Interview: Dr. Elizabeth G. Nabel
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Dr. Nabel rose to national prominence as a result of her research into the molecular genetics of cardiovascular disease, conducted at the University of Michigan where she became Director of the Cardiovascular Research Center. She is also extremely knowledgeable about differences in the way heart disease affects women. As the Director of the NHLBI she now oversees an annual budget of 2.9 billion and an extensive national research portfolio of basic and clinical research aimed at preventing, diagnosing, and treating heart, lung and blood diseases. Dr. Nabel is also the recipient of many awards and serves on the editorial board of many scientific journals including the New England Journal of Medicine.
This interview was conducted in May, 2006.
- The Multiple Risk Factors for Heart Disease
- A Demographic Shift in Heart Disease
- The Epidemic of Obesity in Children
- Treatment of Heart Disease Has Outpaced Prevention
- Paying Attention to Risk Factors for Men and Women
- Heart Disease Is Treatable, Not Curable
- The Medical Community's Resistance to New Information
- The Economics of Critical Follow-up Care
- Why Patients Don't Take Their Medication: They Can't Afford It, and They Feel Fine
- The Future of Cardiology: Predictive, Preemptive, Personalized
The Multiple Risk Factors for Heart Disease
INTERVIEWER: How did medical researchers come to understand the risk factors for heart disease?
NABEL: The story of heart disease in this country is a very, very interesting one. Heart disease was on a sharp increase from about the 1900s until 1970 or so. Post-World War II, as our vets were coming back and reentering the workforce, the [United States] Public Health Service made the observation that men in their 50s and 60s were dying of heart disease and we didn't know the cause, so [it] initiated the Framingham Heart Study in Framingham, Massachusetts.
The idea was to begin to try to understand the causes of heart disease in this country, and so this very important longitudinal study of three generations of individuals was initiated. As a result of the Framingham Heart Study, we began to identify the risk factors for heart disease.
Beginning in 1961 with [what is now considered] a very important landmark paper in the Annals of Internal Medicine written by Dr. [William] Kannel, the "factors of risk" for heart disease were first identified. We now know those risk factors are high blood pressure, high blood cholesterol, smoking, diabetes, family history, and male gender. As a result, we have now taken that information, and we have taught it to our public extensively.
What's very interesting about those factors is that we now recognize that it's not just a single factor that leads to heart disease, but it's the constellation of factors. That probably is the overwhelming success story of the Framingham Heart Study. It's not just intervening in one singly, but it's intervening in the constellation of risk factors.
For example, one individual might have high blood pressure and might be a smoker, but their blood cholesterol may be normal and they [may] have no family history of heart disease. Well, that's an individual in which efforts should be taken to lower blood pressure and [who is a candidate] for smoking cessation. We know that the interaction of those two risk factors can certainly elevate your risk for heart disease.
In another individual, it may be a very strong family history of high blood cholesterol and then a known high blood cholesterol. In that individual, it's going to be very important to intervene with diet and probably cholesterol-lowering medication, and that individual's going to need to pay attention to their blood cholesterol all along.
Every medical student grows up knowing what the risk factors are for heart disease. Every physician ought to be able to rattle them off the tip of their tongue. Furthermore, we hope that members of our society, our population, our public, know those risk factors as well. Clearly they've heard about them through the press, TV, media, their doctors' offices. The question is, have they adopted them into their own lives? Have they really made changes in terms of their own lifestyle? That's very hard to gauge. We have indirect evidence that people are starting to act on their risk factors.
A Demographic Shift in Heart Disease
INTERVIEWER: To get back to treatment for a moment, has treatment of heart disease been successful? Are people living longer, healthier lives?
NABEL: We're doing far more procedures now on individuals in their 80s than we ever did, say, 10 or 15 years ago. [In other words], what we've observed is that there has been a shift in the age at which people suffer from heart disease or die from heart disease. After World War II, individuals were dying in their 50s and 60s. Enter the Framingham Heart Study and the identification of risk factors around 1970, and large national efforts to reduce risk factors since the 1970s, we now see that individuals are suffering from heart disease in their mid- to late 70s and their 80s and dying in their 80s.
