ann. behav. med. DOI 10.1007/s12160-014-9590-2
ORIGINAL ARTICLE
Type D Personality is Unrelated to Major Adverse Cardiovascular Events in Patients with Coronary Artery Disease Treated by Intracoronary Stenting Thomas Meyer, Ph.D., M.D. & Sharif Hussein, M.S. & Helmut W. Lange, M.D. & Christoph Herrmann-Lingen, M.D.
# The Society of Behavioral Medicine 2014
Abstract Background Previous research in cardiac patients suggested that type D personality, defined as a combination of negative affectivity (NA) and social inhibition (SI), was associated with adverse outcome. Purpose The objective of this prospective study was to examine the independent prognostic value of type D in patients with coronary artery disease (CAD). Methods A total of 465 patients completed the Type D Scale (DS14) questionnaire before undergoing stent implantation and were followed up for 5 years. Results In a Cox regression model adjusted for selected confounders, we found a trend towards NA for the prediction of nonfatal major adverse cardiovascular event (MACE, hazard ratio (HR)=1.07, 95 % confidence intervals (CIs)=0.99−1.14, p=0.074), while, in contrast, SI was a significant and independent predictor of better outcome (HR=0.92, 95 % CI= 0.86−0.99, p=0.027). Conclusions In a cohort of CAD patients, the type D pattern was not linked to adverse outcome, whereas SI was negatively associated with MACE. Keywords Coronary heart disease . Negative affectivity . Prognosis . Social inhibition . Type D personality T. Meyer : S. Hussein : C. Herrmann-Lingen Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany H. W. Lange Practice for Cardiology, Heart Center Bremen, Bremen, Germany C. Herrmann-Lingen (*) Psychosomatic Medicine and Psychotherapy, University of Göttingen Medical Centre and German Centre for Cardiovascular Research, von-Siebold-Str. 5, 37075 Göttingen, Germany e-mail: [email protected]
Introduction In addition to standard risk factors including depression, acute and chronic emotional distress has been linked to adverse outcomes in patients with coronary artery disease (CAD) [1]. Previous studies identified personality traits such as hostility and anger proneness as major determinants of chronic stress, which conversely appeared to precipitate cardiac events in high-risk individuals [2]. In the mid-1990s, in search of personality traits identifying psychologically vulnerable patients at increased risk of cardiovascular complications, Denollet and colleagues introduced the concept of the “distressed,” or type D, personality which, by definition, referred to a propensity to experience psychological distress characterized by chronic negative emotions and an inhibition of selfexpression in social interactions [3]. Subjects who scored high on this trait tended to feel inhibited and reticent with others and frequently reported adverse feelings, such as dysphoria, anxiety, tension, and irritability [4]. The results of a series of clinical studies, most of which were published by the Dutch-Belgian study group around Denollet, reported on the specificity and reliability of this personality construct to predict mortality and other clinical events in CAD patients, even after adjusting for somatic disease severity and symptoms of depression [5–12]. The authors reported that type D personality is an independent predictor of adverse events, including cardiac death, myocardial infarction, and the need for cardiac revascularization. Clinical evidence was presented, suggesting that the type D pattern exerted adverse effects on a patient’s perceived health status following myocardial infarction [3, 13], heart failure [14], and coronary artery bypass surgery [15]. Furthermore, type D was reported to predict the occurrence of lifethreatening arrhythmias following implantable cardioverter defibrillator (ICD) treatment [16] and, moreover, increased
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mortality in ICD patients independent of the frequency of shock delivery [17]. In addition, type D has also been regarded as a vulnerability factor for distress in the general population [18]. The potentially deleterious effects of type D were claimed to result from higher levels of cortisol or a larger cortisol awakening response [19, 20], excessive sympathetic activity [21], increased oxidative stress burden [22], and a dysfunctional pro- versus anti-inflammatory cytokine balance [23, 24]. However, recent studies in cardiovascular patients with different diseases have failed to reproduce the positive link between type D and adverse cardiovascular outcomes, thus raising doubts as to the value of the type D construct as a prognostic indicator [25–29]. Given these controversial results, assessment of the prognostic relevance of type D in cardiovascular patients deserves further attention and requires additional clinical studies by independent investigators and in larger samples [30, 31]. In this prospective study, we examined the prognostic validity of the type D construct in a cohort of consecutive CAD patients referred for coronary stenting.
was carried out in accordance with the Helsinki Declaration and approved by the local ethics committees of the Bremen State Medical Association and the University of Göttingen. Psychometric Assessment Before undergoing PCI, patients were asked to complete the Type D Scale (DS14). This instrument is a measure of negative affectivity (NA) and social inhibition (SI) with seven fivepoint Likert-scaled items ranging from 0=false to 4=true for each subscale and is regarded as the current standard for identifying the type D pattern [4]. The NA items cover feelings of dysphoria, worries, and irritability, while the seven SI items ask about discomfort in social interactions, reticence, and social poise. In line with previous research, a cutoff of 10 on both self-rated subscales was used to classify subjects as type D (i.e., NA of ≥10, SI of ≥10). The psychometric properties of the German DS14 include high internal consistency (Cronbach’s α>0.86) and adequate construct validity and can be considered equivalent to the Dutch version [33, 34]. Follow-up
Methods Participants and Procedures Consecutive patients aged 18 years or older who had undergone elective coronary stenting at a referral center for interventional cardiology in Bremen, Germany, in cooperation with the university teaching hospital “Links der Weser” were enrolled in this study [32]. Recruitment of patients took place from November 2004 to June 2006. All eligible patients complained of symptoms of angina pectoris and/or had abnormal stress test results suggestive of a diagnosis of CAD. Patients with ST-segment elevation myocardial infarction or hemodynamic instability due to critically impaired left ventricular function were excluded from the study. Additional exclusion criteria were severe somatic and mental comorbidity, such as end-stage renal or heart failure, known major depression, or somatization disorder, as well as insufficient knowledge of the German language. Coronary stenting was performed using standard techniques, and after sheath removal, the patients were placed on platelet inhibitor therapy. Baseline demographic and clinical data including cardiovascular risk factors such as hypertension, obesity, smoking status, diabetes mellitus, and hypercholesterolemia were obtained from patients’ medical records. Details from the percutaneous coronary intervention (PCI) procedure such as target vessel, localization, and morphology of luminal narrowing, single versus multivessel disease, as well as size and type of the intracoronary stent (bare-metal versus drug-eluting stent) were documented. All participants provided written informed consent before index PCI was performed. The study protocol
