Cardiovascular Implications of Stress and Depression

By Kevin T. Larkin

Cardiovascular Implications of Stress and Depression provides an in-depth examination on how exposure to stress influences risk for cardiovascular disease and how depression is associated with this relationship. This authoritative volume examines causal pathways linking stress, depression and cardiovascular disease. In addition, it provides mechanistic insights into how environmental stress can lead to cardiovascular diseases. Current information about mechanistic factors, clinical and epidemiological aspects, and management issues associated with stress/depression are presented. These insights demonstrate how the mechanisms behind chronic stress and depression lead to cardiovascular diseases. In addition, their role in existing diseases (such as obesity, hypertension, and diabetes) is explored.

• Provides the latest information on how stress leads to depression and how stress/depression interacts to accelerate cardiovascular diseases, including stroke
• Delivers insights on how mechanisms of stress/depression affect vasculature
• Explores how to best research this topic from human and pre-clinical models

• Language: English
• Publisher: Academic Press
• Release date: Aug 27, 2019
• ISBN: 9780128150160

Book preview

States

Chapter 1

Stress, depression, and cardiovascular disease

Kevin T. Larkina; Paul D. Chantlerb    a Department of Psychology, West Virginia University, Morgantown, WV, United States

b Division of Exercise Physiology, Robert C. Byrd Health Sciences Center, School of Medicine, West Virginia University, Morgantown, WV, United States

Abstract

Psychological factors have long been hypothesized to increase risk for numerous medical diseases, including cardiovascular disease (CVD). Because the physiological mechanisms through which psychological factors lead to disease pathology are unknown, psychological factors have not been granted the status as recognized risk factors. In 2014, the American Heart Association recommended that depression be granted the status as a risk factor for CVD. Based upon the extensive body of literature that has revealed an association between depression and CVD, this chapter introduces a collection of scholarly works by depicting both causal and corollary models linking stress and depression with CVD. The various physiological mechanisms that explain how the nervous system transduces environmental stress into depression and CVD are also outlined and serve to organize the remaining chapters of this book.

Keywords

Stress; Depression; Cardiovascular disease; Type A behavior pattern

Contents

Basic definitions

Conceptual models linking stress with depression and cardiovascular disease

Mechanisms linking stress with cardiovascular disease

Conclusion

References

Cardiovascular disease (CVD) has held the unenviably position of being the leading cause of death in industrialized nations for almost a century (Heron and Anderson, 2016). Today, CVD accounts for 1 out of every 4 deaths for men and women in the United States (Centers for Disease Control and Prevention, 2017), and even higher mortality rates worldwide (Mendis et al., 2011). Coupled with cerebrovascular disease (stroke), the third leading cause of death, diseases of the circulatory system account for considerably more morbidity and mortality in the world than any other health condition. Not surprisingly, these diseases represent one of the world’s largest health care concerns, leading to significant costs to the health care system, lost productivity among workers, and serious restrictions to life activities and mobility for those affected by them. Despite gains made in the assessment and treatment of diseases of the circulatory system over the latter half of the 20th century that resulted in reductions in morbidity and mortality, we are again noticing an increased incidence of CVD (Heron and Anderson, 2016).

The vast majority of cases of diseases of the circulatory system are associated with the underlying process of atherosclerosis. Atherosclerosis is the progressive blockage of blood flow through arteries that occurs over decades as the body responds to regular injuries to endothelial cells comprising artery walls caused by perturbed blood flow, heightened arterial pressure, and/or exposure to toxins circulating in the bloodstream. Based upon our understanding of atherosclerosis, it is not surprising that the earliest risk factors for CVD identified were variables that influenced the atherosclerotic process. For example, the diagnosis of essential hypertension presumably promotes endothelial injury through the impact of having chronically elevated arterial pressures throughout daily life. High levels of circulating blood lipids (i.e., hypercholesterolemia), result in coating the endothelium with fatty streaks and eventually fatty plaques, also promoting cellular injury and an impaired bodily response to that injury. Finally, recognizing that tobacco smoke contains many chemicals toxic to the endothelium, one can easily identify biologically plausible mechanisms through which these risk factors for CVD exert their negative health effects by promoting atherosclerosis and eventually the onset of CVD.

