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The Clinical Impact of Negative Psychological States: Expanding the Spectrum of Risk for Coronary Artery Disease

From the Department of Society, Human Development and Health, Harvard School of Public Health, Boston, Massachusetts (L.D.K.); the Division of General Medicine, Columbia College of Physicians & Surgeons, and the Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY (K.W.D.); and the Division of Cardiology, St. Luke's–Roosevelt Hospital Center, and the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (A.R.).

Address correspondence and reprint requests to Laura D. Kubzansky, PhD, Department of Society, Human Development, and Health, Harvard School of Public Health, 677 Huntington Ave., Boston, MA 02115. E-mail: Lkubzans{at}hsph.harvard.edu

	ABSTRACT

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Objectives: Research has demonstrated a gradient relationship between depression and the risk of adverse cardiovascular events among both initially healthy individuals and those with known cardiac disease. Moreover, recent investigators have demonstrated that adverse outcomes are even associated with the presence of relatively mild symptoms, as measured by self-report scales like the Beck Depression Inventory. The association between even mild depressive symptoms and sequelae of cardiac disease raises the following question: Is the spectrum of psychological factors associated with cardiac disease greater than previously recognized?

Methods: To address this issue, we consider a small but emerging literature that has focused on effects of other negative psychologic states on cardiovascular health.

Results: Five negative states that have been linked in varying degrees to cardiovascular disease or disturbances are identified, including hopelessness, pessimism, rumination, anxiety, and anger. Considering a broader spectrum of risk may help to understand more fully the mechanisms by which depression and other negative affective states influence coronary heart disease risk.

Key Words: coronary artery disease • hopelessness • rumination • pessimism • anger • anxiety

Abbreviations: CAD = coronary artery disease; CABG = coronary artery bypass graft; MI = myocardial infarction; BDI = Beck Depression Inventory.

	INTRODUCTION

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
An increasing literature has demonstrated a gradient between the magnitude of depressive symptoms and the likelihood of subsequent adverse cardiovascular events, both among populations of initially healthy individuals and among those with known cardiac disease (1,2). Although one might expect to observe a level at which depressive symptoms begin to exert cardiotoxic effects, no consistent threshold has been found. Rather, as illustrated in Figure 1, investigators have demonstrated that cardiotoxic effects are found even when depressive symptoms are somewhat mild (3,4). This association between even mild depressive symptoms and sequelae of coronary artery disease (CAD) raises a practical clinical question: Is the spectrum of psychological factors associated with CAD larger than previously recognized? To address this issue, we examine a small but emerging literature that has focused on the health effects of other negative psychological states. Five negative states that share some similarities with depressive states and have been linked in varying degrees to cardiovascular disease or disturbance in normal cardiovascular physiology are reviewed, including hopelessness, pessimism, rumination, anxiety, and anger. These experiences can all be characterized by the presence of underlying negative cognitions, general negative affect, or both, but each experience can also be differentiated from the others in a number of ways. Where data exists, we examine the existence of a gradient relationship between cardiovascular disease and each of these negative psychological states.

View larger version (19K): [in this window] [in a new window]   Figure 1. Postmyocardial infarction (MI) patients were recruited and assigned to 1 of 4 categories based on the Beck Depression Inventory (BDI), ranging from no depressive symptoms (BDI <5) to moderate to severe depressive symptoms (BDI 19). During the 5-year follow-up period, a gradient relationship was observed between the magnitude of depressive symptoms and the frequency of deaths, with increased events occurring even in patients with mild depressive symptoms (BDI of 5–9). Reprinted with permission from Lesperance et al (4).

