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Cited by 1,426Acute Myocardial Infarction ResearchBlood Coagulation and Thrombosis MechanismsCardiac Health and Mental Health

Circadian variation and triggers of onset of acute cardiovascular disease.

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Muller, J E, Tofler, G H, Stone, P H·1989·Circulation
DOI 10.1161/01.cir.79.4.733
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Abstract

Information obtained during the past decade suggests the need to reexamine the possibility that the onset of myocardial infarction and sudden cardiac death is frequently triggered by daily activities. The importance of physical or mental stress in triggering onset of coronary thrombosis is supported by the findings that 1) the frequencies of onset of myocardial infarction, sudden cardiac death, and stroke show marked circadian variations with parallel increases in the period from 6:00 AM to noon, 2) transient myocardial ischemia shows a similar morning increase, and episodes are often preceded by mental or physical triggers, 3) a ruptured atherosclerotic plaque, often nonobstructive by itself, lies at the base of most coronary thrombi, 4) a number of physiologic processes that could lead to plaque rupture, a hypercoagulable state or coronary vasoconstriction, are accentuated in the morning, and 5) aspirin and beta-adrenergic blocking agents, which block certain of these processes, have been shown to prevent disease onset. The hypothesis is presented that occlusive coronary thrombosis occurs when 1) an atherosclerotic plaque becomes vulnerable to rupture, 2) mental or physical stress causes the plaque to rupture, and 3) increases in coagulability or vasoconstriction, triggered by daily activities, contribute to complete occlusion of the coronary artery lumen. Recognition of the circadian variation--and the possibility of frequent triggering--of onset of acute disease suggests the need for pharmacologic protection of patients during vulnerable periods, and provides clues to mechanism, the investigations of which may lead to improved methods of prevention.

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  • A proposed mechanism for triggering of myocardial infarction is disruption of a vulnerable, but not necessarily stenotic, atherosclerotic plaque in response to hemodynamic stresses; thereafter, hemostatic and vasoconstrictive forces determine whether the resultant thrombus becomes occlusive.

    “A proposed mechanism for the triggering of myocardial infarction is the disruption of a vulnerable, but not necessarily stenotic, atherosclerotic plaque in response to hemodynamic stresses; thereafter, hemostatic and vasoconstrictive forces determine whether the resultant thrombus becomes occlusive.32”

    From Triggering of Acute Myocardial Infarction by Heavy Physical Exertion -- Protection against Triggering by Regular Exertion (1993) · cites this paper as [32]

