Correspondence
Triggering of Acute Myocardial Infarction by Exercise
N Engl J Med 1994; 330:1156-1157April 21, 1994
- Article
To the Editor:
The articles by Mittleman et al. and Willich et al. (Dec. 2 issue)1,2 suggest that exercise can provoke myocardial infarction, particularly in patients who do not exercise regularly. The accompanying editorial discusses this possibility and weighs the pros and cons of exercise from the viewpoint of its effects on the heart3. However, neither the studies nor the editorial addresses the possibility that patients who had a myocardial infarction during or just after exercise were in a critical state and that the myocardial infarction might well have occurred without the exercise, which simply advanced the infarction by a few hours or days.
The question is whether occasional exercise in relatively sedentary patients produces myocardial infarctions that would not otherwise have occurred in the short term without exercise. It would be unfortunate if patients were advised not to exercise simply on the basis of these studies, since many patients would use such advice as a justification for remaining sedentary.
3 ReferencesJ. Alan Roberts, M.D.
Royal Hampshire County Hospital, Winchester 5022 5DG, United Kingdom1
Mittleman MA ,Maclure M ,Tofler GH ,Sherwood JB ,Goldberg RJ ,Muller JE . Triggering of acute myocardial infarction by heavy physical exertion -- protection against triggering by regular exertion. N Engl J Med 1993;329:1677-1683
Full Text | Web of Science | Medline2
Willich SN ,Lewis M ,Lowel H ,Arntz H-R ,Schubert F ,Schroder R . Physical exertion as a trigger of acute myocardial infarction. N Engl J Med 1993;329:1684-1690
Full Text | Web of Science | Medline3
Curfman GD . Is exercise beneficial -- or hazardous -- to your heart? N Engl J Med 1993;329:1730-1731
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To the Editor:
Does heavy exertion trigger myocardial infarction, as concluded in the two articles and the editorial on this topic? The two studies, using similar methods, confirm the clinical observation that the onset of ischemic chest pain with myocardial infarction occurs not uncommonly during exertion and immediately afterward, but is limited to the first hour after the beginning of the exertion.
The authors of both articles propose that the exertion triggered the onset of infarction. In his editorial, Dr. Curfman speculates about possible mechanisms, including plaque disruption followed by platelet activation and thrombosis. The implication is that the exertion somehow causes the infarction by provoking or accelerating some part of the occlusive process. It is notable that in the U.S. study, 44 of the 54 patients (82 percent) had the onset of pain during exertion, leaving only 10 patients (18 percent) in whom the onset of pain occurred during the first hour after the exertion had ceased.
The processes in the coronary artery that lead to infarction from the moment of plaque damage are likely to extend beyond a few minutes, probably over hours or days, possibly with a fluctuation of the developing or receding platelet and fibrin thrombus1. This thrombus intrudes into the lumen of the coronary artery, potentially reducing the supply of myocardial oxygen. Exercise during this time is highly likely to induce ischemic cardiac pain. The underlying process of unstable angina or impending infarction is indicated by the pain. In some patients the process subsides (unstable angina), in some it progresses to ischemic necrosis (non-Q-wave infarction), and in some it progresses to complete occlusion, usually with a Q-wave acute myocardial infarction.
Many readers may conclude that these two studies demonstrate that if the process of coronary occlusion is under way, pain is brought forward by the physical activity. It may be that the effort does not provoke or trigger infarction but rather leads to a declaration of its impending occurrence. This is more likely to happen in the unfit, because at any given level of exertion, cardiac work (measured by the rate-pressure product) is greater in people who are unfit than in those who are fit.
Caution is required regarding attitudes and advice about a high level of exercise for people who are unaccustomed to it2. However, the metaphor of the two-edged sword is not applicable to the results of these two new studies and should not lead to an ambivalent approach to advice regarding exercise.
