CLINICAL RESEARCH: EFFECT OF DEPRESSION/ANXIETY ON CARDIAC EVENTS
Comparing symptoms of depression and anxiety as predictors of cardiac events and increased health care consumption after myocardial infarction
Jacqueline J. M. H. Strik, MD*,
Johan Denollet, PhD* ,*,
Richel Lousberg, PhD* and
Adriaan Honig, MD, PhD, MRCPsych*
* Department of Psychiatry, Academic Hospital Maastricht/Maastricht University, Maastricht, Netherlands
Department of Psychology and Health, Tilburg University, Tilburg, The Netherlands
Manuscript received November 4, 2002;
revised manuscript received June 30, 2003,
accepted July 29, 2003.
* Reprint requests and correspondence: Dr. Johan Denollet, Department of Psychology and Health, Tilburg University, P.O. Box 90153, 5000 LE Tilburg, The Netherlands.
denollet{at}uvt.nl
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Abstract
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OBJECTIVES: We sought to compare symptoms of depression and anxiety as predictors of incomplete recovery after a first myocardial infarction (MI).
BACKGROUND: Depressive symptoms have been related to post-MI mortality and health care consumption, but little is known about the effect of anxiety. We wanted to examine the effect of emotional distress on health care consumption and whether depressive symptomatology is a better predictor of prognosis than anxiety.
METHODS: Subjects were 318 men (mean age 58 years) who completed the depression, anxiety, and hostility scales from the 90-item symptom check list after they survived a first MI.
RESULTS: After an average follow-up of 3.4 years, there were 25 cardiac events (fatal or non-fatal MI). Symptoms of both depression (hazard ratio [HR] 2.32, 95% confidence interval [CI] 1.04 to 5.18; p = 0.039) and anxiety (HR 3.01, 95% CI 1.20 to 7.60; p = 0.019) were associated with cardiac events, adjusting for age, left ventricular ejection fraction, and use of antidepressants. However, a multivariate analysis including all three negative emotions indicated that symptoms of anxiety (HR 2.79, 95% CI 1.11 to 7.03; p = 0.029) explained away the relationship between depressive symptoms and cardiac events. Regarding health care consumption, anxiety (OR 2.00, 95% CI 1.24 to 3.22; p = 0.005), but not depression/hostility, was a predictor of cardiac rehospitalization and frequent visits at the cardiac outpatient clinic.
CONCLUSIONS: Symptoms of depression and anxiety were associated with cardiac events. Anxiety was an independent predictor of both cardiac events and increased health care consumption and accounted for the relationship between depressive symptoms and prognosis. Symptoms of anxiety need to be considered in the risk stratification and treatment of post-MI patients.
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Abbreviations and Acronyms
| | ASAT | = aspartate aminotransferase | | AZM | = Academic Hospital Maastricht | | CAD | = coronary artery disease | | CHD | = coronary heart disease | | CI | = confidence interval | | HR | = hazard ratio | | LVEF | = left ventricular ejection fraction | | MI | = myocardial infarction | | OR | = odds ratio | | SCL-90 | = 90-item Symptom Check List |
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Negative emotions, such as depression and anxiety, have been related to coronary artery disease (CAD) (1–3) and a poor prognosis after myocardial infarction (MI) (4). Possible mechanisms linking negative emotions to the post-MI period include increased vulnerability to arrhythmias as a result of increased sympathic tone (5) and increased platelet aggregation (6). It is unclear whether treatment of depression may lead to a decrease in post-MI mortality (7), but the findings of a recent study suggest that reducing emotional stress may improve the prognosis (8).
Depression is frequently studied and considered as a pathogenic factor in post-MI patients (9–12). Minor depression and depressive symptoms also have a negative effect on prognosis in cardiac patients (13). The increased risk of cardiac events may extend to patients with symptoms of negative affect other than depression (14,15). In healthy populations, anxiety (1–3) and anger (16) have been associated with the incidence of cardiac events, but less is known about the role of anxiety and anger in post-MI patients. Some studies have found that symptoms of depression and anxiety (17,18) or anxiety alone (19) did not predict mortality in MI patients but did predict quality of life among those MI patients who lived to 12 months. Other studies reported that both depression and anxiety, independent of each other, predicted cardiac events (20) or CAD (21).
