Dr. Joel Kahn on Lipoprotein A – A Hidden Key To Lowering Risk Of Heart Disease

Content By: Ari Whitten & Dr. Joel Kahn

In this episode, I am speaking with Joel Kahn, MD – one of the top integrative cardiologists in the world, founder of the Kahn Center For Cardiac Longevity, and author of numerous books, including his most recent book Lipoprotein (A), The Heart’s Quiet Killer. We will talk about the role of lipoprotein (a) in cardiovascular disease.

Table of Contents

In this podcast, Dr. Kahn and I discuss:

  • The most prominent cause of coronary heart disease
  • The best nutrients for lowering lipoprotein(a)
  • How much lipoprotein is considered normal, and should you get tested?
  • Why most doctors ignore lipoprotein(a)

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Ari: Hey, there. Welcome back to the Energy Blueprint Podcast. I’m your host Ari Whitten and with me now is my friend Dr. Joel Kahn who is a professor of clinical medicine at Wayne State University. He founded The Kahn Center for Cardiac Longevity. He’s the author of The Plant-Based SolutionDead Execs Don’t Get BonusesVegan Sex, and the new book, Lipoprotein(a), The Heart’s Quiet Killer. He’s also widely regarded as one of the top integrative cardiologists in the world. Welcome back, I believe for the third time, Dr. Kahn.

Dr. Kahn: I think so. It’s such a high energy experience anytime I get to be around you and I learn so much on your podcast, so excited to come back.

Ari: Oh, thank you so much. The feeling is very mutual, I always learn a lot whenever we get a chance to talk. Speaking of which, I was just telling you before we started recording that I didn’t know much about this topic of Lipoprotein(a) prior to this. I did some prepping for this podcast and realized how much I didn’t know on it. I’m very excited.

I think that’s probably true of most people that they don’t know much about this topic and yet, it’s very, very important. Also, I want to mention, you said something very funny before we started recording. You said, “I don’t know exactly how to connect Lipoprotein(a) to the topic of energy specifically, other than if somebody’s dead, they don’t have a lot of energy,” [laughs] which I think is a good connection.

Dr. Kahn: You nailed it, but we do want to keep your audience thinking, optimal energy and I suggest life is a good path and we’re going to talk about what we’ve learned to help you live a long and healthy life. I agree with you, most people and most physicians and health care providers could listen to this and learn a lot. I’m quite confident.

Ari: Yes, I would say there’s probably, even just extending that line of logic of that connection of heart disease, dead, low energy. I mean, there’s some nuance, there’s a gray area which is, hey, on the road to dying from heart disease and atherosclerosis, you’re going to have impaired cardiac function, you’re going to have impaired cardiovascular function and that in turn would, I think, reasonably be expected to lower one’s energy levels in the process of heart disease.

Dr. Kahn: Completely, it’s a rabbit trail we’re going down but very few clinicians talk about cardiac energetics. There actually is a big body of literature about ATP formation and problems and developing that, and natural ways to augment it. Cardiologist, sort of a figurehead now with no disrespect, Stephen Sinatra came up with a concept of metabolic cardiology, how to use ribose, CoQ10, L-carnitine to maximize your mitochondria.

I think it was 20 years ago, that was a little early in the game, but it’s when I started adopting some of these energy-boosting strategies in people with heart failure or hypertension. Actually, they’re extremely effective and often allow people to avoid medication. Right, energy for the heart. I don’t know, we have a heart and brain, the two densest mitochondrial organs [unintelligible].

Ari: Yes, indeed. I think the brain is the winner and then the heart is number two, and then maybe [unintelligible] after that.

Dr. Kahn: Yes, good.

The most common causes of atherosclerosis

Ari: I want to start with atherosclerosis. I think that might be a good place to start unless– I was either thinking of starting with that or Lipoprotein(a) first and then atherosclerosis. I want to delve into the sequence of events that lead to atherosclerosis and then talk about how Lipoprotein(a) fits into that. Do you think that way of talking about things is good?

Dr. Kahn: Right, fine.

Ari: Okay. Atherosclerosis, I would say my interpretation, you tell me if you agree, is there’s a lot of people operating in overly simplistic paradigms of how atherosclerosis takes place. It’s either cholesterol. You eat cholesterol, boom, you die from cholesterol, or you have too high of cholesterol levels in the blood, boom, you’re dead.

There’s then the low carb movement, who’s kind of saying, “No, it’s not animal fat. It’s not dietary cholesterol. It’s not saturated fat that has nothing to do with it. All of that stuff’s perfectly heart-healthy. It’s really sugar and or grains, and sugar damages blood vessels that leads to atherosclerosis or it’s inflammation. Some variations of those kinds of arguments. Can you take listeners through what the actual science says? What is the sequence of events look like that lead to atherosclerosis?

Dr. Kahn: Sure. Here in San Diego and much of this work is UCSD, a current professor and a professor that passed on, Dan Steinberg lived about 95, passed away a couple of years ago. Anybody who wants to read the research, the basic science research of Daniel Steinberg, MD. There have been two theories before we go to risk factors and the argument you mentioned. There was something called the response-to-injury theory about atherosclerosis.

Very succinctly, some, everybody hopefully knows that there are 50,000 miles of arteries in the body. When we’re talking atherosclerosis, we’re talking arteries. You can argue and ask questions. Well, there’s 50,000 miles of veins, how come they do not get involved? Generally, they do not. There are a few cases of such extreme elevated cholesterol on a genetic basis that you can see atherosclerosis in veins, which is very uncommon. 50,000 miles of arteries, they are all aligned by a single layer called the endothelium.

One of the molecules made by the endothelium was responsible for the Nobel Prize in Medicine in 1998, that’s nitric oxide. You want to have healthy arteries, normal blood pressure, good strong sexual response, you want endothelium pumping out nitric oxide. The response-to-injury theory probably about 20 years old now, if something damages the endothelium, and that barrier, that wallpaper, that protective cover that separates the red blood cells and all that’s carried from immediately under the endothelium, it’s called the subintimal space.

That as soon as that’s injured, it allows access. It may be an LDL particle or the apoB lipoprotein that helps LDL particles flow through the blood. It could even be potentially an infectious agent because there has been decades of research on whether there is a direct correlation between some sorts of infection, but it’s the injury to the endothelium that triggers it all.

What injures your endothelium? Smoking can injure your endothelium, high saturated fat diets science says can injure your endothelium, a spike in blood pressure, elevated blood sugar, a lot of these are, of course, classic risk factors we’ve known for decades. Elevated homocysteine could injure your endothelium. Probably bacterial and viral particles.

Actually COVID-19 right now is more and more being considered potentially a vascular disease of endothelial damage due to the virus and the hypercoagulable clotting that follows it. This is a fascinating new aspect of medicine that’s very scary. It’s all about endothelium, and even COVID-19 is moving in that direction. All this data we’ve heard about people in ventilators, perhaps even having a higher mortality, and now the attention’s going to blood thinning and all. I don’t want to go down too far.

The competing theory of the development of atherosclerosis is called response-to-retention, RTR. That doesn’t ignore the issue that there can be injury to the endothelium for all the factors I mentioned, and many more, oxidized LDL. We learned in med school five things. Do your mom, dad, brother or sister have early heart disease like a stroke or a heart attack or bypass? Do you have a diagnosis of high blood pressure, diabetes, high cholesterol, and do you smoke? Five big Framingham risk factors.

