Viviane M. Conraads, MD, PhD

Depression has been studied extensively in relation to cardiovascular disease.^1–3 In addition to depression, anger⁴ and anxiety⁵ also may promote coronary artery disease (CAD), suggesting that emotional distress in general may be related to increased cardiovascular risk. Evidence indicates that the general distress shared across depression, anger, and anxiety predicts CAD, even after controlling for each of these specific negative emotions.⁶

THE CONCEPT OF TYPE D PERSONALITY

Lately, there is a renewed interest in broad individual differences in general distress and heart disease.⁷ Since psychologic factors often cluster together in individual patients, biobehavioral research may benefit from the identification of discrete personality subtypes.⁸ This focus on the identification of psychologically vulnerable patients who are at increased risk for adverse outcomes has led to the introduction of the distressed⁹ or type D¹⁰ personality profile in cardiovascular research. This personality construct is defined as follows:

“The type D (distressed) personality profile refers to a general propensity to psychological distress that is characterized by the combination of negative affectivity and social inhibition.”¹⁰

Negative affectivity, or the tendency to experience negative emotions across time and situations, is a major determinant of emotional distress in cardiac patients.^9,10 Patients who score high on this trait frequently report feelings of dysphoria, worry, and tension. Social inhibition, or the tendency to inhibit the expression of emotions or behavior, is a major determinant of social distress.^9,10 Patients who score high on this trait tend to avoid negative reactions from others.

Both traits define psychologically vulnerable patients and can be assessed with the type D scale (DS14).¹⁰ This brief measure consists of a seven-item negative affectivity subscale (eg, I often feel unhappy) and a seven-item inhibition subscale (eg, I am inhibited in social interactions), and has a clear two-factor structure and good reliability (Cronbach’s α = .88 and .86). Patients are classified as type D if they score 10 or higher on both DS14 subscales.¹⁰ The prevalence of type D personality ranges between 20% and 40% across different types of cardiovascular conditions.

The type D construct was designed for the early identification of chronically distressed patients. This article reviews (1) the risk of adverse events associated with type D, (2) the extent to which type D is distinct from depression, (3) the biologic pathways of type D, and (4) the implications of the type D personality profile.

RISK ASSOCIATED WITH TYPE D

Several prospective studies from our group have examined the notion that type D patients are particularly vulnerable to adverse events (Table 1). In patients with CAD, evidence indicates that type D personality is an independent predictor of adverse events, including (cardiac) death, myocardial infarction, and need for revascularization procedures.^11–16 In these studies, type D also emerged as an independent predictor of adverse events after adjustment for anxiety,¹¹ stress,¹³ depression,¹⁶ disease severity,^11–16 and type of invasive treatment.¹⁴ This increased risk associated with the type D profile was observed in the broader group of patients with CAD,^11–15 as well as in patients who survived an initial myocardial infarction.¹⁶

The relationship between type D personality and adverse events has also been investigated in other cardiovascular conditions. Type D has been associated with poor prognosis in patients with peripheral arterial disease,¹⁷ but evidence for the prognostic role of type D in patients with chronic heart failure is mixed. In a study of patients with heart failure following myocardial infarction, type D predicted cardiac death independent of disease severity¹⁸; in a study of heart failure patients who underwent cardiac transplantation, type D was associated with early allograft rejection and increased mortality.¹⁹ However, type D was not associated with cardiac death in a recent, larger heart failure study.²⁰ The link between psychologic factors and heart failure is complex³ and may be less obvious than the type D-CAD link.²⁰ Type D has also been associated with the occurrence of life-threatening arrhythmias following implantable cardioverter defibrillator (ICD) treatment,²¹ and it has been shown to predict an increased risk for mortality in ICD patients, independent from shocks and disease severity.²²

The wide range in odds ratios and confidence intervals indicates disparity in data across these type D studies (Table 1). We recently performed a metaanalysis of prospective studies between 1996 and 2009 to provide a more reliable estimate of the risk associated with type D. In this analysis, type D was associated with a threefold increased risk of adverse events²³; the confidence interval of this pooled odds ratio ranged from 2.7 to 5.1. In addition, type D personality was associated with a threefold increased risk (range, 2.6 to 4.3) of emotional distress over time.²³ From the recent studies that were not included in this meta-analysis, one reported negative findings²⁰ and three others positive findings^16,21,22 on the risk associated with type D.