[This 20- or 30-year shift is] relatively good news. But what we want to be sure of is that individuals understand that their risk for heart disease begins in their 20s and 30s and slowly builds over many years. It's not enough to wake up at age 50 and say, "Hey, I've got to pay attention to my risk for heart disease."
For some individuals, that could be too late, because the heart disease could already have started. It's really an insidious, chronic process that builds up over many decades. The message that we want to communicate is that individuals need to be thinking about their heart health in their 20s and 30s and start adapting healthy lifestyle habits at that point in their life that's going to carry them through to be very healthy, fit 60-, 70-, and 80-year-olds.
Heart disease is really a hidden epidemic. It's a silent disease. One can have signs or symptoms of heart disease that are very subtle, and they may go on for years and years before they're recognized. Interestingly, once [the symptoms are] recognized and an individual begins treatment for heart disease, there still may not be the same emotional attachment to the disease that one might have to another disease: say, cancer.
I believe it comes from the fact that as a society, we've come to accept the fact that, well, when you're old, you've got to die of something, and it might be a stroke or a heart attack, and that's just the way life is. But there are hidden, untoward consequences of that assumption, and those are that we really do fail to recognize serious, important heart disease in individuals when they're much younger.
The Epidemic of Obesity in Children
INTERVIEWER: Some of these unhealthy lifestyle habits have led to a weight problem in this country. How does obesity affect the heart?
NABEL: The other risk factor that in some ways has been sort of silent, I would say over the past decade or so, is overweight [and] obesity. We recognize that obesity/overweight is really an epidemic in this country, particularly in our children. It's estimated that there are 9 million children in the United States now who are overweight or obese. As health care providers, we're very concerned that the progress that we have made in riding the storm of heart disease over the past decade or so may be stopped by the advent of heart disease in our overweight and obese adolescents.
For example, we know that children who are overweight and obese will grow up to be overweight and obese adults. We know that children and adolescents who are overweight and obese are now starting to develop diabetes at rates that we never saw 10 years ago. We know that the sequel of diabetes is cardiovascular disease. We know that the most common cause of death from diabetes is cardiovascular disease. We are very concerned that over the next decade or two, we are going to see this current generation of overweight, obese children go on to have florid diabetes, diabetic complications, and manifestations of heart disease. That will be tragic.
We're very fearful that we will see heart disease in these children in their 40s, whereas if we could have prevented the overweight/obesity and diabetes, they may well have lived into their 70s and 80s before they developed heart disease. So it calls upon us in the health care profession to really begin to work to prevent obesity and overweight in children. In the National Heart, Lung, and Blood Institute [NHLBI], we now have a program called We Can, which is a public education program to really teach health care providers and parents how to help their children make healthy lifestyle choices; how to stay physically active; how to make heart-healthy food choices; how to reduce their sedentary time; and how to take responsibility for their own health.
Treatment of Heart Disease Has Outpaced Prevention
INTERVIEWER: What sorts of changes have occurred in the cardiovascular field over the past several decades?
NABEL: We have new, improved methods for diagnosing heart disease. We can detect heart disease much earlier than we could previously, and once the diagnosis of heart disease has been made, we have fantastic interventions. We have drug-eluding stents to keep blocked coronary arteries open. We have implantable defibrillators which will prevent individuals from incurring sudden death. In many ways, we have cured the prior two most common ways by which people died of heart disease: blocked arteries and sudden death. Individuals are now left with weakness of the heart muscle, which is manifested as heart failure, now often the most common form of heart disease leading to death and disability.
We know, for example, that heart failure is the most common cause for hospitalization for heart disease in this country. So can we make strides to improve the diagnosis and treatment of heart failure? Undoubtedly. There are many avenues of research that are proceeding now by which we can begin to repair the heart muscle much earlier on and prevent the end-stage scarring that occurs in the heart and produces heart failure.