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  1. Master AM: The role of effort and occupation (including physicians) in coronary occlusion. JAMA 1960;174:942-948
  2. Fitzhugh G, Hamilton BE: Coronary occlusion and fatal angina pectoris: Study of the immediate causes and their prevention. JAMA 1933;100:475-480
  3. Sproul J: A general practitioner's views on the treatment of angina pectoris. N Engl J Med 1936;215:443-452
  4. Phipps C: Contributory causes of coronary thrombosis. JAAI 1936;106:761-762
  5. Parkinson J, Bedford DE: Cardiac infarction and coronary thrombosis. Lancet 1928;1:4-11
  6. Muller JE, Stone PH, Turi ZG, Rutherford JD, Czeisler CA, Parker C, Poole WK, Passamani E, Roberts R, Robertson T, Sobel BE, Willerson JT, Braunwald E, and the MILIS Study Group: Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985;313:1315-1322
  7. Willich SN, Linderer T, Wegscheider K, Schroder R, and the ISAM Study Group: Increased risk of myocardial infarc- tion in the morning (abstract). J Am Coll Cardiol 1988; 11:28A
  8. Pell S, D'Alonzo CA: Acute myocardial infarction in a large industrial population: Report of a 6-year study of 1,356 cases. JAMA4 1963;185:831-838
  9. Thompson DR, Blandford RL, Sutton TW, Marchant PR: Time of onset of chest pain in acute myocardial infarction. Int J Cardiol 1985;7:139-146
  10. Goldberg R, Brady P, Chen Z, Gore J, Flessas A, Greenberg J, Thedosiou G, Dalen J, Muller JE: Time of onset of acute myocardial infarction after awakening (abstract). JAm Coll Cardiol 1989;13:133A
  11. Muller JE, Ludmer PL, Willich SN, Tofler GH, Aylmer G, Klangos I, Stone PH: Circadian variation in the frequency of sudden cardiac death. Circulation 1987;75:131-138
  12. Willich SN, Levy D, Rocco MB, Tofler GH, Stone PH, Muller JE: Circadian variation in the incidence of sudden cardiac death in the Framingham Heart Study Population. Am J Cardiol 1987;60:801-806
  13. French AJ, Dock W: Fatal coronary arteriosclerosis in young soldiers. JAMA4 1944;124:1233-1237
  14. Moritz AR, Zamcheck N: Sudden and unexpected deaths of young soldiers: Diseases responsible for such deaths during World War II. Arch Pathol 1946;42:459-494
  15. Tsementzis SA, Gill JS, Hitchcock ER, Gill SK, Beevers DG: Diurnal variation of and activity during the onset of stroke. Neurosurgery 1985;17:901-904
  16. Marler JR, Price TR, Clark GL, Muller JE, Robertson T, Mohr JP, Hier DB, Wolf PA, Caplan LR, Foulkes MA: Morning increase in onset of ischemic stroke. Stroke 1989; (in press)
  17. Selwyn AP, Shea M, Deanfield JE, Wilson R, Horlock P, O'Brien HA: Character of transient ischemia in angina pectoris. Am J Cardiol 1986;58:21B-25B
  18. Schang SJ Jr, Pepine CJ: Transient asymptomatic S-T seg- ment depression during daily activity. Am J Cardiol 1977; 39:396-402
  19. Cohn PF: Silent myocardial ischemia. Ann Int Med 1988; 109:312-317
  20. Stern S, Tzivoni D: Early detection of silent ischemic heart disease by 24-hour electrocardiographic monitoring of active subjects. Br Heart J 1974;36:481-486
  21. Rocco MB, Barry J, Campbell S, Nabel E, Cook EF, Goldman L, Selwyn AP: Circadian variation of transient myocardial ischemia in patients with coronary artery dis- ease. Circulation 1987;75:395-400
  22. Nademanee K, Intarachot V, Josephson MA, Singh BN: Circadian variation in occurrence of transient overt and silent myocardial ischemia in chronic stable angina and comparison with Prinzmetal angina in men. Am J Cardiol 1987;60:494-498
  23. Barry J, Selwyn AP, Nabel EG, Rocco MB, Mead K, Campbell S, Rebecca G: Frequency of ST-segment depres- sion produced by mental stress in stable angina pectoris from coronary artery disease. Am J Cardiol 1988;61:989-993
  24. Singh BN, Nademanee K, Figueras J, Josephson MA: Hemodynamic and electrocardiographic correlates of symp- tomatic and silent myocardial ischemia: Pathophysiologic and therapeutic implications. Am J Cardiol 1986;58:3B-1OB
  25. Freeman LJ, Nixon PGF, Sallabank P, Reaveley D: Psycho- logical stress and silent myocardial ischemia. Am Heart J 1987;114:477-482
  26. Moncada S, Vane JR: Arachidonic acid metabolites and the interactions between platelets and blood-vessel walls. N Engl J Med 1979;300:1142-1147
  27. Millar-Craig MW, Bishop CN, Raftery EB: Circadian vari- ation of blood pressure. Lancet 1978;1:795-797
  28. Davies AB, Bala-Subramanian V, Cashman PMM, Raftery EB: Simultaneous recording of continuous arterial pressure, heart rate, and ST segment in ambulant patients with stable angina pectoris. Br Heart J 1983;50:85-91
