RESEARCH ARTICLE


Prevalence Estimates, Severity, and Risk Factors of Depressive Symptoms among Coronary Artery Disease Patients after Ten Days of Percutaneous Coronary Intervention



Sukaina I. Rawashdeh1, Rasheed Ibdah1, Khalid A. Kheirallah2, Abdullah Al-kasasbeh1, Liqaa A. Raffee3, Nasr Alrabadi4, Iyad S. Albustami5, Rabia Haddad6, Raed M. Ibdah7, Abdel-Hameed Al-Mistarehi2, *
iD

1 Division of Cardiology, Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
2 Department of Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
3 Department of Accident and Emergency Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
4 Department of Pharmacology, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
5 Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan
6 Department of Nursing, King Abdullah University Hospital, Irbid, Jordan
7 Division of Psychiatry, Department of Neuroscience, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan


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© 2021 Rawashdeh et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at Department of Public Health and Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, PO Box: 3030, Irbid (22110), Jordan; Mobile: 00962 7 9828 4360; E-mail: awalmistarehi18@med.just.edu.jo


Abstract

Background:

Depression and cardiovascular disorders are significant determinants of health that affect the quality of life and life expectations. Despite the high importance of depression screening among Coronary Artery Disease (CAD) patients, the time being to assess and treat it remains controversial.

Objectives:

This study aims to assess the prevalence estimates and severity of depressive symptoms and determine the risk factors associated with developing such symptoms among CAD patients after ten days of Percutaneous Coronary Intervention (PCI).

Methods:

All patients who underwent elective PCI between October 5, 2019, and Mid-March 2020 and diagnosed with CAD were included in this cross-sectional study. CAD was defined as intra-luminal stenosis of ≥ 50% in one or more of the coronary arteries. Depressive symptoms were screened after ten days of the PCI utilizing the patient health questionnaire-9 (PHQ-9) tool. A linear regression model was used to assess the adjusted effects of independent variables on PHQ-9 scores. Electronic medical records, clinical charts, and PCI and echocardiogram reports were reviewed.

Results:

Out of 385 CAD patients, a total of 335 were included in this study, with a response rate of 87%. The participants' mean (±SD) age was 57.5±10.7 years, 75.2% were males, 43% were current smokers, and 73.7% had below bachelor's education. The prevalence estimates of patients with moderate to severe depressive symptoms (PHQ-9 ≥10) was 34%, mild depression 45.1%, and normal 20.9%. Female gender, low educational level and diabetes mellitus were found to be the significant independent predictors of depression among our cohort with (t(333) = 3.68, p<0.001); (t(333) = 5.13, p<0.001); and (t(333) = 2.79, p=0.042), respectively.

Conclusion:

This study suggests a high prevalence of depressive symptoms among CAD patients after ten days of PCI. Approximately one out of three patients with CAD have significant symptoms of depression, which is an alarming finding for clinicians. Moreover, this study demonstrates a lack of sufficient depression recognition and management in similar study settings. Integration of mental health assessment and treatment among patients with CAD as soon as after PCI is recommended for optimal and effective treatment and to obtain the best outcomes.

Keywords: Depression, Major depressive disorder, Coronary artery disease, Ischemic heart disease, Catheterization, Percutaneous coronary intervention, Jordan.



1. INTRODUCTION

Depression and cardiovascular disorders are two of the most common diseases worldwide and constitute major growing public health problems that affect the quality of life and life expectations [1-3]. Major depressive disorder (MDD) is one of the leading causes of disability worldwide, and its global prevalence ranges from 10.1% to 12.3% [3, 4]. Previous studies shed light on a possible direct association between various cardiac diseases and stress-related disorders such as depression, exhaustion, and anxiety [5, 6]. Nonetheless, depression is highly prevalent among coronary artery disease (CAD) patients; up to 45% of CAD patients could suffer from clinically significant depressive symptoms, and up to 20% diagnosed with MDD [7-9]. Compared to the general population and those without CAD, CAD patients were found to be two- to three-folds more likely to have a diagnosis of depression [10, 11] and similar to the rates of MDD in patients with cancer [12], and diabetes mellitus (DM) [13].

Depression is not only common in CAD patients but also considered an independent risk factor for major adverse cardiovascular events, associated with poor progression of CAD and increased CAD-related mortality [14-17]. Two systemic reviews and meta-analyses showed that depressed post-myocardial infarction patients have a 2- to 2.5-fold increased risk for all-cause mortality [18, 19]. Both pathophysiologic and behavioral mechanisms could explain the connection between depression and CAD, including inflammation, increased platelet activity and aggregation, and autonomic nervous system dysfunction [20]. Besides, depressed patients are less likely to participate in healthy behaviors, including following a healthy diet, maintaining regular exercise, medication adherence, and stress reduction [20].

Even though safe and effective treatments for MDD are available, depression remains underdiagnosed and undertreated [21]. Besides, the link between depression and cardiovascular diseases was known for decades, described by Malzberg in 1937, demonstrating that patients with severe depression had higher mortality than the general population [22]. The rates of depression recognition and treatment remain low in CAD patients; in a previous study conducted on hospitalized cardiac patients, only 11% of patients with depression received adequate antidepressant therapy [23]. Besides the importance of depression screening among such patients, the controversy may be related to the time of assessment and when should psychopharmacotherapy be given.

This study aims to estimate the prevalence rates of depressive symptoms, evaluate depression severity among CAD patients after ten days of diagnosis, and determine the predictors of developing depressive symptoms among these patients. This study's novelty lies in its time frame as depression screening was performed after a little time of CAD diagnosis.

