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toward evolving information which will permit the prevention or amelioration of these diseases. Research activities are concerned with the total cardiovascular system, the kidney, and the endocrinological and nervous factors which control these organ systems; disease states, and their etiological agents, which are important factors, in the development of cardiovascular and renal disease; and gerontology.

The organization of the Institute's research is on three levels. Laboratory studies are conducted in chemical pharmacology, the chemistry of natural products, and cellular physiology. Combined laboratory-clinical work is in five areas: cardiovascular hemodynamics, kidney, and electrolyte metabolism, general metabolism, physiology and pharmacology of the autonomic nervous system, and technical development of diagnostic instruments. Clinical investigations at present are carried on in general medicine and experimental therapeutics, in surgery, and in gerontology.

Many notable research achievements have been made. Advances in basic knowledge include the finding that the liver plays a role in controlling the partial contraction of small blood vessels which is essential for maintaining normal blood pressure; the confirmation through experimental animal preparations that the kidney and the endocrine glands controlling it are of great importance in the development of heart failure; and the discovery that there exists in the body a system of several chemical parts, a deficiency of any part of which may adversely affect fat metabolism and thereby foster hardening of the arteries.

Among accomplishments resulting in improved therapy has been the development of a powerful new drug, procaine amide, which has the ability to abolish the irregular heart rhythms which frequently prove fatal in patients recovering from coronary attacks and in persons under anesthesia during operations. Another advance has been the development of a truly short-acting intravenous anesthetic which may be effective in reducing the hazards of surgery now experienced by elderly patients. Further significant contributions have been the determination of the limitations of drugs used to prevent the growth or formation of blood clots and establishing criteria for a better anticlotting agent; the development of the electrokymograph—the instrument which records heart border movements—as a diagnostic and research tool; and the synthesis of a number of compounds for study of their actions on the cardiovascular system.

During the current fiscal year, $2,986,000 has been earmarked for research conducted by the Institute. A number of studies in progress are directed toward developing new therapeutic agents and toward furthering understanding of the action of existing cardiovascular drugs. Of particular interest are studies of compounds which possess the ability to block the destruction of drugs in the body. Such compounds, derivatives of a substance known as SKF 525, prolong the action of many drugs, including the barbiturates and analgesics. Several of these inhibitory agents have been synthesized, and their possible therapeutic value is now being investigated. Clinical study in the past year of another remarkable drug, phenylbutazone, indicates that it exerts powerful antirheumatic effects comparable to those of cortisone and ACTH, although it produces many serious side reactions. Because of the encouraging results experienced, however, investigations are going forward on other synthetic nonsteroidal compounds which may exert a local tissue effect without imposing major hormonal imbalances.

Work with natural products is chiefly concerned with the isolation from plant sources of substances which affect the cardiovascular system, and with the synthesis of compounds with blood-pressure-lowering action. Plant materials under study come from many parts of the world, including South Africa, Cuba, and the West Indies, and South America. One substance has been isolated from leaves of Rhododendron maximum, obtained in West Virginia and North Carolina, which in very small quantities produces a marked lowering of blood pres

The structure of this material is now under intensive chemical investigation.

Studies in metabolism are concentrating on mechanisms of lipid transport, an area of great importance to the understanding of atherosclerosis. This work continues the investigations which earlier resulted in the delineation of a biochemical system in the body, involving at least five components related to control of the level of abnormal fatty molecules in the blood. Assay methods have been developed for determining quantities or activities of the components, and a number of patients are being assayed for the content of these “clearing factor” components in their plasma.

sure.

One of the problems under investigation in kidney and electrolyte metabolism concerns the mechanism of edema formation in cardiac failure. It is not clear why the kidney is unable to respond to fluid accumulation by increasing the rate of excretion of salt and water, nor is the role of the adrenals and other endocrine glands established. The development of a technique for producing the congestive heart failure syndrome in dogs has provided a means whereby these and other questions may be investigated.

Among the principal clinical studies under way is an investigation of essential hypertension. Patients are being studies to further classify their disease and some of the newer therapeutic agents will be tried to study patient response. A study of surgical interest is concerned with the diagnosis of intra-auricular septal defects. Preliminary animal work has indicated that the nitrous oxide technique has many advantages over oxygen methods, and it is anticipated that the new technique will be soon subjected to critical trial in appropriate cases.

