NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

STATEMENT OF CLAUDE LENFANT, DIRECTOR

BUDGET REQUEST

Senator HARKIN. Let us now go to Dr. Claude Lenfant, Director of the Heart, Lung, and Blood Institute.

Dr. LENFANT. Thank you, Mr. Chairman.

Senator HARKIN. I just wanted to see what you have here, $1.112 billion, a 3.75-percent increase.

Dr. LENFANT. That is correct.

Senator HARKIN. Please, proceed.

Dr. LENFANT. Thank you, Mr. Chairman.

In past years I have appeared before you and told you that our cardiovascular research programs have been very successful. Indeed, mortality rates from these diseases continue to decline.

For example, we can estimate that 425,000 additional cardiovascular deaths would have occurred in 1988 had the death rate not declined between 1967 and 1987.

Of course, this has happened because of our ever-increasing ability to diagnosis and treat cardiovascular patients, especially those with coronary heart disease.

However, there is a tradeoff for this success, and we must not be lulled into a false sense of security. It is now very clear from demographic shifts that the prevalence and, therefore, the burden of cardiovascular disease is increasing.

Our concern for this situation is matched only by our concern with the increased death rate from pulmonary diseases that we continue to observe year after year.

These problems, Mr. Chairman, can be solved only by intensified research to identify early those at risk of cardiovascular and pulmonary disease, and by developing more effective therapies.

PREPARED STATEMENT

My written statement describes an array of research avenues that we are actively pursuing on heart, lung and blood disease. Also mentioned are achievements with public health and cost saving benefits.

These accomplishments reflect the breadth of our program in basic, clinical and demonstration research. To conclude, I would like to underscore the contributions of our centers supported clinical research, which in our opinion has so greatly contributed to the health of the American people.

I would be pleased to answer questions, Mr. Chairman.

[The statement follows:]

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STATEMENT OF DR. CLAUDE LENFANT

It is my pleasure to speak to you once again about the programs of the National Heart, Lung, and Blood Institute (NHLBI). Since its inception, the Institute has been strongly committed to disease prevention, a goal that has been greatly furthered by basic, clinical, and population-based studies designed to identify risk factors for cardiovascular, lung, and blood diseases. Interventions to reduce the impact of the three major cardiovascular risk factors--hypertension, cigarette smoking, and high cholesterol--have paid off handsomely in terms of reduced mortality. Findings from new studies are now bringing more precision to our indicators of risk for certain subgroups of the population. For example, the Framingham Heart Study recently reported results of echocardiographic studies that revealed increased left ventricular mass to be a powerful predictor of future heart problems in Blacks and in elderly persons. The recently initiated Cardiovascular Health Study, which focuses on individuals ages 65 to 90 years, is examining combinations of risk factors, such as elevated cholesterol, glucose intolerance, insulin resistance, and obesity, to identify patterns that may presage coronary events. The findings should provide important information for an age group in whom hypertension and high blood cholesterol are quite prevalent and yet are not as strongly associated with the risk of developing cardiovascular disease as in younger people. Significant public health benefits and cost savings are likely as we refine our ability to identify persons who will benefit from medical and lifestyle intervention and focus our efforts and resources where the return will be the greatest.

Evidence of benefits that can result from reducing serum cholesterol levels continues to accumulate. Two recent studies, one using drugs and the other using a combination of strict diet and behavioral changes, reported that lowering cholesterol actually causes regression of atherosclerotic changes in arteries. These results underscore the public health gains to be realized by the National Cholesterol Education Program (NCEP). The NCEP "know your cholesterol number" message is reaching the community: in 1988, 66 percent of adults had their cholesterol levels measured as compared with 35 percent in 1983. The interest of people in knowing their blood cholesterol levels is reflected in increased public cholesterol screenings. To be successful, cholesterol screening must lead ultimately to a reduction in the risk of coronary heart disease (CHD), an objective that can be accomplished only if proper assessment techniques are used and adequate education and follow-up are provided. The NHLBI Recommendations Regarding Public Screening for Measuring Blood Cholesterol have been widely distributed in the expectation that they will improve the quality of public screenings.

