ST elevation myocardial infarction triggers
ST Elevation Myocardial Infarction Microchapters
ST elevation myocardial infarction triggers On the Web
Several factors have been associated with an increased risk of developing ST elevation myocardial infarction (STEMI). These factors include physical exertion, psychological stress, sexual activity, diurnal (daily) variations in cortisol and platelet aggregation and circannual (yearly) variations in lipids and infectious etiologies, exposure to pollution and or particulate matter, cocaine and ingestion of a recent fatty meal.
Muller et al have developed the following nomenclature to categorize and analyze data pertaining to triggers of MI :
(1) Trigger: An activity that produces short-term physiological changes that may lead directly to onset of acute CVD.
(2) Acute risk factor: A short-term physiological change, such as a surge in arterial pressure or heart rate, an increase in coagulability, or vasoconstriction, that follows a trigger and may result in disease onset.
(3) Hazard period: The time interval after trigger initiation associated with an increased risk of disease onset because of the trigger. The onset and offset times of the hazard period, which could also be designated a “vulnerable period,” may be sharply defined, as in heavy exertion, or less well defined, as with respiratory infection. The duration of the hazard period may also vary, eg from < 1 hour during heavy physical exertion to weeks or months with bereavement.
(4) Triggered acute risk prevention (TARP): Cardiovascular risk reduction that focuses on the short-term increase in risk associated with a trigger.
Putting Relative Risk of MI and Absolute Risk of MI Into Clinical Context
In the following sections, you will read that certain triggers are associated with a dramatic rise in the relative risk of having an MI (e.g. heavy exertion among patients with a sedentary lifestyle increases their risk of an MI 107 fold). These dramatic increases in relative risk, must, however, be placed in the appropriate clinical context.
It must be born in mind that while triggers are frequent events, MI or sudden death are relatively infrequent events. The risk of sudden death with exercise provides a nice example. The relative risk of sudden death within 30 minutes after >/= 6 METS of exercise goes up 16.9 fold. However, because sudden death is so infrequent, this translates into 1 sudden cardiac death for every 1.51 million episodes of heavy exertion.  The number of absolute events is even lower among nurses in the Nurses Health Study undertaking mild to meoderate exertion: 1 sudden death for every 36.5 hours of exertion. 
While the presence of triggers increases the relative risk of MI dramatically, the absolute number of MIs attributable to the trigger may be quite low.
A dramatic rise in the relative risk of a very, very, very infrequent event therefore translates clinically into a very small rise in the absolute number of events attributable to the trigger.
Physical Exertion and MI
Physical exertion, especially if the exertion is much more intense than the individual usually performs has been associated with the onset of STEMI.    The ONSET study demonstrated that intense exertion (defined as >/= 6 metabolic equivalents of METS) within the previous hour was associated with a 5.9 fold rise in the risk of MI .
Studies linking physical exertion to MI:
- The ONSET Study: Relative risk = 5.9 
- The Stockholm Heart Epidemiology Program (SHEEP): Relative risk = 6.1 
- The Triggers and Mechanisms of Myocardial Infarction (TRIMM) study: Relative risk = 2.1 
Impact of a sedentary lifestyle: The relative risk of MI quoted above increases dramatically among those individuals who lead a sedentary lifestyle. For those in poor physical condition, the relative risk was 107 fold higher in the ONSET study. In contrast, among those individuals who reported that they engaged in physical activity 5 days a week or more, the risk was only doubled.
Mechanism: It has been hypothesized that exertion increases blood pressure, pulse and oscillatory shear which in turn may increase the risk of plaque rupture.
Physical Exertion and Sudden Death
While the above discussion pertains to documented nonfatal MI, approximately a quarter of MI patients may die of sudden death or fatal MI before reaching the hospital. In a cohort of 21,481 male physicians in the United States who by self report who had no prior history of coronary artery disease, there was a 16.9 fold rise in the risk of sudden cardiac death within 30 minutes of intense exertion (>/= 6 METS) . Similar to what has been reported with respect to the onset of MI, there was no increase in the risk of sudden death with heavy exertion among those nurses who exercised more than 2 hours per week.
Psychological stress associated with anger , work related stressful events , wartime bombing   , earthquakes  and other natural disasters has been associated with an increased risk of onset of myocardial infarction.
