THE CAROLINA-CAIRO CONNECTION JAMES F. TOOLE, M.D., L.L.B., RICHARD JANEWAY, M.D., AND (BY INVITATION) MICHEL A. IBRAHIM, M.D., PH.D., OSAMAH ELWAN, M.D. AND YAHIA TAHER, M.D. WINSTON-SALEM, NORTH CAROLINA
As the first North Carolinian to address this meeting, I take the opportunity to welcome the American Clinical and Climatological Association to North Carolina. It is astonishing to me that this Association, interested as it is in good climate, has never before met in our state. The only reason that I can think of is the modesty of even its most illustrious citizens who would not promote our state in competition with others. As it lies between Virginia and South Carolina, it may justly be called a valley of humility between two mountains of conceit. You may be amazed when I tell you that this very area of Pinehurst has an incidence and prevalence of stroke which is among the highest of any part of the world. Therefore it seems appropriate that I should talk about stroke and its use as an indicator for the prevalence of hypertension and atherosclerosis in population groups. There is considerable geographic difference in cerebrovascular disease morbidity and mortality in various parts of the world; this suggests to us that there may be environmental, cultural or other geographically determined risk factors. Because cerebral circulatory diseases are usually caused by hypertension or atherosclerosis, stroke can be used as a detector for these two disorders. Furthermore, stroke is apparent to family, patient and observer; therefore it is our best method for screening populations for incidence and prevalence of hypertension and atherosclerosis. We have taken advantage of this to design a project for elucidation of the geopathology of atherosclerosis and hypertension. There are enormous variations in stroke morbidity and mortality around the world.' For example, in Japan the rate is 550/100,000 and in the United States is 146/100,000. In Japan,2 the majority of stroke deaths are hemorrhagic and hypertensive complications, while in the United States in the white population infarctions due to atherosclerosis lead. In blacks they are hemorrhagic strokes due to hypertension.3 Even when differences in diagnostic habits of physicians and death certification practices and perhaps in the adequacy of medical care are taken into account, there is no question that the incidence and prevalence of stroke varies enormously with geography. Many risk factors for stroke are not hereditary but are implanted during youth. Therefore, a person leaving an area of high stroke risk 66
CAROLINA-CAIRO CONNECTION
67
maintains that increased risk despite moving to an area of low risk. People raised in areas of low risk do not increase their risk when they move to an area of high risk. This is best exemplified by the NI-HONSAN study4 of Japanese in Hiroshima, Honolulu, and San Francisco in whom it has been found that there is a progressive decrease in stroke risk in age and sex-matched Japanese residing in the three locations, with the highest risk being in Hiroshima, the lowest in San Francisco, and Honolulu being intermediate.5 Furthermore, it has been shown that Isei Japanese moving from the mainland to Honolulu or the West Coast of the United States carry with them the original risk that they had in Japan. Their Nisei offspring have a greater risk than the subsequent Sansei generation who have even less risk for stroke but a vastly increased risk for coronary artery disease. This has, of course, led to speculation that the risk factor may be dietary or cultural. Alternatively one might consider that the risk is related to altitude or water supply. North Carolina's coastal plains have almost the highest totals of cerebrovascular and coronary artery disease death rates in the nation while the State's Blue Ridge has had some of the lowest.6 Gordon, Kahn, and Farman7 report a similar correlation between altitude and the incidence of cerebrovascular disorder for the entire USA. A recent report states that "hard" water is associated with a reduced risk of heart disease, hypertension, and stroke while "soft" water with greater levels of cadmium, zinc, lead, and copper is associated with increased risk.8 Others have termed this report erroneous citing that in Evans County, Georgia, USA, where the water is extremely "hard" the incidence of heart disease, hypertension, and stroke is three times that of the rest of the USA.9 These conflicting reports are complicated by the fact that altitudes vary as does water supply. In Egypt, on the other hand, the Nile water supply is a constant, altitude varies less than 300 feet, the population in each area and its customs are homogeneous, with distance from the sea and ambient temperature being the apparent variables. Therefore we have a unique opportunity to test the hypothesis that water supply, distance from the ocean or altitude or both are risk factors for atherosclerosis or hypertension or both. Stroke represents one of the major medical problems of Egypt.'0 Egyptian studies of the different clinical types of cerebrovascular diseases (TIA, infarction and hemorrhage) have shown that infarction is the most prevalent. We have proposed a major study of the epidemiology of hypertension and atherosclerosis in three carefully selected communities located along the Nile at increasing distances from the Mediterranean. For indicators we will ascertain incidence and prevalence of stroke in these communities and use the data to:
TOOLE ET AL.
