LETTERS
sure (from 21.5 f 2.7 to 16.7 f 1.6 mm Hg).” These two statements are obviously mutually exclusive. The second is the stated criterion of the “cardiac index less than 2.7 liters/ min per m2.” In the Results the authors report “a significant increase in cardiac output (from 4.9 f 0.37 liters/min. . .) before treatment to 6.0 f 0.38 liters/min. . . .” If the “standard” figure of body surface area of 1.73 m2 is used, then the mean cardiac index before treatment was 2.83 liters/min per m2, which is above the range stated as criterion for admission to the study. Donald S. Ruffett, MD Department of Medicine Hartford Hospital Hartford, Connecticut
References 1. Gillasple TA, Ambos HD, Bobel BE. et al: Effects of dobutamine in patients with acute myocardial infarction. Am J Cardiol 39566-594, 1977
REPLY
The values for pulmonary arterial occlusive pressure and cardiac index should indeed have read “10 mm Hg or more” and “2.7 liters/min or more” rather than “less than” those values. We regret the errors in notation. Thomas A. Gillespie, MD H. Dieter Ambos Burton E. Sobel, MD, FACC Robert Roberts, MD, FACC Cardiovascular Division Department of Internal Medicine Washington University School of Medicine St. Louis. Missouri
OBESITY AND ISCHEMIC
HEART DISEASE
The results of Rabkin et al.l leave no doubt that a higher body mass index is significantly associated with development of myocardial infarction, sudden death and coronary insufficiency. However, I find their conclusion that “overweight is a definite risk factor” is not adequately proved by their data. Definition requires that a risk factor must have a proved causal relation to the disease implied, and it seems to me that this is not fulfilled in the case of obesity and ischemic heart disease. The possibility exists that subjects who start to experience the results of an early and slight coronary atherosclerosis react with self-restriction with regard to physical activity, without admitting this to themselves. It is more than natural that someone who tires more easily than usual and experiences a slight shortness of breath or other indications that “‘he is not in a good physical shape” will react with a reduced desire for sports and other physical activities and that this response will result in weight gain. Such a sequence of events has not been excluded by Rabkin et al. and therefore, although I fully accept their findings that a greater incidence of ischemic heart disease is found in obese subjects, I would like to add a word of caution to their conclusion that obesity is a “risk factor” in the development of coronary atherosclerosis. Shlomo Stern, MD, FACC Hebrew University-Hadassah Medical School and Shaare Zedek Hospital Jerusalem, Israel
622
March 1976
The American Journal of CARDIDLDDY
1. Rabkla SW, Mathewson FAL, Hsu P: Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26 year obsewation period: The Manitoba Study. Am J Cardiol 39:452-458. 1977
REPLY
The requirement for a causal relation is not part of the definition of a risk factor in general usage: 1. “The coronary risk factors are those abnormalities-demonstrable in persons free of clinical CHD (coronary heart disease)“-known to be associated with significantly increased risk of developing the disease in subsequent years.“’ 2. “An attribute which appears to occur more commonly among persons with coronary heart disease than control subjects is defined as a risk factor. It is implied in this particular definition that an association between the disease and a risk factor is not necessarily causal.‘12 3. “The risk factor concept in coronary heart disease (CHD) is based on the finding of statistically significant associations between incidence of CHD and values for the variables in question. Studies performed so far have not shown that any of the risk factors are actually causative.“” 4. “Follow-up studies of persons judged to be free of CHD at entry examination have identified several characteristics associated with increased risk of CHD in future years. Age, arterial blood pressure and serum cholesterol concentration uniformly emerge as important risk factors.“4 5. “Epidemiological studies have shown a significant relationship between the incidence of CHD and various prospective characteristics commonly termed risk factors.‘15 Finding an association is only one step in the proof of causation. We hoped that our finding of an association between body weight and ischemic heart disease would stimulate hypotheses in this field and we are interested to read Stern’s. Although we have no evidence to support or refute his hypothesis that early coronary atherosclerosis limits physical activity, which in turn causes an increase in body weight, some comments are in order. The young age of our cohort at entry means that the coronary atherosclerosis would have had to exert its effects when these men were in their 20’s so that they would be overweight at entry. This and the fact that physical inactivity is one of many variables in the equation yielding overweight do not make this hypothesis attractive to us. S. W. Rabkin, MD, FACC F. A. L. Mathewson, MD, FACC University of Manitoba Department of Medicine (Section Cardiology) and Social and Preventive Medicine Winnipeg, Manitoba, Canada References 1. Stemler J: Lectures on Preventive Cardiology. New York, Grune 8 Stranon. 1967, p 748 2. Epstein FHz The epidemiology of coronary heart disease. A review. J Chronic Dis 18: 735-774. 1965 3. Wllhelmeen L, We&l H, Tlbblns 0: Multivariate analysis of risk factors for coronary hearl disease. Circulation 48:950-956. 1973 4. Keys A, Aravanls C, Blackburn H, Probability of middle aged men developing coronarv heart disease in five years. Circulation 45:815-628. 1972 5. Brand dJ, R-an RH. Bh& RI, et al: Multivariate prediction of coronary heart disease in the Western Collaborative Group Study compared to the findings of the Framingham Study. Circulation 53:346-355. 1976
Volume 41
et al:
