromes

    Am Heart J

    (2003)
  • JS Rumsfeld et al.

    Predictors of quality of life following acute coronary syndromes

    Am J Cardiol

    (2001)
  • MD Sullivan et al.

    Functional status in coronary artery disease: a one-year prospective study of the role of anxiety and depression

    Am J Med

    (1997)
  • JA Spertus et al.

    Association between depression and worse disease-specific functional status in outpatients with coronary artery disease

    Am Heart J

    (2000)
  • A Perski et al.

    Emotional distress before coronary bypass grafting limits the benefits of surgery

    Am Heart J

    (1998)
  • B Bryant et al.

    Prediction of outcome after coronary artery surgery

    J Psychosom Res

    (1989)
  • CA Beck et al.

    Predictors of quality of life 6 months and 1 year after acute myocardial infarction

    Am Heart J

    (2001)
  • JA Fauerbach et al.

    Depression following acute myocardial infarction: a prospective relationship with ongoing health and function

    Psychosomatics

    (2005)
  • D Koszycki et al.

    An open-label trial of interpersonal psychotherapy in depressed patients with coronary disease

    Psychosomatics

    (2004)
  • J Fogel et al.

    Quality of life in physical health domains predicts adherence among myocardial infarction patients even after adjusting for depressive symptoms

    J Psychosom Res

    (2004)
  • BH Brummett et al.

    Effect of smoking and sedentary behaviour on the association between depressive symptoms and mortality from coronary heart disease

    Am J Cardiol

    (2003)
  • A Forrester et al.

    Depression following myocardial infarction

    Int J Psychiatry Med

    (1992)
  • N Frasure-Smith et al.

    Depression following myocardial infarction: impact on 6-month survival

    JAMA

    (1993)
  • N Frasure-Smith et al.

    Depression and 18-month prognosis after myocardial infarction

    Circulation

    (1995)
  • F Lesperance et al.

    Depression and one-year prognosis in unstable angina

    Arch Intern Med

    (2000)
  • RM Carney et al.

    Major depressive disorder predicts cardiac events in patients with coronary artery disease

    Psychosom Med

    (1988)
  • SJ Schleifer et al.

    The nature and course of depression following myocardial infarction

    Arch Intern Med

    (1989)
  • HA Lett et al.

    Depression as a risk factor for coronary artery disease: evidence, mechanisms and treatment

    Psychosom Med

    (2004)
  • N Frasure-Smith et al.

    Gender, depression, and one-year prognosis after myocardial infarction

    Psychosom Med

    (1999)
  • PA Pirraglia et al.

    Depressive symptomatology in coronary artery bypass graft surgery patients

    Int J Geriatr Psychiatry

    (1999)
  • C Welin et al.

    Independent importance of psychosocial factors for prognosis after myocardial infarction

    J Intern Med

    (2000)
  • F Lesperance et al.

    Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infarction

    Circulation

    (2002)
  • K Rees et al.

    Psychological interventions for coronary heart disease

    Cochrane Database Syst Rev

    (2004)
  • LF Berkman et al.

    Enhancing Recovery in Coronary Heart Disease Patients Investigators (ENRICHD). Effects of treating depression and low social support on clinical events after myocardial infarction: the Enhancing Recovery in Coronary Heart Disease Patients (ENRICHD) Randomized Trial

    JAMA

    (2003)
  • C Mathers et al.

    The burden of disease and injury in Australia. Australian Institute of Health and Welfare

    (1999)
  • M Sobieraj et al.

    The impact of depression on the physical health of family members

    Br J Gen Pract

    (1998)
  • DC Haas

    Depression and disability in coronary patients: time to focus on quality of life as an endpoint

    Heart

    (2006)
  • F Lesperance et al.

    The seduction of death

    Psychosom Med

    (1999)
  • H Schipper et al.

    Quality of life studies: definitions and conceptual issues

  • G Guyatt et al.

    Measuring health related quality of life

    Ann Intern Med

    (1993)
  • IB Wilson et al.

    Linking clinical variables with health-related quality of life: a conceptual model of patient outcomes

    JAMA

    (1995)
  • M Dempster et al.

    Measuring health related quality of life of people with ischaemic heart disease

    Heart

    (2000)
  • DR Thompson et al.

    Quality of life in patients with coronary heart disease—I: assessment tools

    Health Qual Life Outcomes

    (2003)
  • SM Hunt et al.

    A quantitative approach to perceived health status: a validation study

    J Epidemiol Community Health

    (1980)
  • JE Ware et al.

    The MOS 36-item Short-form Health Survey (SF-36). I. Conceptual framework and item selection

    Med Care

    (1992)
  • M Bergner et al.

    The Sickness Impact Profile: development and final revision of a health status measure

    Med Care

    (1981)
  • L Valenti et al.

    An improved questionnaire for assessing quality of life after acute myocardial infarction

    Qual Life Res

    (1996)
  • S Hofer et al.

    The MacNew Heart Disease health-related quality of life instrument: a summary

    Health Qual Life Outcomes

    (2004)
  • R Mayou et al.

    Quality of life in cardiovascular disease

    Br Heart J

    (1993)
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