The present nationwide cohort study investigated the impact of pre-existing depression on mortality in patients with established CAD undergoing PCI. Our study showed that pre-existing depression was not associated with in-hospital mortality or all-cause death in either the angina or AMI groups during a median follow-up period of 2.2 years. However, for patients with angina less than 65 years of age, patients with pre-existing depression had 1.77-times higher all-cause mortality compared with patients without depression. Among them, younger patients with angina who took anti-depressants also showed higher in-hospital mortality and all-cause mortality rates. In the AMI cohort, pre-existing depression was not associated with all-cause mortality.
Our study was conducted using recent NHI claims data on more than 90,000 participants from 2013 to 2017. The prevalence of depression differed depending on the criteria defined by the authors . In our population, the prevalence of depression was 7.3%. In Korean epidemiologic data, the prevalence of major depressive disorder was 4.2–9.1%, which is similar to that of the present study . Furthermore, in case-control studies or studies conducted with self-questionnaires, the prevalence of depression may be affected by several factors, such as recall bias, dementia status, physical function, and marital status. Accordingly, the current study used well-controlled and reliable NHI claims data to alleviate these factors [12,13]. In addition, considering recent nationwide situations in clinical practice and lack of data to determine the relationship between depression and all-cause mortality, the present study was designed.
In 1992, Berkman et al. reported that pre-admission depression was not associated with mortality from myocardial infarction within 6 months . However, the study had a small sample size and selectively included patients from certain hospitals. In 2009, Abrams et al. evaluated the effects of pre-existing and in-hospital psychiatric comorbidities, including depression, anxiety, posttraumatic stress, bipolar, and psychotic disorders, on prognosis after AMI. One-year mortality was significantly associated with pre-existing psychiatric comorbidity, but not with in-hospital psychiatric comorbidity . However, this study did not separately analyze prognosis confined to depression. A nationwide cohort study, which included 170,771 patients with first-time myocardial infarction in Denmark between 1995 and 2014 showed that pre-existing depression increased all-cause mortality by 11%. This association was stronger with current antidepressant use by 22% . However, for treatment of CAD, there has been a significant improvement in the design and carrier systems of devices and the development of new drugs. This study did not reflect these recent enhanced properties.
In the current study, after propensity score matching, pre-existing depression was not associated with all-cause mortality in patients with either angina or AMI who underwent PCI. One possibility of these findings is that the effect size of depression on all-cause mortality may not be large enough to detect a statistically significant difference. Another possibility is that depression may be an indirect mortality factor affecting obesity, diabetes, and medical adherence [17,18]. In addition, CAD events are major stressful life events, and these episodes can be traumatic in people not prepared for such events . Considering that CAD events can have a stronger psychological and physiological effect than depression, another possibility is that the effect of depression on mortality may be diluted.
We also observed the impact of depression on mortality in younger patients with angina, but not in patients with AMI. In other words, the severity of CAD may be a more important factor on mortality than pre-existing depression. Since angina is a less severe disease with a longer life expectancy than myocardial infarction , the influence of depression might be more pronounced. A previous epidemiologic study reported that depression is an independent predictor of mortality due to CAD in young individuals . Depression may elicit adverse microvascular responses among younger patients . Therefore, since depression is an important risk factor in younger populations, additional medical attention is required in younger patients with co-morbid depression and angina.
The strengths of the present study are as follows. First, in most previous studies, the assessment of depression occurred during or within a few weeks after index hospitalization. However, our study evaluated the clinical impact of pre-existing depression before CAD events. Second, strict study participants using the ICD code F32.X-33.X were evaluated, and subgroup analyses were performed by setting criteria for antidepressant use. Third, to assess the effect of depression on mortality in patients with CAD, the current study was conducted with a homogeneous large-scale cohort (i.e., patients with the first episode of CAD undergoing PCI).
Our study also had several limitations. First, the current study was based on administrative data from the HIRA in South Korea. Similar to previous studies using administrative databases, our study lacked clinical patient data and test results. Thus, our findings might be limited by uncertainties in unmeasured confounding variables that may affect patient management [12,13]. Second, although we used a database from a quasi-governmental organization, there is a possibility that this data did not fully reflect patient outcomes. Additionally, we did not specify the cause of death. Third, the results do not imply a causal relationship between variables. However, the two variables (depression and mortality) have a clear temporal relationship. Fourth, our study did not evaluate the severity of depression. However, the Denmark nationwide cohort study reported that the severity of depression does not affect all-cause mortality .
In conclusion, pre-existing depression is not associated with in-hospital mortality or all-cause death in patients with CAD undergoing PCI during a median follow-up period of 2.2 years. However, in younger patients with angina, pre-existing depression is associated with higher mortality. These findings should be further investigated and validated through additional studies.