sure (from 21.5 f 2.7 to 16.7 f 1.6 mm Hg).” These two statements are obviously mutually exclusive. The second is the stated criterion of the “cardiac index less than 2.7 liters/ min per m2.” In the Results the authors report “a significant increase in cardiac output (from 4.9 f 0.37 liters/min. . .) before treatment to 6.0 f 0.38 liters/min. . . .” If the “standard” figure of body surface area of 1.73 m2 is used, then the mean cardiac index before treatment was 2.83 liters/min per m2, which is above the range stated as criterion for admission to the study. Donald S. Ruffett, MD Department of Medicine Hartford Hospital Hartford, Connecticut
References 1. Gillasple TA, Ambos HD, Bobel BE. et al: Effects of dobutamine in patients with acute myocardial infarction. Am J Cardiol 39566-594, 1977
REPLY
The values for pulmonary arterial occlusive pressure and cardiac index should indeed have read “10 mm Hg or more” and “2.7 liters/min or more” rather than “less than” those values. We regret the errors in notation. Thomas A. Gillespie, MD H. Dieter Ambos Burton E. Sobel, MD, FACC Robert Roberts, MD, FACC Cardiovascular Division Department of Internal Medicine Washington University School of Medicine St. Louis. Missouri
OBESITY AND ISCHEMIC
HEART DISEASE
The results of Rabkin et al.l leave no doubt that a higher body mass index is significantly associated with development of myocardial infarction, sudden death and coronary insufficiency. However, I find their conclusion that “overweight is a definite risk factor” is not adequately proved by their data. Definition requires that a risk factor must have a proved causal relation to the disease implied, and it seems to me that this is not fulfilled in the case of obesity and ischemic heart disease. The possibility exists that subjects who start to experience the results of an early and slight coronary atherosclerosis react with self-restriction with regard to physical activity, without admitting this to themselves. It is more than natural that someone who tires more easily than usual and experiences a slight shortness of breath or other indications that “‘he is not in a good physical shape” will react with a reduced desire for sports and other physical activities and that this response will result in weight gain. Such a sequence of events has not been excluded by Rabkin et al. and therefore, although I fully accept their findings that a greater incidence of ischemic heart disease is found in obese subjects, I would like to add a word of caution to their conclusion that obesity is a “risk factor” in the development of coronary atherosclerosis. Shlomo Stern, MD, FACC Hebrew University-Hadassah Medical School and Shaare Zedek Hospital Jerusalem, Israel
622
March 1976
The American Journal of CARDIDLDDY
1. Rabkla SW, Mathewson FAL, Hsu P: Relation of body weight to development of ischemic heart disease in a cohort of young North American men after a 26 year obsewation period: The Manitoba Study. Am J Cardiol 39:452-458. 1977
REPLY
The requirement for a causal relation is not part of the definition of a risk factor in general usage: 1. “The coronary risk factors are those abnormalities-demonstrable in persons free of clinical CHD (coronary heart disease)“-known to be associated with significantly increased risk of developing the disease in subsequent years.“’ 2. “An attribute which appears to occur more commonly among persons with coronary heart disease than control subjects is defined as a risk factor. It is implied in this particular definition that an association between the disease and a risk factor is not necessarily causal.‘12 3. “The risk factor concept in coronary heart disease (CHD) is based on the finding of statistically significant associations between incidence of CHD and values for the variables in question. Studies performed so far have not shown that any of the risk factors are actually causative.“” 4. “Follow-up studies of persons judged to be free of CHD at entry examination have identified several characteristics associated with increased risk of CHD in future years. Age, arterial blood pressure and serum cholesterol concentration uniformly emerge as important risk factors.“4 5. “Epidemiological studies have shown a significant relationship between the incidence of CHD and various prospective characteristics commonly termed risk factors.‘15 Finding an association is only one step in the proof of causation. We hoped that our finding of an association between body weight and ischemic heart disease would stimulate hypotheses in this field and we are interested to read Stern’s. Although we have no evidence to support or refute his hypothesis that early coronary atherosclerosis limits physical activity, which in turn causes an increase in body weight, some comments are in order. The young age of our cohort at entry means that the coronary atherosclerosis would have had to exert its effects when these men were in their 20’s so that they would be overweight at entry. This and the fact that physical inactivity is one of many variables in the equation yielding overweight do not make this hypothesis attractive to us. S. W. Rabkin, MD, FACC F. A. L. Mathewson, MD, FACC University of Manitoba Department of Medicine (Section Cardiology) and Social and Preventive Medicine Winnipeg, Manitoba, Canada References 1. Stemler J: Lectures on Preventive Cardiology. New York, Grune 8 Stranon. 1967, p 748 2. Epstein FHz The epidemiology of coronary heart disease. A review. J Chronic Dis 18: 735-774. 1965 3. Wllhelmeen L, We&l H, Tlbblns 0: Multivariate analysis of risk factors for coronary hearl disease. Circulation 48:950-956. 1973 4. Keys A, Aravanls C, Blackburn H, Probability of middle aged men developing coronarv heart disease in five years. Circulation 45:815-628. 1972 5. Brand dJ, R-an RH. Bh& RI, et al: Multivariate prediction of coronary heart disease in the Western Collaborative Group Study compared to the findings of the Framingham Study. Circulation 53:346-355. 1976
Volume 41
et al:
