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The search for plasma lipoproteins began at the turn of the century. It was not until 1949 that a meeting of the Faraday Society celebrated the separation of the alpha and beta lipoproteins. At that moment, ultracentrifugists in Berkeley were already busily converting "alpha" to high density lipoprotein and "beta" to low density lipoprotein; the modern era of lipoproteins had begun. Over the succeeding 10 years, a quarrel over whether the level of Sf 0-20 or cholesterol was the more powerful risk factor ended with an eclipse of the analytical ultracentrifuge and a surge of interest in the biological side of lipoproteins. The postheparin clearing factor became lipoprotein lipase, and free fatty acids were discovered. In 1960, abetalipoproteinemia and Tangier disease suggested that the apolipoproteins must be specific and spurred a hunt for their number and nature. The first amino acid sequences aroused speculation of "amphipathic helices." By 1970, conversion of hyperlipidemia to five types of hyperlipoproteinemia led to worldwide fascination with electrophoretic patterns, "floating beta," and "the Friedewald formula" as codes for genetic abnormalities leading to early coronary artery disease. A few years later, the appearance of "familial combined hyperlipidemia" confounded the phenotyping, and the discovery of the low density lipoprotein receptor heralded the coming of true genotypes. This is a Bethesda-based story of the "climb to base camp" preceding the joining of molecular biology with the research on lipoproteins, dyslipoproteinemia, and atherosclerosis.

The history of randomized, controlled, clinical trials is reviewed. Cooperative clinical trials are reviewed and summarized, and specific needs for future trials are identified. Improved policy on resource allocation decisions for clinical trials vs other forms of research is necessary, particularly as such trials begin to translate improved therapeutic knowledge into community level disease control.

In this overview of the achievements of the National Heart, Lung, and Blood Institute (NHLBI), the major developments in each major form of heart disease since the birth of the Institute 35 years ago are reviewed. In the case of congenital heart disease, it has become possible to establish an accurate diagnosis, often by noninvasive methods, and to correct by surgical treatment almost all congenital cardiac malformations. The major challenge now is to eliminate these disorders; this will require an understanding of the fundamental molecular basis of these lesions. Acquired valvular heart disease can also now be characterized by hemodynamic, angiographic, as well as noninvasive techniques, principally echocardiography. Surgical treatment is usually successful, but improvement in the durability of valves without thromboembolic potential remains an important challenge. While essential hypertension can now be managed pharmacologically in almost every patient and while such management reduces the excess mortality resulting from this condition, current research focuses on elucidating the underlying basis of this disorder. Atherosclerosis remains the most common cause of cardiac and vascular disease. Although its cause has not been defined, several abnormalities in lipid metabolism that play an etiologic role in many patients with atherosclerosis have been identified. The treatment of these disorders with cholesterol-binding resins, which increase the number of cellular receptors for low-density lipoprotein, and with inhibitors of the enzyme required for cholesterol biosynthesis holds considerable promise. Noninvasive techniques will be used increasingly for detection of atherosclerosis in asymptomatic persons and for determining the efficacy of therapy. The mortality resulting from acute myocardial infarction has been reduced in half by the development of coronary care units and the prompt treatment of potentially fatal ventricular tachyarrhythmias. Current research is focused on preventing pump failure by limiting infarct size; lysis of coronary thrombi now appears to be the most promising method of accomplishing this. Chronic angina pectoris can be relieved by the judicious use of three classes of drugs--organic nitrates, beta-adrenergic blockers, and calcium antagonists, and two mechanical approaches--percutaneous transluminal coronary angioplasty and coronary artery bypass grafting--are usually successful in relieving angina in patients who do not respond adequately to medical management. Whether or not any of these approaches prolong life is not yet settled.(ABSTRACT TRUNCATED AT 400 WORDS)

Since its creation as the National Heart Institute in 1948, the National Heart, Lung, and Blood Institute (NHLBI) has led a national biomedical research program in heart, lung, blood, and blood vessel diseases, and has become increasingly involved in complex clinical trials to validate its research findings. In addition, NHLBI sponsors demonstrations and educational activities to apply proved research findings in the health care community. NHLBI's approach to these responsibilities involves acquiring new and basic information, testing and evaluating the information, and applying it to improve prevention, detection, and treatment of disease. New equipment such as the heart-lung machine and the pacemaker, better diagnostic procedures, new operative and treatment devices, new drugs, and increased use of preventive medicine have dramatically reduced mortality from heart attack, hypertension and stroke.