In 2020, you go to your doctor, if you ask, “Hey, can you estimate for me my risk of a heart attack in the next 10 years?” They’re probably plugging in the same five risk factors into a Framingham risk or American Heart Association risk. There are a few that now incorporate high-sensitivity C-reactive protein. There’s even one that incorporates your heart calcium score. We haven’t really progressed is the point I’m making.

In reality, there’s at least a couple dozen factors that may injure your endothelium that aren’t part of the Framingham database, but science is very strong, and you can assay and measure essentially all of these. The newest one you can measure is called oxidized phospholipids. It’s now a blood test you can measure. Response-to-retention says there may be injury, but unless that cholesterol particle gets trapped in this subintimal space, if it can go in and go out, you’re not going to get a plaque.

Hopefully, you’ll heal that injury. It can be called an erosion or a little– That’s the best word. That’s what [unintelligible]. It’s the retention in that, particularly Apolipoprotein B. The Apolipoprotein that carries a lot of cholesterol, some triglyceride like material through the blood can get trapped right under those endothelial cells, macrophages, we view them as foreign. They can get oxidized there, they can get engulfed. You get foam cells, you get a mediator cytokines, you get all kinds of white cells coming in, you get inflammation, and all of a sudden you’ve got–

Ari: [crosstalk] the foam cells are these macrophages, these white blood cells are going in, they’re trying to eat up and consume the gunk that’s there and then they themselves die full of gunk and then they look like foam cells.

Dr. Kahn: You got lysozymes exploding and enzymes, but the point is it’s the retention. You’ve got particles and the leading particle- and we’ll talk where lipoprotein(a) fits in this, is apoB gets trapped right under the endothelium, big-time response going on, and you have a subintimal plaque that if that continues and the inflammatory response is strong and the driving factors of blood pressure, cholesterol, and all the other things remain, you will start to grow atheroma. That is felt to be right now where it’s at.

Then when we talked about why clinical risk factors, lab evaluation, you should know your blood pressure, you should know your standard lipid profile, you should probably consider, particularly if you’re overweight, metabolic syndrome, big waistline, you should probably ask for an advanced lipid profile, which is going to give you your LDL particle number which has been shown to be more accurate than just LDL if you’re dealing with metabolic syndrome, pre-diabetes, diabetes.

I, of course, want you to get your lipoprotein(a) checked. We’ll talk about why. You should know inflammation, at least get your high-sensitivity C-reactive protein. That’s going to get them in a shortlist, and hopefully, it’ll continue to grow. We need to identify more and more precipitating causes or aggravating causes because we’re still dealing in 2020 with this being the single biggest cause of death in men and women. We’ve made inroads, but we certainly have not made many in the prevention of atherosclerosis.

Ari: What you said there, that this is the single biggest killer is maybe worth mentioning, especially in light of the context we’re in now where everybody’s worried about dying of COVID-19. It’s worth mentioning that I think it’s something like 650,000 people a year in the United States alone die from cardiovascular disease, is that number accurate?

Dr. Kahn: That’s right, coronary heart disease, the consequence of clogged arteries, which could be heart attack, stroke, that entire spectrum. About a third of them, I think I got that right, a third of them are recurrent cases. We’ve already identified the persons being a heart patient post bypass, post-stent, post-stroke, and we’re not able to prevent their premature death. The rest are a first time up. That number, it’s been number one in the United States for men and women for 102 years since 1918. It’s been leading the charge.

Yes, we’ve made tremendous progress but we have by no means tamed the beast. There was a spoof on social media this past week that the government has locked down in quarantine all fast-food restaurants and such. It almost looked like saying, [unintelligible 00:13:19] in the onion. It wasn’t the onion, very tongue in cheek. We can only pray that’s just one component of it.

I just want to go back. The keto and the Paleo, and we have this argument. Is it primarily insulin resistance? Is it primarily sugar in the diet? Is it primarily saturated fat from animal sources in the diet. Each and every one of those is half an hour or an hour, so we won’t go down there unless you want to on any one of those topics.

The most common nutritional causes of atherosclerosis

Ari: I want to get your quick take even without delving into all the specifics. If you were to quantify, let’s say, on a scale of 1 to 10, the validity of the sugar causes atherosclerosis hypothesis or the validity of the animal foods, saturated fat, dietary cholesterol causes atherosclerosis. How would you quantify each of those in terms of their contributions to the actual problem of atherosclerosis on a scale of 1 to 10?

Dr. Kahn: If you take the whole spectrum of scientific foundation for those, those two theories, saturated fat diet versus added sugar diet have been raging as a debate since about 1970 when Ancel Keys and John Yudkin, Minneapolis versus London started fighting over it in different publications in different books of which Ancel Keys had many multiples. The research behind him was a giant of epidemiology, but nonetheless, this debate has been raging.

When you step back within the last three weeks, or what many people feel the peak of scientific independent unbiased quality research is done by somebody called that Cochrane Database or the Cochrane Library. When they put out a research project, you can have more trust than any random meta-analysis in any medical journal that the weaker studies have been exited, the strong studies is using something called the GRADE criteria, have been included.

They just published three weeks ago that reducing saturated fat in the diet will on average lower your risk of dying of heart disease or having a heart attack or being admitted to hospital by 21%. If you lower your saturated fat in the diet more, you will lower your risk of developing these very frequent and adverse events even more. It’s linear. The lower you go, the more benefit you see. That should have resolved this conversation after 70 years of research on saturated fat and the diet, but three weeks later in a journal called Journal American College of Cardiology, is a new meta-analysis. [crosstalk] Saturated fat–

Ari: [crosstalk] I was going to say that I do see the one that you’re referring to just now, but I saw this neuro one [unintelligible] saturated fat is innocent.

Dr. Kahn: With the neuro one, it’s interesting. Yes, it is innocent. Enjoy your meat, your eggs, or cheese. This keeps cycling over and over. You never know if this is meaningful, but 8 of the 12 authors had to disclose at the end of the study that they take beef and dairy funding for their research, 8 of the 12.

One of the additional ones is well known to have a connection but perhaps not directly funded because I think he would have declared it. In balancing quality, where do you decide? It’s such an amazing look at the media. Let me tell you, the Cochrane Database, the result got no media [unintelligible]. The enjoy your meat cheese and egg article got headlines all over the place that it doesn’t matter–

Ari: What’s the saying? Everybody loves good news?

Dr. Kahn: Yes, to have their bad habits reassured. In the Western societies, in the United States, we have tremendously too much added sugar. Everybody in the keto paleo group hates nutritional epidemiology except when it works in their favor. There are meta-analyses and nutritional studies that say sugar is correlated with coronary heart disease. More sugar or sugar-sweetened beverages, more heart disease. We like those studies, I guess, when they come out that way. They’re not randomized, and they’re not basic biochemistry.

It’s really unclear how sugar could cause atherosclerosis. Is it because you’re probably going to weigh a little more, or have a little more inflammation, or change the pattern of your lipids to a more pro-inflammatory, what’s called type B pattern? Maybe. There is no sugar in the plaque of arteries as opposed to there is apoB which is the carrier of cholesterol where it goes all through [unintelligible].

Ari: What about that initial endothelial injury? Is it plausible that elevated sugar levels in the bloodstream, the sugar itself could cause some physical damage to the endothelium?