2. MATERIALS AND METHODS

2.1. Study Design, Patients Participation, and Recruitment

This is a single-centered, cross-sectional study conducted between October 5, 2019, and Mid-March 2020 in the cardiac catheterization center at King Abdullah University Hospital (KAUH), north of Jordan. The study included all patients who were diagnosed with stable CAD with neither previous nor family history of depression, and admitted for elective percutaneous coronary intervention (PCI). Out of 462 patients admitted for elective PCI during the period as mentioned earlier, 385 had a confirmed CAD diagnosis via angiography. CAD diagnosis was defined as intra-luminal stenosis of ≥50% in the left main coronary artery or ≥70% in one or several major epicardial arteries or significant branches (>2 mm in diameter). This definition is consistent with the American College of Cardiology Foundation, American Heart Association, and European Society of Cardiology definitions for CAD [24-26]. Exclusion criteria included patients who: 1) were under the age of 18 years, 2) were already on antidepressant drugs, 3) had a previous or family history of depression before PCI, 4) had depression secondary to substance abuse or any organic disorder as thyroid disorders or cancer, or 5) presented with the acute coronary syndrome. Also, subjects with congenital heart disease or who were unwilling to consent were excluded. Patients who showcased the following health complications after PCI: intubated, in shock, transferred to the intensive care unit, acute pulmonary edema, fatigued, or in active pain were also excluded.

Electronic medical records, clinical charts, PCI reports, and nursing records of all included patients were reviewed, and detailed socio-demographic information, comorbidities, previous history of CAD, and PCI findings were recorded for participants who consented to the study. A review of the Echocardiogram obtained the ejection fraction.

Participants' risk and severity of depressive symptoms were assessed using the Arabic version of the 9-item Patient Health Questionnaire (PHQ-9) after ten days of the PCI [28]. The validity, reliability, and accuracy of this tool were assessed elsewhere [27-30]. PHQ-9 consists of nine items following the MDD diagnostic criteria in the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV). Participants’ responses were coded using a 4-point Likers scale: 3 = nearly every day; 2 = more than half of the days; 1 = several days; 0 = not at all. Item points (0-3) were added to the total score depending on the patient's choice for each item. A final score ranging between 0 and 27 was calculated for each patient. Higher scores indicated increased depression severity. PHQ-9 is a dual-purpose instrument that can grade the severity of depressive symptoms and establish MDD diagnosis risk [29, 30]. The total score of the PHQ-9 questionnaire for each participant was interpreted as follows: no (0-4), mild (5-9), moderate (10-14), moderately severe (15–19), and severe (20-27) risk of depression [29, 30]. PHQ-9 score ≥10 had a sensitivity of 88% and 85-88% specificity for the MDD [29, 30].

2.2. Ethical Standards

This study was approved by the Institutional Review Board (IRB) of Jordan University of Science and Technology and King Abdullah University Hospital (IRB reference number is 36/132/2020). Signed informed consent was collected from each participant before enrollment. The survey was anonymous, and the recruited information was kept confidential. This study was conducted following the 1964 Helsinki declaration, as revised in 2009 and its amendments or comparable ethical standards [31]. The study protocol was registered at the Registry website with a unique identification number of 6106 [32].

2.3. Data Statistical Analysis

Data were analyzed and proceeded using the IBM Statistical Package for the Social Sciences (SPSS) software for Windows, version 25.0 (Armonk, NY: IBM Corp). This was important in establishing the central tendencies, dispersion, variance, and skewness of the data. Categorical data variables were described using frequency and percentage, while continuous data variables were presented using mean and standard deviation (SD). An independent sample t-test, or one-way ANOVA was conducted to examine the variances in depression scores based on the demographic and clinical-comorbid variables. Similarly, multiple-linear regression analysis was employed to assess the adjusted effects of independent variables on PHQ-9 scores. A p-value of less than 0.05 was considered statistically significant.

3. RESULTS

3.1. Demographical Details

Out of 385 CAD diagnosed patients, a total of 335 patients were included in this study, with a response rate of 87% (Fig. 1). The participants' average (±SD) age was 57.5 (±10.7) years, ranging between 27 and 87. More than three-quarters of participants (75.2%) were males, 65.4% were unemployed, 73.7% reported having below bachelor's education, and 43% were current smokers. The mean (±SD) body mass index (BMI) was 28.1 (± 3.0) kg/m2, ranging between 20 and 36 kg/m2. The mean ejection fraction was 51.72 (SD=9.69) percent, ranging between 24% and 69%. A high skewness level was found in the ejection fraction variable (-1.18), so it was categorized into ≥45% (79.1%) and <45 (20.9%). The vast majority of participants had comorbidities such as hyperlipidemia, hypertension, and previous history of CAD. More than half of the patients (57.6%) had DM. Detailed demographic information and clinical-comorbid features are summarized in Table 1.

Fig. (1). Participants flow chart.

Table 1. Demographics and clinical characteristics of coronary artery disease patients (n=335).
Factors Categories Frequency Percentage (%) M (±SD) Range
Age - - - 57.46 (±10.69) 27-87 years
Gender Male 252 75.2 - -
Female 83 24.8 - -
Education Level Below Bachelor 247 73.7 - -
Bachelor’s degree or higher 88 26.3 - -
Employment status Employed 116 34.6 - -
Unemployed 219 65.4 - -
Smoking Smoker 144 43.0 - -
Non-smoker 191 57.0 - -
Hypertension Yes 271 80.9 - -
No 64 19.1 - -
Hyperlipidemia Yes 295 88.1 - -
No 40 11.9 - -
Diabetes mellitus No 142 42.4 - -
Yes 193 57.6 - -
Previous history of CAD Yes 257 76.7 - -
No 78 23.3 - -
Ejection Fraction ≥45% 265 79.1 51.72 (±9.69) 24-69%
<45% 70 20.9 - -
BMI (Kg/m2) - - 28.10 (±3.00) 20-36

3.2. The Prevalence Rates of Depressive Symptoms

As shown in Fig. (2), Approximately one-fifth of the sample (n=70) reported no depressive symptoms, while 45.1% (n=151) showed mild depressive symptoms. About 26.3% (n=88) had moderate depressive symptoms and 7.2% (n=24) displayed moderately severe depressive symptoms. Additionally, two participants (0.6%) had severe depression risk. Overall, the PHQ-9 mean score was 8.0 (SD=4.1), ranging between 0 and 21. The prevalence estimate of MDD, PHQ-9 score ≥ 10, was 34% (144 out of 335).

