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Chest Pain in Patients With Cardiac and Noncardiac Disease DAVID S. SHEPS, MD, MSPH, FRANCIS CREED, MD,

AND

RAY E. CLOUSE, MD

Objective: To describe factors influencing chest pain expression in patients with cardiac or noncardiac disease. Methods: The authors conducted a case presentation and review of literature. Results: Causes of chest pain are diverse. Psychologic factors influence chest pain expression commonly in patients with or without cardiac disease. Conclusions: Physicians and other therapists must be aware of psychologic influences on chest pain expression to provide optimal treatment to their patients. Key words: chest pain, angina, ischemia, depression. PIMI ⫽ Psychophysiologic Investigations of Myocardial Ischemia; GERD ⫽ gastroesophageal reflux disease.

INTRODUCTION he reporting of chest pain is very common in clinical practice (1). In 2000, an estimated 8.9 million trips to physician offices in the United States—1% of the total—were prompted by chest pain and related symptoms (2). That same year, an estimated 5.8 million hospital emergency department visits—5.4% of the total—were prompted by reports of chest pain (3). Symptoms of chest pain are a major source of concern for patients and physicians alike because they can sometimes be the harbinger of acute life-threatening events in patients with or without previously documented cardiac disease. However, many patients who describe chest pain that sounds identical to the type associated with significant cardiac disease can actually be free of such disease. In fact, statistics show that more than 50% of patients referred to cardiologists for chest pain are ultimately found to have noncardiac chest pain; that is, their chest pain is not shown to be caused by cardiac ischemia (4,5). Further complicating the issue, even patients with documented ischemic cardiac disease can have chest pain complaints that are not ischemic in origin and instead may be related to other conditions. The astute clinician will be aware of these subtleties and treat the patient accordingly. The mechanisms of cardiac pain and the neuropathways and influences on pain perception are not well understood (6). The specific substances that trigger the painful condition and culminate in chest discomfort have not been agreed on in totality. However, many authorities believe that adenosine, which is produced as a byproduct of ischemia, is the main chemical mediator of cardiac chest pain. Other substances, including bradykinin, histamine, and serotonin, have also been implicated (7,8). Adenosine in high enough concentration

T

From the University of Florida and the Malcom Randall VA Medical Center, Gainesville, Florida (D.S.S.); the School of Psychiatry and Behavioural Science, University of Manchester, U.K. (F.C.); and the Division of Gastroenterology, Washington University School of Medicine, St. Louis, Missouri (R.E.C.). Address correspondence and reprint requests to David S. Sheps, MD, MSPH, University of Florida, P.O. Box 100181, Gainesville, FL 100181– 0181. E-mail: [email protected] Received for publication March 5, 2004; revision received May 11, 2004. This review was developed from a panel presentation at the March 2003 American Psychosomatic Society conference in Phoenix, Arizona. This report was supported in part by research grants R01 HL072059 and R01 HL026501A2 (Dr. Sheps) and DK53060 and DK59364 (Dr. Clouse) from the National Institutes of Health, Rockville, MD. This material was developed in part through the use of Department of Veterans Affairs facilities. DOI: 10.1097/01.psy.0000146330.80895.77 Psychosomatic Medicine 66:861– 867 (2004) 0033-3174/04/6606-0861 Copyright © 2004 by the American Psychosomatic Society

injected intravenously will produce chest pain in the majority of individuals, even in people without heart disease. We have shown that certain naturally occurring substances such as beta endorphin can counteract the angina pectoris-like pain provoked by intravenous bolus injections of adenosine (9). Therefore, although byproducts of ischemia such as adenosine may directly produce chest pain, presumably by activating cardiac nociceptors, the magnitude of pain perception can be influenced by levels of naturally occurring substances such as beta endorphin. We also have shown that depression and type A behavior pattern are related to both expression of pain versus silent myocardial ischemia and beta endorphin responses during exercise (10). Patients with coronary disease who have a depressed mood, even without clinical depression, have higher rates of pain reporting. Chest pain also can arise from noncardiac sources, particularly the gastrointestinal tract. As is true with cardiac chest pain, both peripheral stimuli (as from the esophagus) and psychologic factors interact in producing the final report of pain. The purpose of this case report and review is to discuss the differential diagnosis of chest pain from a mechanistic point of view with a goal of giving clinicians a broad understanding of factors underlying its production and influencing its presentation. CASE REPORT A Case of Noncardiac Chest Pain in a Patient With Documented Cardiac Disease A 66-year-old woman with a history of cardiovascular disease sought medical attention for chest pain. At age 52, she experienced a myocardial infarction and underwent coronary artery bypass grafting. This was followed several years later by a second myocardial infarction that left her with markedly reduced left ventricular function (ejection fraction approximately 25%), physical limitation, breathlessness, and angina. At age 64, she developed an arrhythmia, and a pacemaker was inserted. One year later, she experienced a new type of chest pain that could not be attributed to cardiac dysfunction or ischemia, and she was referred to a gastroenterologist. The gastroenterologist noted the patient’s anxiety about heart disease. Her father and two siblings had died at age 50 to 60 years from coronary heart disease; her surviving brother also had been given this diagnosis. Besides chest pain, heartburn and abdominal pains were described to this physician. Heartburn had been present for several years and previously had been responsive to antireflux therapy. The patient reported dizziness, nausea, a sensation that her legs might give way, and difficulty focusing her eyes. At times, she had pronounced 861