That is all good news, but the other piece that we always have to keep in mind is the fact that our treatment of the acute events of heart disease -- sudden death, heart attack -- are events that have resulted from 20, 30, 40 years of a gradual buildup of heart disease. Our emphasis really must be on early prevention if we're going to stem the tide in a way that we all hope that we can.
Paying Attention to Risk Factors, for Men and Women
INTERVIEWER: To prevent this "gradual buildup" of heart disease, people have to know what to look for. What are some symptoms that might indicate a problem?
NABEL: Many symptoms of heart disease are insidious and have a very slow onset. They can be very subtle: something as difficult to put your finger on as a little bit of shortness of breath when you walk; a little bit of shortness of breath when you exercise. Then, all of a sudden, you're feeling a little more fatigued or a little more tired at the end of the day, or perhaps a little more tired when you're doing an activity that you previously could do without any difficulty. Those sort of subtle symptoms are difficult to detect and understand. Often, individuals who are in the prime of their life will attribute it to a busy, hectic lifestyle, a heavy workload, other stressors in their lives, and really not want to acknowledge it. Denial still is a major factor that prevents many of us from recognizing the symptoms of heart disease.
We're taught during our cardiology training that angina -- chest pain representing blockages in heart arteries -- will manifest itself as substernal, crushing chest pain, the elephant sitting on my chest that anyone could detect. Well, in some individuals that's the case, but in other individuals, it's far more subtle. It's a little bit of jaw pain; it's a little bit of shoulder pain; it's a little bit of back pain; it's a little bit of pain radiating down the arm; or it could be some pain that feels like stomach indigestion.
The important lesson that we've learned recently is that women in particular often experience symptoms of heart disease in a manner that's very different from men. Women's symptoms can often be far more subtle than men's. In the past, we've often referred to these symptoms that many men experience, [such as the crushing chest pain], as being typical symptoms, and therefore, the symptoms that women experience as being atypical. Well, it's time we get rid of this misnomer.
The symptoms that are characteristic of heart disease [cover] a broad spectrum, and all of them are important. The message that we need to communicate to women in particular is to pay attention to that shortness of breath, that little bit of fatigue, that aching or gnawing feeling that just isn't right, particularly if it occurs after exercise or an activity or a stressful event; pay attention to that and seek medical help.
INTERVIEWER: And people need to pay attention to risk factors as well...
NABEL: [Right.] We now recognize that there are five or six risk factors for heart disease: high blood pressure, high blood cholesterol, diabetes, smoking, family history, and we used to say male gender. Many of those are risk factors that you can do something about. The difficulty is, you don't feel the risk factors, so often you don't identify them in yourself until you seek help from your physician.
Let's take blood pressure, for example. You may have a blood pressure of 110/70, which is a normal blood pressure, or you may have a blood pressure of 160/95, which is an abnormal blood pressure—high blood pressure. You may feel no difference between those two blood pressures. Yet one blood pressure, the 160/95, is really a silent killer, because if it goes untreated for a long period of time, it will increase the likelihood that you'll develop a stroke or heart failure or other forms of heart disease.
Again, the message the individual needs to recognize is that one needs to seek regular, routine medical help to identify the risk factors. Once you've identified risk factors, lay out a plan for how to deal with those risk factors with your health care provider, and then work hard to adhere to that plan. In other words, if you have high blood pressure, say 160/95, and you've identified that, I'm going to work first on physical lifestyle intervention, engaging in regular physical activity or a diet that's low in sodium in order to try to lower that blood pressure. Make sure that you go back and have your blood pressure checked regularly so that you can see whether those lifestyle interventions are really having an effect.
If they're not having the effect that you need, make sure you see your physician. Lowering your blood pressure through medication may be required as the next step. It really takes a sense of personal responsibility in many ways for an individual to stay on top of the risk-factor profile.
Heart Disease Is Treatable, Not Curable
INTERVIEWER: Once treated for heart disease, can an individual ever be free of it?