Fig. (2). Percentages of depression severity (n=335).

Table 2. The differences in PHQ-9 total score based on demographics and clinical-comorbid variables (n=335).
Variable Categories PHQ-9 score
Mean (±SD)
t (333) p-value 95% CI
Gender Male 7.50 (±3.94) -4.00 <0.001 1.03 - 3.04
Female 9.54 (±4.28) - - -
Employment status Employed 7.59 (±4.01) -1.33 0.18 -0.30 - 1.55
Unemployed 8.22 (±4.16) - - -
Educational level Below Bachelor 8.74 (±4.07) 5.72 <0.001 1.83 - 3.75
Bachelor or higher 5.94 (±3.50) - - -
Smoking Smoker 8.03 (±4.19) 0.91 -0.94 - 0.84
Non-smoker 7.98 (±4.07) -0.11 -
Hypertension Yes 8.26 (±3.98) 0.01 -2.49 - -0.26
No 6.89 (±4.51) -2.42 -
Hyperlipidemia Yes 8.13 (±4.08) 0.10 -2.47 – 0.24
No 7.02 (±4.25) -1.60 -
Diabetes mellitus Yes 8.51 (±4.18) 0.008 -2.08 – -0.30
No 7.31 (±3.94) -2.65
Previous history of CAD Yes 8.08 (±4.07) 0.52 -1.39 – 0.70
No 7.74 (±4.28) -0.64 -
Ejection Fraction ≥45% 7.91 (±4.24) -0.80 0.42 -0.64 – 1.53
<45% 8.35 (±3.62) - - -

3.3. Differences in Depression Score Based on Demographic and Clinical-comorbid Variables

An independent t-test was used to examine the differences in mean PHQ-9 scores by demographical and clinical-comorbid variables (Table 2). Significant differences in PHQ-9 mean scores were detected by gender, educational level, hypertension, and DM. Female participants had significantly (t (333) = 4.00, p<0.001) higher mean PHQ-9 score (9.54 ± 4.28) compared to their male counterparts (7.50 ± 3.94). Participants with below bachelor’s educational level had significantly (t (333) = 5.72, p<0.001) higher mean depression score (8.74 ± 4.07) compared to those with bachelor’s education or higher (5.94 ± 3.50). Participants with HTN had a significantly higher mean PHQ-9 score (8.26 ± 3.98) compared to their counterparts without such comorbidity (6.89 ± 4.51) (t (333) = 2.42, p=0.01). DM participants had significantly (t (333) = 2.65, p=0.008) higher mean PHQ-9 score (8.51 ± 34.18) compared to non-diabetic participants (7.31 ± 3.98).

No significant differences in mean PHQ-9 scores were detected by occupational status (t (333) =1.33, p=0.18); smoking status (t (333) =-0.11, p=0.91); hyperlipidemia (t (333) =0.86, p=0.10); previous history of CAD (t (333) =-0.64, p=0.52); and ejection fraction (t (333) =0.80, p=0.42).

3.4. Predictors of Depressive Symptoms among CAD Patients

A multiple-linear regression model was used to determine the adjusted effects of independent variables, including demographical details and the clinical-comorbid variables, on PHQ-9 scores to determine the depressive symptoms predictors. The entire model was established to be significant and explained 13% of the variance in PHQ-9 scores (F (11, 333) = 5.33, p<0.001). The model is summarized in Table 3.

Female gender showed (t (333) = 3.68, p<0.001), low educational level had (t (333) = 5.13, p<0.001), and diabetic patients (t (333) = 2.79, p=0.042) were significant predictors of PHQ-9 scores after controlling for the other variables in the model. Age, occupation, smoking status, hypertension, hyperlipidemia, previous history of CAD, BMI, and ejection fraction were not significant predictors of PHQ-9 scores (p>0.05 for each variable).

