Institutes and Research Divisions
Heart, Lung, and Blood Institute
Important Events in NHLBI History
NHLBI Legislative Chronology
Biographical Sketch of NHLBI Director
Director's of NHLBI
- angiogenesis in breast cancer
- etiology of excess cardiovascular disease in diabetes mellitus
- gene-nutrient interactions in the pathogenesis of congenital heart defects
- innovative ventricular assist systems.
Quality-of-life endpoints have become important measures in clinical trials. The division initiated a multicenter, randomized clinical trial to test the efficacy of interventions that provide social support and ameliorate depression in post-MI patients in FY 1995. Coronary heart disease death and reinfarction are the primary endpoints. Secondary outcomes include health-related quality of life and adherence to medical and lifestyle change regimens.
Another clinical trial recently begun will compare the impact on total mortality of a strategy of attempting to maintain sinus rhythm with antiarrhythmic drugs to a strategy of merely controlling the heart rate. Important secondary endpoints will include quality of life and cost of therapies.
Several trials have suggested that beta-blockers improve ventricular function in congestive heart failure and may also reduce mortality. While a reasonable theoretical basis and suggestive clinical studies exist, the concept that beta-blockers reduce mortality in congestive heart failure patients remains unproven. The division has initiated a clinical trial to determine whether the addition of a beta-blocking agent to standard therapy reduces the total mortality of patients with moderate to severe congestive heart failure.
In FY 1995 the division supported Specialized Centers of Research on the genetic determinants of high blood pressure and ischemic heart disease in blacks. Solicitations of applications were issued for research on elucidation of mechanisms responsible for myocardial dysfunction, specifically, those involved in the transition from cardiac hypertrophy to overt heart failure; and for research on atherosclerotic lesions using human tissues.
Division of Epidemiology and Clinical Applications
In FY1995 the division continued to give special attention to minority health issues. Obesity prevention in young Native Americans, CHD risk factors in middle-age black adults, and hypertension care among inner city minorities are a few examples. A study associated with atherosclerosis in larger arteries was extended to include the effect of hypertension on smaller arteries in the eyes and brains of blacks and whites.
A clinical trial to determine whether the combined incidence of nonfatal myocardial infarction (MI) and fatal CHD differs between hypertensives receiving alternative antihypertensive pharmacological treatment was initiated. A subset of hypercholesterol-emic patients will be studied to determine whether reducing serum cholesterol levels with a lipid-lowering drugh decreases the incidence of nonfatal MI and fatal CHD. The effects of selected diet patterns on blood pressure will be examined in another group of patients.
Behavioral studies are an important component of clinical trials and have been included in several intervention projects. A few examples supported by the division include:
- multicenter study to examine the effect of communitywide education on reducing the time from onset of cardiac symptoms to receipt of medical care.
- behavioral interventions in primary care to encourage sedentary patients to increase their physical activity.
- clinical trial to study the effects of psychosocial support on morbidity and mortality in patients recently hospitalized with acute MI.
- Multicenter clinical trials are being conducted to study the effects of various medical treatments for cardiac problems.
Some issues being investigated are:
- impact of implantable cardioverter defibrillators on survival of coronary bypass patients.
- effects on mortality of beta-blockers to standard therapy for chronic congestive heart failure.
- effect on mortality of two strategies of antiarrhythmic drug therapy in patients with atrial fibrillation.
Other projects supported by the division include:
- efforts directed toward genetic and nongenetic determinants of CHD and cardiovascular risk factors in population-based studies of twins and families.
- a pilot project comparing the effectiveness of an implantable cardiac defibrillator with conventional drug therapy in reducing mortality in patients who have been resuscitated from sudden cardiac death.
- a pilot study evaluating the effects of specific dosages of various drugs or drug combinations on several biochemical markers for atherosclerotic CVD in patients with peripheral arterial disease.
Office of Prevention, Education, and Control
OPEC, located in the NHLBI Office of the Director, is the institute's technology transfer arm, relaying the results of heart, lung, and blood research to health care professionals, their patients, and the public. Its function is to disseminate and translate up-to-date research findings that will help practitioners be more effective, and provide scientific knowledge to patients and the public that will enable them to make "healthy decisions."
The institute has targetted six areas for educational emphasis with OPEC. They include: high blood pressure; cholesterol; asthma; heart attack alert; sleep disorders; and obesity. Three of these (high blood pressure, cholesterol, and obesity) address major modifiable risk factors for CVD.