However, there has been a tendency to focus on only one negative emotion at a time (15). Hence, the question remains whether symptoms of depression play a specific role in the prognosis of post-MI patients or whether symptoms of other negative emotions such as anxiety and anger have a comparable adverse effect on recovery after MI. In psychiatric patients, anxiety and depression frequently co-occur, and co-morbid anxiety has been associated with a greater severity of depressive disorder and a poor response to anti-depressive treatment (22–27). In depressed post-MI patients, evidence suggests that co-morbid anxiety rather than pure depression may account for reduced heart rate variability as a cardiotoxic factor (28). Of note, pharmacologic treatment of anxiety may also decrease the risk of major depression (27).
Most studies investigating the relationship between psychological factors and prognosis after MI focus on mortality and new cardiac events (29–31). Negative emotions may also have an adverse effect on other "softer" end points such as angina, quality of life, and incomplete recovery (32). The effect of depression on angina and re-hospitalization is even more strongly established than its effect on mortality (33). This is reason for concern because adverse outcomes also represent increased health care costs (34).
The purpose of the present study was twofold. First, we wanted to examine whether depression is a better predictor of incomplete recovery after MI than anxiety. Second, we wanted to examine the effect of emotional distress not only on major cardiac events but also on re-hospitalization and increased health care consumption.
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Methods
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Patients.
Between May 1994 and September 1999, a total of 407 eligible male patients were admitted to the First Heart Aid of the Academic Hospital of Maastricht (AZM) with acute MI. Inclusion criteria of the present study were male gender, first MI, clinical picture and electrocardiographic signs typical of acute MI, and a maximum value of the enzyme aspartate aminotransferase (ASAT) of at least 80 U/l (twice above the upper limit) (35). Patients were excluded who had a major psychiatric disorder other than affective disorders (e.g., schizophrenia, dementia, present psychotic episode). Additionally, patients who were unable to communicate reliably (e.g., because of cognitive dysfunction or not speaking Dutch) or with a co-morbid life-threatening disease were excluded. The local ethics committee approved this study.
Of the 407 eligible patients, 89 (21.9%) refused to participate and 318 (78.1%) gave written, informed consent before inclusion. A refusal rate of 21.9% is comparable to other studies in which MI patients were screened for depression (12,29). Of the 318 patients, 14 were treated in a randomized, placebo-controlled trial of fluoxetine during 25 weeks (36). After the trial, they were offered further treatment at the mood disorder clinic of AZM if necessary. Furthermore, another 11 patients were treated with antidepressants by the general practitioner or at the mood disorder clinic of AZM.
Assessment of emotional distress.
The 90-item Symptom Check List (SCL-90), which is a well-validated and widely used self-assessment scale (37,38), was used to measure emotional distress. Each of the items of the SCL-90 ranges from 0 to 4, with 0 indicating no complaint and 4 maximal complaint. Patients filled out the SCL-90 one month after MI at home or during the first post-MI visit at the outpatient clinic of the Department of Cardiology. The scales of "depression" (16 items), "anxiety" (10 items), and "hostility" (6 items) from the SCL-90 were scored for the purpose of the present study. These scales were conceptualized as markers of emotional distress. In previous research, we evaluated the SCL-90 depression scale in patients with post-MI depression and found it to be a valid instrument, with a sensitivity of 81.1% and a specificity of 83.5%. In comparison, the Beck Depression Inventory had a sensitivity of 83.8% and a specificity of 71.7% (39).
End points.
The end points in this study were major cardiac events and health care consumption during an average follow-up period of 3.4 years (range 1 to 70 months). Major cardiac events were defined as cardiac death or recurrent MI, as diagnosed by the attending cardiologist. Increased health care consumption was defined as cardiac rehospitalization and/or frequent visits (>6 visits during follow-up) at the cardiac outpatient clinic. Patients without cardiac events during the follow-up period and with an average number of visits at the cardiac outpatient clinic were considered to be "event free."
Cardiac variables.
Left ventricular ejection fraction (LVEF) was recorded one month after MI as a measure of disease severity. Data on intervention at the time of MI (thrombolysis, percutaneous transluminal coronary angioplasty, coronary artery bypass graft surgery), medication (beta-blockers, platelet aggregation inhibitors, angiotensin-converting enzyme inhibitors), and cardiovascular risk factors (smoking, hypertension, hypercholesterolemia, diabetes) were taken from the patients' records.
Analyses.