Table 3. The predictors for depression among coronary artery disease patients (n=335) using Multiple Linear regression.
Variables Unstandardized β t (333) p-value 95% CI. Part Square
Age -0.03 -1.40 0.16 -0.08 – 0.01 0.49
Gender (male) -2.06 -3.68 <0.001 -3.16 – -0.96 3.57
Occupation -0.15 -0.27 0.78 -0.26 – 0.96 0.01
Education (Bachelor or higher) -2.52 -5.13 <0.001 -3.48 – -1.55 6.76
Smoking 0.84 1.75 0.08 -0.10 – 1.79 0.81
Hypertension 0.62 1.02 0.30 -0.57 – 1.81 0.25
Hyperlipidemia -0.46 -0.62 0.53 -1.91 – 0.99 0.09
Diabetes mellitus 1.85 2.79 0.04 0.25 – 1.80 1.81
Previous history of CAD 0.18 0.33 0.73 -0.90 – 1.28 0.02
BMI 0.04 0.59 0.55 -0.10 – 0.18 0.09
Ejection Fraction -0.46 -0.86 0.39 -1.51 – 0.59 0.23
Table 4. Comparison of the present study findings with other studies from different countries on depression among IHD patients.
First Author, Year Location of Study Setting Sample Size (CAD Patients) Age, Years
(mean ± SD) or (range)
Females,
n (%)
Depression Assessment Symptoms of Depression,
n (%)*
Present study Jordan Outpatients 335 57.46 ± 10.69 83 (24.8%) PHQ-9 144 (34%)
Al-Zaru et al., 2020 [30] Jordan Outpatients 174 58.6 ± 10.2 84 (48.3%) CDS 93 (53.4%)
Alkafaji et al., 2020 [31] Iraq Inpatients 120 20 - 80 44 (36.7%) BDI 58 (48.3%)
Shiotani et al., 2002 [32] Asia Inpatients 1,042 63 ± 11 (19.4 %) SDS 438 (42%)
Myers et al., 2012 [33] Israel Inpatients 632 52 - BDI 176 (27.8%)
Seecheran et al., 2019 [34] Trinidad and Tobago Outpatients 1203 62.5 ± 13.1 632 (52.5%) PHQ-9 301 (25%)
Sharma Dhital et al., 2018 [35] Nepal Outpatients 168 53.01 ± 13.91 66 (39.3%) HADS 40 (23.8%)
Davidson et al., 2010 [36] USA Inpatients 453 25 - 93 190 (42%) Structured Psychiatric Interview 109 (24.0%)
Ziegelstein et al., 2000 [37] USA Inpatients 204 60 88 (43.1%) BDI 35 (17.2%)
Lauzon et al., 2003 [38] Canada Inpatients 550 60 116 (21%) BDI 191 (35%)
Kuhlmann et al., 2019 [39] German Inpatients 1,024 62.7 ± 10.2 197 (19.2%) PHQ-9 463 (45.2%)

4. DISCUSSION

Medical literature focused on the cardiac treatment of CAD patients and the technic and complications associated with catheterization procedures with less attention to the mental health problems among this population. The current study demonstrated that symptoms of depression were common among CAD patients after ten days of PCI. Also, the prevalence estimate of MDD was high, 34% or about four in every ten patients, as indicated by the PHQ-9 cut-off point of ≥10. Female gender, low educational level, and DM were independent predictors for high PHQ-9 scores, indicating a higher risk of depression. These results suggest that potential depression comorbidity may be under-estimated and underdiagnosed among our CAD patients. These findings are alarming, considering the lack of sufficient depression screening, recognition, and management in similar study settings. Integrating mental health assessment and treatment among patients with CAD, especially in a short time after PCI, is crucial for optimum health. The findings call for harmonization of care between healthcare providers and making changes in the instituting policies to enhance referral and management of potential depression among CAD patients.

Previous studies revealed a relatively high heterogeneity in the prevalence estimates of depressive symptoms among CAD patients, as shown in Table 4. These prevalence estimates’ discrepancy could be attributed to the different methods and designs used in the included studies, such as the different tools for assessing depression. However, these studies, as well as our study, reported a high prevalence of depressive symptoms among CAD patients that ranged between 17% and 53% [33-43].

The prevalence of depressive symptoms among CAD patients in the current study was 34%, which was lower than the previously reported estimates among Jordanian patients with CAD, as they estimated a prevalence rate of 53.4% using a cut-off point of 90 in the Cardiac Depression Scale (CDS) screening tool [33]. This difference in prevalence estimates could be attributed to the different cohorts investigated, methods, tools, and time-frame as the latter study included a smaller sample size with more females than our study. Besides, Al-Zaru et al. included a significant number of patients with cancer and thyroid disorders (31%), which could overestimate the prevalence of depressive symptoms [33]. However, patients with these conditions were not included in our study. Also, the cut-off point of 90 in the CDS has higher sensitivity for depression as it included mild, moderate, and severe depressive patients while our study, using PHQ-9 cut-off point of ≥ 10 for estimating the prevalence estimate of MDD, excluded 45.1% mild depressive patients. Still, the superiority of the other self-report questionnaires over PHQ-9 in the screening of depression remains controversial [44, 45]. While our study was conducted after ten days of PCI, Al-Zaru et al. included patients with a previous CAD history regardless of the time lag between survey and catheterization procedure [33]. These variations may contribute to discrepancies between prevalence estimates reported in the literature and the current study.

On the other hand, our estimated prevalence of depressive symptoms among CAD patients was comparable to the findings of Lauzon et al., where they reported a prevalence of 35% among Canadian CAD patients [41]. Moreover, two studies estimated the prevalence of depression among CAD patients before and after the PCI; Wang et al. [46] used a combination of Hospital Anxiety and Depression Scale and the Mini-International Neuropsychiatric Interview to identify patients with depression, while Li et al. [47] determined depression prevalence based on Zung Self-Rating Depression Scale. These two studies reported depression in nearly 40% of the postoperative patients, increasing more than ten percentage points than before the operation [46, 47].

Several previous works showed that depression is associated with a higher risk of developing cardiovascular diseases [5, 6, 48-50]. A recent study conducted by Daskalopoulou et al. examined depression as a possible risk factor for 12 cardiovascular diseases in approximately 2 million men and women; it was shown that depression was prospectively associated with cardiac, cerebrovascular, and peripheral diseases, with no evidence of disease specificity [6]. Smeijers et al. investigated levels of psychological distress (depressive symptoms, perceived stress, general anxiety), illness-related anxiety, and personality factors among patients with takotsubo cardiomyopathy [51]. Takotsubo cardiomyopathy is an acute and transient condition characterized by left ventricular wall motion abnormality combined with symptoms and signs mimicking acute MI, predominantly in postmenopausal women [52-54]. The authors studied 18 patients with takotsubo cardiomyopathy and two comparison groups: 19 healthy controls and 19 patients with heart failure [51]. It was shown that takotsubo cardiomyopathy was associated with higher levels of depressive symptoms, more illness-related anxiety, and less openness than healthy controls, and No differences between Takotsubo cardiomyopathy and heart failure patients regarding the psychological measures [51]. Other studies concordant with Smeijers et al. findings and reported a significant association between Takotsubo cardiomyopathy and psychiatric disorders such as depression [55-59].