Dr. Kahn: Whether it can do it acutely, I don’t think that’s known. In fact, there are studies have a glass of orange juice rich in sugar and it doesn’t affect your endothelial function. Have a glass of cream, it will within an hour harm your endothelial function. I don’t think sugar has a direct toxic effect. There is this process called glycation. These actually are interesting topics.

If you eat a lot of processed food and let’s just say high in sugar, of course, your blood sugar may stay high from that combination. You have your sausage McMuffin with your doughnut with your flavored coffee or coffee with whipped cream on it, your sugar goes up. When your sugar stays high, your blood sugar on average, you can measure by the hemoglobin A1C if you’re wearing a continuous glucose monitor, it’s easier to measure. There is a process called glycation. You can literally sugarcoat. Just think of a sugar-coated donut.

You can sugarcoat proteins, fats, and carbohydrates. There is something called glyco-LDL. You can glycate your LDL, it makes it more damaging and more injurious. That may be a pathway. You can sugarcoat your blood vessels and the endothelial coating called the glyco. There actually is a coating on the endothelium called the glycocalyx.

Without going too deep, it is certainly true that if your long term habit is a diet rich in added sugars, which is the American way– We’re used to having a little sugar and now we have 100 plus pounds a year, I think it’s 140 pounds a year. You are setting yourself up for a variety of chronic diseases, bad habits. I love saturated fat but I have no sugar in my diet is in my mind not a wise pattern for brain health, gut health and cardiovascular health and probably some cancers. Things metastasize more in a high saturated fat environment too. We’re talking cheese, beef, pepperoni pizzas, croissants, lard, butter. These are where the rich sources of saturated fat exist.

Ari: I remember, it must have been maybe 2016-ish, 2017, I remember seeing David Katz, who I think is a friend of yours, somebody I recently had on the podcast. I remember an article of his talking about a meta-analysis that had just come out that was quantifying the degree of contribution of saturated fat and sugar to heart disease.

What it concluded, and this was widely misrepresented by a lot of people, what it concluded was that saturated fat and sugar were relatively equal in terms of the harms done and the increased risk of cardiovascular disease. Am I remembering that accurately? You probably know what I’m referring to.

Dr. Kahn: I actually haven’t. It’s not clicking. I don’t want to step on David’s toes who is obviously very bright and wonderful with the literature. I still would say, I’m a big fan, always going to Valter Longo, University of Southern California, and the structure he has. He analyzes science questions, nutrition questions, something called the five pillars. What does the biochemistry say? What are the randomized studies say? What does the epidemiology say? What is centenarian studies say?

If you look at elderly people that are enjoying great health, the Blue Zones concept, what are they eating? Finally, a big picture complex system. Anyway, there’s much more foundation to nail a high saturated fat diet into the wall as a major contributor to atherosclerotic cardiovascular disease, then sugar, but they both need to be nailed. In reality, that’s just the Western diet, it’s too much of salt, oil, sugar, refined flours. Pretty hard to sort it out because anybody who’s eating a lot of added sugar is almost certainly eating it in association with all the other foods, so hard to parse it out.

Just connecting the energy for a minute. There’s these cool little acute feeding studies. Acute feeding study, I think it was 51 healthy women around the age of 50. 930 calorie breakfast because that is the average number of calories in a McDonald’s breakfast meal, that a person carries out 930 calories. One was laden with saturated fat and one was laden with polyunsaturated fat to bring I think about 40% of the calories in the meal were either from saturated fat or polyunsaturated fat vegetable oil.

They did it on cognitive function and executive function and memory, a huge deterioration within an hour or two by eating the typical meal that a person’s buying at a drive-in or gas station, family gathering with yellow bags and white bags all over the place. Bad stuff, it got to poison mitochondria, although I’m not sure that has specifically been studied.

Ari: I did find, while you were talking there, this article I was referring to by David Katz. It’s called Sugar and Saturated Fat: Feeding the Parasites of Science. I was a year late. It was from 2015. Time flies, but I’ll read you the– It was a meta-analysis by Dr. Dariush Mozaffarian.

Dr. Kahn: Oh, sure.

Ari: There’s one key line where Dr. David Katz sums up what was found. He said, “Among the clear answers was this. When net saturated fat calories were replaced with sugar, things got no better, but they got no worse either. In other words, the net effect of saturated fat calories on health was just about equivalent to the net effect of commensurate sugar calories.” It’s saying, in other words, sugar and saturated fat seem to be, based on this meta-analysis, roughly equally harmful in terms of cardiovascular disease outcomes.

Dr. Kahn: That is what you’re bringing up is a consistent finding. You can take a big database like Harvard School of Public Health, you think of Walter Willett, Frank Hu, some of these giants of nutrition epidemiology. They’ve got 130,000 doctors and nurses, followed for 30 years, answering questionnaires every four years, 57 pages of incredible detail about their food and their lifestyle. You can model, they’ve created a model. What if we take away 3% of the calories of saturated fat and substitute it at 4%.

When you run those models and you plug in refined sugar, you find it of neutral health benefit or adverse. You plug in whole grains, you’ll see cardiovascular risk projections go down. You plug in polyunsaturated fats, you’ll see cardiovascular risk reduction drop a lot. You put in monounsaturated fats, drops. You put in extra virgin olive oil in place of lard and butter, they just published that eight weeks ago, drops a lot, so you can play those games.

There’s no doubt if you said, “I’m going to stop eating butter and I’m going to start eating Hershey butters,” or some equivalent like that. It’s equally true to talk about junky vegan diets versus whole food plant-strong diets, they’ve done that differentiation. Quality of the food, and what’s substituting for it, you might choose. If you read the Cochrane databases that I’m going to cut back on the saturated fat in my diet, think long and hard of what you’re putting on your plate and it should be all the foods you and I enjoy, brightly colored, whole food, plant food, garden-fresh choices, then health improves.

Ari: This might be taking us further down the rabbit hole here, but is it possible that as far as saturated fat consumption and the link with cardiovascular disease, is it possible that there’s a segment of the population, let’s say it’s, I don’t know, 25% or something like that, one in four people who are especially prone to having big elevations in LDL cholesterol in response to going on a low-carb high fat diet. That portion of the population is skewing the overall data to say, yes, there’s an increased risk, but really the increased risk is for this specific segment of people that has that kind of response.

Dr. Kahn: Yes, there are responses to what you just said that you can relate to, and it is about the right number. You can send your own blood off, and as far as I identify, there’s a lab called Boston Heart Lab that a lot of cardiology and metabolic lipid people use. It’s just your tubes go to a specialty lab. They do an analysis of your blood sterols. They come back with a report that says you have a cholesterol profile that indicates you’re a hyper producer of cholesterol or you have a cluster profile that suggests you’re a hyper absorber.

It’s about 25% to 30% of people. You put fats in the gut, you will absorb more than average. There’s a little receptor called the Niemann receptor and it’s under genetic control like so much of what we have. That was what concerns me when people say, “I’m going to go do a high animal fat keto diet,” and not check labs because it’s 25% to 30% of people, your cholesterol might go 200 to 600. I’ve seen that many times, so have a lot of people go on four to six weeks because you’re a hyper absorber, and you just started dumping a lot more.