Unfortunately, smoking tobacco products, having high cholesterol, and exhibiting high blood pressure accounts for less than half of the variance in predicting onset of CVD (Centers for Disease Control and Prevention, 2017). In this regard, many nonsmokers with perfectly normal cholesterol and blood pressure levels can succumb to a myocardial infarction (i.e., heart attack) and/or stroke, and many individuals who have extensive smoking histories accompanied by untreated hypertension and hypercholesterolemia show no evidence of CVD, even at advanced ages. Our inability to predict onset of CVD accurately from recognized risk factors has led to a search for additional variables that may indeed capture some unique explanatory variance in making these sorts of predictions.

The influence of psychological factors on medical health conditions has been a fertile ground for research for some time, so it was only natural that scientists began examining potential psychological risk factors for CVD. In fact, one could trace theories linking medical conditions to temperaments back to the Greek physician, Hippocrates (460–375 BC), who proposed that medical conditions resulted from an imbalance of various humors in the body that were each associated with specific personality profiles. Although contemporary personality theory traces its roots back to some of the beliefs of early scientists like Hippocrates, adoption of the belief that personality type influenced specific medical disease progression was never fully adopted, partly because a biologically plausible mechanism for such associations was lacking.

In the early part of the 20th century, physiologist Walter Cannon (1915) and endocrinologist Hans Selye (1955) made significant contributions in outlining how exposure to various environmental stimuli, mainly those that elicited strong emotional reactions, led to a cascade of physiological responses that affected most organ systems in the body. Borrowing the terms stress and strain from mechanical engineers, they described how exposure to environmental events (i.e., stress) was met with an expected and predictable physiological response of the organism (i.e., strain). The importance of their work cannot be understated in providing clues to the potential mechanisms for explaining how stressful events encountered in life could alter the physiological processes that affected blood flow and ultimately the process of atherosclerosis. If indeed the brain transduces environmental events into the physiological sequelae of atherosclerosis, much like it transduces sound or light waves to neural signals, organisms exposed to certain types of toxic environments may be at greater risk for developing CVD. Consequently, if individual differences existed in the magnitude or pattern of these physiological responses to stress, then these specific personality or behavioral profiles could be assessed and identified as potential psychological risk factors for CVD.

One of the initial forays into the search for specific psychological risk factors for CVD was done by cardiologists Friedman and Rosenman (1959) who coined the term Type A Behavior Pattern (TABP) to refer to a constellation of highly prevalent behaviors observed among their cardiac patients. This pattern of behaviors was characterized by a chronic sense of time urgency and impatience, showing competitiveness even in non-competitive situations, and easily-aroused hostility, and was detected using a structured interview designed to evoke behavioral displays of these traits (Rosenman, 1978). Although showing initial promise as a recognized behavioral risk factor, subsequent trials failed to corroborate initial reports (e.g., Dimsdale et al., 1978; Johnston et al., 1987; Shekelle et al., 1985) and TABP was never uniformly accepted as an established risk factor for predicting CVD onset. Subsequent investigations focused on other psychosocial constructs that might enhance our ability to comprehend how exposure to stress increased risk for CVD and functioned as a behavioral risk factor for CVD. Among those that were examined, depression emerged as the one that is most strongly associated with onset of CVD among initially healthy adults as well as for subsequent cardiac events among patients diagnosed with coronary heart disease (for meta-analytic reviews, see Rugulies, 2002; Barth et al., 2004, respectively). In fact, it has been argued that presence of a diagnosis of depression or its less severe counterpart, dysphoric mood, was as strongly associated with CVD as having high blood pressure, high cholesterol, or smoking tobacco. In recognition of this status, the American Heart Association published a statement recommending that depression be considered an established risk factor for poor prognosis among patients with CVD in 2014 (Lichtman et al., 2014).

