University of Groningen
Shades of a blue heart
Moreira da Rocha de Miranda Az, Ricardo
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Publication date: 2018
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Moreira da Rocha de Miranda Az, R. (2018). Shades of a blue heart: An epidemiological investigation of depressive symptom dimensions and the association with cardiovascular disease. University of Groningen.
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Chapter 6
Association of recognized and
unrecognized myocardial
infarction with depression and
anxiety in 125,750 individuals:
the LifeLines Cohort Study
Iozzia G & de Miranda Azevedo R, Roest AM, Van der Harst P, Rosmalen JGM, de Jonge P. Investigating the Longitudinal Association of Arterial Stiffness and Carotid Intima-Media Thickness With Depressive Symptom Dimension in Middle-Aged Individuals. Clinical Epidemiology. (To be submitted)
INTRODUCTION
The relationship between depression and coronary heart disease (CHD) has been extensively investigated and several studies reported an association between both conditions1-4. The prevalence of depression is two to three times higher in patients with CHD as compared with the general population5. In addition, depression is associated with the onset of CHD and the risk of mortality in patients with CHD6,7. Similarly, recent studies reported that the 12-month prevalence of generalized anxiety disorder (GAD) in patients with CHD ranges from 10.4 to 18.7%8-10. In the general population, the 12-month prevalence of GAD is much lower, ranging from 1.7 to 3.1%11. Equivalent to depression, anxiety disorders are also associated with an increased risk of CHD and cardiac death12, and are predictive of adverse cardiac outcomes following myocardial infarction (MI) as well13,14.
MI is one of the most severe manifestations of CHD. The annual incidence of MI in people aged between 30-69 years in the United Kingdom is 600 per 100,000 for men and 200 per 100,000 for women15. MI is acute and patients usually experience symptoms16, however, MI can also be accompanied by minor, atypical and completely unrecognized symptoms17,18. This phenomenon is known as ‘unrecognized MI’. Unrecognized MI can be detected with an electrocardiogram (ECG)19. The prevalence of unrecognized MI in older individuals (i.e. > 60 years) of the general population ranges between 3.4 - 6.4%20-23. In younger individuals, the prevalence ranges between 0.3 - 0.5%17,24,25.
To date, only one study investigated the association between unrecognized MI and depression, suggesting that a psychological rather than a physiological pathway explains the increased odds of having depression in patients with recognized MI26. The association of MI with depression and anxiety has been instead established only in patients with recognized MI27,28. Still, addressing the association between unrecognized MI and depressive or anxiety disorders might provide novel insights regarding the aetiology of post-MI depression and anxiety. Specifically, if this aetiology is predominantly physiological (i.e. caused by inflammatory processes or autonomic tone), the recognition of the MI may be less ABSTRACT
BACKGROUND: Myocardial infarction (MI) has frequently been associated with depression and anxiety, but no study has focused on the relationship between the recognition of MI and its association with depression and anxiety. The aim of this study is to investigate the association of recognized and unrecognized MI with depression and anxiety.
METHODS: Analyses included 125,750 individuals enrolled in the LifeLines cohort. Depressive and anxiety disorders were assessed with the Mini International Neuropsychiatric Interview (MINI). Unrecognized MI was flagged in participants who did not report a history of MI but had ECG signs indicative of MI. Logistic regression was performed to study the association of depressive and anxiety disorders with MI recognition status. Multivariable adjustment for demographics, smoking, somatic comorbidities and health related quality of life (HRQOL) was performed. RESULTS: Participants with recognized MI had significantly higher odds of having depressive and anxiety disorders as compared with participants without MI (depression: OR=2.00; 1.50-2.67;p<0.001, anxiety: OR = 1.62; 1.34-1.96; p < .001), but those with unrecognized MI did not (depression: OR = 1.38; 0.90-2.09; p = .137, anxiety: OR = 0.89; 0.66-1.21; p = 0.460). About half of the increased odds for depression and anxiety in persons with recognized MI were accounted by multivariable adjustment.
CONCLUSIONS: The odds of having depressive and anxiety disorders were not significantly increased in participants with unrecognized MI when compared with participants without MI. Thus, recognition of MI plays an important role in the aetiology of post-MI anxiety and depression, suggesting a psychological rather than a physiological pathway.
INTRODUCTION
The relationship between depression and coronary heart disease (CHD) has been extensively investigated and several studies reported an association between both conditions1-4. The prevalence of depression is two to three times higher in patients with CHD as compared with the general population5. In addition, depression is associated with the onset of CHD and the risk of mortality in patients with CHD6,7. Similarly, recent studies reported that the 12-month prevalence of generalized anxiety disorder (GAD) in patients with CHD ranges from 10.4 to 18.7%8-10. In the general population, the 12-month prevalence of GAD is much lower, ranging from 1.7 to 3.1%11. Equivalent to depression, anxiety disorders are also associated with an increased risk of CHD and cardiac death12, and are predictive of adverse cardiac outcomes following myocardial infarction (MI) as well13,14.
MI is one of the most severe manifestations of CHD. The annual incidence of MI in people aged between 30-69 years in the United Kingdom is 600 per 100,000 for men and 200 per 100,000 for women15. MI is acute and patients usually experience symptoms16, however, MI can also be accompanied by minor, atypical and completely unrecognized symptoms17,18. This phenomenon is known as ‘unrecognized MI’. Unrecognized MI can be detected with an electrocardiogram (ECG)19. The prevalence of unrecognized MI in older individuals (i.e. > 60 years) of the general population ranges between 3.4 - 6.4%20-23. In younger individuals, the prevalence ranges between 0.3 - 0.5%17,24,25.
To date, only one study investigated the association between unrecognized MI and depression, suggesting that a psychological rather than a physiological pathway explains the increased odds of having depression in patients with recognized MI26. The association of MI with depression and anxiety has been instead established only in patients with recognized MI27,28. Still, addressing the association between unrecognized MI and depressive or anxiety disorders might provide novel insights regarding the aetiology of post-MI depression and anxiety. Specifically, if this aetiology is predominantly physiological (i.e. caused by inflammatory processes or autonomic tone), the recognition of the MI may be less important. If the aetiology of post-MI depression and anxiety is mainly ABSTRACT
BACKGROUND: Myocardial infarction (MI) has frequently been associated with depression and anxiety, but no study has focused on the relationship between the recognition of MI and its association with depression and anxiety. The aim of this study is to investigate the association of recognized and unrecognized MI with depression and anxiety.
METHODS: Analyses included 125,750 individuals enrolled in the LifeLines cohort. Depressive and anxiety disorders were assessed with the Mini International Neuropsychiatric Interview (MINI). Unrecognized MI was flagged in participants who did not report a history of MI but had ECG signs indicative of MI. Logistic regression was performed to study the association of depressive and anxiety disorders with MI recognition status. Multivariable adjustment for demographics, smoking, somatic comorbidities and health related quality of life (HRQOL) was performed. RESULTS: Participants with recognized MI had significantly higher odds of having depressive and anxiety disorders as compared with participants without MI (depression: OR=2.00; 1.50-2.67;p<0.001, anxiety: OR = 1.62; 1.34-1.96; p < .001), but those with unrecognized MI did not (depression: OR = 1.38; 0.90-2.09; p = .137, anxiety: OR = 0.89; 0.66-1.21; p = 0.460). About half of the increased odds for depression and anxiety in persons with recognized MI were accounted by multivariable adjustment.