Following index PCI, study participants received routine medical care provided by their general practitioners and/or cardiologists. For assessment of post-procedural survival and major adverse cardiovascular events during 5-year follow-up, patients were contacted by letter, and in the case of information not being received within 4 weeks of mailing, the patients or their physicians were contacted by telephone to complete the follow-up data. In addition, hospital medical records were reviewed for data on major adverse cardiovascular events (MACEs) and death. Primary outcome measures were allcause mortality and MACEs, defined as nonfatal myocardial infarction or stroke. Statistical Analyses All statistical analyses were calculated on a personal computer using SPSS 19.0 for Windows (SPSS, Inc., Chicago, IL, USA). Demographic and clinical data are presented as means±standard deviations or frequencies and percentages. Continuous variables were compared by Student’s t tests, while categorical variables were tested by χ2 tests. Pearson’s χ2 tests and odds ratios were calculated to assess differences in primary outcome measures between the two groups of type D versus non-type D subjects. The Kaplan-Meier method and log-rank tests were used to compare the cumulative incidence of adverse events separately for deaths and MACEs. In addition, Cox regression analyses were performed to evaluate whether type D is an independent predictor of all-cause death or MACE. Using a simultaneous enter approach, we created a first series of models adjusting for sex, age, body mass index,
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smoking status, history of coronary artery bypass graft surgery, and type D. These variables were chosen because of their known epidemiological significance as cardiac risk factors. In a second series of Cox regression models with time to death or MACE as dependent variables, we included the same set of independent variables, except that the separate continuous NA and SI raw data were substituted for the categorized type D variable. These models were computed with and without the interaction term between NA and SI. The results from these calculations are reported as adjusted hazard ratios with their associated 95 % confidence intervals (CIs). In all tests, a p value of ≤0.05 was regarded as statistically significant.
Results Characteristics of Type D and Non-type D Patients at Baseline From a total of 470 PCI patients enrolled in this study, complete baseline data were available in 465 study participants (98.9 %). The majority of study participants (n=321, 69.0 %) were classified as non-type D, while n=144 patients were categorized as type D. Patients with positive type D scores were significantly younger than their non-type D counterparts (61.9±10.9 versus 64.3±9.2 years, p=0.005). In addition, the type D patients differed significantly from the non-type D patients with respect to smoking habits (27.1 % in the type D group as compared to 19 % in the non-type D group, p= 0.02) and their higher prevalence of hypercholesterolemia (76.4 versus 63.9 %, p=0.036). No significant differences Table 1 Baseline characteristics of the study cohort of patients undergoing percutaneous coronary intervention for CAD stratified according to type D personality
Frequencies (in percent) or means and standard deviations of the indicated variables are shown as well as the corresponding p values for the differences between the two groups MACE major adverse cardiovascular event, PCI percutaneous coronary intervention a
Revascularization was defined as PCI and/or aortocoronary bypass graft surgery during follow-up
were found between the two groups with respect to other cardiovascular risk factors or procedural variables related to PCI, as shown in Table 1. Type D Personality Does Not Predict Survival After Intracoronary Stenting In the total study cohort with complete baseline and follow-up data, there were 42 deaths during follow-up. Twelve out of 144 type D patients (8.3 %) and 30 out of 321 (9.3 %) nontype D patients died within the first 5 years after index PCI. This difference in mortality did not reach a statistical significance (p=0.861). The Kaplan-Meier plot shown in Fig. 1a documents the cumulative risk of death in the two groups. In a Cox regression model adjusted for selected confounders (p= 0.001), we found that age (hazard ratio (HR)=1.05, 95 % CI= 1.01−1.09, p=0.005), smoking (HR=2.31, 95 % CI=1.14 −4.70, p=0.020), and body mass index (HR=0.92, 95 % CI=0.84−1.00, p=0.050) were all predictive of increased mortality, whereas type D personality was not (p=0.547). Evidence Against Type D as a Prognostic Marker for Nonfatal MACEs In the total study cohort, nonfatal MACEs were documented in 31 subjects (6.7 %), including 20 patients (4.3 %) with nonfatal myocardial infarction and 13 patients (2.8 %) with a stroke. In the non-type D group, the percentage of individuals with MACE was 6.9 % (n=22) as compared to 6.3 % in type D patients (n=9, p=0.841). The corresponding Kaplan-Meier plot (Fig. 1b) and log-rank test confirmed that there was no
Type D personality, (n=144)
Non-type D personality (n=321)
p value
Sex (male), n (%) Age (years) Body mass index Hypercholesterolemia, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Smoking, n (%) History of bypass surgery, n (%) History of myocardial infarction, n (%) Positive family history, n (%)
103 (71.5) 61.9±10.9 28.4±4.5 110 (76.4) 116 (80.6) 34 (23.6) 39 (27.1) 21 (14.6) 38 (26.4) 63 (43.8)
253 (78.8) 64.3±9.2 27.8±3.6 205 (63.9) 261 (81.3) 75 (23.4) 61 (19) 35 (10.9) 85 (26.5) 117 (36.4)
0.106 0.005 0.141 0.036 0.413 0.692 0.020 0.459 0.795 0.250
Multivessel disease, n (%) Proximal stent localization, n (%) Drug-eluting stent, n (%) Mortality, n (%) MACE, n (%) Revascularizationa, n (%)
74 (51.4) 63 (43.8) 18 (12.5) 12 (8.3) 9 (6.3)
164 (51.1) 120 (37.4) 54 (16.8) 30 (9.3) 22 (6.9)
0.439 0.287 0.714 0.861 0.841
28 (19.4)
58 (18.1)
0.936
ann. behav. med. Fig. 1 Five-year cumulative risk of death (a) and nonfatal major adverse cardiac events (MACE, b−d) in CAD patients by type D personality (a, b) and each of its two constituent components NA (c) and SI (d), respectively. Eventfree survival rates are presented for patients classified either as type D (black lines) versus nontype D (gray lines) or elevated (black lines) versus normal (gray lines) scores on the DS14 NA and SI subscales (≥10), respectively
significant difference between type D and non-type D patients (p=0.819). Cox regression analysis, with time to first MACE as dependent variable, corroborated the notion that type D does not independently predict nonfatal MACE. Furthermore, the entire model did not reach a statistical significance (p=0.145). Social Inhibition and Negative Affectivity as Predictors of Outcome Given that type D failed to predict MACE in PCI patients, we next tested the impact of its two components, SI and NA, on a 5-year follow-up. To this end, we calculated the corresponding Kaplan-Meier curves (Fig. 1c, d) and, furthermore, computed Cox regression models including the continuous raw data on the NA and SI subscales, together with their interaction term, in addition to other covariates as predictors of outcomes. For time to death as dependent variable, both DS14 subscales and their interaction term failed to predict mortality (p≥0.70), while the whole model was significant (p=0.011, Table 2). Notably, for time to first nonfatal MACE as dependent variable, the constituent component SI emerged as a significant and independent predictor for survival (HR=0.86, 95 % CI=
0.75−1.00, p=0.048). However, neither NA (p=0.749) nor its interaction term with SI (p=0.287) was linked to outcome (Table 3). Since we found no effects of the interaction term on either death or MACE rates, we computed additional Cox models by omitting this interaction term. For time to death, no changes to the model could be found (data not shown). However, we observed a trend towards a higher frequency of MACE in patients with elevated NA scores (HR=1.07, 95 % CI=0.99 −1.14, p=0.074), while, in contrast, SI remained significantly related to better outcome (HR=0.92, 95 % CI=0.86−0.99, p= 0.027) (Table 4). Adjusting the Cox models for additional baseline confounders did not result in any major changes to the presented models. In particular, none of the models suggested an adverse prognostic effect of type D or the NA × SI interaction.
