TOPICS > Health

Heart Disease Discovery

April 3, 1997 at 12:00 AM EDT
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MARGARET WARNER: There’s a fascinating new development today in the fight against heart disease. A study by Harvard scientists published today in the New England Journal of Medicine found that ordinary inflammation of the blood vessel walls may be as important a risk factor for heart attacks and strokes as high blood pressure or cholesterol. It’s just the latest of several important developments in the battle against America’s No. 1 killer.

Some 700,000 Americans suffer one or more heart attacks each year, and though many don’t die from their first attack, coronary heart disease ultimately kills more than 450,000 people annually. That accounts for one in four deaths nationwide. Yet, those numbers represent an improvement. A recent study by the Harvard School of Public Health found that the death rate from heart disease fell 34 percent between the years 1980 and 1990.

SPOKESMAN: Take 36 at the top.

MARGARET WARNER: Just in the past year there have been significant developments in both prevention and treatment, ranging from new insights into the value of drinking red wine and grape juice to prevent heart attacks, to new drugs that dramatically reduce the mortality rate in people who get heart attacks, to new less invasive surgical procedures that avoid the dangers of traditional open heart surgery. Today’s latest news in the New England Journal of Medicine may suggest an entirely new way to think about diseases of the heart.

MARGARET WARNER: And here to discuss today’s news and other recent developments are Dr. Paul Ridker, the lead researcher of the study published today. He is a cardiologist at the Brigham & Women’s Hospital in Boston. And Dr. Bernard Gersh, the chief of cardiology at Georgetown University Medical Center. He’s also chairman of the Council of Clinical Cardiology of the American Heart Association.

Welcome to you both. Dr. Ridker, tell us–describe more fully your findings today. What news have you really discovered about the cause of heart attacks?

DR. PAUL RIDKER, Brigham and Women’s Hospital: Well, many heart attacks, as you know, occur in individuals who really, as far as we can tell, have no overt or apparent risk factor. What we’ve described in our work is the idea that inflammation, that is, the body’s attempt to respond to injury, may, in fact, be a risk factor or risk marker for the future occurrence of cardiovascular disease.

That hypothesis has been with us actually for a few years. In fact, some very excellent basic science work in the laboratory setting has suggested that inflammatory process, if you like, the body’s attempt to repair injury, is intimately involved in the acute setting of a heart attack when the blood clot actually occurs and when the blood flow to the heart actually stops, that the inflammatory process is somehow involved. And other investigators have suggested perhaps that this inflammatory mechanism might be there a little a little bit before that perhaps, among smokers who went on to have coronary deaths, or among our patients with unstable angina A syndrome; that’s where they pre-heart attack. What we tried to do is ask the question: Was this inflammation present many years before of a heart attack ever occurred?

MARGARET WARNER: And in very healthy people, or apparently healthy people.

DR. PAUL RIDKER: Well, that’s right. What we actually did is employ the Physicians Health Study, a large scale randomized trial of aspirin that was begun by Dr. Charlie Henigen in Boston in 1980, and in that study we had 22,000 very healthy physicians. They’re marvelous subjects to study because they give us excellent follow-up and excellent compliance with their medications. And they were all healthy. None of them had a prior heart attack, a prior stroke, or any chronic disease.

What we then did is ask the question: If we measure a particular protein that happens to be called C-reactive protein, and really that is just a protein that our liver makes in response to injury or response to chronic irritation–we measured the level of this protein in these individuals when they were healthy. And what we found was that all of them had normal levels because, in fact, they were healthy, but those individuals at the upper end of normal had about a threefold increase risk in going on to have a heart attack and about a twofold increase in risk of going on to have a stroke.

MARGARET WARNER: Explain to us in layman’s terms, if you can, what you mean really by inflammation, inflammation of the blood vessel walls, and would a person know they had it?

DR. PAUL RIDKER: Well, inflammation in a very broad sense is the body’s attempt to respond to an injury or an irritation. The kind of inflammation we’re talking about here, though, I prefer to call micro-inflammation or a low grade, smoldering kind of inflammation because really these individuals are completely healthy. They have no symptoms and in no way do they feel ill. They’re perfectly fine, so there’s no way they would know they might have more inflammation than other individuals.

MARGARET WARNER: And what does the inflammation do, though, to cause the heart attack?

DR. PAUL RIDKER: Well, that’s actually a terrific question, and we don’t really know. I think there’s at least three possibilities that are worth considering that are consistent with our findings. One is that atherosclerosis, the very process by which cholesterol builds up in the arteries and eventually leads to a narrowing and eventually to heart attack may, itself, be an inflammatory disease.

That is to say that atherosclerosis is present and is the actual irritation in the arteries that we are measuring when we measure this protein. Another possibility is that this protein, C-reactive protein, and the atherosclerosis work in tandem, if you like, and that they accelerate the process for each other, and that they’re intimately related, and lead to a rupture of what we call an atherosclerotic plaque at the time of the heart attack. And a third, very intriguing possibility is that perhaps the inflammation, the irritation in our blood vessels, actually precedes the atherosclerosis.

That’s particulary interesting because if that turns out to be the case, we have to ask the next question, which is where did that inflammation come from in the first place. And, again, there’s been some interesting laboratory data suggesting that perhaps a chronic infection that might be present in some individuals but not in others might be the source of that inflammation. It’s important to point out, however, that all three of these hypotheses, I think, are equally consistent with the data, and clearly we don’t have that sorted out yet.

MARGARET WARNER: This gives a new explanation, does it not, why to aspirin has been shown to reduce the risk of heart attacks?