68
1. Ascertain whether there may be a difference in prevalence in population subgroups within Egypt and in Egypt vis-a-vis the United States. 2. Determine whether environmental factors such as ambient temperatures, mineral content of water, and altitude are risk factors in Egypt which can be compared with other countries. 3. Determine variations in blood pressure with age and sex. 4. Determine hematocrit, blood lipids, and cholesterol for normative data. 5. Screen a random sample population aged 5 through 44 years for heart sounds to determine prevalence of rheumatic heart disease. We will utilize these data to determine: (a) the rate at which blood pressure increases in juveniles and adults in Egypt. (b) the extent to which environmental determinants of blood pressure are related to blood pressure. (c) familial aggregation of blood pressure and stroke. (d) the prevalence of heart murmurs suggestive of rheumatic or congenital heart disease. The results of this study will be used to determine the emphasis by the Egyptian government on blood pressure control, stroke prevention, diagnosis, and care through assigning priorities for specialized centers for education, research, and distribution of health care facilities. If differences in stroke characteristics between Egypt and the USA are found, we would aim to determine avenues for further investigation and elucidation of risk factors. A final objective is to develop a model for epidemiological studies in Egypt, none of which have been undertaken on such a scale and with international cooperation. If successful, this could become a model for other Arab countries. REFERENCES
1. HATANO, S., SHIGEMATSU, I., AND STRASSER, T.: Hypertension and Stroke Control in the Community. Proceedings of the World Health Organization, Tokyo, March 11-13, 1974.
2. CEREBROVASCULAR DISEASES: Prevention, Treatment, and Rehabilitation, Report of the World Health Organization Meeting, Geneva, Switzerland, 1971, WHO Series No. 469. 3a. NEFZGER, M.D., ET AL.: Three-area epidemiological study of geographic differences in stroke mortality. I. Background and methods. Stroke 8(No. 5): 546-550, Sept.-Oct. 1977. 3b. STOLLEY, P. D., ET AL.: Three-area epidemiological study of geographic differences in stroke mortality. II. Results. Stroke 8(No. 5): 551-557, Sept.-Oct. 1977. 4. KAGAN, A., PAPPER, J., AND RHOADS, G. G., ET AL.: Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California:
CAROLINA-CAIRO CONNECTION
5. 6a.
6b. 7. 8. 9.
10.