Intense anger (fist / teeth clenched) has been associated with a risk in the risk of MI in the 2 hours following the episode in the following studies:
The psychosocial stressors that precipitated the anger were as follows:
- Argument with family members (25%)
- Conflicts at work (22%)
- Legal problems (8%)
Bereavement and the Broken Heart Syndrome
Stress cardiomyopathy which is also known as Left Ventricular Apical Ballooning Syndrome, Takotsubo cardiomyopathy, or Ampulla-shaped cardiomyopathy is a cardiac syndrome characterized by a reversible transient apical ventricular dysfunction. Since the cardiomyopathy is often triggered by emotional stress, such as the death of a loved one, the condition is sometimes also referred to as the Broken Heart Syndrome. In 2006, the syndrome was renamed Stress Cardiomyopathy, and was classified as an acquired cardiomyopathy. 
The typical presentation of someone with takotsubo cardiomyopathy is a sudden onset of congestive heart failure or chest pain associated with EKG changes suggestive of an anterior wall acute MI. During the course of evaluation of the patient, a bulging out of the left ventricular apex with a hypercontractile base of the left ventricle is often noted. It is the hallmark bulging out of the apex of the heart with preserved function of the base that earned the syndrome its name "tako tsubo", or octopus trap in Japan, where it was first described. Evaluation of individuals with takotsubo cardiomyopathy typically include a coronary angiogram, which does not reveal any significant blockages that would cause the left ventricular dysfunction. Provided that the individual survives their initial presentation, the left ventricular function improves within days to weeks. Takotsubo cardiomyopathy is more commonly seen in post-menopausal women. Often there is a history of a recent severe emotional or physical stress.
Work Related Stress
An aggressive timeline or deadline at work has been associated with a rise in the risk of MI:
- The SHEEP study: 6 fold rise
- The ONSET study: 2.3 fold rise
Firing an Employee
The stress of firing an employee has been associated with a rise in the risk of MI:
- The ONSET study: 2.2 fold rise
Natural disasters have been associated with an increased risk of MI. The best documented association has been with earthquakes. For instance the 1994 earthquake in Los Angeles was associated with a 4 fold rise in the risk of sudden death and a 35% rise in the relative risk of a non-fatal MI.   It is notable that the association of earthquakes with MI is variable depending upon the time of day that the earthquake occurs. The LA earthquake occurred just after 4 A.M., just when platelet aggregation may be at a peak (see below). However, the earthquake that struck San Francisco Bay in 1989 at 5 P.M. was not associated with an increased risk of MI. 
Wartime Stress and Missile Attacks
Within 50 miles of the world trade center, there was a 49% increase in the relative risk of an MI in the 60 days following the 9/11 attack: There were 118 MIs in the 60 days after the attack versus 79 MIs in the 60 days before (p=0.01). How much of this is attributable to particulate matter versus psychological stress is not clear. 
The stress of missile attacks has been associated with a doubling in the risk of non fatal MI and sudden death. 
The stress of sporting events has been associated with an increased risk of MI in a population. An example that has been cited is the 50% increase in the risk of MI or stroke among Dutch men associated with the loss of Holland to France in the 1996 European football finals. It is notable that no such rise in risk was observed among Dutch women or the French.   The World Cup of soccer has been associated with a doubling of MI incidence. 
The association of sexual activity with the onset of MI may represent components of physical exertion as well as psychologic stress. In both the SHEEP and the ONSET studies, recent sexual activity increased the risk of MI by 2.5 fold . Again, to place this relative risk into clinical context, it should be noted that only 3% of MI patients had had sexual intercourse within the past 2 hours prior to the onset of MI. It should also be noted that the increase in risk of MI with sexual activity did not differ between patients with and without a history of coronary artery disease.
The risk of MI with sexual intercourse is a frequent concern among patients who have coronary artery disease. Again, the data above indicates that recent sexual activity doubles the risk of an MI, and this may on the surface appear to be disconcerting to both a patient and healthcare professional. But again, to place this relative risk into context, the absolute risk must be taken into account. The average risk of an MI in a patient at average risk has been estimated to be about 1 chance in a million during any given hour during middle age. Sexual activity increases that risk to 2 in a million per hour for the 2 hours after sexual intercourse. If the annual risk of MI is about 1%, weekly sexual intercourse will increase this annual risk to just 1.01%.  As is the case with physical exertion, regular exercise (6 METS >/= 3 times per week) reduced the relative risk of MI with sexual intercourse from 3.0 to 1.2 in the ONSET study.