DR. PAUL RIDKER: Well, one of the particularly intriguing findings in these data is that the Physicians Health Study provided us the opportunity to evaluate directly the effects of aspirin, an agent traditionally considered an anti-platelet or a blood-thinning drug because the Physicians Health Study participants were actually randomized to aspirin therapy or to placebo, which were a dummy drug. In fact, it was the Physicians Health Study many years ago that demonstrated for the first time that if you took an aspirin every other day that you could reduce your overall risk of a heart attack by about 44 percent.

What the new data suggests is that the magnitude of the benefit of aspirin differs somewhat in different patients; that is, the individuals in our study who, despite being healthy at baseline, had higher levels of this inflammatory marker seemed to get a larger benefit from being on preventive aspirin than did the individuals who had lower levels of this. I’d like to point out, however, that everybody benefitted from the aspirin. It’s just a different effect in these different groups.

MARGARET WARNER: All right. I want to bring Dr. Gersh into this and ask you both this question. All the stories that I read today said, and Dr. Gersh, let’s start with you on this, that despite these findings, people shouldn’t run out and get tested for this C-reactive protein, even though, in fact, it may predict way in advance the risk of heart attack. Do you agree with that?

DR. BERNARD GERSH, Georgetown University Medical Center: I agree. I think it would be premature to go out and be tested and then if the levels are high, do we have a specific form of therapy, no. I think that the study does a greater benefit from aspirin in people with C-reactive protein. And I think the fascinating part of this study–and it is a fascinating study–is it points to a whole new almost hypothesis for heart attacks and atherosclerosis, namely the inflammation theory. And it’s going to point to a new source of investigation over the next few years, but it’s too early to take the next step and say we should be tested for this, and if so have some other form of treatment.

MARGARET WARNER: Do you agree, Dr. Ridker, too soon for people to go get tested?

DR. PAUL RIDKER: Yes, I do. You have to understand that this is an epidemiologic study. Essentially, we’ve made an observation in these healthy individuals that if you measure this particular protein, they seem to be at increased risk over the next six to eight years of their lives of having their first heart attack or their first stroke. On the other side of the coin is–now this is not an experimental study–basic laboratory work needs to be done to sort out the mechanism. And, in fact, we need confirmation of this observation in several other studies before I think we can have confidence in actually trying to decide whether or not to measure a new factor.

MARGARET WARNER: Dr. Gersh, what do you think, turning to other developments, is the most promising new development say in the drug area?

DR. BERNARD GERSH: Well, just to go back to one aspect of this study which combines both the old and the new is the story of aspirin. I mean, aspirin began as an anti-inflammatory agent. We then for the last five or ten years have used it mainly as a drug to prevent blood clots by inhibiting platelets, and now maybe it’s going around full circle again and becomes an anti-inflam–maybe it works because it’s an anti-inflammatory agent as well, so it’s sort of interesting to see that what goes around comes around.

MARGARET WARNER: And choose maybe one other drug that in the past year has shown particular promise.

DR. BERNARD GERSH: Well, there actually have been a number. The one area that I think fulfilled the promise of the 1980′s and was concerned in the 1990′s were the clot-dissolving or thrombolytic drugs. And it was almost 90 years ago that Dr. Herrick in the United States postulated that the heart attack would lead to a blood clot in an artery supplying a heart, and 80 years later we’ve realized that dissolving these clots is feasible and very effective, and basically all that work was done in the 80′s, but I think we’ve learned even more in the 90′s about how effective these drugs are in all age groups, irrespective of sex.

MARGARET WARNER: And what about in the surgery area? We hear a lot about these new non-invasive procedures. We don’t have to saw the guy’s chest open anymore.

DR. BERNARD GERSH: I think you must be talking about what we call minimally invasive surgery, or keyhole surgery. And it’s important, I think, to emphasize that this is new and promising, but it’s not just one kind of an operation. There is one operation in which the incision is very small. The patient is not put on the heart-lung bypass machine. They don’t go onto that heart-lung machine. And a bypass is done to usually just one artery. It is a small incision.

It’s a limited operation because you can only bypass one artery, and many people who need bypass surgery need three or four arteries bypassed or two. The other form of minimally invasive surgery, if I can use that term, involves new technology which will enable the patient to go on bypass through a small incision. And obviously it has the great potential to reduce hospital stay and reduce mobility and pain, and it’s exciting, and we need to follow very closely, and I would stay tuned over the next year. There will be a lot more information.

MARGARET WARNER: And Dr. Ridker, briefly, before we go, this has to do with lifestyle versus medical breakthroughs and which has done more to reduce the mortality rate. A recent study suggested it’s actually most the medical breakthrough. What’s your view on that?

DR. PAUL RIDKER: Well, it’s a very interesting question. We clearly have made tremendous changes in our ability to reduce the case fatality rate for heart attacks. That is to say, when individuals now have heart attacks, as Dr. Gersh has pointed out, we have some excellent therapies that if given very rapidly and if patients recognize theirs signs and symptoms and can get to the hospital quickly, our colleagues can do a very good job in keeping the patient alive.

So part of that benefit we now see is in case fatality rates. On the other hand, it remains a fact that a great majority of heart disease nonetheless will occur, and we have a tremendous opportunity in primary prevention; that is, in stopping the patient from ever having their first heart attack. So what it really all boils down to is smoking cessation, blood pressure control, cholesterol reduction, exercise, and diet. And, in fact, if we can comply with those, I think our patients will do quite well and hopefully won’t see Dr. Gersh or I.

MARGARET WARNER: Great. Well, thank you both very much. We do have to leave it there. Thank you both.