Occupational stress, heart disease and heart attacks

Robert F. Carter and Dr. Donald M. Rocklin, M.D., FACC  

                Medical science now strongly supports the propositions that long-term job stress, particularly high demands with low control, causes heart disease and myocardial infarctions, and that short-term emotional distress, particularly anger, causes myocardial infarctions and sudden cardiac deaths.  There is also evidence that chronically working extremely long hours causes heart disease and heart attacks.  Forty years ago these causal relationships were believed by some, doubted by many, and largely unstudied.  Through extensive epidemiological and laboratory research, the contribution of psychological stress, occupational stress in particular, and emotional upset to heart disease and cardiac death has become much clearer, and the biochemical, cellular and neuroelectrical mechanisms much better understood.  

                It has been felt anecdotally and intuitively for centuries that terrible experiences cause heart attacks.  At the time of and shortly after earthquakes, the death of a loved one, divorce, and other instances of extreme emotion, people have myocardial infarctions at a much-increased rate.1  For example, there was a 49% increase in hospital admissions for myocardial infarctions in 16 emergency departments in hospitals studied within a 50-mile radius of the World Trade Center in the 60 days after Sept. 11, 2001, compared with the 60 days prior to Sept. 11.2  Cardiac deaths in surviving spouses occur at a significantly increased rated in the months following the death of a spouse.3  Earthquakes result in increases in heart attacks in the days following the event,4 particularly when the earthquake occurs in the early morning hours.  

                In a myocardial infarction, the blood supply to a part of the heart muscle is disrupted by vessel blockage from a ruptured arterial plaque, from hemorrhage into an arterial plaque, or arterial spasm.  Sudden cardiac death may be a complication of acute myocardial infarction, or be a ‘primary’ rhythm disturbance without infarct. Either way loss of adequate pumping of blood to the vital organs results in rapid death follows, in an hour or less.5  Heart attacks and sudden cardiac deaths occur most frequently between 6 a.m. and noon, mirroring the circadian rhythm of circulating adrenal cortical hormones, controlling autonomic nervous system tone which regulates vascular wall tension, platelet activity, etc.6  

                A workers’ compensation case prompted our close attention to the current state of medical science concerning the role of psychological stress in heart attacks.7 Since long-term stress, long working hours, and short-term emotional upset may be present in the workplace generally and are not wholly unknown in the legal profession, we felt that a brief discussion of the science might be of general interest.  Of equal interest, perhaps, there is experimental and anecdotal evidence that low-dose aspirin and beta-blockers interrupt the pathophysiological mechanisms by which short-term emotional distress produces heart attacks.  These mechanisms and this evidence are discussed below.

A. Epidemiological evidence of the effect of long-term stress.  

                That long-term job stress, particularly high demands with low control, causes heart disease and heart attacks is no longer seriously questioned.   The studies of long-term stress, like all epidemiological studies concerning causation, rely for their significance on a determination of  “relative risk,” abbreviated “RR.”   “Relative risk” means the risk of a particular result, such as heart disease or heart attack, in a studied population with a certain characteristic, such as long-term stressful work or hypertension, when compared with a control population which either does not have the particular characteristic, or has the particular characteristic at a lower, “normal” rate.8 “Relative risk” is also used interchangeably with  “odds ratio,” or “OR,” and “hazard ratio,” or “HR,” which are used synonymously in the epidemiological studies.      

                The largest and most authoritative study of coronary heart disease risk factors is the “INTERHEART” study, published first in 2004 in the Lancet, a premier medical journal.9 INTERHEART involved 12,461 persons hospitalized for myocardial infarction, and compared them with 14,637 matched controls.  The authors compared physical findings and patient history to measure the effects of all known risk factors, including “psychosocial factors,” meaning psychological stress and specifically including chronic work stress.  The effects of known protective factors, such as regular physical exercise, were also studied. People who had heart attacks suffered from psychosocial stress 2.67 times (267%) more frequently that the control population who did not have heart attacks.10  

