The prevalence of depressive symptoms after acute myocardial infarction (AMI) ranges from 10-50%,1–3 and post-AMI depression has been associated with adverse health-related outcomes such as mortality and poor quality of life.4,5 Therefore, national guidelines recommend that patients be appropriately screened and treated for depression after AMI to improve health-related outcomes.6,7 Previous studies have been conducted about the diagnostic accuracy of using depressive screeners such as the Patient Health Questionnaire-9 (PHQ-9), the Beck Depression Inventory-II, and the Hospital Anxiety and Depression Scale to assess patients who participate in cardiac rehabilitation (CR).8–10
Depressive symptoms after AMI may be related to psychological reactions to acute stressful events11 and may be transient or persistent based on the individual risk factors for depressive symptoms of each patient.12 Therefore, knowledge of the time course of depressive symptoms after AMI and the risk factors for persistent depressive symptoms is important when planning further treatments for post-AMI depressive symptoms. However, only a few longitudinal studies have investigated this issue.12–14 In a prospective study conducted in the United States involving patients who had minor or major depressive disorder 8-10 d after AMI, the depressive disorder persisted for 3 mo after AMI in 51% of individuals.13 In a prospective study conducted in the Czech Republic, the prevalence of depressive symptoms (Beck Depression Inventory score ≥14) 1 d after the onset of AMI was 22%, which sharply decreased to 9% after 3-5 d and gradually increased after discharge to 15% after 6 mo.14 However, these studies did not investigate the factors that were associated with persistent depressive symptoms after AMI.
In a prospective study conducted in the United Kingdom, acute distress or fear during the adaptation to acute coronary syndrome was associated with subsequent depressive symptoms.15 Conversely, patients who engaged in regular physical activity (PA) did not experience fear or acute distress. In a Norwegian cohort study, regular PA decreased the development of depressive symptoms after myocardial infarction.16 In another large cohort study, self-reported exercise reduced both depression and all-cause mortalities.17 According to a Chinese cross-sectional study, depressive patients with acute coronary syndromes were 1.7 times more likely to be physically inactive than nondepressive patients, though PA was measured by a single question.18 Although the degree of PA in patients with AMI varies depending on ethnicity,19 the association between PA and depressive symptoms has not been extensively investigated, especially in Asian populations. Moreover, previous studies did not consider important potential confounders for the association between depressive symptoms and PA, such as cardiorespiratory functional capacity and ejection fraction.20,21 Previous studies have reported that post-AMI depressive symptoms are associated with a lower left ventricular ejection fraction and lower functional capacity.22,23 The focus on PA is especially critical as this is a modifiable risk factor, whereas it is much more difficult to intervene with or change other potentially associated variables, such as ejection fraction or employment status. Therefore, if depressive symptoms are independently associated with decreased PA, PA should be promoted in patients experiencing depressive symptoms after AMI.24,25
The present study aimed to investigate the prevalence, time course, and risk factors of depressive symptoms in patients who have experienced AMI. We also investigated the risk factors for persistent depressive symptoms among patients who experienced them immediately after AMI, as well as the association between post-AMI depressive symptoms and PA after adjusting for possible confounders.
Seoul National University Bundang Hospital is designated as one of the Regional Cardiocerebrovascular Centers (RCCs) in South Korea.26 Following the RCC protocol, most of the patients with AMI are referred to the Department of Rehabilitation for CR. Among the patients who were admitted to Seoul National University Bundang Hospital for the treatment of AMI between August 2015 and March 2019, 1545 hospitalized patients were referred for CR. Among these 1545 patients, 925 patients completed the PHQ-9 during the acute hospitalization period and 666 patients completed the PHQ-9 at 3 mo after AMI. Because we focused on the association of depressive symptoms with PA and functional capacity, which were measured only at 3 mo after AMI, we conducted the study based on the patients who completed the PHQ-9 at 3 mo after AMI (see Supplemental Digital Content 1, available at: https://links.lww.com/JCRP/A373). Among these 666 patients, 40 patients who had missing values in any independent variables for this study were further excluded, and a total of 626 patients were finally included in the study.
