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(Circulation. 1995;92:327-333.)
© 1995 American Heart Association, Inc.

Articles

Job Strain and the Prevalence and Outcome of Coronary Artery Disease

Mark A. Hlatky, MD; Lai Choi Lam, MS; Kerry L. Lee, PhD; Nancy E. Clapp-Channing, MPH; Redford B. Williams, MD; David B. Pryor, MD; Robert M. Califf, MD; Daniel B. Mark, MD, MPH

From the Division of Health Services Research, Department of Health Research and Policy, and the Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, Calif; and the Division of Cardiology, Department of Medicine, and the Division of Behavioral Medicine, Department of Psychiatry, Duke University Medical Center, Durham, NC.

Correspondence to Mark A. Hlatky, MD, Stanford University School of Medicine, HRP Redwood Bldg, Room 265, Stanford, CA 94305-5092.

	Abstract

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Background It has been hypothesized that jobs that have both high psychological demands and low decision latitude ("job strain") can lead to coronary disease. The objective of this study was to test whether job strain was correlated with the presence of coronary disease at angiography or with long-term outcome in patients with angiographic coronary disease.

Methods and Results Employed patients under the age of 65 years undergoing diagnostic coronary angiography completed a self-administered questionnaire about their job duties and work environment. Job strain was measured by the method of Karasek. Patients were separated into three groups, based on extent of coronary disease: significant disease (75% stenosis), insignificant disease (>0% but <75% stenosis), and normal coronary arteries. Statistical analyses were performed using logistic regression and the Cox proportional hazards model. The 1489 patients enrolled had a median age of 52 years; 76% were male and 88% were white. By design, all patients were employed, 60% in white-collar jobs and only 16% in jobs requiring heavy labor. Traditional cardiac risk factors were most prevalent in the 922 patients with significant coronary artery disease, at intermediate levels in the 204 patients with insignificant disease, and least prevalent in the 363 patients with normal coronary arteries (all P<.01). Job strain was actually more common in patients with normal coronary arteries (35%) than in patients with insignificant (26%) or significant disease (25%, P<.002). In a multivariate analysis, job strain was not significantly correlated with the presence of coronary disease. Job strain was not correlated with angina frequency at the time of angiography. Job strain was not a predictor of cardiac events (cardiac death or nonfatal myocardial infarction) during follow-up.

Conclusions Job strain was not correlated with the prevalence or severity of coronary artery disease in a cohort of patients undergoing coronary angiography. The outcome of patients with angiographically defined coronary disease was not affected by the level of job strain as measured by the method of Karasek.

Key Words: stress • coronary disease • prognosis

	Introduction

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Psychological stress in the workplace is generally regarded by the public as an important cause of coronary heart disease. While epidemiological studies have amply demonstrated a strong, consistent relation between coronary disease and cigarette smoking, high blood cholesterol, hypertension, diabetes, and family history,^{1 2} the epidemiological evidence supporting the relation between coronary disease and job stress is relatively sparse. Blue-collar workers have shown higher rates of coronary disease than white-collar workers in some studies,^{3 4 5} but other studies suggest this may be explained by more adverse levels of traditional coronary risk factors.⁶ The effect of type A personality on coronary artery disease has been extensively studied,^{7 8 9} and the role of social support in patients with coronary disease has come under increasing scrutiny.^{10 11 12} These studies did not, however, directly assess the role of job-related stress in coronary disease.

Methodological limitations may have contributed to the difficulty in examining the relation between stress and coronary heart disease. Stress is difficult to define operationally, and only recently have instruments to measure job stress in epidemiological studies become available. Karasek and coworkers^{13 14} have developed a measure of "job strain" that assesses the interaction between a worker and the job environment. These authors have hypothesized that high psychological demands on the job in workers with low decision latitude cause job strain, which in turn leads to the development of coronary artery disease. Karasek and coworkers¹³ found that this measure of job strain was correlated with cardiac death in a cohort of Swedish men. They also found a relation between job strain and the prevalence of myocardial infarction in the National Health and Nutrition Examination¹⁵ and a relation between job strain and echocardiographic measures of left ventricular hypertrophy.¹⁶ In contrast, using this same measure of job strain, the Honolulu Heart Study found no relation between job strain and the subsequent incidence of coronary artery disease in a prospective cohort study.¹⁷

Coronary disease risk factors may predict the development of coronary atherosclerosis, the precipitation of an acute cardiac event in persons with preexisting disease, or both. Previous studies of job strain and coronary disease have not included documentation of coronary atherosclerosis by angiography. The purpose of the present study was therefore to assess the impact of job strain on angiographically defined coronary atherosclerosis and on the prognosis of patients with angiographically defined coronary artery disease.

