Overview and Dedication Henry Buchwald, MD,
is the leading cause of death in the industrialized world, responsible for ending one out of every two lives. The survivors of acute atherosclerotic events and those with long-term atherosclerotic cardiovascular disease often are forced to limit their physical activity and their aspirations. We, as surgeons, and most of us as physicians, have generally been concerned only with the end-stages of atherosclerosis, and then only with the management of the complications of this disease. The etiology of the disease, the treatment of the process of atheromata accumulation, and the modification of risk factors have been peripheral concerns, at best, of the medical profession. It is for the purpose of increasing awareness and capsulizing knowledge of one aspect of the basic atherosclerosis disease process, namely, its relationship to circulating lipids, that this symposium is
Atherosclerosis L
presented.
It is proper to dedicate this symposium on arterial disease to a cardiovascular surgeon who has had the imagination to see beyond the confines of his craft, a man capable of a youthful appraisal of an old problem. This individual has a deep-seated faith in the continuous dialogue between the laboratory and the clinical. He believes in the testing of hypotheses by the principles of science and statistics. He has been for many years my teacher and associate, Richard L. Vareo, MD. Most appropriately, this symposium starts with a review of the epidemiological and statistical bases for the associa¬ tion between dietary and serum lipids and atherosclerosis by one of the world's most renowned epidemiologists, Jeremiah Stamler, MD. With his co-workers, Dr Stamler has accumulated overwhelming data to demonstrate that the dietary fat content, the serum cholesterol level, and the incidence of atherosclerosis are clearly correlated in
Accepted
publication July 1, 1977. Department of Surgery, University of Minnesota Medical School, Minneapolis. Reprint requests to Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455 (Dr Buchwald). From the
for
PhD
different countries and in
population cohorts. They are the people primarily responsible for the lipid dietary conscious¬ ness of today. In his report, Dr Stamler reviews the recent trends in the atherosclerosis epidemic; he explores the role of certain habitual dietary constituents and coronary heart disease; he gives the data for the axiomatic statement that the higher the cholesterol concentration, the greater is the rate of atherosclerosis; he places into perspective hyperlipidemia, hypercholesterolemia, and hyperlipoproteinemia; and, finally, he reminds us that the incidence of severe atherosclerosis is ascribable to a multiplicity of risk factors, cardinal among which is the serum cholesterol
concentration. Jean Davignon, MD, director of the Department of Lipid Metabolism and Atherosclerosis Research of the Clinical Research Institute of Montreal, is a practicing internist and lipidologist, as well as an internationally recognized lipid bioresearcher. He is not by training a pathologist. His report on the pathophysiological basis of the lipid hypoth¬ esis is, therefore, not a pathologist's description of the atherosclerotic plaque. He offers a detailed analysis of the multifactorial pathogenesis of atherosclerosis, including a discussion of endothelial injury, the proliferation of intimai smooth-muscle cells, the role of the platelet, the role of cholesterol as raw material and irritant, the influence of inflammation, and the participation of lysosomal components. For the tumor physician, he has reviewed the evidence concerning the monoclonal hypoth¬ esis of atherosclerosis representing a benign neoplasm. And for the immunologist, the data for the synergy of hypercholesterolemia and immune complex disease as the basic origin of atherosclerosis is presented. In the report, "The Lipid Hypothesis: Genetic Basis," the authors dissect for us the relationships of the plasma lipids and lipoproteins, their origins and interactions, and their association with atherosclerosis. They guide us through the rich mosaic of genetic models of the hyperlipoproteinemias and clearly distinguish between the protective and the atherogenic lipoproteins. No authors are better suited for
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
