® presentation, which is titled “Advances in the Management of Hypercholesterolemia.” I’m Howard Weintraub. I’m a cardiologist. I am a clinical professor of medicine at the NYU Grossman School of Medicine and I’m the clinical director of the NYU Center for the Prevention of Cardiovascular Disease. It is my pleasure to be joined by Dr Alan Brown, who is the director of the division of cardiology at the Advocate Lutheran General Hospital in Park Ridge, Illinois. We’ll be discussing hypercholesterolemia and its management in a variety of patient populations, including consideration of the use of the newer PCSK9 monoclonal antibodies.

Alan, what would you consider to be causes leading to hypercholesterolemia and resulting effects on peoples’ health, namely genetic and environmental?

I’m going to steal a line from an old friend of mine, Gregg Fonarow, who says that genetics load the gun and environment pulls the trigger. Most people with dyslipidemia have some underlying genetic predisposition. There are groups where it’s a very clear, single gene as in familial hypercholesterolemia. The majority of the population has more minor genetic abnormalities that lead to elevated cholesterol. As they gain weight or they eat a diet high in saturated fat or cholesterol, you start to see the numbers go up, often after adolescence. Both genetic and environmental factors contribute to dyslipidemia, and we know that leads to the potential for cardiovascular disease, whether it is cerebrovascular coronary disease or peripheral vascular disease.

Consequences of Hypercholesterolemia

Howard, I know you have spent a lot of your career dealing with multiple risks for cardiovascular disease—not just lipids but hypertension, cigarette smoking, and other things—as a former board member of the American Society for Preventive Cardiology. I’ve had the pleasure of serving with you on that. Do you want to talk about all the different risk factors that contribute to cardiovascular disease, beyond lipids, and why we need to have a multidisciplinary approach?

That’s a very good question, Alan. It’s fairly obvious that if all you do is focus on 1 risk factor and ignore the blood pressure, diabetes, smoking, obesity, inactivity, and the increasingly important issues of genetics, as you just pointed out, you’re going to have a woefully inadequate response. One of the things that separates us as the preventive cardiologists is that we have to keep our eyes open on the whole horizon and call attention to everything. Those efforts, in my experience, have led to very gratifying results in reducing the severity of atherosclerosis and made a real impact on the likelihood of stroke, MI [myocardial infarction], or severe peripheral vascular disease. You already brought up in our discussion before the meeting that the younger generation may potentially not have as good of a health outlook as their parents. This is related to obesity and the pursuing effects of insulin resistance, metabolic syndrome, and prediabetes, which some people are now talking about. We’re really getting in on this feature. You can’t underestimate the role of multifactor evaluation and really diligent attention. Making it well into your eighth and ninth decades of life without having had stents in your body, stitches on your sternum, or balloons being putting into your femoral artery has a certain degree of merit.

Cardiovascular Disease Risk Factors

There are certain issues that I know that you’ve discussed and that we all have to deal with certainly on a day-to-day basis. Those are namely the effects of things that are not in our control, such as age and gender. These are things that we now know have very significant impact. The coronavirus pandemic has shown us that ethnicity, demographics, and socioeconomic status can also have a very big impact on health. The ways people get health care and use health care also ultimately impact whether individuals end up being beneficiaries of this or suffering with it. Please let us know your thoughts.

Yes, I certainly agree. Obviously, age is the single biggest risk factor for developing cardiovascular disease. There’s not a lot we can do about it, even though many of us attempt to act younger than we are, much to the dismay of our spouses, in many cases.

What we know is that cardiovascular disease is still the No. 1 killer out of all causes of mortality in the United States. That’s true for both men and women. Years ago, we thought women had a lesser incidence of cardiovascular disease, but we know better than that now. They often have it 10 years later than men. The theory is that they possibly may have some protection from estrogen during their premenopausal period, but they clearly have an equal incidence of cardiovascular disease. It’s still the No. 1 cause of death—more than all the cancers combined.

