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Apolipoprotein B (ApoB) is a protein that plays an important role in the development of heart disease. Elevated blood levels of ApoB indicate an increased risk.
Actually, ApoB may be a stronger predictor of risk than commonly used lipid markers such as LDL-cholesterol (1).
ApoB is an important component of lipoproteins that participate in the formation of atherosclerosis.
To help you understand the role of ApoB, I will start by briefly explaining the role of lipoproteins in atherosclerosis. I will then discuss the apolipoproteins and their different classes. Finally, I will explain the role of ApoB and how it can be used to assess the risk of heart disease.
Atherosclerosis may be described as chronic inflammation of the arterial wall. It is caused by a complex interplay between lipoproteins, white blood cells (macrophages), the immune system, and the arterial wall’s normal elements.
Atherosclerosis is initiated when an apoB-containing lipoprotein particle is caught in the vessel wall. This leads to an inflammatory cascade, resulting in the progression of atherosclerosis.
Atherosclerosis leads to the formation of plaques within the walls of the arteries. These plaques may subsequently cause blockages and limit blood flow to tissues and organs such as the heart and the brain.
A rupture of an atherosclerotic plaque (plaque rupture) may lead to thrombosis (blood clotting), causing an artery’s abrupt occlusion (blockage). If this occurs in a coronary artery, it may cause an acute myocardial infarction (acute heart attack).
Cholesterol and Lipoproteins
Although cholesterol is an essential substance for most cells in our body, elevated blood levels may play a role in the initiation and progression of atherosclerosis.
In animal models, atherosclerosis will not occur in the absence of greatly elevated levels of plasma cholesterol. High blood levels of cholesterol also appear to be an important contributor to atherosclerosis in humans.
However, the role of cholesterol is most often oversimplified. Many individuals with high blood cholesterol never develop heart disease, and many patients with heart disease don’t have high cholesterol levels.
In fact, cholesterol’s role in heart disease appears to be determined by the lipoproteins that carry the cholesterol in the bloodstream rather than the cholesterol itself.
Let me explain.
Because fats are insoluble in water, cholesterol can not be transported in blood on its own.
The body’s solution to this problem is to bind fats to proteins that function as transport vehicles carrying different types of fats such as cholesterol, triglycerides, and phospholipids. These combinations of fats and protein are termed lipoproteins
It is important to emphasize that it is the lipoproteins (not the cholesterol) that interact with the arterial wall and initiate the cascade of events that leads to atherosclerosis (2).
Cholesterol is only one of many components of lipoproteins. Therefore, measurements of total cholesterol provide little information about the amount and types lipoproteins particles in the circulation.
There are five major types of lipoproteins; chylomicrons, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
Lately, the role of another lipoprotein, called lipoprotein(a) or Lp(a), has been highlighted (3).
A standard lipid profile will tell us how much cholesterol is being carried by the different lipoproteins. Hence, the level of LDL-cholesterol and HDL-cholesterol will tell us how much cholesterol is found within LDL and HDL particles, respectively.
Scientific data tells us that there is a strong correlation between LDL-cholesterol and heart disease risk, although this has been debated by some investigators (3, 4).
However, measurements of the number of LDL-particles appear more predictive of risk than the cholesterol mass within these particles (represented by LDL-cholesterol) (5,6).
Lipoproteins are comprised of apolipoproteins, phospholipids, triglycerides, and cholesterol. However, the lipoproteins vary in the major proteins present and their lipid components differ.
Different lipoproteins contain different types of apolipoproteins. The type of apolipoprotein present determines the structure and function of the lipoprotein.
There are several classes of apolipoproteins and many subclasses (7).
I’ll just mention a few examples.
ApoA1 is the major protein component of HDL (8).
ApoA5 is a marker of increased triglyceride concentrations and a risk factor for heart disease in some populations (9).
ApoD has antioxidant and anti-inflammatory activity. It may play a role in diseases of the nervous system and the aging process (10).
ApoE has several subclasses. Human ApoE exists as three common isoforms, ApoE2, ApoE3, and ApoE4 (11).
ApoE4 is a major genetic risk factor for late-onset Alzheimer’s disease (12).
Retention of ApoB containing lipoprotein particles within the arterial wall is an essential part of the early atherosclerotic process.
Lipoproteins that promote atherosclerosis are termed atherogenic. ApoB is an important component of all atherogenic lipoproteins.
Human ApoB has two main forms, apoB48 and apoB100. ApoB48 is synthesized mainly by the small intestine, and ApoB 100 ,is synthesized by the liver (13).
From the viewpoint of atherosclerosis and cardiovascular risk, apoB100 is the important one.
ApoB 48 is primarily found in chylomicrons whereas ApoB 100 is found in chylomicrons, LDL, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and Lp(a) particles.
Atherogenic lipoproteins such as LDL, VLDL, and Lp(a) all contain one ApoB molecule per particle. Hence, measurements of ApoB reflect the number of atherogenic particles.