Regarding CAD specifically, two independent reviews found that the relative risk for the onset of CAD was 1.64 for depressed compared to non-depressed individuals followed for an average of 13 years [16, 60]. Studies that have followed large population samples for from 4 to 10 years have found that both major depression [61] and depressive symptoms [62] predict incident CAD in individuals initially free of heart conditions, controlling for common risk factors. Even increasing recognition of this relationship led both American and European treatment guidelines to recommend routine screening for depression and anxiety in CAD patients [63]; this relationship remains underestimated in developing countries.

This study revealed a significantly higher risk of depression among females than males, which is concordant with previous studies' findings [33, 37, 38, 64, 65]. Some studies reported a 1.7-fold higher incidence and prevalence in women [66, 67]. This gender disparity could be attributed to the hormonal (biological) effects, amongst other issues, such as cultural differences, education, and diet [66]. The traditional role of Jordanian women as responsible for their families could be a source of stress. Besides, the housework responsibility of women could increase the risk of depression [38]. Moreover, in Jordanian culture, women's actions are more likely to be criticized than men's. Gender role (masculinity) may also predispose women to be more susceptible to depression compared to males.

Our study did not find significant differences in PHQ-9 scores by age, concordant with a previous study from Jordan [33] and other studies [38, 64]. On the other hand, this finding contradicts Konrad et al.'s study, conducted in Germany, where it was reported that older patients with CAD faced a higher risk for depression than their younger peers [68]. Our finding could be explained by the more religious participation of older people than younger people in Muslim countries such as Jordan, which may help patients mitigate their current conditions.

Besides being female, the study's findings showed that low educational level was a risk factor for developing depression among CAD patients. Likewise, Dhital et al. found that levels of depression were more prevalent among illiterate respondents and those with low educational levels [38]. Also, Al-Abbudi et al., a study conducted in a neighboring country, found that 85% of depressed ischemic heart disease patients were of low educational level or illiterate [65]. In contrast to this finding, a study conducted by the National Heart Association of Malaysia revealed that education level is not associated with depression [69]. This discrepancy in findings might be due to the inclusion of different samples and the study settings.

Regarding comorbidities associated with higher depression scores, our study found that hypertension and DM were associated with higher PHQ-9 scores, based on univariate analysis, which is concordant with Bahall et al. findings [64]. However, after adjusting for potential confounding factors, including demographic characteristics and the clinical-comorbid variables, hypertension did not predict PHQ-9, while DM was the only comorbidity as a significant predictor for higher PHQ-9 scores and subsequent development depression.

Increased depression risk among DM patients was suggested by our findings, which is concordant with a previous study conducted in Jordan, where it was reported that more than one-third of diabetic patients had depression, according to PHQ-9 [13]. A case-control study conducted by Anderson et al. reported that the odds of depression in diabetic patients were twice as high as those in the non-diabetic comparison group (OR = 2.0, 95% CI 1.8–2.2) [70]. Also, Al-Ghamdi et al. concluded that depression is more common among diabetic patients (34%) compared to non-diabetics (13%) (p<0.001) [71]. This finding might be due to more somatic symptoms related to DM, which interrupt the CAD patients' daily activities and caused them to feel more depressed. Besides, the somatic symptoms and behaviors related to diabetes, such as tiredness, sleeping, and poor appetite or overeating, are highlighted in the PHQ-9 but not in others [72].

There are several limitations to this study. First, this study's cross-sectional design addresses only one point in time that lacks temporality and comparison of depression prevalence estimates before and after CAD diagnosis. It also lacks a comparison, control, group. Therefore, we could not provide evidence for a causal relationship between depression and CAD. A prospective cohort will be a better fit to assess this relationship. Second, the number of enrolled patients was relatively small, although the response rate was high; a total of 18 CAD patients declined to participate. This decline could be due to the cultural perspective regarding depression and the social stigma attached to mental health problems, especially in developing countries. Thus, a response bias may have occurred if the non-responders refused the participation as they felt uninterested or depressed. However, at the beginning of this study, we intended to include a larger sample size of CAD patients and make the study design a case-control one, but the COVID-19 crisis that affected Jordan in mid-March restricted such plans [73-77]. Third, PHQ-9 is a screening tool that needs a psychiatrist to conduct a structured clinical interview to confirm depression diagnosis. This could have overestimated the prevalence estimated of depression among our patients with CAD [78, 13]. Fourth, the patients’ truthfulness for their responses to the questions asked is controversial as some responses may not have told the truth on purpose to prevent doctors’ concern for mental health rather than cardiovascular health or that negative patients' stigma to state how they really feel. However, we assured participants of the results' confidentiality to avoid such effects of underestimating the reported depression estimates.

Regardless of the limitations, this study provided baseline estimates for potentially depressive symptoms among CAD patients within developing country settings and established potential predictors for the risk of depression. Future investigations of this research problem should focus on utilizing a follow-up approach and consider psycho-behavioral or pharmacological interventions to estimate the effects of treating depression on cardiac health among CAD patients, assess the benefits of supportive psychotherapy until cardiac condition stable, and better investigate the bidirectional relationship between depression and cardiac health. Larger-scale studies with proper depression assessment are needed to validate our findings and help implement change to no longer understate depression associated with cardiovascular diseases. Investigation of the efficacy of depression treatment in lowering the morbidity and mortality rates secondary to cardiac disease is also a research need.

