Episode 56
Cholesterol and Heart Disease
Apolipoprotein B (apoB) is the causative agent in atherosclerosis. If your apoB is low, you will not develop atherosclerosis. However, if your apoB is high, you could die young.
We know this because of genetic studies of people with different levels of apoB and their health outcomes.
What is Atherosclerosis of the heart?
Atherosclerosis is a progressive laying down of "plaque" in the wall of the coronary arteries. Since the coronary arteries feed the heart, this can lead to three outcomes:
- The plaque impinges on the artery. Thus, the plaque will decrease blood flow to the heart. This can lead to angina or a poorly working cardiac muscle.
- The plaque can rupture (burst) into the artery. Next the body repairs this by clotting the blood. Thus, the blood flows to that portion of the heart is stopped. Without blood flow, the heart muscle starves, and if the flow isn't restored, that part of the heart will die. This is a heart attack or myocardial infarction.
- The plaque can have no result. Meaning, it isn't stopping blood flow to lead to angina, and it doesn't occlude the artery.
What is in the plaque?
In the above artery, you can see the yellow cholesterol in the wall. This is a "soft" plaque, like porridge.
The plaque is not inside the vessel. The artery is lined by a layer called the intima. So how does cholesterol get from the inside of the blood vessel to behind the layer?
The Process of Atherosclerotic Plaque Formation
Lipoprotein Entry into the Arterial Wall: The process begins when ApoB-containing lipoproteins pass through the endothelial layer of arteries. Normally, this layer acts as a barrier, but factors like high blood pressure or inflammation can make it more permeable, allowing these particles to accumulate beneath the endothelial cells.
Retention and Modification: Once inside the arterial wall, ApoB lipoproteins are trapped by proteoglycans (components of the extracellular matrix). These retained lipoproteins undergo modifications, such as oxidation, which makes them more likely to trigger inflammatory responses.
Inflammatory Response: The modified lipoproteins activate endothelial cells and attract immune cells like monocytes. These monocytes enter the arterial wall and transform into macrophages. Macrophages engulf the modified lipoproteins, turning into foam cells, which are a hallmark of early atherosclerotic plaque.
Plaque Development: Over time, foam cells accumulate, leading to the formation of fatty streaks in the arterial wall. Smooth muscle cells migrate into the intimal layer of the artery, contributing to the formation of a fibrous cap that covers the plaque. This cap consists of connective tissue, calcium, and cholesterol deposits.
Progression and Complications: As the plaque grows, it narrows the artery and restricts blood flow. If the fibrous cap ruptures, it can lead to the formation of a blood clot (thrombus), which may block the artery entirely, causing a heart attack or stroke.
Preventing Plaque Formation
Understanding how ApoB-containing lipoproteins contribute to atherosclerosis underscores the importance of managing blood cholesterol levels. Lifestyle changes such as diet, exercise, and medications like statins can reduce LDL levels, lowering the risk of plaque formation and subsequent cardiovascular events.
Atherosclerosis is a gradual process that starts with the seemingly harmless entry of ApoB lipoproteins into arterial walls. By addressing the risk factors that promote lipoprotein retention and inflammation, the progression of atherosclerosis can be slowed or prevented.
LDL particle size
LDL particles can vary in size, and it was previously believed smaller, denser LDL particles were more atherogenic than larger, buoyant ones. However, research has shown that the number of LDL particles, regardless of size, is a more significant determinant of cardiovascular risk. Studies indicate that the concentration of LDL particles is more closely associated with atherosclerosis than the size of the particles themselves.
The ApoB Factor: Why It's a Big Deal
ApoB is a protein found on the surface of atherogenic lipoproteins, including LDL, VLDL, and IDL. Each of these particles contains one ApoB molecule, making ApoB a direct measure of the number of atherogenic particles in the blood. This measurement is crucial because it provides a clearer picture of the atherogenic burden in the bloodstream than LDL-C alone.
Why ApoB is the Star Player
Direct Measure of Risk: ApoB directly measures the number of atherogenic particles, providing a more accurate assessment of cardiovascular risk.
Independent of Particle Size: Unlike LDL size, which can vary and complicate risk assessment, ApoB consistently reflects the number of risk-contributing particles.
Predictive Power: Numerous studies have shown that ApoB is a better predictor of cardiovascular events than LDL-C or other traditional lipid measures.
ApoB: Direct Measurement of Atherogenic Particles
Apolipoprotein B (ApoB) is the main protein component of several lipoproteins, including low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and lipoprotein(a). Each atherogenic particle contains one molecule of ApoB, making ApoB a direct measure of the number of atherogenic particles circulating in the bloodstream.