On the other hand, HDL does not contain ApoB and is not atherogenic. In fact, HDL appears to play a protective role, and high numbers of HDL particles are associated with less risk of heart disease (2).
As mentioned before, ApoA-1 is the principal apolipoprotein on the HDL paritcle.
Thus, the ApoB/ApoA-1 ratio represents a measure of the balance between particles that promote and protect from athersclerosis.
The ApoB/ApoA1 ratio may be more effective at predicting heart attack risk than either the apoB or apoA1 measure alone (14).
Usually, 85-90 percent of apoB is found in LDL particles. Thus, apoB reflects LDL particle number, similar to LDL-P.
Evidence suggests that apoB is a better tool to predict cardiovascular risk than LDL-cholesterol and non-HDL-cholesterol (15).
Furthermore, apoB may be elevated despite normal or low levels of LDL-cholesterol (16).
ApoB also appears to predict risk when LDL-cholesterol has been lowered by statin therapy.
Normal Range For Apolipoprotein B
Although measurements of apoB are not widely available, the assay has been standardized and does not require a fasting sample.
The normal range for apoB is 40-125 mg/dL.
ApoB levels are higher in men than women and tend to increase with age.
Here is how apoB levels are looked at in terms of risk of heart disease:
- Less than 130 mg/dL (1.3 g/L)is considered desirable in individuals without risk factors.
- Less than 110 mg/dL (1.1 g/L) is considered desirable in low or intermediate-risk individuals.
- Less than 90 mg/dL (0.9 g/L) is desirable in high-risk individuals, such as those with heart disease or diabetes.
How to Lower Apolipoprotein B
Many experts will recommend the same general measures to lower apoB as they do for lowering LDL-cholesterol. Hence, eating less saturated fat and cholesterol from meat and dairy products is often regarded as a first step. Furthermore, increased consumption of vegetables, fiber, and mono-and polyunsaturated (omega-3) fatty acids is recommended.
However, some dietary interventions may affect LDL-cholesterol and apoB differently. For example, some studies have indicated that carbohydrate restriction may lower apoB, independent of whether the intake of saturated fat is high or low (17).
Patients with high levels of triglycerides and low HDL-cholesterol may have high apoB levels despite normal or low LDL-cholesterol. These patients may derive most benefit from low-carbohydrate diets (18).
Cholesterol lowering drugs such as statins, ezetimibe, and PCSK-9 inhibtors usually lower apoB levels.
Physical exercise has also been shown to lower apoB and positively affect the apoB/apoA1 ratio (19).
20 thoughts on “Apolipoprotein B (ApoB) and Risk of Heart Disease”
Atherosclerosis is initiated when an apoB-containing lipoprotein particle is caught in the vessel wall.”
The immediate questions must be: why (is it caught)? what (under what conditions)? how (it is caught (mechanism))?
why is nothing else apparently caught?
That’s the million dollar question. We have to assume that many factors are involved; the status/permeability of the endothelium, the number of apoB containg particles, external facors like smoking, the presence of diabetes etc.
Sorry, I am slow to respond.
Is the initiating “event” an injury to the endothelium (ultimate cause).
Therefore, we need to understand that aspect first – there are potentially many causes (of injury) events.
To start with, perhaps a weakened endothelium due to “shortened” glycocalyx caused by a hi-carb diet?
Or perhaps low vitamin C levels.
Or as you imply many different things like smoking.
So the key question is:
Can the apoB-containing lipoprotein particle cause the injury or does this particle arrive on the scene subsequently (deliberately as part of the repair process or accidently?) ?
Any thoughts on my questions?
Dr.- Within the factors you mention, given what I have read on the subject, the only one that seems to be beyond our control with either drug or behavioral modification is “status/permeability of the endothelium,” which I assume you mean the inner lining of arteries. Of all the issues with ApoB, it seems this is the most concerning. Where is medicine vis-a-vis its diagnostic ability to determine an objective status/permeability of the endothelium and more importantly, suggested remedy for diagnosed susceptibility to ApoB.
Always good reading Doc. Keep writing.
Since I am pretty much new to blog writing this was really helpful in understanding more about heart diseases and I’m really excited to dig deep more and curate valuable context.
Keep up the good work.
Great read and helpful, Thanks.
I’m already on 20mg rosuvastatin daily and adhere to a low-carbohydrate diet. My ApoB is still 116 and I don’t know what to do to lower it further.
No diabetes, BMI of 21, good waist/height ratio.
Typically, should the statin be increased or should a PCSK9 inhibitor be added?
I am also not sure about diet. I eat low-carb with a lot of vegetables. I don’t consume much saturated fat (a little from cottage cheese.) Is the low-carb or Esselstyn-type diet superior for this condition.
I have done a ton of research and I’m stuck at this point. It’s VERY frustrating.