The National High Blood Pressure Education Program (NHBPEP) was established in 1972 with a goal of reducing death and disability related to high blood pressure through professional, patient, and public education. Strategies to achieve this goal include stimulating education and information programs to increase public awareness about the disease, promoting activities encouraging detection of the disease especially for underserved groups, encouraging hypertensive patients to seek medical care and follow their doctor's advice, providing education programs and materials for health professionals, and providing technical support to community health programs so they may carry these activities to their geographic areas.
Since its creation, the NHBPEP has released five joint national committee (JNC) reports on the detection, evaluation, and treatment of high blood pressure. Each report has been based on the latest scientific research related to hypertension control and reflects the state-of-the-art regarding hypertension management.
The fifth JNC report, issued in 1992, includes and updates earlier recommendations for both pharmacologic and nonpharmacologic therapies for high blood pressure.
NHBPEP also released the Hypertension and Chronic Renal Failure Report, which gives an overview of this mounting public health problem; a Report on High Blood Pressure in Pregnancy, which affects about 10 percent of all pregnancies; and a new Report on Primary Prevention of Hypertension.
The National Cholesterol Education Program (NCEP) was launched in 1985. Its goal is to reduce illness and death from coronary heart disease in the United States by lowering the prevalence of high blood cholesterol. Through its educational efforts directed at the public, patients, and health professionals, the NCEP aims to raise awareness and understanding about high blood cholesterol as a risk factor for coronary heart disease and the benefits of lowering high blood cholesterol as a means of preventing coronary heart disease. Success of program efforts is demonstrated by the results of cholesterol awareness surveys conducted in 1983, 1986, and 1990 that show dramatic improvements in cholesterol-related knowledge, attitudes, and practices among physicians and the public
In 1992 the NCEP convened a new adult treatment panel to update the existing guidelines for detecting and treating high blood cholesterol in adults. The panel's report was completed in June 1993. The NCEP published the report of the children and adolescents panel and developed booklets to help parents and children adopt heart healthy eating patterns. The program endorsed the expert panel recommendations for heart healthy eating by the general population to lower average cholesterol levels, and it developed methods to improve the accuracy of cholesterol measurement. In its educational activities, the NCEP is pursuing a dual strategy to encourage blood cholesterol reduction by high-risk individuals and by the general population.
The National Asthma Education Program (NAEP) was initiated in March 1989 to raise awareness of asthma as a serious, chronic disease and to promote more effective management of asthma through professional and patient education. The NAEP released two expert panel reports on asthma, International Guidelines on Diagnosis and Management of Asthma and Asthma and Pregnancy Report, in 1992. The international guidelines were developed by asthma experts from several countries and will be translated and distributed throughout the world.
The NAEP initiated activities to help health professionals and patients implement the recommendations of the expert panel's report on diagnossis and management of asthma. Examples include developing a speaker's kit for use by health care professionals in workshops or training sessions on dissemination of panel recommendations, preparing and asthma management kit to aid health professionals working with patients on disease control, producing a pamphlet for patients emphasizing that asthma can be controlled, and distributing information to schools that will enable the staff to develop skill related to asthma management and control.
The National Heart Attack Alert Program (NHAAP) was initiated in June 1991 to reduce morbidity and mortality from acute myocardial infarction (AMI) and sudden death through the education of physicians, nurses, emergency medical service personnel, and other health professionals about the importance of rapid identification and treatment of individuals with heart attack, symptoms and signs. To date, the program has developed recommendations for emergency department management of individuals with characteristic signs of AMI. In addition, it has prepared background papers on 911 emergency telephone systems; acquisition of emergency medical services systems, including staff and equipment; emergency medical dispatching procedures; and factors associated with patient/bystander delays in seeking care.
The NHLBI Obesity Education Initiative (OEI) was launched in 1991 to educate the public and health professional about the risk factors associated with obesity. Obesity is not only an independent risk factor for CVD, but also a contributor to high blood pressure and high blood cholesterol and is related to sleep apnea. The program is using both high-risk and population based strategies to educate those groups about the relationship of overweight with heart disease and impaired lung function. The first targets persons with adverse health effects and medical complications associated with obesity. An expert panel will convene to address issues such as identification, evaluation, and treatment of obesity. A strategy development workshop was held in September 1992 to plan the population-based effort for the general public as well as special subgroups.