COMPARING DEPRESSION AND TYPE D

Many studies report on depression and cardiac disease,^1–3 but both conceptual differences and clinical evidence indicate that type D and depression are distinct forms of distress (Table 2). Conceptually, type D focuses not only on depressive affect but also on the general distress shared across negative emotions,¹⁰ and it is based on the notion that social inhibition modulates the effect of negative emotions on cardiac prognosis.²⁴ While depression refers to an episodic distress factor (patients may go in and out of depressive episodes), the type D construct focuses on an underlying factor that predisposes patients to more chronic forms of distress.⁸

Clinical evidence shows that, after adjustment for depression, type D remained a predictor of adverse cardiac events in CAD.^16,24,25 Following ICD implantation, anxious type D patients were at risk of ventricular arrhythmias, whereas depression did not predict arrhythmias.²¹ Type D also exerts an adverse effect on patients’ health status following coronary bypass surgery,²⁶ heart failure,²⁷ or myocardial infarction,²⁸ adjusting for depressive symptoms. Type D is related to biomarkers of increased stress levels independent of depression^29–31 and, unlike depression, type D is not confounded by the severity of cardiac disorder.³²

Following myocardial infarction, only one of four distressed patients met criteria for both type D and depression; most had one form of distress but not the other.³² Research in healthy³³ and in cardiac³⁴ populations confirmed that items from depression and type D scales reflect different distress factors. After adjustment for depression at baseline, type D also predicted the incidence,³⁵ persistence,³⁶ and severity^37,38 of depression and anxiety. However, these findings do not imply that depression and type D are antonymous perspectives or that one perspective is better than the other in predicting outcomes; rather, we would like to argue that both constructs represent complementary perspectives that have added value.²³

 

BIOLOGIC PATHWAYS OF TYPE D

A number of biologic pathways have been suggested to explain the effect of type D (Table 3). Some have suggested dysregulation of the hypothalamicpituitary-adrenal axis in patients with type D personality.³⁹ In fact, type D has been associated with greater cortisol reactivity to stress in healthy individuals⁴⁰ and with higher awakening³⁰ and daytime³¹ cortisol levels in CAD patients. Autonomic dysregulation can also be inferred in type D individuals on the basis of a higher resting heart rate⁴¹ and cardiovascular hyperreactivity^40,42 and decreased heart rate variability⁴³ in response to stress. In addition, type D has been related to reduced heart rate recovery after exercise in patients with heart failure.⁴⁴ These indices of excessive sympathetic or inadequate parasympathetic modulation of heart rate predict poor cardiac prognoses.⁴⁵

Other studies found that type D was associated with inflammatory dysregulation. In healthy adults, type D has been related to higher concentrations of C-reactive protein.⁴¹ In heart failure patients, type D is associated with increased plasma levels of the proinflammatory cytokine tumor necrosis factor (TNF)-α and its soluble receptors 1 and 2.^46,47 Increased TNF-α levels may cause suppression of bone-marrow–derived endothelial progenitor cells (EPCs) that play an important role in maintaining vascular integrity. The negative affectivity component of type D has been shown to predict decreased circulating EPC counts in healthy individuals⁴⁸; another study found that these EPC numbers were reduced by more than 50% in heart failure patients with a type D personality.⁴⁹ Type D personality is also associated with an increased oxidative stress burden in patients with chronic heart failure.²⁹ Studies on genetic linkage⁵⁰ and heritability⁵¹ further support biologic underpinnings of the type D construct.

Regarding pathways that may explain the effect of type D, some issues are of special interest. First, genetic factors contribute to stability in type D personality, but environmental factors may induce changes in type D characteristics over time.⁵¹ Hence, given this role of environmental influences over time, behavioral intervention would be feasible and useful in type D patients. Second, type D can promote heart disease indirectly through behavioral pathways. Type D has been associated with a sedentary lifestyle,^41,52 an unhealthy diet,⁵³ and a passive coping style.^54,55 Poor adherence to medical treatment^56,57 and reluctance to consult clinical staff⁵⁸ may jeopardize the working relationship with type D patients in clinical care. Intervention may focus on the management of these behavioral risk factors in type D patients. Third, many of these biologic^{40–43,48,50,51} and behavioral^41,52–54 pathways have also been documented in healthy type D individuals, which suggests that these associations cannot be explained away by the confounding effect of underlying cardiovascular disease.