All data were entered into a computerized data base and analyzed using SPSS version 6.0 (SPSS Inc., Chicago, Illinois) standard software. According to the results of follow-up, patients were classified into one of three groups: patients with a major cardiac event; patients with increased health care consumption; and event-free patients. To determine the prognostic power of emotional distress, scores on the depression, hostility, and anxiety subscales were dichotomized according to the cut-off values for high-risk psychopathology (38): 23 for depression; 12 for anxiety; and 7 for hostility. The LVEF was dichotomized at 50%, using standards of a former publication on CAD patients (8). A median split was used to dichotomize patients according to age (median 58 years) and the number of visits at the outpatient cardiology clinic (median 6 visits). Differences in baseline characteristics between the three groups were tested by the independent t test for continuous variables and the chi-square test for all dichotomous variables. Fisher exact probabilities were calculated when they were expected.
Multivariate Cox regression analysis was used to examine the SCL-90 depression, anxiety, and hostility subscales separately as predictors of major cardiac events. To select appropriate co-variates for statistical control, all baseline variables were dichotomized (at predetermined points). Those variables significantly related to major cardiac events in the univariate Cox regression models were entered into the multiple Cox regression analysis, followed by the addition of the SCL-90 depression, anxiety, and hostility subscales. Because anti-depressive agents can flaw the impact of depression on cardiac prognosis, we also included the use of antidepressants as a co-variate in our model. Finally, a stepwise multivariate Cox regression analysis, including all three negative emotions (SCL-90 subscales of depression, anxiety, and hostility), was used to examine these emotions as independent predictors of major cardiac events.
Regarding analysis of SCL-90 depression, anxiety, and hostility subscales as predictors of health care consumption, univariate logistic regressions were first performed. Those baseline variables significantly related to health consumption were entered in a multivariate logistic regression model, followed by the addition of the SCL-90 subscales. Finally, multivariate logistic regression with all three negative emotions was used. A two-tailed p value  0.05 was considered to be significant.
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Results
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Patients.
The average (±SD) age of the 318 included men was 58 ± 11 years, and the mean LVEF and maximum ASAT scores were 51 ± 9.8% and 247 ± 182 U/l, respectively. There were no differences between the participating and non-participating groups with respect to age, maximum ASAT, or LVEF. Of the 318 participants, 91.9% were prescribed platelet aggregation inhibitors, 58.2% beta-blockers, 45.2% lipid-lowering drugs, 36.2% angiotensin-converting enzyme inhibitors, 9% diuretics, and 5.7% oral antidiabetic agents. Fifty-four percent of patients were smoking before MI, 20.4% were known to have hypercholesterolemia, 8.5% had diabetes, and 28% had hypertension. Next, we evaluated whether not only age and LVEF but also medication and risk factors for CAD were associated with the distress variables of depression, anxiety, and hostility (Table 1). Age under 58 years was associated with patients with depressive symptoms (p = 0.031), as was smoking (p = 0.003). Diabetes, prescription of oral antidiabetic agents, and platelet aggregation inhibitors were associated with symptoms of anxiety (p = 0.043, 0.047, and 0.026, respectively). Hyperlipidemia was associated with symptoms of hostility (p = 0.022), as was smoking (p = 0.026). According to the psychological assessment one month after MI, 47.1% of the patients scored above the cut-off value of the SCL-90 depression subscale, 59.5% above the anxiety subscale, and 62.1% above the hostility subscale.
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Table 1 Baseline Demographic Data, Medications, and Coronary Artery Disease Risk Factors and Their Univariate Relationship With Depression, Anxiety, and Hostility
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Cardiac events.
One hundred forty-four patients (45.2%) were event-free during follow-up, whereas 25 (7.9%) had experienced a major cardiac event. On univariate Cox regression analyses (Table 2), LVEF 50% was significantly associated with cardiac death or recurrent MI (p = 0.031). There was also a trend for age >58 years (p = 0.066). The other cardiovascular variables (i.e., beta-blockers, invasive intervention, smoking, hypercholesterolemia, hypertension, and diabetes) were not associated with cardiac events (Table 2) or health care consumption (Table 3).
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Table 3 Increased Health Care Consumption as a Function of Age, Cardiovascular Variables, and Emotional Distress at Baseline
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Symptoms of anxiety, but not depression, were associated with cardiac events on univariate analysis (Fig. 1). After adjusting for age, LVEF, and the use of antidepressants, symptoms of both depression and anxiety were associated with cardiac events (p = 0.039 and 0.019, respectively) (Table 4). There was no relation with hostility.