CONCLUSIONS: The odds of having depressive and anxiety disorders were not significantly increased in participants with unrecognized MI when compared with participants without MI. Thus, recognition of MI plays an important role in the aetiology of post-MI anxiety and depression, suggesting a psychological rather than a physiological pathway.
METHODS
Study design and participants
LifeLines are a multidisciplinary, prospective population-based cohort study of 167,729 participants living in the northern part of The Netherlands. LifeLines aims to analyse the complex interaction between genomic, phenotypic and environmental factors related to chronic disorders29. Baseline data were collected between 2006 and 201329. Participants receive a follow-up questionnaires every 1,5 years and are invited for a medical visit every five years. Written informed consent was obtained after the procedure and methods of the study were explained to participants.
Of the 167,729 participants enrolled in the LifeLines study, some were not included in our analyses. The most common reasons for not inclusion of participants were: being younger than 18 years old or having missing data for assessment of depressive and anxiety disorders. Participants were allowed to refuse participating in the psychiatric interviews. In the present study, the total sample included 125,750 participants (59% women) aged between 18 and 93 years (mean = 44.2 years, SD = 12.6 years).
Assessment of recognized and unrecognized myocardial infarction
During the baseline visits, a 12-lead electrocardiogram (ECG) was recorded with a Welch Alyn DT100. All ECG data were automatically processed using the WelchAllyn CardioPerfect software (version 1.6.2.1105) to obtain measurements and interpretations. Abnormal ECGs were examined by a cardiologist and classified as MI or not MI.
The diagnosis of recognized MI was based on the combination of self-reported history of MI and ECG abnormalities or self-reported history of MI and use of antithrombotic medications. Unrecognized MI was diagnosed in participants who did not report a history of MI but who had ECG signs suggestive of MI. Other participants were classified as not having had MI30.
psychological (e.g. related to the experience of having a life-threatening disease), recognition of the MI may be a necessary precursor. Therefore, in this study we investigated the association of recognized MI and unrecognized MI with depressive and anxiety disorders. We hypothesized that the odds of having depression and anxiety are significantly increased in participants with recognized MI when compared with participants without MI. We also hypothesized that the awareness of having MI would further contribute to the increased odds of having depression and anxiety.
METHODS
Study design and participants
LifeLines are a multidisciplinary, prospective population-based cohort study of 167,729 participants living in the northern part of The Netherlands. LifeLines aims to analyse the complex interaction between genomic, phenotypic and environmental factors related to chronic disorders29. Baseline data were collected between 2006 and 201329. Participants receive a follow-up questionnaires every 1,5 years and are invited for a medical visit every five years. Written informed consent was obtained after the procedure and methods of the study were explained to participants.
Of the 167,729 participants enrolled in the LifeLines study, some were not included in our analyses. The most common reasons for not inclusion of participants were: being younger than 18 years old or having missing data for assessment of depressive and anxiety disorders. Participants were allowed to refuse participating in the psychiatric interviews. In the present study, the total sample included 125,750 participants (59% women) aged between 18 and 93 years (mean = 44.2 years, SD = 12.6 years).
Assessment of recognized and unrecognized myocardial infarction
During the baseline visits, a 12-lead electrocardiogram (ECG) was recorded with a Welch Alyn DT100. All ECG data were automatically processed using the WelchAllyn CardioPerfect software (version 1.6.2.1105) to obtain measurements and interpretations. Abnormal ECGs were examined by a cardiologist and classified as MI or not MI.
The diagnosis of recognized MI was based on the combination of self-reported history of MI and ECG abnormalities or self-reported history of MI and use of antithrombotic medications. Unrecognized MI was diagnosed in participants who did not report a history of MI but who had ECG signs suggestive of MI. Other participants were classified as not having had MI30.
psychological (e.g. related to the experience of having a life-threatening disease), recognition of the MI may be a necessary precursor. Therefore, in this study we investigated the association of recognized MI and unrecognized MI with depressive and anxiety disorders. We hypothesized that the odds of having depression and anxiety are significantly increased in participants with recognized MI when compared with participants without MI. We also hypothesized that the awareness of having MI would further contribute to the increased odds of having depression and anxiety.
role limitations due to emotional problems37. To prevent overlap with the psychiatric disorders, only the PCS was used in the present study. The RAND-36 has been validated in the general population and across patient groups suffering from different medical conditions37.
Statistical analysis
Descriptive statistics were reported for all study variables. We checked for significant differences between participants with recognized MI and unrecognized MI across the covariates. Student’s t-tests and chi-square tests were used for continuous and binary variables, respectively.
Multiple logistic regression analysis was conducted to assess the association between MI status and the occurrence of depressive and anxiety disorders. Odds ratios (ORs) were used to represent the risk of having depression and anxiety disorders associated with MI status. For the ease of interpretation of the ORs, three dummy variables were created to represent MI status: two dummy variables used “no MI” as the reference category (0 “no MI”, 1 “recognized MI”; 0 “no MI”, 1 “unrecognized MI”) and one used unrecognized MI as the reference (0 “unrecognized MI”, 1 “recognized MI”).
All predictive models included multiple covariate adjustment. Three models were used to assess the association between MI status and the occurrence of depression and anxiety disorders (Model 1, 2 and 3). In model 1, adjustment for age and sex was performed. In model 2, additional adjustment for self-reported somatic comorbidities and smoking was performed. In model 3, additional adjustment for HRQOL was performed. A confidence level of α = 0.05 two tailed was used to indicate statistical significance. All analyses were conducted using SPSS 22.0 (IBM Corp., Armonk, NY, USA). Interaction effects between MI status and sex Assessment of depressive and anxiety disorders Current (i.e. past 2 weeks) depressive (major depressive episode or dysthymic mood) and anxiety disorders (panic disorder with or without agoraphobia, agoraphobia without panic disorder, social anxiety disorder and GAD) were assessed through the Mini-international neuropsychiatric interview (MINI 5.0.0) at baseline. The MINI is a systematic interview and was administered for assessing the major Axis I psychiatric disorders based on the DSM-IV and ICD-10 criteria31 (Sheehan et al., 1998). Dichotomous items (yes/no) assessing the presence of symptoms were used. The complete assessment took mostly about 15 to 20 minutes. The MINI has been found to be a valid and reliable clinical interview and showed a good diagnostic concordance with the Structured Clinical Interview for DSM-III-R (SCID)31. The MINI assessment was performed by trained research assistants.
Assessment of the covariates
Covariates were chosen based on previous literature as they are well known confounders of the association between CHD and depression32-34. The following covariates were included: self-reported history of somatic diseases related to heart disease (diabetes, kidney disease and congestive heart failure [CHF]); self-reported smoking status (“Do you currently smoke or have you smoked in the past month?”) and health related quality of life (HRQOL). HRQOL was assessed through the RAND 36-Item Health Survey (RAND-36). The RAND-36 consists of 36 items distributed across eight scales on physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. Each scale ranges between 0 and 100, with 100 indicating increased HRQOL and 0 indicating maximum disability35. Total scores can be computed for a physical component summary (PCS) and a mental component summary (MCS) of HRQOL36. The PCS covers physical functioning, pain and role limitations due to physical health, whereas the MCS covers emotional well-being and
role limitations due to emotional problems37. To prevent overlap with the psychiatric disorders, only the PCS was used in the present study. The RAND-36 has been validated in the general population and across patient groups suffering from different medical conditions37.