                For people with long-term work stress in particular, the INTERHEART study found that the relative risk of acute myocardial infarction was 2.14, or 214% of normal, i.e. 114% above normal, when the populations were matched for other known risk factors.   The relative risks of the various contributory factors for heart attacks, compared with the population in general in the INTERHEART study, were, in order of importance:

High cholesterol 3.25
Current smoking 2.87
Psychosocial 2.67
Diabetes 2.37
Stressful Work 2.14
Hypertension 1.91
Abdominal obesity 1.62

See, A. Rosengren, et al., op. cit., at 953; A. Yusef et al., op. cit., at 937, 941; L. Brookes et al., op. cit., at Table 1.   That is, the broad risk category “psychosocial” risk included other psychological stressors besides stressful work, such as stress at home, loss of control over one’s life, and depression.  When stressful work is studied in isolation, it carries a relative risk of 2.14, or 214% of normal, of heart attack.11 (Protective factors studied in the INTERHEART study moderately reduced the risk of heart attack below a relative risk of 1, i.e. below normal: daily consumption of fruit and vegetables, 0.7; regular exercise, 0.8; regular alcohol intake, 0.91.)  

                The large size of the INTERHEART study population resulted in an extremely high confidence level, or “confidence interval,” in the statistical certainty of the findings of relative risk: 99% confidence that the findings are true.12 Therefore these are true effects scientifically.

                Cardiac risk factors, as all other medical risk factors, are defined scientifically only by the epidemiological determination of relative risk: that is, causation is always only a matter of the degree to which a causative factor increases the incidence and prevalence of the pathological condition at issue.  The only way we know that smoking causes lung cancer and heart attacks, the only way we know that breathing asbestos dust causes pleural mesothelioma and pulmonary asbestosis, and the only way we know that isocyanate monomer causes asthma, is by the determination of relative risk by careful epidemiological studies.   

                The INTERHEART study determined that 90.4% of heart disease and heart attacks could be explained by the combined nine risk factors which it identified and studied, as discussed above: “a truly startling and unanticipated result.”13 According to the authors of the INTERHEART study, despite some small variations between countries: …”raised lipids, smoking and psychosocial factors were the most important risk factors in all regions of the world.”14 

B. Other important studies of long-term stress.

                In a well-controlled prospective cohort study which continued for 25.6 years, long-term job stress, defined by high job demands but little control over the demands by the employee, was found to cause heart disease and cardiovascular death in people who began the study with no heart disease.  The rate of death from heart attacks of employees with stressful work was 220% of the rate in the control population of employees with low-stress jobs.   See, M. Kivimaki et al., “Work stress and risk of cardiovascular mortality: prospective cohort study of industrial employees (British Medical Journal 2002; 325: 1-5).  A total of 812 Finnish people with manufacturing jobs and no heart disease were studied over an average period of 25.6 years.  The study was controlled for other cardiac risk factors.  Those employees who had high job demands and relatively little control over the flow of the demands had a relative risk for cardiovascular mortality of 2.2, or 220% of normal compared with the control group with low job strain.   Prospective studies are the best type of epidemiological studies because any bias from retrospective analysis is eliminated; but they are difficult to perform, expensive, and slow.  

                Strikingly, employees who had higher job strain developed high serum cholesterol at a higher rate than the low-job-strain employees as early as 5 years into the study.  Id. at 2 and 4, Table 4.  The implication, of course, is that stressful jobs cause increased serum lipids, that elevated cholesterol may be caused by extrinsic factors in addition to diet, lack of adequate exercise and teetotaling, and that high serum lipids lead to coronary artery disease.  Chronic stress accelerates coronary atherosclerosis in animal experiments.  See, e.g., Z. Zukowska, Atherosclerosis and angiogenesis, Pharmacol.  Rep.  2005 57 Suppl: 229-34.15     

                In a significant survey article by an Australian researcher who is perhaps the leading expert on the cardiovascular effects of stress, Dr. GeoffreyTofler reports:

...the weight of evidence for a role for psychosocial factors in sudden cardiac death has become compelling and in one review of 96 published studies on this topic, a positive association was observed in 92 percent.