NABEL: There are some common myths about heart disease. One of the myths is that once you do have heart disease, it can be treated, and you can be cured, and it goes away, and you don't have to worry about it again. Well, that clearly is a myth, because once you have heart disease, it really does stay with you for the rest of your life. Yes, there are many wonderful treatments and interventions that cardiologists have available to reduce your burden of illness, so to speak, or to prevent death. But it is still a disease that you have with you that you need to take care of.
There are many celebrities in our society who certainly do have heart disease and have received successful treatments: former President Bill Clinton, Larry King, Vice President Dick Cheney. All are examples of individuals who have heart disease, who have been successfully treated but now must continue those ongoing treatments to ensure their health.
The far easier road, for sure, is to prevent the heart disease from developing in the first place, identifying potential risk factors for heart disease early on. Do what you can to reduce those risks so you never get to the point where you need bypass surgery or an implantable defibrillator or have a heart attack and need placement of a drug-eluding stent in a crisis situation, or have damage to your heart such that you end up with heart failure for many years and need to take five or six different medications.
No one really wants to be in that position. It's much easier to start in your 20s and your 30s and your 40s paying attention to those risks. Know your blood pressure. Know your cholesterol. Know whether or not you're at risk for diabetes. If you smoke, quit. If you have a family history of heart disease, know what that risk is and discuss it with your physician. And, importantly, stay physically active. We know that the combination of physical activity plus a heart-healthy diet are two easy steps that you can take to really improve your heart health -- not only improve your own heart health, but improve the heart health of your family as well.
The Medical Community's Resistance to New Information
INTERVIEWER: It's not only personal responsibility, is it? The medical community needs to implement these findings into the care they provide, correct?
NABEL: It's interesting, but there tends to be a resistance to accepting new medical information even though it may be backed up by many, many well-conducted clinical studies. The Framingham Heart Study is an interesting example. Beginning in the early 1970s, we began to accrue information that indicated that high blood pressure, if untreated, would lead to stroke, heart failure, and death. Indeed, the National Heart, Lung, and Blood Institute acted on that information and initiated a number of clinical studies looking at the effects of treated versus untreated high blood pressure and the target blood pressure to which one should treat.
The Institute took all of that information and established the National High Blood Pressure Education Program [NHBPEP] in the mid-1970s. The purpose of that national education program was to develop guidelines, recommendations for the diagnosis and treatment of high blood pressure. Those have come out as our JNC [Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure] recommendations.
Now, interestingly, even though experts came together, considered the evidence, and came out with recommendations, overwhelmingly supporting the diagnosis and treatment of high blood pressure, and even providing a target blood pressure to treat to, there has been resistance in the medical community to adopt those guidelines and implement them in daily medical practice.
The reasons, I think, are complicated and difficult to understand, yet one of the important missions of our Institute is to continue to produce those guidelines for the treatment of high blood pressure on a regular basis and furthermore, begin to understand what the resistance is toward acceptance in the medical community, so that we can find ways to get that information out to practitioners and to the public and make sure that the guidelines will be accepted and implemented.
We learned first about high blood pressure. In many ways, it was an easy number to measure: a simple arm cuff. Cholesterol was a little more difficult, because cholesterol required the development of chemical assays in order to actually measure not just total cholesterol but the different cholesterol components in the blood: the low-density lipoprotein [LDL], or bad cholesterol; the high-density lipoprotein [HDL], or good cholesterol. Indeed, our Institute was instrumental in developing those assays, which then could be taken into a hospital laboratory and used on a day-to-day basis.
It wasn't until the mid-1980s, 1985 in fact, that the NHLBI developed the National Cholesterol Education Program [NCEP], an education program that paralleled in many ways the National High Blood Pressure Education Program. Again, we brought in experts in the cholesterol field. We had them conduct a series of clinical studies to look at the evidence for potential benefit for treating high blood cholesterol, and we had accrued considerable clinical data to suggest that, indeed, untreated high blood cholesterol leads to heart attack, stroke, and death. Treatment of high blood cholesterol reduces the risk for heart attack, stroke, and death.