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Figure 1 Cardiac events during follow-up as a function of emotional distress at baseline. Open bars = low score; solid bars = high score.
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Table 4 Poor Outcome as a Function of One Negative Emotion at a Time, Adjusting for Age, Left Ventricular Ejection Fraction, and Use of Antidepressants
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Increased health care consumption.
Of the 318 male patients with a first MI, 149 (46.9%) had increased health care consumption (i.e., frequent visits to the outpatient cardiac clinic or rehospitalizations due to cardiac events) up to six years after MI. On univariate analyses (Table 3), there were no cardiovascular variables related to increased health care consumption, although there was a trend for LVEF 50% to be related to increased health care consumption (p = 0.069).
Regarding emotional distress as a determinant, depressive and anxious symptoms at baseline were associated with increased health care consumption during follow-up (p = 0.047 and 0.004, respectively) (Table 3). After adjusting for age, LVEF, and the use of antidepressants, anxiety was the only negative emotion that was significantly associated with the secondary end point (odds ratio [OR] 2.00, 95% confidence interval [CI] 1.23 to 3.26; p = 0.006) (i.e., frequent cardiac outpatient visits and rehospitalizations due to cardiac events) (Table 4). Hostility was not related to increased health care consumption.
Independent predictors of end points.
A multivariate analysis including all three negative emotions indicated that symptoms of anxiety (hazard ratio [HR] 2.79, 95% CI 1.11 to 7.03; p = 0.029) (Table 5) explained away the relationship between depressive symptoms and cardiac events. This stepwise multivariate Cox regression also retained LVEF <50% (HR 2.29, 95% CI 1.01 to 5.21; p = 0.047) and age >58 years (HR 2.44, 95% CI 1.01 to 5.88; p = 0.047) as independent predictors of major cardiac events (Table 5, top). Neither depression (p = 0.44) nor hostility (p = 0.39) predicted major cardiac events in this multivariate model. Regarding increased health care consumption, a stepwise logistic regression model again retained anxiety (OR 2.00, 95% CI 1.24 to 3.22; p = 0.005) as an independent predictor of frequent visits to the outpatient cardiac clinic or rehospitalizations due to cardiac events (Table 5, bottom). Neither depression (p = 0.65) nor hostility (p = 0.93) predicted increased health care consumption. In other words, anxiety accounted for the relationship between depression and cardiac events, and anxiety was the only significant predictor of increased health care consumption in survivors of acute MI.
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Discussion
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The findings of the present study showed that symptoms of both depression and anxiety were associated with an increased risk of adverse cardiac events. However, anxiety was an independent predictor of cardiac events and increased health care consumption and accounted for the relationship between depression and prognosis. These findings support the notion that psychological factors are related to a poor prognosis after MI (1–3) and indicate that symptoms of anxiety need to be considered in the risk stratification and treatment of post-MI patients.
The fact that anxiety was a stronger predictor of cardiac outcome in MI patients than depressive symptomatology is a novel finding. A recent review of negative emotions and the onset of coronary heart disease (CHD) in initially healthy individuals also concluded that research should not ignore the risk associated with anxiety (40). The present study focused on patients with established CHD to examine the relative impact of symptoms of depression and anxiety on prognosis. Although most previous research focused on either anxiety (1–3) or depression (4) as single risk indicators, these negative emotions were investigated simultaneously in the present study. Although there was a trend for depressive symptoms to predict cardiac outcome on univariate analysis, anxiety explained away this association on multivariate analysis. In fact, anxiety was associated with a more than twofold increased risk (HR 2.79, 95% CI 1.11 to 7.03; p = 0.029) of cardiac death or recurrent MI after controlling for disease severity (i.e., LVEF 50%; HR 2.29, 95% CI 1.01 to 5.21; p = 0.047) and age (HR 2.44, 95% CI 1.01 to 5.88; p = 0.047). The fact that anxiety, but not depression, was retained as an independent predictor of cardiac outcome is in line with the findings of a recent study by Watkins et al. (28), who found that high levels of anxiety, measured 6 ± 3 days after MI, but not depression, were independently associated with reduced vagal control in post-MI patients. Previous research in our own group also indicated that anxiety was a significant predictor of clinical depression in a sample of 206 post-MI patients (39). Hostility was not associated with cardiac prognosis or increased health care consumption in the present study.