Discussion Using the DS14 questionnaire, we assessed the putative significance of the type D construct in predicating long-term outcome in a large sample of PCI-treated CAD patients but
ann. behav. med. Table 2 Results from a Cox regression model in a cohort of patients undergoing percutaneous coronary intervention for CAD with time to death as dependent variable and the indicated independent variables including hazard ratios, 95 % confidence intervals (CI), and the corresponding p values Whole model (p=0.011)
Hazard ratio
95 % CI
p values
Sex (male)
0.81
0.37−1.80
0.608
Age (years) Smoking Body mass index History of bypass surgery DS14 NA DS14 SI DS14 NA × DS14 SI
1.05 2.07 0.91 2.03 0.99 0.99 1.00
1.01−1.09 0.99−4.33 0.83−1.00 0.93−4.43 0.89−1.11 0.88−1.10 0.99−1.0
0.010 0.053 0.047 0.076 0.874 0.812 0.743
DS14 NA and DS14 SI indicate an elevated score on the negative affectivity or social inhibition subscale of the Type D Scale 14-item questionnaire including their interaction term (DS14 NA × DS14 SI) DS14 Type D Scale
failed to find evidence for its predictive value. All-cause mortality and prevalence of nonfatal MACEs were similar in the group of patients categorized as non-type D and their type D counterparts. In the light of the existing literature, our study adds to a currently growing list of publications reporting null effects for the prognostic impact of the DS14 questionnaire and thus raises doubts about the conceptualization of the underlying psychological construct as a valid cardiac risk factor. In our clinical study, we attempted to predict 42 deaths and 31 MACEs experienced in 71 subjects among the total study population of 465 CAD patients and found no association between type D personality and adverse outcome, neither in univariate nor multivariate analyses. This finding is particularly remarkable since the frequencies of two most important cardiovascular risk factors, namely, smoking and hypercholesterolemia, were significantly higher in the type D group Table 3 Cox regression model with time to MACE as dependent variable and the indicated independent variables including negative affectivity (NA), social inhibition (SI), and their interaction term (NA × SI) on the Type D Scale (DS14) questionnaire Whole model (p=0.050)
Hazard ratio
95 % CI
p values
Sex (male) Age (years) Smoking Body mass index
0.98 1.03 2.72 1.04
0.43−2.24 0.99−1.07 1.15−6.42 0.96−1.14
0.961 0.144 0.022 0.329
History of bypass surgery DS14 NA DS14 SI DS14 NA × DS14 SI
2.72 1.02 0.86 1.00
1.12−6.61 0.91−1.13 0.75−1.00 0.99−1.01
0.027 0.749 0.048 0.287
Table 4 Cox regression model with time to nonfatal MACE as dependent variable and the indicated independent variables Whole model (p=0.044)
Hazard ratio
95 % CI
p values
Sex (male) Age (years) Smoking Body mass index
1.03 1.03 2.72 1.05
0.45−2.34 0.99−1.08 1.16−6.39 0.96−1.14
0.942 0.146 0.021 0.325
History of bypass surgery DS14 NAa DS14 SIb
2.82 1.07 0.92
1.16−6.84 0.99−1.14 0.86−0.99
0.022 0.074 0.027
a Elevated score on the NA subscale of the Type D Scale 14-item questionnaire b
Elevated score on the SI subscale
DS14 Type D Scale, NA negative affectivity, SI social inhibition
as compared to the non-type-D patients. Regardless of the positive association of smoking and history of myocardial infarction in the group of patients with type D, we found no indication of adverse effects of type D categorization on long-term survival. In our sample, we observed that participants classified as type D were significantly younger than non-type D subjects which, of course, might influence survival and prevalence of cardiovascular complications. The higher percentage of type D personality traits in younger samples was also found in a large population-based survey of 5,000 Germans aged 35 to 74 years [18]. Since in late adulthood, the frequency of type D appears to decrease in both sexes, the initial assumption of a stable trait over time is not substantiated. The observation that, in our study population, wellestablished risk factors were positively associated with cardiovascular outcome, but not type D personality, and deleterious complications rather occurred more often, albeit not significantly, in type D patients suggests that results from a larger sample would probably not differ. Our negative result can, therefore, not simply be explained by insufficient statistical power. If anything, increasing the number of patients could yield a positive association between type D and a favorable prognosis. In line with our data, the Tilburg group has recently reported on the lack of a prognostic impact of type D in a cohort of 1,234 consecutive PCI patients enrolled in the RapamycinEluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry [29]. Although depression was independently associated with a 1.6-fold increased risk of 7-year mortality after adjusting for type D personality, the authors found no direct link between type D personality and all-cause mortality. Confirming these data, we additionally demonstrate here that there is also no evidence for a prognostic value of type D in predicting nonfatal events (either stroke, myocardial
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infarction, or the combination of both). Similar results for mortality were obtained in two recently published studies in 641 and 111 heart failure patients [25, 28] as well as in a heterogeneous sample of 1,040 cardiac patients recruited from different acute care and cardiac rehabilitation centers [27]. In a recently published meta-analysis based on prospective type D studies with hard endpoints, Grande and colleagues suggested that this personality construct affects prognosis only in CAD patients, but not in patients with chronic heart failure [35]. However, in the light of our data and the study by Damen and co-workers, even this conclusion appears questionable [29]. In an attempt to generate hypotheses regarding mechanisms behind this negative finding, we substituted the separate NA and SI scores for the type D classification in our Cox regression models. Using this approach, we unexpectedly observed a significant negative association between the occurrence of nonfatal MACEs and SI. While there were fewer MACEs in subjects with higher scores on the SI subscale, we observed a trend towards adverse outcome in patients with elevated NA scores. Hence, an additional finding of our study is that in CAD patients, prognostic effects of NA and SI were opposite to each other. This observation sheds light on the failure of type D to predict prognosis, as the two constituent components may elicit, at least in part, antagonistic effects on the frequency of MACE. Thus, it will be interesting to test the hypotheses that the psychological construct of negative affectivity may just be a proxy for depression in predicting adverse outcome [31], while the protective effect of