However, we have not yet demonstrated conclusively in man that lowering LDL cholesterol will decrease the progression or prevent coronary artery disease. That is a hypothesis; the so-called lipid hypothesis. It is supported by strong circumstantial epidemiologic data, supported by animal data, but has not yet been validated conclusively in man.

Thus, a major investment of the Institute is in multicenter clinical trials designed to test this hypothesis. In aggregate, they cost the Institute almost $25 million a year. They have been underway for several years, and are scheduled to end between 1982 and 1984.

As to what to do until additional evidence is in, obviously, we cannot move out loudly with aggressive programs like the national high blood pressure education program. We can, however, seek additional facts and search for ways to make existing facts available to the public, especially those at high risk, so that they can make an informed choice. In this regard, the public would be wise to hedge their bets and become familiar with the dietary guidelines for Americans published earlier this year. They are consistent with the available facts on hand and represent prudent advice that may, indeed, be quite beneficial. Thank you.

Mr. RICHMOND. Dr. Levy, I am sorry I had to run off to vote and was not able to welcome you here. It is always a pleasure and an honor to have you testify before our subcommittee.

Dr. LEVY. Thank you.

Mr. RICHMOND. As we have heard from you and from our distinguished scientists yesterday, there are three major risk factors in cardiovascular disease-high blood pressure, smoking, and high blood cholesterol levels.

Dr. LEVY. That is correct.

Mr. RICHMOND. Of these three, what do you think is the most important in development of heart disease?

Dr. LEVY. It is hard to weight any one over the other; they are all important. Certainly, in individuals whose cholesterol-LDL-is low or absent, one does not see atherosclerosis; LDL is a handmaiden of the process. Without LDL-without cholesterol-in the bloodstream, atherosclerosis would not occur.

Thus, Mr. Chairman, I would have to say that if cholesterol is not the first, it is among the top one or two modifiable risk factors.

Mr. RICHMOND. When we say cholesterol, we always also are assuming we are saying saturated fats-is that correct? In other words, we very frequently group the words, cholesterol and saturated fats, as one phrase.

Dr. LEVY. My discussion dealt with the cholesterol levels in the blood. A major determinant of the level of cholesterol and LDL in the blood is the amount of saturated fat, total fat, and cholesterol we consume in our diet.

Mr. RICHMOND. It appears from the latest publication of the Food and Nutrition Board that they reject that connection between diet and heart disease. Do you think their work represents anything new that would lead to this rejection?

Dr. LEVY. The report does not deal with, or review, or present new facts. The report looks at old evidence and comes up with an opinion. In fact, the report accepts that LDL cholesterol is a major risk factor

for coronary artery disease. It seems to reject, however, the notion that altering diet will change in any way or have a major effect on the average American's cholesterol level.'

Mr. RICHMOND. In other words, you say that on the one hand they accept the fact that cholesterol will lead to a higher incidence of heart disease, but they do not believe you can help your cholesterol in any way by diet. Is that correct?

Dr. LEVY. No; they talk about the average or healthy American, and that is of course, a difficulty. What is the average or healthy American? The whole concept behind the risk factors, Mr. Chairman, is that one feels very healthy when one has a number of these risk factors. We identify them in healthy individuals so that we can keep the individual healthy, we hope-so that we can prevent the individual from manifesting coronary artery disease.

It is really a view of existing evidence. Is the cup half full or half empty? And this group came up with a report which is somewhat at variance with other consensus reports. It looked at the same evidence that has existed-not new evidence.

Mr. RICHMOND. Dr. Levy, you have been in this field all your life, frankly. How long have scientists been exploring this connection between diet and heart disease, as far as you know?

Dr. LEVY. This goes back to the turn of the century and the work of Annichnokov, a Russian scientist. The lipid hypothesis, in one way or another, has been spoken to for well over a half a century.

Mr. RICHMOND. So, for half a century we have been leaning toward the advice to people that could possibly have heart disease that they would be wise to limit their consumption of foods containing high degrees of saturated fats, just because of the gradual mounting of information indicating that direction to take. Am I correct?

Dr. LEVY. With various degrees of strength and different degrees of conviction, that opinion has existed for over 80 years now.

Mr. RICHMOND. Why has it taken so long to explore this connection, would you say?