	HOPELESSNESS

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Hopelessness is characterized by persistent negative feelings and expectations about the future as well as a loss of motivation (5). A sense of hopelessness seems to lead to more negative evaluations of new situations and less effective coping strategies, and thus the perception that one will not accomplish anything meaningful. Whether hopelessness represents a relatively severe constellation of depressive symptoms or can be distinguished from depression has been debated. Some investigators have argued that hopelessness is a sufficient but not a necessary cause of depression (6). Arguing that they are distinct, Everson (6) has observed that hopelessness predicts CAD incidence independent of depression. Moreover, population-based studies suggest that hopelessness is equally prevalent in men and women, whereas depression is clearly more prevalent among women (7). However, given the similarities between hopelessness and depression, one would expect hopelessness also to have a strong relationship with cardiac outcomes. This has been found in a number of studies even when hopelessness was measured using only one or two items. When studies examined hopelessness according to degrees ("moderate" versus "severe"), a gradient relationship was observed (6,8). Other data also suggests a gradient between hopelessness and the progression of carotid atherosclerosis (9). These data suggest that subsyndromal levels of hopelessness, like subsyndromal depression, may also be associated with adverse pathophysiological effects, but such studies have not yet sufficiently stratified levels of hopelessness to determine if even mild symptoms of hopelessness are associated with adverse clinical outcomes.

	PESSIMISM

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Pessimism is typically conceptualized as a cognitive style that is one possible precursor to depression (10). Although investigators generally agree that pessimism is characterized by underlying negative cognitions, two different forms of these cognitions have been considered. One conceptualization—"dispositional pessimism"—is derived from a model of self-regulation and is characterized by the tendency to expect negative outcomes. These expectations may then influence a range of behaviors, including how hard people pursue their goals or how well they adapt to adverse circumstances (11).

Another conceptualization of pessimism—"pessimistic explanatory style"—is characterized by the tendency to routinely explain events in a negative way (12). Theorists who have examined explanatory styles note that the ways life events are explained may vary in terms of internality, stability, and globality. Individuals with a pessimistic explanatory style generally explain bad events as being caused by themselves rather than others (internal), as a result of chronic rather than transient factors (stable), and generalizable to other situations (global). At the same time, good events are generally discounted by pessimists and are interpreted as having an external cause, being transient in nature, and the result of specific rather than global causes. A pessimistic explanatory style has been linked to a sense of hopelessness and is marked by the view that problems are stable and internal, and so reflect one's shortcomings (12). In general, it appears that the two measures of pessimism tap related but distinct constructs.

Although the two forms of pessimism are not typically studied together, research has linked adverse cardiovascular outcomes with both forms of pessimism. For example, in studies of patients recovering from coronary artery bypass graft (CABG) surgery, individuals who reported greater dispositional pessimism preoperatively demonstrated a slower rate of recovery after surgery and were twice as likely to be rehospitalized 6 months later for problems, including postsurgical sternal wound infection, angina, myocardial infarction (MI), the need for another bypass surgery, or angioplasty (11). These effects were independent of sociodemographic and clinical variables, as well as the diagnosis of depression. Other work stemming from the Normative Aging Study has also suggested a link between pessimistic explanatory style and the risk of adverse cardiac outcomes (13). Among 1306 initially healthy men, those with a more optimistic explanatory style were at approximately half the risk of developing MI or cardiac death relative to those with a more pessimistic explanatory style. These data are significant in that they provide evidence that negative cognitive styles, like chronic negative emotional states, may be associated with adverse cardiac outcomes.

	RUMINATION

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Rumination is the tendency to think repetitively and passively, often about situations that caused negative emotions, and to focus on these symptoms of distress (14). Thus, rumination is generally conceptualized as a maladaptive cognitive reaction to negative events that serves to exacerbate negative feelings and symptoms. The conceptual linkage between rumination and depression has also been debated. Some investigators view rumination as increasing vulnerability for future depressive episodes such that someone prone to think about a negative event perseveratively is at risk for clinical depression (15). In contrast, others have conceptualized rumination as a state that accompanies depression (16). Some research has found a relationship between rumination and soft cardiovascular end points such as poor recovery of arterial blood pressure after exposure to a stressful laboratory task (17). Given the preliminary findings on blood pressure recovery and the shared cognitive aspects of rumination and depression, we might expect that rumination may also increase risk of adverse cardiovascular events. However, to our knowledge, rumination has not yet been tested for a potential association to hard CAD outcomes.