I’ve had CD for years, asymptomatic responses to stress tests, stent implementation, and currently take 10mg crestor and 10mg Ezetimibe. I make sure to have protein with every meal and try to keep my diet in check. I’m not afraid of dairy or occasional red meat. After all, my blood type is O+. Like you, I do not suffer from other diseases. My numbers are cholesterol 113, LDL 38 and Apob 49. I attribute much of that numbers success to meds and diet but I believe I’ve only been able to achieve them, along with good health, with a vigorous exercise program I’ve maintained for 40+ years. I exercise heavily at least 3X per week, incorporating resistance (weight) for 45 minutes, 20 minutes of intense aerobics (twice resting heart rate) and stretch/relaxation for 20 minutes. As a male, loss of muscle mass is always an issue and I believe that resistance training aids in slowing that process. I think that’s important for females, too. I’m now 75 and able to maintain my training regimen and active life, even with arthritis. In fact, I think muscle support for my joints through resistance training is an anti-arthritis remedy. I’m not fat, not overweight, and don’t have, as Arnold would say, “girly, old man arms.” I say this because I did not see anything in your remarks regarding regular, intense exercise. While my BMI may be 25-26, it is the result of muscle mass rather than fat. And when I say aerobic exercise, I don’t mean walking on a treadmill and reading with headphones on. If you are exercising at a sufficient intensity, you should have trouble talking and should be breathing heavily. I would be interested to hear from you in six months if you initiate a solid exercise program. I’d bet you would be very happy with your ApoB results…good luck
Try eliminating refined carbs, adding whole grains and legumes, and eliminating all meat, fish, dairy, and eggs from your diet. See https://nutritionfacts.org/ for a guide to a plant-based, whole food diet.
I’m in the same situation and would love an informed opinion. The Esselstyn diet seems highly unnatural. Though I am already 95% vegan, he takes it a step further by requiring nearly 0 fat, which would be very difficult for me to do. Curious about the value of doing this and whether it can help with those of us who have high Apo(b) but otherwise good health markers. Are there other options?
Doesn’t ApoB more or less track with particle size? When broken down by particle size, large and medium LDL particles have no association with heart disease, but small dense LDL particles are greatly associated. So isn’t ApoB basically just a proxy for Small-LDL-P? Kind of like triglyceride/HDL ratio is a proxy for particle size as well?
Tough when this test is rarely available. Low carb diets can increase LDL-C through legitimate processes – but LDL-P remains uncertain.
More sand, but how many trucks?
Thank you for this post.
Two questions- hasn’t it been shown that the body makes cholesterol irrespective of cholesterol ingested? Other dietary factors drive high cholesterol?
“The normal range for apoB is 40-125 mg/dL.”
I believe these numbers are normal for the American population- which overwhelmingly suffers from metabolic disorder, with a significant percentage of that undiagnosed. In other words- aren’t they very high?
I am not a doctor, but my low carb diet over the last three years has led my internal medicine doc to take me of my diabetes pill to see if I can maintain a HbA1c below 6 for me a 76 year male. I am 5’10, 31 waist and 148 lbs. No joint pains and never get the flus. The health care system concludes that a diabetic suffers from metabolic syndrome and LDL needs to be below 2 mmol/l and a statin is prescribed. I am on 5mg Crestor. LDL is 1.49/mmol/L
Why then do I keep discovering that this conclusion comes from studies using a population base that is typically on a high carb diet (the pyramid) This diet that includes fructose contributes to the glycation of LDL and this small LDL is likely more damaging to the arteries. Fluffy LDL, I read, actually heals arteries. But statins prevent this healing function and may trigger the onset of diabetes. In lay terms when you discover the fire fighters as the only ones at the scene of the fire, you could suspect they started the fire. What I need to know is whether the ratio of Triglycerides to HDL is a more reliable yet an imperfect predictor of the risk of heart disease over the next 10 years for me than LDL Thank you
“the status/permeability of the endothelium, the number of apoB containg particles, external facors like smoking, the presence of diabetes etc.”
Whole food bland based diet solves this problem…Nitric Oxide production and endothelial repair: see Dr. Caldwell Esselstyn ‘s work.
So much virtue signaling in these posts. We have the Low Carb High Animal Fat zealots who want to convince themselves that high ApoB is not a problem as long as your Trigs are low and HDL high and we have the Esselstyn nuts who believe his lie that plants can magically reverse clogged arteries. Then we have outcome based data from quality studies in humans confirmed by Mendelian randomization that high ApoB independent of ANY other risk factors (inflammation, particle size, HDL, trigs you name it) is causal in CVD. People with genetically crazy low ApoB have 0 heart disease. And low carb is awesome btw, provided you do it plant based or Mediterranean style. All the LC benefits without the strokes and heart attacks. Win win.
snarky! I like it! Hearing more and more docs that maintain up to date knowledge of the latest research say “all they care about is ApoB”. HDL, LDL, HDL/LDL ratio, triglycerides, etc all are meaningless except ApoB. Currently so few people are tested for ApoB; they are only guessing at the healthy range and “who” are getting tested??? Mostly people w problems.