69
Prevalence of stroke. In: Cerebrovascular Diseases. Trans. 10th Princeton Conference, Scheinberg, P. (ed.), Raven Press, New York, 1976, pp 267-268. OMAE, T., TAKESHITA, M., AND HIROTA, Y.: The Hisayama study and joint study on cerebrovascular diseases in Japan. In: Cerebrovascular Diseases. Trans. 10th Princeton Conference, Scheinberg, P. (ed.), Raven Press, New York, 1976, pp 255-266. SAUER, H. I., ET AL.: Cardiovascular disease patterns in Georgia and North Carolina. Public Health Report 81: 455, 1966. HEYMAN, A., ET AL.: Geographic differences in mortality from stroke in North Carolina. 1. Analysis of death certificates. Stroke 7(No. 1): 41, Jan.-Feb. 1976. GORDON, R. S., KAHN, H. A., AND FARMAN, S.: Altitude and cerebrovascular death rates show apparent relationship. Stroke 8: 274, 1977. SHAPER, A. G.: Soft water, heart attacks, and stroke. JAMA 230: 130-131. 1974. HEYDEN, S.: The hard facts behind the hard water therapy and ischemic heart disease. J. Chronic Dis. 29: 149-157, 1976. ELWAN, O., ET AL.: Etiological studies of recent cerebrovascular thrombotic disorders in Egyptians. Proc. 1st. Pan African Conference for Neurological Sciences, 1973, pp 197216. DISCUSSION
DR. PAUL (Boston): "Several years ago we were intrigued by the frequency of cerebral hemorrhage in Japan and the relative infrequency then of atherosclerotic cerebrovascular disease. We were not clearly impressed that there was more hypertension in Japan than in the United States, nor was there evidence pathologically that the cerebral vessels were different. Three weeks ago, when I was in Japan again, we heard some very interesting material from two pathologists, Ooneda and Yamori, suggesting a very interesting explanation for this. There is a stroke-sensitive strain of rats, which if fed the usual low saturated fat Japanese diet, has a very high frequency of cerebral hemorrhage. When these same rats are given a diet high in saturated fats, the amount of cerebral hemorrhage is markedly decreased. These pathologists have made correlations epidemiologically in Northern Japan's prefectures with changes in the Japanese diet during the westernization process. During this period the diet has had an increasing amount of saturated fat and cholesterol. The frequency of cerebral hemorrhage is also decreasing and the frequency of cerebral thrombosis increasing. They have suggested that the old adage that the lower the cholesterol, and the lower the saturated fat intake the better may not pertain at least in Japan. The necrotizing lesions which are seen in the rats cerebral vasculature tend to disappear when the fat intake of these animals is increased. It may therefore, Dr. Toole, be useful to have further information about lipid content of the diets of these populations." DR. TOOLE (Winston-Salem) "Thank you, Dr. Paul. I didn't mention the details of our project which includes taking three communities, each of 5,000, and screening children age eight and above for heart sounds to determine the incidence of rheumatic heart disease; to take a sample population from 15-45 and determine blood pressure and lipid profiles. We will take everybody above 45 and examine each individual for blood pressure, lipids, and evidence of neurologic disease." DR. CRAIGE (Chapel Hill): "Could I ask a question, Dr. Toole, about the dietary aspects of this study? It is my impression that in Northern Japan where there is a high incidence of stroke, the intake of salt is about 25 grams a day, and I have the impression that Soul Food in eastern North Carolina has a somewhat similar content, although I don't know of any studies of that. Is a dietary survey going to be part of your data also?" DR. TOOLE (Winston-Salem): "Yes sir. The dietary habits of the groups will be studied in great detail." DR. HORWITZ (Philadelphia): "I want to make two comments. One from the point of
70
TOOLE ET AL.
view of animals and the other from that of people. We have a number of groundhogs in the zoo in Philadelphia, who for a number of years have been on low-fat and low-carbohydrate diets. 60% of them die of stroke or coronary disease before the age of five years. From a human point of view, I want to say that Dr. Francis Wood told me once, that many years ago he was with a group that decided to go on low-cholesterol, low-fat diets. Dr. Wood and another physician decided that they would be controls. And I believe that up to a year ago they were the only two that were still alive." DR. CHALMERS (New York): "We've heard so much about the one-sided arguments that CAT scanners have too great a share of the costs of medical care. It appears from what you said that you're going to have to use a CAT scanner in these three locations to determine whether the patients have a hemorrhage or a thrombosis, because that's critical to your end point in an epidemiologic study. Does this mean we're going to have to start digging up money for CAT scanners for such epidemiologic studies?" DR. TOOLE (Winston-Salem): "I don't know, Dr. Chalmers. It might be of interest, as an aside, to tell you that the cost of a head scanner is now less than that of a tractor trailer. Any of you who drive over a highway know there are enormous numbers of tractor trailers around. You can buy a used head scanner for less than $100,000. Who would have predicted when the Wright Brothers initiated powered flight in eastern North Carolina in 1903 what would be happening 75 years later? I think our CAT scanners are going to get cheaper and they're going to be everywhere. I might also tell you Egypt has none. The Middle East has one; all of Africa evidently has three. Winston-Salem, North Carolina has four."