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D. S. SHEPS et al. churning in her stomach, palpitations, and shaking of her arms and legs. The following investigations were normal: ultrasound of the gallbladder and abdomen, barium upper gastrointestinal radiographs, and upper gastrointestinal endoscopy. Heartburn sensation was produced with both acid and saline esophageal instillation during a Bernstein provocation test, an inconclusive finding. Twenty-four-hour ambulatory pH monitoring revealed normal esophageal acid exposure times. Based on these findings, the gastroenterologist continued empiric treatment with antireflux medications, noted that the patient was stressed and tearful during consultation, and referred her to a psychiatrist. The psychiatrist also noted that the patient appeared depressed and was tearful, seemed hopeless about the possibility of improving, and was avoiding social contact. Other features extracted during the initial interview included insomnia, poor energy level, and symptoms compatible with panic attacks. Because of the latter, she had not wanted her husband out of her sight over the past year out of fear that she would have another myocardial infarction and die. The patient also described symptoms of a previous major depressive episode approximately 1 year before she saw the psychiatrist. The episode had been precipitated by the death of a close friend and a statement from her cardiologist that her cardiac medications would affect her eyesight. Because of her physical limitations, artwork had been her only hobby. There was no earlier personal or family history of depression. TABLE 1. Duration

She initially was treated with a tricyclic antidepressant and then with a selective serotonin reuptake inhibitor. Within 5 weeks, she had improved considerably with a marked reduction in her self-reported depression symptoms. Her chest pain improved greatly and she was willing to be left alone by her husband. She was beginning to regain social confidence and eventually made a complete recovery from the psychologic point of view. She was able then to cope with her cardiac disease as she had done for 10 years before this depressive illness. GASTROENTEROLOGIC ASPECTS OF CHEST PAIN There are many causes of chest pain, and clinical presentation typically determines the order of cardiac and noncardiac investigations (See Table 1 for differential diagnosis of chest pain (11)). The most common explanations for noncardiac chest pain are gastroenterologic. Recurrent, discrete pain accompanies a variety of upper gastrointestinal tract disorders, but gastroesophageal reflux disease (GERD) most commonly is implicated. At least 40% of patients with chest pain without cardiac disease who undergo comprehensive testing for GERD will have an indicator of pathological reflux, either esophagitis at endoscopy or an elevated esophageal acid exposure time during ambulatory pH monitoring (12). Many of these patients can be identified with a therapeutic trial of antireflux treatment. Two weeks of a high-dose proton pump inhibitor regimen will suppress chest pain episodes in more than 80% of this subset with evidence of pathologic reflux

Differential Diagnosis of Episodic Chest Pain Resembling Angina Pectoris* Quality

Provocation

Visceral (pressure) Visceral (pressure) Superficial (rarely visceral)

During effort or emotion Spontaneous

Rest, nitroglycerin Nitroglycerin

Spontaneous (no pattern)

Time

Recumbency, lack of food Spontaneous, cold liquids, exercise Lack of food, acid foods Spontaneous; food Head and neck movement; palpation Emotion, tachypnea Movement, palpation Often spontaneous

Food, antacid

Effort angina

5–15 min

Rest angina

5–15 min

Mitral prolapse

Mins–hours

Esophageal reflux

10 min–1 hr

Visceral

Esophageal spasm

5–60 min

Visceral

Peptic ulcer

Hrs

Visceral, burning

Biliary disease

Hrs

Cervical disc

Hyperventilation

Variable, gradually subsides 2–3 min

Visceral (wax and wane) Superficial

Musculoskeletal

Variable

Superficial

Pulmonary

30 min ⫹

Visceral (pressure)