Despite evidence linking depression to CVD, it is still not given the same status as treating high blood pressure and high cholesterol or encouraging smoking cessation in most medical settings. One reason that depression screening has not been readily adopted in these health care settings pertains to our lack of knowledge pertaining to how exposure to environmental stress can lead to the neuropsychiatric sequelae of depression or perturbations in blood flow that lead to atherosclerosis within the cardiovascular system. If the mechanisms linking stress with depression and CVD were established and understood, it might result in greater adoption of strategies to assess psychological risk factors for CVD in contemporary health care settings. This edited volume aims to provide readers with a comprehensive appraisal of the literature linking stress and depression with CVD, with special attention to the various physiological mechanisms through which stress exerts its negative health effects on both the nervous and circulatory systems.

Basic definitions

Prior to introducing conceptual models of potential relations among these variables, it is important to consider basic definitions of key terms. Although we have already introduced a brief description of the process of atherosclerosis as the underlying mechanism for CVD, it is important to recognize that there are other cardiovascular problems that occur that also lead to significant health consequences, including death. These include disturbances in the pacing of the heart’s contractions (e.g., arrhythmias), compromised mechanical functioning of the four valves of the heart, infections that invade the pericardium that surrounds the heart, and genetic physical abnormalities of the heart itself. Because atherosclerosis underlies the majority of cases of coronary heart disease, stroke, and peripheral vascular disease, we will use the term CVD synonymously with cardiovascular problems caused by atherosclerosis. When other cardiovascular conditions are considered and discussed throughout this volume, we will refer to them by name rather than lumping them together with cardiovascular conditions caused by atherosclerosis.

As noted above, Selye (1955) differentiated stress from strain by referring to stress as the environmental precipitant of the disease and strain as the physiological processes that occur as the body adapted to or attempted to adapt to the precipitating event or circumstance. In this regard, stress is the stimulus and strain is the response. We will make the same distinction here. It needs to be said, however, that not all researchers make this distinction, as many measures of stress used in clinical and research settings actually measure the magnitude of the response to the stress (i.e., strain) or one’s perception of the severity of the stressful event. For purposes of this volume, the term stress will refer to the specific stimuli or alterations in environmental contexts to which an organism is exposed, much like Selye’s usage of this term. Although our use of the term stress typically refers to stimuli external to the organism, it is true that internal stimuli can also trigger physiological responses comparable to those evoked by exposure to external stressors. For example, experiencing an angina attack in the middle of the night may elicit a physiological response comparable to those that occur when confronting a bear in the woods. In this regard, both external and internal stimuli can justifiably be considered sources of stress.

In contrast to CVD that refers to restricted blood flow in the circulatory system and stress that most commonly occurs in the external environment, depression and depressive symptoms presumably largely occurs in the brain. In fact, there is a substantial literature documenting the changes in neural functioning that occurs in the central nervous system and neuroendocrine system associated with depression (e.g., Davidson et al., 2002; Thase et al., 2015). Depression itself is a mood state characterized by a range of cognitive (reduced concentration, thoughts of hopelessness or worthlessness, suicidal thinking), emotional (e.g., feeling sad or empty, loss of interest in previously pleasurable activities), behavioral (e.g., inactivity, social withdrawal), and physical symptoms (e.g., fatigue, restlessness, sleep disturbance, weight loss or gain, altered appetite). When the mood state persists for at least 2 weeks and is associated with a reduction in daily functioning, but with no instances of mania or hypomania, a Major Depressive Disorder is diagnosed (American Psychiatric Association, 2013). The prolonged experience of depressive mood states for over 2 years duration in adults meets diagnostic criteria for Persistent Depressive Disorder or Dysthymia (American Psychiatric Association, 2013). Both Major Depressive and Persistent Depressive Disorders must be distinguished from Bipolar Disorder that involves altered mood rhythms that vacillate between depressive moods and periods of extreme energy and activation. For purposes of this book, the term depression will refer to the diagnosed conditions of either Major Depressive or Persistent Depressive Disorders, but not the diagnosis of Bipolar Disorder, and the term depressive symptoms will refer to the underlying cognitive, behavioral, emotional, and physical symptoms upon which these diagnoses are made. Although humans can be diagnosed with depressive disorders, animals cannot. However, animals can display behaviors that resemble depressive symptoms (e.g., social withdrawal, restlessness, reduced grooming, inactivity). Therefore, research on animals can shed light on relations between stress, depressive symptoms, and CVD outcomes, but are of lesser value in relating stress and CVD with the complex symptomatology of clinically diagnosed depressive disorders.