Dr. LEVY. We are dealing, Mr. Chairman, with a chronic disease. Coronary artery disease, as I indicated in my opening statement when you were out voting, is a process that develops over decades; the atherosclerotic process begins in childhood and advances slowly even in patients with genetic disorders. It usually only manifests itself in the fifth, sixth or seventh decade of life. Our problem has then been clearly establishing cause and effect. When we deal with coronary disease, we still have to rely on hard end points like heart attack and death which occurs at the end of this lengthy process. Unfortunately, our noninvasive techniques are not yet as certain as we would like them to be in diagnosing or evaluating coronary artery disease at an early stage.

To wait for events like heart attack and death means we need large numbers of people and long periods of time. We do not have the luxury of someone testing a new antibiotic for an infection or a new ointment for a rash. To show that cholesterol lowering is effective in a process that takes decades to develop, one needs a large number of patients and long periods of time. When one deals with studies that require large numbers of patients and long periods of time, one has to worry about factors like volunteer dropout; one has to worry about the degree of

lowering that can be achieved. I would have to say that until the early 1970's we were rather naive as to how difficult it was to prove or test the lipid hypothesis.

We now have the sample size calculations. These were the basis for the clinical trials that we began in the early 1970's. We hope these trials will give us the information we need in the next 5 years.

Mr. RICHMOND. Dr. Levy, in your personal estimation, do you think the Academy should have put out the report in the manner that it did? Dr. LEVY. The Academy certainly has, and the members have the right to their opinion and the right to give advice. It was perhaps a shame that the report was presented first to the public at a press conference rather than shared among the scientists and the scientific community. It is a shame that the impression conveyed to the public was that this represented new facts and new information rather than another look at old information.

Mr. RICHMOND. In your personal opinion, do you think the Academy was attempting to make public policy, and do you think it should?

Dr. LEVY. I would sort of defer from addressing the question regarding the Academy's intent. I am not sure what they were attempting to do, but certainly we have always thought of the Academy as advisory, not as policymaking.

Mr. RICHMOND. Of course, that is their mandate.

Lastly, Dr. Levy, as a prominent scientist and public official yourself, can you advise this subcommittee what we ought to do next about this terribly serious problem?

Dr. LEVY. Certainly, the fact that this subcommittee is holding a hearing and giving a full airing to the subject is very useful to the American public which unfortunately, has been confused.

Certainly, in terms of what would be most effective, what we need, Mr. Chairman and perhaps I would be thought guilty of bias in saying it—are additional facts. We need this committee's and Congress support to allow us to go out and research the issue further, to obtain the facts, so that there will be more hard evidence to discuss.

Mr. RICHMOND. In other words, you think Congress should continue supporting the National Heart, Lung, and Blood Institute and help you do the necessary research to finalize this problem. Is that correct? [Laughter.]

it

Dr. LEVY. That is why, Mr. Chairman, I commented about my potential bias. But we are not alone in researching the role of diet in cardiovascular disease; other sister agencies are involved. We think, as is evident from the attention this issue has received in the press, is of major importance, especially when one considers the magnitude of the problem-coronary artery disease. Obtaining the facts needed to settle the issue, indeed, deserves much attention. Mr. RICHMOND. Thank you, Dr. Levy. Mr. Brown? Mr. BROWN. I have no questions, Mr. Chairman.

Mr. RICHMOND. Mr. Panetta?

Mr. PANETTA. Thank you, Mr. Chairman.

Dr. Levy, if somebody walked into your office and you determined that that person was a healthy individual, and he asked you for specific guidance you say, "reduction of cholesterol," or "too much cholesterol"-as to cholesterol intake and what would be appropriate from your point of view, what would you advise that individual?

Dr. LEVY. Mr. Panetta, I will give you a slightly lengthy answer and say that my advice would be predicated on that individual, his age, sex, family history, and the presence or absence of risk factor habits or traits.

Assuming that the individual is a middle-aged male who has no evidence of coronary artery disease, we may find a family history of heart disease or hypertension. My recommendations would be based on the findings. I would recommend to the individual, if he smoked, not to; if I found his blood pressure was elevated, I would attempt to help bring that blood pressure under control. Depending on the level of blood pressure elevation, I would either start with nutritional recommendations or move, after validating the finding of the high blood pressure on several occasions, to treat it aggressively with drugs.