social inhibition is mediated by introversion (or low extraversion), which, in some studies, has been reported as being negatively correlated with depression [36–38]. However, from our current data, we can neither establish that NA and depression are redundant to some extent nor do we have evidence that SI effects are linked to higher levels of introversion. In PCI patients, the Denollet group reported a modulating effect of SI on NA for the prediction of adverse outcome [9, 39]. To demonstrate the impact of SI on cardiac prognosis, the authors had to create a personality type that differed from type D in which patients were required to score ≥10 on both subscales. For this purpose, patients were coded as “1” if they scored ≥10 on NA and ≤9 on SI and “0” if they scored ≤9 on both subscales [9]. Using these criteria, we were also unable to demonstrate any additional value of the type 1 classification for predicting adverse outcome in our cohort (data not shown). However, in line with our data, Schmidt and colleagues recently demonstrated in Brazilian PCI patients that 1-year MACEs were significantly associated with negative affectivity at baseline, but not with other psychological characteristics studied [40]. Our study has several limitations that should be mentioned. First, according to the design of our study, we present only observational data, and therefore, any causal conclusion might be inadequate. Second, since there is no central registry in
Germany and cause-specific mortality was only available for some of the deceased patients, we are unable to distinguish between cardiac and non-cardiac deaths. In our study cohort, the number of nonfatal MACEs as compared to deaths was relatively low. Furthermore, the lack of control for depression is a potential limitation, inasmuch as effects of negative affectivity may not be entirely different from depression. However, our study also has several strengths, which lie mainly in the nearly complete coverage of objective cardiac health outcomes and the inclusion of a relatively large and clinically well-characterized sample. In conclusion, our study demonstrates that the DS14-based categorization of type D does not allow a prediction of adverse outcome in CAD patients. Despite a significantly higher rate of established cardiovascular risk factors such as smoking and history of myocardial infarction in type D patients as compared to non-type D subjects, neither mortality nor frequency of nonfatal MACEs significantly differed between the two groups. However, we found that NA and SI may elicit antagonistic effects on MACE, since elevated SI scores, but not NA scores, were linked to better outcome. Thus, the failure to predict fatal and nonfatal cardiovascular risks by means of the DS14 questionnaire in a typical sample of CAD patients may result from possibly antagonistic effects of its two constituent components NA and SI on long-term outcome. Acknowledgments The authors particularly thank Dr. Mohammad N. Pasalary, Bremen, for his expert assistance in data acquisition. Authors’ Statement of Conflict of Interest and Adherence to Ethical Standards Authors Meyer, Hussein, Lange, and Herrmann‐Lingen declare that they have no conflict of interest. All procedures, including the informed consent process, were conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.
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necrosis factor (TNF)-α and TNF-α receptors in chronic heart failure. Int J Cardiol. 2006; 113: 34-38. Denollet J, Schiffer AA, Kwaijtaal M, et al. Usefulness of Type D personality and kidney dysfunction as predictors of interpatient variability in inflammatory activation in chronic heart failure. Am J Cardiol. 2009; 103: 399-404. Pelle AJ, Pedersen SS, Schiffer AA, Szabó BM, Widdershoven JW, Denollet J. Psychological distress and mortality in systolic heart failure. Circ Heart Fail. 2010; 3: 261-267. Coyne JC, Jaarsma T, Luttik ML, van Sonderen E, van Veldhuisen DJ, Sanderman R. Lack of prognostic value of Type D personality for mortality in a large sample of heart failure patients. Psychosom Med. 2011; 73: 557-562. Grande G, Romppel M, Vesper JM, Schubmann R, Glaesmer H, Herrmann-Lingen C. Type D personality and all-cause mortality in cardiac patients. Data from a German cohort study. Psychosom Med. 2011; 73: 548-556. Volz A, Schmid JP, Zwahlen M, Kohls S, Saner H, Barth J. Predictors of readmission and health related quality of life in patients with chronic heart failure: a comparison of different psychosocial aspects. J Behav Med. 2011; 34: 13-22. Damen NL, Versteeg H, Boersma E, et al. Depression is independently associated with 7-year mortality in patients treated with percutaneous coronary intervention: Results from the RESEARCH registry. Int J Cardiol. 2013; 167: 2496-2501. Smith TW. Toward a more systematic, cumulative, and applicable science of personality and health: lessons from type D personality. Psychosom Med. 2011; 73: 528-532. Coyne JC, de Voogd JN. Are we witnessing the decline effect in the Type D personality literature? What can be learned? J Psychosom Res. 2012; 73: 401-407. Meyer T, Hussein S, Lange HW, Herrmann-Lingen C. Anxiety is associated with a reduction in both mortality and major adverse cardiovascular events five years after coronary stenting. Eur J Prev Cardiol. 2013; 61: 9307-9315. Grande G, Jordan J, Kümmel M, et al. Evaluation of the German Type D Scale (DS14) and prevalence of the Type D personality pattern in cardiological and psychosomatic patients and healthy subjects. Psychother Psychosom Med Psychol. 2004; 54: 413-422. Emons WH, Meijer RR, Denollet J. Negative affectivity and social inhibition in cardiovascular disease: evaluating type-D personality and its assessment using item response theory. J Psychosom Res. 2007; 63: 27-39. Grande G, Romppel M, Barth J. Association between type D personality and prognosis in patients with cardiovascular diseases: a systematic review and meta-analysis. Ann Behav Med. 2012; 43: 299310. Farmer A, Redman K, Harris T, et al. Neuroticism, extraversion, life events and depression. The Cardiff Depression Study. Br J Psychiatry. 2002; 181: 118-122. Cox BJ, McWilliams LA, Enns MW, Clara IP. Broad and specific personality dimensions associated with major depression in a nationally representative sample. Compr Psychiatry. 2004; 45: 246-253. Jylhä P, Melartin T, Isometsä E. Relationships of neuroticism and extraversion with axis I and II comorbidity among patients with DSM-IV major depressive disorder. J Affect Disord. 2009; 114: 110-121. Kupper N, Denollet J. Type D personality as a prognostic factor in heart disease: assessment and mediating mechanisms. J Pers Assess. 2007; 89: 265-276. Schmidt MM, Quadros AS, Abelin AP, et al. Psychological characteristics of patients undergoing percutaneous coronary interventions. Arq Bras Cardiol. 2011; 97: 331-337.