As the first North Carolinian to address this meeting, I take the opportunity to welcome the American Clinical and Climatological Association to North Carolina. It is astonishing to me that this Association, interested as it is in good climate, has never before met in our state. The only reason that I can think of is the modesty of even its most illustrious citizens who would not promote our state in competition with others. As it lies between Virginia and South Carolina, it may justly be called a valley of humility between two mountains of conceit. You may be amazed when I tell you that this very area of Pinehurst has an incidence and prevalence of stroke which is among the highest of any part of the world. Therefore it seems appropriate that I should talk about stroke and its use as an indicator for the prevalence of hypertension and atherosclerosis in population groups. There is considerable geographic difference in cerebrovascular disease morbidity and mortality in various parts of the world; this suggests to us that there may be environmental, cultural or other geographically determined risk factors. Because cerebral circulatory diseases are usually caused by hypertension or atherosclerosis, stroke can be used as a detector for these two disorders. Furthermore, stroke is apparent to family, patient and observer; therefore it is our best method for screening populations for incidence and prevalence of hypertension and atherosclerosis. We have taken advantage of this to design a project for elucidation of the geopathology of atherosclerosis and hypertension. There are enormous variations in stroke morbidity and mortality around the world.' For example, in Japan the rate is 550/100,000 and in the United States is 146/100,000. In Japan,2 the majority of stroke deaths are hemorrhagic and hypertensive complications, while in the United States in the white population infarctions due to atherosclerosis lead. In blacks they are hemorrhagic strokes due to hypertension.3 Even when differences in diagnostic habits of physicians and death certification practices and perhaps in the adequacy of medical care are taken into account, there is no question that the incidence and prevalence of stroke varies enormously with geography. Many risk factors for stroke are not hereditary but are implanted during youth. Therefore, a person leaving an area of high stroke risk 66
CAROLINA-CAIRO CONNECTION
67
maintains that increased risk despite moving to an area of low risk. People raised in areas of low risk do not increase their risk when they move to an area of high risk. This is best exemplified by the NI-HONSAN study4 of Japanese in Hiroshima, Honolulu, and San Francisco in whom it has been found that there is a progressive decrease in stroke risk in age and sex-matched Japanese residing in the three locations, with the highest risk being in Hiroshima, the lowest in San Francisco, and Honolulu being intermediate.5 Furthermore, it has been shown that Isei Japanese moving from the mainland to Honolulu or the West Coast of the United States carry with them the original risk that they had in Japan. Their Nisei offspring have a greater risk than the subsequent Sansei generation who have even less risk for stroke but a vastly increased risk for coronary artery disease. This has, of course, led to speculation that the risk factor may be dietary or cultural. Alternatively one might consider that the risk is related to altitude or water supply. North Carolina's coastal plains have almost the highest totals of cerebrovascular and coronary artery disease death rates in the nation while the State's Blue Ridge has had some of the lowest.6 Gordon, Kahn, and Farman7 report a similar correlation between altitude and the incidence of cerebrovascular disorder for the entire USA. A recent report states that "hard" water is associated with a reduced risk of heart disease, hypertension, and stroke while "soft" water with greater levels of cadmium, zinc, lead, and copper is associated with increased risk.8 Others have termed this report erroneous citing that in Evans County, Georgia, USA, where the water is extremely "hard" the incidence of heart disease, hypertension, and stroke is three times that of the rest of the USA.9 These conflicting reports are complicated by the fact that altitudes vary as does water supply. In Egypt, on the other hand, the Nile water supply is a constant, altitude varies less than 300 feet, the population in each area and its customs are homogeneous, with distance from the sea and ambient temperature being the apparent variables. Therefore we have a unique opportunity to test the hypothesis that water supply, distance from the ocean or altitude or both are risk factors for atherosclerosis or hypertension or both. Stroke represents one of the major medical problems of Egypt.'0 Egyptian studies of the different clinical types of cerebrovascular diseases (TIA, infarction and hemorrhage) have shown that infarction is the most prevalent. We have proposed a major study of the epidemiology of hypertension and atherosclerosis in three carefully selected communities located along the Nile at increasing distances from the Mediterranean. For indicators we will ascertain incidence and prevalence of stroke in these communities and use the data to:
TOOLE ET AL.
