disadvantages) will allow patients, presently on low sodium diets, to eat normal foods, since the sodium can be eliminated from the body with the resin.

Other studies are evaluating the varying types of sympathectomy (both total and partial) to determine the degrees of removal of nerves necessary, and methods for predicting in advance those patients who would benefit from the operation. One investigator is studying by anatomical and physiological means, the distribution of the sympathetic nerves commonly removed in sympathectomies.

The significance of hormones and glandular function as factors in high blood pressure are being investigated. One scientist, by removing a part, but not all, of the adrenal cortex (the outer shell of the adrenal glands which are on top of the kidneys) has been able to help a number of hypertensive patients. A marked drop in arterial pressure was noted, with relief from headache and shortness of breath. Findings such as these hold out hope that adrenal-cortex surgery may be an important development for hypertension sufferers—until some therapy based on correcting the as yet unknown cause is discovered.

The development of the new drug, bexamethonium, and its use alone and in combination with others, such as hydrazinophthalazine, give hope of effectiveness in reducing pressure for long periods in patients with hypertension, including critical types. Studies indicate that hexamethonium produces a more complete blockade of sympathetic nerve impulses than any other drug so far studied in humans. Successful management of severe hypertension was reported, including cases of malignant hypertension kept under control for periods ranging from 5 to 11 months.

The study of a number of chemical agents which have the ability to lower blood pressure has determined many of their inherent limitations. In addition to defining the limitation of existing drugs and evaluating their worth to determine the more superior ones, investigators are creating new compounds through synthesis which may have suitable biologic properties, and are seeking still other compounds from natural sources.

Research is under way which indicates that basic biochemical changes in the kidneys and blood stream may have an important bearing on the problem of hypertension. An approach has developed which involves the recognition of counteracting chemical systems that regulate blood elevation. These systems are normally in equilibrium. The present investigations concern those changes in the blood and in the kidneys that are traceable to an upset in this natural balance. Full understanding of this important area of investigation can be expected to yield useful information.

The goal of research in high blood pressure is to find the underlying mechanisms. While this ultimate goal is being sought, the research itself brings data on a wide front-answers and questions that arise from the very nature of progressing research. There are many minute paths to be explored, any one of which may lead to larger paths, perhaps to roads, perhaps to blind endings. Yet each lead must be searched out.

Thus there are many, and there will be increasing numbers of points of departure or embarkation. But the more science learns and knows, the better able its agents are to establish the subjects for investigation, and the hope is strong that before too long the treatment of hypertension will be based on understandable mechanisms.

HARDENING OF THE ARTERIES AND ARTERIOSCLEROTIC HEART DISEASE

Along with high blood pressure-and often coexisting with it-hardening of the arteries is another major form of cardiovascular disease. Arteriosclerosis is the term that has been applied since 1830 to the common chronic arterial diseases of this nature, particularly of the hardening process in the great artery from the heart, the aorta. Today the term is used all inclusively, embracing atherosclerosis and a great variety of arterial changes.

This all inclusive term is used to describe secrious conditions as well as some of little consequence. An artery, for example, has three walls. Hardening of the middle wall is a common phenomenon of the aging process, but does not impede the flow of blood materially and consequently is of less importance.

The arteries themselves are a number of vessels through which the blood passes from the heart to the various parts of the body. They go out from the heart as branches from the trunk of a tree, becoming smaller until they terminate in tiny arterioles. Arteries are the lifeline of the body, since they carry the blood that is a necessary nutrient for the life of every part.

Trouble in this arterial system through the more serious forms of arteriosclerosis is the underlying cause of many afflictions and is the basis of coronary deaths, deaths from cerebral apoplexy, and many kidney deaths. If it involves the arteries leading to the brain, for instance, it may result in slow starvation of brain tissue and a degeneration of the intellect. This slow dying at the top due to arteriosclerosis of the brain is a distressing organic infirmity.

The disease at various sites may develop many pathologic facets. For example, arteriosclerosis of the aorta may be revealed as calcification, hemorrhage into a plaque, ulceration, narrowing and/or occlusion of the mouths of renal and iliac vessels, superimposed thrombosis, and subsequent embolism.

The major form of arteriosclerosis, and the form responsible for most of the damage that has been described, is called atherosclerosis, so named in 1906.

STATISTICS

Well over half of all fatalities from heart disease may be traced to atherosclerosis. It has been called the major disease of our era.