Visceral

Relief

Nitroglycerin

Food, antacid

Location

Comment

Substernal radiates Substernal radiates Left anterior

1st episode vivid

Substernal epigastric Substernal radiates

Often nocturnal No pattern, variable character Rarely radiates Mimics angina

Time, analgesia

Substernal, epigastric Epigastric, radiates Arm, neck

Stimulus removal

Substernal

Time, analgesia

Multiple

Facial paresthesia Tenderness

Rest, time, bronchodilator

Substernal

Dyspneic

Time, analgesia

Colic Not relieved by rest

* Reprinted from Heart Disease, A Textbook of Cardiovascular Medicine (11). 862

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CARDIAC AND NONCARDIAC CHEST PAIN (13). Such an approach is cost-effective and obviates the need for additional testing in many patients. The remaining half of patients lacking nonGERD physical illnesses will have no evidence of pathological reflux by objective testing and presumably have a functional disorder. This group has been well studied both clinically and physiologically; the results of such studies have helped unravel mechanisms underlying a variety of functional syndromes (14). Roughly one third will report pain with acid instillation into the esophagus or in connection with reflux events during pH monitoring. Although some authorities consider these patients as having GERD, their symptomatic responsiveness to acid suppression is diminished. They also resemble the remaining patients (whose chest pain episodes appear unrelated to acid) in their response to inflation of an intraesophageal balloon. In fact, pain reproduction with luminal distention is sufficiently characteristic of patients with chest pain who have no pathologic indicators of GERD that a carefully designed distention protocol can completely segregate them from control subjects (15). Balloon distention has been used as a provocative test in a variety of tubular gut organs (16). In each region researchers have studied, patients with symptoms unexplained on pathologic grounds report pain or discomfort at lower distention volumes. This threshold shift applies not only to noxious stimuli, but also is reflected in painful responses to nonnoxious distention volumes (allodynia). Potential explanations include enhanced peripheral sensitivity or central response bias, but the most ubiquitous explanation in the gastrointestinal tract has been response bias, ie, downadjustment of severity ratings through cognitive mechanisms. Data supporting this have been comprehensively reviewed by Whitehead and Palsson (16). That this mechanism is at work in unexplained chest pain is supported by studies using electrical esophageal stimulation and cortical-evoked potentials (17,18). Potentials measured over somatosensory brain regions are similar in patients with chest pain and control subjects during electrical esophageal stimulation, even with pain reproduction in the symptomatic patients. Concurrent measurement of heart rate variability during the experiments provides evidence for an abnormal brain stem response in the subjects with chest pain (18). Thus, available information suggests that abnormal central processing of the incoming signal, possibly accompanied by an abnormal autonomic response, is a core abnormality in patients with chest pain unexplained by pathologic disorders. Although the principal errors may have a central basis, the pathophysiological process is not isolated from peripheral, somatic events and can be initiated or perpetuated by a noxious stimulus. In the case of the esophagus and chest pain, acid appears to be relevant. For example, acid instillation into the distal esophagus lowers the sensation threshold to a distending stimulus (19). In other regions of the gastrointestinal tract, repeated stimulation with a noxious distention stimulus progressively reduces the threshold volume required to induce pain in susceptible individuals with functional complaints Psychosomatic Medicine 66:861– 867 (2004)

(20). Mucosal inflammation also has been identified as a modulating peripheral factor; infectious gastroenteritis can precipitate the clinical manifestations of irritable bowel syndrome, an intestinal disorder that shares many pathophysiological characteristics with unexplained chest pain (21). Consequently, gastroesophageal reflux, serving as a recurring acidic and distending stimulus either at physiological or pathologic levels, can provoke the central processing errors that ultimately may be required for chest pain production. These findings further underscore the importance of managing reflux disease and suppressing reflux events (sometimes to levels below that seen in physiological conditions) to assist in symptom management. They also help demonstrate the close relationship between somatic and central events and reveal a potential mechanism by which psychiatric disorders could interface with these processes. At least 70% of patients presenting with unexplained chest pain meet lifetime criteria for a psychiatric diagnosis, with the most common being anxiety states, depression, and somatization disorder (22). Longitudinal data are unavailable to demonstrate that psychiatric disorders actually produce the pathophysiological mechanisms described here in patients with chest pain. It seems plausible, however, that currently active anxiety or affective disorders, for example, could induce response bias or augment chest pain reporting in other ways. One model proposed to help in conceptualizing factors involved in the chest pain process is shown in Figure 1 (23). Heightened sensory activity reflects the central processing errors as well as transient or, in some cases, ongoing peripheral hypersensitivity that may be feeding them. In the gastrointestinal tract, abnormal motility responses also are commonly observed and may represent, in part, autonomic dysregulation. This has not been established fully. The physiological abnormalities are sensitive to effects at the level of the gut and in the cognitive/ psychologic milieu. Such phenomena likely are sufficient but not required for the initiation or perpetuation of the core abnormal-