All of OPEC's education programs work in partnership with a wide range of organizations--governmental, professional, voluntary, community, private, industry, and educational--that have focused their activities on NHLBI-related health information and education. OPEC collaborates with these organizations to help achieve its program goals, disseminate educational materials, and obtain feedback for new program development. Mass media are used to achieve program goals.
NHLBI Appropriations -- Grants and Direct Operations
[Amounts in thousands of dollars]
|1950|| 8,634 ||2,091||10,725
|1Since 1973 includes research grants and research manpower development awards; and excludes contracts.
Division of Lung Diseases
Lung diseases are among the leading causes of death and disability in the United States. Excluding cancer, it accounts for 224,000 deaths annually, and is a contributing cause to perhaps an equal number of additional deaths.
More than 25 million persons suffer from chronic bronchitis, emphysema, asthma, or other obstructive or interstitial lung diseases. In 1993, pulmonary diseases accounted for 27 percent of all hospitalizations of children under 15 years of age.
The division plans and directs research in lung diseases, encompassing basic and targeted research, clinical trials and demonstration trials, national pulmonary SCORs, technological development, and application of findings. The division assesses the national need for research in the causes, prevention, diagnosis, and treatment of lung diseases; in technological development; and for manpower training in these areas.
Minority training is an important priority within the division. The Minority National Research Service Award, the Minority School Faculty Development Award, the Research Development Award for Minority Faculty, and the Short-Term Research Training for Minority Students Award are among the research career and training programs it supports.
The NHLBI established six centers for gene therapy in FY 1993. Presently, the centers are focusing mainly on cystic fibrosis (CF) research but include other areas associated with gene therapy for heart, lung, and blood diseases. Basic, preclinical, and clinical studies are directed toward developing safe, efficient, and efficacious vehicles for delivering genes to appropriate target cells. Basic science and clinical findings are identifying new directions needed to generate improved gene transfer vectors, to manage the inflammatory and immune consequences of vector transfer, and to develop alternative vector systems.
Asthma research is an important area of support for the division. In FY 1995, major focus was directed towards:
- gene mapping studies to locate and identify genes important to asthma. Discoveries in this field will facilitate the development of new modes of treatment and will lead to an understanding of causal interactions between the genes and environmental factors that are relevant in asthma.
- development and evaluation of innovative approaches to ensure optimal disease management and prevention in the elementary school setting.
- clinical trial to investigate long-term effects of two short-acting, beta-agonist treatment regimens. As part of the research effort, an inexpensive and easily reproducible method for testing the accuracy and precision of peak flow meters was developed for use in monitoring asthma.
- clinical trial to examine the effectiveness and side effects of two long-acting, beta-agonist treatment regimens. The long-term effects of three different asthma medications will be examined in a 5-year, multicenter clinical trial conducted among 1,000 children.
- collaborative study with the NICHD to determine the effects of asthma and its treatment on pregnancy and the effects of pregnancy on asthma.
The division is very active in public education programs that increase awareness of asthma and its public health consequences, that promote study of the association between asthma and the environment, and that reduce asthma morbidity and mortality throughout the world. In collaboration with the World Health Organization, itrecently published a report entitled Global Strategy for Asthma Management and Prevention. Presently, it is preparing a report on the diagnosis and management of asthma in the elderly.
Smoking-related diseases are a major cause of mortality and morbidity in the United States. The division has an ongoing randomized trial that examines the effect of inhaled corticosteroids on the natural history of lung function in continuing smokers.
The division supports efforts associated with acquired immunodeficiency syndrome (AIDS) and tuberculosis (TB) research. Specific programs include:
- clinical study of cardiopulmonary complications of HIV infection in infants and children.
- several programs to address pathobiology of Pneumocystis carinii, basic cell biology of pulmonary manifestations of AIDS.
- development of lung-specific drug delivery systems for enhanced TB treatment, and behavioral interventions for control of TB.
Several new programs were begun in FY 1995. Included among them are:
- prospective randomized clinical trial to assess novel treatment methods in patients at risk for developing adult respiratory distress syndrome.
- epidemiological study to investigate causes and environmental and genetic risk factors for sarcoidosis.
- a study of causes of noninfectious pneumonia, an often fatal complication of bone marrow transplantation.