Statistical analysis
Descriptive statistics were reported for all study variables. We checked for significant differences between participants with recognized MI and unrecognized MI across the covariates. Student’s t-tests and chi-square tests were used for continuous and binary variables, respectively.
Multiple logistic regression analysis was conducted to assess the association between MI status and the occurrence of depressive and anxiety disorders. Odds ratios (ORs) were used to represent the risk of having depression and anxiety disorders associated with MI status. For the ease of interpretation of the ORs, three dummy variables were created to represent MI status: two dummy variables used “no MI” as the reference category (0 “no MI”, 1 “recognized MI”; 0 “no MI”, 1 “unrecognized MI”) and one used unrecognized MI as the reference (0 “unrecognized MI”, 1 “recognized MI”).
All predictive models included multiple covariate adjustment. Three models were used to assess the association between MI status and the occurrence of depression and anxiety disorders (Model 1, 2 and 3). In model 1, adjustment for age and sex was performed. In model 2, additional adjustment for self-reported somatic comorbidities and smoking was performed. In model 3, additional adjustment for HRQOL was performed. A confidence level of α = 0.05 two tailed was used to indicate statistical significance. All analyses were conducted using SPSS 22.0 (IBM Corp., Armonk, NY, USA). Interaction effects between MI status and sex Assessment of depressive and anxiety disorders Current (i.e. past 2 weeks) depressive (major depressive episode or dysthymic mood) and anxiety disorders (panic disorder with or without agoraphobia, agoraphobia without panic disorder, social anxiety disorder and GAD) were assessed through the Mini-international neuropsychiatric interview (MINI 5.0.0) at baseline. The MINI is a systematic interview and was administered for assessing the major Axis I psychiatric disorders based on the DSM-IV and ICD-10 criteria31 (Sheehan et al., 1998). Dichotomous items (yes/no) assessing the presence of symptoms were used. The complete assessment took mostly about 15 to 20 minutes. The MINI has been found to be a valid and reliable clinical interview and showed a good diagnostic concordance with the Structured Clinical Interview for DSM-III-R (SCID)31. The MINI assessment was performed by trained research assistants.
Assessment of the covariates
Covariates were chosen based on previous literature as they are well known confounders of the association between CHD and depression32-34. The following covariates were included: self-reported history of somatic diseases related to heart disease (diabetes, kidney disease and congestive heart failure [CHF]); self-reported smoking status (“Do you currently smoke or have you smoked in the past month?”) and health related quality of life (HRQOL). HRQOL was assessed through the RAND 36-Item Health Survey (RAND-36). The RAND-36 consists of 36 items distributed across eight scales on physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. Each scale ranges between 0 and 100, with 100 indicating increased HRQOL and 0 indicating maximum disability35. Total scores can be computed for a physical component summary (PCS) and a mental component summary (MCS) of HRQOL36. The PCS covers physical functioning, pain and role limitations due to physical health, whereas the MCS covers emotional well-being and
RESULTS
Descriptive statistics
Table 1 presents the baseline characteristics of the sample. The total sample included 125,750 participants (59% female) with a mean age of 44.2 years (SD = 12.6 years). Of the total sample, 4,263 (3.4%) were classified as having any depressive disorder and 12,373 (9.8%) as having any anxiety disorder. Unrecognized MI was present in 565 (0.4%) participants and recognized MI in 1095 (0.9%) participants.
Characteristics of participants according to myocardial infarction status
Comparisons of participants with recognized and unrecognized MI are shown in table 2. Participants with unrecognized MI were significantly younger (53.2 versus 60.3 years; p < 0.001) and more often women (52.4% versus 21.9%; p < 0.001) as compared with participants with recognized MI. In addition, participants with unrecognized MI had a significantly lower prevalence of diabetes, kidney diseases and CHF than participants with recognized MI. The PCS of HRQOL was significantly higher in participants with unrecognized MI as compared with participants with recognized MI. (TABLE 2 HERE)
Comparisons between participants with unrecognized MI and participants without MI are shown in Table 3. Participants with unrecognized MI were significantly older (53.2 versus 44.0 years; p < 0.001) and more often men (47.6% versus 40.8 %; p = 0.001) as compared with participants without MI. Moreover, participants with unrecognized MI had a significantly higher prevalence of diabetes and CHF than participants without MI. The PCS of HRQOL was significantly higher in participants without MI as compared with participants with unrecognized MI.
(TABLE 3 HERE) Previous evidence suggests that sex is an effect modifier in the
association between depression and medical prognosis in patients with MI38. Therefore, we assessed for potential interaction effects between sex and the dummy variables representing MI status (“Recognized MI” versus “no MI”; “Unrecognized MI” versus “no MI”; “Recognized MI” versus “Unrecognized MI”).
RESULTS
Descriptive statistics
Table 1 presents the baseline characteristics of the sample. The total sample included 125,750 participants (59% female) with a mean age of 44.2 years (SD = 12.6 years). Of the total sample, 4,263 (3.4%) were classified as having any depressive disorder and 12,373 (9.8%) as having any anxiety disorder. Unrecognized MI was present in 565 (0.4%) participants and recognized MI in 1095 (0.9%) participants.
Characteristics of participants according to myocardial infarction status
Comparisons of participants with recognized and unrecognized MI are shown in table 2. Participants with unrecognized MI were significantly younger (53.2 versus 60.3 years; p < 0.001) and more often women (52.4% versus 21.9%; p < 0.001) as compared with participants with recognized MI. In addition, participants with unrecognized MI had a significantly lower prevalence of diabetes, kidney diseases and CHF than participants with recognized MI. The PCS of HRQOL was significantly higher in participants with unrecognized MI as compared with participants with recognized MI. (TABLE 2 HERE)
Comparisons between participants with unrecognized MI and participants without MI are shown in Table 3. Participants with unrecognized MI were significantly older (53.2 versus 44.0 years; p < 0.001) and more often men (47.6% versus 40.8 %; p = 0.001) as compared with participants without MI. Moreover, participants with unrecognized MI had a significantly higher prevalence of diabetes and CHF than participants without MI. The PCS of HRQOL was significantly higher in participants without MI as compared with participants with unrecognized MI.
(TABLE 3 HERE) Previous evidence suggests that sex is an effect modifier in the
association between depression and medical prognosis in patients with MI38. Therefore, we assessed for potential interaction effects between sex and the dummy variables representing MI status (“Recognized MI” versus “no MI”; “Unrecognized MI” versus “no MI”; “Recognized MI” versus “Unrecognized MI”).
