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. Author manuscript; available in PMC: 2015 Jul 3.
Published in final edited form as: Maturitas. 2012 Sep 28;73(4):305–311. doi: 10.1016/j.maturitas.2012.09.005

Gender and Sex Differences in Prevalence of Major Depression in Coronary Artery Disease Patients: A Meta-Analysis

Shamila Shanmugasegaram a, Kelly L Russell b, Adrienne H Kovacs b,c, Donna E Stewart b,c, Sherry L Grace a,b,c,d,e
PMCID: PMC4490896  CAMSID: CAMS4479  PMID: 23026020

Abstract

Background

Depression is related to increased morbidity and mortality in the general population and among patients with coronary artery disease (CAD). The prevalence of major depression is two-times higher in women than men in the general population, but whether this pattern holds true in the CAD population has not been established.

Objective

To test, through quantitative synthesis, whether women with CAD have a greater prevalence of major depression than men.

Method

MEDLINE, EMBASE, and PsycINFO electronic databases were searched. Authors of key articles were contacted to identify other relevant publications. The titles and abstracts were screened by the first author and the selected full-text articles were independently screened by the first and second authors based on pre-defined inclusion criteria. Major depression had to be diagnosed through structured clinical interviews during cardiac-related hospitalization or post-CAD hospitalization. Meta-analysis was undertaken using the Review Manager 5 software program. All pooled analyses were based on random-effects models.

Results

Eight eligible cohort and cross-sectional studies reporting data for 2072 participants (509 [24.6%] women) were included. Overall, major depression was observed in 95 (18.7%) women and 187 (12.0%) men. In the pooled analysis, prevalence of major depression was significantly greater in women compared to men (odds ratio=1.77, 95% confidence interval=1.21–2.58, p<.01). Heterogeneity was considered low to moderate (I2=36.0%).

Conclusion

Consistent with the general population, the prevalence of major depression is two-times greater in women than men with CAD. Women with CAD may warrant greater emphasis in efforts to identify and treat depression.

Keywords: Depression, Sex differences, Women, Men, Coronary artery disease

Cardiovascular Disease (CVD) is the leading cause of mortality worldwide,1 and is a significant contributor to morbidity and health-related costs.2 Recently, there has been growing interest in non-traditional cardiac risk factors such as psychosocial factors. Research shows that depression is related to a greater risk of coronary artery disease (CAD) onset, and poorer long-term prognosis among those with established CAD.3 Specifically, depressive symptomatology confers a relative risk between 1.5 and 2.5 for future cardiac morbidity and mortality,4 and a dose-response relationship has been established.5

In cardiac patients, the prevalence of major depression ranges around 15% to 20%,4 which is approximately three times higher than what is found in age-matched, community-based prevalence studies.6, 7 Further, the prevalence of elevated depression symptoms has been reported to be as high as 50%.5 A more recent systematic review of eight studies including a total of 10,785 patients demonstrated that major depression was identified in 19.8% of acute myocardial infarction patients.8

Beginning at puberty and persisting through adult life, the prevalence and incidence of depressive disorders are higher in females than in males.9 Specifically, depression is two times greater in women compared to men.10 Biological factors such as hormones, and psychosocial factors such as role overload have been postulated to explain this gender difference.11 Although it has been suggested that sex differences in the prevalence of major depression among cardiac patients exist,12, 13 to date, no systematic review or meta-analysis has examined this question. The higher burden of CVD- and CAD-related mortality among women, the greater prevalence of depression among women in the general population, and guidelines calling for depression screening in CHD patients, from which women in particular may benefit, emphasize the need to systematically assess the presence or absence of a gender gap in depression. The objective of this study was to examine whether women with CAD experience greater prevalence of major depression than men with CAD, through a systematic review and meta-analysis of all observational studies that have examined the prevalence of major depression among CAD patients by sex.

Method

Eligibility criteria

Types of studies

Observational studies presenting original, primary data on the prevalence of major depression in CAD, analyzed by sex, were considered. The exclusion criteria were: i) meta-analyses, systematic reviews, case-series, case reports, published letters, comments, editorials, non-peer reviewed publications (e.g., dissertations), and ii) studies published in a language other than English. No year of publication restriction was imposed. In the case of multiple publications of the same cohort, the most recent article that best addressed the research question was chosen.