	Methods

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Stable patients undergoing coronary angiography at Duke University Medical Center from March 1986 through June 1990 were approached for entry into a prospective study of employment patterns in patients with coronary heart disease.¹⁸ Those patients who provided informed consent were given a self-administered questionnaire that assessed their employment status, the characteristics of their job, and other quality-of-life domains.¹⁸ For the purpose of the present analysis, patients were included if they were referred for evaluation of chest pain or equivalent ischemic symptoms, were less than 65 years of age, were employed, and did not require intensive cardiac care at the time of angiography. Patients with primary valvular, congenital, pericardial, or myocardial disease were excluded.

Baseline data consisting of multiple descriptors of the patient's history, physical examination, and laboratory findings were collected prospectively at the time of coronary angiography. These data were entered into the Duke Cardiovascular Disease Database, using methods that have been described previously.^{19 20} Significant coronary artery disease was defined at 75% stenosis in a major coronary vessel, insignificant disease was defined as angiographic evidence of atherosclerosis that narrowed the lumen by >0% and <75%, and normal coronary arteries were defined as no angiographic evidence of coronary atherosclerosis. All patients were contacted at 3 to 6 months, 12 months, and annually thereafter to document outcome. The mean follow-up time for the study population was 4 years.

All patients completed a self-administered questionnaire that assessed baseline functional capabilities, quality of life, socioeconomic status, and descriptions of their job duties and work environment.¹⁸ Jobs were classified according to the criteria of the 1980 US Commerce Department Standard Occupational Classification²¹ into one of six categories: managerial and professional specialty; technical, sales, and administrative support; service; farming; forestry and fishing; precision production, craft, and repair; and operators, fabricators, and laborers. The physical demands of the job were classified using the criteria of the Department of Labor²² into one of four classes: sedentary, light, medium, and heavy.

Job stress was assessed using the method of Karasek and associates.^{14 16} Patients rated 11 statements about their jobs on a 4-point scale: 4, strongly agree; 3, agree; 2, disagree; and 1, strongly disagree. Responses to these items were used to form two scales (decision latitude and psychological demands), using the formula presented in Table 1. Job strain was defined as the combination of high psychological demands and low decision latitude. In this study we analyzed job strain both as a binary variable (present or absent) and as a continuously valued job strain index. High job strain as a binary variable was defined as present if the patient's decision latitude was less than 24 on a scale ranging from a low of 8 to a high of 32 and psychological demands were greater than 32 on a scale ranging from a low of 12 to a high of 48 (C. Pieper, personal communication). To provide a more sensitive measure of the extent of job strain, we also defined a continuously valued job strain index by transforming the original values of decision latitude and psychological demands onto scales from 0 (best) to 10 (worst) and then multiplying these two terms to form a job strain index that ranged from 0 (low) to 100 (high):

View this table: [in this window] [in a new window]   Table 1. Statements Used to Define Job Strain

Categorical data from patients with different degrees of coronary disease were tested for statistical significance using the ² test, and continuously valued data were tested using nonparametric ANOVA. Correlations between variables were assessed using Spearman rank correlation. Multivariate analysis of factors related to the presence of coronary disease was performed using logistic regression. The primary analysis used logistic regression with the binary end point of significant coronary disease (75% stenosis) present or absent. Secondary analyses used a binary logistic model to determine whether job strain discriminated patients with normal coronary arteries from patients with any angiographic evidence of coronary atherosclerosis (ie, significant or insignificant coronary disease), and the final analysis used ordinal logistic regression with all three patient groups separated in the dependent variable. Survival data were summarized using Kaplan-Meier life table methods, and multivariate survival analysis was performed using the Cox proportional hazards model. All analyses were performed using the SAS software package (Cary, NC).