Table 1. Characteristics of participants Characteristics Total sample (N = 125,750) Age M (SD) 44.2 (12.6) Women, n (%) 73,907 (59) Smoking, n (%) 25,889 (21.3) Diabetes, n (%) 2913 (2.3) Kidney disease, n (%) 648 (0.5) Congestive heart failure, n (%) 874 (0.7) Health related quality of life M (SD) 52.5 (7.1) Any DEP disorder, n (%) 4263 (3.4) MDD, n (%) 2835 (2.3) Dysthymia, n (%) 1428 (1.1) Any ANX disorder, n (%) 12373 (9.8) GAD, n (%) 5434 (4.3) Social anxiety disorder, n (%) 1158 (0.9) PD – Agoraphobia, n (%) 2899 (2.3) PD + Agoraphobia, n (%) 1003 (0.8) Agoraphobia – PD, n (%) 467 (3.2) ECG abnormalities, n (%) 829 (0.7) Recognized myocardial infarction, n (%) 1095 (0.9) Unrecognized myocardial infarction, n (%) 565 (0.4) DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder; GAD: generalized anxiety disorder; PD: panic disorder Association between MI status and anxiety/depressive disorders
The results of the multIvariable logistic regression analyses are listed in Table 4. The odds of having anxiety disorders were increased in participants with recognized MI as compared with participants without MI (OR = 1.62 [1.34-1.96]; p < 0.001). The association remained statistically significant after adjusting for comorbidities, smoking and HRQOL. The odds of having anxiety disorders were not increased in participants with unrecognized MI versus participants without MI (OR = 0.89 [0.66 – 1.21]; p = 0.460). In accordance, there were significant differences between recognized and unrecognized MI (OR = 1.87 [1.27 – 2.76]; p = 0.002). Depression was increased in participants with recognized MI versus participants without MI (OR = 2.00 [1.50 – 2.67]; p < 0.001). However, depression was not increased in participants with unrecognized MI versus participants without MI (OR = 1.38 [0.90-2.09]; p = 0.137). There were no significant differences in the odds of having depressive disorders when comparing participants with recognized and unrecognized MI (OR = 1.66 [0.95 – 2.88]; p = 0.072).
Table 1. Characteristics of participants Characteristics Total sample (N = 125,750) Age M (SD) 44.2 (12.6) Women, n (%) 73,907 (59) Smoking, n (%) 25,889 (21.3) Diabetes, n (%) 2913 (2.3) Kidney disease, n (%) 648 (0.5) Congestive heart failure, n (%) 874 (0.7) Health related quality of life M (SD) 52.5 (7.1) Any DEP disorder, n (%) 4263 (3.4) MDD, n (%) 2835 (2.3) Dysthymia, n (%) 1428 (1.1) Any ANX disorder, n (%) 12373 (9.8) GAD, n (%) 5434 (4.3) Social anxiety disorder, n (%) 1158 (0.9) PD – Agoraphobia, n (%) 2899 (2.3) PD + Agoraphobia, n (%) 1003 (0.8) Agoraphobia – PD, n (%) 467 (3.2) ECG abnormalities, n (%) 829 (0.7) Recognized myocardial infarction, n (%) 1095 (0.9) Unrecognized myocardial infarction, n (%) 565 (0.4) DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder; GAD: generalized anxiety disorder; PD: panic disorder Association between MI status and anxiety/depressive disorders
The results of the multIvariable logistic regression analyses are listed in Table 4. The odds of having anxiety disorders were increased in participants with recognized MI as compared with participants without MI (OR = 1.62 [1.34-1.96]; p < 0.001). The association remained statistically significant after adjusting for comorbidities, smoking and HRQOL. The odds of having anxiety disorders were not increased in participants with unrecognized MI versus participants without MI (OR = 0.89 [0.66 – 1.21]; p = 0.460). In accordance, there were significant differences between recognized and unrecognized MI (OR = 1.87 [1.27 – 2.76]; p = 0.002). Depression was increased in participants with recognized MI versus participants without MI (OR = 2.00 [1.50 – 2.67]; p < 0.001). However, depression was not increased in participants with unrecognized MI versus participants without MI (OR = 1.38 [0.90-2.09]; p = 0.137). There were no significant differences in the odds of having depressive disorders when comparing participants with recognized and unrecognized MI (OR = 1.66 [0.95 – 2.88]; p = 0.072).
Table 3. Characteristics of participants according to myocardial infarction status Characteristics Unrecognized MI (N=565) No MI (N=123,612) P value Age M (SD) 53.2 (11.9) 44.0 (12.5) <.001 Women, n (%) 296 (52.4) 73127 (59.2) .001 Smoking, n (%) 122 (22.1) 25421 (21.3) .629 Diabetes, n (%) 43 (7.6) 2711 (2.2) <.001 Kidney disease, n (%) 2 (0.4) 626 (0.5) .618 Congestive heart failure, n (%) 12 (2.2) 646 (0.5) <.001 Health related quality of life M (SD) 51.3 (7.7) 52.5 (7.1) <.001 Any DEP disorder, n (%) 23 (4.1) 4171 (3.4) .353 MDD, n (%) 15 (2.7) 2774 (2.2) .511 Dystymia, n (%) 8 (1.5) 1397 (1.2) .508 Any ANX disorder, n (%) 46 (8.1) 12153 (9.8) .178 GAD, n (%) 21 (3.7) 5343 (4.3) .480 Social anxiety disorder, n (%) 3 (0.5) 1144 (0.9) .328 PD – Agoraphobia, n (%) 6 (1.1) 2865 (2.3) .048 PD + Agoraphobia, n (%) 6 (1.1) 984 (0.8) .478 Agoraphobia – PD, n (%) 19 (3.4) 3974 (3.2) .842
DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder;
GAD: generalized anxiety disorder; PD: panic disorder Table 2. Characteristics of participants stratified by myocardial infarction status Characteristics Recognize d MI (N=1095) Unrecognized MI (N=565) P value Age M (SD) 60.3 (11.0) 53.2 (11.9) <.001 Women, n (%) 240 (21.9) 296 (52.4) <.001 Smoking, n (%) 207 (19.3) 122 (22.1) .185 Diabetes, n (%) 150 (13.7) 43 (7.6) .001 Kidney disease, n (%) 17 (1.6) 2 (0.4) .034 Congestive heart failure, n (%) 211 (19.6) 12 (2.2) <.001 Health related quality of life M (SD) 48.1 (9.0) 51.3 (7.7) <.001 Any DEP disorder, n (%) 50 (4.6) 23 (4.1) .643 MDD, n (%) 32 (2.9) 15 (2.7) .756 Dysthymia, n (%) 18 (1.7) 8 (1.5) .719 Any ANX disorder, n (%) 123 (11.2) 46 (8.1) .048 GAD, n (%) 44 (4.0) 21 (3.7) .764 Social anxiety disorder, n (%) 9 (0.8) 3 (0.5) .507 PD – Agoraphobia, n (%) 16 (1.5) 6 (1.1) .500 PD + Agoraphobia, n (%) 10 (0.9) 6 (1.1) .769 Agoraphobia – PD, n (%) 57 (5.2) 19 (3.4) .089
DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder; GAD: generalized anxiety disorder; PD: panic disorder