- multi-institutional collaboration to create a molecular profile of bronchopulmonary dysplasia that will provide insight into thecondition and offer directions for developing new reagents for clinical interventions.
Division of Blood Diseases and Resources
Blood diseases, including both acute and chronic disorders, resulted in 271,000 deaths in 1994; 262,000 of them were due to thrombotic disorders and 9,000 were due to diseases of the red blood cells and bleeding disorders.
The division develops, administers, and coordinates programs that will reduce morbidity and mortality caused by blood diseases and lead to their primary prevention. These programs include hemophilia, Cooley's anemia, sickle cell disease, and disorders of hemostasis and thrombosis. The division also has a major responsibility to ensure the adequacy and safety of the Nation's blood supply. A full range of activities, including studies of transmission of disease through transfusion, development of methods to inactivate viruses in donated blood, improvement of blood donor screening procedures, research to reduce human error in transfusion medicine, and studies of emerging diseases that may be transmitted by blood transfusion, are used to achieve this goal.
The division's overall responsibilities are met by an integrated and coordinated program of grants, contracts, training and career development awards, and academic awards. Special emphasis is given to training and career development programs targeting minority students, faculty members, and investigators at minority schools.
Stem cell biology was an area of major focus in FY 1995. Advances in characterization and purification of hematopoietic stem cells enabled investigators to begin to examine different sources of the cells and to pursue strategies designed to hasten the translation of basic research into clinical application. Among the areas studied were:
The new SCORs in hematopoietic stem cell biology were initiated to develop improved treatments for both inherited and acquired hematologic disorders found in blood cell production and other blood diseases.
- hematopoietic growth factors and cytokines.
- stem cell transplantation.
- aplastic anemias and other nonneoplastic disorders of the bone marrow.
- pathophysiology of bone marrow in AIDS and related hematologic disorders.
Thalassemia is another research area within the division. Ongoing studies examine:
Sickle cell research is another high priority area and is supported through Comprehensive Sickle Cell Centers. A mutidisciplinary approach is directed towards membrane function, red cell rheology, and adherence of red cells to vascular endothelium.
- genetics, pathophysiology, prevention, diagnosis, and treatment of the disease.
- development of pharmacologic agents that enhance fetal hemoglobin production or rehydrate red blood cells.
- gene therapy.
- development of animal models.
Unrelated-donor marrow transplantation and pathogenesis, prevention, diagnosis, and treatment of complications of transplantation are current areas of investigation. Special attention is directed to studies of transplantation of stem cells from marrow, peripheral, and cord blood.
The division to has been very active in disseminating its research findings to the medical community through workshops, meetings, and consensus development conferences. Topics have included plasma transfusion, platelet transfusion therapy, diagnosis of deep-vein thrombosis, impact of routine HIV antibody testing of blood and plasma donors on public health, infectious disease testing for blood transfusions, stem cell therapy, and immune function in sickle cell disease.
National Center on Sleep Disorders Research
The National Center on Sleep Disorders Research (NCSDR) plans, directs, and supports a program of basic, clinical, and applied research; health education; and prevention-related research in sleep and sleep disorders. It maintains surveillance over developments in its program areas; assesses the national need for research on the causes, diagnosis, treatment, and prevention of sleep disorders; and coordinates sleep research activities across the Federal Government.
Since its inception, the NCSDR has initiated several activities. A study that involves existing epidemiological cohorts is being conducted to determine if sleep apnea is an independent or contributing risk factor for the development of cardiovascular and cerebrovascular disease. The center, in collaboration with NICHD, established the Back to Sleep campaign to reduce the risk of SIDS. In FY 1995, the NCSDR coordinated and released a NIH-wide program announcement in Basic and Clinical Research on Sleep and Wakefulness.
In collaboration with the National Aeronautics and Space Administration (NASA) the center supports research on sleep and microgravity as part of the Neurolab Project. A new initiative for a sleep academic award was approved and will soon be released. The NCSDR collaborated and coordinated a number of NIH- and Governmentwide activities including an NIH Workshop on Molecular Biology and Genetic Approaches to Sleep Control, and joint activities with the National Sleep Foundation and the Department of Transportation on the Drive Alert Arrive Alive Program.