CLINICAL IMPLICATIONS OF TYPE D

The findings from type D research have a number of clinical implications. Type D is associated with an increased risk of adverse events,²³ chronic distress,^35–38 and suicidal ideation.⁵⁹ Type D may also have an adverse effect on the outcome of invasive treatment.^{14,19,21,22,24,26,60}

Type D was associated with mortality and morbidity at 9 months¹⁴ and 2 years²⁴ following coronary artery stenting, and with impaired health status 1 year following bypass surgery.²⁶ Type D also predicted mortality and allograft rejection following heart transplantation,¹⁹ and an increased risk of ventricular arrhythmia²¹ and mortality²² in ICD patients. Researchers from the Cleveland Clinic have shown that type D is a risk factor for anxiety in ICD patients.⁶⁰

Regarding the DSM-IV classification by the American Psychiatric Association,⁶¹ type D qualifies for the diagnosis “psychological factors affecting medical condition” (Section 316). In keeping with this classification, the diagnostic category type D affects (1) the course of cardiovascular conditions,²³ (2) the treatment of these conditions,^56,57 and (3) the working relationship with medical staff.⁵⁸ At present, no clinical trial has examined whether intervention for distress among type D patients alters their risk for adverse events. Nevertheless, some have argued that it is plausible for type D patients to learn new strategies to reduce their level of general distress.⁶² Previous research with patients experiencing symptoms like those of type D patients suggests that psychotherapy, social skills training, stress management, and relaxation training may reduce stress in these patients and improve their ability to express their emotions to others.⁶² Others have suggested that stress management training, including communication skills and problem-solving, may further improve the risk profile and health in cardiac patients.⁶³

It is possible that type D patients may benefit from close monitoring of their clinical condition and from aggressive management of their risk factor profile to prevent adverse clinical events. Cardiac rehabilitation is an effective approach to treating risk factors and enhancing well-being in CAD.^63,64 A few studies have examined the effect of cardiac rehabilitation in type D patients. One study found a significant decrease in the social inhibition component of type D following cardiac rehabilitation, but there was no change in the prevalence of type D at 1-year follow-up.⁶⁵ Although the type D profile tends to remain stable during rehabilitation,^65,66 evidence shows that type D patients who participate in cardiac rehabilitation improve in physical and mental health status.⁶⁶ Cardiac rehabilitation may also ward off further deterioration in negative affect,⁶⁷ which, in turn, has been associated with better survival in patients who participated in rehabilitation.⁶⁸ Future studies need to examine the effect of cardiac rehabilitation and other personalized approaches to treatment in type D patients.

CONCLUSIONS

General distress shared across negative emotions^6,23 may partly account for the role of depression, anxiety, and anger in cardiovascular disorders.^1–5 Some cardiac patients are more likely to experience distress than others. Type D may identify these psychologically vulnerable patients who tend to experience general distress.²³ This propensity to general distress differs from depression, predicts adverse outcomes, is linked to plausible biologic pathways, and highlights the chronic nature of psychologic distress in some cardiac patients.

After adjustment for depression, type D remains significantly associated with an increased risk of adverse events in patients with CAD.^16,24,25 However, this association is less obvious in patients with heart failure, and type D did not predict survival in one heart failure study.²⁰ Although initial findings suggest a number of plausible biologic and behavioral pathways, more research is needed to explain the adverse effect of type D on cardiovascular outcomes. Future research also needs to investigate whether type D patients may benefit from close monitoring of their risk factors and a more personalized approach to behavioral and cardiac treatment.

Overall, the current understanding of type D indicates that general distress should not be ignored in the link between mind and heart, and that cardiovascular patients who have a type D personality profile are particularly vulnerable to the adverse clinical effects of general distress. The DS14¹⁰ is a brief, well-validated measure of type D that could be incorporated into clinical research and practice to identify patients who are at risk of chronic distress and poor prognosis.

Depression has been studied extensively in relation to cardiovascular disease.^1–3 In addition to depression, anger⁴ and anxiety⁵ also may promote coronary artery disease (CAD), suggesting that emotional distress in general may be related to increased cardiovascular risk. Evidence indicates that the general distress shared across depression, anger, and anxiety predicts CAD, even after controlling for each of these specific negative emotions.⁶

THE CONCEPT OF TYPE D PERSONALITY

Lately, there is a renewed interest in broad individual differences in general distress and heart disease.⁷ Since psychologic factors often cluster together in individual patients, biobehavioral research may benefit from the identification of discrete personality subtypes.⁸ This focus on the identification of psychologically vulnerable patients who are at increased risk for adverse outcomes has led to the introduction of the distressed⁹ or type D¹⁰ personality profile in cardiovascular research. This personality construct is defined as follows:

“The type D (distressed) personality profile refers to a general propensity to psychological distress that is characterized by the combination of negative affectivity and social inhibition.”¹⁰

Negative affectivity, or the tendency to experience negative emotions across time and situations, is a major determinant of emotional distress in cardiac patients.^9,10 Patients who score high on this trait frequently report feelings of dysphoria, worry, and tension. Social inhibition, or the tendency to inhibit the expression of emotions or behavior, is a major determinant of social distress.^9,10 Patients who score high on this trait tend to avoid negative reactions from others.