G. Tofler, “Psychosocial factors in sudden cardiac arrest,” Up to Date, July 10, 2012, citing H. Hemingway, “Social and psychological influences on sudden cardiac death, ventricular arrhythmia and cardiac autonomic function,” European Heart Journal 2001; 22: 1082.  See also, e.g., G. Tofler, Psychosocial and other social factors in acute myocardial infarction, Up to Date Jan. 2009, at 3-4.  

                The survey article by Dr. David Krantz, et al., “Effects of Mental Stress in Patients with Coronary Artery Disease,” Journal of the American Medical Association, 2000; 283(14): 1800-1802, reviews numerous medical studies which provide the firm basis for believing that (1) chronic stress causes coronary artery disease, and that (2) stress is particularly dangerous, both chronically and in the short term, particularly for people with existing coronary artery disease.  Stress causes the “release of catecholamines [e.g. adrenalin] and corticosteroids, concomitant increases in heart rate, cardiac output, and blood pressure, and changes in processes relevant to hemostatis and thrombosis [clotting].”  Id. at 1800.  The mechanism for promoting atherosclerosis is thought to be by action on the lining of the coronary blood vessels and/or the direct “triggering of lethal arrhythmias through alterations of cardiac neural transmission.”  Id., loc. cit.  Psychological stress causes the release of natural chemical substances which cause atherosclerosis in the long run and in the short run cause platelets to become sticky and predispose the blood to coagulate. Blockages in the coronary arteries may result.16    

                In a long-term study, researchers found that persons with a chronic sense of time-urgency/impatience had a relative risk of heart attack of 4.45, that is, they were 4.45 times as likely as normal to have a non-fatal heart attack as persons who had a low level of time-urgency/impatience.  The study closely examined a population of heart attack victims selected from admissions to coronary or intensive care units of Boston hospitals, matched with a population controlled for age and sex, from the same community.  (Persons with fatal heart attacks could obviously not be studied.)  S. Cole et al., “Time urgency and risk of non-fatal myocardial infarction,” International Journal of Epidemiology 2001:30, 363-369.   

                See also, K.  Matthews et al., “Chronic work stress and marital dissolution increase risk of post trial mortality in men from the Multiple Risk Factor Intervention Trial ( MRFIT).  Archives of Int.  Med. (2002);162a: 309.   The study followed for nine years12,866 men with no evidence of coronary heart disease (CHD) but with risk factors of hypertension, high cholesterol, and cigarettes.   Although the study focused on the cardiac effect of marital dissolution, it also found that persons with high work stress, measured by high job demands and low decision-making ability to control demands, significantly  increased cardiovascular disease mortality, with a very high confidence level of 99.4%.17  

                Thus chronic job stress has now been shown to cause heart disease and heart attacks to a significant degree in many epidemiological studies.  It is accepted as a major causal factor in the medical literature concerning heart disease and death, causing large increases in heart disease and death.

C.  Short-term emotional distress, particularly anger, triggers heart attacks and sudden cardiac death.  

                Emotional upset can trigger heart attacks and sudden cardiac death, and emotional upset specifically can trigger ventricular arrhythmias, especially in people with preexisting coronary artery disease.  Research physicians have demonstrated that emotional upset is the most common trigger of heart attacks, followed by unaccustomed physical activity; that mental stress triggers ventricular arrhythmias in persons with coronary artery disease; and that emotional turmoil, particularly anger, increases the risk of heart attack very significantly.  The mechanisms for these effects are experimentally demonstrable in controlled laboratory conditions.   We will discuss these studies and conclusions below.  