Ari: I’ve seen people who have just integrated the habit of Bulletproof Coffee, and not to throw Dave Asprey under the bus, but something similar to that. They just start adding a bunch of butter to their diet or go low-carb keto, start adding a bunch of fat, they think that is all good, helps them burn fat, so they start piling on the fat. Then a month or two later, they check their blood labs, and their cholesterol, their LDL is just off the charts.

Dr. Kahn: They are hyper absorbers. We have to send the blood off, there’s no other way to know that. People with apoE4, if you have a family history of heart disease or early Alzheimer’s dementia, some people go get a blood test. It’s an Apolipoprotein, we don’t hear a lot about Apolipoprotein E2, E3, E4. If you inherit one apoE4 from one parent, or if you inherit two of them from both parents, your risk of Alzheimer’s can be 10, 12 times higher at a younger age. A high saturated fat diet, in that case, is felt to be a poor choice.

You do not handle high-fat diets in terms of your lipids and ultimately, perhaps your brain function, but you won’t know that without advanced testing. apoE4, the one you get it from both your parents is maybe 1% or 2% of the public. The apoE4 is maybe 10% to 15%. I haven’t looked at statistics recently.

It’s minor, but that would be a bad idea. Actually, a high saturated fat diet will acutely raise your lipoprotein(a) just to bring it back. If you know you have a high lipoprotein(a), which we’ll get to whenever you want, you might choose not to keep provoking it with a acute rise that you get after palmitic or stearic acid.

Ari: Got it, [crosstalk]–

Dr. Kahn: There’s so many acids that we call the long-chain fatty acids, most concerning for atherosclerosis.

Ari: I want to move on to lipoprotein(a) in a second. I just want to wrap up this whole atherosclerosis conversation and again come back to this if you could rate– having said everything you just said, can you rate the saturated fat, the role of saturated fat, or the role of sugar from a scale of 1 to 10, how much do you think each of those two factors contributes to the big picture of the whole atherosclerosis burden?

Dr. Kahn: 80%, 20% is where I’d put it. The excess–

Ari: Saturated fat 80%, so essentially, you think it’s a very big contributor?

Dr. Kahn: If everybody went whole food, plant-based, and drunk Mountain Dew and Coca Cola, I think we’d see a big drop in heart disease, but we wouldn’t completely reach the bottom until we get green tea and sparkling water. [chuckles]

Ari: So that’s not misinterpreted, you’re not advocating Mountain Dew and Coca-Cola. You’re just saying in a hypothetical scenario where we still had a high sugar load, but we eliminated a lot of the dietary fat and saturated fat, in particular, you think just doing that even with the high sugar intake would drop heart disease dramatically?

Dr. Kahn: I would. It’s also, calorie density, fats have nine calories whereas sugars have four per unit. You will make a bigger impact on nutrition for calorie-rich meals and the driving concern about obesity and weight gain by reducing the foods we mentioned over and over that are high in saturated fat.

Ari: This is also not to say that you disagree that added sugars, refined sugars of the diet are a big contributor to many other diseases, but you’re speaking specifically in the context of cardiovascular disease, you don’t think it’s necessarily one of the biggest drivers.

Dr. Kahn: Well, yes, 20% it’s a big piece. If you’re giving me two options, 80, 20, I still think the 70 are a history of the database that suggests saturated fat and cardiovascular disease is a real issue for the public is so strong and the sugar is clearly real, but it’s a weaker signal.

The link between lipoprotein(a) and atherosclerosis

Ari: Where does lipoprotein(a) fit into this? We have this big picture of atherosclerosis, all these different factors, smoking, dietary factors, being sedentary, being overweight, chronic inflammation, all of those things feeding into endothelial injury, which drives atherosclerosis, how does lipoprotein(a) feed into this?

Dr. Kahn: A great segue from everything we talked about. You come to my clinic and you say, “I’m 48 years old. I just don’t want to be a statistic. Run those fancy labs, do some vascular imaging, look at my endothelium, all this can be done and tell me how I’m doing.” We go through the numbers and we put together a program of fitness and sleep and stress management and nutrition and targeted supplements and all the numbers come back.

The best estimates are and this has mainly been studied maybe in people after a heart attack, we’ve reduced the risk for a event or a second event.

50%, 60% would be an enormous number, but 50%, 60%. There is a big hunk left, which is why you hear all the time, “I can’t believe Bob died. He was fit and eating well and all. He’d been to the doctor,” or we can substitute Sally or Shelly or whatever name we want. It’s a very gender equal opportunity to develop heart disease, have a heart attack, and die.

There’s something called a residual risk that after we’ve had a statin and an aspirin and a diet improvement, there still is a big piece that we cannot tame to this point. Of that piece, and there’s many, many, many peer-reviewed research studies on residual risk after optimal medical therapy and lifestyle training.

Lipoprotein(a) is the biggest untargeted, unmeasured, untreated factor in why there still is a big piece of the pie that we’ve not addressed in the cardiology community as of 2020. It needs to be elevated at high up and it needs to be identified and we can tell what it is and how it works and what the future looks like, but it’s as important as when we first learned about LDL cholesterol in the 1950s. It’s just not yet prime time.

What is lipoprotein(a)?

Ari: I want to get clarity and maybe quantify some things here. Tell me if your numbers differ from mine. It is my understanding that if we look at the big picture of cardiovascular disease as a whole, I’m excluding various genetic cardiovascular diseases, but coronary artery disease specifically. That almost all of that, maybe 80% of it is nutrition and lifestyle factors that drive this disease process.

You’re saying even if everybody had optimal nutrition and lifestyle, there is still some segment of the population and from what it sounds like, maybe one in five people who have this genetic issue of lipoprotein(a) being really elevated and that lipoprotein(a) by itself, even in the presence of optimized nutrition and lifestyle factors can drive coronary artery disease in some small segment of people. Is that accurate to phrase it that way or how would you reframe it?

Dr. Kahn: There is a famous say and you’re right on, “Your genes load the gun, but your lifestyle pulls the trigger.” The worst thing you can do is be high genetic risk and have a heart unfriendly lifestyle. You’re kind of stacking the odds that you may become a victim and potentially early in life, but even with a really great lifestyle, genetics matter.

The scientific studies range 20% to 30% of all incidents of cardiovascular disease can be attributed mainly to genetic factors and a big hank are the by 70%, 80% are lifestyle. Do you smoke? Are you overweight? Is waistline excessive? Do you sleep? Do you have a fitness protocol, and what’s your nutrition like?

You’re absolutely right, there are studies that suggest if you control what’s controllable, it’s about an 80% drop in your risk of having a heart attack. Huge, let’s talk about that. It’s huge, it’s wonderful. We need to institute programs of– it’s called primordial prevention. Never become a heart patient, always be a healthy person by activating this early in life. Maybe if it’s okay with you, Ari, let me just unpack in about three minutes what lipoprotein(a) is?

Ari: Sure.

Dr. Kahn: Everybody has heard of LDL cholesterol. Well, you’ve got a ball-like– it looks like a baseball. It’s packed inside with cholesterol and ACL triglyceride esters, but the precursor to triglyceride, but that’s fat and fat doesn’t dissolve in the blood. We have to have a mechanism to move these fats around the body to go to the liver and to take them out of the tissues and use them in the brain, although, whether they can cross the blood-brain barrier is another issue.