this task than Charles J. Glueck, MD, and Peter 0. Kwiterovich, Jr, MD, both leading lipoprotein geneticists. They are the two individuals primarily responsible for early hyperlipoproteinemia detection programs and cord blood studies in this country. Their collaboration in this effort highlights their dedication to the subject, since Dr Glueck is a professor of medicine at the University of Cincinnati College of Medicine, and Dr Kwiterovich, as a professor of pediatrics and medicine at Johns Hopkins University, resides in Baltimore. Tatu A. Miettinen, MD, is a professor of medicine in Helsinki, Finland, and a most esteemed international authority in lipidology. He is both a basic researcher, with particular expertise in mechanisms of cholesterol dynam¬ ics, and a clinician with a large series of well-studied hyperlipidemic patients treated by diet, drugs, partial ileal bypass, and portacaval shunt. Both aspects of his endeav¬ ors are demonstrated in his report. His erudite contribu¬ tion is not for casual consumption. Rather, it is a concise insight into cholesterol flux from the gut to the liver to the tissues, and back to the liver and the gut, with discussion of modifying mechanisms, synthesis, and transport. New data regarding obesity and its role in cholesterol synthesis, as well as in gallstone formation, can be found in this effort. David Kritchevsky, MD, is associate director of the Wistar Institute in Philadelphia and Wistar Professor of Biochemistry, University of Pennsylvania. His name is a household word in the lipid field. Trends have never fascinated him and he is suspicious of unifocal solutions. His own research is a model of planning and precision. His data lead to his conclusions, without the intercession of faith. Dr Kritchevsky's report gives clear evidence to support his statement that the dietary contribution towards the total plasma cholesterol level is a sum of everything in the diet, and not just the lipid component. That the percentage of total fat, the relative saturation of the fat, and the cholesterol content of food are the exoge¬ nous regulators of the plasma cholesterol concentration is a convenient, but not totally accurate, simplification. Dr Kritchevsky documents that cholesterol levels and atherogenicity are related to fat structure, animal vs vegetable protein (animal protein is more atherogenic, all other factors being equal), the complexity of the carbohydrate source, the presence of different fibers (alfalfa decreases atherogenicity, bran does not), the hardness of water, and the presence of certain trace elements in the diet. The next article, entitled, "Management of Hyperlipidemia: Diet and Drugs," is a beautiful outline for the practitioner, discussing why, when, where, and what to use in non-surgical treatment. The authors, Daniel Steinberg, MD, and S. M. Grundy, MD, start out with a simplified schema for diagnosis and classification based on only three readily available laboratory tests: plasma cholesterol level, plasma triglycéride level, and the "refrigerator test" for chylomicronemia. They shatter the myth that typing the hyperlipidemias and treating them appropriately is an esoteric art. Indeed, they stress the empiricism of rational therapy and the fact that the treatment program may need
to be continually adjusted. After all, the long-term therapy of any disease is not static. The authors stress that diet and drug treatment is a life-time commitment and, therefore, they do not take it lightly. Weight reduction and low-
cholesterol, low-fat diets are reviewed, with a presentation
of the alternatives of substituting either carbohydrates or unsaturated fats for the saturated fat content of the diet. The action, effects, dose, side effects, and possible compli¬ cations of bile acid binding resins (cholestyramine resin, colestipol hydrochloride, clofibrate, nicotinic acid, plant sterols, D-thyroxin, and probucol are briefly outlined. The authors caution that drug therapy be superimposed on diet and that it is not a substitute for diet. They end with an explicit guideline of when to employ diet and drug treat¬ ment, clearly distinguishing between the "normal" choles¬ terol level in our society and the "ideal." Dr Grundy, research-educated at Rockefeller University, is an expert in the enterohepatic cholesterol and bile acid cycles. Several years ago, he joined the esteemed lipid group at San Diego, headed by Dr Daniel Steinberg, a practicing internist, a lipid biochemist, and a world authority on hypocholesterolemic drug mechanisms. H. William Scott, MD, is known to all surgeons. Professor and chairman of the Department of Surgery at Vanderbilt University, Nashville, Tenn, he has served, among his other distinctions, as president of the American College of Surgeons and president of the American Surgical Association. A teacher and researcher in many fields, including ulcer disease and