If the individual's cholesterol is above 210 mm percent or so, I would want to see why it is at that level. With levels between 210 and 250 that are related to elevations in the LDL, I would talk to the patient about the fact that he ought to seek a diet lower in saturated fat and cholesterol, lower in total fat. If the cholesterol was between 250 and 300 and, again, the elevation was in LDL, I would not recommendand I am talking, by the way, about my personal office practice in all of these comments-I would direct the patient that diet change is indicated, that he should hedge his bets, that we do not have all the information to guarantee that lowering the saturated fat and cholesterol in the diet is helpful, but we do have a tremendous amount of circumstantial information to suggest that it would be worthwhile for him to lower the fat and cholesterol in the diet.

If his cholesterol was above 300 percent and it was due to elevation in the LDL, I would be even more aggressive. So my comments relate to the individual, the level of cholesterol, and the other factors present in that individual at that time. The more risk factors I find in an individual, the more aggressive I will be in advising control of those risk factors that are modifiable, like diet and smoking.

Mr. PANETTA. I think what you have said is, obviously, with regard to the individual who comes into your office, and what you determine specifically of the cholesterol issue to be that person's cholesterol level, that you would make your judgment based on that. Is that correct?

Dr. Levy. I would make my judgment based, in part, on that; that is exactly correct.

Mr. PANETTA. For the individual who has below the 210 in terms of cholesterol level and generally, in terms of the other areas, does not smoke and so on, would you make any specific recommendation to that individual with regard to cholesterol?

Dr. LEVY. Normally, I probably would not. It would depend on the individual's family history and other risk factors. Also, it would certainly depend on the individual's age because 210 mm percent before the age of 20 is decidedly abnormal. If I found the cholesterol at 170, 180, or 190, I would not make specific recommendations to that individual.

Mr. PANETTA. For that individual who does not have that kind of high cholesterol intake, as long as that person maintains whatever steady diet he has been engaged in, then he is OK in terms of that area?

Dr. LEVY. Let me say, Mr. Panetta, that I make that recommendation based on the evidence we have on hand now in terms of the value of cholesterol lowering. We do not have the final evidence.

There is no doubt that cholesterol is a graded risk factor, and a cholesterol level of 210 puts an individual more at risk for cardiovas cular disease than an individual with a cholesterol of 190.

Mr. PANETTA. The specific problem we have here is that everybody agrees that where you have the risk factors and where you have the problems, such as a history of heart disease, hypertension, and so on, clearly, cholesterol intake should be reduced. The real problem comes in with regard to the individual who does not have a high cholesterol showing, because I think the report refers to a healthy person. Who knows what a healthy person is or how that is defined? I understand that problem.

With regard to the person who does not have these risk factors and is showing a relatively stable cholesterol count, then you are not going to tell that person-let me ask you this. Are you going to tell that person, "Reduce your cholesterol in any event?"

Dr. LEVY. At this point in time, I wil not, but I would point out that from the surveys we have done over the last several years, which look at the distribution of lipids and lipoproteins in the United States, that 50 percent of adult males have cholesterols above 210 and that over 25 percent have cholesterols above 235 mm percent. So we are talking to a large number of the otherwise healthy American people.

Mr. PANETTA. You are saying, as a general message to the public, "You ought to reduce your cholesterol intake," as a general message? Dr. LEVY. The general message, because there are so many Americans at risk for this major killer process, is exactly that one should seek diets lower in salt, lower in fat, lower in cholesterol.

Mr. PANETTA. That would be a general statement to the American public?

Dr. LEVY. Yes; because of the nature of the number of American people who are at risk.

Mr. PANETTA. Thank you.

Mr. RICHMOND. Thank you, Mr. Panetta.

Dr. Levy, thank you so much for your testimony. We certainly appreciate it.

Ladies and gentlemen, we have a vote on the floor for final passage on our supplemental appropriations bill, in which you are all interested, so I will declare a 10-minute recess. Then we will hear from Dr. Phillip Handler.

[Recess taken.]

Mr. RICHMOND. Dr. Levy, we are very honored to have our ranking minority member, Mr. Wampler, with us here this morning. He did not have an opportunity to ask you any questions so I wonder if Mr. Wampler and Mr. Grassley could ask you questions before we go on to Dr. Handler? Mr. Grassley?

Mr. GRASSLEY. Thank you, Mr. Chairman.

Is the Department of Health and Human Services today giving a major grant support or clinical trials to better determine whether fat and cholesterol avoidance helps reduce risk of heart disease?

Dr. LEVY. The Department of Health and Human Services. through the National Heart, Lung, and Blood Institute, has invested close to