Conceptual models linking stress with depression and cardiovascular disease

Although bi-directional pathways exist between stress and CVD, of primary importance here is the causal association between stress as the stimulus and CVD as the pathogenic response. This is not to say that experiencing a heart attack or stroke does not constitute a source of stress, but that we are mostly interested in how a broad range of stressful life events leads to CVD over time. In other words, if exposure to stress functions as a behavioral risk factor for CVD, it must precede the onset of disease. What is unclear in this model is whether depression is directly involved in this causal pathway or whether it serves as simply a correlated outcome. These two conceptual models are depicted in Fig. 1.1. In Panel A, exposure to environmental stress influences brain functioning that causes depression and/or depressive symptoms. Over time, the brain changes that occur with experiencing a depressed mood lead to physiological perturbations in the circulatory system that lead to atherosclerosis.

Fig. 1.1 (A) Depression mediates the relation between stress and CVD and (B) Depression as a corollary of the relation between stress and CVD.

In contrast, the corollary model depicted in Panel B reveals independent links between stress and both the brain changes that occur with experiencing depression or depressive symptoms and the restrictions in blood flow caused by atherosclerosis. The corollary model assumes no causal role for depression, although it still functions as a credible marker for CVD through their shared lineage.

In Section One of this book, evidence supporting these two conceptual models will be examined in order to gain a comprehensive understanding of the role of depression in explaining how stress leads to CVD. Evidence for relations among stress, depression, and cardiovascular disease has accumulated in three separate bodies of literature: human epidemiologic studies, translational research that emanates from animal models, and human intervention research using therapeutic strategies known to influence these health conditions. In Chapter 2, Rutledge and Gould review the body of evidence from prospective epidemiological trials on humans that examines relations between stress and depression with onset of CVD or experiencing subsequent cardiac events among patients with pre-existing CVD. Next, in Chapter 3, Grippo reviews the extant animal literature linking depressive behaviors of animals with cardiovascular consequences, with a special focus on translational studies extending animal research to human pre-clinical and clinical studies. Experimental methods for inducing depressive symptoms in animals by exposing them to stress is a highlight of this work. Finally, in Chapter 4, Cavanagh, Gaffey, Rosman, and Burg review clinical trials aimed at treating either depression or CVD using pharmacotherapeutic agents or psychological interventions, including stress management, cognitive behavior therapy, and nutritional and exercise interventions. By examining the evidence from these three bodies of literature, we can begin to determine the proper role for depression in explaining the relation between exposure to stress and CVD outcomes. Although the differentiation between depression as a causal psychological phenomena and as a corollary phenomenon may not be as important for establishing depression as a behavioral risk factor for CVD, it is critical for developing intervention and prevention programs that target reducing behavioral risk for CVD. If depression is not part of the causal pathway linking stress with CVD, it is unlikely that the numerous evidence-based interventions we have for treating depression will influence subsequent incidence of CVD.