Key Points:
Direct Indicator of Particle Number: Since each atherogenic lipoprotein particle has one ApoB molecule, measuring ApoB provides an accurate count of these particles. This is crucial because the more atherogenic particles present, the higher the risk of these particles penetrating the arterial walls and contributing to plaque formation.
Independent of Cholesterol Content:
The cholesterol content does not influence ApoB measurement within these particles. Therefore, it provides a clearer picture of cardiovascular risk, especially in cases where LDL cholesterol (LDL-C) levels might be normal, but the number of LDL particles (and thus ApoB) is high.
HDL-TG Ratio: A Marker of Lipid Metabolism
The HDL-TG ratio, which is the ratio of high-density lipoprotein cholesterol (HDL-C) to triglycerides (TG), is used as a marker to assess lipid metabolism and insulin resistance. A high HDL-TG ratio generally indicates a favorable lipid profile and a lower risk of cardiovascular disease. However, this ratio has limitations:
Indirect vs direct measure:
Indirect Measurement: The HDL-TG ratio provides an indirect measure of cardiovascular risk. It does not directly quantify the number of atherogenic particles but rather gives a sense of lipid metabolism status. While a low HDL-C and high TG level can indicate higher cardiovascular risk, it doesn't directly account for the number of atherogenic particles present.
Variability and Confounding Factors:
Several factors can influence the ratio, including lifestyle, diet, and metabolic disorders, which can confound its predictive value for cardiovascular risk. Additionally, HDL-C levels alone have not consistently been shown to correlate with reduced cardiovascular risk, as HDL particles can vary in functionality.
Why ApoB is More Important
Predictive Power: Numerous studies have shown that ApoB is a stronger predictor of cardiovascular events than the HDL-TG ratio. For instance, the INTERHEART study highlighted that ApoB levels were more predictive of myocardial infarction than other lipid markers, including the HDL-TG ratio.
Comprehensive Risk Assessment: ApoB accounts for all atherogenic particles, providing a more comprehensive assessment of cardiovascular risk compared to measures that only consider cholesterol content or ratios of different lipid components.
Focusing on the Right Metric
In summary, the focus has shifted from LDL particle size to the number of atherogenic particles, as measured by ApoB. This shift is grounded in the understanding that cardiovascular disease risk is more closely linked to the number of these particles rather than their size or cholesterol content alone. Therefore, ApoB provides a more accurate and reliable measure for assessing cardiovascular risk.
Conclusion
While both ApoB and the HDL-TG ratio can provide valuable information about lipid metabolism and cardiovascular risk, ApoB is considered more important due to its direct measurement of atherogenic particles. This makes it a more reliable and comprehensive marker for assessing the risk of atherosclerosis and related cardiovascular events.
Citations:
Sniderman, A. D., & Tsimikas, S. (2014). Apolipoprotein B. Circulation, 129(11), 1112-1120.
Packard, C. J., & Shepherd, J. (1999). Lipoprotein heterogeneity and apolipoprotein B metabolism. Atherosclerosis, 141(1), 27-42.
McQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., ... & Yusuf, S. (2008). Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. The Lancet, 372(9634), 224-233.
Cromwell, W. C., & Otvos, J. D. (2004). Low-density lipoprotein particle number and risk for cardiovascular disease. Current Atherosclerosis Reports, 6(5), 381-387.
Mora, S., Otvos, J. D., Rifai, N., Rosenson, R. S., Buring, J. E., & Ridker, P. M. (2009). Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation, 119(17), 931-939.
Packard, C. J., & Shepherd, J. (1999). Lipoprotein heterogeneity and apolipoprotein B metabolism. Atherosclerosis, 141(1), 27-42.
Sniderman, A. D., & Furberg, C. D. (2008). Age as a modifiable risk factor for cardiovascular disease. The Lancet, 371(9623), 1547-1548.
Cromwell, W. C., & Otvos, J. D. (2004). Low-density lipoprotein particle number and risk for cardiovascular disease. Current Atherosclerosis Reports, 6(5), 381-387.
Sniderman, A. D., & Tsimikas, S. (2014). Apolipoprotein B. Circulation, 129(11), 1112-1120.
Harchaoui, K. E., Visser, M. E., Kastelein, J. J., Stroes, E. S., & Dallinga-Thie, G. M. (2009). Triglycerides and cardiovascular risk. Current Cardiology Reviews, 5(3), 216-222.