                This pathological mechanism, by which emotional stress may precipitate acute cardiac events, can be muted or prevented by a single low-dose aspirin or by beta-blockers.  Beta blockers are pharmaceutical inhibitors of the activation of the beta-receptors in the adrenergic nervous system, including the beta1 receptors which, when activated, caused contraction and excitability of the heart muscle.18 See, e.g., M.A. Mittleman, et al., “Triggering of Acute Myocardial Infarction Onset by Episodes of Anger,” Circulation 1995;92: 1720-1725; and see, A Murray et al., “Triggering of Acute MI onset by episodes of anger,” Circulation (American Heart Association) 1995:92: 1720-1725.  The principal findings of these studies are discussed below; the authors note the ability of aspirin and beta-blockers to prevent the triggering effect.  And c.f.,  H. D. Critchley et al.,  “Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism,” Brain (2005), 128: 75-85, semble.  That is, the cascade of physiological responses to emotional stress: the increased stickiness of the platelets and their tendency to cause clots, the electrical imbalance between the right and left sides of the ventricle of the heart, and the inhibited vasodilation (and even vasoconstriction) of atherosclerotic coronary arteries in persons with CHD is reduced or prevented by uncoated baby aspirin or beta-blockers, thus lowering the likelihood that a heart attack will be triggered by the emotional stress.19 

                The previously cited review articles by Dr. Geoffrey Tofler also confirm, based on the epidemiological and experimental studies, that short-term emotional upset  often triggers a heart attack or sudden cardiac death.  See also, A, G. Tofler et al., “Analysis of possible triggers of acute myocardial infarction (the MILIS study),” American Journal of Cardiology 1990:66-22-27 (Emotional upset was found to be the most common trigger for heart attack [18.4%], followed by exercise [14%]). (MILIS was the Multicenter Investigation of the Limitation of Infarct Size study, 1978-1983).   

                Descriptions of several studies may be illustrative.  In a Harvard Medical School study, 1623 patients who had acute myocardial infarction were studied immediately following their heart attack and compared with two control populations.  “The relative risk of myocardial infarction in the 2 hours after an episode of anger was 2.3...” or 230% of normal, with a confidence interval of 95%.   M.A. Mittleman, et al., “Triggering of Acute Myocardial Infarction Onset by Episodes of Anger,” Circulation 1995;92: 1720-1725.  See also, to the same effect, J.  Moller et al., “Do episodes of anger trigger myocardial infarction?  A case-crossover analysis in the Stockholm Heart Epidemiology Program (SHEEP),” Psychosomatic Medicine (1999); 61:842-849.  In this study of 699 patients admitted to coronary care units with myocardial infarctions, the authors studied the patients’ exposure during the period immediately preceding the heart attack, compared with exposure of a control population.  The study found that the patients who had heart attacks were nine times more likely to have been “very angry” during the hour preceding the heart attack than the control population; that is, the relative risk heart attacks from short-term anger was 9, with a 95% confidence level.  In fact, in those of the patients who had no premonitory symptoms, such as chest pain or flushing, the relative risk was 15.7, or 1,570% of normal, also with a 95% confidence interval.  The data also suggested an increased trigger effect among patients who reported that they used non-overt strategies of coping with aggressive situations, such as not protesting when being treated unfairly (i.e., those who held anger in), and among those who did not use beta blockers.  See also Dr. Tofler’s review articles, A, G. Tofler et al., “Psychosocial factors in sudden cardiac arrest,” Up To Date, uptodate.com  (July 10, 2012); and G. Toffler et al., Psychosocial and other social factors in acute myocardial infarction,” Up To Date, uptodate.com (Mar. 29, 2012), to the same effect.  And see  C. Pignalberi et al., “Psychological stress and sudden death,” Ital. Heart J. Suppl. (Oct. 2002); 3(10): 1011-1021, semble.    

                “Physical and mental activities (involving emotions) serve as triggers of daily life [for] ischemia [lack of blood supply] in CAD [coronary artery disease] patients.” A, D. Krantz et al., “Effects of mental stress in patients with coronary artery disease,” Journal of the American Medical Association (2000); 283(14): 1800-1802.  Dr. Krantz’s review article cites additional medical studies which demonstrate that:

Mental stressors can provoke ischemia in 40% to 70% of patients with CAD.  This ischemia is usually silent...  Anger is an especially potent trigger of ischemia.”