  29. Quyyumi AA, Efthimiou J, Quyyumi A, Mockus LJ, Spiro SG, Fox KM: Nocturnal angina: Precipitating factors in patients with coronary artery disease and those with variant angina. Br Heart J 1986;56:346-352
  30. Ginsburg R, Bristow MR, Davis K, Dibiase A, Billingham ME: Quantitative pharmacologic responses of normal and atherosclerotic isolated human epicardial coronary arteries. Circulation 1984;69:430-440
  31. Ganz P, Alexander RW: New insights into the cellular mechanisms of vasospasm. Am J Cardiol 1985;56:11E-1SE
  32. Furchgott RF, Zawadzki JV: The obligatory role of endo- thelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 1980;288:373-376
  33. Gage JE, Hess OM, Murakami T, Ritter M, Grimm J, Krayenbuehl HP: Vasoconstriction of stenotic coronary arteries during dynamic exercise in patients with classic angina pectoris: Reversibility by nitroglycerin. Circulation 1986;73:865-876
  34. Brown BG, Lee AB, Bolson EL, Dodge HT: Reflex con- striction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circulation 1984;70:18-24
  35. Mudge GH Jr, Grossman W, Mills RM Jr, Lesch M, Braun- wald E: Reflex increase in coronary vascular resistance in patients with ischemic heart disease. N Engl J Med 1976; 295:1333-1337
  36. Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, Ganz P: Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. NEngl JMed 1986;315:1046-1051
  37. Ganz W: Coronary spasm in myocardial infarction: Fact or Fiction? Circulation 1981;63:487-488
  38. Deanfield JE, Shea M, Kensett M, Horlock P, Wilson RA, de Landsheere CM, Selwyn AP: Silent myocardial ischemia due to mental stress. Lancet 1984;2:1001-1005
  39. Rozanski A, Bairey CN, Krantz DS, Friedman J, Resser KJ, Morell M, Hilton-Chalfen S, Hestrin L, Bietendorf J, Ber- man DS: Mental stress and the induction of silent myocardial ischemia in patients with coronary artery disease. N Engl J Med 1988;318:1005-1012
  40. Verrier RL, Hagestad EL, Lown B: Delayed myocardial ischemia induced by anger. Circulation 1987;75:249-254
  41. Deanfield JE, Shea MJ, Wilson RA, Horlock P, de Land- sheere CM, Selwyn AP: Direct effects of smoking on the heart: Silent ischemic disturbances of coronary flow. Am J Cardiol 1986;57:1005-1009
  42. Willich SN, Pohjola-Sintonen S, Bhatia S, Shook TL, Tofler GH, Muller JE, Curtis DG, Williams GH, Stone PH: Sup- pression of silent ischemia by metoprolol without altering the morning increase of platelet aggregability in patients with stable coronary artery disease. Circulation 1989;79(in press)
  43. Frishman W, Charlap S, Kimmel B, Teicher M, Cinnamon J, Allen L, Strom J: Diltiazem, nifedipine, and their combina- tion in patients with stable angina pectoris: Effects on angina, exercise tolerance, and the ambulatory electrocar- diographic ST segment. Circulation 1988;77:774-786
  44. Dargie HJ, Lynch PG, Krikler DM, Harris L, Krikler S: Nifedipine and propranolol: A beneficial drug interaction. Am J Med 1981;71:676-682
  45. Khurmi NS, Bowles MJ, Raftery EB: Are anti-platelet drugs of value in the management of patients with chronic stable angina? A study with ticlodipine. Clin Cardiol 1986;9:493 -498
  46. DeWood MA, Spores J, Notske R, Mouser LT, Burroughs R, Golden MS, Lang HT: Prevalence of total coronary occlusion during the early hours of transmural myocardial infarction.N EnglJMed 1980;303:897-902
  47. Davies MJ, Thomas AC: Thrombosis and acute coronary- artery lesions in sudden cardiac ischemic death. N Engl J Med 1984;310:1137-1140
  48. Ambrose JA, Winters SL, Stern A, Eng A, Teichholz LE, Gorlin R, Fuster V: Angiographic morphology and the pathogenesis of unstable angina pectoris. JAm Coll Cardiol 1985;5:609-616
  49. Sherman CT, Litvack F, Grundfest W, Lee M, Hickey A, Chaux A, Kass R, Blanche C, Matloff J, Morgenstern L, Ganz W, Swan HJC, Forrester J: Coronary angioscopy in patients with unstable angina pectoris. N Engl J Med 1986; 315:913-919
  50. Davies MJ, Thomas AC: Plaque fissuring the cause of acute myocardial infarction, sudden ischemic death, and crescendo angina. Br Heart J 1985;53:363 -373
  51. Nakagawa S, Hanada Y, Koiwaya Y, Tanaka K: Angio- graphic features in the infarct-related artery after intracoro- nary urokinase followed by prolonged anticoagulation: Role of ruptured atheromatous plaque and adherent thrombus in acute myocardial infarction in vivo. Circulation 1988; 78:1335-1344
  52. Constantinides P: Plaque fissures in human coronary throm- bosis. JAtheroscler Res 1966;1:1-17