ORIGINAL ARTICLE
Type D Personality is Unrelated to Major Adverse Cardiovascular Events in Patients with Coronary Artery Disease Treated by Intracoronary Stenting Thomas Meyer, Ph.D., M.D. & Sharif Hussein, M.S. & Helmut W. Lange, M.D. & Christoph Herrmann-Lingen, M.D.
# The Society of Behavioral Medicine 2014
Abstract Background Previous research in cardiac patients suggested that type D personality, defined as a combination of negative affectivity (NA) and social inhibition (SI), was associated with adverse outcome. Purpose The objective of this prospective study was to examine the independent prognostic value of type D in patients with coronary artery disease (CAD). Methods A total of 465 patients completed the Type D Scale (DS14) questionnaire before undergoing stent implantation and were followed up for 5 years. Results In a Cox regression model adjusted for selected confounders, we found a trend towards NA for the prediction of nonfatal major adverse cardiovascular event (MACE, hazard ratio (HR)=1.07, 95 % confidence intervals (CIs)=0.99−1.14, p=0.074), while, in contrast, SI was a significant and independent predictor of better outcome (HR=0.92, 95 % CI= 0.86−0.99, p=0.027). Conclusions In a cohort of CAD patients, the type D pattern was not linked to adverse outcome, whereas SI was negatively associated with MACE. Keywords Coronary heart disease . Negative affectivity . Prognosis . Social inhibition . Type D personality T. Meyer : S. Hussein : C. Herrmann-Lingen Department of Psychosomatic Medicine and Psychotherapy, University of Göttingen, Göttingen, Germany H. W. Lange Practice for Cardiology, Heart Center Bremen, Bremen, Germany C. Herrmann-Lingen (*) Psychosomatic Medicine and Psychotherapy, University of Göttingen Medical Centre and German Centre for Cardiovascular Research, von-Siebold-Str. 5, 37075 Göttingen, Germany e-mail: [email protected]
Introduction In addition to standard risk factors including depression, acute and chronic emotional distress has been linked to adverse outcomes in patients with coronary artery disease (CAD) [1]. Previous studies identified personality traits such as hostility and anger proneness as major determinants of chronic stress, which conversely appeared to precipitate cardiac events in high-risk individuals [2]. In the mid-1990s, in search of personality traits identifying psychologically vulnerable patients at increased risk of cardiovascular complications, Denollet and colleagues introduced the concept of the “distressed,” or type D, personality which, by definition, referred to a propensity to experience psychological distress characterized by chronic negative emotions and an inhibition of selfexpression in social interactions [3]. Subjects who scored high on this trait tended to feel inhibited and reticent with others and frequently reported adverse feelings, such as dysphoria, anxiety, tension, and irritability [4]. The results of a series of clinical studies, most of which were published by the Dutch-Belgian study group around Denollet, reported on the specificity and reliability of this personality construct to predict mortality and other clinical events in CAD patients, even after adjusting for somatic disease severity and symptoms of depression [5–12]. The authors reported that type D personality is an independent predictor of adverse events, including cardiac death, myocardial infarction, and the need for cardiac revascularization. Clinical evidence was presented, suggesting that the type D pattern exerted adverse effects on a patient’s perceived health status following myocardial infarction [3, 13], heart failure [14], and coronary artery bypass surgery [15]. Furthermore, type D was reported to predict the occurrence of lifethreatening arrhythmias following implantable cardioverter defibrillator (ICD) treatment [16] and, moreover, increased
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mortality in ICD patients independent of the frequency of shock delivery [17]. In addition, type D has also been regarded as a vulnerability factor for distress in the general population [18]. The potentially deleterious effects of type D were claimed to result from higher levels of cortisol or a larger cortisol awakening response [19, 20], excessive sympathetic activity [21], increased oxidative stress burden [22], and a dysfunctional pro- versus anti-inflammatory cytokine balance [23, 24]. However, recent studies in cardiovascular patients with different diseases have failed to reproduce the positive link between type D and adverse cardiovascular outcomes, thus raising doubts as to the value of the type D construct as a prognostic indicator [25–29]. Given these controversial results, assessment of the prognostic relevance of type D in cardiovascular patients deserves further attention and requires additional clinical studies by independent investigators and in larger samples [30, 31]. In this prospective study, we examined the prognostic validity of the type D construct in a cohort of consecutive CAD patients referred for coronary stenting.