Epidemiological research.-Much knowledge of heart disease can be gained by studying an average community over a period of time to find out how many people have it, what types they have, at what ages it develops, and what factors seem to be associated with it. Such a study is being conducted by the Heart Institute at Framingham, Mass., in cooperation with the town's health department and physicians and the State department of health and medical society.

About two-thirds of the adults in this community between the ages of 30 and 60 have been given a thorough physical examination to determine whether or not they have arteriosclerotic or hypertensive heart disease. Persons in the study will be given followup examinations every 2 years to accumulate data on how heart disease develops.

This approach is expected to produce a number of significant results. It may provide definite information as to which factors or characteristics are present in people who develop heart disease. A byproduct of the study will be the accumulation of data on incidence and prevalence. A further result will be an appraisal of the value and efficiency of various methods and procedures for diagnosing heart disease.

Biometric research.-In statistical research of the Institute, dáta on heart disease mortality and morbidity in various segments of the population are being collected and analyzed. Also, studies, which have important bearing on both the research and control programs are being carried on to furnish a factual basis for planning and conducting heart-disease activities. Consultation and assistance is also supplied, within and without the Institute, in planning of research projects which involve complex statistical techniques or extensive statistical processing.

Grants for research.-Heart-disease research in universities and hospitals all over the country is being fostered and supported by the Heart Institute, through research grants. Under this program, funds are granted to individual scientists for carrying out important heart-disease projects. These grants are making it possible for institutions to expand their existing heart research activities, to undertake new studies, and to conduct investigations in neglected areas in the cardiovascular field. In effect, the program is serving to enlist non-Government facilities and scientists in the research attack.

The stimulation given by the grant program has significantly raised the level of heart research. During the fiscal years 1949–53, a total of 1,784 grants were made for research projects, amounting to $20,262,298 in research support. For the current fiscal year, $6,843,000 has been allotted for making research grants. These sums represent research progress that could not otherwise have been made, since the program supports only projects for which institutional funds are not adequate. It does not take the place of support from foundations, private philanthropy, or voluntary health organi tions.

Promising investigations are being supported in all areas of heart disease. Major emphasis is being placed on problems of high blood pressure, hardening of the arteries, heart failure, surgery, and the physiology of the cardiovascular system. Among the most fruitful of the studies being conducted are those concerned with the role of cholesterol in the development of arteriosclerosis, the hereditary and environmental factors related to cardiovascular disorders, the evaluation of dietary factors in hypertension, new surgical procedures, development of the artificial heart, exploration of renal function, and the therapeutic use of new drugs and hormonal substances such as ACTH and cortisone.

Research construction grants.—Existing research laboratories are extremely crowded and the expansion of heart and blood-vessel investigations throughout the country is limited because of lack of suitable space. Some impetus was given the research attack on heart disease in 1950 through Heart Institute grants for construction of additional vitally neded research facilities. Grants totaling slightly more than $6 million were made to 26 institutions located in 17 States.

These grants made possible the strengthening and enlarging of a number of established research centers, as well as giving material assistance to some institutions just beginning heart-research activities. No grants have been made since 1950 as funds were not available for this purpose.

TRAINING

Research fellowships.-There is a shortage of skilled investigators devoting their talents to the cardiovascular diseases. Also, researchers already trained in some field or fields need additional skills to increase their competency. The research-fellowships program is helping to relieve this dual scarcity by offering encouragement and assistance to some of the most brilliant and promising minds to enter upon a research career in the heart-disease field. At present, two types of fellowships are awarded : postdoctorate fellowships for those with a doctor's degree, and special fellowships for doctors and others who have demonstrated exceptional competence or unusual ability. The term of a fellowship is usually for 1 year, and the amount of the stipend given depends on the type of award. A fellow may conduct his work at any institution where interests and facilities are suitable for the type of research he plans to do.

In its first 5 years, the National Heart Institute awarded 422 fellowships, with training stipends amounting to $1,380,290. The amount which has been appropriated for this purpose for the current fiscal year is $580,000.

Clinical traineeships.—The number of cardiologists and heart specialists in active practice today is far too low compared with the amount of heart disease in the Nation. The Institute's traineeship program provides a means of partly meeting the need for more clinical personnel specializing in heart and bloodvessel diseases.