Figure 1. A conceptual model describing the factors relevant to symptom production in unexplained chest pain and other functional gastrointestinal disorders (23). Adapted with permission. 863

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D. S. SHEPS et al. ities. Treatment approaches that emanate from this review and model are conspicuous. Attempts first are made to eliminate any identified noxious stimuli. In the case of unexplained chest pain, initiation or augmentation of antireflux therapy typically is undertaken, as was done in this case. If active anxiety or depression symptoms are present, psychologic or psychopharmacologic therapy may be effective. Interventions targeted specifically at the underlying core abnormalities are limited, although antidepressants and some other psychopharmacologic agents may have benefit. Interpreting the effect of an antidepressant in this setting must therefore be undertaken with caution. Tricyclic antidepressants, in particular, may have direct benefits on the core processes (24,25). These medications are effective at lower dosages than commonly used for psychiatric indications, have rapid onset of action (unlike that seen in depression), and have benefits that are independent of measured changes on psychometric scales (26). As one might expect from reviewing the model in Figure 1, the direct effects of low-dose tricyclic antidepressants are reduced in the presence of active major depression (27). A comprehensive management strategy often involves antireflux measures, treatment targeted toward active anxiety or depression symptoms, and, in some patients, tricyclic antidepressants (and possibly some other antidepressants) for their assistance in controlling the specific somatic complaint. Several newer areas of investigation may provide additional help in management. One relates to trying to identify a peripheral event that is more directly responsible for pain and, therefore, remains an undiscovered target for treatment. Although pain often is loosely attributed to “esophageal spasms,” conventionally measured motor abnormalities in the esophagus do not appear responsible for the symptom (28). Recent work using high-resolution intraluminal ultrasonography suggests that sustained contraction of the longitudinal esophageal muscle, the activity of which is not measured by conventional manometry or visualized radiographically, precedes the onset of pain in many instances (29). These findings are being further studied for their specificity. Investigators also are interested in better identifying susceptibility factors for developing the previously described core abnormalities. To date, the most consistent predictor has been somatization tendencies; for example, somatization is a predictor of pain with balloon distention in the gastrointestinal tract and of functional symptoms after infectious gastroenteritis (30). The fact that a tendency toward multiple unexplained symptoms in more than one organ system may underlie the susceptibility to any single syndrome, including unexplained chest pain, may ultimately broaden our thinking toward isolated symptoms/ syndromes while actually focusing the management approach. Chest Pain in Cardiac Patients: Sex Differences and Management Although clinicians must first seek to determine if chest pain is related to a new or worsening cardiac or gastrointes864

tinal cause, it is important that they recognize that ruling out these possibilities does not spell the end of treatment for the patient. As this case illustrates, the numerous investigations into physical causes of the disease did nothing to relieve this woman’s extreme worry about her illness. This patient had depressive disorder with panic attacks. When these disorders were managed, depressive symptoms improved, health anxiety decreased, pain reporting diminished, and health-related quality of life improved. An extensive literature relating psychologic factors to pain presentation reveals the strong association between noncardiac chest pain and the presence of anxiety and affective disorders (31). Various studies have indicated that 30% to 70% of patients with noncardiac chest pain meet criteria for these diagnoses (31–33). Thurston and colleagues have recently reviewed the subject of chest pain in the absence of coronary disease from a biopsychosocial perspective (34). People who are experiencing depression present with pain at higher rates than people without such a disorder. Furthermore, there are statistically significant differences between men and women in pain perception and presentation. Women generally have an increased sensitivity to pain compared with men on laboratory pain measurements (35), and pain sensitivity varies across the menstrual cycle (36). Relationships between depression scores, beta endorphin levels, and symptoms of angina during exercise in patients with coronary artery disease have also been described (37). Population-based research has shown that women are more likely than men to report temporary and persistent pain and to report more severe pain (38,39). Many painful conditions such as migraine, arthritis, and back and temporomandibular disorders are more prevalent in women. Sex differences in chest pain reporting may relate to biologic, cultural, and psychologic variations; social role expectations also may contribute. It also is clear, even after controlling for differences in pain, other medical conditions, and economic factors, that women seek more pain-related health care than men (38,40). Women are more likely than men to use analgesics even after controlling for differences in pain, other medical conditions, and economic factors (odds ratio, 1.39) (41). Laboratory findings have shown that women display greater sensitivity to a variety of experimental pain stimuli compared with men, although the effect sizes for sex differences are moderate (42). Even in patients with documented coronary artery disease and pain related to coronary ischemia, sex differences in pain perception can be demonstrated (43). The National Heart, Lung and Blood Institute-sponsored Psychophysiologic Investigations of Myocardial Ischemia (PIMI) study was designed to test the hypothesis that psychophysiological factors affect the manifestations of chest pain in coronary patients (44). The PIMI investigators recruited approximately 200 patients for extensive studies. All participants had coronary artery disease, which had been documented by either previous myocardial infarction and/or cardiac catheterization evaluation. During a qualifying visit, patients underPsychosomatic Medicine 66:861– 867 (2004)