  53. Barger AC, Beeuwkes R III, Lainey LL, Silverman KJ: Hypothesis: Vasa vasorum and neovascularization of human coronary arteries. A possible role in the pathophysiology of atherosclerosis. N Engl J Med 1984;310:175-177
  54. Falk E: Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis: Characteristics of coro- nary atherosclerotic plaques underlying fatal occlusive thrombi. Br Heart J 1983;50:127-134
  55. Brown BG, Gallery CA, Badger RS, Kennedy JW, Mathey D, Bolson EL, Dodge HT: Incomplete lysis of thrombus in the moderate underlying atherosclerotic lesion during intra- coronary infusion of streptokinase for acute myocardial infarction: Quantitative angiographic observations. Circula- tion 1986;73:653-661
  56. Little WL, Constantinescu M, Applegate RJ, Kutcher MA, Burrows MT, Kahl FR, Santamore WP: Can coronary angiography predict the site of a subsequent myocardial infarction in patients with mild-to-moderate coronary artery disease? Circulation 1988;78:1157-1166
  57. Oliver MF: Prevention of coronary heart disease-Propa- ganda, promises, problems, and prospects. Circulation 1986; 73:1-9
  58. Fujita M, Franklin D: Diurnal changes in coronary blood flow in conscious dogs. Circulation 1987;76:488-491
  59. Ehrly AM, Jung G: Circadian rhythm of human blood viscosity. Biorheology 1973;10:577-583
  60. Tofler GH, Brezinski DA, Schafer AI, Czeisler CA, Ruther- ford JD, Willich SN, Gleason RE, Williams GH, Muller JE: Concurrent morning increase in platelet aggregability and the risk of myocardial infarction and sudden cardiac death. N Engl J Med 1987;316:1514-1518
  61. Brezinski DA, Tofler GH, Muller JE, Pohjola-Sintonen S, Willich SN, Schafer AI, Czeisler CA, Williams GH: Morning increase in platelet aggregability: Association with assump- tion of the upright posture. Circulation 1988;78:35-40
  62. Rosing DR, Brakman P, Redwood DR, Goldstein RE, Beiser GD, Astrup T, Epstein SE: Blood fibrinolytic activity in man: Diurnal variation and the response to varying intensi- ties of exercise. Circ Res 1970;27:171-184
  63. Andreotti F, Davies GJ, Hackett DR, Khan MI, De Bart ACW, Aber VR, Maseri A, Kluft C: Major circadian fluctu- ations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death, and stroke. Am J Cardiol 1988;62:635-637
  64. Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L: Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab 1971;33:14-22
  65. Reis DJ: Potentiation of the vasoconstrictor action of topical norepinephrine on the human bulbar conjunctival vessels after topical application of certain adrenocortical hormones. J Clin Endocrinol Metab 1960;20:446-456
  66. Robertson D, Johnson GA, Robertson RM, Nies AS, Shand DG, Oates JA: Comparative assessment of stimuli that release neuronal and adrenomedullary catecholamines in man. Circulation 1979;59:637-643
  67. Green LH, Seroppian E, Handin RI: Platelet activation during exercise-induced myocardial ischemia. NEnglJMed 1980;302:193-197
  68. Mathis PC, Wohl H, Wallach SR, Engler RL: Lack of release of platelet factor 4 during exercise-induced myocar- dial ischemia. N Engl J Med 1981;304:1275-1278
  69. Estelles A, Tormo G, Aznar J, Espana F, Tormo V: Reduced fibrinolytic activity in coronary heart disease in basal condi- tions and after exercise. Thromb Res 1985;40:373-383
  70. Winther K, Tofler GH, Jimenez A, Brezinski D, Loscalzo J, Muller JE: Comparison of the effect of upright posture and exercise on platelet aggregability and fibrinolytic activity (abstract). JAm Coll Cardiol 1989;(in press)
  71. Shannon RP, Wei JY, Rosa RM, Epstein FH, Rowe JW: The effect of age and sodium depletion on cardiovascular response to orthostasis. Hypertension 1986;8:438-443
  72. Nabel EG, Ganz P, Gordon JB, Alexander RW, Selwyn AP: Dilation of normal and constriction of atherosclerotic coro- nary arteries caused by the cold pressor test. Circulation 1988;77:43-52
  73. De Servi S, Ferrario M, Rondanelli R, Corsico G, Poma E, Ghio S, Mussini A, Angoli L, Bramucci E, Bre E, Specchia G: Coronary vasoconstrictor response to cold pressor test in variant angina: Lack of relation to intracoronary thrombox- ane concentrations. Am Heart J 1987;114:511-515
  74. Fitchett D, Toth E, Gilmore N, Ehrman M: Platelet release of beta-thromboglobulin within the coronary circulation dur- ing cold pressor stress. Am J Cardiol 1983;52:727-730
  75. Mangue M, Haynes EM, Lipner H: Coagulation and fibrin- olytic responses to exercise and cold exposure. Aviat Space Environ Med 1984;55:291-295