was carried out in accordance with the Helsinki Declaration and approved by the local ethics committees of the Bremen State Medical Association and the University of Göttingen. Psychometric Assessment Before undergoing PCI, patients were asked to complete the Type D Scale (DS14). This instrument is a measure of negative affectivity (NA) and social inhibition (SI) with seven fivepoint Likert-scaled items ranging from 0=false to 4=true for each subscale and is regarded as the current standard for identifying the type D pattern [4]. The NA items cover feelings of dysphoria, worries, and irritability, while the seven SI items ask about discomfort in social interactions, reticence, and social poise. In line with previous research, a cutoff of 10 on both self-rated subscales was used to classify subjects as type D (i.e., NA of ≥10, SI of ≥10). The psychometric properties of the German DS14 include high internal consistency (Cronbach’s α>0.86) and adequate construct validity and can be considered equivalent to the Dutch version [33, 34]. Follow-up
Methods Participants and Procedures Consecutive patients aged 18 years or older who had undergone elective coronary stenting at a referral center for interventional cardiology in Bremen, Germany, in cooperation with the university teaching hospital “Links der Weser” were enrolled in this study [32]. Recruitment of patients took place from November 2004 to June 2006. All eligible patients complained of symptoms of angina pectoris and/or had abnormal stress test results suggestive of a diagnosis of CAD. Patients with ST-segment elevation myocardial infarction or hemodynamic instability due to critically impaired left ventricular function were excluded from the study. Additional exclusion criteria were severe somatic and mental comorbidity, such as end-stage renal or heart failure, known major depression, or somatization disorder, as well as insufficient knowledge of the German language. Coronary stenting was performed using standard techniques, and after sheath removal, the patients were placed on platelet inhibitor therapy. Baseline demographic and clinical data including cardiovascular risk factors such as hypertension, obesity, smoking status, diabetes mellitus, and hypercholesterolemia were obtained from patients’ medical records. Details from the percutaneous coronary intervention (PCI) procedure such as target vessel, localization, and morphology of luminal narrowing, single versus multivessel disease, as well as size and type of the intracoronary stent (bare-metal versus drug-eluting stent) were documented. All participants provided written informed consent before index PCI was performed. The study protocol
Following index PCI, study participants received routine medical care provided by their general practitioners and/or cardiologists. For assessment of post-procedural survival and major adverse cardiovascular events during 5-year follow-up, patients were contacted by letter, and in the case of information not being received within 4 weeks of mailing, the patients or their physicians were contacted by telephone to complete the follow-up data. In addition, hospital medical records were reviewed for data on major adverse cardiovascular events (MACEs) and death. Primary outcome measures were allcause mortality and MACEs, defined as nonfatal myocardial infarction or stroke. Statistical Analyses All statistical analyses were calculated on a personal computer using SPSS 19.0 for Windows (SPSS, Inc., Chicago, IL, USA). Demographic and clinical data are presented as means±standard deviations or frequencies and percentages. Continuous variables were compared by Student’s t tests, while categorical variables were tested by χ2 tests. Pearson’s χ2 tests and odds ratios were calculated to assess differences in primary outcome measures between the two groups of type D versus non-type D subjects. The Kaplan-Meier method and log-rank tests were used to compare the cumulative incidence of adverse events separately for deaths and MACEs. In addition, Cox regression analyses were performed to evaluate whether type D is an independent predictor of all-cause death or MACE. Using a simultaneous enter approach, we created a first series of models adjusting for sex, age, body mass index,
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smoking status, history of coronary artery bypass graft surgery, and type D. These variables were chosen because of their known epidemiological significance as cardiac risk factors. In a second series of Cox regression models with time to death or MACE as dependent variables, we included the same set of independent variables, except that the separate continuous NA and SI raw data were substituted for the categorized type D variable. These models were computed with and without the interaction term between NA and SI. The results from these calculations are reported as adjusted hazard ratios with their associated 95 % confidence intervals (CIs). In all tests, a p value of ≤0.05 was regarded as statistically significant.
Results Characteristics of Type D and Non-type D Patients at Baseline From a total of 470 PCI patients enrolled in this study, complete baseline data were available in 465 study participants (98.9 %). The majority of study participants (n=321, 69.0 %) were classified as non-type D, while n=144 patients were categorized as type D. Patients with positive type D scores were significantly younger than their non-type D counterparts (61.9±10.9 versus 64.3±9.2 years, p=0.005). In addition, the type D patients differed significantly from the non-type D patients with respect to smoking habits (27.1 % in the type D group as compared to 19 % in the non-type D group, p= 0.02) and their higher prevalence of hypercholesterolemia (76.4 versus 63.9 %, p=0.036). No significant differences Table 1 Baseline characteristics of the study cohort of patients undergoing percutaneous coronary intervention for CAD stratified according to type D personality
Frequencies (in percent) or means and standard deviations of the indicated variables are shown as well as the corresponding p values for the differences between the two groups MACE major adverse cardiovascular event, PCI percutaneous coronary intervention a
Revascularization was defined as PCI and/or aortocoronary bypass graft surgery during follow-up
were found between the two groups with respect to other cardiovascular risk factors or procedural variables related to PCI, as shown in Table 1. Type D Personality Does Not Predict Survival After Intracoronary Stenting In the total study cohort with complete baseline and follow-up data, there were 42 deaths during follow-up. Twelve out of 144 type D patients (8.3 %) and 30 out of 321 (9.3 %) nontype D patients died within the first 5 years after index PCI. This difference in mortality did not reach a statistical significance (p=0.861). The Kaplan-Meier plot shown in Fig. 1a documents the cumulative risk of death in the two groups. In a Cox regression model adjusted for selected confounders (p= 0.001), we found that age (hazard ratio (HR)=1.05, 95 % CI= 1.01−1.09, p=0.005), smoking (HR=2.31, 95 % CI=1.14 −4.70, p=0.020), and body mass index (HR=0.92, 95 % CI=0.84−1.00, p=0.050) were all predictive of increased mortality, whereas type D personality was not (p=0.547). Evidence Against Type D as a Prognostic Marker for Nonfatal MACEs In the total study cohort, nonfatal MACEs were documented in 31 subjects (6.7 %), including 20 patients (4.3 %) with nonfatal myocardial infarction and 13 patients (2.8 %) with a stroke. In the non-type D group, the percentage of individuals with MACE was 6.9 % (n=22) as compared to 6.3 % in type D patients (n=9, p=0.841). The corresponding Kaplan-Meier plot (Fig. 1b) and log-rank test confirmed that there was no