Table 3. Characteristics of participants according to myocardial infarction status Characteristics Unrecognized MI (N=565) No MI (N=123,612) P value Age M (SD) 53.2 (11.9) 44.0 (12.5) <.001 Women, n (%) 296 (52.4) 73127 (59.2) .001 Smoking, n (%) 122 (22.1) 25421 (21.3) .629 Diabetes, n (%) 43 (7.6) 2711 (2.2) <.001 Kidney disease, n (%) 2 (0.4) 626 (0.5) .618 Congestive heart failure, n (%) 12 (2.2) 646 (0.5) <.001 Health related quality of life M (SD) 51.3 (7.7) 52.5 (7.1) <.001 Any DEP disorder, n (%) 23 (4.1) 4171 (3.4) .353 MDD, n (%) 15 (2.7) 2774 (2.2) .511 Dystymia, n (%) 8 (1.5) 1397 (1.2) .508 Any ANX disorder, n (%) 46 (8.1) 12153 (9.8) .178 GAD, n (%) 21 (3.7) 5343 (4.3) .480 Social anxiety disorder, n (%) 3 (0.5) 1144 (0.9) .328 PD – Agoraphobia, n (%) 6 (1.1) 2865 (2.3) .048 PD + Agoraphobia, n (%) 6 (1.1) 984 (0.8) .478 Agoraphobia – PD, n (%) 19 (3.4) 3974 (3.2) .842
DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder;
GAD: generalized anxiety disorder; PD: panic disorder Table 2. Characteristics of participants stratified by myocardial infarction status Characteristics Recognize d MI (N=1095) Unrecognized MI (N=565) P value Age M (SD) 60.3 (11.0) 53.2 (11.9) <.001 Women, n (%) 240 (21.9) 296 (52.4) <.001 Smoking, n (%) 207 (19.3) 122 (22.1) .185 Diabetes, n (%) 150 (13.7) 43 (7.6) .001 Kidney disease, n (%) 17 (1.6) 2 (0.4) .034 Congestive heart failure, n (%) 211 (19.6) 12 (2.2) <.001 Health related quality of life M (SD) 48.1 (9.0) 51.3 (7.7) <.001 Any DEP disorder, n (%) 50 (4.6) 23 (4.1) .643 MDD, n (%) 32 (2.9) 15 (2.7) .756 Dysthymia, n (%) 18 (1.7) 8 (1.5) .719 Any ANX disorder, n (%) 123 (11.2) 46 (8.1) .048 GAD, n (%) 44 (4.0) 21 (3.7) .764 Social anxiety disorder, n (%) 9 (0.8) 3 (0.5) .507 PD – Agoraphobia, n (%) 16 (1.5) 6 (1.1) .500 PD + Agoraphobia, n (%) 10 (0.9) 6 (1.1) .769 Agoraphobia – PD, n (%) 57 (5.2) 19 (3.4) .089
DEP: depressive disorders; MDD: major depression disorder; ANX: anxiety disorder; GAD: generalized anxiety disorder; PD: panic disorder
Interaction effects between MI status and sex
The interaction term between sex and the dummy variable representing the comparison of participants with recognized MI and participants without MI was statistically significant when predicting the occurrence of anxiety disorders even after adjustment for all the study covariates (OR = 0.61 [0.39-0.96]; p = 0.033). After stratifying the sample according to sex, the odds of having anxiety disorders were statistically significant in men (OR = 1.51 [1.18-1.94]; p = 0.001) but not in women (OR = 0.93 [0.63-1.39]; p = 0.733). However, none of the other interaction terms were statistically significant (p > 0.05). M ul tip le lo gi st ic re gr es sio n M od el 1 M od el 2 M od el 3 Anx ie ty O R (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e Anx ie ty O R (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e Anx ie ty OR (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e iz ed M I v er su s n o M I 1. 62 (1 .3 4-1. 96) ; p< .0 01 2.0 0 (1 .5 0-2. 67) ; p< .0 01 . 1. 40 (1 .1 4-1. 72) ; p= .0 01 1. 49 (1. 08 -2. 05) ; p= .0 15 1. 31 (1. 07 -1. 61) ; p= .0 10 1. 30 (0. 94 -1. 80) ; p=. 107 ni ze d M I v er su s n o M I 0. 89 (0. 66 -1. 21) ; p=. 460 1. 38 (0. 90 -2. 09) ; p=. 137 0. 87 (0. 63 -1. 19) ; p=. 377 1. 40 (0. 91 -2. 15) ; p=. 128 0. 86 (0. 62 -1. 18) ; p=. 356 1. 38 (0. 89 -2. 13) ; p=. 145 zed M I ver sus ni ze d M I 1. 87 (1 .2 7-2. 76) ; p= .0 02 1. 66 (0. 95 -2. 88) ; p=. 072 1. 72 (1 .1 4-2. 59) ; p= .0 10 1. 22 (0. 68 -2. 19) ; p=. 510 1. 50 (0. 99 -2. 27) ; p=. 057 1. 00 (0. 55 -1. 82) ; p=. 988 s r at io ; C I: c on fid en ce in te rv al; M I: m yo ca rd ia l in fa rc tio n
Interaction effects between MI status and sex
The interaction term between sex and the dummy variable representing the comparison of participants with recognized MI and participants without MI was statistically significant when predicting the occurrence of anxiety disorders even after adjustment for all the study covariates (OR = 0.61 [0.39-0.96]; p = 0.033). After stratifying the sample according to sex, the odds of having anxiety disorders were statistically significant in men (OR = 1.51 [1.18-1.94]; p = 0.001) but not in women (OR = 0.93 [0.63-1.39]; p = 0.733). However, none of the other interaction terms were statistically significant (p > 0.05). e 4. M ul tip le lo gi st ic re gr es sio n M od el 1 M od el 2 M od el 3 Anx ie ty O R (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e Anx ie ty O R (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e Anx ie ty OR (9 5% C I); p-va lu e De pr essi on O R (9 5% C I); p-va lu e gn iz ed M I v er su s n o M I 1. 62 (1 .3 4-1. 96) ; p< .0 01 2.0 0 (1 .5 0-2. 67) ; p< .0 01 . 1. 40 (1 .1 4-1. 72) ; p= .0 01 1. 49 (1. 08 -2. 05) ; p= .0 15 1. 31 (1. 07 -1. 61) ; p= .0 10 1. 30 (0. 94 -1. 80) ; p=. 107 ec og ni ze d M I v er su s n o M I 0. 89 (0. 66 -1. 21) ; p=. 460 1. 38 (0. 90 -2. 09) ; p=. 137 0. 87 (0. 63 -1. 19) ; p=. 377 1. 40 (0. 91 -2. 15) ; p=. 128 0. 86 (0. 62 -1. 18) ; p=. 356 1. 38 (0. 89 -2. 13) ; p=. 145 ogni zed M I ver sus ec og ni ze d M I 1. 87 (1 .2 7-2. 76) ; p= .0 02 1. 66 (0. 95 -2. 88) ; p=. 072 1. 72 (1 .1 4-2. 59) ; p= .0 10 1. 22 (0. 68 -2. 19) ; p=. 510 1. 50 (0. 99 -2. 27) ; p=. 057 1. 00 (0. 55 -1. 82) ; p=. 988 dd s r at io ; C I: c on fid en ce in te rv al; M I: m yo ca rd ia l in fa rc tio n
Paradoxically, HRQOL explained the increased odds for anxiety when individuals with recognized and unrecognized MI were compared. These findings suggest that also the physical discomfort related to having recognized MI, which is by definition more symptomatic than unrecognized MI, explains the higher odds of having anxiety. Individuals with recognized MI are thought to have increased size and duration of the myocardial ischemia, as well as a different location of it, that could explain why recognized MI is more symptomatic than unrecognized MI39-41. Care should be taken before making such assumptions, as these differences have not been empirically demonstrated26.