Thus, because the risk is small, because the frequency of sexual activity is relatively small, and because the period of increased risk is short (approximately 2 hours) the absolute risk of MI associated with sexual intercourse is quite small.
Air Pollution / Fine Particulate Matter
Exposure to high levels of ambeint air pollution (exposure to fine particulate matter in the past 2 - 24 hours) has been associated with a transient elevation in the risk of myocardial infarction . There is a rise in CRP and plasma viscosity following exposure to fine particulate matter and it has been speculated that the pulmonary inflammation that follows such exposure may trigger a systemic state of hypercoagulability . Exposure to fine particulate matter has also been associated with changes in autonomic tone manifested by sinus tachycardia  , as well as a reduction in heart rate variability   . Finally, ventricular arrhythmias as manifested by firing of AICDs has been associated with exposure to fine particulate matter .
Acute severe infection, such as pneumonia, can trigger myocardial infarction . A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor.Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.
A Heavy Meal
There have been reports of a 4 fold rise in the risk of MI following a heavy meal. 
This rise in risk may account for a second peak in the circadian variation in the onset of MI around 8 P.M. in the evening. The mechanism underlying the association is not clear. It has been speculated that ingestion of a heavy fatty meal may be associated with a rise in prothrombotic factors and heart rate, and a reduction in vascular reactivity.  
Circadian Variation in the Onset of STEMI
Most MIs occur in the early morning hours when cortisol and adrenaline rise and platelets are more activated. This diurnal variation is obliterated with aspirin therapy, pointing to the putative role of platelets in the initiation of MI.       
Relative Frequency of Triggers in Association with MI
When a creful history is obtained, approximately half (48%) of MI patients will report a trigger . It is notable that 13% of patients will report that there were of 2 or more triggers. The following triggers were most commonly associated with the onset of MI in the Multicenter Investigation of Limitation of Infarct Size (MILIS) study :
- Emotional upset (18%)
- Moderate physical activity (14%)
- Heavy physical activity (9%)
- Lack of sleep (8%)
- Overeating (7%)
STEMI Triggers in Popular Culture
Following the sudden death of Tim Russert of NBC's Meet the Press on June 13th 2008, many laypeople and physicians alike have asked "what are the triggers of a sudden heart attack"? Barbara Walters speculated that Tim Russert may have died from "the stress of the job". Others were concerned about a recent weight gain and lack of sleep. This chapter reviews the literature pertaining to triggers of acute MI.
- Muller JE, Abela GS, Nesto RW, Tofler GH (1994). "Triggers, acute risk factors and vulnerable plaques: the lexicon of a new frontier". J. Am. Coll. Cardiol. 23 (3): 809–13. PMID 8113568. Unknown parameter
- Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE (2000). "Triggering of sudden death from cardiac causes by vigorous exertion". N. Engl. J. Med. 343 (19): 1355–61. PMID 11070099. Unknown parameter
- Whang W, Manson JE, Hu FB; et al. (2006). "Physical exertion, exercise, and sudden cardiac death in women". JAMA. 295 (12): 1399–403. PMID 16551711. doi:10.1001/jama.295.12.1399. Unknown parameter
- Willich SN, Lewis M, Löwel H, Arntz HR, Schubert F, Schröder R (1993). "Physical exertion as a trigger of acute myocardial infarction. Triggers and Mechanisms of Myocardial Infarction Study Group". N. Engl. J. Med. 329 (23): 1684–90. PMID 8232457. Unknown parameter
- Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998). "Prediction of coronary heart disease using risk factor categories". Circulation. 97 (18): 1837–47. PMID 9603539. Unknown parameter
- Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE (1993). "Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of Myocardial Infarction Onset Study Investigators". N. Engl. J. Med. 329 (23): 1677–83. PMID 8232456. Unknown parameter
- Hallqvist J, Möller J, Ahlbom A, Diderichsen F, Reuterwall C, de Faire U (2000). "Does heavy physical exertion trigger myocardial infarction? A case-crossover analysis nested in a population-based case-referent study". Am. J. Epidemiol. 151 (5): 459–67. PMID 10707914. Unknown parameter
- Giri S, Thompson PD, Kiernan FJ; et al. (1999). "Clinical and angiographic characteristics of exertion-related acute myocardial infarction". JAMA. 282 (18): 1731–6. PMID 10568645. Unknown parameter
- Siscovick DS, Weiss NS, Fletcher RH, Lasky T (1984). "The incidence of primary cardiac arrest during vigorous exercise". N. Engl. J. Med. 311 (14): 874–7. PMID 6472399. Unknown parameter
- Glass RI, Zack MM (1979). "Increase in deaths from ischaemic heart-disease after blizzards". Lancet. 1 (8114): 485–7. PMID 85066. Unknown parameter
- Franklin BA, Bonzheim K, Gordon S, Timmis GC (1996). "Snow shoveling: a trigger for acute myocardial infarction and sudden coronary death". Am. J. Cardiol. 77 (10): 855–8. PMID 8623739. doi:10.1016/S0002-9149(97)89181-3. Unknown parameter
- Mittleman MA, Maclure M, Sherwood JB; et al. (1995). "Triggering of acute myocardial infarction onset by episodes of anger. Determinants of Myocardial Infarction Onset Study Investigators". Circulation. 92 (7): 1720–5. PMID 7671353. Unknown parameter
- Möller J, Theorell T, de Faire U, Ahlbom A, Hallqvist J (2005). "Work related stressful life events and the risk of myocardial infarction. Case-control and case-crossover analyses within the Stockholm heart epidemiology programme (SHEEP)". J Epidemiol Community Health. 59 (1): 23–30. PMC . PMID 15598722. doi:10.1136/jech.2003.019349. Unknown parameter
- Johnston SC, Sorel ME, Sidney S (2002). "Effects of the September 11th attacks on urgent and emergent medical evaluations in a Northern California managed care plan". Am. J. Med. 113 (7): 556–62. PMID 12459401. Unknown parameter
- Vukovic DS, Krotin ME, Babic MM, Zivanovic BM (2005). "Anxiety level and responses to stress caused by air raids among patients with ischemic heart disease". Prehosp Disaster Med. 20 (4): 249–52. PMID 16128473.
- Trichopoulos D, Katsouyanni K, Zavitsanos X, Tzonou A, Dalla-Vorgia P (1983). "Psychological stress and fatal heart attack: the Athens (1981) earthquake natural experiment". Lancet. 1 (8322): 441–4. PMID 6131167. Unknown parameter
- Möller J, Hallqvist J, Diderichsen F, Theorell T, Reuterwall C, Ahlbom A (1999). "Do episodes of anger trigger myocardial infarction? A case-crossover analysis in the Stockholm Heart Epidemiology Program (SHEEP)". Psychosom Med. 61 (6): 842–9. PMID 10593637.
- Koton S, Tanne D, Bornstein NM, Green MS (2004). "Triggering risk factors for ischemic stroke: a case-crossover study". Neurology. 63 (11): 2006–10. PMID 15596741. Unknown parameter
- Maron BJ, Towbin JA, Thiene G; et al. (2006). "Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention". Circulation. 113 (14): 1807–16. PMID 16567565. doi:10.1161/CIRCULATIONAHA.106.174287.
- Akashi YJ, Barbaro G, Sakurai T, Nakazawa K, Miyake F (2007). "Cardiac autonomic imbalance in patients with reversible ventricular dysfunction takotsubo cardiomyopathy". QJM. 100 (6): 335–43. PMID 17483198. doi:10.1093/qjmed/hcm028.
- Azzarelli S, Galassi AR, Amico F, Giacoppo M, Argentino V, Tomasello SD, Tamburino C, Fiscella A. (2006). "Clinical features of transient left ventricular apical ballooning". Am J Cardiol. 98 (9): 1273–6. PMID 17056345.