We’ve spent the past decade educating ourselves and others about the importance of identifying cardiovascular disease in both men and women, and also about some of the gender differences. Women present with different types of symptoms and different risks for procedures. A lot has been done in that arena. As far as the ethnicities go, we know that particularly for hypercholesterolemia, certain ethnic groups have a higher incidence. French Canadians have a higher incidence of familial hypercholesterolemia [FH]. We see that in Lebanese patients and Dutch patients. In fact, FH was first described in South Africa in the Dutch Afrikaners. There are populations—especially those who tend to cluster together and have a founder effect because they live in similar communities—where we see higher incidences of hypercholesterolemia. We know that lower socioeconomic groups, partly because of ethnicity and partly because of status and lifestyle, tend to have a higher conglomeration of risk factors, including hypertension, obesity, and diabetes. Some of that is probably related to ethnicity, but in the lower socioeconomic groups—it’s unfortunate, but the least expensive food, for example, is often the food that’s highest in saturated fat. In many cases, there are what we call food deserts in those localities where they really can’t find a place to get fresh produce or other healthy food, but there’s a McDonald’s right down the street. It becomes less expensive to feed the family and more satisfying to eat a high-fat meal that suppresses your hunger. The amounts of sodium and fat all lead to health issues.

All these things work together. We have to be aware of all of them. When we talk about diversity and inclusion, we mostly think about ethnicity or language, but there are many dimensions of diversity, including socioeconomic group, gender, and age. As we move forward in health care, we’re going to have to consider all those things if we want to be good stewards of the health of our communities.

I agree with you. Actually, the 2018 ACC/AHA [[American College of Cardiology/American Heart Association] guidelines identify Southeast Asians as a group at considerable cardiovascular risk. We at NYU have seen a lot of patients from Central America, South America, and the islands with a particular virial inversion of mixed lipid abnormalities. Many of them have very elevated triglycerides. There is this ethnic predisposition toward certain dyslipidemias. Our cardiology fellows are constantly astounded when they see a small, thin, Indian woman who’s 35 years of age, nondiabetic, and a nonsmoker who comes in with a proximal LAD [left anterior descending coronary artery] infarction. They go, “Wait a minute. This isn’t supposed to happen.”

I’m glad you brought that up, Howard. You mean “South Asian,” rather than “Southeast Asian.”

We actually have a South Asian Cardiovascular Center at Advocate Lutheran General Hospital because we have such a high population of Indian and Pakistani individuals in the Chicago area. You’re absolutely right. They have 3 to 4 times the risk. There’s a lot of theory as to why that is. They tend to have insulin resistance, as well as high incidence of elevated LP(a) [lipoprotein (a)]. The National Lipid Association is about to publish a very comprehensive discussion of that. I’m sorry I left that out. I’m glad you brought that up. That’s very important. It’s important for all physicians to be aware of the high incidence of early heart disease in South Asian patients, so thank you for that.

It’s something that used to be an issue only in urban areas like New York or Chicago, but now as people spread out and there are communities growing in multiple parts of the country, doctors need to recognize where this is from and how it all works. As you pointed out, you have these issues in Chicago. We’ve been seeing them at Bellevue Hospital for years. Jamie Underberg, who I’m sure you know well and is part of our convention center, runs the lipid clinic at Bellevue. We also have a dedicated prevention fellow. He and the fellow are constantly amazed by some of the genetic lipid disorders that come in and those that are there in an ethnicity where there is significant cardiovascular risk. That used to be attributed only to long-standing type 1 diabetes, renal disease, and smoking. This is very important. It’s something that we’re going to need to pay more attention to, particularly with attention drawn to disparities between different socioeconomic groups and demographics. This is something our trainees need to know about, and our colleagues need to be very well educated about this as well.

That’s very well said. As you pointed out, the COVID-19 [coronavirus disease 2019] crisis has really emphasized the importance of understanding the effects of disease and health care systems on diverse populations. My suspicion is that all our health care systems are going to change forever based on those experiences. This pandemic really affected certain ethnic and socioeconomic groups with such vigor compared with others.