Mechanisms linking stress with cardiovascular disease

As mentioned previously, one of the reasons that behavioral risk factors may receive a lower priority than the established risk factors of smoking tobacco, having high blood pressures, or exhibiting hypercholesterolemia in clinical settings is the lack of clarity surrounding the behavioral and physiological mechanisms linking stress to CVD. Because stress, for the most part, results from one’s surrounding environment and atherosclerosis occurs in the circulatory system, it is important to consider biologically plausible mechanisms regarding how stress infects the organism and causes the dramatic changes in the cardio-vasculature that lead to onset of CVD. Clearly, there is no direct portal through which events like loss of a loved one seep through the skin into the vascular bed leading to reductions in arterial flow. In this regard, experts in this field agree that the linkage between environmental stress and atherosclerosis relies on the nervous system, the organ system responsible for transducing environmental stimuli (e.g., sound waves; light spectra) into neural phenomena that enable the brain and other organ systems in the body to develop appropriate responses to these stimuli. In brief, the transduction of stressful events occurring in the environment to pathogenic processes in the cardio-vasculature requires a functional nervous system that is capable of detecting these events, appraising them as being threatening or presenting a challenge for the organism to overcome, and orchestrating a physiological response capable of coping with or handling the event in the most efficient way. The purpose of Section Two of this volume is to examine several behavioral and/or physiological mechanisms that have been proposed to explain how exposure to stress might lead to restricted blood flow that occurs in CVD. This is not a new question, as it was proposed shortly after the association between depression and CVD was discovered and reported. In an early review examining potential mechanisms linking depression and CVD, Carney et al. (1995) identified increased sympathetic nervous system activity and reduced parasympathetic activity as physiological mechanisms that potentially explained how onset of depression led to an increased risk for CVD. These authors also suggested that reductions in adherence to cardiac treatment regimens or less engagement in healthy behaviors (e.g., consuming healthy diets, exercising regularly, limiting consumption of alcohol, and not using tobacco) may be other avenues through which depression increased risk for CVD. They dismissed the hypothesis that the depression-CVD linkage could be associated with cardio-toxic side effects of anti-depressant medication, mainly because strong associations between depression and CVD were evident among depressed patients who had not been treated with anti-depressant medications.

Almost a decade later, Lett et al. (2004) reviewed the literature again and added several new biologically plausible mechanisms through which depression might increase risk for CVD. These included increased platelet aggregation, hypothalamic pituitary adrenal (HPA) dysregulation, and immune system alterations via inflammatory responses markers. Skala et al. (2006) confirmed these findings in a review a few years later, and added new information pertaining to imbalances among blood clotting mechanisms for explaining how depression increases risk for CVD, specifically the balance between prothrombotic and antithrombotic processes. Dysfunction within the endothelium itself was also introduced as a potential mechanism based on evidence showing reduced flow-mediated dilation among cardiac patients with higher scores on measures of depressive symptoms (Sherwood et al., 2005). Additionally, shared genetic substrates as well as plasma concentrations of Omega-3 polyunsaturated fatty acids were reported as showing promise as underlying mechanisms for explaining the depression-CVD association (Skala et al., 2006). Given that over a decade has passed since these initial forays examining underlying mechanisms linking depression with CVD were published, the time is ripe to examine the progress made in understanding how stress gets under the skin and into the circulatory system, ultimately leading to atherosclerotic complications. The remaining chapters of this volume serve this purpose and lead to a greater understanding of the biologically plausible mechanisms that link stress with CVD for both scientists examining how stress and depression lead to increased risk for CVD and health care providers who will likely pay closer attention to these modifiable risk factors in hopefully reducing the consequences of the disabling array of diseases that affect the cardiovascular system.