About

Nine out of ten times, heart attack is a result of atherosclerosis. 300,000 people in the United States die each year from heart attacks, and many thousands more suffer less serious, but sometimes disabling, attacks. Much of this is premature death and disability. Fully two-thirds of all men about the age of 50 exhibit severe grade or coronary artery sclerosis at autopsy.

Atherosclerosis has been found present even in children as young as 3 years, or absent in octogenarians. This is the evidence that the disease is not necessarily an inevitable byproduct of the aging process.

PREVENTION AND TREATMENT

Current investigations of atherosclerosis and arteriosclerosis are uncovering new facets of the problems that cause medical authorities no longer to shrug this disease off as one of the indispensable penalties of living. Francis Bacon remarked that to brand a disease as incurable was to establish neglect and carelessness as if by law. The modern times have paraphrased this; for since the National Heart Act became law in 1948 perhaps no other area of a medical problem has been subject to such widespread, concerted attention, or worked upon so assiduously, and with such careful analytic technique. In spite of many hopeful approaches that may presage a significant breakthrough in this most significant front of attack, the cause of arteriorsclerosis is essentially unknown. Association of obesity with arteriosclerosis is suspected and there is research evidence pointing in that direction. In the absence of further evidence from the studies that are underway, the conclusion has been reached by many investigators and clinicians that weight reduction may improve the prognosis in atherosclerotic heart disease.

It is well know that males in their fourth decade dominate over females of this age in their susceptibility to atherosclerosis. Recent experiments have shown that estrogen administration to cholesterol fed chicks inhibits coronary atherogenesis, without influencing aorta therogenesis, suggesting further research in effects of sex hormones on the disease. This is one but of many research approaches to the problem of prevention of the disease. Another, which is concerned with the relationship of fatty particles in the blood, will be discussed later.

Studies now underway may open up the possibility that a routine blood test can be developed to detect early the serious form of hardening of the arteries, and at the same time provide physicians with a blueprint for immediate action to counter defects in blood causing the condition. This possibility stems from research work on the role of heparin in the body's ability to handle fat.

Although there are no tests now generally applicable to screening and early detection of atherosclerosis, studies of serial electrocardiograms, and examination of various blood fractions using the ultracentrifuge, and sometimes employing a newly developed infrared light technique for identifying components, may make it possible in the future to identify the disease in a subclinical stage.

Secondary methods of prevention deal with the complications of atherosclerosis, such as thrombosis and occlusion, cardiac arrhythmias, cardiac enlargement, acute pulmonary edema, and cerebral atherosclerosis. Anticoagulants have been developed which prevent the extension of a thrombus, and investigations on the prophylactic values of these drugs are underway. Already anticoagulant therapy is saving many lives.

The diseases of peripheral blood vessels together cause a vast amount of disability, but physician education through programs of cardiovascular training is stimulating an appreciation of what can be done in the proper management of these diseases. Lay education programs regarding the importance of good foot hygiene, early and proper prenatal care, weight control, avoidance of constricting wearing apparel, and elimination of occupational equipment and work methods and habits that interfere with the circulation are cutting the toll in disability.

RESEARCH GOALS

It is a frequently expressed belief that atherosclerosis is caused by underlying metabolic defects which may themselves be primary or which may be secondary to disorders of the endocrine organs and which may be accentuated or retarded by dietary or nutritional factors.

An important lead that has excited much interest concerns the existence of certain constituents of blood plasma and their relationship to vascular damage in atherosclerosis. The researchers who made the discovery and other cooperating groups subsequently have been utilizing in exploration of this field the ultracentrifuge, a large instrument which whirls blood components or other study materials at a force 200,000 to 300,000 times that of gravity in order to separate them. By this technique was established the existence in the blood serum of man and animals of certain abnormal complexes of lipids and proteins, now referred to as lipoproteins.

Some evidence was obtained that certain of these lipoproteins have a definite relationship to the development of myocardial infarction. Studies in a number of places are further exploring possible relationships.