CONCLUSION

This study suggests a relatively high prevalence estimate of depressive symptoms among CAD patients after ten days of PCI. Approximately one in three patients with CAD have symptoms of major depressive disorder. Female gender, low educational level, and diabetes mellitus were independent predictors for high depression risk among CAD patients. These findings are alarming, considering the lack of sufficient depression screening, recognition, and management in similar study settings. Integration of mental health assessment and treatment among patients with CAD as soon as after PCI is crucial for optimum health. Advanced cohort studies related to depression and the necessity of psychopharmacotherapy in CAD patients are suggested.

LIST OF ABBREVIATIONS

CAD = Coronary Artery Disease
PCI = Percutaneous Coronary Intervention
PHQ-9 = Patient Health Questionnaire-9
SD = Standard Deviation
MDD = Major Depressive Disorder
DM = Diabetes Mellitus
KAUH = King Abdullah University Hospital
IRB = Institutional Review Board
SPSS = Statistical Package for the Social Sciences
BMI = Body Mass Index

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

All procedures performed in this study were reviewed and ethically approved by the Institutional Review Board (IRB) and the research and ethics committee at King Abdullah University Hospital and Jordan University of Science and Technology (IRB reference number: 36/132/2020).

HUMAN AND ANIMAL RIGHTS

No animals were used in this research. All human research procedures followed were in accordance with the ethical standards of the committee responsible for human experimentation (institutional and national), and with the Helsinki Declaration of 1964, as revised in 2009 and its amendments.

CONSENT FOR PUBLICATION

Written informed consent was obtained from all participants included in this study.

AVAILABILITY OF DATA AND MATERIALS

The datasets generated and analyzed during the current study are available with the corresponding author [A.A] and can be provided on a reasonable request according to IRB approval restrictions.

FUNDING

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest, financial or otherwise.

ACKNOWLEDGEMENTS

Declared none.