Socioeconomic Status and Hypercholesterolemia

 The next thing I’d like to mention, as you’ve brought this up, is this rising concern about worsened cardiovascular outcomes. It turns out, interestingly, that this has been directed toward younger groups. You have people—and oddly enough, women particularly—entering the cardiac care group at an age that is much lower than anticipated by the people who make models for budgets. You get people who are now having very costly cardiac ailments and even more costly cardiac interventions. As a consequence, stresses are placed on society, on the budget, and more important, on these individuals’ lives.

One of the problems with stroke is that it is frequently not a mortal event, but it can be something that changes someone’s quality of life forever. You can’t underestimate the role of genetics and then obesity in even moderate degrees, along with the genetic predisposition toward more glucose intolerance. Now, we’re finding an even newer player, which is steatosis or the condition of NASH—nonalcoholic steatohepatitis. This all becomes involved with glucose intolerance and diabetes, dyslipidemia, and cardiovascular disease. We’re paying the price as this tornado begins to roll even more, flattening a lot of the expectations in health care. People are becoming consumers of health care, but economically, we’re hoping they’d simply be paying premiums and not actually using many of these dollars. I’m sure you guys have had a problem with this in Chicago as well.

Cardiovascular Disease in Younger Populations

At this point, we’re going to look at guidelines. When doctors think about what they’re going to do, they have historically enjoyed or looked for guidelines. You and I could talk for hours about our affections and disaffections toward some of the guidelines and what each of them have done over the last several decades to either make people more enthusiastic or, in some cases, to disenfranchise. There were guidelines from the ACC [American College of Cardiology] and AHA [American Heart Association] in November 2018, which were followed about 10 months later by European guidelines. This is very important when it comes down to how decisions are made, because a lot of doctors find that this is their blueprint or their recipe for how they want to treat their patients. One of the things that’s important has been consent of shared decision-making. I’m sure when doctors started telling patients about their condition, a lot of the time it wasn’t, “So tell me what you want to do. Do you want to take a drug? Do you not want to take a drug?” Then the patient swears on several Bibles that they’re going to do the very best they can. Depending on the follow-up or absence thereof, people can get lost in the shuffle. Discussion with the patient is so important. I’d love to hear your take on this, because I’ve thought a lot about this myself in the way I treat my patients. How do you get your patients to consider what would be optimal based on your interpretation of guidelines? In addition, we all know that every medicine that’s ever been developed is said to be an adjunct to lifestyle modification, namely diet and exercise. How do you work these things out and what kind of success have you had?

Let me start with the lifestyle because that will be a shorter answer. First, many of my patients want to be natural. They often say, “Why do I have to go on medication? How come I can’t be natural?” I explain to them that 100 years ago, everybody was natural, and they lived until about 38 years old, on average. So natural is not all it’s cracked up to be. That’s No. 1. No. 2, we do have some data about the importance of lifestyle modification. We have a lot of data that show you can lower your LDL [low-density lipoprotein] approximately 10% but lower your risk of an event even more than that. That’s true even in patients who are being placed on statin, for example. David Blankenhorn showed that 25 years ago via angiograms in people who were on statin plus niacin vs placebo. The folks on medication had less progression of atherosclerosis on follow-up angiogram. That goes without saying. But when you look at the people who were on medication—those who did well and those who didn’t seem to get the benefit of the medicine—the only differentiator between the 2 groups was the percentage of saturated fat and the diet. When patients say to me, “I’m taking my statin and my numbers are good. Can I go eat pizza?” The answer is no. There is good evidence that you’re going to get the best outcomes when you combine lifestyle modification plus the medication, if the medication is appropriate for you.