We wrap this ball of cholesterol and triglycerides in a coding. Actually, one part of the coding is called phospholipids. That’s not that important, but it’s like people say the stitching of a baseball, the apolipoprotein is a protein on the outside and protein is water-soluble and it covers the stitching on a baseball, this ball of cholesterol and triglycerides to allow it to be transported through the blood and be dissolvable.

The lipoprotein that carries the most LDL is called apolipoprotein B. A study after study has shown a really good way to measure your cholesterol is to ask your doctor to measure your level of apolipoprotein B. LDL has apolipoprotein B that correlates with the risk of developing heart disease. VLDL, ILDL some of these other less discussed particles all have an apolipoprotein B.

Boom, 1963, a researcher in Scandinavia studying blood and lipids identifies a particle, not previously identified and it became known as apolipoprotein A. It’s an LDL cholesterol molecule identical. It’s the ball, it’s the phospholipids, it’s the stitching that’s apoB in it, but then there’s two sulfurs. It’s called a disulfide bridge, and there’s this really weird spiky piece called apolipoprotein A.

To get what we call lipoprotein(a), which is a blood test to measure your level, you’ve got an LDL, you got two little sulfurs, and you’ve got a weird tail that’s completely under genetic control. It’s the worst possible combination because you’ve got the LDL which well, carrying cholesterol with the apoB, which if it gets retained under the endothelium can incite a plaque, the response-to-retention therapy. I’ll talk about the two sulfides in a minute.

This long tail is under genetic control. It can be very long or not very long, they’re called Kringles. If anybody is of Scandinavian origin, there’s a Scandinavian pastry called a Kringle. It’s a little like a pretzel. The shape of this tail looks a little bit like that. Somebody was hungry one day and named it Kringle’s very common term in protein, biochemistry, or chemistry.

Finally, what’s on that tail causes widespread inflammation. Now we’ve got a particle that has the cholesterol in it, lipoprotein(a). A particle that drives inflammation, this big tail under genetic control. It turns out the last part is these two sulfide bonds in the tail, they mimic a protein we have in the blood called plasminogen.

If you cut yourself, clot, clot, clot to stop the bleeding and there’s a balance between we want the clot to stop bleeding, we don’t want too much clot, plasminogen is on the side of chewing up clots, so we keep it under control and we don’t get excessive clotting. Turns out, [clears throat] there’s tremendous similarity between plasminogen and lipoprotein(a) in their structure on this tail. Lipoprotein(a) also promotes clotting. [coughs] It promotes plaque, it promotes inflammation, and it promotes clotting by competing with plasminogen to give one gigantic ugly molecule.

Some people say, “Think about baseball and the stitching but all of a sudden, you’ve got spikes everywhere that can injure your vascular endothelium and become retained.” There actually is a theory, excuse me, [coughs] that when pathologists for decades have identified that there’s ApoB in plaques, then most of it may be coming from lipoprotein(a) because it has ApoB. If you’re just measuring how much ApoBs in a plaque in your carotid or in your heart, you haven’t really identified what was the source of an ApoB. All of a sudden, lipoprotein(a) as showing up on the pathology radar screen is potentially driving plaques at least as much.

One out of every four, 90 million Americans inherit this. There’s a chromosome 6, has a gene, one parent gives you it, you’ve got some degree of elevated lipoprotein(a), and if you get it from both parents, you’ve got quite an elevated. If you have twins in a family, they both got the double gene from their parents, they have exactly the same lipoprotein(a) level, it’s under genetic control. [coughs] Excuse me so much. What we’ve learned, one in four people, it’s the most common genetic cardiovascular risk that exists. I may have to take a drink of water. [clears throat]

Your heart attack risk over life may go up four times, three times, and your stroke risk about the same. You can’t think of a better and more perfect storm for disease to have something that you’ve inherited that drives inflammation, plaque, and also drives clotting. That’s kind of the short and sweet. It’s been available as a blood test for a couple of decades, simple little blood test, $30, $40, you can do it at Quest, you can do it at LabCorp. Guidelines to date have not recommended teaching primary care docs or specialists to add this in as a routine blood test, but that’s starting to change 2019, 2020.

Why most doctors ignore lipoprotein(a)

Ari: My understanding of why they haven’t paid that much attention to it is something to the effect of– I think doctors have had an attitude of if it’s genetic and there’s nothing you can do about it, why would you even want to know about it? You can’t do anything about it, even if you know it’s there. As I was prepping for this, there seems to have been some discussion of the idea that this is undruggable. They’ve used that word that like, this is a risk factor that based on the way that drugs have approached dealing with certain things, you use a molecule that interrupts an enzyme and the synthesis of a particular protein or something to that effect.

That’s not possible with this lipoprotein(a) and so there haven’t been good therapeutics that have been able to address it. I did– And this might be jumping ahead, but I did hear some discussion of a different kind of therapeutic approach where they would interfere with the mRNA from actually manufacturing the protein or using something like antibodies to clear it from the bloodstream, but this idea of RNA therapeutics to prevent the body from over-manufacturing this lipoprotein(a). What are your thoughts on all of that?

Dr. Kahn: You’ve done good reading. You can give some reasonable support to the idea. We’ve known about lipoprotein(a) for 60 years and at least for 20 years, we know– I mean, I learned about it 20 years ago. We know that it is not just predictive of increased risk, it causes increased risk. It’s in plaques. We know its physiology, quite well-described, always going to learn more. The futility or the nihilism has been what you said. Is there a FDA-approved drug that we can educate doctors at grand rounds in lunchtime and other ways and encourage them to draw the blood test because there’s a therapy that has made it through the hoops of the FDA?

To date, in 2020, you’d say if that’s your criteria for educating about this cholesterol particle and its risk, we’re not quite ready. There’s a whole lot of other ways to look at it. Let me talk about a minute while we do know about what treats it. It is simply a blood test. It has been mentioned for at least a decade, if you are in a family history where you’ve had mom, dad, brothers, sisters, aunts, uncles, grandparents, early heart disease, heart attack, bypass stent, drop dead, early stroke, I’ll add one in I haven’t mentioned, the heart has four valves, little doors that open and close made of collagen.

One of those four valves is called the aortic valve. It is not uncommon to have your aortic valve get calcified, rigid, and unable to open. It causes you to be short of breath, get chest pain, black out, and you could die. It’s very easy to detect with a stethoscope and an echocardiogram and there is an operation to take your bad aortic valve out and put in a new one. Lipoprotein(a) has the unfortunate ability to cause aortic stenosis. No other cluster of particle we know of has been shown to do that. It’s not just leaving arteries to the heart, to the sexual organs, the kidneys and the brain at risk, it’s actually affecting this heart valve.

One out of every seven aortic valve operations is believed to be due to an elevated lipoprotein(a) and it’s not on the panel to draw. You could argue, by the time these people are identified, they’re so far advanced knowing that they had an elevated lipoprotein(a) or not is not going to be a major value. You’ll get to the question, one, do you want to know you have an intelligent audience? I have an intelligent patient base. Would you like to know more about your risks so you can make intelligent assessments? I want to go get a heart calcium CT scan. I’m going to have an advanced carotid ultrasound, a CIMT.