McQueen, M. J., Hawken, S., Wang, X., Ounpuu, S., Sniderman, A., Probstfield, J., ... & Yusuf, S. (2008). Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. The Lancet, 372(9634), 224-233.
Transcript
>> Dr. Terry Simpson: In the topic about heart disease, you're going to
Speaker:hear a lot about cholesterol. And it
Speaker:gets confusing, because you're going to hear about good cholesterol,
Speaker:bad cholesterol, LDL, hidl,
Speaker:apob, small size, large
Speaker:size, what does it all mean?
Speaker:You're going to hear people state that LDL isn't important, but
Speaker:that the size of particle or the oxidation is important.
Speaker:And while all of this gets obscure,
Speaker:today we're going to make sense of the madness
Speaker:and show you how size isn't
Speaker:important.
Speaker:I am, your chief medical explanationist, doctor Terry Simpson,
Speaker:and this is fork U forked
Speaker:university, where we make sense of the madness. Busting
Speaker:a few myths and teach you a little bit about food
Speaker:is not always medicine.
Speaker:Maybe you heard about LDL being the bad
Speaker:cholesterol and HDl being the good cholesterol. And we
Speaker:have to check your HDl triglyceride level
Speaker:on and on and on. It really gets
Speaker:confusing. Stripping away the good and bad
Speaker:labels, we know that cholesterol, first of all, doesn't just
Speaker:float around in your blood. Cholesterol is oil based
Speaker:or waxy. And since your blood is water
Speaker:based, we have to carry the cholesterol in
Speaker:something. And so the cholesterol is placed in these
Speaker:little packages of protein, and
Speaker:those proteins are classified by their weight in a
Speaker:centrifuge. And over time, we found that these
Speaker:low density lipoproteins, that those
Speaker:packages are responsible for
Speaker:leaving deposits in the walls of your
Speaker:arteries. And those deposits are called
Speaker:atherosclerosis. And if you get a bunch of them together,
Speaker:it's called a plaque. And those
Speaker:plaques, when they rupture, lead to a heart attack
Speaker:or to a stroke, or if they impinge on the
Speaker:artery, meaning they start decreasing the flow of the
Speaker:artery to the heart, they lead to heart ischemia
Speaker:or angina. So
Speaker:LDL isn't a one size fits all villain.
Speaker:All the LDL particles vary in size, density,
Speaker:oxidation, et cetera. So we're going to sort
Speaker:of strip away one of the more common myths that I
Speaker:heard, that you have to worry about
Speaker:LDL, particle size. As if you couldn't hear
Speaker:enough. We're going to strip that away because you don't
Speaker:need to care about the size anymore. Size of the
Speaker:LDL particle isn't important. And you don't have to
Speaker:remember these old terms, like pattern a, large fluffy
Speaker:particles are good. Pattern B, small dense
Speaker:particles, are bad. Because the recent
Speaker:research has shifted focus from the LDL particle
Speaker:size to one of the lipoproteins
Speaker:that surrounds the cholesterol, called apolipoprotein B,
Speaker:which we will call ApoB.
Speaker:Think of it this way. If you want to
Speaker:not have messy tea, you
Speaker:put your loose tea in something
Speaker:like a teabag. Think about the
Speaker:teabag as being partially held
Speaker:together by one of these apob molecules,
Speaker:right? So every single teabag, or
Speaker:LDL particle carries one of
Speaker:these little proteins, that Apop protein. Think of the tea
Speaker:as the cholesterol. But that protein is a
Speaker:passport that allows that
Speaker:teabag to enter into the cell
Speaker:wall of the artery,
Speaker:not just passively, but it's actively
Speaker:transported in. If there's an LDL particle, it's actively
Speaker:transported into this cell wall.
Speaker:And if there are too many LDL, particles in
Speaker:that cell to be metabolized by that
Speaker:cell, it tosses the LDL particles
Speaker:out the backside of the cell into the wall of the
Speaker:artery between the first and second layer.
Speaker:That's where they build up, that's where they oxidize,
Speaker:and that's where they can ultimately get so large
Speaker:that they impinge on the artery wall, leading
Speaker:to less blood flow to, like, the heart
Speaker:artery, or less blood flow to the brain,
Speaker:which can cause ischemia, a heart attack, or stroke.
Speaker:The key is how many apob
Speaker:particles there are. Now, we used
Speaker:to think that that was the answer. The size
Speaker:of the particle. We used to think small particles.