Id. at 1800 (emphasis supplied), citing, inter alia, M.M. Burg, et al., “Role of behavioral and psychological factors in mental stress-induced silent left ventricular dysfunction in coronary artery disease,” Journal of the American College of Cardiology, 1993: 22:440-448; and A. Rozanski et al., Mental stress and the induction of myocardial ischemia in patients with coronary artery disease,” New England Journal of Medicine 1988; 318: 1005-1011. See also, R.D. Lane, “Psychological stress preceding idiopathic ventricular fibrillation,”  Psychosomatic Medicine 2005; 67:359-365:

Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease.

Id.  The study, at a 96% confidence level, found that surviving patients with apparently normal hearts who suffered ventricular fibrillation were much more likely to have suffered significant emotional stress in the 24 hours prior to their life-threatening cardiac events compared with matched controls.   

                The evidence is that emotional stress immediately induces potentially fatal heart arrythmias, especially in vulnerable people, via what is essentially sympathic nervous system discharge.  The work of Dr.Rachel Lampert and her colleagues at Yale Medical School has shown conclusively that even the stress of being required quickly to subtract backwards by sevens triggers ventricular arrhythmias in persons with heart disease.  See, R. Lampert, et al., “Destabilizing Effects of Mental Stress on Ventricular Arrhythmias in Patients with Implantable Cardioverter-defibrillators,” Circulation (American Heart Association) 2000; 101: 158-164. In this study, patients with coronary artery disease and implanted ventricular defibrillators when asked to subtract by seven from a three-digit number or asked to recall episodes of anger suffered ventricular tachycardia which required shocks from the defibrillator.20 The authors concluded that:

Mental stress alters VT [ventricular tachycardia, a too-rapid contraction of the heart ventricle] and termination without evidence of ischemia.  This suggests that mental stress may lead to sudden death through the facilitation of lethal ventricular arrhythmias.

Id. at 158 (emphasis supplied.)  Moreover, the triggering of the arrhythmia was correlated with a significant increase in circulating catecholamines (adrenalin, also known as epinephrine, and norepinephrine).   

                Dr. Lampert and her colleagues have also shown directly that anger produces ventricular arrhythmias.  See, R. Lampert, et al: “Emotional and Physical Precipitants of Ventricular Arrhythmia,” Circulation (American Heart Association) 2002; 106:1800-1805. In heart disease patients with implantable cardioverter-defribrillators, the study showed that anger produces ventricular arrhythmias (relative risk 1.83, confidence level of 96%).   And see, M. Burg, R. Lampert et al., “Psychological traits and emotion-triggering of ICD [implanted cardioverter-defibrillators] shock-terminated arrhythmias,”  Psychosomatic Medicine, 2004; 66:898-902.(finding a strong correlation of cardiac arrhythmia with strong emotion in a clinical laboratory study of 240 ICD patients at Yale).   

                In fact, medical neuroscience researchers can now show in detail how mental stress causes ventricular arrhythmias; that is, the correlation of mid-brain arousal by stress with the electrical impulse imbalances in the ventricle mediated by the sympathetic nervous system.  See, H.D. Critchley et al.,  “Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism,” Brain (2005), 128: 75-85.  The study was initiated because “Abundant evidence implicates mental and physical stress associated with everyday living in the precipitation of sudden cardiac death;” the authors sought to understand the physiological mechanism.  Id. at 76.  Patients with coronary artery disease were tested with electrocardiogram and PET scans while being mentally stressed by rapid serial subtraction by 7 from a cued starting point over a three-minute period.  A strongly positive relationship was shown between stress-induced “right-lateralized asymmetry in midbrain activity and proarrhythmic abnormalities of cardiac repolarization;” that is, electrical abnormalities in the resetting of the electrical system of the heart after discharge, which electrical abnormalities induce arrhythmia.  Id. at 75.  The authors concluded that:

A right-left asymmetry in sympathetic drive across the surface of the heart disrupts the electrophysiological homogeneity of ventricular repolarization, predisposing to arrhythmia.  Our findings highlight a proximal brain basis for stress-induced cardiac arrhythmic vulnerability.

