Review and special article
Depression as a predictor for coronary heart disease: a review and meta-analysis1

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Abstract

Objective: To review and quantify the impact of depression on the development of coronary heart disease (CHD) in initially healthy subjects.

Data sources: Cohort studies on depression and CHD were searched in MEDLINE (1966–2000) and PSYCHINFO (1887–2000), bibliographies, expert consultation, and personal reference files.

Data selection: Cohort studies with clinical depression or depressive mood as the exposure, and myocardial infarction or coronary death as the outcome.

Data extraction: Information on study design, sample size and characteristics, assessment of depression, outcome, number of cases, crude and most-adjusted relative risks, and variables used in multivariate adjustments were abstracted.

Data synthesis: Eleven studies met the inclusion criteria. The overall relative risk [RR] for the development of CHD in depressed subjects was 1.64 (95% confidence interval [CI]=1.29–2.08, p<0.001). A sensitivity analysis showed that clinical depression (RR=2.69, 95% CI=1.63–4.43, p<0.001) was a stronger predictor than depressive mood (RR=1.49, 95% CI=1.16–1.92, p=0.02).

Conclusion: It is concluded that depression predicts the development of CHD in initially healthy people. The stronger effect size for clinical depression compared to depressive mood points out that there might be a dose-response relationship between depression and CHD. Implications of the findings for a broader bio-psycho-social framework are discussed.

Introduction

The identification of psychological predictors for coronary heart disease (CHD) has produced inconsistent results. Since the 1950s, research on this issue has most often looked into psychological aspects that are associated with a postulated tendency of individuals to wear themselves down.1, 2, 3, 4 The most widely known construct from this research tradition is the “type A behavior pattern,” a conglomerate of a hostile and hard-driving behavior, including competitiveness and chronic feelings of time urgency.5, 6 Although a large cohort study, published in 1975, showed an independent effect of type A behavior on CHD incidence,7 later research projects were either not able to replicate this finding8, 9 or reported contradictory results.10 Research on one type A component, hostility, produced an immense body of psychological and psychophysiological literature.3, 11 However, similar to research on type A behavior, results from prospective epidemiologic studies on hostility and CHD have been highly inconsistent.12, 13

In recent years, depression has emerged in the discussion on the impact of psychological aspects on coronary risks. Several prognostic studies have shown that depression is a predictor for survival after myocardial infarction.14, 15, 16 However, whether depression has an impact on the development of CHD in initially healthy subjects is less clear. In 1987, Booth-Kewley and Friedman17 showed in a meta-analysis a strong association between depression and CHD, but most of the studies included in that review were cross-sectional in design. In a response to these findings, Matthews18 restricted her meta-analysis to prospective studies. Only three such studies were found and the association between depression and development of CHD vanished.

While these two meta-analyses in the late 1980s suffered because there were so few prospective studies, the situation has changed substantially during the last 10 years; there are now many studies using a prospective cohort design. It is the objective of this paper to systematically review all of these cohort studies and to perform an updated meta-analysis of them.

Section snippets

Inclusion criteria

The review included prospective cohort studies on initially healthy subjects with depression as the predictor and CHD as the outcome. Case-control and cross-sectional studies were not eligible because of the strong evidence that the presence of CHD increases the likelihood of the onset of depression.19

The eligible types of exposure were unipolar clinical depression assessed by clinical procedures and depressive mood measured by a standardized psychometric scale. Several studies have shown that

Studies included

The electronic literature research resulted in 1758 articles (Figure 1). The scanning of the titles/abstracts resulted in the elimination of 1234 articles in Step 1 and 458 articles in Step 2, leaving 66 articles. An additional 17 potentially eligible articles were identified through reference lists and other sources, resulting in a total of 83 articles. Of these 83 articles, 11 met the final inclusion criteria (Step 3).31, 32, 33, 34, 35, 36, 41, 42, 43, 44, 45 Studies were excluded at Step 3

Discussion

The review and the meta-analyses have shown that depression is associated with the development of CHD in initially healthy people. Although both clinical depression and depressive mood showed a statistically significant overall effect size, sensitivity analyses revealed that clinical depression is the stronger and more consistent predictor.

Perhaps the greatest challenge in investigating the causal link between depression and CHD incidence is the possibility that both depression and future

Acknowledgements

This study was supported by the National Heart, Lung, and Blood Institute Behavioral Factors in Cardiovascular Disease Training Grant (2-T32-HL 07365). I am grateful to Drs. Birgit Aust, John Frank, Katherine Frohlich, Niklas Krause, and S. Leonard Syme for their insightful comments on an earlier draft of this paper.

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