Traineeships are available to doctors under 40 years of age who have completed a year's general internship and an additional year of training and experi

Since their purpose is to improve the competency of physicians in the diagnosis, prevention, and treatment of heart disease, they may be carried out at any institution where well-rounded cardiovascular training is given.

Traineeships given during the 1949–53 fiscal period numbered 232, with stipends totaling $771,495. For the current fiscal year, $400,000 is available for the program.

Teaching grants.—It is important that medical schools have strong and upto-date courses of instruction in the cardiovascular diseases, so that medical students may be well-equipped with the most recent knowledge in this field. This is particularly essential because of the rapid and marked advances that are being made in researh.

The program of teahing grants-in-aid is making it possible for medical schools to coordinate and improve their teaching of heart-disease subjects and to place adequate emphasis on the cardiovascular field. Institutions are not restricted to a rigid plan in developing their teaching programs, and the funds are utilized in varying ways by different schools. The grants are approved for a 1-year period, but may be renewed annually from appropriated funds.

Two hundred and forty-five teaching grants, amounting to $3,608,819, were made by the Heart Institute in its first 5 years. During this period grants were made on the basis of a maximum of $14,000 to 4-year medical schools and $8,000 to 2-year schools. These have now been increased to $25,000 for 4-year schools and $15,000 for 2-year school ; $2,682,000 is available for the current

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fiscal year.

HEART DISEASE CONTROL

The purpose of control activities is to bring about, through public health techniques, the widest possible application of methods and measures which have been proven to be effective in finding, preventing, diagnosing, and treating heart disease. Application of existing knowledge can considerably reduce death, disability, and suffering from heart ailments. Funds for conducting control activities are provided in the annual appropriation of the National Heart Institute, and are administered by the Bureau of State Services of the Public Health Service.

Grants to States.-Grants-in-aid are made to the States and Territories to assist them in developing community programs for controlling heart disease.

The grants are made according to a formula based on the population and economic needs of the State. Each State is required to match each $2 of Federal money with $1 of its own money. Federal money available for such grants in the current fiscal year is $1,125,000.

Grants help State and local health departments to employ and train staffs to find and refer heart disease cases to private physicians for diagnosis and treatment; to furnish follow-up services in the home; to provide training opportunities to physicians and public health workers; and in other ways to aid in restoring those with heart disease to near-normal life and useful activity. Generally, State plans include provision for several of the following: Medical direction, professional and lay education, clinic improvement, public health nursing services, and medical social services.

Technical assistance.--Assistance is also given the States by providing information on technical matters relating to control. Knowledge and experience which is gained in conducting pilot studies and demonstrations is made available. One of the activities in this connection is cooperation with tuberculosis surveys so that chest plates taken to discover tuberculosis are also examined for possible indications of heart disease. Another activity is promoting the safe use of drugs which prevent blood clots, and important and frequently lifesaving treatment for many persons suffering heart attacks. Use of these drugs requires accurate laboratory control by persons trained in the technique of quickly determining blood-clotting time. The training of such technicians is being aided by teams which move from State to State, providing instruction in the essential laboratory procedures.

INFORMATION AND EDUCATION

The importance of widely disseminating information on all aspects of heart disease was recognized by Congress, which included a specific provision in the National Heart Act to "establish an information center on research, prevention, diagnosis, and treatment of heart diseases, and collect and make available, through publications and other appropriate means, information as to, and the practical application of, research and other activities."

A steadily developing program of professional and public information is being carried out. Activities include the preparation and distribution of heart-disease information-education articles, leaflets, pamphlets, reports, and other publications; planning and development of audiovisual materials, exhibits, radio and television broadcasts and transcriptions; maintenance of an inquiry and reference service; and cooperation with other agencies and organizations in planning and executing informational and educational projects on diseases of the heart and blood vessels.

COOPERATION

The total Public Health Service heart program is administered as the Federal Government's participation in a national collaborative undertaking against heart disease, joining the partnership of all interests in the cardiovascular field. The National Heart Instiute has close working relationships with the American Heart Association, State health departments, foundations, medical schools, universities, hospitals, and other agencies and institutions actively concerned with heart disease. This cooperation with other organizations is resulting in avoidance of unnecessary duplication, in defining suitable spheres of operation, and the formulation of programs to achieve overall objectives most effectively. It is also resulting in a truly united front in the attack on heart disease.