Types of participants

Studies that assessed depression by sex in adults over the age of 18 with CAD were considered. Participants must have had a history of hospitalization for reasons related to CAD including the following: myocardial infarction, cardiac revascularization (coronary artery bypass graft surgery or percutaneous coronary intervention), or those with unstable angina.

Types of outcome measures

Major depression had to be diagnosed through structured clinical interviews during cardiac-related hospitalization or post-CAD hospitalization. Diagnoses of Major Depressive Disorder had to be consistent with diagnostic criteria presented in the Diagnostic and Statistical Manual, Fourth Edition, Text Revision (DSM-IV TR) criteria for Major Depression.14 In addition, depression prevalence had to be stratified and presented by sex.

Information sources

Studies were identified by searching electronic databases, scanning reference lists of articles, and consulting experts in the field. The Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effectiveness, MEDLINE, ISI Web of Science, Excerpta Medica Database (EMBASE), PsycINFO, and Google Scholar were searched for prior systematic reviews and meta-analysis. In addition, reference lists of chapters in the latest edition of the Canadian Guidelines for Cardiac Rehabilitation and Cardiovascular Disease Prevention15 were examined for reviews on sex differences in prevalence of major depression in CAD patients. MEDLINE (1950-Present), EMBASE (1980-Present), and PsycINFO (1806-Present) electronic databases were searched for primary articles. The last search was performed on March 12, 2010. Authors of key articles were contacted to identify other relevant publications. RefWorks16 was used to store the citations and a Microsoft Excel 2003 database was used to record the process. All database searches were conducted with the assistance of information specialists at the University Health Network library. The search strategies were reviewed by SS, SLG and KLR. The search strategy for MEDLINE is presented in Appendix A.

Study selection

Duplicate records from different databases were excluded. Using a conservative threshold for exclusion, the retrieved records were independently screened by title and abstract (SS). Any ambiguity in titles and abstracts led to the retrieval of the full-text article. The selected full-text articles were independently assessed for eligibility using a standardized form (SS and KLR), and differences were resolved by discussion with the senior author (SLG).

Data Extraction

A data extraction form was developed, pilot-tested on two randomly-selected included studies, and revised accordingly. The first author (SS) extracted data from studies that met inclusion criteria, while the second author (KLR) independently verified the material. Disagreements were reconciled through consensus in face-to-face meetings. If no agreement could be reached, consultation with the senior author (SLG) was undertaken.

The information extracted from each included study included sociodemographic variables (e.g., age, education level, family income), CAD diagnosis, method of CAD diagnosis, time elapsed between CAD diagnosis and diagnosis of depression, heart disease risk factors, cardiac medication use, interview used to evaluate major depression, and prevalence of major depression.

Quality Assessment

To determine the validity of eligible studies, a pair of reviewers (SS and KLR) working independently determined with adequate reliability the methodological quality of the included studies using the Newcastle-Ottawa Scale.17 The Newcastle-Ottawa Scale is a nine-point scale that allocates points on the basis of the process of selection of the cohorts (0 –4 points), of the comparability of the cohorts (0 –2 points), and of the identification of the exposure and of the outcomes of study participants (0 –3 points). In addition, the overall quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE18) criteria. A summary of findings and evidence profile table were generated through the software GRADEpro.19

Statistical Approach

Meta-analysis was performed using the software Review Manager 5.20 The meta-analysis was performed using a random-effects model to compute odds ratios. Heterogeneity was tested with the Breslow-Day test and the method proposed by Higgins21 was used to measure inconsistency (i.e., the percentage of total variation across studies due to heterogeneity). For each study, we plotted the effect by the inverse of its standard error. Egger’s regression intercept of funnel plot asymmetry was computed to test the presence of publication bias.22

Results

Figure 1 presents the flow diagram of study selection. A total of eight studies were identified for inclusion in the review. The search for previous reviews on this topic resulted in identification of one narrative review.13

Figure 1.