During the acute hospitalization period, baseline PHQ-9 evaluations were conducted in patients who were referred to CR by a coordinating nurse in the RCC. Follow-up evaluations, including the PHQ-9, Korean Activity Scale Index (KASI), and International Physical Activity Questionnaire (IPAQ), were performed through telephone interview by the coordinating nurse from the RCC as well.
The PHQ-9 was administered at baseline and 3 mo after AMI. The validity and reliability of the Korean version of the PHQ-9 has been established, and depressive symptoms were indicated if PHQ-9 scores were ≥5.27 To compare the depressive symptoms at 3 mo and baseline, we analyzed 522 of 626 included patients who had completed the PHQ-9 at baseline as well. Among the patients who had depressive symptoms at baseline, those who still had depressive symptom after 3 mo were categorized into a “persistent depressive symptoms” group, while the remaining patients were categorized into a “transient depressive symptoms” group.
The KASI and IPAQ assessments were performed 3 mo after AMI. The KASI is a Korean revised version of the Duke Activity Status Index (DASI),28,29 which is a simple 12-item self-assessment tool for estimating functional capacity. The KASI score ranges from 0 to 79 (KASI functional class; II: 46 > KASI ≥ 24, III: 24 > KASI ≥ 4, IV: KASI < 4).30 Lower KASI scores are considered indicative of worse functional capacity. When 99 patients were subjected to the KASI and the treadmill exercise test according to the Bruce protocol, the Spearman correlation coefficient between KASI and treadmill exercise time was 0.62 (P = .0001).30 The IPAQ is used to measure the level of PA based on metabolic equivalent values, enabling the classification of patients into inactive, minimally active, and health-enhancing PA (HEPA) groups.31 The reliability and validity of the Korean version of the IPAQ has been verified.32 Functional capacity and PA were dichotomized as follows for the analysis: KASI ≥46 (high functional capacity) versus <46 (low functional capacity), inactive versus minimal activity, or HEPA.
Patients who attended one or more hospital-based monitored CR sessions within 3 mo of discharge were considered to have participated in CR. Electronic medical records were retrospectively reviewed to investigate baseline demographic and clinical characteristics, including age, sex, body mass index, employment status, marital status, educational level, risk factors for AMI (diabetes, hypertension, dyslipidemia, and smoking status), ejection fraction, and whether percutaneous coronary intervention was performed. For employment status, individuals who were unemployed and individuals who were retired were not investigated separately. Instead, considering that the legal retirement age of South Korea is 60 yr, further analysis was conducted by dividing unemployed patients into working-age unemployment (<60 yr) and retirement-age unemployment (≥60 yr) groups. The study was performed in accordance with the guidelines of the Declaration of Helsinki and was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No. B-2005-612-117).
We examined differences in baseline characteristics between the two groups using the χ2 test for categorical variables and the Mann-Whitney U test for continuous variables (depressive symptoms vs no depressive symptoms at 3 mo after AMI, persistent depressive symptoms vs transient depressive symptoms). Multiple logistic regression analysis for depressive symptoms at 3 mo after AMI was performed using a forward stepwise method (Pentry = .05, Premoval = .10). Variables included in the univariate analysis were age (continuous), sex, body mass index, marital status, employment status, education, ejection fraction (continuous), history of diabetes, history of hypertension, history of dyslipidemia, smoking, participation in CR, and functional capacity. Variables that exhibited P values < .10 in the univariate analysis were sex, employment status, and functional capacity, and they were included in the multivariate analysis.
To test a linear trend between the four KASI functional classes and depressive symptoms, we used a linear-by-linear association. To investigate the association between PA and depressive symptoms at 3 mo after AMI, multiple logistic regression was performed by sequentially adjusting for possible confounders, including age, sex, employment status, and functional capacity. Statistical significance was defined as a two-sided P < .05. All data analyses were carried out using SPSS software version 20.0 (IBM).
PREVALENCE OF DEPRESSIVE SYMPTOMS AFTER AMI
Among the 522 patients who completed the PHQ-9 at baseline, 30% (n = 155) showed depressive symptoms immediately after the onset of AMI (Figure). Among those, 19% (n = 30) continued to have persistent depressive symptoms 3 mo after AMI. In contrast, among those who did not have depressive symptoms at baseline, the rate of newly occurring depressive symptoms at 3 mo after AMI was only 7% (n = 25). Of the 155 patients with depressive symptoms, the rate of transient symptoms was 81% (n = 125). Among the 626 patients who completed the PHQ-9 at 3 mo after AMI, the prevalence of depressive symptoms was 12% (n = 76).