I’m going to use this as a springboard to eat better, exercise, manage my weight, control my inflammation, optimize my nutrition, get my mitochondria [unintelligible]. It’s only RA, you can get them on me. Would you want to know you’re at risk, even if there isn’t a specific therapy? A little bit like APOE, would you want to know if your parents had early Alzheimer’s that you have or haven’t inherited something? That’s an ethical question people struggle with. We haven’t moved down the road, partly because of all those issues.

Over the past 30, 40 years, there are things that have been found to lower it.

By far, the most effective that’s available right now and has been for 50 years is niacin. Vitamin B3 which lowers LDL cholesterol, lowers triglycerides, raises HDL, can do a very fine job of lowering lipoprotein(a) and people with elevated levels. You always have to watch for brashes and flushing and liver and gout and some other issues, but we’ve used the drugs over-the-counter, very inexpensive. From an academic standpoint, we don’t have a 2,000-patient, 10-year outcome trial. It’s a generic or over-the-counter use, it’d be a very expensive study. There’s actually nobody even planning such a study, but many, many people do their reading.

Women that are period menopausal and get on hormone replacement therapy will drop their lipoprotein(a) if that fits in their lifestyle and choices. Coenzyme Q10 drops it a little, not much. Whole-food, plant-based diets drop it a little, not much. The L-Carnitine we mentioned before for mitochondrial support can drop lipoprotein(a) 20%. A lot of people do a lot of this, but then there’s a drug. You’re right, there is a drug called an antisense oligonucleotide. In a study published last year, in almost 300 people with heart disease and elevated lipoprotein(a), it was able to drop lipoprotein(a) by 80% by injecting this. It’s called ASO. I always say it’s an oligosense nucleotide once a week.

They’re embarking right now on a randomized study of this drug. It was a little company called Akcea. Now, Novartis has the rights because you need a big giant company with hundreds of millions of dollars. There’s going to be a study with I think about 7,500 people randomized to this drug or placebo to do what the FDA requires. Are you going to see lower strokes, heart attacks, deaths, hospitalizations, all-cause mortality? That trial which is starting in 2020 or has started, has been delayed for sure by COVID-19, but we can only pray it was anticipated to take four years that it’ll still get done in 2024, 2025.

Real people are dying, having heart attacks, having strokes, having heart surgeries in 2020 because of lipoprotein(a) so we obviously do need therapy.

The normal and elevated levels of lipoprotein(a)

Ari: A couple of things I want to quantify. One is to what extent in this, I think, it’s one out of five or one out of four people who have elevated Lp(a), to what extent is it elevated? Is it elevated 40% above normal or optimal, or is it elevated 500% above optimal?

Dr. Kahn: That’s a great question. You can measure it very accurately. The unit you measured in is one of two different ways adding to confusion. You can measure it in a unit called milligrams per deciliter. Under 30 milligrams per deciliter is considered the normal range, over 50 is where you start to see elevated risk. I have patients that that number is 200, 300, 400, 500. It’s pretty rare to see higher than that. Then there is a different assay where you report it out in nanomoles per liter. Under 75 is normal, over 125 begins to be measurable risk, and it’s linear and it can be higher.

You can have a blood level 300, 400 500, by either determination, and there clearly is a correlation between the height of your blood level and the risk over years. Recognizing, important to say, since this is a genetic abnormality, you’ve had an elevated level since you’ve been 6 months, 12 months, it’s believed by about year two, whatever your lipoprotein(a) level is, it’s going to stay there for most of your life. It’ll vary up and down some, but so you’ve been exposed to a potentially pro-inflammatory plow plaque, pro-coagulation molecule for far longer than a smoker smoked and far longer than a fastfood eater’s eating fast food, just by the nature of the beast.

You want to find out your blood levels.

The best nutrients to balance your lipoprotein(a) and reduce risk of atherosclerosis

Ari: It sounds like– I’m guessing here what is common, maybe a more typical range of elevation is somewhere in the order of 100% to 200% above the normal optimal range.

Dr. Kahn: Correct, but 5% of the American public are significantly high. Most are closer. It’s a bell-shaped curve with a really long tail because some people have these phenomenally high. Also, to answer your question, there’s a thousandfold difference from the lowest to the highest levels recorded, much more variability in the concentration of this particle in the blood than LDL cholesterol which doesn’t have anywhere near that variability, maybe as a tenfold but thousandfold for the natural levels of lipoprotein(a).

I don’t want to go into all the biochemistry and structure of that tail that creates the molecule lipoprotein(a), but these kringles, you can have a few of them, or you can have these long chains. If you have a few of them, that’s where the blood levels get real high and if you have these long chains, you just don’t make as many of them and the blood levels a little lower. It’s some complex but very well-researched data on why there’s such variability in blood levels.

Ari: Having said that, and this is mostly genetic, you mentioned that a number of things, for example, carnitine, CoQ10, whole-food, plant-based diet, I think there was a few other things you mentioned can lower it, but they’re all relatively small effects, or carnitine is 20% and so on. How would you quantify the totality? Let’s say somebody did all of those positive things, they were starting with lipoprotein(a) level that’s 100% above the optimal range, they could potentially lower it by what, 30%, 50%?

Dr. Kahn: Well, if we can add niacin to that list, inexpensive over-the-counter and monitored carefully, sometimes, you can get 80% reduction. I mean, serious reductions, which is on par what this hopeful ASO, mRNA approach, it’s just embarking and trials can get routinely, but it is possible.

Ari: The nutrition lifestyle and supplement changes can get a total reduction that’s on par with potentially the best therapeutic that we might have which hasn’t even been released yet.

Dr. Kahn: Right. If the patient’s willing to work hard, the doctor is willing to work hard, very slow titration, particularly niacin. If I can, there’s one other little piece of story that gets to therapy. A question that’s worth asking is, “Why do we have this monster in our blood?” People have asked that question and nobody knows for sure. If you were bleeding during childbirth, you might not want to have plasminogen breaking up the clots and putting you at risk of dying. [crosstalk]

Ari: Sorry to interrupt. This is actually one of the important things I wanted to ask because when I was watching the RNA therapeutics and people speaking from the frame of, “Oh, we have this excess protein that’s just causing all these problems and it shouldn’t be there so we should just modify our RNA so it stops producing this protein.” For me, I have big red flags going off and I hear some someone talking like that because I’m like, usually, most things in the body, even if there’s some biochemical in there or some protein or something that increases risk, for one thing, it also tends to decrease risk for something else. It didn’t [crosstalk] by mistake.

My question was, as soon as this guy’s talking about the RNA therapeutics to reduce that protein, I’m like, “Well, what other disease is that going to cause?”

Dr. Kahn: It’s a great question, comes up all the time. Can you inhibit the pathway that grades cholesterol with statins without some potential, harm? We know there’s some risks to statins like blood sugar and myopathy and the rest. The best belief is humans develop the ability to produce lipoprotein(a) in about 25% of population about 40 million years ago, that’s what’s estimated. There’s only a couple of great apes, baboons, and the lowly hedgehog are the only species on the planet that can produce lipoprotein(a), and humans.

The hedgehog spontaneously developed it. The great apes, the baboon and I share so much similarity in our DNA, there’s clearly- or at least reasonably something about our lineage from the forest that explains that. One other thing happened 40 million years ago if you study biochemistry, is humans lost the ability to make vitamin C. It’s not a very well-known fact, but your dog, your cat and a squirrel can make all the vitamin C to support healthy physiology and maintain it. Humans can’t make one milligram of vitamin C at any phase of their life, simple enzyme in the liver that we’ve lost forever.