Figure 1

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Flow diagram of study selection

Study characteristics

Table 1 displays the characteristics of the included studies. Three studies applied the Structured Clinical Interview for DSM Disorders (SCID23) to assess major depression, whereas the four other studies used one of the following structured clinical interview schedules: Diagnostic Interview Schedule, Modified version of the US National Institute of Mental Health Diagnostic Interview Schedule, Mini International Neuropsychiatric Interview, and Anxiety Disorders Interview Schedule-IV. One used the interviewer-administered semi-structured Hamilton Rating Scale for Depression. A decision was made to include the article as it was published in 1997, before the validation of the Depression Interview and Structured Hamilton (DISH).

Table 1.

Characteristics of included studies

Authors, country, year of publication Sample (size, CAD) Clinical interview for assessment of major depression Study design (time period) Women Men Quality
Number Major depression (%) Number Major depression (%)
Carney et al., United States, 1987 50, CAD Diagnostic Interview Schedule Cross-sectional 14 4 (29%) 36 5 (14%) 3
Connerney et al., United States, 2001 309, CABG Modified version of the US National Institute of Mental Health Diagnostic Interview Schedule Longitudinal (follow up at 1 year) 102 18 (18%) 207 45 (22%) 3
Lesperance et al., Canada, 2004 481, ACS Structured Clinical Interview for DSM Disorders Cross-sectional 91 12 (13%) 390 23 (6%) 3
Mitchell et al., Canada, 2005 115, CABG Mini International Neuropsychiatric Interview Longitudinal (≤28 days pre-CABG, and follow-up between 6 and 12 weeks post-CABG) 55 13 (25%) 60 6 (10%) 5
Pedersen et al., Netherlands, 2008 710, PCI Structured Clinical Interview for DSM Disorders Longitudinal (baseline, and follow-up at 6 and 18 months) 160 28 (18%) 550 73 (13%) 3
Sullivan et al., United States, 1997 198, CAD Hamilton Rating Scales for Depression (semi-structured clinical interview) Longitudinal (baseline and follow-up at 1 year) 34 8 (24%) 164 17 (10%) 3
Swardfager et al., Canada. 2009 99, CAD Structured Clinical Interview for DSM Disorders Cross-sectional 18 5 (28%) 81 12 (15%) 2
Todaro et al., United States, 2005 110, CAD Anxiety Disorders Interview Schedule-IV Cross-sectional 35 7 (20%) 75 6 (8%) 3
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ACS, acute coronary syndrome; CAD, Coronary Artery Disease; MI, Myocardial Infarction; PCI, Percutaneous Coronary Intervention; CABG, Coronary Artery Bypass Graft

All studies were observational in design. The studies by Carney et al. (1987), Lesperance et al. (2004), Swardfager et al. (2009), and Todaro et al. (2005) were cross-sectional in design, whereas the other studies were longitudinal. The included studies observed 2072 participants in total, of which 509 (24.6%) were female. The studies were conducted in the United States, Canada, and Netherlands. No authors reported a source of study funding.

Quality of Evidence

The methodological quality of each study as assessed based on the Newcastle-Ottawa Scale for cohort studies17 is shown in Table 1. Table 2 shows the summary of findings and evidence profile of the included studies. Using the GRADE criteria,18 the overall quality of evidence was rated to be “low.” The primary reason for the low rating was the lack of adjustment for potential confounding variables.

Table 2.

Summary of findings and evidence profile of included studies

Quality assessment Summary of findings Importance
No of patients Effect Quality
No of studies Design Limitations Inconsistency Indirectness Imprecision Other considerations Females versus Males control Relative (95% CI) Absolute
Major Depression
8 observational studies serious1 serious2 no serious indirectness no serious imprecision none 95/509 (18.7%) 187/1563 (12%) OR 1.77 (1.21 to 2.58) 74 more per 1000 (from 22 more to 140 more) LOW CRITICAL
11.8% 73 more per 1000 (from 21 more to 139 more)
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1

Confounding variables were not adjusted

2

I squared=36.0%

Meta-Analytic Results

Figure 2 shows the prevalence of major depression by sex for each included study, as well as the effect size and confidence interval. In the pooled analysis, prevalence of major depression was significantly greater in women compared to men with CAD (odds ratio=1.77, 95% confidence interval=1.21–2.58, p<.01).

Figure 2.

Figure 2

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Forest plot of sex differences in prevalence of major depression in CAD patients

Heterogeneity was considered low to moderate (I2=36.0%). The shape of the funnel plot suggested lack of publication bias. Egger’s regression test provided no evidence of small sample bias. The size of estimate did not appear to vary with sample size, implying our results are not influenced by publication bias.