Research in other laboratories has been directed largely toward the acquisition of new methods that will permit a more searching approach to the entire problem of atherosclerosis. Chemical methods have been developed for the estimation of naturally occurring serine, ethanolamine, and choline, which enter into the molecular structure of the phospholipids. By their use in a definite study of the several types of phospholipids, it should become possible to determine the extent to which all phospholipids subserve a single general function or the extent to which each plays a unique role in a body metabolism. Other studies, utilizing a number of enzyme systems and isolated metabolic fragments of molecules, are aimed at an elucidation of the metabolic transformations of cholesterol, the fatty substance present in the lesions found in atherosclerosis.

Of particular interest is the development by investigators of a clearing-factor, so-called because by its effect upon the state of fat in the blood liquid, it has the ability to clear the milky condition of the blood. Of greater significance, however, is its ability to alter that portion of fat which combines with protein in such a physical state as perhaps to foster deposit of fat in the arterial wall.

For some 10 years it has been known that the turbidity of serum, due to fat globules present after a meal, could be reduced, or cleared, by the chemical heparin or similar compounds. Study has revealed that it is not heparin itself, but an enzyme-like material which can be formed from a precursor among the serum proteins, by certain tissues (heart, lung), in the presence of heparin. Some major problems occupying many research scientists in this one area of the study of atherosclerosis are:

1. Which fatty particles in the blood are actually related to atherosclerosis? 2. Is this association a cause of the disease or a result of it?

3. Can these abnormal lipids in the blood provide evidence of existent or developing heart disease?

4. If a medicine could be developed to clear the blood of these fatty particles, would it be therapeutic or prophylactic?

In this one area of atherosclerosis research, a single scientist or a team of workers somewhere in the world may open an avenue of investigations that will develop into a way for great numbers of people to escape from the slavery of disability and the tragedy of untimely death. It is a strategic area, and interpretative of the statement sometimes made that because heart disease is widely prevalent and essentially unexplored, and because there are sound reasons to believe that important solutions to certain problems may be discovered reasonably soon, research in the cardiovascular area probably offers the greatest challenge of all chronic illnesses.

Since atherosclerosis is responsible for 9 out of 10 heart attacks, investigations aimed at coronary attacks are another facet of arteriosclerosis research. Several years ago a substance known as dicumarol was discovered to retard the clotting

of blood if administered by mouth. There were reasons to believe that if this were given immediately after a "heart attack" the immediate outlook and the incidence of complications might be favorably affected. The results in small groups of patients seemed encouraging.

Then, under the auspices of the American Heart Association and with the financial support of the Public Health Service, a cooperative study was carried on in 16 hospitals in 10 cities scattered from Boston to San Francisco. A thousand patients who had suffered heart attacks were treated according to a careful plan, with half receiving dicumarol daily, and the other half receiving none. The study showed that the agent was of benefit and could save and prolong lives. The answer to a vital question was thus obtained in less than 2 years by this cooperative study, whereas 1 team working alone would have taken perhaps an entire decade to secure the same information.

Further investigations of dicumarol and other anticlotting agents have been continuing in a number of laboratories. The therapeutic success caused a need for more research to improve and keep on improving on these drugs until their ultimate potentialities are completely realized.

As a result of research, requirements for a better anticoagulant have been set up. It can be of the dicumarol type, but must be characterized by greater reproducibility of therapeutic effect; it must be absorbed completely and have stability of biological effect while in the body. Another type of suitable anticoagulant would have the general properties of heparin, but would be more stable in the body, possess a longer duration of activity, have a wider spread between effective and dangerous dosage, and be obtainable through organic synthesis. Work in progress is directed to the development of such an agent, which would not only be of benefit in the therapy of cardiovascular diseases, but would also facilitate many of the problems of surgery, particularly on a mass scale.

OTHER TYPES OF HEART DISEASE

Less than 10 percent of the deaths each year from diseases of the heart and circulation (heart disease) are caused by the remainder of the more than 20 types of heart disease.

These many other forms do, however, indicate the complexity and range of the total problem of heart disease. Both in terms of numbers of persons whom they strike and of human and economic losses, too, they are of very real importance. They account for some 30,000 deaths each year. They cause great disability in many of those whom they afflict. They impose a heavy burden in expense and

care.

The current state of knowledge and its application in several of these types of heart disease are particularly of interest because against them the greatest advances have been made. The fact that they are ranked today among the less important types of heart disease is evidence that they have been reduced in rank by the benefits of research and its application. For example:

Syphilitic heart disease and aneurysm of the aorta are disappearing; they are rare today owing both to early diagnosis and proper treatment of the original syphilis infection and to better treatment of aoritis (involvment of the heart's great artery) when it is discovered. Twenty years ago syphilis was one of the major causes of heart disease.