	ANXIETY

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Anxiety arises out of a sense of threat and is characterized by a perceived inability to predict, control, or obtain desired results (18). A variety of anxiety disorders have been classified as formal clinical diagnoses, including the various forms of phobic anxiety, panic disorder, posttraumatic stress disorder, and generalized anxiety disorder. Of these, primarily phobic disorder has been studied in relation to adverse CAD events. Several large studies have noted a relationship between phobic anxiety and sudden cardiac death (19). However, the association between other forms of anxiety or subsyndromal anxiety and CAD has not been systematically studied. One study considered the risk of coronary disease in relation to worry, an important cognitive component of anxiety (20). Compared with men reporting the lowest levels of worry, men with the highest levels were at approximately 2.5 times the risk for nonfatal MI, but men with moderate levels of worry were also at elevated risk. This study could not determine whether the actual content of the worry mattered, or if it was simply the severity of worry that conferred risk. Interestingly, similar effects were observed in a subsample of the Framingham Study, which examined the risk of coronary disease during a 20-year follow up of 749 initially healthy women. There was a significant association of anxiety symptoms with MI and coronary death among homemakers, although not among employed women (21). Findings suggested that among homemakers, reporting any symptoms of tension (on a self-report measure) was associated with a sixfold increase in risk relative to those who reported no symptoms, even after controlling for a wide range of other cardiovascular risk factors. Such findings are particularly striking given that these assessment methods are likely to capture subclinical symptomatology as well as more severe emotional problems.

These observations are consistent with other research that has found that anxious or depressed individuals experience multiple difficulties, even when they may not formally qualify for a clinical diagnosis (22). In a recent study in a primary care patient population, 48% of those individuals who met study criteria and screened positive for high anxiety levels did not have a diagnosable anxiety disorder (23). However, these individuals were found to have rates of functional impairment comparable to their counterparts with diagnosable anxiety disorders. These findings parallel those reported for subclinical depression, which has been found to produce more total disability days than major depression in a prior study (24). Such findings do not identify at what level symptoms can become problematic, but do indicate that the range of symptoms with which problems can arise may be greater than previously considered.

	ANGER AND HOSTILITY

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Anger and hostile feelings are strongly associated with each other; generally, anger is considered the emotional aspect of hostility. In turn, hostility is more representative of a more enduring disposition or personality style. Hostility has been defined as a cynical, suspicious, and resentful attitude toward others, often leading to negative social exchanges and more opportunities to experience anger. In contrast, not all individuals with high levels of anger can be characterized as hostile. Unlike depressive and anxiety disorders, professionally diagnosed, syndromal anger and hostility are not yet recognized by psychiatric nosology. As a result, anger and hostility have been measured by widely different scales, each of which may assess a different type of anger or hostility. To date, a small number of studies have considered whether there is a gradient relationship between the magnitude of anger and the frequency of subsequent adverse cardiac events. In one study, symptoms of anger were associated with coronary heart disease risk in a dose–response relation over 7 years of follow up among initially healthy men (25). It is interesting to note that levels of risk increased significantly for men who reported only two to four symptoms and dramatically for those reporting over five symptoms. In another study of 12,986 black and white men and women over approximately 4 years, risk of coronary disease was approximately twofold comparing normotensive individuals reporting high levels of anger with those reporting low levels (26). Again, the risk of coronary disease increased monotonically with increasing levels of reported anger. A gradient relationship between hostility and CAD recurrence has also been noted some studies (27,28), although findings are not consistent across all studies.

	POTENTIAL CLINICAL RELEVANCE

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
The recent international INTERHEART study indicated that over 90% of patients with MI had one or more of nine major CAD risk factors, and that psychosocial distress was among the leading risk factors (29). Because psychosocial risk factors may contribute to the pathogenesis of atherosclerosis and the occurrence of cardiac events, identification of psychosocial risk factors in clinical practice may be important. Studies that have compared effects of various psychosocial factors on cardiac-related outcomes simultaneously have generally suggested that when they persist over time, even seemingly low levels of distress can be toxic, particularly among those with established disease (30). If chronic but low levels of distress can contribute to the pathogenesis of CAD, they represent windows of opportunity for earlier clinical intervention. Because event risk accumulates as CAD risk factors cluster (31), the identification and treatment of psychologic distress might be particularly important among patients with known CAD.