- Leor J, Kloner RA (1996). "The Northridge earthquake as a trigger for acute myocardial infarction". Am. J. Cardiol. 77 (14): 1230–2. PMID 8651102. Unknown parameter
- Leor J, Poole WK, Kloner RA (1996). "Sudden cardiac death triggered by an earthquake". N. Engl. J. Med. 334 (7): 413–9. PMID 8552142. Unknown parameter
- Brown DL (1999). "Disparate effects of the 1989 Loma Prieta and 1994 Northridge earthquakes on hospital admissions for acute myocardial infarction: importance of superimposition of triggers". Am. Heart J. 137 (5): 830–6. PMID 10220631. Unknown parameter
- Allegra JR, Mostashari F, Rothman J, Milano P, Cochrane DG (2005). "Cardiac events in New Jersey after the September 11, 2001, terrorist attack". J Urban Health. 82 (3): 358–63. PMID 16000653. doi:10.1093/jurban/jti087. Unknown parameter
- Meisel SR, Kutz I, Dayan KI; et al. (1991). "Effect of Iraqi missile war on incidence of acute myocardial infarction and sudden death in Israeli civilians". Lancet. 338 (8768): 660–1. PMID 1679475. Unknown parameter
- Witte DR, Bots ML, Hoes AW, Grobbee DE (2000). "Cardiovascular mortality in Dutch men during 1996 European football championship: longitudinal population study". BMJ. 321 (7276): 1552–4. PMC . PMID 11124170.
- Toubiana L, Hanslik T, Letrilliart L (2001). "French cardiovascular mortality did not increase during 1996 European football championship". BMJ. 322 (7297): 1306. PMC . PMID 11403063. Unknown parameter
- N Engl J Med 2008; 358:475-483.
- Muller JE, Mittleman MA, Maclure M, Sherwood JB, Tofler GH (1996). "Triggering myocardial infarction by sexual activity. Low absolute risk and prevention by regular physical exertion. Determinants of Myocardial Infarction Onset Study Investigators". JAMA. 275 (18): 1405–9. PMID 8618365. Unknown parameter
- Möller J, Ahlbom A, Hulting J; et al. (2001). "Sexual activity as a trigger of myocardial infarction. A case-crossover analysis in the Stockholm Heart Epidemiology Programme (SHEEP)". Heart. 86 (4): 387–90. PMC . PMID 11559674. Unknown parameter
- Tofler GH, Muller JE (2006). "Triggering of acute cardiovascular disease and potential preventive strategies". Circulation. 114 (17): 1863–72. PMID 17060396. doi:10.1161/CIRCULATIONAHA.105.596189. Unknown parameter
- Peters A, Dockery DW, Muller JE, Mittleman MA (2001). "Increased particulate air pollution and the triggering of myocardial infarction". Circulation. 103 (23): 2810–5. PMID 11401937. Unknown parameter
- Peters A, Döring A, Wichmann HE, Koenig W (1997). "Increased plasma viscosity during an air pollution episode: a link to mortality?". Lancet. 349 (9065): 1582–7. PMID 9174559. doi:10.1016/S0140-6736(97)01211-7. Unknown parameter
- Peters A, Fröhlich M, Döring A; et al. (2001). "Particulate air pollution is associated with an acute phase response in men; results from the MONICA-Augsburg Study". Eur. Heart J. 22 (14): 1198–204. PMID 11440492. doi:10.1053/euhj.2000.2483. Unknown parameter
- Pope CA3rd, Dockery DW, Kanner RE, Villegas GM, Schwartz J (1999). "Oxygen saturation, pulse rate, and particulate air pollution: A daily time-series panel study". Am. J. Respir. Crit. Care Med. 159 (2): 365–72. PMID 9927345. Unknown parameter
- Peters A, Perz S, Döring A, Stieber J, Koenig W, Wichmann HE (1999). "Increases in heart rate during an air pollution episode". Am. J. Epidemiol. 150 (10): 1094–8. PMID 10568625. Unknown parameter
- Liao D, Creason J, Shy C, Williams R, Watts R, Zweidinger R (1999). "Daily variation of particulate air pollution and poor cardiac autonomic control in the elderly". Environ. Health Perspect. 107 (7): 521–5. PMC . PMID 10378998. Unknown parameter
- Pope CA, Verrier RL, Lovett EG; et al. (1999). "Heart rate variability associated with particulate air pollution". Am. Heart J. 138 (5 Pt 1): 890–9. PMID 10539820. Unknown parameter
- Gold DR, Litonjua A, Schwartz J; et al. (2000). "Ambient pollution and heart rate variability". Circulation. 101 (11): 1267–73. PMID 10725286. Unknown parameter
- Peters A, Liu E, Verrier RL; et al. (2000). "Air pollution and incidence of cardiac arrhythmia". Epidemiology. 11 (1): 11–7. PMID 10615837. Unknown parameter
- Smeeth L, Thomas SL, Hall AJ, Hubbard R, Farrington P, Vallance P (2004). "Risk of myocardial infarction and stroke after acute infection or vaccination". N. Engl. J. Med. 351 (25): 2611–8. PMID 15602021. doi:10.1056/NEJMoa041747. Unknown parameter
- Saikku P, Leinonen M, Tenkanen L, Linnanmaki E, Ekman MR, Manninen V, Manttari M, Frick MH, Huttunen JK. (1992). "Chronic Chlamydia pneumoniae infection as a risk factor for coronary heart disease in the Helsinki Heart Study.". Ann Intern Med. 116 (4): 273–8. PMID 1733381.