Participants with recognized MI were at significantly increased risk of having anxiety but not depressive disorders when compared to those with unrecognized MI. However, this particular comparison group was composed by a low number of cases (565 with unrecognized MI). Among these participants with unrecognized MI, less than 20 (3%) had a depressive disorder. This low number of cases with comorbidity might have reduced statistical power to detect significant associations. In opposition, about 10% of the participants with unrecognized MI had anxiety disorders, which is substantially higher than in the case of depressive disorders. Therefore, care should be taken when interpreting these results. Moreover, the prevalence of depressive disorders in participants with MI and in the general population is lower than elsewhere-reported42. The prevalence of anxiety disorders is slightly higher than in previous reports11.
Although our results may suggest a psychological pathway, a definitive answer of whether the increased odds for anxiety and depression in individuals with recognized MI is caused by psychological or physiological factors is yet to be delivered. Furthermore, the answer is probably more complex than a simple dichotomy. The increased risk of anxiety and depressive disorders may be explained by interactions of diverse psychological (e.g. burden of receiving a diagnosis of a life-threatening disease, cardiac illness misconceptions, resilience, HRQOL) and physiological (e.g. heart disease severity, increased platelet activation, inflammatory biomarkers, autonomic nervous function) factors. Discussion Main findings The present study investigated if the odds of having depressive and anxiety disorders are significantly increased in individuals with recognized and unrecognized MI in a large community sample. Individuals with recognized MI have significantly increased odds of having anxiety disorders when compared with individuals without MI, even after adjustment for chronic diseases, smoking and HRQOL was performed. Notwithstanding, participants with unrecognized MI do not have significantly increased odds of having anxiety disorders. Regarding depressive disorders, the odds were significantly increased in participants with recognized MI when compared with participants without MI, but adjustment for HRQOL seemed to explain the association. Participants with unrecognized MI did not have increased odds of having depressive disorders when compared with participants without MI.
A recent study investigated the association of recognized and unrecognized MI with depression26. This study was conducted in a Dutch sample of elderly individuals, and authors reported that only men with recognized MI were at a significant risk of having depressive disorders when compared with men without MI. Men with unrecognized MI were not at significantly increased risk of having depression when compared with men without MI26. Authors of this study suggested that the awareness of having cardiovascular disease plays an important role on the long-term risk for the onset of depression26.
Results of the present analyses provide some insights for better understanding the important role of the recognition of MI in the aetiology of post-MI anxiety and depression. Participants with unrecognized MI are not at increased risk of having either anxiety or depressive disorders when compared with individuals without MI, but participants with recognized MI are. These findings suggest that the psychological awareness of being diagnosed with MI may substantially contribute to the significantly increased odds of having depressive and anxiety disorders.
Paradoxically, HRQOL explained the increased odds for anxiety when individuals with recognized and unrecognized MI were compared. These findings suggest that also the physical discomfort related to having recognized MI, which is by definition more symptomatic than unrecognized MI, explains the higher odds of having anxiety. Individuals with recognized MI are thought to have increased size and duration of the myocardial ischemia, as well as a different location of it, that could explain why recognized MI is more symptomatic than unrecognized MI39-41. Care should be taken before making such assumptions, as these differences have not been empirically demonstrated26.
Participants with recognized MI were at significantly increased risk of having anxiety but not depressive disorders when compared to those with unrecognized MI. However, this particular comparison group was composed by a low number of cases (565 with unrecognized MI). Among these participants with unrecognized MI, less than 20 (3%) had a depressive disorder. This low number of cases with comorbidity might have reduced statistical power to detect significant associations. In opposition, about 10% of the participants with unrecognized MI had anxiety disorders, which is substantially higher than in the case of depressive disorders. Therefore, care should be taken when interpreting these results. Moreover, the prevalence of depressive disorders in participants with MI and in the general population is lower than elsewhere-reported42. The prevalence of anxiety disorders is slightly higher than in previous reports11.
Although our results may suggest a psychological pathway, a definitive answer of whether the increased odds for anxiety and depression in individuals with recognized MI is caused by psychological or physiological factors is yet to be delivered. Furthermore, the answer is probably more complex than a simple dichotomy. The increased risk of anxiety and depressive disorders may be explained by interactions of diverse psychological (e.g. burden of receiving a diagnosis of a life-threatening disease, cardiac illness misconceptions, resilience, HRQOL) and physiological (e.g. heart disease severity, increased platelet activation, inflammatory biomarkers, autonomic nervous function) factors. Discussion Main findings The present study investigated if the odds of having depressive and anxiety disorders are significantly increased in individuals with recognized and unrecognized MI in a large community sample. Individuals with recognized MI have significantly increased odds of having anxiety disorders when compared with individuals without MI, even after adjustment for chronic diseases, smoking and HRQOL was performed. Notwithstanding, participants with unrecognized MI do not have significantly increased odds of having anxiety disorders. Regarding depressive disorders, the odds were significantly increased in participants with recognized MI when compared with participants without MI, but adjustment for HRQOL seemed to explain the association. Participants with unrecognized MI did not have increased odds of having depressive disorders when compared with participants without MI.
A recent study investigated the association of recognized and unrecognized MI with depression26. This study was conducted in a Dutch sample of elderly individuals, and authors reported that only men with recognized MI were at a significant risk of having depressive disorders when compared with men without MI. Men with unrecognized MI were not at significantly increased risk of having depression when compared with men without MI26. Authors of this study suggested that the awareness of having cardiovascular disease plays an important role on the long-term risk for the onset of depression26.
Results of the present analyses provide some insights for better understanding the important role of the recognition of MI in the aetiology of post-MI anxiety and depression. Participants with unrecognized MI are not at increased risk of having either anxiety or depressive disorders when compared with individuals without MI, but participants with recognized MI are. These findings suggest that the psychological awareness of being diagnosed with MI may substantially contribute to the significantly increased odds of having depressive and anxiety disorders.
The present study also has strengths. The large sample of 125,750 participants enabled us with enough statistical power for answering most of the research questions. Moreover, the occurrence of depressive and anxiety disorders was assessed through a structured clinical interview, which might capture more details in comparison with self-reports43. Despite the advantage to use this structured interview, an additional combination with self-report questionnaires could further improve the quality of the assessment44.
Conclusions
There are indications suggesting that both anxiety and depression were not significantly increased in participants with unrecognized MI when compared with participants without MI. Therefore, recognition of the MI might play an important role in the aetiology of post-MI anxiety and depression, suggesting a psychological rather than a physiological pathway. Future research should focus on the association between unrecognized MI and anxiety in a prospective longitudinal design.
Prospective etiologic studies accounting for these interactions are warranted.
Limitations and strengths
Findings should be interpreted in the light of study limitations. First, the cross-sectional design does not allow inferring on causality of the association between the recognition of MI and the occurrence of depressive and anxiety disorders. Nonetheless, our findings are in line with a previous longitudinal study investigating the risk of depression in individuals with recognized and unrecognized MI26.