As far as the shared decision-making, I’m interested in taking a second on that. They say the most important part of caring for patients is caring for the patient. That is, to really care about them and let them know you care about them. Probably the most important thing that anyone ever said to me in my career is to consider how you influence people. This is not about how you make friends or how you keep your spouse but about how you become influential. The way you influence others has absolutely nothing to do with what they think about you. It has everything to do with how they feel about themselves when they’re in your presence. The first part of the shared decision-making piece is for that patient to understand that you truly care about them and to believe that you have their best interest at heart, which means taking a few minutes to make them feel good about themselves when they’re in your presence. This is true whether we’re dealing with colleagues at a committee or a medical organization or whether we’re dealing with other people. I have found over the years that the biggest impact that leads to a really valuable shared decision-making discussion is to make sure the patient understands that you care about them as a person. After that, it is really important for them to feel as if they were part of the decision of what’s going to happen going forward. Our job is to arm them with the data, explain how much we care about them, give them what we think is reasonable for them, and see if they agree once they have the data in hand. That is really important. It’s important in everything we do. It enhances compliance with our treatment and also reduces conflicts with patients and colleagues.

Lifestyle Modifications to Manage Hypercholesterolemia

I couldn’t agree more with what you’ve said. I’m going to go 1 step further. Along with caring, it’s also listening. I’ve seen a lot of individuals in their 30s and early 40s who were summarily told by their primary care doctor, “Your LDL [low-density lipoprotein] is X, and you need a statin.” Many of these people, as you already pointed out, want to be “natural,” so they immediately run to the internet. They decide that the doctor is an agent of big pharma and trying to do all kinds of dastardly things to them, because when you google the word 

, glowing reports don’t immediately show up on your doorstep. I invariably listen to them. We talk at length about their diet. We talk about their expectations. I let them know specifically what I anticipate might happen. I let them know that in my approach of aggressively, thoroughly approaching risk factors, I don’t grade on a curve, but I also would like very much for them to have the best possible outcome. In doing that I am giving in to get my own way when I encourage them to follow an enlightened diet or nutritional pattern, to stop smoking, to lose weight, and to exercise. We set realistic goals, and I give them several months to do this. I give them enough time for them to figure out whether they can tolerate the diet, whether they feel put in some culinary hell by what I’m asking them to do, or whether they find that it’s a lifestyle that’s entirely livable. Then we reconvene in 4 months, which is enough time for them to get all this information together and also to be able to see a reasonable impact, if there is 1.

I agree with you. Getting 10% reductions at the end of the year is probably a very realistic number, not what patients believe they should be able to get. They hear about the fantastic stories of people like Dean Ornish and others. They don’t really know what Ornish’s diet and lifestyle are like. They’re not quite ready to give up booze, red meat, and oils, or to have to exercise and meditate, but this is what it is. I find, interestingly, that people come back. If I just tell them, “Here’s a pill,” these are the people who take the medicine for a month and don’t refill it again. These statistics are everywhere. This is something I agree with you about, and by listening, you show that you care and that ultimately, your concern is to improve their cardiovascular outcome. I also tell them, “I can do this with your help or without it. I’d love your cooperation with this, because it means that if you do need medicine, you’ll be on fewer medicines. That means we’ll be able to do this in a way that is more acceptable to you.” I tell them “But if you look at me and say, ‘My life is not going to be worth living unless I have a cheeseburger every week.’ ” I tell them, “Fine. Then understand that you’re going to need to get your LDL down a certain degree, whatever it is, and that we might need to use more medicine.” If I need to do more of the heavy lifting, I’m prepared to do it, but this is part of our agreement. I don’t want to say 

, but this is the agreement that I forge with patients. All these things involve listening and having the patient feel that you care. They must feel that they are not being summarily given a judgment that they don’t have a chance to discuss and don’t completely understand, that they feel might be somewhat arbitrary and is contrary to what they’d like. As you put it, they’d like to be natural. That’s completely correct.

Advances in the Management of Hypercholesterolemia

Consequences of Hypercholesterolemia

Cardiovascular Disease Risk Factors

Socioeconomic Status and Hypercholesterolemia

Cardiovascular Disease in Younger Populations

Lifestyle Modifications to Manage Hypercholesterolemia

Hypercholesterolemia: Shared Decision-Making