jejunoileal bypass surgery for obesity, he has for 15 years been active in the study of atherosclerosis and its metabolic modification in the laboratory animal. In this area, his laboratory has developed study programs that have given this field of metabolic surgery a firm foundation. In his article on "Heal Bypass in the Control of Hyperlipidemia and Atherosclero¬ sis," Dr Scott takes the reader through the logical progres¬ sion of laboratory work to clinical application. His unchallenged studies comparing ileal resection, partial gastrectomy, truncal vagotomy and antrectomy, truncal and selective vagotomy with pyloroplasty, pyloroplasty alone, ligation of the intestinal lymphatics, and large doses of the drugs cholestyramine and clofibrate have lead Dr Scott to the conclusion "that ileal bypass is the most effective method available today for lipid reduction." The second surgical approach discussed in this sympo¬ sium is the portacaval shunt. It is reviewed by its clinical originator, Thomas E. Starzi, MD, professor and chairman of the Department of Surgery, University of Colorado, Denver. Dr Starzi previously achieved world-wide recogni¬ tion for his work in transplantation and hepatic metabo¬ lism. Drs Starzi, Putnam, Koep, and the other members of Dr Starzl's team draw on their experience with children with glycogen storage disease and hyperlipidemia success¬ fully treated by end-to-side portacaval shunt as the basis for their transfer of the surgical approach to primary familial hyperlipidemias. Three patients with homozygous type II hyperlipidemia have, at this time, undergone portacaval shunt by the Denver group. There was a substantial fall in plasma cholesterol levels in each case,
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
deposits in the skin and reversal of cardiovascular partial tendons, and, possibly, complications. One patient died 18 months after operation, apparently from a cardiac arrhythmia. The other two patients are in good health, one after subsequent heart valve replacement and double coronary artery bypass. The authors briefly review the clinical and research literature in this field. They point out that "The use of portacaval shunt to ameliorate hyperlipidemia accepts a trade-off of suboptimal conditions of liver perfusion in return for metabolic improvements that are derived from these suboptimal conditions." They suggest that, at this time, portacaval shunt management for hyperlipidemia be reserved for the homozygous type II individual. The group of Samuel H. Brooks, PhD, Dennis H. Le
résorption
of xanthomatous a
Croissette, MD, and David H. Blankenhorn, MD, of the University of Southern California, Los Angeles, and the California Institute of Technology, Jet
Propulsion Labora¬
tory, Pasadena, Calif, have been instrumental in the
development of sensitive arteriography, as well as noninvasive or less invasive, techniques for precise arterial atherosclerosis assessment. They are the leaders in the use of longitudinal diagnostic computerized arterial appraisal to evaluate atherosclerotic plaque regression. In their report, entitled, "Determinants of Atherosclerosis Pro¬ gression and Regression in Man," they review improve¬ ments in computerized axial tomography, ultrasound methods, and contrast angiography leading to low-risk arterial assessment with high enough resolution to measure changes in atherosclerotic lesions in individual patients. It is their goal to test the lipid-atherosclerosis hypothesis not by large intervention trials using epidemiological end-points, but by direct arterial evaluation of lesion risk factors in small clinical programs. The authors of the final article, Basil M. Rifkind, MD, and Robert I. Levy, MD, wrote the book on intervention trials to test the lipid-atherosclerosis hypothesis. Before assuming the directorship of the National Heart, Lung, and Blood Institute, Dr Levy initiated the Lipid Research Clinics Program, a multi-million dollar national and inter¬ national primary intervention trial. Dr Rifkind, chief of the Lipid Metabolism Branch, National Heart, Lung, and Blood Institute, currently heads this meticulously planned undertaking. These men have lived with the problems of
New
design, length of study, requisite number of subjects, setting of the entry cholesterol concentration, selection of the method of intervention, prediction of the percent of cholesterol lowering that will be achieved, probability assessment, standardization of procedures, central coordi¬ nation, study management, protocol adherence, recruit¬ ment, and risk/benefits ethics. They share some of these problems with the readers of this symposium and, I believe, trial