There are people that believe these two things happened around the same time and they’re linked. When you no longer make vitamin C, you are at risk of creating weak collagen because vitamin C is absolutely important in creating the cross-links that create collagen. Blood vessels are collagen. It is a theory. Linus Pauling, PhD, won two Nobel prizes, wrote a paper in 1990, “As we lost vitamin C, as our arteries became prone to injury, some people had a random development of lipoprotein(a) by this plasminogen gene being copied, but in a novel way.”

Suddenly, if their blood vessels were weak and they were bleeding, scurvy is that disease of your gums bleeding and such, they have the ability to stop, break down in clots, and may have had an advantage. There’s even a study, if you have an intracranial hemorrhage and an elevated lipoprotein(a), statistically, you might do a little better because it might promote the balance of stopping the bleeding. Not that we use lipoprotein(a) as a pro-clotting therapy, but it’s exactly what you said.

In the therapeutic world, there is a idea that upping your vitamin C, whether you do that through diet, produce, or whether you do that through exogenous vitamin C as is very popular right now during COVID and at all times, again, going back, line is fine, has an appeal that if you found out your lipoprotein(a) was high, you might want to pack vitamin C into your diet, improve the quality of your blood vessels which there’s reason to believe that’s true, and maybe blocked the harm that lipoprotein(a) causes the blood vessels. Interesting little side note because the vitamin C story doesn’t get mentioned a lot.

Ari: Very, very interesting. Let me ask you, I guess directly on the RNA therapeutics. Do you think that would be something you would recommend to people or not?

Dr. Kahn: I would. We have to have a therapy that isn’t just, “We’re going to stent your heart and replace your aortic valve or read about your obituary.” This is the real deal.

Ari: If you can get similar reductions with nutrition and lifestyle and supplement interventions, why not do that instead? Is it just the difficulty behaviorally of people not actually doing those things?

Dr. Kahn: Well, nobody’s going to fund the lifestyle niacin randomized trial of enough size to really measure outcomes. Niacin for a month might cost $5. You’re just simply not going to get anybody funded. There’s hardly any prescription niacin around anymore. It’s just good quality over-the-counter stuff.

Ari: Just explain one layer, more of why that wouldn’t get funded for people who don’t quite understand the rationale.

Dr. Kahn: You would really, really have to catch the attention. Either you can get a donor like a anti-aging scientist in New York, Nir Barzilai has a $100-million study on metformin and aging, but he got it all from independent funding donations. You can still do research that way, but you can imagine how difficult it is to raise $80 million to $100 million to study 4,000 people with metformin and other generic drug that has no cachet. One of the metformin trials, wildly positive, well, it’s not a pharmaceutical house that’s going to benefit. What if an over-the-counter niacin drug was wildly beneficial? It’s not a pharmaceutical house.

The reality is you could try and get the attention day and age and make a big proposal. Nobody’s driving down that path right now whereas, of course, with a powerhouse like Novartis, should this drug be beneficial? Would I recommend it? Absolutely, but the process, you got to take 7,600 maybe patients. Half of them are going to get a fake therapy placebo, half are going to get the real therapy, and you’re going to have to watch for bleeding outcomes and liver outcomes and blood sugar and brain. It’s a roll of the dice. Certainly, can’t say for sure this is going to be a winner, but I hope it is.

Ari: I don’t want to be putting words in your mouth, but I just want to add, like, in other words, when there’s research on a drug that can potentially be sold and at a profit and a lot of money to be made, that is much, much easier to get funding for and for it to actually get studied compared to supplement and nutrition, dietary and lifestyle changes for which no pharmaceutical company has the potential to make a whole bunch of money out of. Is that accurate?

Dr. Kahn: It’s true. The kind of trial they’re doing for this drug, I can’t tell you the ticket. If it’s a quarter-billion-dollar cost, I bet you it’s hundred million plus. It’s commonly said it can be as much as a billion dollars to take a novel new drug and bring it all the way to market. That protects us to some extent and there is really no competition. This research is going out worldwide, but this is the big trial and it’s being done right here in the United States. I think the Cleveland Clinic is the main central test center.

Testing for lipoprotein(a)

Ari: Do you recommend everybody to get tested for lipoprotein(a)?

Dr. Kahn: The traditional recommendation was high-risk families. There is a very dynamic group in Europe called the European Society of Cardiology. In November, 2019, they redid their guidelines, for the first time, got press all over. Their recommendation was everybody should consider just checking it once in your life, probably earlier the better, only looking for those real outliers that are very high, in the hundreds in terms of the blood level to give them some counseling on future risk and how to address it with lifestyle, maybe by optimizing everything else, blood sugar, blood cholesterol.

What you didn’t hear me say but is very important, on the list of therapies, I didn’t say statins, the number one most prescribed. Statins rarely drop lipoprotein(a), there’s a couple of small reports that say it can, and they very often cause it to go up. You want to jack with me? I’ll just raise presumably the production of lipoprotein(a) in the liver. We don’t know-

Ari: Statins do lower LDL or LDLC effectively, but you’re saying the body can respond to that by increasing lipoprotein(a).

Dr. Kahn: -it’s actually a totally different pathway, the pathway by which cholesterol is made and ultimately packaged into LDL cholesterol with ApoB. It’s a completely different liver pathway than lipoprotein(a)’s production. We don’t know why a statin which works on one pathway to lower LDL cholesterol causes very often a reaction, and it can double. You can have a Apolipoprotein(a) of a hundred and on a statin, it’s 180 or 200 if you bother to recheck it. Many people don’t recheck it. [chuckles]

Ari: Wow. Is it feasible? I’m not saying this necessarily would be common, but is it feasible that for some subset of people, you could take a statin, effectively lower LDL and yet, despite that, because of the reaction in lipoprotein(a), actually have an increased risk of cardiovascular or coronary artery disease?

Dr. Kahn: It’s possible. I don’t want to step on the toes of some really wonderful, prominent academics. The leading academic on lipoprotein(a) is in San Diego at UCSD and has an incredible repertoire of publications. The general recommendation is still use statins, lower the LDL, deal with the blood sugar, the blood pressure, the lifestyle, the diet, the sleep, the stress, and don’t recheck the lipoprotein(a). You use it in your algorithm of risk, but we have no reason to really know if it changes what that means if it went up. I find that-

Ari: That sounds like negligence to me.

Dr. Kahn: -well, you can only create the possibility that it’s harmful. If you measure LDL-P, LDL particle number, and you look at the number of particles, even in people with high lipoprotein(a) levels, there’s more LDL-P particles circulating to– Response to retention therapy cause plaque. If you really drop down your LDL particle number, even if the number of, lipoprotein(a) particles goes up, the ideas is you’ve still led to a more favorable overall picture, but it’s clearly inadequate till we have a therapy that directly drives down both. That’s when you’ll take residual risk and compact it into a very small piece of the pie, which is what we need.

Ari: To the point that we were discussing earlier about– You were talking about the role of lipoprotein(a) and clotting, to me, this almost feels like getting oneself into a mess of using one drug that solves one problem but causes another, then adding another drug to deal with that problem, then adding another drug to deal with that problem. I’ve been in an internal medicine ward, seeing people who are on 12, 15, 18 different prescription drugs and then have further problems. Then they get on a problem for that drug and drug for that problem and for that problem.

