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going analyses of the distribution of HLA combinations will provide a basis for reevaluating and revising recruitment goals.


What problems are you experiencing in continuing to expand the Bone Marrow Registry?

Answer. As the size of the registry has increased, so also have the costs associated with donor center support and file maintenance. We are pressing the contractor to obtain better cost figures for these legitimate and growing needs so that we can provide funds for them.

A principal reason for the large increase in the registry is the technique of using widely publicized recruitment drives to benefit specific patients. These drives are helpful, but they also create problems for us. For example, recruitment from these drives has been so successful that the funds available for HLA typing were initially insufficient. In addition, few minority families have participated in patient-specific drives, so that the majority of donors added to the file have genetic backgrounds similar to those already included. Also, because the expectations of families who undertake such drives have been raised, their disappointment is greater if a donor cannot be found. On the other hand, when these drives are targeted to minority populations, they have been very helpful in expanding the numbers of donors from underrepresented groups in the registry.


Question. We know, of course, that asthma attacks occur because the airways are narrowing and the person has increasing difficulties in getting enough oxygen, and we know that this effect can be reversed by medication. Doctor, what is the mechanism that actually causes asthma?

Answer. For years asthma was thought to be only an acute, sudden tightening of the airways. We now know that it is a more chronic condition in which underlying inflammation plays an important role. The three major processes in asthma are: 1) airway obstruction, or narrowing; 2) airway hyperresponsiveness to a variety of stimuli; and 3) inflammation. Although much needs to be learned about the precise mechanisms of asthma, we know that it is a complex interaction among inflammatory cells, mediator substances, and the cells and tissues of the airway. To the patient, obstruction of the airways is the problem. It results from constriction of the muscles surrounding the airway, excess mucus production, and airway swelling.

Question. What is it that actually causes the airways to suddenly constrict causing an asthma attack?

Answer. An individual with asthma has airway hyperresponsiveness, or an exaggerated bronchoconstrictor response to many physical, chemical, and pharmacological agents, such as allergens, environmental irritants, viral respiratory infections, cold air, or exercise. For example, when an individual with asthma inhales a substance such as animal dander, the usual response is a narrowing of the airway, caused by the constriction of the smooth muscles surrounding the airway. This constriction of smooth muscle involves the release of inflammatory substances from the cells that line the airway, which attract and activate other inflammatory substances circulating in the blood. The combined effect of all these substances is injury to the lining of the airway, which increases its sensitivity to inhaled allergens. As a result, the walls of the airways swell, produce more mucus, and become more hyperresponsive. Inflammation keeps the airways in a chronically irritated state that predisposes them to further episodes of obstruction. the past, the usual therapy for asthma relied solely upon controlling the bronchoconstriction. Now, as emphasized in the recently released report "Guidelines for Diagnosis and Management of Asthma," from the National Asthma Education Program, control of inflammation is viewed as an important part of asthma treatment.



Question. I understand that last year NIH recommended against proceeding with a diet study that focused on health effects of carefully controlled diets on women. Your Institute and the Cancer Institute are involved in this effort. I understand that whether or not NIH proceeds with this study has come into question and has been the focus of a good bit of controversy. in your view Doctor is the merit of proceeding with the Diet Fit Study?

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Answer. The Diet Fit trial is designed to test whether a low fat diet will prevent the development of breast cancer and heart disease in postmenopausal women. A trial of the size proposed in Diet Fit would test with high confidence whether this low fat diet would reduce the development of two common, chronic diseases in women coronary heart disease and breast cancer. For this reason, we have expressed interest in supporting this study and have worked with the National Cancer Institute on a study design that would best serve the needs of both of our programs. At the present time we are cosponsor of a pilot study to assess the feasibility and acceptability of the proposed dietary intervention by the population we want to reach. Although there are many significant difficulties to overcome in conducting a successful, large scale trial, from our perspective such a study has the potential to yield useful and important information.


Question. At these hearings last year, the Committee expressed a desire that your Institute's research efforts reflect a better balance of health and behavior research. The Committee also stated that it would like to see such topics as health and behavior in the workplace and evaluation of service programs added to the Institute's priorities. Could you comment on any developments regarding these concerns?

Answer. Since 1980, the National Heart, Lung, and Blood Institute (NHLBI) has coordinated the NHLBI Workplace Initiative. It has been an important element of three of the NHLBI education programs: the National High Blood Pressure Education Program, the National Cholesterol Education Program, and the NHLBI Smoking Education Program. The NHLBI Workplace Initiative activities will now also be incorporated into our newest national education program, the National Heart Attack Alert Program. The goal of the NHLBI Workplace Initiative is to reduce premature cardiopulmonary morbidity and mortality.