will convince the reader that intervention trials are not to be undertaken casually. Yet, they must be done. They are the only currently feasible way to prove definitively that cholesterol reduction is beneficial. In concluding, the authors offer a brief summary of current trials. One is a
secondary intervention trial, utilizing a surgical modality— the partial ileal bypass operation—as the method for lipid
reduction. This symposium emphasizes the following points: 1. Atherosclerosis is the primary health problem in the industrialized world and of legitimate concern to all physi¬ cians. 2. The precise etiology of this disease has not been fully defined; however, knowledge of origin and mechanisms is, today, broad and growing. 3. Clinically, hyperlipidemia, primarily hypercholester¬ olemia, is the chief risk factor for atherosclerosis. Here, too, genetic and environmental causes are being defined, but have not been definitively specified. 4. The practicing doctor, physician and surgeon, can readily diagnose and subsequently treat hyperlipidemia. 5. The current armamentarium of therapy includes dietary, drug, and surgical measures. 6. It remains for the researcher and for the clinical intervention trials to prove or disprove firmly the lipidatherosclerosis hypothesis by the scientific method, Koch's principles, and statistical validity. 7. Until such proof or denial of the hypothesis is forth¬ coming, it is wise, conservative, and prudent to treat hyperlipidemia in our patients.
Nonproprietary
Names and Trademarks of Drugs
Colestipol hydrochloride -Colestid. Protucol—Biphenabid, Lorelco.
Requirement
for Authors
Congress recently passed The Copyright Revision Act of 1976, effective Jan 1, 1978, which affects the American Medical Association's procedure for reviewing manuscripts submitted for publication. In view of this law, all transmittal letters accompanying manuscripts submitted for publication should contain the following language: "In consideration of the AMA taking action in reviewing and editing my submission, the author(s) undersigned hereby transfers, assigns, or otherwise conveys all copyright ownership to the AMA in the event that such work is published by the AMA."
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
is the leading cause of death in the industrialized world, responsible for ending one out of every two lives. The survivors of acute atherosclerotic events and those with long-term atherosclerotic cardiovascular disease often are forced to limit their physical activity and their aspirations. We, as surgeons, and most of us as physicians, have generally been concerned only with the end-stages of atherosclerosis, and then only with the management of the complications of this disease. The etiology of the disease, the treatment of the process of atheromata accumulation, and the modification of risk factors have been peripheral concerns, at best, of the medical profession. It is for the purpose of increasing awareness and capsulizing knowledge of one aspect of the basic atherosclerosis disease process, namely, its relationship to circulating lipids, that this symposium is
Atherosclerosis L
presented.
It is proper to dedicate this symposium on arterial disease to a cardiovascular surgeon who has had the imagination to see beyond the confines of his craft, a man capable of a youthful appraisal of an old problem. This individual has a deep-seated faith in the continuous dialogue between the laboratory and the clinical. He believes in the testing of hypotheses by the principles of science and statistics. He has been for many years my teacher and associate, Richard L. Vareo, MD. Most appropriately, this symposium starts with a review of the epidemiological and statistical bases for the associa¬ tion between dietary and serum lipids and atherosclerosis by one of the world's most renowned epidemiologists, Jeremiah Stamler, MD. With his co-workers, Dr Stamler has accumulated overwhelming data to demonstrate that the dietary fat content, the serum cholesterol level, and the incidence of atherosclerosis are clearly correlated in
Accepted
publication July 1, 1977. Department of Surgery, University of Minnesota Medical School, Minneapolis. Reprint requests to Department of Surgery, University of Minnesota Medical School, Minneapolis, MN 55455 (Dr Buchwald). From the
for
PhD
different countries and in