RISK FACTORS FOR DEPRESSIVE SYMPTOMS 3 MO AFTER AMI
The prevalence of depressive symptoms 3 mo after AMI was significantly higher in women (P = .006), unemployed patients (P = .001), and patients with low functional capacity (P < .001) (Table 1). Although no significant risk factors for persistent depressive symptoms were identified, low functional capacity exhibited a marginally significant association (P = .081). As KASI class increased, the proportion of depressive symptoms significantly increased (P < .001) (see Supplemental Digital Content 2, available at: https://links.lww.com/JCRP/A374). After multiple logistic regression analysis, the risk of depressive symptoms significantly increased in KASI class III (OR = 3.79: 95% CI, 1.67-8.63) and KASI class IV (OR = 5.54: 95% CI, 2.26-13.62) compared with KASI class I (Table 2).
Table 1 -
Baseline Characteristics According to Depressive Symptoms at 3 mo After Myocardial Infarctiona
||No Depressive Symptomsb (n = 550)
||Depressive Symptomsc (n = 76)
||Transient Depressive Symptomsd (n = 125)
||Persistent Depressive Symptomse (n = 30)
||61.9 ± 12.0
||65.0 ± 13.5
||62.2 ± 12.0
||63.1 ± 11.1
|BMI, ≥25 kg/m2
|Education, Below high school
|Ejection fraction, %
||54.2 ± 10.1
||53.6 ± 11.4
||53.3 ± 10.1
||51.9 ± 11.1
|History of diabetes
|History of hypertension
|History of dyslipidemia
|Low functional capacityf
Abbreviations: BMI, body mass index; CR, cardiac rehabilitation; PCI, percutaneous coronary intervention; STEMI, ST-elevation myocardial infarction.
aData are presented as mean ± SD or n (%).
bAmong 626 patients who completed the Patient Health Questionnaire-9 (PHQ-9) at 3 mo, 550 patients did not have depressive symptom (PHQ-9 score <5).
cAmong 626 patients who completed the PHQ-9 at 3 mo, 76 patients had depressive symptoms (PHQ-9 score ≥5).
dOf 626 patients who conducted the PHQ-9 at 3 mo, 522 patients had conducted the PHQ-9 at baseline as well. Among these patients, 125 had depressive symptom at baseline but not at 3 mo.
eOf 522 patients who conducted the PHQ-9 at 3 mo and at baseline, 30 patients had depressive symptoms at both periods.
fKorean Activity Scale/Index (KASI) score measured at 3 mo, <46, corresponding to KASI functional classes II-IV.
Table 2 -
Multiple Logistic Regression Analysis of Depressive Symptoms and Low Functional Capacity Demonstrated as the Korean Activity Status Index (KASI) (n = 626)
|KASI Functional Class
||Patients With Depressive Symptomsa, n
||ORb (95% CI)
|I (n = 317)
|II (n = 236)
|III (n = 44)
|IV (n = 29)
|II-IV (n = 309)
aPatient Health Questionnaire-9 (PHQ-9) score was measured 3 mo after myocardial infarction. A PHQ-9 score of ≥5 was considered indicative of having depressive symptoms.
bAdjusted for age (continuous), sex, and employment status (employed or unemployed).
The association between sex and depressive symptoms was no longer statistically significant after adjusting for variables including functional capacity (P = .118) (see Supplemental Digital Content 3, available at: https://links.lww.com/JCRP/A375). However, with additional analysis, we found that the proportion of women with decreased functional capacity (KASI <46) was significantly higher than that of men (P < .001) (see Supplemental Digital Content 4, available at: https://links.lww.com/JCRP/A376).
After separating working-age unemployment (<60 yr) and retirement-age unemployment (≥60 yr), working-age unemployment was significantly associated with depressive symptoms at 3 mo (P < .001), whereas retirement-age unemployment was not (P = .119) (see Supplemental Digital Content 5, available at: https://links.lww.com/JCRP/A377).