Second, the potential misclassification of unrecognized MI and depressive or anxiety disorders (i.e. false positive diagnoses) might reduce the association, as the diagnostic criteria for all these conditions is not always reliable. However, we tried to validate the cases with unrecognized MI, by providing comparisons with participants without MI. Participants with unrecognized MI displayed significantly higher figures for traditional cardiovascular risk markers, such as age, sex, diabetes, CHF and worsened HRQOL.
Third, although the MINI attempts to reproduce the diagnostic criteria of the DSM-IV, it is not applied by clinicians, which could compromise its ability to make valid diagnoses. Findings of the present study should be replicated while using other clinical diagnostic interviews.
Fourth, in the present study adjustment for left-ventricular ejection fraction (LVEF), an important marker of heart disease severity was not able to be performed, as this variable has not been measured in Lifelines. A previous study reported that LVEF is an important confounder in the association between depression and adverse medical prognosis in patients with recognized MI38. Future studies should consider including statistical adjustment for LVEF, as it could potentially explain the increased odds for having depressive and anxiety disorders in participants with recognized MI. However, we did adjust for the PCS of HRQOL, which can also be used to reflect cardiovascular disease severity.
The present study also has strengths. The large sample of 125,750 participants enabled us with enough statistical power for answering most of the research questions. Moreover, the occurrence of depressive and anxiety disorders was assessed through a structured clinical interview, which might capture more details in comparison with self-reports43. Despite the advantage to use this structured interview, an additional combination with self-report questionnaires could further improve the quality of the assessment44.
Conclusions
There are indications suggesting that both anxiety and depression were not significantly increased in participants with unrecognized MI when compared with participants without MI. Therefore, recognition of the MI might play an important role in the aetiology of post-MI anxiety and depression, suggesting a psychological rather than a physiological pathway. Future research should focus on the association between unrecognized MI and anxiety in a prospective longitudinal design.
Prospective etiologic studies accounting for these interactions are warranted.
Limitations and strengths
Findings should be interpreted in the light of study limitations. First, the cross-sectional design does not allow inferring on causality of the association between the recognition of MI and the occurrence of depressive and anxiety disorders. Nonetheless, our findings are in line with a previous longitudinal study investigating the risk of depression in individuals with recognized and unrecognized MI26.
Second, the potential misclassification of unrecognized MI and depressive or anxiety disorders (i.e. false positive diagnoses) might reduce the association, as the diagnostic criteria for all these conditions is not always reliable. However, we tried to validate the cases with unrecognized MI, by providing comparisons with participants without MI. Participants with unrecognized MI displayed significantly higher figures for traditional cardiovascular risk markers, such as age, sex, diabetes, CHF and worsened HRQOL.
Third, although the MINI attempts to reproduce the diagnostic criteria of the DSM-IV, it is not applied by clinicians, which could compromise its ability to make valid diagnoses. Findings of the present study should be replicated while using other clinical diagnostic interviews.
Fourth, in the present study adjustment for left-ventricular ejection fraction (LVEF), an important marker of heart disease severity was not able to be performed, as this variable has not been measured in Lifelines. A previous study reported that LVEF is an important confounder in the association between depression and adverse medical prognosis in patients with recognized MI38. Future studies should consider including statistical adjustment for LVEF, as it could potentially explain the increased odds for having depressive and anxiety disorders in participants with recognized MI. However, we did adjust for the PCS of HRQOL, which can also be used to reflect cardiovascular disease severity.
11. de Graaf R, ten Have M, van Gool C, van Dorsselaer S. Prevalence of mental disorders and trends from 1996 to 2009. results from the netherlands mental health survey and incidence study-2. Soc Psychiatry Psychiatr Epidemiol. 2012;47(2):203-213. 12. Roest AM, Martens EJ, de Jonge P, Denollet J. Anxiety and risk of incident coronary heart disease A meta-analysis. J Am Coll Cardiol. 2010;56(1):38-46. 13. Roest AM, Martens EJ, Denollet J, De Jonge P. Prognostic association of anxiety post myocardial infarction with mortality and new cardiac events: A meta-analysis. Psychosom Med. 2010;72(6):563-569. 14. Celano CM, Millstein RA, Bedoya CA, Healy BC, Roest AM, Huffman JC. Association between anxiety and mortality in patients with coronary artery disease: A meta-analysis. Am Heart J. 2015;170(6):1105-1115. 15. National Clinical Guideline Centre (UK). . 2013. 16. Kumar P CM. Kumar and clark's clinical medicine. 7th ed. UK: Saunders Elsevier; 2009. 17. Valensi P, Lorgis L, Cottin Y. Prevalence, incidence, predictive factors and prognosis or silent myocardial infarction: A review of the literature. Archives of Cardiovascular Diseases. 2011;104(3):178-188. 18. Pride YB, Piccirillo BJ, Gibson CM. Prevalence, consequences, and implications for clinical trials of unrecognized myocardial infarction. Am J Cardiol. 2013;111(6):914-918. 19. Sheifer S, Manolio T, Gersh B. Unrecognized myocardial infarction. Ann Intern Med. 2001;135(9):801-811. 20. Ikram MA, van Oijen M, de Jong FJ, et al. Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease. Stroke. 2008;39(5):1421-1426. 21. Sheifer S, Gersh B, Yanez N, Ades P, Burke G, Manolio T. Prevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly. J Am Coll Cardiol. 2000;35(1):119-126. References 1. Gan Y, Gong Y, Tong X, et al. Depression and the risk of coronary heart disease: A meta-analysis of prospective cohort studies. BMC Psychiatry. 2014;14:371. 2. Lesperance F, Frasure-Smith N. Depression in patients with cardiac disease: A practical review. J Psychosom Res. 2000;48(4-5):379-391. 3. 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):802-813. 4. 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):814-822. 5. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: A clinical review. Eur Heart J. 2014;35(21):1365-1372. doi: 10.1093/eurheartj/eht462. 6. Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: A meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006;27(23):2763-2774. 7. Meijer A, Conradi HJ, Bos EH, et al. Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: Individual patient data meta-analysis. Br J Psychiatry. 2013;203:90-102. 8. Martens EJ, de Jonge P, Na B, Cohen BE, Lett H, Whooley MA. Scared to death? generalized anxiety disorder and cardiovascular events in patients with stable coronary heart disease the heart and soul study. Arch Gen Psychiatry. 2010;67(7):750-758. 9. Parker GB, Owen CA, Brotchie HL, Hyett MP. The impact of differing anxiety disorders on outcome following an acute coronary syndrome: Time to start worrying? Depress Anxiety. 2010;27(3):302-309. 10. Todaro JF, Shen B, Raffa SD, Tilkemeier PL, Niaura R. Prevalence of anxiety disorders in men and women with established coronary heart disease. Journal of Cardiopulmonary Rehabilitation and Prevention. 2007;27(2):86-91.