In Fig. 1.2, several biologically plausible behavioral and physiological mechanisms for linking stress and depression with CVD that have been historically identified are presented and serve as the organization for the remainder of this book. These include the magnitude and patterning of autonomic and neuroendocrine responses to stress (Chapter 5), cardiac changes (e.g., electrical conductance, cardiac remodeling) and vascular alterations (peripheral arterial disease; arterial stiffness and atherosclerosis) that occur in response to stress (Chapter 6), central nervous system involvement (e.g., brain signaling; cerebrovascular functioning) in response to stress (Chapter 7), inflammatory system responses to stress (Chapter 8), physiological influences of social support and lack thereof (Chapter 9), alterations in health behaviors, including dietary and exercise behaviors, smoking tobacco and use of other substances (such as electronic cigarettes with or without nicotine), and engagement with health care providers (Chapter 10), and alterations in the brain-microbiome-gut interaction in response to stress and depression (Chapter 11). Each chapter considers (a) how exposure to stress influences the proposed behavioral or physiological mechanism, and (b) whether the proposed mechanism has been shown to be associated with increased incidence of CVD. Additionally, the association of the proposed mechanism with the presence of depression and/or depressive symptoms is also introduced to gain an understanding of how depressed mood fits into the hypothesized causal pathways depicted in Fig. 1.1.

Fig. 1.2 Potential mechanisms through which exposure to stress leads to CVD onset.

Conclusion

As the disease encumbered with the status of being the leading cause of death and disability around the world, CVD continues to present challenges to scientists who study it and health care providers who treat patients who suffer from it. Psychological factors, primarily exposure to stress and depression, hold much promise in advancing our understanding and predicting risk for CVD, but have not been uniformly adopted as risk factors by the medical community. Consequently, psychological factors are not often thoroughly assessed as often as the traditional risk factors of hypertension, hypercholesterolemia, and tobacco use. We argue that the status of psychological risk factors would be more widely adopted if we understood the biologically plausible mechanisms responsible for explaining psychosocial risk for CVD. By thoroughly examining the current state of the literature examining these mechanisms as they relate to stress and depression, we will be in a better position to focus on the most promising avenues for future research. Based on the evidence presented in the chapters that follow, we aim to achieve the ultimate purpose of expediting the development of effective strategies for reducing risk for CVD associated with both exposure to stress and the experience of depression and other negative mood states.

References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders (DSM-5). fifth ed. Washington, DC: American Psychiatric Association Publishing; 2013.

Barth J., Schumacher M., Herrmann-Lingen C. Depression as a risk factor for mortality in patients with coronary heart disease: a review and meta-analysis. Psychosom. Med. 2004;66(6):802–813.

Cannon W.B. Bodily Changes in Pain, Hunger, Fear and Rage: An Account of Recent Researches into the Function of Emotional Excitement. Appleton; 1915.

Carney R.M., Freedland K.E., Rich M.W., Jaffe A.S. Depression as a risk factor for cardiac events in established coronary heart disease: A review of possible mechanisms. Ann. Behav. Med. 1995;17(2):142–149.

Centers for Disease Control and Prevention, National Center for Health Statistics. Underlying Cause of Death 1999-2016 on CDC WONDER Online Database, released December, 2017. Data are From the Multiple Cause of Death Files, 1999-2016, As Compiled from Data Provided by the 57 Vital Statistics Jurisdictions through the Vital Statistics Cooperative Program. 2017.

Davidson R.J., Pizzagalli D., Nitschke J.B., Putnam K. Depression: Perspectives from affective neuroscience. Annu. Rev. Psychol. 2002;53(1):545–574.

Dimsdale J.E., Hackett T.P., Hutter A.M., Block P.C., Catanzano D.M. Type A personality and extent of coronary atherosclerosis. Am. J. Cardiol. 1978;42(4):583–586.

Friedman M., Rosenman R.H. Association of specific overt behavior pattern with blood and cardiovascular findings; blood cholesterol level, blood clotting time, incidence of arcus senilis, and clinical coronary artery disease. J. Am. Med. Assoc. 1959;169(12):1286–1296.

Heron M., Anderson R.N. Changes in the Leading Cause of Death: Recent Patterns in Heart Disease and Cancer Mortality. NCHS data brief, no 254 Hyattsville, MD: National Center for Health Statistics; 2016.