Id. at 75.  The authors trace the predecessor and analogous studies which have allowed this depth of understanding.  The authors confirm that “Emotional challenges and mental and physical stress are associated with arrhythmogenesis, again via efferent autonomic activity, and patients with pre-existing cardiac disease are especially vulnerable.”  And they are able to show in considerable detail just how the firing off of the neural mid-brain centers in response to emotional stress activates the sympathetic nervous system to cause the right-left ventricular electrical imbalance which triggers the ventricular arrhythmia, especially in people with coronary artery disease.   

D. Chronically working long hours appears to increase the risk of heart disease and heart attack.

                Although less well studied, there is strong evidence that working chronically long hours, independently from the degree of psychological stress of the job, increases CHD and sudden cardiac death. This finding emerged from a large prospective study of British civil servants, known as the Whitehall study.  See, M.K., Virtanen et al., “Overtime work and incident coronary heart disease: the Whitehall II prospective cohort study,” European Heart Journal (2010, July); 31(14):1737-44. The Whitehall study also showed a linear relationship: the more overtime hours worked, the higher the risk of heart disease and cardiac death.  The graduated effect of the extent of overtime work on the increase in cardiac risk is, medically speaking, also persuasive: the greater the overtime, the greater the risk.  In the study, 6,014 employees free from CHD at the beginning of the study were followed for an average of eleven years.  Controlling for all other known cardiac risks,  study participants who regularly worked 3-4 hours of overtime per day had an increased incidence of fatal and non-fatal heart attacks, with a relative risk of 1.67.   

                The risk factors for CHD and heart attacks are cumulative.  For attorneys practicing in workers’ compensation, awareness of the cardiac risks associated with work, including their own work, may be helpful; and carrying a few baby aspirin may not be a bad idea for some of us.21 


1  See generally, current review articles by a leader in the field for many years: Geoffrey Tofler, Psychosocial and other social factors in acute myocardial infarction, Uptodate.com, May 29, 2012; G. Toffler, Psychosocial factors in coronary and cerebral vascular disease, Uptodate.com Feb. 7, 2012; and G. Toffler, Psychosocial factors in sudden cardiac arrest, Uptodate.com, July 10, 2012. Uptodate.com is a highly regarded medical textbook updated frequently and used widely by physicians on a subscription basis. 

2  See, J.R. Allegra, et al., Cardiac events in New Jersey after the Sept. 11, 2001, terrorist attack.  J. Urban Heatlh 2005; 82:358. 

3  C.M. Parkes et al., Broken hearts: a statical study of increased mortality among widowers.  Br. Med. J. 1969; 1:740. 

4   L. J. Kloner, The Northridge earthquake as a trigger for acute myocardial infraction, Am. J. Cadiol. 1996, June 1;77(14); 1230-32 (Northridge, CA, earthquake followed by a 35% increase in the number of admissions for myocardial infarction to coronary care units; D. Tichopoulos et al., Psychological stress and fatal heart attack: the Athens (1981) earthquake natural experiment. Lancet 1983; 1:411; J. Leor, et al., Sudden cardiac death triggered by an earthquake. N. Engl. J. Med. 1966; 334; 413.

5  See, D. Zipes, “Sudden Cardiac Death,” Circulation 1998;98;2334-2351; and see an account of sudden cardiac death for laymen, “Sudden Cardiac Arrest” at the Cleveland Clinic web site: http://my.clevelandclinic.org/heart/disorders/electric/scd.aspx

6  See, as examples of many studies, J.E. Muller, “Circadian variation in the frequency of sudden cardiac death,” Circulation 1987; 75:131; H.R. Arntz, et al., “Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases.” European Heart J. 2000: 21:315; S.N. Willich et al., Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population, Am. J. Cardiology 1987; 60:801.