Type D personality, (n=144)
Non-type D personality (n=321)
p value
Sex (male), n (%) Age (years) Body mass index Hypercholesterolemia, n (%) Hypertension, n (%) Diabetes mellitus, n (%) Smoking, n (%) History of bypass surgery, n (%) History of myocardial infarction, n (%) Positive family history, n (%)
103 (71.5) 61.9±10.9 28.4±4.5 110 (76.4) 116 (80.6) 34 (23.6) 39 (27.1) 21 (14.6) 38 (26.4) 63 (43.8)
253 (78.8) 64.3±9.2 27.8±3.6 205 (63.9) 261 (81.3) 75 (23.4) 61 (19) 35 (10.9) 85 (26.5) 117 (36.4)
0.106 0.005 0.141 0.036 0.413 0.692 0.020 0.459 0.795 0.250
Multivessel disease, n (%) Proximal stent localization, n (%) Drug-eluting stent, n (%) Mortality, n (%) MACE, n (%) Revascularizationa, n (%)
74 (51.4) 63 (43.8) 18 (12.5) 12 (8.3) 9 (6.3)
164 (51.1) 120 (37.4) 54 (16.8) 30 (9.3) 22 (6.9)
0.439 0.287 0.714 0.861 0.841
28 (19.4)
58 (18.1)
0.936
ann. behav. med. Fig. 1 Five-year cumulative risk of death (a) and nonfatal major adverse cardiac events (MACE, b−d) in CAD patients by type D personality (a, b) and each of its two constituent components NA (c) and SI (d), respectively. Eventfree survival rates are presented for patients classified either as type D (black lines) versus nontype D (gray lines) or elevated (black lines) versus normal (gray lines) scores on the DS14 NA and SI subscales (≥10), respectively
significant difference between type D and non-type D patients (p=0.819). Cox regression analysis, with time to first MACE as dependent variable, corroborated the notion that type D does not independently predict nonfatal MACE. Furthermore, the entire model did not reach a statistical significance (p=0.145). Social Inhibition and Negative Affectivity as Predictors of Outcome Given that type D failed to predict MACE in PCI patients, we next tested the impact of its two components, SI and NA, on a 5-year follow-up. To this end, we calculated the corresponding Kaplan-Meier curves (Fig. 1c, d) and, furthermore, computed Cox regression models including the continuous raw data on the NA and SI subscales, together with their interaction term, in addition to other covariates as predictors of outcomes. For time to death as dependent variable, both DS14 subscales and their interaction term failed to predict mortality (p≥0.70), while the whole model was significant (p=0.011, Table 2). Notably, for time to first nonfatal MACE as dependent variable, the constituent component SI emerged as a significant and independent predictor for survival (HR=0.86, 95 % CI=
0.75−1.00, p=0.048). However, neither NA (p=0.749) nor its interaction term with SI (p=0.287) was linked to outcome (Table 3). Since we found no effects of the interaction term on either death or MACE rates, we computed additional Cox models by omitting this interaction term. For time to death, no changes to the model could be found (data not shown). However, we observed a trend towards a higher frequency of MACE in patients with elevated NA scores (HR=1.07, 95 % CI=0.99 −1.14, p=0.074), while, in contrast, SI remained significantly related to better outcome (HR=0.92, 95 % CI=0.86−0.99, p= 0.027) (Table 4). Adjusting the Cox models for additional baseline confounders did not result in any major changes to the presented models. In particular, none of the models suggested an adverse prognostic effect of type D or the NA × SI interaction.
Discussion Using the DS14 questionnaire, we assessed the putative significance of the type D construct in predicating long-term outcome in a large sample of PCI-treated CAD patients but
ann. behav. med. Table 2 Results from a Cox regression model in a cohort of patients undergoing percutaneous coronary intervention for CAD with time to death as dependent variable and the indicated independent variables including hazard ratios, 95 % confidence intervals (CI), and the corresponding p values Whole model (p=0.011)
Hazard ratio
95 % CI
p values
Sex (male)
0.81
0.37−1.80
0.608
Age (years) Smoking Body mass index History of bypass surgery DS14 NA DS14 SI DS14 NA × DS14 SI
1.05 2.07 0.91 2.03 0.99 0.99 1.00
1.01−1.09 0.99−4.33 0.83−1.00 0.93−4.43 0.89−1.11 0.88−1.10 0.99−1.0
0.010 0.053 0.047 0.076 0.874 0.812 0.743
DS14 NA and DS14 SI indicate an elevated score on the negative affectivity or social inhibition subscale of the Type D Scale 14-item questionnaire including their interaction term (DS14 NA × DS14 SI) DS14 Type D Scale
failed to find evidence for its predictive value. All-cause mortality and prevalence of nonfatal MACEs were similar in the group of patients categorized as non-type D and their type D counterparts. In the light of the existing literature, our study adds to a currently growing list of publications reporting null effects for the prognostic impact of the DS14 questionnaire and thus raises doubts about the conceptualization of the underlying psychological construct as a valid cardiac risk factor. In our clinical study, we attempted to predict 42 deaths and 31 MACEs experienced in 71 subjects among the total study population of 465 CAD patients and found no association between type D personality and adverse outcome, neither in univariate nor multivariate analyses. This finding is particularly remarkable since the frequencies of two most important cardiovascular risk factors, namely, smoking and hypercholesterolemia, were significantly higher in the type D group Table 3 Cox regression model with time to MACE as dependent variable and the indicated independent variables including negative affectivity (NA), social inhibition (SI), and their interaction term (NA × SI) on the Type D Scale (DS14) questionnaire Whole model (p=0.050)
Hazard ratio
95 % CI
p values
Sex (male) Age (years) Smoking Body mass index
0.98 1.03 2.72 1.04
0.43−2.24 0.99−1.07 1.15−6.42 0.96−1.14
0.961 0.144 0.022 0.329
History of bypass surgery DS14 NA DS14 SI DS14 NA × DS14 SI
2.72 1.02 0.86 1.00
1.12−6.61 0.91−1.13 0.75−1.00 0.99−1.01
0.027 0.749 0.048 0.287
Table 4 Cox regression model with time to nonfatal MACE as dependent variable and the indicated independent variables Whole model (p=0.044)
Hazard ratio
95 % CI
p values
Sex (male) Age (years) Smoking Body mass index
1.03 1.03 2.72 1.05
0.45−2.34 0.99−1.08 1.16−6.39 0.96−1.14
0.942 0.146 0.021 0.325
History of bypass surgery DS14 NAa DS14 SIb
2.82 1.07 0.92
1.16−6.84 0.99−1.14 0.86−0.99
0.022 0.074 0.027
a Elevated score on the NA subscale of the Type D Scale 14-item questionnaire b
Elevated score on the SI subscale
DS14 Type D Scale, NA negative affectivity, SI social inhibition