11. de Graaf R, ten Have M, van Gool C, van Dorsselaer S. Prevalence of mental disorders and trends from 1996 to 2009. results from the netherlands mental health survey and incidence study-2. Soc Psychiatry Psychiatr Epidemiol. 2012;47(2):203-213. 12. Roest AM, Martens EJ, de Jonge P, Denollet J. Anxiety and risk of incident coronary heart disease A meta-analysis. J Am Coll Cardiol. 2010;56(1):38-46. 13. Roest AM, Martens EJ, Denollet J, De Jonge P. Prognostic association of anxiety post myocardial infarction with mortality and new cardiac events: A meta-analysis. Psychosom Med. 2010;72(6):563-569. 14. Celano CM, Millstein RA, Bedoya CA, Healy BC, Roest AM, Huffman JC. Association between anxiety and mortality in patients with coronary artery disease: A meta-analysis. Am Heart J. 2015;170(6):1105-1115. 15. National Clinical Guideline Centre (UK). . 2013. 16. Kumar P CM. Kumar and clark's clinical medicine. 7th ed. UK: Saunders Elsevier; 2009. 17. Valensi P, Lorgis L, Cottin Y. Prevalence, incidence, predictive factors and prognosis or silent myocardial infarction: A review of the literature. Archives of Cardiovascular Diseases. 2011;104(3):178-188. 18. Pride YB, Piccirillo BJ, Gibson CM. Prevalence, consequences, and implications for clinical trials of unrecognized myocardial infarction. Am J Cardiol. 2013;111(6):914-918. 19. Sheifer S, Manolio T, Gersh B. Unrecognized myocardial infarction. Ann Intern Med. 2001;135(9):801-811. 20. Ikram MA, van Oijen M, de Jong FJ, et al. Unrecognized myocardial infarction in relation to risk of dementia and cerebral small vessel disease. Stroke. 2008;39(5):1421-1426. 21. Sheifer S, Gersh B, Yanez N, Ades P, Burke G, Manolio T. Prevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly. J Am Coll Cardiol. 2000;35(1):119-126. References 1. Gan Y, Gong Y, Tong X, et al. Depression and the risk of coronary heart disease: A meta-analysis of prospective cohort studies. BMC Psychiatry. 2014;14:371. 2. Lesperance F, Frasure-Smith N. Depression in patients with cardiac disease: A practical review. J Psychosom Res. 2000;48(4-5):379-391. 3. 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):802-813. 4. 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):814-822. 5. Hare DL, Toukhsati SR, Johansson P, Jaarsma T. Depression and cardiovascular disease: A clinical review. Eur Heart J. 2014;35(21):1365-1372. doi: 10.1093/eurheartj/eht462. 6. Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: A meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006;27(23):2763-2774. 7. Meijer A, Conradi HJ, Bos EH, et al. Adjusted prognostic association of depression following myocardial infarction with mortality and cardiovascular events: Individual patient data meta-analysis. Br J Psychiatry. 2013;203:90-102. 8. Martens EJ, de Jonge P, Na B, Cohen BE, Lett H, Whooley MA. Scared to death? generalized anxiety disorder and cardiovascular events in patients with stable coronary heart disease the heart and soul study. Arch Gen Psychiatry. 2010;67(7):750-758. 9. Parker GB, Owen CA, Brotchie HL, Hyett MP. The impact of differing anxiety disorders on outcome following an acute coronary syndrome: Time to start worrying? Depress Anxiety. 2010;27(3):302-309. 10. Todaro JF, Shen B, Raffa SD, Tilkemeier PL, Niaura R. Prevalence of anxiety disorders in men and women with established coronary heart disease. Journal of Cardiopulmonary Rehabilitation and Prevention. 2007;27(2):86-91.
32.Frasure-Smith N, Lespérance F, Talajic M. Depression following myocardial infarction: Impact on 6-month survival. JAMA. 1993;270(15):1819-1825. 33.Carney R, Freedland K, Miller G, Jaffe A. Depression as a risk factor for cardiac mortality and morbidity - A review of potential mechanisms. J Psychosom Res. 2002;53(4):897-902. 34.Khot UN, Jia G, Moliterno DJ, et al. Prognostic importance of physical examination for heart failure in non–ST-elevation acute coronary syndromes: The enduring value of killip classification. JAMA. 2003;290(16):2174-2181. 35.Hays RD, Sherbourne CD, Mazel RM. The rand 36-item health survey 1.0. Health Econ. 1993;2(3):217-227. 36.Hays R, Prince-Embury S, Chen H. RAND-36 health status inventory. San Antonio, TX: Psychological Corporation; 1998. 37.Hays RD, Morales LS. The RAND-36 measure of health-related quality of life. Ann Med. 2001;33(5):350-357. 38.Doyle F, McGee H, Conroy R, et al. Systematic review and individual patient data meta-analysis of sex differences in depression and prognosis in persons with myocardial infarction: A MINDMAPS study. Psychosom Med. 2015;77(4):419-428. 39.Cohn PF, Fox KM, Daly C. Silent myocardial ischemia. Circulation. 2003;108(10):1263-1277. 40.Cabin HS, Roberts WC. Quantitative comparison of extent of coronary narrowing and size of healed myocardial infarct in 33 necropsy patients with clinically recognized and in 28 with clinically unrecognized (“silent”) previous acute myocardial infarction. Am J Cardiol. 1982;50(4):677-681. 41.Schelbert EB, Cao JJ, Sigurdsson S, et al. Prevalence and prognosis of unrecognized myocardial infarction determined by cardiac magnetic resonance in older adults. JAMA. 2012;308(9):890-896. 42.Center for Behavioral Health Statistics and Quality. Behavioral health trends in the united states: Results from the 2014 national survey on drug use and health. http://www.samhsa.gov/data/. Updated 2015. Accessed 04/03, 2016. 22. Nadelmann J, Frishman WH, Ooi WL, et al. Prevalence, incidence and prognosis of recognized and unrecognized myocardial infarction in persons aged 75 years or older: The bronx aging study. Am J Cardiol. 1990;66(5):533-537. 23. Ammar K, Samee S, Makwana R, et al. Echocardiographic characteristics of electrocardiographically unrecognized myocardial infarctions in a community population. Am J Cardiol. 2005;96(8):1069-1075. 24. Maradit-Kremers H, Crowson C, Nicola P, et al. Increased unrecognized coronary heart disease and sudden deaths in rheumatoid arthritis - A population-based cohort study. Arthritis Rheum. 2005;52(2):402-411. 25. Sigurdsson E, Thorgeirsson G, Sigvaldason H, Sigfusson N. Unrecognized myocardial infarction: Epidemiology, clinical characteristics, and the prognostic role of angina pectoris: The reykjavik study. Ann Intern Med. 1995;122(2):96-102. 26. Jovanova O, Luik AI, Leening MJ, et al. The long-term risk of recognized and unrecognized myocardial infarction for depression in older men. Psychol Med. 2016:1-10. 27. Thombs BD, Bass EB, Ford DE, et al. Prevalence of depression in survivors of acute myocardial infarction. Journal of general internal medicine. 2006;21(1):30-38. 28. Tully PJ, Cosh SM. Generalized anxiety disorder prevalence and comorbidity with depression in coronary heart disease: A meta-analysis. J Health Psychol. 2013;18(12):1601-1616. 29. Scholtens S, Smidt N, Swertz MA, et al. Cohort profile: LifeLines, a three-generation cohort study and biobank. Int J Epidemiol. 2015;44(4):1172-1180. 30. Leening MJ, Kavousi M, Heeringa J, et al. Methods of data collection and definitions of cardiac outcomes in the rotterdam study. Eur J Epidemiol. 2012;27(3):173-185. 31. Sheehan D, Lecrubier Y, Sheehan K, et al. The mini-international neuropsychiatric interview (MINI): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59:22-33.