Hyperthyroid heart disease or thyrotoxic heart disease is practically extinct because of early recognition and proper treatment of the condition-toxic goiter. Subacute bacterial endorcarditis, a complication of rheumatic heart disease and congenital heart disease, has been reduced within 10 years from a mortality of 99 percent to a point where it is curable in from 80 to 90 percent of all cases; the antibiotics, aided by better diagnosis and other measures evolved from research, have made this conquest possible.

Diphtheritic heart disease and fatalities from it, once far from rare, have decreased almost to the vanishing point.

Congential heart disease was not many years ago considered a hopeless condition. Today, much can be done to help those afflicted lead a normal life. It has recently been said that probably half of those with congenital heart defects now seen can be either completely cured surgically or much benefited and that more progress has been made in the understanding of the significance of congenital malformations and in their recognition than in any other type of heart disease.

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In view of this, a brief summary of congenital heart disease serves to highlight the fact that many kinds of accomplishments have been made in the range of the less common or "minor" heart diseases.

CONGENITAL HEART DISEASE

Congential heart disease is caused by a heart or blood vessel imperfectly formed before birth; there are more than a dozen types of these defects which are presently diagnosable. Sometimes the defect is so severe that the newborn can live for only a short time. Sometimes it is so mild that it is not recognized during a long lifetime.

STATISTICS

Although only a very small fraction of all children born come into the world with such malformations, this kind of heart disease still accounts for a substantial amount of disability and death. In the United States each year, some 8,000-9,000 lives are lost from this cause. In 1948, it accounted for the death of 7,300 babies under 1 year of age, another 500 under 5 years, and 575 children between the ages of 5 and 25.

PREVENTION AND TREATMENT

Not long ago, heart disease present at birth was considered unpreventable and incurable. Today there is not only some knowledge of and means for prevention, but also the march of progress in surgery is continuing to make possible correction and benefiting of more and more of the various types of defects.

In the light of present knowledge, primary prevention centers on protecting the mother. Research has disclosed evidence that virus infections during pregnancy, particularly German measles, vitamin deficiencies, metabolic and endocrine disturbances, and radiation are possible malformation causes when present during the first 3 months of pregnancy. This suggests, among others, such measures for protecting the mother as avoidance or treatment of viral infections during early pregnancy, good diet with supplementary vitamins, avoidance of exces sive radiation, and proper management of metabolic and endocrine disturbances. Secondary prevention-aimed against complications developing after birthinvolves treatment of the infant or child. The complications of congenital malformations are subacute bacterial endocarditis and cerebral thrombosis. The former can be prevented through the prophylactic use of antobiotics or the sulfonamides prior to and following operative procedures, such as tonsillectomies, dentistry, etc. Cerebral thrombosis can be prevented by preventing dehydration for all cyanotic (blue coloration) patients.

Although no specific screening test for early detection is available, chest X-ray surveys, especially in preschool and school children, can help to detect cases in the subclinical stage-before manifestations become apparent to outward appearance.

Treatment is the area in which much good news is being made daily in hospitals and clinics in many parts of the country. Because of recent advances, surgery can now restore to a normal or nearly normal life many children who would have been marked for invalidism or death had they been born 15 or 20 years ago. At least half of the types of malformations can be surgically benefited, and almost every one of the others may be added to the list in the near future as research goes on.

Further, there has been a spreading of knowledge of the surgical techniques necessary to perform the complicated, difficult operative procedures. Formerly, only in a few great medical centers could they be carried out. Now, in almost every part of the country there are places where congenital heart surgery is being done with great skill and success. Up-to-date diagnostic information has also been spread more widely in recent years, through courses and clinics for physicians sponsored cooperatively by medical societies, heart associations, health departments, medical schools, and teaching hospitals-so that more and more doctors are becoming better and better trained in recognizing the infant or child with congenital heart disease. Heart-disease programs are aiding in the providing of facilities for identifying those with congenital heart disease and in referral to appropriate centers for precise diagnosis and possible surgical treatment. The program of the Children's Bureau of the United States Department of Health, Education, and Welfare for regional centers is an important resource, as is the utilizing of cooperatively sponsored vocational rehabilitation facilities aided federally through the Office of Vocational Re