	Results

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From March 1986 to June 1990, 1850 employed patients undergoing diagnostic cardiac angiography agreed to participate in this study. Patients were excluded who had prior coronary bypass surgery (n=48) or coronary angioplasty (n=76), were 65 years of age or older (n=196), had evidence of primary valvular or myocardial disease (n=37), or were from the Department of Veterans Affairs Hospital (n=4). Thus, 1489 patients were enrolled in the study, 922 (62%) with significant coronary artery disease, 204 (14%) with insignificant coronary artery disease, and 363 (24%) with normal coronary arteries by angiography. The median age was 52 years, 76% of the population was male, and 88% were white.

By design, all patients were employed at the time of angiography. The jobs were primarily white collar in nature: 29% managerial or professional; 23% technical or sales; 8% service; 4% farming, fishing, or forestry; 17% in precision crafts or production; and 19% operators, fabricators, or laborers. The median work week was 40 hours, and the mean work week was 45.4 hours. The physical demands of the jobs in this population were not high: 15% were sedentary, 14% were light, 55% were moderate, and 16% included heavy labor.

Job strain was present in 28% of the patients. The prevalence of job strain was lowest in those employed as managers and professionals (20%), highest in laborers (36%), and intermediate in those employed in technical and sales (29%); farming, fishing, and forestry (27%); precision crafts (27%); and service occupations (31%). Job strain varied inversely with age: 33% in those less than 45 years old, 30% in those 45 to 54 years old, and 23% in those 55 to 64 years old. Job strain was more common in women (43%) than in men (23%).

Prevalence of Disease
Traditional cardiac risk factors and clinical descriptors were markedly different among patients with significant, insignificant, and no coronary artery disease at angiography (Table 2). Patients with coronary disease were more likely to be older, to be male, to smoke cigarettes, and to have diabetes, hypertension, and hypercholesterolemia (all P<.01). Patients with coronary disease were also more likely to have typical angina and a history of prior myocardial infarction (Table 2). The level of risk factors in patients with insignificant disease was intermediate between the levels in patients with significant coronary disease and in patients with normal coronary arteries (Table 2).

View this table: [in this window] [in a new window]   Table 2. Baseline Clinical and Demographic Factors According to Disease State

All patients had jobs with similar physical demands and work weeks (Table 3). Patients with coronary disease were significantly less likely to have white-collar jobs, but this was entirely due to the sex differences in coronary disease prevalence and type of work. All three groups of patients agreed equally often with the statements, "my job is stressful" (84%) and "job stress can cause a heart attack" (91%).

View this table: [in this window] [in a new window]   Table 3. Job Characteristics According to Disease State

Job strain was defined as high psychological demands in the setting of low decision latitude. Decision latitude was slightly lower and psychological demands were substantially higher among patients with normal coronary arteries (Table 3). Thus, job strain was significantly more common among patients with normal coronary arteries (35%) than in patients with either insignificant (26%) or significant coronary artery disease (25%) (P=.002). The job strain index was also significantly higher among patients without coronary disease (median, 20) than among those with either significant or insignificant coronary disease (median, 18) (P=.0001).

A multivariate analysis was performed to assess the impact of job strain on the presence of coronary disease after adjustment for differences in age, sex, smoking status, diabetes, hypertension, hypercholesterolemia, typical angina, and history of myocardial infarction. After adjustment for these previously established correlates of coronary disease, the presence of job strain (odds, 0.98; confidence limits, 0.71 to 1.36) and higher values of the job strain index (odds, 1.00; confidence limits, 0.99 to 1.01) were no longer significantly correlated with the presence of coronary disease (P=.21 and P=.63, respectively). The binary logistic analyses yielded similar findings when patients with insignificant coronary disease were grouped with patients with significant disease rather than with patients with normal coronary arteries. The results were also similar when all three groups were analyzed separately by ordinal logistic regression.