Both traits define psychologically vulnerable patients and can be assessed with the type D scale (DS14).¹⁰ This brief measure consists of a seven-item negative affectivity subscale (eg, I often feel unhappy) and a seven-item inhibition subscale (eg, I am inhibited in social interactions), and has a clear two-factor structure and good reliability (Cronbach’s α = .88 and .86). Patients are classified as type D if they score 10 or higher on both DS14 subscales.¹⁰ The prevalence of type D personality ranges between 20% and 40% across different types of cardiovascular conditions.

The type D construct was designed for the early identification of chronically distressed patients. This article reviews (1) the risk of adverse events associated with type D, (2) the extent to which type D is distinct from depression, (3) the biologic pathways of type D, and (4) the implications of the type D personality profile.

RISK ASSOCIATED WITH TYPE D

Several prospective studies from our group have examined the notion that type D patients are particularly vulnerable to adverse events (Table 1). In patients with CAD, evidence indicates that type D personality is an independent predictor of adverse events, including (cardiac) death, myocardial infarction, and need for revascularization procedures.^11–16 In these studies, type D also emerged as an independent predictor of adverse events after adjustment for anxiety,¹¹ stress,¹³ depression,¹⁶ disease severity,^11–16 and type of invasive treatment.¹⁴ This increased risk associated with the type D profile was observed in the broader group of patients with CAD,^11–15 as well as in patients who survived an initial myocardial infarction.¹⁶

The relationship between type D personality and adverse events has also been investigated in other cardiovascular conditions. Type D has been associated with poor prognosis in patients with peripheral arterial disease,¹⁷ but evidence for the prognostic role of type D in patients with chronic heart failure is mixed. In a study of patients with heart failure following myocardial infarction, type D predicted cardiac death independent of disease severity¹⁸; in a study of heart failure patients who underwent cardiac transplantation, type D was associated with early allograft rejection and increased mortality.¹⁹ However, type D was not associated with cardiac death in a recent, larger heart failure study.²⁰ The link between psychologic factors and heart failure is complex³ and may be less obvious than the type D-CAD link.²⁰ Type D has also been associated with the occurrence of life-threatening arrhythmias following implantable cardioverter defibrillator (ICD) treatment,²¹ and it has been shown to predict an increased risk for mortality in ICD patients, independent from shocks and disease severity.²²

The wide range in odds ratios and confidence intervals indicates disparity in data across these type D studies (Table 1). We recently performed a metaanalysis of prospective studies between 1996 and 2009 to provide a more reliable estimate of the risk associated with type D. In this analysis, type D was associated with a threefold increased risk of adverse events²³; the confidence interval of this pooled odds ratio ranged from 2.7 to 5.1. In addition, type D personality was associated with a threefold increased risk (range, 2.6 to 4.3) of emotional distress over time.²³ From the recent studies that were not included in this meta-analysis, one reported negative findings²⁰ and three others positive findings^16,21,22 on the risk associated with type D.

COMPARING DEPRESSION AND TYPE D

Many studies report on depression and cardiac disease,^1–3 but both conceptual differences and clinical evidence indicate that type D and depression are distinct forms of distress (Table 2). Conceptually, type D focuses not only on depressive affect but also on the general distress shared across negative emotions,¹⁰ and it is based on the notion that social inhibition modulates the effect of negative emotions on cardiac prognosis.²⁴ While depression refers to an episodic distress factor (patients may go in and out of depressive episodes), the type D construct focuses on an underlying factor that predisposes patients to more chronic forms of distress.⁸

Clinical evidence shows that, after adjustment for depression, type D remained a predictor of adverse cardiac events in CAD.^16,24,25 Following ICD implantation, anxious type D patients were at risk of ventricular arrhythmias, whereas depression did not predict arrhythmias.²¹ Type D also exerts an adverse effect on patients’ health status following coronary bypass surgery,²⁶ heart failure,²⁷ or myocardial infarction,²⁸ adjusting for depressive symptoms. Type D is related to biomarkers of increased stress levels independent of depression^29–31 and, unlike depression, type D is not confounded by the severity of cardiac disorder.³²

Following myocardial infarction, only one of four distressed patients met criteria for both type D and depression; most had one form of distress but not the other.³² Research in healthy³³ and in cardiac³⁴ populations confirmed that items from depression and type D scales reflect different distress factors. After adjustment for depression at baseline, type D also predicted the incidence,³⁵ persistence,³⁶ and severity^37,38 of depression and anxiety. However, these findings do not imply that depression and type D are antonymous perspectives or that one perspective is better than the other in predicting outcomes; rather, we would like to argue that both constructs represent complementary perspectives that have added value.²³

 