Speaker:Wow. They're the bad ones, because when we looked at the research,
Speaker:we saw small particles had more atherosclerosis. Is this
Speaker:confusing you? But think about this. The more small
Speaker:particles you have, you're gonna have more
Speaker:apob, because if you bake a lot of little tea
Speaker:bags, you gotta sew it together with that apolipoprotein
Speaker:b, and that's a problem.
Speaker:The particle number gives us a count of
Speaker:how many of these atherogenic particles there are.
Speaker:We call them atherogenic because the ApOB
Speaker:particle is the thing, the particle that
Speaker:leads to atherosclerosis. Doesn't matter
Speaker:how large, how much tea is in the
Speaker:teabag, how much cholesterol
Speaker:is in the LDL particle. What matters
Speaker:is how many of them are circulating in your blood.
Speaker:Now, I've, heard people say, well,
Speaker:cholesterol's important. It is. Cholesterol's
Speaker:used in every cell. It is. Cholesterol's used to
Speaker:make steroid hormones, like testosterone, estrogen.
Speaker:It is. Cholesterol's important to your brain. It
Speaker:is. But too much cholesterol, like too much
Speaker:water or too much salt, or too much blood
Speaker:sugar, is bad. Too much
Speaker:cholesterol leads to atherosclerosis.
Speaker:Some people say God doesn't make mistakes. Well, I don't know if God
Speaker:made a mistake or not. We're not going to live forever. But if
Speaker:you want to live longer, you want to have less
Speaker:atherosclerosis. There have been
Speaker:a number of articles that have shown this, that it is
Speaker:the number of apob particles,
Speaker:nothing, not the size of
Speaker:the molecule. And there's two ways of looking at this.
Speaker:If you have a bunch of little tiny molecules of ldl, which
Speaker:have small particles, and they get in and they're tossed out
Speaker:to the back, well, it's going to take a lot of those
Speaker:to build one large cholesterol particle which is
Speaker:equally actively transported in. So
Speaker:you have a lot of large, fluffy particles, you'll have a
Speaker:faster buildup. Now, what are things that increase
Speaker:apob in your body? One of them
Speaker:is sugar. That's why
Speaker:diabetics need to be under better control, because
Speaker:more glucose in your blood, the more spikes you have, the more
Speaker:insulin resistance you have, the more diabetes you have, you're making
Speaker:more APOB particles. The more apob particles, the more
Speaker:atherosclerosis, the higher your risk of heart disease.
Speaker:That's all. That's as simple as that.
Speaker:So here's the key. This month,
Speaker:when you go to your doctor, APOB is the
Speaker:test you want to ask for. They'll give you a standard
Speaker:cholesterol panel. It'll have your hdl, your
Speaker:ldl, your total cholesterol, your
Speaker:triglycerides. Ask to get an
Speaker:APOb test. And while you're at it, also ask to get a
Speaker:PSA test, because this month, this month,
Speaker:we want you to do cancer screening. So, American
Speaker:Cancer Society, what's my number? Screen me,
Speaker:etcetera. So there's been lots of
Speaker:meta analysis of participants showing how APOB is a stronger
Speaker:predictor of heart events than cart particle
Speaker:size. And I won't bore you with it, but if you want to find out more of
Speaker:the detail and more of those for the nerdy bunches of
Speaker:you, and most of you are nerds, go to the blog associated with
Speaker:this@yourdoctorsorders.com or four
Speaker:q.com.
Speaker:now, how can diet and lifestyle affect the
Speaker:apob number? We already talked about refined grains,
Speaker:but saturated fat like red
Speaker:meat increases apob
Speaker:particles. Lean meat,
Speaker:plant based fats like olive oil and
Speaker:avocado don't. They might actually
Speaker:decrease APOb number. So changing your diet from
Speaker:saturated fats to less saturated fats when you get
Speaker:below 9%, we see that change.
Speaker:I know the low carb people never like this because
Speaker:they want to wave off cholesterol, because every
Speaker:article out there shows that low carb and keto diets lead to
Speaker:higher ldl numbers,
Speaker:increasing the fiber in your diet. Soluble fiber, like
Speaker:foods found in oats, beans, and fruits,
Speaker:reduce the number of ldl and apob particles in your
Speaker:bloodstream. How do they do that? Because here's
Speaker:what happens when your liver
Speaker:makes ldl. Because this cholesterol is made and you're packaged
Speaker:in your liver, what happens is it doesn't
Speaker:just throw it into your bloodstream. It makes
Speaker:all these ldl particles and puts it into your bile.