Johnston D.W., Cook D.G., Shaper A.G. Type A behaviour and ischaemic heart disease in middle aged British men. Br. Med. J. 1987;295(6590):86–89.

Lett H.S., Blumenthal J.A., Babyak M.A., Sherwood A., Strauman T., Robins C., Newman M.F. Depression as a risk factor for coronary artery disease: evidence, mechanisms, and treatment. Psychosom. Med. 2004;66(3):305–315.

Lichtman J.H., Froelicher E.S., Blumenthal J.A., Carney R.M., Doering L.V., Frasure-Smith N., Freedland K.E., Jaffe A.S., Leifheit-Limson E.C., Sheps D.S., Vaccarino V., Wulsin L., On behalf of the American Heart Association Statistics Committee of the Council on Epidemiology and Prevention and the Council on Cardiovascular and Stroke Nursing. Depression as a risk factor for poor prognosis among patients with acute coronary syndrome: Systematic review and recommendations. Circulation. 2014;129(12):1350–1369.

Mendis S., Puska P., Norrving B., eds. Global Atlas on Cardiovascular Disease Prevention and Control. Geneva: World Health Organization; 2011.

Rosenman R.H. The interview method of assessment of the coronary-prone behavior pattern. In: Dembroski T.M., Weiss S., Shields J., Haynes S.G., Feinleib M., eds. Coronary-Prone Behavior. New York: Springer-Verlag; 1978:55–69.

Rugulies R. Depression as a predictor for coronary heart disease: a review and meta-analysis. Am. J. Prev. Med. 2002;23(1):51–61.

Selye H. Stress and disease. Science. 1955;122(3171):625–631.

Shekelle R.B., Hulley S.B., Neaton J.D., Billings J., Borhani N.O., Gerace T.A., Jacobs D.R., Lasser N.L., Mittlemark M.B., Stamler J., For the MRFIT Research group. The MRFIT behavior pattern study. II. Type A behaviour and incidence of coronary heart disease. Am. J. Epidemiol. 1985;122(4):559–570.

Sherwood A., Hinderliter A.L., Watkins L.L., Waugh R.A., Blumenthal J.A. Impaired endothelial function in coronary heart disease patients with major depression. Am. J. Cardiol. 2005;46(4):656–659.

Skala J.A., Freedland K.E., Carney R.M. Coronary heart disease and depression: a review of recent mechanistic research. Can. J. Psychiatr. 2006;51(12):738–745.

Thase M.E., Hahn C., Berton O. Neurobiological aspects of depression. In: Gotlib I.H., Hammen C.L., eds. Handbook of Depression. third ed. New York: Guilford Press; 2015:187–217.

Section 1

Evidence linking stress with depression and cardiovascular disease

Chapter 2

Epidemiological evidence linking stress and depression with CVD

Thomas Rutledgea,b; Hilary M. Goulda    a Psychology Service (116B), VA San Diego Healthcare System, San Diego, CA, United States

b UC San Diego Department of Psychiatry, La Jolla, CA, United States

Abstract

Epidemiological research represents arguably the largest source of evidence supporting relationships between stress, depression, and cardiovascular disease (CVD). Measured in various formats, stress and depression predict both CVD onset and CVD progression in epidemiological research. These relationships replicate across decades of research, manifest over shorter-term and longer-term follow-up periods, and remain stable across different countries as well as ethnic and gender groups. Finally, stress and depression relationships with CVD in epidemiological research are evident across different clinical definitions of CVD—e.g., fatal and non-fatal outcomes, acute and long-term CVD events, CAD progression, cardiac readmissions and healthcare costs, CVD treatment adherence and behavioral CVD risk factors—that increase the plausibility of the relationships. This chapter summarizes the epidemiological literature describing stress, depression, and CVD associations. Areas of emphasis include the varied definitions of stress and depression, relative merits of the epidemiological evidence, and directions for future epidemiological research likely to yield the greatest value.