Two sensitivity analyses were performed by: (1) type of interview to assess depression and (2) sample size. For the former sensitivity analysis which examined the three studies that used the SCID,23 the prevalence of major depression was significantly different between women and men (odds ratio=1.68, 95% confidence interval=1.15–2.46, p<.05). For the latter, sensitivity analysis excluding Carney et al.’s study24 (sample size less than five for women), the prevalence of major depression was significantly greater in women compared to men (odds ratio=1.75, 95% confidence interval=1.17–2.63, p<.01).

Discussion

It has been demonstrated that comorbid depression is related to significantly poorer prognosis after coronary events,12, 25, 26 and that women in the general population have significantly greater burden of depression than men. This is the first meta-analysis to examine whether a sex difference exists in the prevalence of major depression in adults with CAD. In 1563 men and 509 women with CAD, results showed that women with CAD have approximately twice the prevalence of major depression as men. This is consistent in magnitude to the sex difference observed in the general population.10

The overall prevalence of comorbid major depression in men was 12.0% and in women was 18.7%. The overall depression rate in this study was approximately 14.3%, which is lower than the overall 19.8% prevalence reported in the systematic review of acute myocardial infarction patients by Thombs et al.8, 27 This discrepancy may be explained by the broader range of cardiac diagnosis included herein. Although no systematic review or meta-analysis has been published on sex differences to date, the findings herein are consistent with a previous narrative review13 and the burden reported in other chronic illnesses. For instance, the burden of major depression in stroke is estimated to be somewhat higher at 33%,28 but in this population the burden is similarly significantly higher among women than men.29 In contrast, a study examining gender disparity in depression rates in patients with advanced cancer reported no significant gender difference.30 The authors concluded that men and women may be equally likely to develop depression under highly stressful circumstances.

The multifactorial factors that may explain the greater prevalence of major depression in women than men in non-cardiac samples have been reviewed elsewhere.29 However, in the cardiac population, other explanatory factors may include physiological changes related to the menopausal transition in women, social factors such as role overload, role conflict, low socioeconomic status, and lower functional capacity among female cardiac patients than males.13

The findings herein hold important implications for depression treatment.The M-HART and ENRICHD trials of cardiac patients showed trends toward hazard and favoured usual care, respectively, for women.34–36 Given the greater burden of depression among women, clearly there is an urgent need to develop interventions shown to be safe and effective for this population. Recently, the COPES trial offering problem-solving therapy and/or pharmacotherapy and using a stepped-care approach showed promise in not only reducing depression, but also in counteracting the poorer health outcomes associated with comorbid depression.32 These positive effects in reducing depression were generalized to men and women. Most recently, the SUPRIM trial demonstrated that a cognitive behavioural therapy intervention with stress management resulted in significantly lower fatal and non-fatal first recurrent events and significantly fewer recurrent myocardial infarctions in adjusted analyses when compared to controls. Given the proven benefits of cardiac rehabilitation such as decrease in mortality and depression rates, health care providers should encourage both male and female cardiac patients to participate in these programs.

Limitations

Caution is warranted when interpreting these results. First, the overall quality of the evidence was rated as “low”, thus the results herein should be interpreted with caution. Second, the current study synthesized only studies published in English, which may limit the generalizability of these findings. Third, there was heterogeneity in the patient samples used in the included studies (e.g., post-myocardial infarction and revascularization patients). Fourth, most studies did not consider depression treatments (i.e., patients with effective treatment may not meet mood disorder criteria) or timing of depression in relation to their disease onset or hospitalization. Finally, multivariate analyses to adjust for potential confounding variables such as severity of depression, and receipt and type of depression treatment were not considered in any studies identified through the thorough search of the literature.

Conclusions

This meta-analysis demonstrated that, similar to the general population, the prevalence of major depression is approximately two-times greater in women with CAD compared to men. The prevalence of comorbid depression was high, even among men. Given the poorer prognosis associated with comorbid major depression in CAD, the findings emphasize the need to devote more attention to identify and address potential factors that could account for gender differences in depression.

Figure 3.