Indeed, those expert panels began to formulate guidelines for the diagnosis and treatment of high blood cholesterol. The guidelines began in 1985, and when they were first released to the community, they met equal resistance in terms of acceptance, understanding, and implementation. Again, part of the research that we're doing here at the NHLBI is to begin to understand what is the resistance in the medical community to accepting these guidelines and implementing them.
The Economics of Critical Follow-up Care
INTERVIEWER: Why wouldn't a physician act in the best interest of the patient if the evidence is there?
NABEL: For me, it really is quite difficult to understand. Physicians must intuitively understand that treatment is good for their patient. But whether there's a conscious effort at the kind of rigorous follow-up that's required to get an individual at the target level where they need to be may be a component. In other words, an individual might come into my office with a blood pressure of 160/90, and we start with a low-sodium diet and physical activity; we institute some antihypertensive medication. They come back, and their blood pressure is 150/90. Well, that's not good enough. It's going to take much more effort, much more work, to get it down to the level where we want it, probably closer to 120/70 or so.
That might not be very exciting work to do for the physician, but it's critically important work for that patient. I think it brings into context the importance of health care providers, the health care community; that much of the effort or the work for lowering cardiac risk factors doesn't need to be performed by the primary care physician or by the internist or by the cardiologist, but certainly can be done by other health care providers in the office who have individuals come in for blood pressure or cholesterol checks, or who provide a blood pressure cuff to an individual to take home and ask them to keep daily recordings of their blood pressure and place a phone call once a week: what are your recordings; how is it going; are we on track or not?
Sometimes it's that meticulous, careful follow-up that's lacking. That, quite honestly, is not a billable activity by a physician or a health care clinic, but it is critically important in terms of long-term care of the individual. We would certainly hope that the health insurance community would recognize that careful, rigorous follow-up to help individuals achieve their target levels is important if we are to reduce health care costs long term, and that it makes economic sense to provide incentives for health care providers so that they help their patients get to the numbers where they need to be.
There may be other factors that are contributing as well that are just difficult to define. What we have learned, for example, in the treatment of heart attack is that if reimbursement to the hospital or to the physician group is based upon meeting various targets in treatment, post-heart attack, the success in reaching those target levels increases tremendously.
One hates to think that there needs to be economic incentives, but that may be the case. It may be time that we just wake up and face reality and put those economic incentives in place. Let's face it: our ultimate goal here is to improve people's lives, to improve their health care status, to help them get to the target levels where they need to be in order to have a heart-healthy life. These short-term economic incentives certainly may pay off in terms of avoiding the long-term consequences which can be quite costly to our society, not just in terms of health care bills, but also quality of life and longevity [and productivity] and other issues that are important to an individual.
Why Patients Don't Take Their Medication: They Can't Afford It, and They Feel Fine
INTERVIEWER: So follow-up in cardiac care may not be "exciting" for a physician, as you explained. But why wouldn't a patient take his or her medication if it were prescribed?
NABEL: Quite honestly, one of the most common reasons for poor compliance in taking high blood pressure medication is the cost of the medication. If an individual does not have health insurance and their blood pressure medication may cost them upwards of $100 a month, they may simply not have the money to pay for it. That individual may elect, instead of taking the blood pressure medication every day, [to] take it every other day, because that's perhaps all they can afford. The consequence of that is the physician then sees that although they're prescribing the medication, [the patient is] not achieving the goal. The physician can [become] frustrated and lose patience.
What the physician really needs to do is stop, step back, and take the time and really visit with the patient, understand what some of the factors may be. This really needs to be a partnership with the individual. Again, it's helpful to bring in the community of health care providers as well and really understand what the issues are that either lead to poor compliance or a lack of interest.
Another major factor for not taking a medication on a regular basis is the fact that if you don't feel high blood pressure, if you don't feel high blood cholesterol, you're not motivated to take that medication. You have no pain that you're trying to remove. It is a silent symptom, so to speak, and it really takes an extra degree of motivation on behalf of the individual. [To] take that pill religiously every morning or every evening for a symptom that they don't feel, it costs them money; it may have some subtle side effects that they don't like or enjoy, and [the individual must] be motivated enough to think, boy, I'm really doing this to prevent some disease that I might develop 20 or 30 years down the road. It really does take a very motivated individual to be thinking that far out in the future.