Participation in CR was not significantly associated with depressive symptoms at 3 mo after AMI (P = .146). A total of 121 patients among 626 patients were counted as participating in CR. Of the 121 patients, 103 patients (95%) attended ≤3 sessions. Among the patients who attended CR, the mean number of CR session was 2.9 ± 2.2 in patients with depressive symptoms and 2.0 ± 1.4 in patients without depressive symptoms at 3 mo after AMI, and the difference was not significant (P = .077).
After adjusting for covariates with a P value less than .10 in Table 1 via forward stepwise multiple logistic regression, low functional capacity (OR = 2.20: 95% CI, 1.28-3.79, P = .004) and lack of employment (OR = 1.82: 95% CI, 1.09-3.04, P = .023) remained significant risk factors for depressive symptoms.
DEPRESSIVE SYMPTOMS AND PHYSICAL ACTIVITY
The proportion of “inactive” on the IPAQ was measured 3 mo after AMI, and was significantly higher in patients with depressive symptoms (59%, n = 45) than in patients without (40%, n = 220) (P = .001). Patients with depressive symptoms at 3 mo after AMI exhibited a 1.76-fold increase in the rate of “inactive” on the IPAQ after adjusting for age, sex, employment, and functional capacity (OR = 1.80: 95% CI, 1.09-2.98, P = .023) (Table 3).
Table 3 -
Crude and Multiple-Adjusted ORs of Depressive Symptoms for Low Physical Activity
at 3 mo After Myocardial Infarction (n = 626)
||OR (95% CI)
|Adjusted for age
|Adjusted for age and sex
|Adjusted for age, sex, and employment
|Adjusted for age, sex, employment, and functional capacitya
aFunctional capacity; dichotomized as Korean Activity Scale Index (KASI) classes I and II-IV.
We investigated the change in the prevalence of depressive symptoms and the characteristics of patients with transient or persistent depressive symptoms at 3 mo after AMI. The prevalence of depressive symptoms was higher in women, the unemployed, and patients with low functional capacity. In addition, there was a significant association between post-AMI depressive symptoms and low PA after adjusting for covariates including functional capacity.
The prevalence of depressive symptoms was 30% at baseline, which decreased to 12% 3 mo after AMI. This time course is in line with the results of a Czech study, in which the prevalence of depressive symptoms after percutaneous coronary intervention decreased from 22% at baseline to 10% after 3 mo.14 Consistent with previous findings, the prevalence of depressive symptoms in our study was significantly higher in women.33,34 Women may exhibit a higher prevalence of post-AMI depressive symptoms because they experience more perceived stress than men during the first year of recovery after AMI,12,35 which is known to be associated with depressive symptoms.36 Unemployed patients also had a higher prevalence of depressive symptoms, which is consistent with previous findings.12,37
According to a systematic review, employment is especially beneficial for general mental health and the prevention of depressive symptoms.38 Specifically, considering the legal retirement age of 60 yr in South Korea, working-age unemployment was associated with depressive symptoms, whereas retirement-age unemployment was not. This suggests that employment at working age may play a protective role in preventing depressive symptoms after AMI and may help stratify the high-risk group of depressive symptoms. In addition, a previous study demonstrated that unemployment status predicted less improvement in peak oxygen uptake after CR.39 Unemployment is not only a potential risk factor for depressive symptoms, but can also be an obstacle to CR itself,40 so a specially customized CR program may be required.
The association between sex and depressive symptoms was no longer statistically significant after adjusting for variables including functional capacity. We hypothesized that functional capacity may be among the major factors that can explain the higher prevalence of depressive symptoms in female patients. Some studies have reported that women experience a greater decline in functional capacity than men after AMI41,42; however, few studies have taken functional capacity into account when examining the association between sex and post-AMI depressive symptoms. Our findings support the notion that low functional capacity contributes to the relatively higher prevalence of depressive symptoms among women. Although exercise-based CR can increase functional capacity after AMI, women have a lower rate of participation in CR.43,44 Therefore, systematic efforts to promote the use of exercise-based CR in female patients are required to reduce the gap in post-AMI depressive symptom prevalence between men and women.