REFERENCES

[1] Bozzini S, Falcone C. The interface of coronary artery disease and depression: Pathophysiology and diagnosis. J Cardiovasc Dis 2015; 2(2): 1015.
[2] Correll CU, Solmi M, Veronese N, et al. Prevalence, incidence and mortality from cardiovascular disease in patients with pooled and specific severe mental illness: A large-scale meta-analysis of 3,211,768 patients and 113,383,368 controls. World Psychiatry 2017; 16(2): 163-80. [Erratum in: World Psychiatry. 2018;17 ]. [1]. [:120. PMID: 28498599; PMCID: PMC5428179].
[3] Murray CJ, Lopez AD. Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study. Lancet 1997; 17;349(9063): 1436-42.
[4] GBD 2016 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016. Lancet 2017; 16;390(10100): 1211-59.
[5] van der Wall EE. Cardiac disease and depression; a direct association? Neth Heart J 2016; 24(9): 495-7.
[6] Daskalopoulou M, George J, Walters K, et al. Depression as a risk factor for the initial presentation of twelve cardiac, cerebrovascular, and peripheral arterial diseases: Data linkage study of 1.9 million women and men. PLoS One 2016; 22;11(4): e0153838.
[7] Carney RM, Freedland KE. Depression in patients with coronary heart disease. Am J Med 2008; 121(11)(Suppl. 2): S20-7.
[8] Thombs BD, de Jonge P, Coyne JC, et al. Depression screening and patient outcomes in cardiovascular care: a systematic review. JAMA 2008; 12;300(18): 2161-71.
[9] Thombs BD, Bass EB, Ford DE, et al. Prevalence of depression in survivors of acute myocardial infarction. J Gen Intern Med 2006; 21(1): 30-8.
[10] Piwoński J, Piwońska A, Sygnowska E. Is there an association between depressive symptoms and coronary artery disease in the Polish adult population? Kardiol Pol 2014; 72(1): 50-5.
[11] Ansari I, Fallahi F, Babakhani E, et al. The relationship between depression and ischemic heart disease among middle aged people: a case control study 2019.
[12] Snyderman D, Wynn D. Depression in cancer patients. Prim Care 2009; 36(4): 703-19.
[13] Khassawneh AH, Alzoubi A, Khasawneh AG, et al. The relationship between depression and metabolic control parameters in type 2 diabetic patients: A cross-sectional and feasibility interventional study. Int J Clin Pract 2021; 75(4)e13777
[14] Yusuf S, Hawken S, Ounpuu S, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004; 364(9438): 937-52.
[15] Pizzi C, Manzoli L, Mancini S, Bedetti G, Fontana F, Costa GM. Autonomic nervous system, inflammation and preclinical carotid atherosclerosis in depressed subjects with coronary risk factors. Atherosclerosis 2010; 212(1): 292-8.
[16] Wulsin LR, Singal BM. Do depressive symptoms increase the risk for the onset of coronary disease? A systematic quantitative review. Psychosom Med 2003; 65(2): 201-10.
[17] Kop WJ, Stein PK, Tracy RP, Barzilay JI, Schulz R, Gottdiener JS. Autonomic nervous system dysfunction and inflammation contribute to the increased cardiovascular mortality risk associated with depression. Psychosom Med 2010; 72(7): 626-35.
[18] van Melle JP, de Jonge P, Spijkerman TA, et al. Prognostic association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med 2004; 66(6): 814-22.
[19] Barth J, Schumacher M, Herrmann-Lingen C. Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom Med 2004; 66(6): 802-13.
[20] Celano CM, Huffman JC. Depression and cardiac disease: A review. Cardiol Rev 2011; 19(3): 130-42.
[21] Kessler RC, Berglund P, Demler O, et al. The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 2003; 289(23): 3095-105.
[22] Malzberg B. Mortality among patients with involution melancholia. Am J Psychiatry 1937; 93: 1231-8.
[23] Huffman JC, Smith FA, Blais MA, Beiser ME, Januzzi JL, Fricchione GL. Recognition and treatment of depression and anxiety in patients with acute myocardial infarction. Am J Cardiol 2006; 98(3): 319-24.
[24] Weintraub WS, Karlsberg RP, Tcheng JE, et al. ACCF/AHA 2011 key data elements and definitions of a base cardiovascular vocabulary for electronic health records: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Clinical Data Standards. J Am Coll Cardiol 2011; 58(2): 202-22.
[25] Task Force Members. 2013.
[26] Messerli FH, Mancia G, Conti CR, Pepine CJ. Guidelines on the management of stable angina pectoris: Executive summary: The task force on the management of stable angina pectoris of the European society of cardiology. Eur Heart J 2006; 27(23): 2902-3.
[27] AlHadi AN, AlAteeq DA, Al-Sharif E, et al. An arabic translation, reliability, and validation of Patient Health Questionnaire in a Saudi sample. Ann Gen Psychiatry 2017; 16: 32.
[28] Samrah SM, Al-Mistarehi AH, Aleshawi AJ, et al. Depression and coping among COVID-19-infected individuals after 10 days of mandatory in-hospital quarantine, irbid, jordan. Psychol Res Behav Manag 2020; 13: 823-30.
[29] Kroenke K, Spitzer RL, Williams JB. The PHQ-9: Validity of a brief depression severity measure. J Gen Intern Med 2001; 16(9): 606-13.
[30] Levis B, Benedetti A, Thombs BD. Accuracy of Patient Health Questionnaire-9 (PHQ-9) for screening to detect major depression: individual participant data meta-analysis. BMJ 2019; 365: l1476.
[31] Declaration of Helsinki. Ethical principles for medical research involving human subjects. J Indian Med Assoc 2009; 107(6): 403-5.
[32] Rawashdeh S. https://www.researchregistry.com/register-now#user-researchregistry/registerresearchdetails/5f84282d32bca80015e30335/
[33] Al-Zaru IM, Alhalaiqa F, Dalky HF, Arramadan KA, Batiha AM. Depression in nonhospitalized jordanian patients with coronary artery disease. J Nurs Res 2020; 28(1)e66
[34] Alkafaji AZM, Risun AH. Prevalence rate of depression among ischemic heart diseases patients in al-diwaneya province / iraq. Med-Leg Update 2020; 20: 1030-5.
[35] Shiotani I, Sato H, Kinjo K, et al. Depressive symptoms predict 12-month prognosis in elderly patients with acute myocardial infarction. J Cardiovasc Risk 2002; 9(3): 153-60.
[36] Myers V, Gerber Y, Benyamini Y, Goldbourt U, Drory Y. Post-myocardial infarction depression: Increased hospital admissions and reduced adoption of secondary prevention measures--a longitudinal study. J Psychosom Res 2012; 72(1): 5-10.
[37] Seecheran N, Jagdeo CL, Seecheran R, et al. Screening for depressive symptoms in cardiovascular patients at a tertiary centre in Trinidad and Tobago: investigation of correlates in the SAD CAT study. BMC Psychiatry 2020; 20(1): 498.
[38] Sharma Dhital P, Sharma K, Poudel P, Dhital PR. Anxiety and depression among patients with coronary artery Disease Attending at a cardiac center, kathmandu, nepal. Nurs Res Pract 2018; 20184181952
[39] Davidson KW, Burg MM, Kronish IM, et al. Association of anhedonia with recurrent major adverse cardiac events and mortality 1 year after acute coronary syndrome. Arch Gen Psychiatry 2010; 67(5): 480-8.
[40] Ziegelstein RC, Fauerbach JA, Stevens SS, Romanelli J, Richter DP, Bush DE. Patients with depression are less likely to follow recommendations to reduce cardiac risk during recovery from a myocardial infarction. Arch Intern Med 2000; 160(12): 1818-23.