	RELATED AREAS OF FUTURE INVESTIGATION

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Evidence that even low levels of depressive symptoms can predict risk of CAD raises a number of interesting clinical questions about the effects of states of distress more generally. For instance, many studies demonstrating a link between low levels of depressive symptoms and adverse outcomes have assessed depressive symptomatology using measures that capture only recent depressive experience (typically over the last week or month) rather than lifetime exposure. Examination of findings from the various studies suggests that measures that capture the chronicity or lifetime experience of depression demonstrate stronger, more consistent effects of depression on atherosclerotic risk (1). It is as yet unclear if mild persistent depression can be cardiotoxic or if it serves as a proxy measure for history of more severe depressive episodes. If it is the former, at what point in the time course of depressive symptoms do they begin to confer CAD risk? For example, we know that depression invokes a number of disturbances, ranging from activation of the sympathetic nervous system and the hypothalamic–pituitary adrenocortical (HPA) axis to platelet function disruption and behavioral problems. However, the level of depressive symptoms that causes such abnormalities remains to be identified. Interestingly, a strong gradient relationship to CAD has been noted for some other well-established psychosocial risk factors, including social support and socioeconomic status. Accordingly, our observations strengthen the need to study all potential psychosocial risk factors for a potential gradient relationship to CAD or CAD recurrence. In addition, the data reviewed here suggest a need to further study factors that may not be classically conceived as psychosocial cardiovascular risk factors such as pessimism and to consider subthreshold levels of other factors such as anxiety. Identifying various forms of distress, even in their less severe states, may provide an important avenue for early intervention.

A different approach might also try to identify pathophysiological factors known to be associated with adverse cardiac outcomes such as presence of high cortisol levels and other markers of HPA hyperactivity, inflammation, and/or markers of sympathetic nervous system stimulation. Studies could try to determine the presence and level of psychologic distress associated with such pathophysiological abnormalities, including mild subsyndromal forms of distress. If fruitful, testing for such pathophysiology could in itself become an early screen for psychologic dysfunction. Furthermore, it is possible that chronic distress regardless of severity may be sufficient to motivate potentially risky behaviors (e.g., smoking or overeating) designed to alleviate discomfort in the short-term. Such behaviors may become habitual, but provide only momentary relief and fail to address underlying negative cognitions or affect. As a result, accelerating trajectories of CAD risk may then be established in those with low but chronic levels of distress. Study of the association between subsyndromal forms of psychologic distress and adverse behaviors like smoking or overeating may also help to inform effective treatment and therapeutic interventions.

	CONCLUSIONS

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 
Effective treatment of psychosocial risk factors in the context of clinical medical practice requires an accurate characterization of who is at risk and how pathophysiological processes are set in motion. Examination of the CAD risk profile across the spectrum of symptoms and syndromes that may characterize psychological discomfort, including subsyndromal conditions, might better inform both our models of epidemiologic prediction and elucidate the pathophysiological pathways linking negative psychological states and CAD. For instance, if cognitive vulnerabilities such as a pessimistic explanatory style prove to increase risk for cardiac events and invoke pathophysiological dysfunction, then we need to expand the spectrum of risk we generally consider. Expanding the spectrum of risk may then enhance our capacity for early intervention as well as inform clinical judgments of who is at risk. Moreover, a more detailed examination of the spectrum of risk may also inform the development of more effectively timed and more specifically tailored behavioral interventions (32). Taken together, these insights can help to bring preventive cardiology practices into the behavioral realm. However, to determine whether subclinical negative psychological states like pessimism, worry, and rumination are indeed cardiotoxic and that their early identification can improve cardiovascular outcomes, a reproducible body of clinical data is needed.

	NOTES

TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 

In accordance with CME accreditation guidelines, the authors of this article disclosed no real or potential conflicts of interest.

DOI:10.1097/01.psy.0000164012.88829.41

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TOP ABSTRACT INTRODUCTION HOPELESSNESS PESSIMISM RUMINATION ANXIETY ANGER AND HOSTILITY POTENTIAL CLINICAL RELEVANCE RELATED AREAS OF FUTURE... CONCLUSIONS NOTES REFERENCES

 

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