2 ReferencesAlan J. Goble, M.D.
Heart Research Centre, Carlton, Victoria 3053, Australia1
Fuster V ,Badimon L ,Badimon JJ ,Chesebro JH . The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:242-50, 310
Full Text | Web of Science | Medline2
Siscovick DS ,Weiss NS ,Fletcher RH ,Lasky T . The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984;311:874-877
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To the Editor:
The articles by Willich et al. and Mittleman et al. would have been more informative if consideration had been given to potential interactions between the strenuous exercise and the time of day that the myocardial infarctions occurred. A portion of the data reported by Willich et al. confirms the repeated observation1-3 that the risk of acute coronary events is higher during the morning hours just after awakening; however, the authors ignored the question of whether the risk of myocardial infarction associated with strenuous exercise interacts with the circadian system. The investigators appear to have data that could address the question of whether the two-to-sixfold increase in the risk of myocardial infarction associated with strenuous exercise is invariable or whether there is a higher risk associated with vigorous exercise performed at a particular time of day, such as the first few hours after awakening. It is important to this issue because of the implications for decisions about when to schedule exercise, including diagnostic exercise tests.
3 ReferencesPatrick J. O'Connor, Ph.D.
University of Georgia, Athens, GA 306021
Muller JE ,Stone PH ,Turi ZG , et al. Circadian variation in the frequency of onset of acute myocardial infarction. N Engl J Med 1985;313:1315-1322
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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
CrossRef | Web of Science | Medline3
Goldberg RJ ,Brady P ,Muller JE , et al. Time of onset of symptoms of acute myocardial infarction. Am J Cardiol 1990;66:140-144
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Author/Editor Response
The authors reply:
To the Editor: Dr. Roberts questions whether the infarctions that occurred after heavy exertion “would not otherwise have occurred in the short term without exercise.” As we stated in the article, the data from this study do not permit differentiation of an infarction that would have occurred several hours later, even without heavy exertion, from one that would never have occurred had the patient avoided exertion at that particular time. However, on the basis of data from other studies, it has been hypothesized that the conditions for a myocardial infarction are established when a triggering activity disrupts a vulnerable atherosclerotic plaque; the intensity of the thrombogenic stimulus, the degree of vasoconstriction, and coagulability then determine whether coronary occlusion occurs1. If a patient had postponed exertion to a time when the plaque was not vulnerable or if coagulability or vasoconstriction had been insufficient, the infarction might not have occurred.
Dr. Goble suggests that exertion merely reveals the impending occurrence of infarction. In our study, only 10 percent of the 1228 patients reported symptoms consistent with a discrete onset of myocardial ischemia in the week before the infarction, and the exclusion of these patients did not alter our results. We agree with Dr. Goble that, in this subgroup, exertion may have revealed rather than caused a thrombotic occlusion. However, in the majority of cases, we hypothesize that exertion initiated the process of plaque disruption and the formation of an occlusive thrombus within one hour. This hypothesis is supported by our finding of an induction time of under 1 hour and evidence from experimental models of plaque disruption in which occlusive arterial thrombus develops in less than 30 minutes2.
Dr. O'Connor notes that the increased risk of coronary events in the morning arouses concern over the safety of exercise in the morning. Our study, at present, has insufficient data on exertion in the early morning to provide a definitive answer to Dr. O'Connor's question. Murray et al. noted that the relative risk of a cardiac event during exercise in the morning, as compared with exercise in the afternoon, was 1.27 (95 percent confidence interval, 0.25 to 6.55)3. Since the base-line risk of myocardial infarction is small, even a relative risk of 7 would produce only a small increase in the absolute risk, which would be insufficient to justify a recommendation to avoid exertion in the morning.
Finally, we agree with the concern of all three correspondents that our findings not be an impediment to regular exercise as recommended by the American Heart Association4. Although our data provide strong evidence that exertion can trigger infarction and is indeed a two-edged sword, the beneficial effects of regular exertion greatly outweigh the harm it can produce. Further study of the manner in which exertion triggers myocardial infarction may lead to a better understanding of the process, which in turn may facilitate the prevention of myocardial infarction after exertion and other potential triggers.
4 ReferencesMurray A. Mittleman, M.D.C.M., M.P.H.
Geoffrey H. Tofler, M.B.
James E. Muller, M.D.