In order to achieve this goal, the NHLBI Workplace Initiative promotes research and educational projects and materials to reduce cardiopulmonary morbidity and mortality among workers and their families. For example, the NHLBI has funded several studies examining efficient and effective ways to cstablish cardiopulmonary risk factor reduction programs at the workplace. One workplace demonstration and education study, which was conducted at the University of Michigan in cooperation with General Motors Corporation and the United Auto Workers, sought to reach blue-collar workers, a group at particularly high risk for cardiopulmonary disease. The study investigators and NHLBI staff are currently translating study findings into a set of practical guidelines. These guidelines, called "Wellness Outreach at Work," will assist interested professionals in establishing and maintaining programs for employees.

Another study at the University of Minnesota is examining the impact of workplace-based intervention projects on smoking and obesity in a project involving 32 firms. In this study, cross-sectional surveys of employees evaluate the impact of the interventions on smoking and obesity. analyses examine differential effects on employee subgroups. In addition, characteristics of the worksites that facilitate or hinder program effectiveness are examined.


A workshop, sponsored by the NHLBI and the University of California at Irvine, examined physical and psychosocial characteristics of the worksetting and their relationships with cardiovascular disease. Evidence of an independent association between occupational stress and the incidence of

coronary heart disease and subsequent mortality has stimulated interest in defining the proportion of risk attributable to modifiable factors in the work environment. Based upon recommendations from the workshop, the Institute is developing an initiative to address occupational stress and cardiovascular disease.

The NHLBI Workplace Initiative also maintains an active technology transfer effort that relies upon seminars and other cooperative activities and dissemination of educational materials. For example, the Institute developed a kit of materials for professionals and workers primarily related to the three major modifiable risk factors: cigarette smoking, high blood pressure, and high blood cholesterol. The kit includes technical documents for health professionals, guides for workplace program planners, brochures and materials for workers, and order forms for additional publications.


Question. What types of new cholesterol awareness education programs do you currently have in place?


Answer. In 1990, the Institute's National Cholesterol Education Program (NCEP) released the report of the Population Panel, which recommended that healthy Americans adopt an eating pattern low in saturated fat, total fat, and cholesterol in order to reduce average blood cholesterol levels in the population. Various mechanisms are now being used to communicate this message to the public. New television public service announcements have been developed to promote heart-healthy eating. A revised fact sheet is being distributed to educate the public about low saturated fat, low cholesterol eating patterns. New recipes have also been added to expand the range of the Stay Young at Heart kit, a point-of-purchase nutrition education program. On April 8, 1991, the NCEP released the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. The report reaffirms young people from the age of about two years should take part in the population eating pattern as a principal means for coronary heart disease prevention. The report also recommends that children from families at high risk for coronary heart disease have their cholesterol level measured to determine whether they require individualized medical attention to help lower their cholesterol. The report will be widely disseminated to health professionals and will be presented and discussed at professional meetings. Educational booklets for parents and their children are being readied to explain how to adhere to a cholesterol-lowering diet. A new round of television public service announcements will use a family theme to promote heart-healthy eating for adults and children. The Institute is also planning to an initiative to encourage schools to incorporate information about hearthealthy eating into their curricula and to offer heart-healthy menu choices in their cafeterias.


Question. What role can we in Congress play in the education, prevention, and behavior modification program?

Answer. Philosophical and policy support by Congress, particularly in the last decade, has provided the impetus and means to define our prevention science research agenda and to translate the outcomes of prevention research into prevention, education, and control programs. The Congress continues to play a critical role in providing its insight about priorities. The Institute is encouraged by the contributions of the Congress included in its report language and in its deliberations to help formulate public health policy in the area of prevention, education, and control. We look forward to the continued support of the Congress in disseminating our increased knowledge regarding populations at risk, particularly minority groups.


Question. Could you tell us the current status of your artificial heart


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Answer. Two major activities are continuing. First, an electrically powered, implantable left ventricular assist system (LVAS) has completed rigorous laboratory reliability tests that demonstrated two years of continuous operation without failure. The device is being prepared for clinical evaluation in patients with advanced congestive heart failure. It will be the first use of an LVAS designed for extended use that only requires externally worn batteries to transmit electrical energy across the intact skin to power the implanted device. Clinical Centers in Pittsburgh and St. Louis are collaborating with the New England Research Institute to develop the clinical evaluation protocols and to guide the Investigational Device Exemption (IDE) through the Food and Drug Administration (FDA). The first LVASS are expected to be available in a few months and will be finally tested in a series of animals. Following necessary approvals of all aspects of the program; patient implants should begin in the Spring of 1992.

Second, the program to develop an implantable, electrically powered artificial heart to replace the failing heart is in the fourth of six phases. To date, four concepts for an implantable system have been designed, and prototypes for them have been built. A reliability model has been established for each of the systems and production problems are being evaluated. Animal tests have begun to measure performance so that required improvements can be identified. The objective of the current program is to demonstrate the potential of the four systems to function safely and effectively in a clinical setting over a five-year lifetime.

Question. Have there been any recent major breakthroughs in technology regarding artificial hearts?