- Andraws R, Berger JS, Brown DL. (2005). "Effects of antibiotic therapy on outcomes of patients with coronary artery disease: a meta-analysis of randomized controlled trials.". JAMA. 293 (21): 2641–7. PMID 15928286.
- Lipovetzky N, Hod H, Roth A, Kishon Y, Sclarovsky S, Green MS (2004). "Heavy meals as a trigger for a first event of the acute coronary syndrome: a case-crossover study". Isr. Med. Assoc. J. 6 (12): 728–31. PMID 15609883. Unknown parameter
- Miller GJ, Martin JC, Mitropoulos KA; et al. (1991). "Plasma factor VII is activated by postprandial triglyceridaemia, irrespective of dietary fat composition". Atherosclerosis. 86 (2-3): 163–71. PMID 1872911. Unknown parameter
- Vogel RA, Corretti MC, Plotnick GD (1997). "Effect of a single high-fat meal on endothelial function in healthy subjects". Am. J. Cardiol. 79 (3): 350–4. PMID 9036757. Unknown parameter
- Mittleman MA, Mintzer D, Maclure M, Tofler GH, Sherwood JB, Muller JE (1999). "Triggering of myocardial infarction by cocaine". Circulation. 99 (21): 2737–41. PMID 10351966. Unknown parameter
- Mittleman MA, Lewis RA, Maclure M, Sherwood JB, Muller JE (2001). "Triggering myocardial infarction by marijuana". Circulation. 103 (23): 2805–9. PMID 11401936. Unknown parameter
- Muller JE, Stone PH, Turi ZG; et al. (1985). "Circadian variation in the frequency of onset of acute myocardial infarction". N. Engl. J. Med. 313 (21): 1315–22. PMID 2865677. Unknown parameter
- Willich SN, Levy D, Rocco MB, Tofler GH, Stone PH, Muller JE (1987). "Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study population". Am. J. Cardiol. 60 (10): 801–6. PMID 3661393. Unknown parameter
- Marler JR, Price TR, Clark GL; et al. (1989). "Morning increase in onset of ischemic stroke". Stroke. 20 (4): 473–6. PMID 2648651. Unknown parameter
- Behar S, Halabi M, Reicher-Reiss H; et al. (1993). "Circadian variation and possible external triggers of onset of myocardial infarction. SPRINT Study Group". Am. J. Med. 94 (4): 395–400. PMID 8475932. Unknown parameter
- Tofler GH, Muller JE, Stone PH; et al. (1992). "Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group". J. Am. Coll. Cardiol. 20 (5): 1049–55. PMID 1401601. Unknown parameter
- Ridker PM, Manson JE, Buring JE, Muller JE, Hennekens CH (1990). "Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians". Circulation. 82 (3): 897–902. PMID 2203556. Unknown parameter
- Parker JD, Testa MA, Jimenez AH; et al. (1994). "Morning increase in ambulatory ischemia in patients with stable coronary artery disease. Importance of physical activity and increased cardiac demand". Circulation. 89 (2): 604–14. PMID 8313548. Unknown parameter
- Tofler GH, Stone PH, Maclure M; et al. (1990). "Analysis of possible triggers of acute myocardial infarction (the MILIS study)". Am. J. Cardiol. 66 (1): 22–7. PMID 2193495. Unknown parameter