Our findings confirm studies which concluded that depression and anxiety may be predictors of cardiac events after MI (20,21). The follow-up period (1 year) in studies that could not confirm a relationship between depression/anxiety and cardiac events (17,18) was considerably shorter than the follow-up period in the present study (average 3.4 years). It may be that cardiac events related to affective dysregulation after MI tend to occur more in long-term periods. The timing of the assessment may also be important. In a study reporting that both depression and anxiety did not predict outcome at three years after MI (41), the depression and anxiety symptoms were assessed in the hospital. In the present study, these symptoms were assessed at one month after MI.
Study limitations.
The limitations of this study include the relatively small number of cardiac events, the exclusion of female patients, and the lack of information on depression treatment during the course of follow-up. However, as yet, it is not clear whether treatment of post-MI depression can improve the prognosis (42). Another limitation concerns the use of only one instrument to assess specific symptoms of depression and anxiety. Undoubtedly, measures of depressive symptoms may yield significant prognostic information in post-MI patients (40)..At the present time, we do not know what elements of depression predict cardiac mortality. However, the present findings suggest that, in addition to assessing depressive symptomatology, it is equally important to assess other negative emotions, including anxiety.
Apart from a cardiac prognosis, the present study also examined the prognostic role of emotional distress on health care consumption. Depression not only precedes cardiac death and recurrent MI but also may predict morbidity (33). We found that anxiety was an independent predictor of frequent visits to the outpatient cardiac clinic or rehospitalizations due to cardiac events. There was a trend for symptoms of depression to also be related to increased health care consumption, but once again, anxiety accounted for this association in the multivariate model. Hence, it is also important to detect and treat emotionally distressed patients from an economic point of view, given the fact that increased health care consumption entails a significant increase in health care costs among patients with CHD (34).
These findings have implications for clinical research and practice. First, biobehavioral research on CHD has largely focused on depression and depressive symptoms (9–12). It is timely to also include other psychological factors such as anxiety (40). Second, the identification of CHD patients who experience anxiety may lead to more accurate risk estimates in clinical practice. Compared with the Beck Depression Inventory, total Hospital Anxiety and Depression Scale (combination of the anxiety and depression subscale) proved to be more sensitive and specific to depression after MI than the subscales separately (39). This appears to be in line with the results of the present study (i.e., the fact that symptoms of anxiety were predictive of cardiac events in addition to symptoms of depression). Third, as yet, it is not clear whether pharmacologic (36) or behavioral (42,43) treatment of depression can influence the prognosis of post-MI patients (7,44). The present study indicated that besides depression, anxiety is also important in the prediction of cardiac outcome. This finding may help to explain why an intervention that was specifically designed to treat depression (37) failed to improve the prognosis of post-MI patients (44). A more comprehensive approach to treatment, including exercise training and individualized treatment of a wide variety of psychological factors, may be more successful in improving the cardiac prognosis (8).
Conclusions.
We found that anxiety was an independent predictor of cardiac events and increased health care consumption after controlling for disease severity and age. Moreover, anxiety accounted for any associations between depressive symptoms and prognosis. These findings support the notion that symptoms of emotional distress are related to the cardiac prognosis after MI. Yet, they also indicate that, apart from depressive symptoms, other symptoms of emotional distress must be considered to optimize risk stratification and treatment.
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N. Frasure-Smith and F. Lesperance
Depression and Anxiety as Predictors of 2-Year Cardiac Events in Patients With Stable Coronary Artery Disease
Arch Gen Psychiatry,
January 1, 2008;
65(1):
62 - 71.
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A. Szekely, P. Balog, E. Benko, T. Breuer, J. Szekely, M. D. Kertai, F. Horkay, M. S. Kopp, and J. F. Thayer
Anxiety Predicts Mortality and Morbidity After Coronary Artery and Valve Surgery A 4-Year Follow-Up Study
Psychosom Med,
September 1, 2007;
69(7):
625 - 631.
[Abstract]
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A. A Schiffer, J. Denollet, J. W Widdershoven, E. H Hendriks, and O. R F Smith
Failure to consult for symptoms of heart failure in patients with a type-D personality
Heart,
July 1, 2007;
93(7):
814 - 818.
[Abstract]
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K. Piotrowicz, K. Noyes, J. M. Lyness, S. McNitt, M. L. Andrews, A. Dick, W. J. Hall, A. J. Moss, and W. Zareba
Physical functioning and mental well-being in association with health outcome in patients enrolled in the Multicenter Automatic Defibrillator Implantation Trial II
Eur. Heart J.,
March 1, 2007;
28(5):
601 - 607.