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CARDIAC AND NONCARDIAC CHEST PAIN went an exercise test and Holter monitoring; during subsequent visits, they underwent physical stress and mental stress testing. Pain threshold and perception testing were performed at each visit. Psychologic profiles were obtained using instruments that included the Beck Depression Inventory and Spielberger State Anxiety Inventory. Blood was drawn for biochemical analysis from patients at rest and after stressors. Marstock sensory testing was performed to determine warm, cool, heat pain, and cold pain thresholds. Participants included 170 men and 26 women; there were no statistically significant differences in nongender baseline characteristics. However, women reported statistically higher levels of angina in the previous 3 months and during mental stress testing. In this sample, women also had higher angina reporting during exercise testing and during 48-hour ambulatory echocardiography, but the differences were not statistically significant. A higher percentage of women had an elevated sensitivity to painful heat (33% of women compared with 10% of men). Several other thermal parameters obtained by the Marstock test of sensory perception technique also revealed gender differences. Women scored statistically higher on the Beck Depression Inventory, and on trait anxiety, harm avoidance, and reward dependence scales. It should be noted that the depression ratings were still within the normal range, because anyone with clearly abnormal scores was excluded from the study at the outset. The authors concluded that psychologic factors explained the majority of the difference in the participants’ recollection of experiencing angina in the previous 3 months. Other differences during mental stress were not explained by baseline variable differences. The results demonstrated a relationship between low pain thresholds in the laboratory testing and more pain reporting in life outside of the laboratory. Further work from the PIMI study looked at the relationship between low-hot pain thresholds and time to angina on the treadmill in patients with coronary artery disease (45). A significant relationship was found with patients who had increased sensitivity to pain indicated by a low-hot pain threshold having a shorter time to onset to angina during the treadmill tests. This finding supports the contention that abnormal sensitivity to pain is associated with clinical symptoms in patients with disease. Further work is needed to determine whether this finding is reproducible and whether low pain threshold can predict increased pain reporting. One important point clinicians should recognize based on this study is that pain reporting can be influenced in an important way by psychologic factors. Such factors should be considered when patients, including those with documented coronary disease, report chest pain and no obvious ischemic etiology is identified. As the case report underscores, patients with coronary heart disease often have elevated anxiety about their condition that may contribute to their chest pain and/or result from it. Patients and clinicians may find it of interest to know that some recent Psychosomatic Medicine 66:861– 867 (2004)