The center works closely with the NHLBI Office of Prevention, Education, and Control on the sleep education program which includes conducting some focus group research. A number of professional and public/patient education publications were released along with the start of a Sleep Apnea Mass Media Campaign. The center recently published a summary of the report of the Stately Development Workshop on Sleep Education.
Division of Intramural Research
The 16 Bethesda-based laboratories and branches conduct clinical research on the normal and pathophysiologic functioning of the cardiac, pulmonary, blood and endocrine systems and basic research on normal and abnormal cell behavior at the molecular level. A brief synopsis of current research follows.
The Cardiology Branch focuses on the processes involved in microvascular mediated myocardial ischemia, the genetic basis and clinical treatment of hypertrophic cardiomyopathy, and molecular and cellular mechanisms of angiogenesis and restenosis.
The Hematology Branch conducts research on the pathogenesis of hematological diseases at the molecular and cellular levels and on the development of novel therapeutic strategies, including gene therapy. Other activities include research on the pathogenesis and treatment of aplastic anemia and B19 parvovirus-induced disease.
Vasoactive substances regulating blood pressure and hypertension, the molecular events leading to vascular hypertrophy and hyperplasia, and studies of pheochromocytoma are the principal interests of the Hypertension-Endocrine Branch.
The Molecular Disease Branch is concerned with elucidating the molecular mechanisms involved in lipid transport and metabolism in normal individuals and patients with disorders of lipid metabolism and atherosclerosis. The branch also conducts clinical studies on the effects of drugs and diet.
The principal goal of the Molecular Hematology Branch is to develop the understanding and technology necessary to carry out human gene therapy. Targeted diseases include genetic and cardiovascular disease and cancer. Mechanisms and regulation of gene expression are also studied.
Research in the Pulmonary/Critical Care Medicine Branch is directed toward understanding basic mechanisms of inflammatory and immune processes in the pathogenesis of the human lung. Techniques from cellular and molecular biology, with special emphasis on genetic strategies, have been applied in the treatment of cystic fibrosis.
The Laboratory of Animal Medicine and Surgery studies intracardiac flow dynamics with digital acquisition and analysis of color Doppler ultrasound imaging techniques.
The Laboratory of Biochemical Genetics studies the molecular mechanisms that regulate gene expression during embryonic development. Interests include homeobox genes and neuron-specific enhancer sequences.
The Laboratory of Biochemistry is concerned with the elucidation of various mechanisms of metabolic regulation. Special interests include the physiologic and pathologic effects of oxidation, signal transduction, and protein chemistry.
The Laboratory of Biophysical Chemistry investigates physical and chemical properties of molecules in relation to their biochemical functions. Techniques used include nuclear magnetic resonance (NMR), mass spectrometry, and x-ray crystallography.
The goal of the Laboratory of Cardiac Energetics is a better understanding of the cellular processes involved in the performance of work in vivo by the heart. State-of-the-art noninvasive NMR and optical spectroscopy are used and include a 1-meter bore, 4.D tesla NMR for imaging, and spectroscopic studies.
The Laboratory of Cell Biology investigates diverse problems on the molecular basis of cell motility, bioenergetics, heat-shock proteins, and protein structure through a variety of techniques from molecular biology to time-resolved fluorescence spectroscopy.
The Laboratory of Cell Signaling studies the mechanisms by which signal activated phospolipases like phospho-inositide-specific phospholipase C and phosphocholine-specific phospholipase D are modulated and the role these enzymes have in human disease.
Objectives of the Laboratory of Kidney and Electrolyte Metabolism are to understand renal function at the molecular and cellular levels. Areas of interest include epithelial transport, cellular osmoregulation, transport metabolism and hormonal regulation.
The Laboratory of Molecular Cardiology investigates the regulation, expression, and function of contractile proteins in vertebrate muscle and nonmuscle cells. The tools of molecular genetics, protein chemistry, and video-enhanced microscopy are used. Research in the pulmonary and molecular immunology section focuses on topics related to the T-cell activation process, with particular emphasis on the three classes of interleukin-2 receptors.
The Laboratory of Molecular Immunology does research in the T-cells activation process--studies with importance for immunodeficiency, cancer, and autoimmune diseases; the mast cells activation process--an important area for asthma and other allergic diseases; and the mechanisms of drug-induced toxicities, with particular emphasis on the mechanisms of hepatitis resulting from inhalation anesthetics and nonsteroidal anti-inflammatory drugs.