BIOLOGIC PATHWAYS OF TYPE D

A number of biologic pathways have been suggested to explain the effect of type D (Table 3). Some have suggested dysregulation of the hypothalamicpituitary-adrenal axis in patients with type D personality.³⁹ In fact, type D has been associated with greater cortisol reactivity to stress in healthy individuals⁴⁰ and with higher awakening³⁰ and daytime³¹ cortisol levels in CAD patients. Autonomic dysregulation can also be inferred in type D individuals on the basis of a higher resting heart rate⁴¹ and cardiovascular hyperreactivity^40,42 and decreased heart rate variability⁴³ in response to stress. In addition, type D has been related to reduced heart rate recovery after exercise in patients with heart failure.⁴⁴ These indices of excessive sympathetic or inadequate parasympathetic modulation of heart rate predict poor cardiac prognoses.⁴⁵

Other studies found that type D was associated with inflammatory dysregulation. In healthy adults, type D has been related to higher concentrations of C-reactive protein.⁴¹ In heart failure patients, type D is associated with increased plasma levels of the proinflammatory cytokine tumor necrosis factor (TNF)-α and its soluble receptors 1 and 2.^46,47 Increased TNF-α levels may cause suppression of bone-marrow–derived endothelial progenitor cells (EPCs) that play an important role in maintaining vascular integrity. The negative affectivity component of type D has been shown to predict decreased circulating EPC counts in healthy individuals⁴⁸; another study found that these EPC numbers were reduced by more than 50% in heart failure patients with a type D personality.⁴⁹ Type D personality is also associated with an increased oxidative stress burden in patients with chronic heart failure.²⁹ Studies on genetic linkage⁵⁰ and heritability⁵¹ further support biologic underpinnings of the type D construct.

Regarding pathways that may explain the effect of type D, some issues are of special interest. First, genetic factors contribute to stability in type D personality, but environmental factors may induce changes in type D characteristics over time.⁵¹ Hence, given this role of environmental influences over time, behavioral intervention would be feasible and useful in type D patients. Second, type D can promote heart disease indirectly through behavioral pathways. Type D has been associated with a sedentary lifestyle,^41,52 an unhealthy diet,⁵³ and a passive coping style.^54,55 Poor adherence to medical treatment^56,57 and reluctance to consult clinical staff⁵⁸ may jeopardize the working relationship with type D patients in clinical care. Intervention may focus on the management of these behavioral risk factors in type D patients. Third, many of these biologic^{40–43,48,50,51} and behavioral^41,52–54 pathways have also been documented in healthy type D individuals, which suggests that these associations cannot be explained away by the confounding effect of underlying cardiovascular disease.

CLINICAL IMPLICATIONS OF TYPE D

The findings from type D research have a number of clinical implications. Type D is associated with an increased risk of adverse events,²³ chronic distress,^35–38 and suicidal ideation.⁵⁹ Type D may also have an adverse effect on the outcome of invasive treatment.^{14,19,21,22,24,26,60}

Type D was associated with mortality and morbidity at 9 months¹⁴ and 2 years²⁴ following coronary artery stenting, and with impaired health status 1 year following bypass surgery.²⁶ Type D also predicted mortality and allograft rejection following heart transplantation,¹⁹ and an increased risk of ventricular arrhythmia²¹ and mortality²² in ICD patients. Researchers from the Cleveland Clinic have shown that type D is a risk factor for anxiety in ICD patients.⁶⁰

Regarding the DSM-IV classification by the American Psychiatric Association,⁶¹ type D qualifies for the diagnosis “psychological factors affecting medical condition” (Section 316). In keeping with this classification, the diagnostic category type D affects (1) the course of cardiovascular conditions,²³ (2) the treatment of these conditions,^56,57 and (3) the working relationship with medical staff.⁵⁸ At present, no clinical trial has examined whether intervention for distress among type D patients alters their risk for adverse events. Nevertheless, some have argued that it is plausible for type D patients to learn new strategies to reduce their level of general distress.⁶² Previous research with patients experiencing symptoms like those of type D patients suggests that psychotherapy, social skills training, stress management, and relaxation training may reduce stress in these patients and improve their ability to express their emotions to others.⁶² Others have suggested that stress management training, including communication skills and problem-solving, may further improve the risk profile and health in cardiac patients.⁶³

It is possible that type D patients may benefit from close monitoring of their clinical condition and from aggressive management of their risk factor profile to prevent adverse clinical events. Cardiac rehabilitation is an effective approach to treating risk factors and enhancing well-being in CAD.^63,64 A few studies have examined the effect of cardiac rehabilitation in type D patients. One study found a significant decrease in the social inhibition component of type D following cardiac rehabilitation, but there was no change in the prevalence of type D at 1-year follow-up.⁶⁵ Although the type D profile tends to remain stable during rehabilitation,^65,66 evidence shows that type D patients who participate in cardiac rehabilitation improve in physical and mental health status.⁶⁶ Cardiac rehabilitation may also ward off further deterioration in negative affect,⁶⁷ which, in turn, has been associated with better survival in patients who participated in rehabilitation.⁶⁸ Future studies need to examine the effect of cardiac rehabilitation and other personalized approaches to treatment in type D patients.