To examine whether angina severity might be increased by stress at work, we examined the association between the frequency of angina and measures of job strain. There was no significant correlation between the presence or absence of job strain and the frequency of angina (Spearman correlation coefficient, -.021; P=.45), nor was there a significant correlation between the continuously valued job strain index and the frequency of angina (Spearman correlation coefficient, .012; P=.65).

Outcome of Coronary Disease
To determine whether job strain adversely affected the outcome of coronary disease, we examined the effect of job strain measured at the time of coronary angiography on subsequent cardiac events (cardiac death and nonfatal myocardial infarction). We performed separate analyses in patients with and without significant coronary artery disease, since the higher frequency of events in patients with significant disease might overshadow any relation between job strain and prognosis in the remaining patients. There were 42 cardiac deaths and 70 nonfatal myocardial infarctions during follow-up in the patients with significant coronary disease at angiography. The presence of job strain (risk ratio, 1.01; confidence limits, 0.51 to 2.01) and the job strain index (risk ratio, 0.99; confidence limits, 0.96 to 1.02) were not significantly predictive of cardiac death during follow-up (Figure, top graph). Furthermore, presence of job strain (risk ratio, 0.96; confidence limits, 0.62 to 1.46) and the job strain index (risk ratio, 1.00; confidence limits, 0.98 to 1.02) were not significantly predictive of follow-up cardiac events (cardiac death and nonfatal myocardial infarction) (Figure, bottom graph). These results were unchanged after statistical adjustments using the Cox proportional hazards model for the effects of previously established prognostic factors, including ejection fraction, extent of coronary atherosclerosis, and measures of myocardial ischemia.

View larger version (14K): [in this window] [in a new window]   Figure 1. Proportion of patients with significant coronary artery disease without an outcome event (vertical axis) as a function of follow-up time (horizontal axis). In the top graph, the outcome event is cardiac death; in the bottom graph, the outcome event is cardiac death or nonfatal myocardial infarction. In each graph, the solid curve represents patients with job strain and the dashed curve represents patients without job strain.

We also analyzed the effect of job strain on outcome among patients with insignificant coronary disease and normal coronary arteries at angiography. Since there were only three cardiac deaths and three nonfatal myocardial infarctions during follow-up in these patients, we only analyzed total cardiac events. In patients with normal coronary arteries or insignificant disease, presence of job strain was not predictive of the development of subsequent cardiac events (risk ratio, 0.43; confidence limits, 0.05 to 3.67), and the job strain index was not predictive of cardiac events (risk ratio, 0.95; confidence limits, 0.87 to 1.04). These results were unchanged after adjustment for age, sex, left ventricular ejection fraction, and the presence of insignificant coronary artery disease.

	Discussion

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Coronary heart disease is often considered to be a disease of modern industrial society, a view clearly endorsed by almost all (92%) the patients in this study. Popular culture accepts that the stresses of modern life in general and the modern workplace in particular have contributed to the rise of coronary heart disease over the twentieth century. Coronary heart disease mortality has been declining over the past decade, however, while the stresses of modern life continue unabated.

A major difficulty in stress research has been the inherent complexity and subjectivity of the concept and the attendant difficulties in the measurement of stress.²³ The same job conditions, for instance, may be viewed by one person as challenging and by another person as stressful. To avoid this difficulty, it becomes necessary to assess the worker's perception of his or her working conditions, not simply to examine the job title or duties. Karasek and coworkers¹³ have proposed a theoretical framework for assessing the impact the job stress on the worker and have hypothesized that the combination of high job demands coupled with low control over the work environment may be particularly harmful. They termed this concept "job strain" in analogy to the distinction in engineering between stress (the external force applied to a material) and strain (the response of the material to the external force). This formulation offers both a conceptual definition of job strain and an operational technique to measure it by using questionnaires. Previous work by this group of investigators in the United States and Scandinavia^{13 15} suggested that job strain as defined by this measure was correlated with coronary artery disease incidence. A prospective evaluation by the Honolulu Heart Study, however, showed a negative correlation between job strain and subsequent coronary events in Japanese American men.¹⁷ Several of these previous studies did not measure job strain directly in each individual but inferred it from the job title.^{14 15 17} None of these studies adjusted statistically for possible confounding factors, however, and none used angiographic confirmation of disease status.