population cohorts. They are the people primarily responsible for the lipid dietary conscious¬ ness of today. In his report, Dr Stamler reviews the recent trends in the atherosclerosis epidemic; he explores the role of certain habitual dietary constituents and coronary heart disease; he gives the data for the axiomatic statement that the higher the cholesterol concentration, the greater is the rate of atherosclerosis; he places into perspective hyperlipidemia, hypercholesterolemia, and hyperlipoproteinemia; and, finally, he reminds us that the incidence of severe atherosclerosis is ascribable to a multiplicity of risk factors, cardinal among which is the serum cholesterol
concentration. Jean Davignon, MD, director of the Department of Lipid Metabolism and Atherosclerosis Research of the Clinical Research Institute of Montreal, is a practicing internist and lipidologist, as well as an internationally recognized lipid bioresearcher. He is not by training a pathologist. His report on the pathophysiological basis of the lipid hypoth¬ esis is, therefore, not a pathologist's description of the atherosclerotic plaque. He offers a detailed analysis of the multifactorial pathogenesis of atherosclerosis, including a discussion of endothelial injury, the proliferation of intimai smooth-muscle cells, the role of the platelet, the role of cholesterol as raw material and irritant, the influence of inflammation, and the participation of lysosomal components. For the tumor physician, he has reviewed the evidence concerning the monoclonal hypoth¬ esis of atherosclerosis representing a benign neoplasm. And for the immunologist, the data for the synergy of hypercholesterolemia and immune complex disease as the basic origin of atherosclerosis is presented. In the report, "The Lipid Hypothesis: Genetic Basis," the authors dissect for us the relationships of the plasma lipids and lipoproteins, their origins and interactions, and their association with atherosclerosis. They guide us through the rich mosaic of genetic models of the hyperlipoproteinemias and clearly distinguish between the protective and the atherogenic lipoproteins. No authors are better suited for
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
this task than Charles J. Glueck, MD, and Peter 0. Kwiterovich, Jr, MD, both leading lipoprotein geneticists. They are the two individuals primarily responsible for early hyperlipoproteinemia detection programs and cord blood studies in this country. Their collaboration in this effort highlights their dedication to the subject, since Dr Glueck is a professor of medicine at the University of Cincinnati College of Medicine, and Dr Kwiterovich, as a professor of pediatrics and medicine at Johns Hopkins University, resides in Baltimore. Tatu A. Miettinen, MD, is a professor of medicine in Helsinki, Finland, and a most esteemed international authority in lipidology. He is both a basic researcher, with particular expertise in mechanisms of cholesterol dynam¬ ics, and a clinician with a large series of well-studied hyperlipidemic patients treated by diet, drugs, partial ileal bypass, and portacaval shunt. Both aspects of his endeav¬ ors are demonstrated in his report. His erudite contribu¬ tion is not for casual consumption. Rather, it is a concise insight into cholesterol flux from the gut to the liver to the tissues, and back to the liver and the gut, with discussion of modifying mechanisms, synthesis, and transport. New data regarding obesity and its role in cholesterol synthesis, as well as in gallstone formation, can be found in this effort. David Kritchevsky, MD, is associate director of the Wistar Institute in Philadelphia and Wistar Professor of Biochemistry, University of Pennsylvania. His name is a household word in the lipid field. Trends have never fascinated him and he is suspicious of unifocal solutions. His own research is a model of planning and precision. His data lead to his conclusions, without the intercession of faith. Dr Kritchevsky's report gives clear evidence to support his statement that the dietary contribution towards the total plasma cholesterol level is a sum of everything in the diet, and not just the lipid component. That the percentage of total fat, the relative saturation of the fat, and the cholesterol content of food are the exoge¬ nous regulators of the plasma cholesterol concentration is a convenient, but not totally accurate, simplification. Dr Kritchevsky documents that cholesterol levels and atherogenicity are related to fat structure, animal vs vegetable protein (animal protein is more atherogenic, all other factors being equal), the complexity of the carbohydrate source, the presence of different fibers (alfalfa decreases atherogenicity, bran does not), the hardness of water, and the presence of certain trace elements in the diet. The next article, entitled, "Management of Hyperlipidemia: Diet and Drugs," is a beautiful outline for the practitioner, discussing why, when, where, and what to use in non-surgical treatment. The authors, Daniel Steinberg, MD, and S. M. Grundy, MD, start out with a simplified schema for diagnosis and classification based on only three readily available laboratory tests: plasma cholesterol level, plasma triglycéride level, and the "refrigerator test" for chylomicronemia. They shatter the myth that typing the hyperlipidemias and treating them appropriately is an esoteric art. Indeed, they stress the empiricism of rational therapy and the fact that the treatment program may need