CONCLUSIONS

General distress shared across negative emotions^6,23 may partly account for the role of depression, anxiety, and anger in cardiovascular disorders.^1–5 Some cardiac patients are more likely to experience distress than others. Type D may identify these psychologically vulnerable patients who tend to experience general distress.²³ This propensity to general distress differs from depression, predicts adverse outcomes, is linked to plausible biologic pathways, and highlights the chronic nature of psychologic distress in some cardiac patients.

After adjustment for depression, type D remains significantly associated with an increased risk of adverse events in patients with CAD.^16,24,25 However, this association is less obvious in patients with heart failure, and type D did not predict survival in one heart failure study.²⁰ Although initial findings suggest a number of plausible biologic and behavioral pathways, more research is needed to explain the adverse effect of type D on cardiovascular outcomes. Future research also needs to investigate whether type D patients may benefit from close monitoring of their risk factors and a more personalized approach to behavioral and cardiac treatment.

Overall, the current understanding of type D indicates that general distress should not be ignored in the link between mind and heart, and that cardiovascular patients who have a type D personality profile are particularly vulnerable to the adverse clinical effects of general distress. The DS14¹⁰ is a brief, well-validated measure of type D that could be incorporated into clinical research and practice to identify patients who are at risk of chronic distress and poor prognosis.

Depression has been studied extensively in relation to cardiovascular disease.^1–3 In addition to depression, anger⁴ and anxiety⁵ also may promote coronary artery disease (CAD), suggesting that emotional distress in general may be related to increased cardiovascular risk. Evidence indicates that the general distress shared across depression, anger, and anxiety predicts CAD, even after controlling for each of these specific negative emotions.⁶

THE CONCEPT OF TYPE D PERSONALITY

Lately, there is a renewed interest in broad individual differences in general distress and heart disease.⁷ Since psychologic factors often cluster together in individual patients, biobehavioral research may benefit from the identification of discrete personality subtypes.⁸ This focus on the identification of psychologically vulnerable patients who are at increased risk for adverse outcomes has led to the introduction of the distressed⁹ or type D¹⁰ personality profile in cardiovascular research. This personality construct is defined as follows:

“The type D (distressed) personality profile refers to a general propensity to psychological distress that is characterized by the combination of negative affectivity and social inhibition.”¹⁰

Negative affectivity, or the tendency to experience negative emotions across time and situations, is a major determinant of emotional distress in cardiac patients.^9,10 Patients who score high on this trait frequently report feelings of dysphoria, worry, and tension. Social inhibition, or the tendency to inhibit the expression of emotions or behavior, is a major determinant of social distress.^9,10 Patients who score high on this trait tend to avoid negative reactions from others.

Both traits define psychologically vulnerable patients and can be assessed with the type D scale (DS14).¹⁰ This brief measure consists of a seven-item negative affectivity subscale (eg, I often feel unhappy) and a seven-item inhibition subscale (eg, I am inhibited in social interactions), and has a clear two-factor structure and good reliability (Cronbach’s α = .88 and .86). Patients are classified as type D if they score 10 or higher on both DS14 subscales.¹⁰ The prevalence of type D personality ranges between 20% and 40% across different types of cardiovascular conditions.

The type D construct was designed for the early identification of chronically distressed patients. This article reviews (1) the risk of adverse events associated with type D, (2) the extent to which type D is distinct from depression, (3) the biologic pathways of type D, and (4) the implications of the type D personality profile.

RISK ASSOCIATED WITH TYPE D

Several prospective studies from our group have examined the notion that type D patients are particularly vulnerable to adverse events (Table 1). In patients with CAD, evidence indicates that type D personality is an independent predictor of adverse events, including (cardiac) death, myocardial infarction, and need for revascularization procedures.^11–16 In these studies, type D also emerged as an independent predictor of adverse events after adjustment for anxiety,¹¹ stress,¹³ depression,¹⁶ disease severity,^11–16 and type of invasive treatment.¹⁴ This increased risk associated with the type D profile was observed in the broader group of patients with CAD,^11–15 as well as in patients who survived an initial myocardial infarction.¹⁶