The Future of Cardiology: Predictive, Preemptive, Personalized
INTERVIEWER: How has cardiology changed since you entered the field, and what is its future?
NABEL: My generation of cardiologists grew up to be plumbers. We were taught that chest pain, heart attack resulted from a clear blockage in an artery, and our job as a heart doctor was to remove that blockage. We developed very good techniques for doing that. Balloon angioplasty followed by placement of stents, followed by placement of drug-eluding stents, have very nicely treated those blockages in arteries. Heart bypass surgery is another alternative for treating those blockages. But we now recognize that blockages in arteries are really a systemic disease that occurs over a long period of time due to chronic inflammation in the blood vessels.
So we know that atherosclerosis, the process of building up blockages in the arteries, is a systemic process; that is, the process occurs throughout the circulation, throughout the arterial tree -- in the abdominal aorta, in the heart arteries, in the neck arteries, in the leg arteries -- and that the complications of atherosclerosis, the very severe blockage, occurs at very focal sites, specific sites, in the circulation.
As plumbers, we can go in and treat that very specific blockage, that very focal site. But we have to be cognizant of the fact that the disease process is still going on throughout the remainder of the circulation. Certainly the next generation of cardiologists will be developing techniques and tools to really deal with the systemic, chronic, inflammatory nature of atherosclerosis.
At the NHLBI, we believe very strongly that in the future, medicine will be predictive, preemptive, and personalized. What do I mean by that? Medicine will be predictive in the sense that we will be able to predict for a given individual at a very early age what their risk will be for heart disease as well as other diseases.
Now, how will we have that information? We will develop that information through the use of genomics as it applies to heart disease. We are now able to take many of the large population studies that we have invested in over many decades, like the Framingham Heart Study. We can now take the database of information that has accrued over many years. That database in the past has been what we call phenotypic measures, phenotypes. Those are blood pressure level; cholesterol level; BMI, body mass index; the presence or absence of diabetes; the presence or absence of cigarette smoking.
We can take those pieces of information and now add to them the genetic profile of the individuals as well. We are ready to embark on a very new, exciting project with the Framingham Heart Study called Framingham Share. In Framingham Share, we will take the DNA of Framingham participants who have provided informed consent, and we will analyze their DNA for a whole number of what are called single nucleotide polymorphisms, or SNPs. These are markers of genetic variability, which when we combine those markers of genetic variability with their phenotypic data, we can begin to establish a profile of what their genetic risk will be for developing certain types of heart disease.
That's a database that we will then establish here at the National Institutes of Health [NIH]. We will make this database available to investigators who have approved use, who can then do more detailed analysis and come up with a very clear profile of what an individual's risk might be for developing high blood cholesterol, or the risk might be for developing high blood pressure over a series of years.
The preemptive portion is that we're developing new imaging techniques that will be able to detect blockages in arteries at a much earlier stage. We'll be able to detect weaknesses in a heart muscle at a [much] earlier stage that will allow us to step in and intervene much earlier to prevent further development or progression of the disease.
Finally, in terms of personalized medicine, the NHLBI is beginning a number of studies where we will look at an individual's personalized response to treatment. We know, for example, that some individuals respond very well to certain types of blood pressure-lowering medications. Other individuals respond very differently. We can take that information that we've [gathered] from the Framingham participants -- the genetic markers and the phenotypic markers -- and begin to understand how differences in genetic markers can determine how you're going to respond to a particular medication. That's the personalized component.
We will begin to gain this understanding [by analyzing] the Framingham population. Then we will check those results in other populations of individuals who have participated in various clinical trials. For example, in Jackson, Mississippi, we are in the midst of a Jackson Heart Study, which is a large population study of African Americans. Do the findings that we find in Framingham apply to the individuals in Jackson, Mississippi? We'll find that out.