68
1. Ascertain whether there may be a difference in prevalence in population subgroups within Egypt and in Egypt vis-a-vis the United States. 2. Determine whether environmental factors such as ambient temperatures, mineral content of water, and altitude are risk factors in Egypt which can be compared with other countries. 3. Determine variations in blood pressure with age and sex. 4. Determine hematocrit, blood lipids, and cholesterol for normative data. 5. Screen a random sample population aged 5 through 44 years for heart sounds to determine prevalence of rheumatic heart disease. We will utilize these data to determine: (a) the rate at which blood pressure increases in juveniles and adults in Egypt. (b) the extent to which environmental determinants of blood pressure are related to blood pressure. (c) familial aggregation of blood pressure and stroke. (d) the prevalence of heart murmurs suggestive of rheumatic or congenital heart disease. The results of this study will be used to determine the emphasis by the Egyptian government on blood pressure control, stroke prevention, diagnosis, and care through assigning priorities for specialized centers for education, research, and distribution of health care facilities. If differences in stroke characteristics between Egypt and the USA are found, we would aim to determine avenues for further investigation and elucidation of risk factors. A final objective is to develop a model for epidemiological studies in Egypt, none of which have been undertaken on such a scale and with international cooperation. If successful, this could become a model for other Arab countries. REFERENCES
1. HATANO, S., SHIGEMATSU, I., AND STRASSER, T.: Hypertension and Stroke Control in the Community. Proceedings of the World Health Organization, Tokyo, March 11-13, 1974.
2. CEREBROVASCULAR DISEASES: Prevention, Treatment, and Rehabilitation, Report of the World Health Organization Meeting, Geneva, Switzerland, 1971, WHO Series No. 469. 3a. NEFZGER, M.D., ET AL.: Three-area epidemiological study of geographic differences in stroke mortality. I. Background and methods. Stroke 8(No. 5): 546-550, Sept.-Oct. 1977. 3b. STOLLEY, P. D., ET AL.: Three-area epidemiological study of geographic differences in stroke mortality. II. Results. Stroke 8(No. 5): 551-557, Sept.-Oct. 1977. 4. KAGAN, A., PAPPER, J., AND RHOADS, G. G., ET AL.: Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California:
CAROLINA-CAIRO CONNECTION
5. 6a.
6b. 7. 8. 9.
10.
69
Prevalence of stroke. In: Cerebrovascular Diseases. Trans. 10th Princeton Conference, Scheinberg, P. (ed.), Raven Press, New York, 1976, pp 267-268. OMAE, T., TAKESHITA, M., AND HIROTA, Y.: The Hisayama study and joint study on cerebrovascular diseases in Japan. In: Cerebrovascular Diseases. Trans. 10th Princeton Conference, Scheinberg, P. (ed.), Raven Press, New York, 1976, pp 255-266. SAUER, H. I., ET AL.: Cardiovascular disease patterns in Georgia and North Carolina. Public Health Report 81: 455, 1966. HEYMAN, A., ET AL.: Geographic differences in mortality from stroke in North Carolina. 1. Analysis of death certificates. Stroke 7(No. 1): 41, Jan.-Feb. 1976. GORDON, R. S., KAHN, H. A., AND FARMAN, S.: Altitude and cerebrovascular death rates show apparent relationship. Stroke 8: 274, 1977. SHAPER, A. G.: Soft water, heart attacks, and stroke. JAMA 230: 130-131. 1974. HEYDEN, S.: The hard facts behind the hard water therapy and ischemic heart disease. J. Chronic Dis. 29: 149-157, 1976. ELWAN, O., ET AL.: Etiological studies of recent cerebrovascular thrombotic disorders in Egyptians. Proc. 1st. Pan African Conference for Neurological Sciences, 1973, pp 197216. DISCUSSION