Keywords

Cardiovascular disease; Depression, stress, epidemiological; Coronary heart disease; Coronary artery disease

Contents

Methodological considerations

Stress and cardiovascular disease

Depression and cardiovascular disease

Conclusion

References

The epidemiological literature describing associations between stress, depression, and cardiovascular disease (CVD) is extensive, encompassing hundreds of scientific articles, involving participants from dozens of countries, and spanning more than a half century of research (Dimsdale, 2008; Hemingway and Marmot, 1999). Given the sheer size of this literature, and the continued proliferation of research questions and methodologies, high quality systematic and narrative reviews have become an invaluable resource for scientists in the field. The most impactful reviews of epidemiological relationships involving stress, depression, and CVD easily accumulate citation numbers exceeding 1000 (e.g., Musselman et al., 1998; Barth et al., 2004). New topic reviews appear regularly (e.g., Carney and Freedland, 2017; Huffman et al., 2013; Steptoe and Kivimaki, 2013), and the American Psychological Association has published two versions of the cardiac psychology volume, Heart and Mind (in 1996 and 2012, respectively), containing epidemiological research summaries in multiple areas of the field as resources for clinicians and researchers. This chapter will integrate findings from these many prior reviews and resources, in addition to offering novel themes and suggestions for future epidemiological research based on the most recent science.

Methodological considerations

In discussing epidemiological findings from the stress, depression, and CVD literature, it is important to initially address several of the most noteworthy methodological concerns that raise interpretive challenges. The first is that there remains no clear consensus regarding the optimal measurement format of either stress or depression. Variability in measurement is the rule in these literatures rather than the exception. Stress is not recognized as a psychiatric condition itself, but is considered a symptom of or a contributor to many psychiatric conditions. Lacking a diagnostic standard (posttraumatic stress disorder [PTSD] representing arguably the psychiatric disorder most closely associated with stressful life experiences), scientists define stress in epidemiological studies multifariously using measures of work stress, home stress, financial stress, posttraumatic stress, and using subjective (e.g., harassment or loneliness) and objective (e.g., natural disasters, loss of loved ones) stressful life events. Self-report measures of stress in the CVD literature are usually brief—sometimes as short as a single item—and this feature contrasts sharply with measures of depression that sometimes comprise dozens of items or that require lengthy diagnostic interviews to identify.

Depression measures in CVD research are arguably even more diverse than those found in the stress and CVD literature, including multiple diagnostic interviews, brief measures of depression treatment status (e.g., binary questions assessing current or prior treatment for depression), and more than a dozen validated depression questionnaires (Davidson, 2012). The selection of depression measurement format forces methodological tradeoffs between practicality (e.g., brief and easy to administer questionnaires) and validity (diagnostic interviews representing the gold-standard measurement for depressive disorders). Depression questionnaires differ not only in length, but also in content (e.g., measures such as the Beck Depression Inventory [BDI] that include substantial somatic symptom content, versus measures such as the Hospital Anxiety and Depression Scale [HADS] that minimize somatic symptom content).

The result of this measurement heterogeneity is that readers of the epidemiological science reporting stress and depression associations with CVD should consider that many studies may be measuring these factors dissimilarly enough to reduce the congruity of research findings. In practice, researchers have observed methodologies consistent enough across different stress and depression research to aggregate them in most meta-analyses and systematic reviews, with perhaps two periodic modifications: (1) Research comparing depression measured as a psychiatric diagnosis (i.e., meeting criteria for major depressive disorder) consistently show stronger relationships with CVD relative to questionnaire measures of depressive symptoms and are often described separately in quantitative reviews (e.g., Barth et al., 2004; Rugulies, 2002). Whether diagnostic depression is more robustly related to CVD relative to depressive symptom questionnaires because the diagnosis captures greater depression severity, greater duration of symptoms, or both, is unknown; and (2) There is some evidence from epidemiological studies of depression and CVD that separating somatic and cognitive symptom content can improve the strength of depression relationships with CVD (Carney and Freedland,