One of our primary goals in disease prevention is to facilitate appropriate and early application of current research advances related to heart, lung, and blood diseases and to transfusion medicine. The time between the development of advances in new knowledge and their successful transfer into medical practice and to the public has become remarkably short. Let me tell you about some recent activities that are of immediate benefit to the public health of the United States.

Whenever the Institute undertakes a clinical trial of a drug intervention, it does so with the expectation that the results will lead to improved approaches for management and prevention of disease. However, there are times when a clinical trial demonstrates findings that, while unanticipated, are as important as if the original premise of the study had been confirmed. The Cardiac Arrythmia Suppression Trial was designed to evaluate the effectiveness of three antiarrhythmic drugs in preventing sudden death in heart attack survivors with mild arrhythmias. Last April, use of two of the drugs was halted when it became apparent that death occurred almost twice as frequently among those who took the drugs as among those who took a placebo. Because these drugs had been widely prescribed in the United States for mild arrhythmias, these findings have had a widespread, immediate impact on physician practices. Considerable savings of lives and medical costs should result. This experience underscores the importance of the clinical trial as a research tool which, in this case, revealed that the drug, rather than the disease, was the cause of excess mortality.

Women account for about half of all deaths from CHD in the United States and are twice as likely as men to die in the first few weeks after a heart attack. Attention is now being focused on the mechanisms by which CHD develops and progresses in women. For example, the relative freedom from heart attack experienced by women before menopause has generated investigations of the possible protective effect of hormones produced by the ovaries. Recently, investigators reported that natural menopause tends to lower "good" cholesterol, high density lipoprotein, and raise "bad" cholesterol, low density lipoprotein, but estrogen replacement therapy seems to nullify that effect. The NHLBI's Postmenopausal Estrogen/Progestin Interventions (PEPI) trial is evaluating whether various combinations of estrogen and progestational agents reduce risk factors for heart disease. The results are expected to provide a solid basis for preventive treatment recommendations.

The Institute is also focusing a major effort on risk factor modification in selected populations. The Dietary Intervention Study in Children (DISC) is assessing the efficacy and safety of a cholesterol-lowering diet for prepubescent children who have high cholesterol levels. The NHLBI Growth and Health Study is developing important new information about obesity and its consequences in Black and white preteen and teenage girls. The Lung Health Study for early detection and prevention of chronic obstructive pulmonary disease is the first trial of risk factor modification in lung disease.

Considerable attention also is being directed toward a cluster of 11 southeastern states where the death rates from stroke are so high as to warrant the designation "stroke belt." Of particular interest and concern are the observations that, among Blacks in those states, hypertension is more prevalent, more severe, and less well-controlled, and obesity is more common than among Blacks in other regions. The National High Blood Pressure Education Program has developed a multifaceted stroke belt intervention strategy to address the particular problems associated with hypertension control in the Southeast.

This year has been one of great progress in basic and clinical investigations into the pathogenesis of cystic fibrosis (CF). Discovery of the CF gene has expanded opportunities for understanding the underlying biochemical defect and designing new therapies. Translation of these concepts into improved care for CF patients will require years of investigation. On the immediate horizon, however, is a promising therapy that inhibits excessive sodium and water absorption. Building on the basic science observation that a defect exists in sodium absorption in CF cells, a pilot study of aerosol-administered amiloride demonstrated its ability to thin out airway secretions and slow the disease-induced decline in pulmonary function. If confirmed in large clinical studies, these findings will represent an important contribution to modern CF therapy.