The relationship between type D personality and adverse events has also been investigated in other cardiovascular conditions. Type D has been associated with poor prognosis in patients with peripheral arterial disease,¹⁷ but evidence for the prognostic role of type D in patients with chronic heart failure is mixed. In a study of patients with heart failure following myocardial infarction, type D predicted cardiac death independent of disease severity¹⁸; in a study of heart failure patients who underwent cardiac transplantation, type D was associated with early allograft rejection and increased mortality.¹⁹ However, type D was not associated with cardiac death in a recent, larger heart failure study.²⁰ The link between psychologic factors and heart failure is complex³ and may be less obvious than the type D-CAD link.²⁰ Type D has also been associated with the occurrence of life-threatening arrhythmias following implantable cardioverter defibrillator (ICD) treatment,²¹ and it has been shown to predict an increased risk for mortality in ICD patients, independent from shocks and disease severity.²²

The wide range in odds ratios and confidence intervals indicates disparity in data across these type D studies (Table 1). We recently performed a metaanalysis of prospective studies between 1996 and 2009 to provide a more reliable estimate of the risk associated with type D. In this analysis, type D was associated with a threefold increased risk of adverse events²³; the confidence interval of this pooled odds ratio ranged from 2.7 to 5.1. In addition, type D personality was associated with a threefold increased risk (range, 2.6 to 4.3) of emotional distress over time.²³ From the recent studies that were not included in this meta-analysis, one reported negative findings²⁰ and three others positive findings^16,21,22 on the risk associated with type D.

COMPARING DEPRESSION AND TYPE D

Many studies report on depression and cardiac disease,^1–3 but both conceptual differences and clinical evidence indicate that type D and depression are distinct forms of distress (Table 2). Conceptually, type D focuses not only on depressive affect but also on the general distress shared across negative emotions,¹⁰ and it is based on the notion that social inhibition modulates the effect of negative emotions on cardiac prognosis.²⁴ While depression refers to an episodic distress factor (patients may go in and out of depressive episodes), the type D construct focuses on an underlying factor that predisposes patients to more chronic forms of distress.⁸

Clinical evidence shows that, after adjustment for depression, type D remained a predictor of adverse cardiac events in CAD.^16,24,25 Following ICD implantation, anxious type D patients were at risk of ventricular arrhythmias, whereas depression did not predict arrhythmias.²¹ Type D also exerts an adverse effect on patients’ health status following coronary bypass surgery,²⁶ heart failure,²⁷ or myocardial infarction,²⁸ adjusting for depressive symptoms. Type D is related to biomarkers of increased stress levels independent of depression^29–31 and, unlike depression, type D is not confounded by the severity of cardiac disorder.³²

Following myocardial infarction, only one of four distressed patients met criteria for both type D and depression; most had one form of distress but not the other.³² Research in healthy³³ and in cardiac³⁴ populations confirmed that items from depression and type D scales reflect different distress factors. After adjustment for depression at baseline, type D also predicted the incidence,³⁵ persistence,³⁶ and severity^37,38 of depression and anxiety. However, these findings do not imply that depression and type D are antonymous perspectives or that one perspective is better than the other in predicting outcomes; rather, we would like to argue that both constructs represent complementary perspectives that have added value.²³

 

BIOLOGIC PATHWAYS OF TYPE D

A number of biologic pathways have been suggested to explain the effect of type D (Table 3). Some have suggested dysregulation of the hypothalamicpituitary-adrenal axis in patients with type D personality.³⁹ In fact, type D has been associated with greater cortisol reactivity to stress in healthy individuals⁴⁰ and with higher awakening³⁰ and daytime³¹ cortisol levels in CAD patients. Autonomic dysregulation can also be inferred in type D individuals on the basis of a higher resting heart rate⁴¹ and cardiovascular hyperreactivity^40,42 and decreased heart rate variability⁴³ in response to stress. In addition, type D has been related to reduced heart rate recovery after exercise in patients with heart failure.⁴⁴ These indices of excessive sympathetic or inadequate parasympathetic modulation of heart rate predict poor cardiac prognoses.⁴⁵

Other studies found that type D was associated with inflammatory dysregulation. In healthy adults, type D has been related to higher concentrations of C-reactive protein.⁴¹ In heart failure patients, type D is associated with increased plasma levels of the proinflammatory cytokine tumor necrosis factor (TNF)-α and its soluble receptors 1 and 2.^46,47 Increased TNF-α levels may cause suppression of bone-marrow–derived endothelial progenitor cells (EPCs) that play an important role in maintaining vascular integrity. The negative affectivity component of type D has been shown to predict decreased circulating EPC counts in healthy individuals⁴⁸; another study found that these EPC numbers were reduced by more than 50% in heart failure patients with a type D personality.⁴⁹ Type D personality is also associated with an increased oxidative stress burden in patients with chronic heart failure.²⁹ Studies on genetic linkage⁵⁰ and heritability⁵¹ further support biologic underpinnings of the type D construct.