to be continually adjusted. After all, the long-term therapy of any disease is not static. The authors stress that diet and drug treatment is a life-time commitment and, therefore, they do not take it lightly. Weight reduction and low-
cholesterol, low-fat diets are reviewed, with a presentation
of the alternatives of substituting either carbohydrates or unsaturated fats for the saturated fat content of the diet. The action, effects, dose, side effects, and possible compli¬ cations of bile acid binding resins (cholestyramine resin, colestipol hydrochloride, clofibrate, nicotinic acid, plant sterols, D-thyroxin, and probucol are briefly outlined. The authors caution that drug therapy be superimposed on diet and that it is not a substitute for diet. They end with an explicit guideline of when to employ diet and drug treat¬ ment, clearly distinguishing between the "normal" choles¬ terol level in our society and the "ideal." Dr Grundy, research-educated at Rockefeller University, is an expert in the enterohepatic cholesterol and bile acid cycles. Several years ago, he joined the esteemed lipid group at San Diego, headed by Dr Daniel Steinberg, a practicing internist, a lipid biochemist, and a world authority on hypocholesterolemic drug mechanisms. H. William Scott, MD, is known to all surgeons. Professor and chairman of the Department of Surgery at Vanderbilt University, Nashville, Tenn, he has served, among his other distinctions, as president of the American College of Surgeons and president of the American Surgical Association. A teacher and researcher in many fields, including ulcer disease and jejunoileal bypass surgery for obesity, he has for 15 years been active in the study of atherosclerosis and its metabolic modification in the laboratory animal. In this area, his laboratory has developed study programs that have given this field of metabolic surgery a firm foundation. In his article on "Heal Bypass in the Control of Hyperlipidemia and Atherosclero¬ sis," Dr Scott takes the reader through the logical progres¬ sion of laboratory work to clinical application. His unchallenged studies comparing ileal resection, partial gastrectomy, truncal vagotomy and antrectomy, truncal and selective vagotomy with pyloroplasty, pyloroplasty alone, ligation of the intestinal lymphatics, and large doses of the drugs cholestyramine and clofibrate have lead Dr Scott to the conclusion "that ileal bypass is the most effective method available today for lipid reduction." The second surgical approach discussed in this sympo¬ sium is the portacaval shunt. It is reviewed by its clinical originator, Thomas E. Starzi, MD, professor and chairman of the Department of Surgery, University of Colorado, Denver. Dr Starzi previously achieved world-wide recogni¬ tion for his work in transplantation and hepatic metabo¬ lism. Drs Starzi, Putnam, Koep, and the other members of Dr Starzl's team draw on their experience with children with glycogen storage disease and hyperlipidemia success¬ fully treated by end-to-side portacaval shunt as the basis for their transfer of the surgical approach to primary familial hyperlipidemias. Three patients with homozygous type II hyperlipidemia have, at this time, undergone portacaval shunt by the Denver group. There was a substantial fall in plasma cholesterol levels in each case,
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
deposits in the skin and reversal of cardiovascular partial tendons, and, possibly, complications. One patient died 18 months after operation, apparently from a cardiac arrhythmia. The other two patients are in good health, one after subsequent heart valve replacement and double coronary artery bypass. The authors briefly review the clinical and research literature in this field. They point out that "The use of portacaval shunt to ameliorate hyperlipidemia accepts a trade-off of suboptimal conditions of liver perfusion in return for metabolic improvements that are derived from these suboptimal conditions." They suggest that, at this time, portacaval shunt management for hyperlipidemia be reserved for the homozygous type II individual. The group of Samuel H. Brooks, PhD, Dennis H. Le