THE OUTLOOK

The major cause of death, even before old age comes, is heart disease. It accounted, in 1947, for 8.6 percent of the deaths from all causes in the age group, 5 to 19; for 11.4 percent in the ages, 20 to 34; and 35.3 percent of the deaths of those 35 to 54 years of age. In the ages 55 and above, of course, the percentages were far higher, heart disease causing 54.7 percent of the deaths in this group. For all age groups combined, heart deaths accounted in 1947 for 43.3 percent of the deaths from all causes. This year heart disease will cause more than threequarters of a million deaths-more than 1 out of 2 of all deaths in the United States.

The importance of cardiovascular diseases as a cause of death prior to old age emphasizes the fact that the major need of today is the discovery of ways

both of preventing heart disease and also of finding and treating the disease in stages earlier than those in which we now find and treat it.

It is in the therapy of damage the treating of existing disease that the chief medical advances against high blood pressure and the consequences of hardening of the arteries have heretofore been made. Still more benefits for the already-damaged heart and blood vessels will undoubtedly be developed.

But it is from the seeking out of the underlying factors behind the rheumatic, the hypertensive, and the coronary diseases, which account for a vast majority of the deaths from heart ailments, that the greatest dividends will eventually come.

In writing of the fundamental importance of seeking understanding of the mechanisms of heart disease, Dr. Paul White says:

"It is in this direction that attention and support in research by both private and public enterprise should certainly have the utmost priority, since the sooner we understand the causes of diseases, the sooner we can control them and, by reduction of their prevalence, cut down the present heavy need for hospitalization for elaborate study and often prolonged treatment.

** * * it is evident that the sooner we discover and thereby learn to prevent the underlying causes of heart disease, the sooner we shall rescue our young people and middle-aged population from cardiac invalidism and death, and the less effort, time, and money we shall need to plan for and expend in their care. An increasing mortality from heart disease per se in the years to come need cause no alarm, in fact, such may be welcomed provided death comes quickly, comfortably, and quietly while at rest in bed or easy chair at an advanced age, say 90, after a long and happy and useful life.”

Once any of the presently unknown causes underlying these three is discovered, a great deal will have been accomplished. Of course, progress in the control of heart disease in one or all of the three great brackets may be made through the extensive and intensive application of partial measures which have emerged or are emerging almost daily from the laboratory. But medicine's most complete conquests over disease are largely embodied in the history of the discovery of specific or contributory causes of diseases ; the greater benefits almost always await such discovery. Here, then, is the hardest core of the problem.

Scientific research is the method to get at this core, and there is agreement among medical, scientific, and public health authorities that wide, intensive, prolonged, and collaborative investigation, by competent investigators who can devote adequate time and energies to the task, is the paramount factor in develop ing the nationwide heart program. This research, it is also felt, can best be done in an atmosphere of freedom without regimentation and with support from diversified sources rather than from a completely centralized resource.

Results of such research may arise from a modest laboratory where a single scientist makes a discovery for which hundreds of others in great laboratories have been seeking. Or results may come from a large group of workers of which each subgroup concentrates its efforts, in accord with its specialized interest and training, upon one or more aspects of a problem. Both kinds of endeavor, of the individual and of cooperating groups, must be supported and encouraged in any comprehensive and adequate research program. The fields of research from which discoveries of benefit for the heart may come are, moreover, not merely those in which lie the primarily cardiovascular investigations. They may arise from other areas of general medical or basic scientific research, and intelligent support does not circumscribe itself too narrowly. Furthermore, in the United States, with a population becoming increasingly aged, heart and circulatory disease must be considered to a very important degree in their gerontological aspects. Thus, research should seek for basic understanding not only of heart disease problems but also of appropriately related gerontological problems. The sum of the aging problem is not made up of cardiovascular disease problems, but there is a significant relationship, and this relationship is to be taken into account in the development of research programs.

Although the further knowledges that research much provide are highly important, there is much that can be done today in the way of establishing and improving the application of what is known already. This has been stated with wise caution by Dr. Paul White: "Some things we have learned which can be applied at once through community effort, but we must take care at the same

2

Heart Disease (fourth edition); the MacMillan Co., publishers.

2 White, Paul D.: Recent Advances in the Medical Treatment of Heart Diseases. Bulletin of the New York Academy of Medicine, August 1947, second series, vol. 23, No. 8, pp. 441-453.

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