Regarding pathways that may explain the effect of type D, some issues are of special interest. First, genetic factors contribute to stability in type D personality, but environmental factors may induce changes in type D characteristics over time.⁵¹ Hence, given this role of environmental influences over time, behavioral intervention would be feasible and useful in type D patients. Second, type D can promote heart disease indirectly through behavioral pathways. Type D has been associated with a sedentary lifestyle,^41,52 an unhealthy diet,⁵³ and a passive coping style.^54,55 Poor adherence to medical treatment^56,57 and reluctance to consult clinical staff⁵⁸ may jeopardize the working relationship with type D patients in clinical care. Intervention may focus on the management of these behavioral risk factors in type D patients. Third, many of these biologic^{40–43,48,50,51} and behavioral^41,52–54 pathways have also been documented in healthy type D individuals, which suggests that these associations cannot be explained away by the confounding effect of underlying cardiovascular disease.

CLINICAL IMPLICATIONS OF TYPE D

The findings from type D research have a number of clinical implications. Type D is associated with an increased risk of adverse events,²³ chronic distress,^35–38 and suicidal ideation.⁵⁹ Type D may also have an adverse effect on the outcome of invasive treatment.^{14,19,21,22,24,26,60}

Type D was associated with mortality and morbidity at 9 months¹⁴ and 2 years²⁴ following coronary artery stenting, and with impaired health status 1 year following bypass surgery.²⁶ Type D also predicted mortality and allograft rejection following heart transplantation,¹⁹ and an increased risk of ventricular arrhythmia²¹ and mortality²² in ICD patients. Researchers from the Cleveland Clinic have shown that type D is a risk factor for anxiety in ICD patients.⁶⁰

Regarding the DSM-IV classification by the American Psychiatric Association,⁶¹ type D qualifies for the diagnosis “psychological factors affecting medical condition” (Section 316). In keeping with this classification, the diagnostic category type D affects (1) the course of cardiovascular conditions,²³ (2) the treatment of these conditions,^56,57 and (3) the working relationship with medical staff.⁵⁸ At present, no clinical trial has examined whether intervention for distress among type D patients alters their risk for adverse events. Nevertheless, some have argued that it is plausible for type D patients to learn new strategies to reduce their level of general distress.⁶² Previous research with patients experiencing symptoms like those of type D patients suggests that psychotherapy, social skills training, stress management, and relaxation training may reduce stress in these patients and improve their ability to express their emotions to others.⁶² Others have suggested that stress management training, including communication skills and problem-solving, may further improve the risk profile and health in cardiac patients.⁶³

It is possible that type D patients may benefit from close monitoring of their clinical condition and from aggressive management of their risk factor profile to prevent adverse clinical events. Cardiac rehabilitation is an effective approach to treating risk factors and enhancing well-being in CAD.^63,64 A few studies have examined the effect of cardiac rehabilitation in type D patients. One study found a significant decrease in the social inhibition component of type D following cardiac rehabilitation, but there was no change in the prevalence of type D at 1-year follow-up.⁶⁵ Although the type D profile tends to remain stable during rehabilitation,^65,66 evidence shows that type D patients who participate in cardiac rehabilitation improve in physical and mental health status.⁶⁶ Cardiac rehabilitation may also ward off further deterioration in negative affect,⁶⁷ which, in turn, has been associated with better survival in patients who participated in rehabilitation.⁶⁸ Future studies need to examine the effect of cardiac rehabilitation and other personalized approaches to treatment in type D patients.

CONCLUSIONS

General distress shared across negative emotions^6,23 may partly account for the role of depression, anxiety, and anger in cardiovascular disorders.^1–5 Some cardiac patients are more likely to experience distress than others. Type D may identify these psychologically vulnerable patients who tend to experience general distress.²³ This propensity to general distress differs from depression, predicts adverse outcomes, is linked to plausible biologic pathways, and highlights the chronic nature of psychologic distress in some cardiac patients.

After adjustment for depression, type D remains significantly associated with an increased risk of adverse events in patients with CAD.^16,24,25 However, this association is less obvious in patients with heart failure, and type D did not predict survival in one heart failure study.²⁰ Although initial findings suggest a number of plausible biologic and behavioral pathways, more research is needed to explain the adverse effect of type D on cardiovascular outcomes. Future research also needs to investigate whether type D patients may benefit from close monitoring of their risk factors and a more personalized approach to behavioral and cardiac treatment.

Overall, the current understanding of type D indicates that general distress should not be ignored in the link between mind and heart, and that cardiovascular patients who have a type D personality profile are particularly vulnerable to the adverse clinical effects of general distress. The DS14¹⁰ is a brief, well-validated measure of type D that could be incorporated into clinical research and practice to identify patients who are at risk of chronic distress and poor prognosis.