DR. PAUL (Boston): "Several years ago we were intrigued by the frequency of cerebral hemorrhage in Japan and the relative infrequency then of atherosclerotic cerebrovascular disease. We were not clearly impressed that there was more hypertension in Japan than in the United States, nor was there evidence pathologically that the cerebral vessels were different. Three weeks ago, when I was in Japan again, we heard some very interesting material from two pathologists, Ooneda and Yamori, suggesting a very interesting explanation for this. There is a stroke-sensitive strain of rats, which if fed the usual low saturated fat Japanese diet, has a very high frequency of cerebral hemorrhage. When these same rats are given a diet high in saturated fats, the amount of cerebral hemorrhage is markedly decreased. These pathologists have made correlations epidemiologically in Northern Japan's prefectures with changes in the Japanese diet during the westernization process. During this period the diet has had an increasing amount of saturated fat and cholesterol. The frequency of cerebral hemorrhage is also decreasing and the frequency of cerebral thrombosis increasing. They have suggested that the old adage that the lower the cholesterol, and the lower the saturated fat intake the better may not pertain at least in Japan. The necrotizing lesions which are seen in the rats cerebral vasculature tend to disappear when the fat intake of these animals is increased. It may therefore, Dr. Toole, be useful to have further information about lipid content of the diets of these populations." DR. TOOLE (Winston-Salem) "Thank you, Dr. Paul. I didn't mention the details of our project which includes taking three communities, each of 5,000, and screening children age eight and above for heart sounds to determine the incidence of rheumatic heart disease; to take a sample population from 15-45 and determine blood pressure and lipid profiles. We will take everybody above 45 and examine each individual for blood pressure, lipids, and evidence of neurologic disease." DR. CRAIGE (Chapel Hill): "Could I ask a question, Dr. Toole, about the dietary aspects of this study? It is my impression that in Northern Japan where there is a high incidence of stroke, the intake of salt is about 25 grams a day, and I have the impression that Soul Food in eastern North Carolina has a somewhat similar content, although I don't know of any studies of that. Is a dietary survey going to be part of your data also?" DR. TOOLE (Winston-Salem): "Yes sir. The dietary habits of the groups will be studied in great detail." DR. HORWITZ (Philadelphia): "I want to make two comments. One from the point of
70
TOOLE ET AL.
view of animals and the other from that of people. We have a number of groundhogs in the zoo in Philadelphia, who for a number of years have been on low-fat and low-carbohydrate diets. 60% of them die of stroke or coronary disease before the age of five years. From a human point of view, I want to say that Dr. Francis Wood told me once, that many years ago he was with a group that decided to go on low-cholesterol, low-fat diets. Dr. Wood and another physician decided that they would be controls. And I believe that up to a year ago they were the only two that were still alive." DR. CHALMERS (New York): "We've heard so much about the one-sided arguments that CAT scanners have too great a share of the costs of medical care. It appears from what you said that you're going to have to use a CAT scanner in these three locations to determine whether the patients have a hemorrhage or a thrombosis, because that's critical to your end point in an epidemiologic study. Does this mean we're going to have to start digging up money for CAT scanners for such epidemiologic studies?" DR. TOOLE (Winston-Salem): "I don't know, Dr. Chalmers. It might be of interest, as an aside, to tell you that the cost of a head scanner is now less than that of a tractor trailer. Any of you who drive over a highway know there are enormous numbers of tractor trailers around. You can buy a used head scanner for less than $100,000. Who would have predicted when the Wright Brothers initiated powered flight in eastern North Carolina in 1903 what would be happening 75 years later? I think our CAT scanners are going to get cheaper and they're going to be everywhere. I might also tell you Egypt has none. The Middle East has one; all of Africa evidently has three. Winston-Salem, North Carolina has four."