  76. Cryer PE, Haymond MW, Santiago JV, Shah SD: Norepi- nephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events. N Engl J Med 1976;295:573-577
  77. Maouad J, Fernandez F, Barrillon A, Gerbaux A, Gay J: Diffuse or segmental narrowing (spasm) of the coronary arteries during smoking demonstrated on angiography. Am J Cardiol 1984;53:354-355
  78. Belch JJF, McArdle BM, Burns P, Lowe GDO, Forbes CD: The effects of acute smoking on platelet behaviour, fibrino- lysis, and haemorheology in habitual smokers. Thromb Haemost 1984;51:6-8
  79. Siess W, Lorenz R, Roth P, Weber PC: Plasma catechol- amines, platelet aggregation and associated thromboxane formation after physical exercise, smoking or norepineph- rine infusion. Circulation 1982;66:44-48
  80. Allen RA, Kluft C, Brommer EJP: Acute effect of smoking on fibrinolysis: Increase in the activity level of circulating extrinsic (tissue-type) plasminogen activator. Eur J Clin Invest 1984;14:354-361
  81. Allen RA, Kluft C, Brommer EJP: Effect of chronic smoking on fibrinolysis. Arteriosclerosis 1985;5:443-450
  82. Rebecca G, Wagner R, Zebede T, D'Adamo A, Hanlon B, Sandor T, Ganz P, Selwyn A: Pathogenetic mechanisms causing transient myocardial ischemia with mental arousal in patients with coronary artery disease (abstract). Clin Res 1986;34:338A
  83. Levine SP, Towell BL, Suarez AM, Knieriem LK, Harris MM, George JN: Platelet activation and secretion associ- ated with emotional stress. Circulation 1985;71:1129-1134
  84. Ogston D: Fibrinolytic activity and anxiety and its relation to coronary artery disease. J Psychosom Med 1964;8:219-222
  85. Dobkin BH: Orthostatic hypotension as a risk factor for symptomatic occulsive cerebrovascular disease. Neurology 1989;(in press)
  86. Spodick DH, Flessas AP, Johnson MM: Association of acute respiratory symptoms with onset of acute myocardial infarc- tion: Prospective investigation of 150 consecutive patients and matched control patients. Am J Cardiol 1984;53:481-482
  87. Lewis HD Jr, Davis JW, Archibald DG, Steinke WE, Smitherman TC, Doherty JE III, Schnaper HW, LeWinter MM, Linares E, Pouget JM, Sabharwal SC, Chesler E, DeMots H: Protective effects of aspirin against acute myo- cardial infarction and death in men with unstable angina: Results of a Veterans Administration Cooperative Study. N Engl J Med 1983;309:396-403
  88. Beta-blocker Heart Attack Trial Research Group: A random- ized trial of propranolol in patients with acute myocardial infarction. Mortality results. JAMA 1982;247:1707-1714
  89. Mulcahy D, Keegan J, Cunningham D, Quyyumi A, Crean P, Park A, Wright C, Fox K: Circadian variation of total ischemic burden and its alteration with anti-anginal agents. Lancet 1988;2:755-759
  90. Willerson JT, Campbell WB, Winniford MD, Schmitz J, Apprill P, Firth BG, Ashton J, Smitherman T, Bush L, Buja LM: Conversion from chronic to acute coronary artery disease: Speculation regarding mechanisms. Am J Cardiol 1984;54:1349-1354
  91. Badimon L, Badimon JJ, Galvez A, Chesebro JH, Fuster V: Influence of arterial damage and wall shear rate on platelet deposition: Ex vivo study in a swine model. Arteriosclerosis 1986;6:312-320 (Circulation 1989;79:733-743)

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Authors
Muller, J. E., Tofler, G. H., & Stone, P. H.
Affiliations
Brigham and Women's Hospital (US)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
1989-04
Volume
79
Issue
4
Pages
733-743
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/01.cir.79.4.733
OpenAlex
W2076778401
Cited by
1,426
References
0
Citations by year
2026: 23 · 2025: 29 · 2024: 31 · 2023: 38 · 2022: 34 · 2021: 41 · 2020: 31 · 2019: 35 · 2018: 34 · 2017: 39 · 2016: 45 · 2015: 46 · 2014: 46 · 2013: 35 · 2012: 56
FWCI
11.42
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Circulation
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
  • Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Health and Mental Health
Keywords
circadian variation, acute cardiovascular disease, myocardial infarction, sudden cardiac death, stroke, plaque rupture, coronary thrombosis, atherosclerosis, hypercoagulability, coronary vasoconstriction, aspirin, beta-adrenergic blocking agents, morning surge, disease prevention
MeSH terms
Activities of Daily Living, Cerebrovascular Disorders, Circadian Rhythm, Coronary Disease, Coronary Thrombosis, Death, Sudden, Humans, Myocardial Infarction

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