[41] Lauzon C, Beck CA, Huynh T, et al. Depression and prognosis following hospital admission because of acute myocardial infarction. CMAJ 2003; 168(5): 547-52.
[42] Kuhlmann SL, Arolt V, Haverkamp W, et al. Prevalence, 12-month prognosis, and clinical management need of depression in coronary heart disease patients: A prospective cohort study. Psychother Psychosom 2019; 88(5): 300-11.
[43] Lecca M, Saba L, Sanfilippo R, et al. Quality of life in carotid atherosclerosis: The role of co-morbid mood disorders. Clin Pract Epidemiol Ment Health 2016; 12: 1-8.
[44] Cameron IM, Cardy A, Crawford JR, et al. Measuring depression severity in general practice: discriminatory performance of the PHQ-9, HADS-D, and BDI-II. Br J Gen Pract 2011; 61(588): e419-26.
[45] Pettersson A, Boström KB, Gustavsson P, Ekselius L. Which instruments to support diagnosis of depression have sufficient accuracy? A systematic review. Nord J Psychiatry 2015; 69(7): 497-508.
[46] Wang ZJ, Guo M, Si TM, et al. Association of depression with adverse cardiovascular events after percutaneous coronary intervention. Coron Artery Dis 2013; 24(7): 589-95.
[47] Li XM, Li TT. Cong HL, Guo ZG, Song JH, Zhao R, Xiao JY. [Impact of depression on prognosis of patients with coronary heart disease undergoing revascularization]. Chinese 2012; 40(2): 103-99.
[48] Kemp AH, Quintana DS. The relationship between mental and physical health: insights from the study of heart rate variability. Int J Psychophysiol 2013; 89(3): 288-96.
[49] Nemeroff CB, Musselman DL, Evans DL. Depression and cardiac disease. Depress Anxiety 1998; 8(Suppl. 1): 71-9.
[50] Nemeroff CB, Goldschmidt-Clermont PJ. Heartache and heartbreak--the link between depression and cardiovascular disease. Nat Rev Cardiol 2012; 9(9): 526-39.
[51] Smeijers L, Szabó BM, Kop WJ. Psychological distress and personality factors in takotsubo cardiomyopathy. Neth Heart J 2016; 24(9): 530-7.
[52] Ter Bals E, Odekerken DA, Somsen GA. Takotsubo cardiomyopathy complicated by cardiac tamponade. Neth Heart J 2014; 22(5): 246-8.
[53] Postema PG, Wiersma JJ, van der Bilt IA, Dekkers P, van Bergen PF. Takotsubo cardiomyopathy shortly following pacemaker implantation-case report and review of the literature. Neth Heart J 2014; 22(10): 456-9.
[54] Otten AM, Ottervanger JP, Symersky T, Suryapranata H, de Boer MJ, Maas AH. Diagnosis of takotsubo cardiomyopathy is increasing over time in patients presenting as ST-elevation myocardial infarction. Neth Heart J 2016; 24(9): 520-9.
[55] Ghadri JR, Wittstein IS, Prasad A, et al. International Expert Consensus Document on Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and Pathophysiology. Eur Heart J 2018; 39(22): 2032-46.
[56] Templin C, Ghadri JR, Diekmann J, et al. Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy. N Engl J Med 2015; 373(10): 929-38.
[57] Sancassiani F, Carta MG, Montisci R, et al. Takotsubo syndrome is associated with mood disorders and antidepressants use, not with anxiety and impairment of quality of life due to the psychiatric disorder. Clin Pract Epidemiol Ment Health 2018; 14: 26-32.
[58] Wittstein IS, Thiemann DR, Lima JA, et al. Neurohumoral features of myocardial stunning due to sudden emotional stress. N Engl J Med 2005; 352(6): 539-48.
[59] Barton DA, Dawood T, Lambert EA. Sympathetic activity in major depressive disorder: identifying those at increased cardiac risk? J Hypertens 2007; 25(10): 2117-4.
[60] Rugulies R. Depression as a predictor for coronary heart disease. a review and meta-analysis. Am J Prev Med 2002; 23(1): 51-61.
[61] Surtees PG, Wainwright NW, Luben RN, Wareham NJ, Bingham SA, Khaw KT. Depression and ischemic heart disease mortality: evidence from the EPIC-Norfolk United Kingdom prospective cohort study. Am J Psychiatry 2008; 165(4): 515-23.
[62] Marzari C, Maggi S, Manzato E, et al. Depressive symptoms and development of coronary heart disease events: the Italian longitudinal study on aging. J Gerontol A Biol Sci Med Sci 2005; 60(1): 85-92.
[63] Authors/task force members. European guidelines on cardiovascular disease prevention in clinical practice: The sixth joint task force of the european society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts): Developed with the special contribution of the european association for cardiovascular prevention & rehabilitation (EACPR). Eur J Prev Cardiol 2016; 23(11): NP1-NP96.
[64] Bahall M. Prevalence and associations of depression among patients with cardiac diseases in a public health institute in Trinidad and Tobago. BMC Psychiatry 2019; 19(1): 4.
[65] Al-Abbudi S, Lami F, Wady ZA. Prevalence and assessment of severity of depression among ischemic heart disease patients attending outpatient cardiology department baghdad teaching hospital, baghdad, iraq. J Psychiatry 2018; 21: 1-10.
[66] Albert PR. Why is depression more prevalent in women? J Psychiatry Neurosci 2015; 40(4): 219-21.
[67] Kuehner C, Kuehner C. Why is depression more common among women than among men? Lancet Psychiatry 2017; 4(2): 146-58.
[68] Konrad M, Jacob L, Rapp MA, Kostev K. Depression risk in patients with coronary heart disease in Germany. World J Cardiol 2016; 8(9): 547-52.
[69] Eng HS, Yean LC, Das S, et al. Anxiety and depression in patients with coronary heart disease: a study in a tertiary hospital. Iran J Med Sci 2011; 36(3): 201-6.
[70] Anderson RJ, Freedland KE, Clouse RE, Lustman PJ. The prevalence of comorbid depression in adults with diabetes: a meta-analysis. Diabetes Care 2001; 24(6): 1069-78.
[71] Al-Ghamdi AA. A high prevalence of depression among diabetic patients at a teaching hospital in Western Saudi Arabia. Neurosciences (Riyadh) 2004; 9(2): 108-12.
[72] Reddy P, Philpot B, Ford D, Dunbar JA. Identification of depression in diabetes: the efficacy of PHQ-9 and HADS-D. Br J Gen Pract 2010; 60(575): e239-45.
[73] Samrah SM, Al-Mistarehi AW, Ibnian AM, et al. COVID-19 outbreak in Jordan: Epidemiological features, clinical characteristics, and laboratory findings. Ann Med Surg (Lond) 2020; 57: 103-8.
[74] Khassawneh AH, Alrabadi N, Al-Mistarehi AH, Obeidat N, Kheirallah KA. The role of non-state actors in combating COVID-19 spread in Northern Jordan. Ann Med Surg (Lond) 2020; 60: 484-6.
[75] Samrah SM, Al-Mistarehi AH, Kewan T, et al. Viral Clearance Course of COVID-19 Outbreaks. J Multidiscip Healthc 2021; 14: 555-65.
[76] Ramadan M, Hasan Z, Saleh T, et al. Beyond knowledge: Evaluating the practices and precautionary measures towards COVID-19 amongst medical doctors in Jordan. Int J Clin Pract 2021; 75(6)e14122
[77] Al-Mistarehi AH, Kheirallah KA, Yassin A, et al. Determinants of the willingness of the general population to get vaccinated against COVID-19 in a developing country. Clin Exp Vaccine Res 2021; 10(2): 171-82.
[78] Inoue T, Tanaka T, Nakagawa S, et al. Utility and limitations of PHQ-9 in a clinic specializing in psychiatric care. BMC Psychiatry 2012; 12: 73.