Figure 3

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Funnel plot of sex differences in prevalence of major depression in CAD patients

Acknowledgments

We gratefully acknowledge the assistance of University Health Network information specialists Ms. Amy Faulkner and Ms. Rouhi Fazelzad in conducting the electronic database searches. We would also like to express gratitude to Dr. Elie Akl for his feedback on earlier versions of this manuscript.

Funding

Ms Shanmugasegaram is supported in her graduate studies by the Canadian Institutes of Health Research (CIHR) Frederick Banting and Charles Best Canada Graduate Scholarship -Doctoral Award. In addition, Dr. Grace is supported by CIHR salary award #MSH-80489. Role of funding source: CIHR played no role in study design, collection, analysis, interpretation of data, writing of the report, or in the decision to submit the paper for publication. It accepts no responsibility for the contents.

Appendix A. Search strategy: MEDLINE (OVID)

CAD and related terms Component
1 Coronary Disease/ 119195 Advanced
2 Coronary Artery Disease/ 23845 Advanced
3 (coronary adj2 disease*).mp. 173134 Advanced
4 (coronary adj2 arterioscleros*).mp. 740 Advanced
5 Myocardial Infarction/ 120285 Advanced
6 (myocardia* adj2 infarct*).mp. 154280 Advanced
7 Coronary Artery Bypass/ 35924 Advanced
8 (coronary adj2 bypass*).mp. 45005 Advanced
9 (aortocoronary adj2 bypass*).mp. 2438 Advanced
10 CABG.mp. 9027 Advanced
11 Angioplasty, Transluminal, Percutaneous Coronary/ 25153 Advanced
12 (transluminal adj2 coronary).mp. 27549 Advanced
13 (angioplast* adj2 coronary).mp. 11959 Advanced
14 PTCA.mp. 5873 Advanced
15 PCI.mp. 6596 Advanced
16 Exp angina pectoris/ or exp angina, unstable/ 36369 Advanced
17 angina*.mp. 53534 Advanced
18 or/1–17 341894 Advanced
Depression Component
19 Depression/ 54525 Advanced
20 depress*.mp. 298712 Advanced
21 Depressive Disorder, Major/ 11850 Advanced
22 (psychos?s adj2 involutional).mp. 62 Advanced
23 (melanchol* adj2 involutional).mp. 63 Advanced
24 or/19–23 298719 Advanced
25 18 and 24
Gender differences and related terms Component
26 Sex Factors/ 173460 Advanced
27 (sex adj2 factor?).mp. 175250 Advanced
28 (sex adj2 differen*).mp. 27146 Advanced
29 (gender* adj2 differen*).mp. 17503 Advanced
30 (gender* adj2 compar*).mp. 1125 Advanced
31 (gender* adj2 factor?).mp. 1358 Advanced
32 or/26–31 204174 Advanced
Combined Results (CAD, depression, and gender differences) limited to humans and adults
33 25 and 32 373 Advanced
34 Exp animals/ not (exp animals/ and exp humans/) 3436332 Advanced
35 33 not 34 371 Advanced
36 limit 33 to (“all infant (birth to 23 months)” or “all child (0 to 18 years)” or “newborn infant (birth to 1 month)” or “infant (1 to 23 months)” or “preschool child (2 to 5 years)” or “child (6 to 12 years)” or “adolescent (13 to 18 years)”) 28 Advanced
37 limit 33 to (“all adult (19 plus years)” or “young adult (19 to 24 years)” or “adult (19 to 44 years)” or “young adult and adult (19–24 and 19–44)” or “middle age (45 to 64 years)” or “middle aged (45 plus years)” or “all aged (65 and over)” or “aged (80 and over)”) 323 Advanced
38 36 not 37 1 Advanced
39 33 not 38 370 Advanced
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Footnotes

Contributors

SS contributed to writing the paper, initiating the study, designing the study, screening titles, abstracts and articles, analyzing the data, and assessing the methodological quality of individual studies and the overall quality of the evidence. KLR contributed to writing the paper and assisted with screening titles, abstracts and articles, and assessing the methodological quality of individual studies and the overall quality of the evidence. AHK contributed to writing the paper. DES contributed to writing the paper. SLG (the guarantor) and contributed to writing the paper, initiating the study, and monitoring progress.

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