Speaker:Your bile is secreted by your liver and goes into your
Speaker:intestine, and from your intestine, it goes into your
Speaker:bloodstream. Now, when you eat more
Speaker:fiber, the fiber binds
Speaker:to those LDL particles, and those fibers
Speaker:that bind to the LDL particles
Speaker:passively go out of your backside
Speaker:into the toilet. Right.
Speaker:Diets that are high in processed carbs and sugar raise apob
Speaker:levels. And so those diets also have less
Speaker:fiber. So increasing the fiber in your diet not only makes
Speaker:you feel full longer, it decreases your
Speaker:apob particles. I'll give you another
Speaker:example. Whole grains, brown
Speaker:rice, quinoa,
Speaker:oats, corn,
Speaker:all have fiber that
Speaker:decrease apob. Refined grains don't have
Speaker:fiber. Lead to sugar spikes lead to more
Speaker:manufacturing of apob. That's why refined
Speaker:grains aren't good. That's why whole grains are.
Speaker:Okay? Okay, so to wrap
Speaker:this up, while we used to think the size of the
Speaker:LDL particle was important, it really is apob.
Speaker:Ask your doctor for an apob. That's how we
Speaker:get a better picture of your heart. What should your levels be? In the
Speaker:United States, we want your apob levels to be under 100.
Speaker:In Europe, we want them under 70. We'll probably go to under
Speaker:70. Why do we keep changing this every
Speaker:year? Because we have discovered over time that the lower
Speaker:your total cholesterol number is, the healthier
Speaker:you are. Now, there are m those people who say, well, you know,
Speaker:long live people have higher ldls.
Speaker:Okay? If you get to be old, you can have a
Speaker:higher ldl. But remember, there are many other things that
Speaker:influence this. Meaning this. I'll
Speaker:give you one example. There's a genetic
Speaker:predisposition to people called the PCSK nine
Speaker:transport system. And if you have a genetic
Speaker:defect in that, you can have high ldl,
Speaker:but you also have high ldl
Speaker:receptors. Because you have high ldl receptors, you
Speaker:don't have that much ldl in your body. It's cleared very
Speaker:quickly. And those people live
Speaker:long. Remember, longer lived people,
Speaker:still die of heart disease, still die of cancer, still
Speaker:have diabetes, still have cognitive decline. They
Speaker:just put it off for a while.
Speaker:So get your ldl down. Is there a
Speaker:lower level? Well, we know below. I think it's 53. You're probably
Speaker:not going to have heart disease. What do kids
Speaker:need? What do you need to maintain the amount of
Speaker:testosterone and keep your brain well? Remember your lDl.
Speaker:Your brain makes its own cholesterol. It doesn't rely on your
Speaker:liver. Your gonads
Speaker:make your own testosterone and estrogen. They don't rely on your
Speaker:liver. So don't listen to people who say, that's
Speaker:all I terribly important because too much cholesterol, like
Speaker:too much salt, like too much blood sugar is
Speaker:deadly.
Speaker:All right, go to my blog, yourdoctorsorders.com, or
Speaker:fork u.com, to see all
Speaker:of the references and you can look them up for yourself. This
Speaker:episode was written and researched by me, doctor Terry Simpson.
Speaker:And while I am a doctor, I'm not your doctor. Please
Speaker:see your doctor, a western trained, non
Speaker:chiropractic, non eastern trained
Speaker:physician. And if you're curious about, what
Speaker:your LDl APOB number is, please see your regular doctor for
Speaker:that. Podcast is distributed by our friends
Speaker:at Simpler Media than the pod God, Mister Evo
Speaker:Terra. Our production is done by producer Girl Productions, who
Speaker:insist on my hair being perfect even though we're not
Speaker:doing video today.
Speaker:Until next time, stay curious. And
Speaker:remember, food can be a powerful influence on your
Speaker:health.
Speaker:This month is cancer screening month for
Speaker:prostate cancer. See, we want you to know your PSA
Speaker:number, just like I know my APOb number, which is 63.
Speaker:My PSA number is three. We want it under four.
Speaker:So I hope this month you go to the American
Speaker:Cancer Society, get screened, find out your
Speaker:psa number. Because after all, min 50
Speaker:and over, we need to know the number. And I hope
Speaker:yours is less than four. And be sure and check
Speaker:out your apopee number. Also.
Speaker:>> Speaker B: 2.97, I'm happy to report. And
Speaker:yes, that is checked on a regular and frequent basis with
Speaker:me. And thanks for the information on the
Speaker:APOB. I'm never going to drink tea in a
Speaker:teabag again.