Deaconess Hospital, Boston, MA 02215for the Determinants of Myocardial Infarction Onset Study Investigators
1
MacIsaac AI ,Thomas JD ,Topol EJ . Toward the quiescent coronary plaque. J Am Coll Cardiol 1993;22:1228-1241
CrossRef | Web of Science | Medline2
Chesebro JH ,Lam JY ,Badimon L ,Fuster V . Restenosis after arterial angioplasty: a hemorrheologic response to injury. Am J Cardiol 1987;60:10B-16B
CrossRef | Web of Science | Medline3
Murray PM ,Herrington DM ,Pettus CW ,Miller HS ,Cantwell JD ,Little WC . Should patients with heart disease exercise in the morning or afternoon? Arch Intern Med 1993;153:833-836
CrossRef | Web of Science | Medline4
Fletcher GF ,Blair SN ,Blumenthal J , et al. Benefits and recommendations for physical activity programs for all Americans: a statement for health professionals by the Committee on Exercise and Cardiac Rehabilitation of the Council on Clinical Cardiology, American Heart Association. Circulation 1992;86:340-344
Web of Science | Medline
Author/Editor Response
Dr. O'Connor's concern about the interaction between physical exertion and the circadian variation of myocardial infarction was actually addressed in our article. A multivariate logistic-regression analysis revealed that both strenuous activity and an interval of three hours or less from the time of awakening to the event had statistically independent associations with the onset of infarction. An additional stratified analysis confirmed a similar relative risk associated with strenuous activity during each of four quarters of the day (but the number of patients was small). These results suggest that both physical exertion at any time during the day and routine activities after awakening and arising may be triggers of myocardial infarction in patients with coronary artery disease. Our conclusion is supported by a recent report indicating a similar risk of cardiac events in patients with coronary disease who exercised in the morning and in those who exercised in the afternoon1.
The hypothesis that acute exertion may have led to a myocardial infarction that would otherwise have occurred later or may have led to “a declaration of its impending occurrence” appears to be entirely consistent with the concept of triggering supported by the results of our study. Furthermore, patients in a critical state would, because of their symptoms, probably be less likely to exercise and would therefore belong to the group of patients who have a myocardial infarction without prior strenuous activity. Therefore, if the reasoning of Drs. Roberts and Goble is correct, the true relative risk of exercise would tend to have been underestimated in the present studies.
Finally, Roberts and Goble reemphasize an important issue. A sedentary lifestyle is clearly a risk factor for heart disease, whereas regular physical activity has beneficial long-term effects2-4. The present studies provide additional information that physical exertion may be associated with short-term hazards, particularly in patients unaccustomed to exercise (those either with known heart disease or without a previous cardiac event -- that is, with silent heart disease). Current knowledge therefore suggests that patients should be advised to exercise regularly but to avoid overexertion.
4 ReferencesStefan N. Willich, M.D., M.P.H.
Free University of Berlin, 12200 Berlin, GermanyMichael Lewis, M.D.
Zentralklinikum Augsburg, 86156 Augsburg, Germany1
Murray PM ,Herrington DM ,Rettus CW ,Miller HS ,Cantwell JD ,Little WC . Should patients with heart disease exercise in the morning or afternoon? Arch Intern Med 1993;153:833-836
CrossRef | Web of Science | Medline2
Berlin JA ,Colditz GA . A meta-analysis of physical activity in the prevention of coronary heart disease. Am J Epidemiol 1990;132:612-628
Web of Science | Medline3
Sandvik L ,Erikssen J ,Thaulow E ,Erikssen G ,Mundal R ,Rodahl K . Physical fitness as a predictor of mortality among healthy, middle-aged Norwegian men. N Engl J Med 1993;328:533-537
Full Text | Web of Science | Medline4
Paffenbarger RS Jr ,Hyde RT ,Wing AL ,Lee I-M ,Jung DL ,Kampert JB . The association of changes in physical-activity level and other lifestyle characteristics with mortality among men. N Engl J Med 1993;328:538-545
Full Text | Web of Science | Medline
- Citing Articles (1)
Citing Articles
1
Bryan A. Whitson, Dilip S. Nath, Joshua R. Knudtson, Sara J. Shumway. (2006) Cardiopulmonary Bypass in Revascularization and Fluid Management of Exercise-Induced Acute Myocardial Infarction. Journal of Cardiac Surgery 21:5, 480-483
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