7  The head of quality-control for a bearings manufacturer for many years worked twelve or more hours a day and on weekends to keep up with the demands of an extremely challenging job.  He was required to go, on short notice, on a business trip to a parts supplier in California, because a subordinate refused to go.  The subordinate was in charge of the project, making critical new bearings for a jet engine.  The department head was very upset that he suddenly had to take a several-day trip, which would put him further behind in his already heavy load of deadline-driven crucial tasks.   After leaving for LaGuardia in the early morning, he was flying from Dallas to California when he had a heart attack on board the airplane over western Texas, and was pronounced dead in a Texas hospital after the plane made an emergency landing.   The man, in addition to chronic job stress, chronically long working hours and short-term emotional upset, also had marginally high serum lipids and rheumatoid arthritis, (both of whi  ch may have also contributed to his coronary artery disease), and clinically asymptomatic coronary atherosclerosis, discovered on autopsy.  A recent cardiac stress test had been negative.

8  “The relative risk (RR) is the probability that a member of an exposed group will develop a disease relative to the probability that a member of an unexposed group will develop that same disease.

 “RR = P(disease/exposed)   P(disease/unexposed)”

Http://www.biostat.wisc.edu, a biostatistics resource.  See also, Wikipedia: “In statistics and mathematical epidemiology, relative risk (RR) is the risk of an event (or of developing a disease) relative to exposure. Relative risk is a ratio of the probability of the event occurring in the exposed group versus a non-exposed group,” citing  Sistrom CL, Garvan CW (January 2004), "Proportions, odds, and risk". Radiology 230 (1): 12–9. doi:10.1148/radiol.2301031028. PMID 14695382.  “In many cases the relative risk is modified by the duration or intensity of exposure to the causative factors.” The Medical Dictionary; http://medicaldictionary.thefreedictionary.com/relative+risk. Researchers match the control population as closely as possible with the studied population; but sometimes, as in rare diseases, the general background is used, that is, for example, the incidence of mesothelioma or other rare tumors in the whole population.

9  The two principle articles from the INTERHEART study were published together in The Lancet in 2004.   See, A. Rosengren et al., “Association of psychosocial risk factors with risk of acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study): case control study,” Lancet 2004;364: 953 – 962; and,  A. Yusef et al., “Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the  INTERHEART STUDY): case-control study. Lancet 2004; 364: 937-952.  See also, L. Brookes, Msc, “INTERHEART: A Global Case-Control Study of Risk Factors for Acute Myocardial Infarction, Medscape 11/23/08.

10  The INTERHEART study began with 15,152 “incident cases,” i.e. people  identified in coronary care units as having just had a first heart attack within 24 hours.  They were compared with a control population of another 14, 637 people matched with the incident cases with respect to age and sex.  The control population was recruited from other hospital non-cardiac patients, visitors to the hospital, and staff.   Complete data, for purposes of the study, was available for a smaller number of study subjects.  See  A. Rosengren et al., Association of psychosocial risk factors with risk for acute myocardial infarction in 11,119 cases and 13,648 controls from 52 countries (the INTERHEART study): case control study, Lancet 2004;364: 953 - 962; and see, A. Yusef et al., “Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the  INTERHEART STUDY): case-control study. Lancet 2004; 364: 937-952.  See also, L. Brookes, Msc, “INTERHEART: A Global Case-Control Study of Risk   Factors for Acute Myocardial Infarction, Medscape 11/23/08, summarizing the INTERHEART findings. 

11  A. Rosengren, op. cit., at 953.

12  Id.; and L. Brooks, op. cit., at 2, citing S. Yusef, op. cit.

13  See, Cl. Ex. A, L. Brookes et al., op. cit, at 4, citing S. Yusef et al., “Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the  INTERHEART STUDY): case-control study. Lancet 2004; 364: 937-952.  