résorption
of xanthomatous a
Croissette, MD, and David H. Blankenhorn, MD, of the University of Southern California, Los Angeles, and the California Institute of Technology, Jet
Propulsion Labora¬
tory, Pasadena, Calif, have been instrumental in the
development of sensitive arteriography, as well as noninvasive or less invasive, techniques for precise arterial atherosclerosis assessment. They are the leaders in the use of longitudinal diagnostic computerized arterial appraisal to evaluate atherosclerotic plaque regression. In their report, entitled, "Determinants of Atherosclerosis Pro¬ gression and Regression in Man," they review improve¬ ments in computerized axial tomography, ultrasound methods, and contrast angiography leading to low-risk arterial assessment with high enough resolution to measure changes in atherosclerotic lesions in individual patients. It is their goal to test the lipid-atherosclerosis hypothesis not by large intervention trials using epidemiological end-points, but by direct arterial evaluation of lesion risk factors in small clinical programs. The authors of the final article, Basil M. Rifkind, MD, and Robert I. Levy, MD, wrote the book on intervention trials to test the lipid-atherosclerosis hypothesis. Before assuming the directorship of the National Heart, Lung, and Blood Institute, Dr Levy initiated the Lipid Research Clinics Program, a multi-million dollar national and inter¬ national primary intervention trial. Dr Rifkind, chief of the Lipid Metabolism Branch, National Heart, Lung, and Blood Institute, currently heads this meticulously planned undertaking. These men have lived with the problems of
New
design, length of study, requisite number of subjects, setting of the entry cholesterol concentration, selection of the method of intervention, prediction of the percent of cholesterol lowering that will be achieved, probability assessment, standardization of procedures, central coordi¬ nation, study management, protocol adherence, recruit¬ ment, and risk/benefits ethics. They share some of these problems with the readers of this symposium and, I believe, trial
will convince the reader that intervention trials are not to be undertaken casually. Yet, they must be done. They are the only currently feasible way to prove definitively that cholesterol reduction is beneficial. In concluding, the authors offer a brief summary of current trials. One is a
secondary intervention trial, utilizing a surgical modality— the partial ileal bypass operation—as the method for lipid
reduction. This symposium emphasizes the following points: 1. Atherosclerosis is the primary health problem in the industrialized world and of legitimate concern to all physi¬ cians. 2. The precise etiology of this disease has not been fully defined; however, knowledge of origin and mechanisms is, today, broad and growing. 3. Clinically, hyperlipidemia, primarily hypercholester¬ olemia, is the chief risk factor for atherosclerosis. Here, too, genetic and environmental causes are being defined, but have not been definitively specified. 4. The practicing doctor, physician and surgeon, can readily diagnose and subsequently treat hyperlipidemia. 5. The current armamentarium of therapy includes dietary, drug, and surgical measures. 6. It remains for the researcher and for the clinical intervention trials to prove or disprove firmly the lipidatherosclerosis hypothesis by the scientific method, Koch's principles, and statistical validity. 7. Until such proof or denial of the hypothesis is forth¬ coming, it is wise, conservative, and prudent to treat hyperlipidemia in our patients.
Nonproprietary
Names and Trademarks of Drugs
Colestipol hydrochloride -Colestid. Protucol—Biphenabid, Lorelco.
Requirement
for Authors
Congress recently passed The Copyright Revision Act of 1976, effective Jan 1, 1978, which affects the American Medical Association's procedure for reviewing manuscripts submitted for publication. In view of this law, all transmittal letters accompanying manuscripts submitted for publication should contain the following language: "In consideration of the AMA taking action in reviewing and editing my submission, the author(s) undersigned hereby transfers, assigns, or otherwise conveys all copyright ownership to the AMA in the event that such work is published by the AMA."
Downloaded From: http://archsurg.jamanetwork.com/ by a University of Manitoba User on 06/17/2015