Answer. Recent clinical experience with a textured, blood contacting surface suggests that it may be possible in some implantable artificial heart systems to develop surfaces that are virtually free of thromboembolic complications. New blood pumping surfaces and stationary surfaces have been developed that permit the growth of a coating similar to the lining in a natural blood vessel. These new surfaces have been observed in three dozen patients bridged to cardiac transplant. The patients accumulated nearly five years of mechanical circulatory support without embolic complications. Their experience suggest that synthetic surface receptors could evolve to the point where they respond favorably to a changing biological environment and remain biocompatible for the lifetime of the implant.


Question. Are elevated blood cholesterol levels predictors of cardiovascular disease in older persons, women, and minorities?

Answer. Data from 22 U.S. and international studies on cholesterol as a risk factor for heart disease in older persons and women were recently reviewed at an NHLBI-sponsored workshop. They strongly support cholesterol as a risk factor in older men and in middle-aged women. Risk of fatal coronary disease was 32 percent higher in men over age 65 years with cholesterol levels of 240 mg/dl or more, compared with those with cholesterol levels of 200 mg/dl or less. In women under age 65 years, the risk of fatal coronary disease was' more than twice as high among those with cholesterol levels of 240 mg/dl or more when compared to those with cholesterol levels below 240 mg/dl. In women over age 65 years, however, data were much less consistent and fewer studies were available. Although the overall risk of fatal coronary disease was only marginally increased in women over age 65, it was approximately 12 percent higher in those with elevated cholesterol levels. Further data are needed to evaluate the cholesterol-heart disease association in older women. They are currently being collected in NHLBI-sponsored, multi-center studies such as the Cardiovascular Health Study, the Cholesterol Reduction in Seniors Program, and the Framingham Heart Study.

Data for minority groups and for overseas populations were similar to those for White persons in the United States. Risk estimates for cholesterol levels greater than 240 mg/dl compared to cholesterol levels less than 200 mg/dl were essentially identical among 22,000 Black, 6,600 Hispanic, 4,000 Asian, and 316,000 White middle-aged men screened for entry into the Multiple

Risk Factor Intervention Trial (MRFIT), although overall rates of heart disease were lower in the minority subjects. Further assessment of risk associated with elevated cholesterol levels in minority populations will be provided by NHLBI-sponsored studies such as the Strong Heart Study, the Honolulu Heart Program, CARDIA, and the Atherosclerosis Risk in Communities Study (ARIC).


Question. Do you recommend the promotion of low fat, low cholesterol diets among children as a way of preventing heart disease later in life?

Answer. The National Cholesterol Education Program's (NCEP) Population Panel recommends that all healthy Americans, including children over the age of two, follow a dietary pattern lower in saturated fats, total fat and dietary cholesterol than the typical American diet, as a way to prevent coronary heart disease (CHD). The Panel recognizes that the caloric and nutrient needs of growing children are critical to support normal growth and development, and therefore urges prudent movement to the recommended eating pattern. Also, the NCEP Expert Panel on Blood Cholesterol Levels in Children and Adolescents recently released its report. This group reviewed the scientific evidence that atherosclerosis or its precursors begins in childhood and makes recommendations for the detection, evaluation, and treatment of children and adolescents believed to be at risk for CHD later in life by virtue of family history, and elevated levels of low density lipoprotein (LDL) cholesterol. The report also provides strategies for encouraging desirable eating patterns for healthy children and adolescents.

To determine the safety and efficacy of a diet lower in saturated fats, total fat, and dietary cholesterol in growing children, the Institute funds a multi-center, clinical trial, The Dietary Intervention Study in Children (DISC). Since children enrolled in DISC have elevated LDL levels, the diet recommended is more restricted in saturated fats, total fat, and dietary cholesterol than the diet recommended for healthy children. The DISC children will be followed for a minimum of three years to determine the effect of a fat restricted diet on LDL, growth, development, micronutrients, behavior, and cognition.


Question. There seems to be some controversy about the role of salt in raising blood pressure. What do the studies actually show?

Answer. The results of the most relevant studies, recently published following a 1989 NHLBI, reaffirm the importance of salt. Data from 15 observational population studies and 24 clinical trials were analyzed. One of the population studies, called INTERSALT, included 52 centers in 32 countries. In the aggregate, these studies indicated average blood pressures were lowered by approximately 2-4 millimeters of mercury when the usual sodium intake was cut in half. The benefits were somewhat greater in hypertensives. Results of observational studies and trials are remarkably consistent. Blood pressure reductions of these magnitudes might reduce death from heart attacks by 5 percent and death from stroke by 8 percent. The potential number of U.S. deaths averted in middle-age alone is estimated to be 16,000 per year.

The conference papers also included studies of so-called "salt sensitivity", which is the tendency of people to respond differently to large changes in salt intake and urinary excretion over relatively short periods. These findings have considerable importance for understanding mechanisms of blood pressure regulation.


Question. It has been reported that lowering cholesterol may result in violent behavior. Is this a source of concern?

Answer. At the present time, a link between lowering of blood cholesterol and so-called "violent behavior" is only hypothetical. Last fall, the

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