14  S. Yusef, et al., “Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the  INTERHEART study): case-control study. Lancet 2004; 364, at p. 943.  Of considerable interest is also the finding of the INTERHEART study that a family history of cardiac problems, when the effects of the nine identified risk factors are taken into account, has no significant role as an independent  risk factor: the risk factors explain away the apparent role of family history.  Family history, of course, may be associated with, e.g., diet and cholesterol, physical activity, smoking, obesity, holding anger in, etc.  In the nine risk factors, work-related stress was treated as a subcategory of pyschosocial stress, as well as analyzed separately.  A. Rosengren, op. cit.

15  However, studies of the effects of long-term stress on serum lipids, as opposed to studies which focus on myocardial infarctions or cardiac death, are few; the area invites greater research.

16  Adrenaline release induced by stress causes increased oxygen demand and, in response, dilation of coronary arteries in normal people; but in people with arteriosclerosis, adrenaline causes impaired vasodilation or even vasoconstriction.

17  See also, S. Richardson, et al., “Meta-analysis of perceived stress and its association with incident coronary heart disease,” Am. J. of Cardiology 2012; DOI: 10.1016/j.amjcard.2012.08.004. 

18  “Beta-blockers” are pharmaceuticals which block receptor sites on nerves of the adrenergic portion of the sympathetic nervous system, which, by means of adrenaline-related mediators, governs heart rate, blood pressure, and vasoconstriction in the circulatory system.  In the “fight or flight” response, a burst of adrenalin (and other mediators released by the covering of the adrenal glands) results in profound short-term physiological changes.  Beta-blockers mute the response of the circulatory system in general and the cardiovascular system in particular, to those chemicals which are released in response to emotional upset.  See, e.g., F. Gorre and H. Vandekerckhove,“Beta-blockers: focus on mechanism of action. Which beta-blocker, when and why?,” Acta Cardiol. 2010 Oct;65(5):565-70, available from the National Instututes of Health at http://www.ncbi.nlm.nih.gov/pubmed/21125979.

19  Recent evidence has suggested that uncoated baby aspirin are more effective in this regard, and that the phenomenon described as “aspirin resistence” is more likely the difference in response to coated and uncoated aspirin.  See, T. Grosser, et al., Drug Resistance and Pseudoresistance: An Unintended Consequence of Enteric Coating Aspirin, Circulation. 2012, published online before print December 4 2012; K. Thomas, Study Raises Questions on Coating of Aspirin, New York Times Dec. 4, 2012; D. Cox, et al., Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers, Stroke. 2006 Aug; 37(8): 2153-8.

20  The implantable cardioverter-defibrillator (ICD) shocks the fibrillating ventricle to halt the potentially fatal arrhythmia); a well-publicized patient with an ICD has been former Vice President Dick Cheney.

21  In the case which triggered our inquiry, the additive risk factors at work for the claimant’s decedent created a risk of heart attack approximately 11 times normal: long-term job stress, relative risk 2.2; short-term emotional upset, 2.0; extreme working hours, 1.67; elevated serum lipids, 3.25; rheumatoid arthritis, 1.94 (though the effects of rheumatoid arthritis have been little studied): total relative risk 11.06.  Of this increased risk, a relative risk of 5.87 was attributable to the employee’s chronic and acute job stress and to his chronically long working hours.  For an example of a study linking rheumatoid arthritis with an increased risk of cardiac death, see, H. Maradit-Kremers et al., “Cardiovascular death in rheumatoid arthritis: a population-based study,” Arthritis and Rheumatism 2005 March; 52(3):722-32.


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Attorneys at Law
Woodbridge Office Park
One Bradley Road Suite 301
Woodbridge, Connecticut 06525

Toll free: (888)-688-8610
Local: (203)-389-7000
Fax: (203)-389-7004

Donna Civitello: dc.cartercivitello@snet.net 
Robert Carter: bc.cartercivitello@snet.net 
Tara Bonzani: tb.cartercivitello@gmail.com 
Para Español: ms.cartercivitello@gmail.com



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