The present study used coronary angiography to define the presence and severity of coronary artery disease. Significant disease was defined as 75% stenosis in a major coronary artery, since this definition best identifies patients at risk for subsequent cardiac death or myocardial infarction. Lesser degrees of stenosis do not carry the same clinical implications but arise from the same underlying atherosclerotic process. Combining patients with "insignificant" angiographic coronary disease with patients with angiographically normal vessels would tend to dilute any associations between atherosclerotic risk factors and the presence of significant disease.²⁴ We therefore performed additional analyses, first dividing patients into two groups (angiographically normal versus any atherosclerotic lesions at angiography) and then dividing patients into three groups (normal, insignificant disease, and significant disease). These additional analyses confirmed the findings of the primary analysis: Job strain was negatively correlated with the presence of coronary disease in univariate analyses, and this correlation was eliminated by adjustment for other confounding factors. We therefore do not believe that our results are sensitive to the definition of the "diseased" and "normal" population.

The use of coronary angiography to evaluate potential risk factors for coronary disease has both advantages and disadvantages over other study designs.^{25 26 27} Angiographic studies use a cross-sectional design that is more efficient than the prospective follow-up of a large cohort of normal subjects, and consequently studies can be done more rapidly. Studies of new putative risk factors, such as serum lipid subfractions or genetic markers, can therefore be performed more readily using a case-control design with cases and controls defined by angiography.^{24 26 27} Furthermore, the end point at angiography (coronary atherosclerosis) is more precisely defined than end points in cohort studies (usually a composite of cardiac death, nonfatal myocardial infarction, and, in some studies, development of angina). The end point of cohort studies is the result of two processes that may have different risk factors: first, the initial development of coronary atherosclerosis, and second, development of plaque rupture, followed by coronary thrombosis and clinical myocardial infarction or sudden death. It is quite plausible that risk factors for these two stages of the disease process may differ,²⁸ and angiographic studies are very helpful in separating risk factors for atherosclerosis from risk factors for later complications. Studies based on angiography also have significant disadvantages. One serious concern is that patient selection for angiography may distort relations between risk factors and development of disease. However, patients in the Honolulu Heart Study with either angina or prior nonfatal myocardial infarction referred for coronary angiography had similar risk factor profiles to patients who were not referred for angiography.²⁸ In addition, the traditional cardiac risk factors in the present study (Table 2) showed the expected higher prevalence in patients with angiographic coronary disease despite the nonrandom selection for angiography. Similar associations between coronary disease and risk factors have been documented using control subjects drawn from either angiographically normal patients or from neighborhood controls.^{25 29 30}

While the association of traditional cardiac risk factors may not be greatly affected by use of angiography to define disease status, behavioral risk factors appear to be more susceptible to selection biases. In particular, patients with high levels of psychological distress may tend to somatize their distress as chest pain, and their greater level of complaints may lead their physicians to refer them more readily for angiography. These subjects may tend to have both normal coronary arteries and high levels of self-reported job stress, leading to a negative association of job stress with the presence of coronary disease at angiography. Indeed, in a previous study,³¹ we found a significant negative association between measures of psychological distress and coronary atherosclerosis in patients undergoing coronary angiography. Three features of the present study tend to reduce any concerns about selection bias. First, job strain was not correlated with angina severity. Therefore, it is less likely that bias would have been introduced by selection of patients with more severe symptoms for angiography. Second, the multivariate analysis controlled for many other clinical differences between patients with normal and abnormal coronary arteries, and adjustment for these factors eliminated the negative association between job stress and coronary disease. We believe these statistical adjustments largely corrected for the effect of patient selection for angiography. Finally and most importantly, we examined the long-term prognostic implications of job stress in this population and found no significant effect of job stress on the clinical complications of coronary disease. The findings from the cross-sectional study and the cohort study reported here are quite consistent, mutually complementary, and together provide a more complete picture than either alone would have.

