Senator HARKIN. We will discuss this in the next few weeks or so. I'm not committed to that. I'm just asking the question if that would be a proper way to go or not. I don't know.

I can understand what you mean. It's a continuum. If you separate it out, it looks like you are separating these functions out, and how do you assign full-time equivalents to it. I understand all that.

Dr. LENFANT. Mr. Chairman, I cannot underscore enough the point that what is important to assure the success of these prevention education programs is that they be based on research outcome not on some vague ideas. At each of our meetings, for example, where we discuss prevention, we have a science presentation to tell the people who are going to advise us on our next move relative to prevention about the latest information and best information that we have as a basis for that prevention program.

STUDY ON DIET AND FITNESS

Senator HARKIN. Do you have any more comments on the diet fit study other than what Dr. Broder said?

Dr. LENFANT. Yes, we do. Dr. Broder and I are discussing this from time to time and our respective staff discuss that a lot.

I really would like to underscore the point which he was making that the difficulty before making a decision is that we have to assess two factors, one is the feasibility of the study; by this I mean, is it feasible to really reach out to the population group that we want to include in this study.

And the second factor is the acceptability. This is a very important point: Assume that it is feasible to reach the population groups we need to include, but would it be acceptable to these people that we ask them to change diets very significantly because changing the diet is going to cost money. It is going to modify the budgetary constraints which may exist in this family. And for this reason, all our urging to change the diets may, in fact, not be accepted. Therefore, we think acceptability needs to be assessed as well as feasibility.

We do participate in this study. We are not as generous as Dr. Broder is, but we have our fair share in this program.

Senator HARKIN. I am wondering, is it under your department where you do the studies on cholesterol-right?

Dr. LENFANT. Yes.

Senator HARKIN. I'm going to have my staff get a hold of you. I would like to set up some time in the next few weeks to talk with you and anyone else that you might designate about what the latest findings are on cholesterol, treatments.

Dr. LENFANT. We will be most pleased, Mr. Chairman. We will call Mr. Hall and set up a time at your convenience.

QUESTIONS SUBMITTED BY THE SUBCOMMITTEE

Senator HARKIN. Thank you very much, Dr. Lenfant. There will be some additional questions which will be submitted for your response in the record.

The following questions were not asked at the hearing, but were submitted to the Institute for response subsequent to the hearing:]

QUESTIONS SUBMITTED BY THE SUBCOMMITTEE

ROLE OF VIRUS IN ATHEROSCLEROSIS

Question. Dr. Lenfant, as you know, atherosclerosis eventually kills more Americans than almost any other condition. The popular press has reported that "a common viral infection may be the first step in a complex process in which human arteries become clogged as people age...".

What can you tell the Committee about the possibility that a common virus may cause atherosclerosis?

One

Answer. It cannot yet be stated with any certainty whether the known association of viruses of the herpes family with human atherosclerosis is a cause or a consequence of the disease. However, a herpes virus infection is among the plausible hypotheses for early damage to the cells of the blood vessel wall, leading to the subsequent progression of atherosclerosis. herpes virus causes atherosclerosis-like plaques to form in the arteries of chickens. Experiments using animal cells in culture have shown how herpes viruses may enhance the early stages of atherosclerosis. And herpes viruses are commonly found in the human artery wall. One particular herpes virus cytomegalovirus (CMV) appears to increase the risk and severity of the atherosclerosis that often develops in the transplanted heart, compromising its survival.

Because our understanding of the role of viruses in the development of human atherosclerosis is incomplete, and because of the potential for clinically important results, the Institute will continue to support studies in this area.

EVALUATION FUNDS

Question. Dr. Lenfant, I noticed that your research management line or the funds you have for Institute management increase $7,728,000 or 14 percent compared to the 6 percent growth rate for your Institute overall. The research management and support for NIH grows 15 percent overall, so you are not out of line with the rest of NIH. Why is your overhead funding growing so fast?

Answer. The overhead funding growth has increased primarily as the result of decisions outside the control of the Institute to utilize more fully the evaluation authority authorized by Section 2711 of the Public Health Service Act. Section 2711 authorized the Secretary to make available for evaluation up to one percent of any appropriation for payments under any provision of the Public Health Service Act. The increased amounts made available through the evaluation set-aside will support activities of the National Center for Health Statistics' National Health Interview Survey, and initiatives on Health Promotion and Disease Prevention, as well as the activities of the Agency for Health Care Policy and Research.

NATIONAL MARROW DONOR REGISTRY

Question. As of January this year, I understand you have over 260,000 donors in the Bone Marrow Registry. Just a year ago, you had 110,000.

would like to congratulate you on the expansion. number of donors?

What is your goal for the

Answer. There are not yet enough HLA typing data available to determine definitively how many donors are needed. Extrapolation from the best analysis available suggests that a world-wide file of 2 million donors would provide a better than 90 percent chance of finding a donor for patients needing an unrelated-donor marrow transplant. The United States could contribute 1 million or more to such a world-wide file. More information is needed to determine the ethnic and racial composition of the potential U.S. donor population. It is very clear, however, that at least as many minority donors will be needed as their proportionate share of the American population.

On

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

Question. 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.

UNDERLYING CAUSE OF ASTHMA

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.

In

THE DIET FIT STUDY

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?

-

What

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.

HEALTH PROMOTION IN THE WORKPLACE

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. Data 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.

NATIONAL CHOLESTEROL EDUCATION PROGRAM

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

that

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.

CONGRESSIONAL ROLE IN EDUCATION PROGRAMS

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.

ARTIFICIAL HEART PROGRAM

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

program?

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