studies have found that angina pectoris may not be a meaningful indicator of the severity of cardiovascular disease and may not be an independent predictor for cardiac mortality. Dankner and colleagues looked at significant predictors for cardiac mortality and total mortality among 14,697 patients with coronary heart disease (46). Angina pectoris was not a significant predictor for cardiac mortality; it was associated with a slight increased risk for total mortality (1.12 hazard ratio; 95% confidence interval, 1.00 – 1.25). Statistically significant predictors for cardiac mortality were age, past myocardial infarction, New York Heart Association class, and previous cerebrovascular accident. This suggests that the symptom of angina most likely is produced by noncardiac factors in a majority of patients, or at least factors that do not contribute to clinical risk for many patients. In another study, Koide et al. conducted a logistic multivariate regression analysis of predictors of significant coronary stenosis and found that chest pain during treadmill exercise was not a statistically significant predictor of significant coronary stenosis, whereas maximal ST segment depression during exercise, male sex, and hyperlipidemia were (47). More recently, investigators for the Heart and Soul Study found no association between self-reported angina pectoris and objective evidence of inducible myocardial ischemia in 933 patients with known coronary artery disease (48). In this study, 75% of patients with angina pectoris did not have inducible ischemia; conversely, 25% of participants with ischemia had no angina pectoris. The authors went so far as to suggest that it may be time to reevaluate the current approach of using symptoms alone to guide management decisions in patients with established coronary disease as recommended by the American College of Cardiology and the American Heart Association. The literature is, however, inconsistent on this point. Another recently published study of outpatients from the Veterans Affairs system found a significant relationship between the severity of self-reported anginal symptoms and subsequent morbidity, irrespective of differences in age, race, education, or clinical comorbidities (49). In a recent editorial, Evans and Charney discussed the relationship between depression and medical illnesses (50). They wrote: “Simply put, depression makes everything worse. Depression may be part of the cause and the consequences of some medical illnesses, such as cardiovascular disease, stroke, HIV/AIDS, cancer and epilepsy.” With regard to the relationship between depression and increased morbidity and mortality in chronic medical illness, costs for patients with major depression are approximately 50% higher than costs of chronic medical illness alone (51). Patients with both Diagnostic and Statistical Manual of Mental Disorders, 4th edition, depressive and anxiety disorders have been found to have more medically unexplained symptoms compared with patients without these disorders (52). Practical Clinical Significance As the previous sections of this discussion have demonstrated, pain reporting is influenced in a substantial way by 865

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D. S. SHEPS et al. psychiatric and psychologic factors (depression and anxiety, in particular). Therefore, the practicing physician needs to be aware that increased pain reporting— often manifested as chest pain in cardiac patients—frequently is associated with psychiatric and/or psychologic comorbidities. This is clinically important because there is a very high prevalence of major and minor depression in patients with cardiac disorders. Recently, Carney and Freedland have reviewed the subject (53). Depression is so common among patients with coronary heart disease that some experts believe that cardiac patients should be screened for its possible coexistence. Approximately 20% of patients undergoing diagnostic angiography have major depression and a similar percentage have minor depression (53). The depression itself needs to be appropriately treated; such treatment also may potentially improve the prognosis of patients with cardiac disease. It should be pointed out, however, to this date, we have no firm evidence that treating depression reduces the risk of death from cardiac disease. In most cases, the diagnosis of depression is not quite as obvious as in the current case report. Cardiologists who see patients with coronary disease who have chest pain with no obvious cardiac explanation frequently refer them for other organic causes of chest pain but do not even entertain the diagnosis of depression. A simple screening test for depression and anxiety could be very effective for patient management. A simple scale such as the Hospital Anxiety and Depression Scale is very easy for the patient to complete and provides a useful guide to the physician (54). Understandably, many patients undergoing investigations have very marked worries about their health (54,55). Most are reassured after they learn that no serious illness has been detected, but a minority remains anxious. Such anxiety requires active management or the patient is at risk of continued numerous investigations without resolution of symptoms, as occurred in this case. Factors underlying the continued search for medical help with chest pain include childhood exposure to illness or death in the family, childhood abuse, lack of social support in adult life, and current psychologic distress (56). Untreated psychologic distress is the main factor associated with continued impaired health-related quality of life (57). In summary, there are many causes of chest pain in patients with and without underlying cardiac disease. Both depression and anxiety are prevalent among patients presenting with chest pain. Depression, in particular, is associated with more symptom reporting in patients with cardiac and other disorders, may interact at physiological levels to enhance sensitivity to somatic stimuli, and should be carefully considered as either a relevant comorbidity or primary explanation for the pain in patients with this presenting symptom. Psychiatric symptoms should be treated appropriately once detected, and successful treatment can be expected to diminish chest pain reporting. Considering the recognized relationships of depression to higher morbidity and mortality rates in coronary heart 866

disease, benefits of mental health management that extend beyond pain reduction likely will be discovered. In this review, we have sought to underscore the importance of noncardiac explanations of chest pain reporting. Nonetheless, it is worth emphasizing that given the high incidence of cardiac disease, physicians must thoroughly search for such underlying organic disease even in patients with atypical pain presentation. The authors acknowledge the editorial assistance of Victoria White in preparation of this article.

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19. 20. 21. 22. 23. 24.

25. 26. 27.

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