In this study, low functional capacity was significantly related to depressive symptoms and there was a significant linear trend of low functional capacity and depressive symptoms at 3 mo after AMI. A previous meta-analysis in patients with heart disease demonstrated that depressive symptoms were related to reduced exercise capacity as measured via exercise stress tests.45 The relationship between depressive symptoms and low functional capacity may be due in part to reduced motivation for exercise, voluntary deficits in the ability to convert intentions into action.46,47 According to a study that measured the change in functional capacity using the DASI after AMI, functional recovery during the first year was a strong modifiable predictor of long-term mortality.48 Thus, low functional capacity in patients with post-AMI depressive symptoms may represent the mechanism by which depressive symptoms lead to poor prognosis (eg, increased mortality) in these patients.4,5
Furthermore, our findings indicated that depressive symptoms were related to low PA at 3 mo after AMI, even after adjusting for variables including functional capacity. This result suggests that PA decreases further in patients with depressive symptoms than in those without, even when there are no differences in functional capacity between the groups. The pathophysiology of the relationship between PA and depressive symptoms has been widely established, ranging from biological mechanisms, such as those affecting the hypothalamic-pituitary-adrenal axis and oxidative stress, to psychosocial mechanisms, such as self-esteem and social support.49 Low PA has also been reported as a primary factor leading to adverse cardiovascular outcomes in patients with depressive symptoms.24 Cardiac rehabilitation is known to be significantly associated with a decrease in depressive symptoms.50 To improve the prognosis of patients with depressive symptoms after AMI, functional capacity and the level of PA should be evaluated and an appropriate CR program should be implemented.51 Conversely, depressive symptoms can mitigate the improvement of functional capacity during CR,52 thus necessitating adequate screening of patients and active treatment of depressive symptoms.
There are several limitations to this study. First, while Western studies have set the cutoff value of the PHQ-9 score at 10, we set it at 5 as previously validated in Korean patients to account for cultural and regional differences.27 Second, selection bias may have occurred due to the exclusion of patients who did not complete the PHQ-9 at 3 mo after AMI. Some of the known potential risk factors for post-AMI depressive symptoms, such as low ejection fraction,22 diabetes,53 and unemployment, were more prevalent among patients who were not included in the analysis (see Supplemental Digital Content 6, available at: https://links.lww.com/JCRP/A378). Thus, depressive symptoms may have been underestimated in the patients included in the analysis. Third, owing to the cross-sectional design of the study, it was not possible to establish a causal relationship. Fourth, there were limitations when analyzing the effect of CR on depressive symptoms, because the mean CR session in this study was low compared with other previous studies about CR. According to a previous study based on the Korea National Health Insurance Service database, which covers 97% of the Korean population, nationally, only 1.5% of AMI patients attended CR after discharge.54 Factors related to low attendance rate of CR were old age, female sex, rural residence, and low Charlson Comorbidity Index. The CR specialists in Korea and governments are actively seeking solutions to this. Fifth, although anxiety is known to be related with low physical function55 and poor quality of life,56 it was not addressed in the current study. In particular, a previous study about cardiopulmonary rehabilitation revealed that fears about exercise were related to higher levels of anxiety, and avoidance of exercise was associated with lower exercise tolerance.57 Thus, incorporating those factors in a future study will provide better information about increasing PA and functional capacity in patients with AMI. Lastly, while oxygen uptake during maximal exercise intensity is considered the gold standard for assessing functional capacity, we used the Korean revised version of the DASI to measure functional capacity. The DASI has an advantage in that it can be easily and quickly implemented in acute inpatient and outpatient settings when compared with other labor-intensive procedures.28 In addition, the DASI is expected to be widely used as an evaluation index for home-based CR programs, as it is easy to conduct remotely.58
In summary, the prevalence of depressive symptoms changed from 30% at baseline to 12% at 3 mo post-AMI. Low functional capacity and working-age unemployment were independently associated with depressive symptoms after AMI. In addition, our findings indicate that depressive symptoms are an independent risk factor for low PA in patients with AMI. Therefore, systematic screening and treatment for depressive symptoms and efforts to promote CR may help improve PA and functional capacity in Korean patients after AMI. Such efforts may aid in reducing the prevalence of depressive symptoms and related adverse outcomes.
This work was partially funded by the Seoul National University Bundang Hospital Research Fund (06-2020-153) received by Won-Seok Kim. We thank Eunjeong Choi for gathering the data used in this study. The authors also thank the Division of Statistics in the Medical Research Collaborating Center at Seoul National University Bundang Hospital for statistical analyses.
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