[Abstract]
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P. de Jonge, R. H.S. van den Brink, T. A. Spijkerman, and J. Ormel
Only Incident Depressive Episodes After Myocardial Infarction Are Associated With New Cardiovascular Events
J. Am. Coll. Cardiol.,
December 5, 2006;
48(11):
2204 - 2208.
[Abstract]
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L. L. Watkins, J. A. Blumenthal, J. R. T. Davidson, M. A. Babyak, C. B. McCants Jr, and M. H. Sketch Jr
Phobic anxiety, depression, and risk of ventricular arrhythmias in patients with coronary heart disease.
Psychosom Med,
September 1, 2006;
68(5):
651 - 656.
[Abstract]
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E. Shemesh, M. Koren-Michowitz, R. Yehuda, O. Milo-Cotter, E. Murdock, Z. Vered, B. L. Shneider, J. M. Gorman, and G. Cotter
Symptoms of Posttraumatic Stress Disorder in Patients Who Have Had a Myocardial Infarction
Psychosomatics,
June 1, 2006;
47(3):
231 - 239.
[Abstract]
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Y. Aina and J. L. Susman
Understanding Comorbidity With Depression and Anxiety Disorders
J Am Osteopath Assoc,
May 1, 2006;
106(5_suppl_2):
S9 - S14.
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T. M. Hilton, G. Parker, S. McDonald, G. A. Heruc, A. Olley, H. Brotchie, C. Friend, and W. F. Walsh
A Validation Study of Two Brief Measures of Depression in the Cardiac Population: The DMI-10 and DMI-18.
Psychosomatics,
March 1, 2006;
47(2):
129 - 135.
[Abstract]
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J. Denollet, S. S. Pedersen, A. T.L. Ong, R. A.M. Erdman, P. W. Serruys, and R. T. van Domburg
Social inhibition modulates the effect of negative emotions on cardiac prognosis following percutaneous coronary intervention in the drug-eluting stent era
Eur. Heart J.,
January 2, 2006;
27(2):
171 - 177.
[Abstract]
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P. de Jonge, J. Ormel, R. H.S. van den Brink, J. P. van Melle, T. A. Spijkerman, A. Kuijper, D. J. van Veldhuisen, M. P. van den Berg, A. Honig, H. J.G.M. Crijns, et al.
Symptom Dimensions of Depression Following Myocardial Infarction and Their Relationship With Somatic Health Status and Cardiovascular Prognosis
Am J Psychiatry,
January 1, 2006;
163(1):
138 - 144.
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J. P. van Melle, P. de Jonge, J. Ormel, H. J.G.M. Crijns, D. J. van Veldhuisen, A. Honig, A. H. Schene, M. P. van den Berg, and for the MIND-IT investigators
Relationship between left ventricular dysfunction and depression following myocardial infarction: data from the MIND-IT
Eur. Heart J.,
December 2, 2005;
26(24):
2650 - 2656.
[Abstract]
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R. C. Ziegelstein and B. D. Thombs
The brain and the heart: the twain meet
Eur. Heart J.,
December 2, 2005;
26(24):
2607 - 2608.
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N. Frasure-Smith and F. Lesperance
Reflections on Depression as a Cardiac Risk Factor
Psychosom Med,
May 1, 2005;
67(Supplement_1):
S19 - S25.
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J. K. Schulman, P. R. Muskin, and P. A. Shapiro
Psychiatry and Cardiovascular Disease
Focus,
April 1, 2005;
3(2):
208 - 224.
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A Steptoe and D L Whitehead
Depression, stress, and coronary heart disease: the need for more complex models
Heart,
April 1, 2005;
91(4):
419 - 420.
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J. Denollet
DS14: Standard Assessment of Negative Affectivity, Social Inhibition, and Type D Personality
Psychosom Med,
January 1, 2005;
67(1):
89 - 97.
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J. P. van Melle, P. de Jonge, T. A. Spijkerman, J. G. P. Tijssen, J. Ormel, D. J. van Veldhuisen, R. H. S. van den Brink, and M. P. van den Berg
Prognostic Association of Depression Following Myocardial Infarction With Mortality and Cardiovascular Events: A Meta-analysis
Psychosom Med,
November 1, 2004;
66(6):
814 - 822.
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