as compared to the non-type-D patients. Regardless of the positive association of smoking and history of myocardial infarction in the group of patients with type D, we found no indication of adverse effects of type D categorization on long-term survival. In our sample, we observed that participants classified as type D were significantly younger than non-type D subjects which, of course, might influence survival and prevalence of cardiovascular complications. The higher percentage of type D personality traits in younger samples was also found in a large population-based survey of 5,000 Germans aged 35 to 74 years [18]. Since in late adulthood, the frequency of type D appears to decrease in both sexes, the initial assumption of a stable trait over time is not substantiated. The observation that, in our study population, wellestablished risk factors were positively associated with cardiovascular outcome, but not type D personality, and deleterious complications rather occurred more often, albeit not significantly, in type D patients suggests that results from a larger sample would probably not differ. Our negative result can, therefore, not simply be explained by insufficient statistical power. If anything, increasing the number of patients could yield a positive association between type D and a favorable prognosis. In line with our data, the Tilburg group has recently reported on the lack of a prognostic impact of type D in a cohort of 1,234 consecutive PCI patients enrolled in the RapamycinEluting Stent Evaluated At Rotterdam Cardiology Hospital (RESEARCH) registry [29]. Although depression was independently associated with a 1.6-fold increased risk of 7-year mortality after adjusting for type D personality, the authors found no direct link between type D personality and all-cause mortality. Confirming these data, we additionally demonstrate here that there is also no evidence for a prognostic value of type D in predicting nonfatal events (either stroke, myocardial
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infarction, or the combination of both). Similar results for mortality were obtained in two recently published studies in 641 and 111 heart failure patients [25, 28] as well as in a heterogeneous sample of 1,040 cardiac patients recruited from different acute care and cardiac rehabilitation centers [27]. In a recently published meta-analysis based on prospective type D studies with hard endpoints, Grande and colleagues suggested that this personality construct affects prognosis only in CAD patients, but not in patients with chronic heart failure [35]. However, in the light of our data and the study by Damen and co-workers, even this conclusion appears questionable [29]. In an attempt to generate hypotheses regarding mechanisms behind this negative finding, we substituted the separate NA and SI scores for the type D classification in our Cox regression models. Using this approach, we unexpectedly observed a significant negative association between the occurrence of nonfatal MACEs and SI. While there were fewer MACEs in subjects with higher scores on the SI subscale, we observed a trend towards adverse outcome in patients with elevated NA scores. Hence, an additional finding of our study is that in CAD patients, prognostic effects of NA and SI were opposite to each other. This observation sheds light on the failure of type D to predict prognosis, as the two constituent components may elicit, at least in part, antagonistic effects on the frequency of MACE. Thus, it will be interesting to test the hypotheses that the psychological construct of negative affectivity may just be a proxy for depression in predicting adverse outcome [31], while the protective effect of social inhibition is mediated by introversion (or low extraversion), which, in some studies, has been reported as being negatively correlated with depression [36–38]. However, from our current data, we can neither establish that NA and depression are redundant to some extent nor do we have evidence that SI effects are linked to higher levels of introversion. In PCI patients, the Denollet group reported a modulating effect of SI on NA for the prediction of adverse outcome [9, 39]. To demonstrate the impact of SI on cardiac prognosis, the authors had to create a personality type that differed from type D in which patients were required to score ≥10 on both subscales. For this purpose, patients were coded as “1” if they scored ≥10 on NA and ≤9 on SI and “0” if they scored ≤9 on both subscales [9]. Using these criteria, we were also unable to demonstrate any additional value of the type 1 classification for predicting adverse outcome in our cohort (data not shown). However, in line with our data, Schmidt and colleagues recently demonstrated in Brazilian PCI patients that 1-year MACEs were significantly associated with negative affectivity at baseline, but not with other psychological characteristics studied [40]. Our study has several limitations that should be mentioned. First, according to the design of our study, we present only observational data, and therefore, any causal conclusion might be inadequate. Second, since there is no central registry in
Germany and cause-specific mortality was only available for some of the deceased patients, we are unable to distinguish between cardiac and non-cardiac deaths. In our study cohort, the number of nonfatal MACEs as compared to deaths was relatively low. Furthermore, the lack of control for depression is a potential limitation, inasmuch as effects of negative affectivity may not be entirely different from depression. However, our study also has several strengths, which lie mainly in the nearly complete coverage of objective cardiac health outcomes and the inclusion of a relatively large and clinically well-characterized sample. In conclusion, our study demonstrates that the DS14-based categorization of type D does not allow a prediction of adverse outcome in CAD patients. Despite a significantly higher rate of established cardiovascular risk factors such as smoking and history of myocardial infarction in type D patients as compared to non-type D subjects, neither mortality nor frequency of nonfatal MACEs significantly differed between the two groups. However, we found that NA and SI may elicit antagonistic effects on MACE, since elevated SI scores, but not NA scores, were linked to better outcome. Thus, the failure to predict fatal and nonfatal cardiovascular risks by means of the DS14 questionnaire in a typical sample of CAD patients may result from possibly antagonistic effects of its two constituent components NA and SI on long-term outcome. Acknowledgments The authors particularly thank Dr. Mohammad N. Pasalary, Bremen, for his expert assistance in data acquisition. Authors’ Statement of Conflict of Interest and Adherence to Ethical Standards Authors Meyer, Hussein, Lange, and Herrmann‐Lingen declare that they have no conflict of interest. All procedures, including the informed consent process, were conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000.
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