Over the years, I have reported a number of advances resulting from our research program in neonatal respiratory distress syndrome (RDS), and I am happy to report today that a major goal has been achieved. Ever since it was discovered that RDS is caused by a deficiency of surfactant, development of an effective, safe replacement therapy has been a dream of clinicians and basic researchers. In 1989, approval was given for wider use of two experimental surfactant preparations shown effective in improving the course of RDS through clinical studies sponsored by NHLBI. Successful treatment with surfactant replacement is expected to reduce the severity of RDS and need for mechanical ventilation. Long-term follow-up studies are under way to establish the impact of surfactant replacement on the incidence of such complications as bronchopulmonary dysplasia, a serious chronic lung condition that affects 8,000 American newborns each year.

The NHLBI has been a leader in the development of asthma self-management strategies effective in reduction of the frequency and severity of asthma attacks and emergency room visits. Results of our research programs are being widely disseminated through the National Asthma Education Program (NAEP), initiated in 1989 to provide patient, family, professional, and public education about asthma and its management. An NAEP Expert Panel on Management of Asthma has been convened to develop national guidelines for

physicians who treat patients with asthma.

Improved asthma management is needed particularly for Blacks, who are twice as likely as whites to be hospitalized for asthma and three times as likely to die of asthma. Although corresponding data for Hispanics are not available, a number of barriers to effective asthma management exist, such as low educational and literacy levels and lack of access to continuing health care. In response to this need, the Institute recently announced a new research program to develop interventions that address the special needs of Black and Hispanic children. With this coordinated approach, the Institute hopes to play a major role in the control of asthma by helping individuals learn to manage their chronic disease.

We are pleased to report progress in the quest for improved treatment of two hereditary blood disorders, sickle cell anemia and Cooley's anemia. Scientists have developed transgenic mice whose red blood cells make human hemoglobin. They are now able to implant sickle hemoglobin genes in these animals and cause production of the human hemoglobin S found in patients with sickle cell anemia. These developments bring us far closer to having animal models of this disease to facilitate detailed studies and enhanced exploration of experimental treatments. Researchers studying Cooley's anemia have reported success in the development of oral iron chelators, agents that remove the toxic iron accumulation associated with multiple blood transfusions. Several new agents have now been approved for experimental use and it is hoped that they will prove effective in the management of this chronic disease and eventually replace chelators that must be injected daily. During the past year, the size of the National Bone Marrow Registry, now operating under NHLBI management, doubled to include over 78,000 potential donors. Bone marrow transplantation has become an accepted and effective treatment for an increasing number of diseases of the bone marrow and immune system. Over 270 transplants have been performed as a result of the registry. It is anticipated that improved access to tissue-matched donors and better transplant technology will make bone marrow transplantation an acceptable alternative treatment for severe sickle cell anemia and other serious hematologic disorders.

The National Blood Resource Education Program (NBREP) was formally launched in October 1987 to ensure an adequate and safe blood supply and ensure appropriate transfusion of blood and blood components. In the past year, the program released two major reports providing guidance for health professionals --one on the use of red blood cells, platelets, and fresh frozen plasma and the other on the use of autologous blood. In addition, a mass media public education program was begun to supplement efforts of local blood centers in recruiting blood donors. This year an important program focus will be production of a resource kit for blood banking personnel to improve donor recruitment and retention.

Results of AIDS research have already improved the quality and length of life of patients and helped reduce the spread of the AIDS virus. Clinical researchers have focused much attention on the lung, the organ most affected as a result of HIV infection. NHLBI intramural scientists recently reported finding abnormally reduced levels of glutathione, a natural substance in the body necessary for immune function, in the lungs and blood of men infected with the AIDS virus. An aerosolized form of glutathione has been developed and is now being tested in humans to determine whether it can safely restore the deficiency in the lung. Since glutathione plays an important role in enabling the immune system to function normally, it is hoped that increasing the levels of glutathione will help to prevent AIDS-associated lung infections.

These accomplishments reflect the breadth and depth of our programs of basic and clinical research, clinical trials, and public and professional education. We report them with pride and with confidence that they will provide a foundation for many future improvements in the public health of the United States.

Mr. Chairman, the FY 1991 budget request for the National Heart, Lung, and Blood Institute favors basic research and totals $1,112,502,000. I would be pleased to answer any questions that the Committee may have.