It is possible that the negative correlation of job stress with coronary disease at angiography could be due to high job stress leading to more severe coronary disease and unstable symptoms. Since patients with acute ischemic heart disease syndromes (unstable angina or acute myocardial infarction) were enrolled in the current study for logistical reasons, a bias could have been introduced into the analysis. Follow-up of the cohort, however, provided no evidence that job strain increased subsequent cardiac events in patients with either angiographically documented coronary artery disease (Figure) or with insignificant disease or normal coronary arteries. While the confidence limits were relatively narrow for patients with significant disease (risk ratio for cardiac events, 0.96; confidence limits, 0.62 to 1.46), they were broad for patients with insignificant disease (risk ratio, 0.43; confidence limits, 0.05 to 3.67). It is noteworthy that the absolute rate of cardiac events in the latter group during follow-up was quite low despite high levels of job strain.

The lack of correlation of job strain with coronary disease should not be interpreted as indicating that psychological factors have no effect on the development of cardiac disease. The current concepts of the effect of psychological factors on the heart are undergoing considerable refinement as methodology has improved.³² The type A behavior pattern, for instance, was originally shown to be correlated with coronary disease,^{7 9 32 33} but subsequent investigations have shown that the relation is more complex.^{34 35} Specific aspects of the type A pattern, such as hostility, are now considered to be more specific predictors of disease.³⁶ Mental stress also has been shown to trigger myocardial ischemia^{37 38} and cardiac arrhythmias.^{39 40} The psychological responses to psychosocial stressors, including work-related stressors, may indeed affect the development of coronary disease, the precipitation of acute events, or both.³² Since job-related stress is only a fraction of the overall stress of daily life, job stress considered by itself may be poorly correlated with coronary disease.

Job stress was measured in this study by the method of Karasek (Table 1). Although this method has been used widely,^{13 14 15 16 17 41} it is limited by its focus on only job demands as a source of stress at work. This measure does not assess other sources of stress that might arise from employment, such as low job security, inadequate pay, interpersonal conflicts with coworkers or customers, irregular schedules, or the difficulties of juggling family demands and work demands. The concept of job strain may need further development to include all sources of work-related stress. It would be valuable to test the hypothesis that a more refined measure of job stress could show an association with coronary disease.

Study Limitations
This study has a number of limitations. It was performed in the late 1980s in a single institution in the southeastern United States and may not accurately reflect working conditions in other places or at other times. Nonetheless, to the extent that job strain is a generalizable construct, one would expect that its predictions would remain valid even under the conditions of this study. Second, angiographic visualization is an imperfect measure of the extent of coronary atherosclerosis. Angiography has proven accurate enough, however, to document correlations of other risk factors with the presence of coronary artery disease and has been proven to be a strong predictor of the risk of a patient dying of heart disease. Third, we cannot exclude the possibility that job stress in American society is so high and so widely prevalent that variations in the level of job stress have no predictive value. We believe this possibility is unlikely for the specific measure of job strain evaluated,¹³ since job strain was present in a minority (28%) of the study population. Fourth, we measured job strain at only one point in time. Changes in level of job strain over time would tend to blunt associations between job strain and the presence of coronary disease and between job strain and prognosis. Finally, this study examined the effect of a specific measure of job stress, and we cannot exclude the possibility that other measures may be predictive of coronary artery disease development or outcome.

Conclusions
This study provides no support for the hypothesis that job strain, as measured by the method of Karasek, leads either to the development of coronary atherosclerosis or to the precipitation of coronary events in individuals with angiographically documented coronary artery disease. Further research will be needed to determine if other measures of stress, either in the occupational setting or in a general sense, can predict the development of coronary atherosclerosis, cardiac events, or both.

	Acknowledgments

 
This study was supported by research grants HL-36587, HL-45702, and HL-17670 from the National Heart, Lung, and Blood Institute, Bethesda, Md; research grants HS-05635 and HS-06503 from the Agency for Health Care Policy and Research, Rockville, Md; and a grant from the Robert Wood Johnson Foundation, Princeton, NJ.

Received December 28, 1994; accepted January 24, 1995.

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