To what extent is this just going in a downward spiral of more and more symptoms and side effects and more and more drugs to deal with those issues?

Dr. Kahn: Again, the classic example that gets widely used is there’s a substantial number of people on statins like Lipitor that their blood sugar goes up and they start to meet criteria for prediabetic or prediabetic becomes diabetic and now, they’re on metformin because they’re on a statin. God willing, let’s talk to them about lifestyle, exercise, diet, and maybe some alternatives, although statins in many people are the right choice on that anti-statin in general. Yes, absolutely, it can get that sequence going.

The majority of people that will be on this research drug, by the nature of the beast, are going to be on some kind of anti-platelet, anticoagulant like aspirin or clopidogrel or eliquis or Xarelto. Hopefully, but we don’t know that there won’t be a spike in bleeding risk or clotting risk. Clotting risk should go down by lowering lipoprotein(a).Finally, there is a wonderful website called Lipoprotein(a) Foundation on the Web, tries to put together a lot of resources. They’re very conserve in their statements, very science-based, that’s all good, driven by a woman who had a cardiac event from lipoprotein(a) and became as many people do, very committed to educate and honor her.

There’s a letter on that website from the academic at UCSD that brings up the point since hypercoagulability clotting has become such a big factor in COVID-19. His letter was to at least alert people with high levels of lipoprotein(a), to give them more hygienic measures, mask, gloves and all, just be a little cautious. Although to date, nobody’s published the theories, here’s 100 people who are sick from COVID-19, those with lipoprotein(a) had more of the clotting than those who didn’t. It’s a interesting theory right now, but it’s not gone beyond that.

Ari: Got you. I guess, to rephrase my question, I think, to what extent does somebody go on a statin trying to lower the risk of cardiovascular disease, but then increase their insulin resistance and then start to become diabetic as a result of that, also decreasing CoQ10 problems with that, also increasing liproprotein(a) as a side effect of statins. Now, they’re on metformin for their insulin resistance, diabetes. Now, they’re on this antisense RNA therapeutic to deal with their increased lipoprotein(a).

Personally, I come from more of a hardcore, naturalistic paradigm approach to health. It seems to me, to make just way more sense to go, well, the fundamental drivers of the whole atherosclerosis process are nutritional and lifestyle. We know already, as you said, that many of these nutrition, lifestyle, and supplement approaches can lower lipoprotein(a) and LDL dramatically.

Dr. Kahn: And inflammation and blood sugar and blood pressure, right.

Ari: Doing that, instead of solving one problem while causing other problems, it solves all of the problems at once. Now, I get that there’s a nuance of like, there are some people who are genetically prone to just produce astronomical amounts of lipoprotein(a) and almost certainly the case that something like this RNA drug would be of massive benefit to that small segment of the population. Otherwise, it just seems to me that focusing on nutrition and lifestyle just seems like a way smarter approach.

Dr. Kahn: The earlier in life, the better. That’s been shown over and over. If you can maintain your risk profile low from teenage, early adult for decades, it’s a much more effective strategy. It’s also true if you do it through any other measure, genetic engineering or drugs, than if you’re 65 years old, have bypass surgery and you start to make changes. Yes, do them all then, but the impact’s always area under the curve, so 20 beats 65. You could come up with an algorithm, I hadn’t thought about this. If you have high lipoprotein(a) and high LDL cholesterol and three to six months of lifestyle change didn’t hit target, maybe those people shouldn’t get statins.

We do have a drug called Ezetimibe Zetia, we just got a new class of drugs called bempedoic acid, they got FDA-approved. We have those injectable drugs, Praluent and Repatha that lower LDL and modestly lower lipoprotein(a). Maybe that should be the new algorithm. If you only have a high LDL cholesterol and you can’t control it and you need to control it, you got your statins as we’ve been doing, interesting approach. I’ll just say we hope the future is brighter that we will be able to go to chromosome 6 and turn off the Lp(a) gene which is there.

There’s a company that has a big splash in the news now called Verve Therapeutics. They just did some genetic slicing, I think in a mouse model, and were able to engineer genetically driven mice for risk for cardiovascular diseases, dramatic drops in triglycerides and LDL for life by turning it off. That’s really what– Turning it off at the source as long as it doesn’t trigger an increased risk of clotting because of that plasminogen action.

Ari: Got you. Well, Dr. Kahn, this has been fascinating stuff. Do you have any final words or just practical recommendations for people that you want to leave people with as far as getting their lipoprotein(a) levels assessed and your words of advice and what they should do if it’s elevated?

Dr. Kahn: Simple blood test, check it off, LabCorp, Quest. You could probably send it away to WellnessFX and similar labs. Your primary care doc and your cardiologist probably have not ordered these before. Your primary care doc may know very, very little, and I’m not being offensive, your cardiologist may know almost as little. They may resist, “I’ve never ordered one before, what are we going to do about it?” so do a little bit of reading, be kind or just order it on your own, certainly, if you have the family history of valve disease or other cardiovascular events early in life.

I don’t know how you really plan optimal decisions, lifestyle, plus the implication. Would you like your children? I have a lot of patients, 70 years old, with this. Do they want their 35–year-old children to be tested? I don’t know why you wouldn’t, why that couldn’t be spun in a positive way. Okay, there’s controversy what we do about it, but it’s getting a little tighter on our lifestyles just saying that it’s more important. We do that in other disease states, but we haven’t embraced this.

Anyway, it’s been a pleasure. I know we went a little deep down a few roads, but I really appreciate the opportunity. I have no skin in the game, I have a book. I don’t write books to drive Maseratis, I don’t drive Maseratis. I write books because I’m passionate about a topic and I hope it’ll educate.

Ari: You drive Lamborghinis, right? [crosstalk] drive Lamborghinis.

Dr. Kahn: I drive a Chevrolet, I’m here in Detroit. It happens to be a Camaro but it’s just a plain body Camaro.

Ari: Nice. Dr Kahn, it was a pleasure. This is a fascinating topic. If people are interested in getting your book or working with you and being a patient of yours, where is the best place to do that?

Dr. Kahn: Well, that’s kind of you. I’m in Detroit, but telehealth is telehealth and patient in Perth, Australia this morning. It’s drjoelkahn.com. D-R-J-O-E-L-K-A-H-N.com

Ari: Beautiful. Thank you again, my friend. Pleasure connecting with you as always.

Dr. Kahn: Man, I apologize for the couple of coughs, I don’t know what happened. I’m relaxed and I’m in good health. It’s a pleasure. Thank you, man.

Ari: All right, my friend, I’ll talk to you again soon, I hope.

Dr. Kahn: Yes. You bet.

Show Notes

The most common causes of atherosclerosis (6:20)
The most common nutritional causes of atherosclerosis (16:26)
The link between lipoprotein(a) and atherosclerosis (34:40)
What is lipoprotein(a)? (37:00)
Why most doctors ignore lipoprotein(a) (45:28)
The normal and elevated levels of lipoprotein(a) (53:08)
The best nutrients to balance your lipoprotein(a) and reduce risk of atherosclerosis (54:54)
Testing for lipoprotein(a) (01:05:29)


If you want to work with Dr. Kahn, check out his website

Get the book Lipoprotein (A), The Heart’s Quiet Killer.

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