Artherosclerosis- A Long Review

This blog post is about Atherosclerosis. According the National Institute for Health, Atherosclerosis effects about 1 in every 58 Americans, or about 4.6 million people in the United States. Obviously this disease is widespread and because coronary artery disease is associated with cardiovascular disease, it is important to know the ins and outs to stay protected, informed, and healthy! In this brief review of current medical literature, data, and peer-reviewed information I will attempt to outline the causative factors involved with atherosclerosis, tips to prevent developing it, and also debunk some myths. As a disclaimer, I am not a medical doctor or a research scientist, just a man with a passion to try to save the world, one carbohydrate at a time!

To begin with, the exact mechanism for developing atherosclerosis hasn’t officially been chiseled in stone. Researchers from many different camps, holding many different beliefs to be true are arguing, chastising, and muddying up research trying to prove their points as the one and only truth. The bickering won’t end because there is significant financial backing to all the camps, however if you listen closely you can hear the music. Just follow the money and you will find what preconceived notions these “un-biased” researchers are trying to prove. It makes sense, if General Mills is cutting you a 7-figure paycheck every year, you aren’t going to write a paper on how refined cereals are helping cause childhood obesity. Instead you’d pass the blame to the high-fat fast food industry or some other place that isn’t floating you the money. Anyway, the trick to get to the bottom of all the evidence is read as much as you can, compare studies, look at the author’s backgrounds, and make your best judgment in an educated way. This is what I’ve done and I’ve been reading this stuff for a couple years. This doesn’t make me an expert, but I like to think I started out as an unbiased naïve’ student and have taken in everything as a sponge. Without further ado…

According to the Medical Directory website, which is sponsored by the American Heart Association, National Heart, Lung, and Blood Institute, and the Texas Heart Institute atherosclerosis is essentially the hardening of the arteries, specifically the endothelium, intima, and other “layers” of the blood vessels. Plaques form in the arteries and are primarily made up of cholesterol, waste products of cells, calcium, fibrin, fat substances, etc. So there are two things at work here, the hardening of the arteries, and the development of the plaques. The hardening occurs because of aging, high blood pressure, and other diseases, most notably diabetes. It is important to note that diabetes is a very big risk factor for the development of atherogenesis. Diabetics, by definition, have a high level of insulin in the blood, also known as hyperinsulinemia. Basically the pancreas secretes insulin, but the cells in the body can’t absorb them because they are insulin resistant. Insulin is used to drive nutrients (especially glucose or sugar) into the cells. If the cells of the body can’t recognize or use insulin, the pancreas keeps pumping out more and more insulin to keep the blood sugar as close to normal as it can. Normal blood sugar is equal to about 1 teaspoon of sugar, and so you can imagine if someone is regularly eating starchy carbohydrates and is somewhat insulin resistant, or a full blow Type II diabetic, then they are going to need a lot of insulin to get all the sugar they’ve eaten to be absorbed into the cells. For the record, all carbohydrates are broken down into sugars at the end of the day, and a small potato is about five teaspoons, or five times what your normal blood sugar is. So the insulin resistant or diabetic person has all this insulin and sugar floating around in their blood because their cells aren’t responding to the normal insulin levels produced and we get what are called advanced glycation end products or AGE’s. These have also been referred to as free radicals, which cause oxidative stresses in tissues of the body, in this case the vascular system. The ways blood sugar and blood insulin make AGE’s is complex and beyond the scope of this brief blog, but for a more in depth look, pick up Protein Power by Dr. Michael and Mary Eades M.D. It’s a good read. Anyway, these free radicals react with the cells in the arteries by and cause damage. The damaged cells yield a product known as isoprostanes, which can be measured in the urine. Isoprostane levels in the urine or blood can determine how much free radical damage is occurring in the body, and people with diabetes or hyperinsulinemia (high levels of insulin in the blood) have higher isoprostane levels. A paper published in Journal of the American Medical Association called “Activation of Oxidative Stress by Acute Glucose Fluctuations Compared With Sustained Chronic Hyperglycemia in Patients With Type II Diabetes” reported this and went on to further say that the more fluctuation in blood sugar that someone had, the more oxidative stress and isoprostane production was going on. In lay terms, the more drastic the swings in blood sugar (as seen in diabetics, insulin resistant folks, and people following the food pyramid diet) a person had, the more oxidative stress we’d see. This lends itself to producing injury in the vascular tissue, among others, and leading to the beginning of atherosclerosis.

But wait there’s more….

The plaques we were talking about in the vessels don’t just arise from nowhere. Hypothetically, let’s say that a blood vessel is damaged, what happens? The inflammatory response is triggered, as it is every time something in the body gets damaged. Remember when you banged your knee against the table and it got red, hot, and swollen? That was the inflammatory response kicking in. You could feel it, because it was on the surface of your body. The same exact inflammatory response is taking place here, just inside the body where you can’t feel it. To coin a phrase from Dr. Barry Sears, this is called “silent inflammation”. Immune system molecules travel to the affected site to clean up debris, trigger the blood-clotting cascade (which contains fibrin, a molecule found within plaques), induce swelling for increased blood flow, among other functions. The damaged site is prone to absorbing very small, non-dense cholesterol particles (such as VLDL-very low density lipoproteins), and the fatty acids that make up every cell membrane (the outside of the cell) that were originally damaged end up in this matrix of junk and form a plaque. There are many other things that are going on here and continue to happen over time, especially with a lot of damage, but I seriously would write about another 10 pages on it and still not be done. Bottom line, the inflammatory response that is responsible for healing all damaged tissues in the body triggers plaques to be laid down in the vessels. The inflammatory response isn’t all-bad, though. We need it to repair tissue in the muscles and other injured tissues in the body. We just don’t want too much of it in our vessels.

Hypertension has also been touted as a big contributor to the development of hardened arteries and plaques. While high blood pressure can definitely be a sidekick to what is really going on, and cause the plaques to rip loose from the blood vessels, this should not be thought of as the root cause. P.J. Savage and M.F Saad wrote in the British Heart Journal that hyperinsulinemia is a major cause of increased smooth muscle in the vascular tissue (thicker blood vessels that can cause a more dramatic narrowing when stimulated), arterial wall lipid deposition (fatty acids and cholesterols deposited on the blood vessel), hypertension, and dyslipedemia (high levels of cholesterol or related molecules. Hyperinsulinemia can lead to high blood pressure because it increases Sympathetic Nervous System stimulation. This is your body’s “fight or flight” response. With respect to hypertension, sympathetic activation results in increased kidney sodium retention. You retain more sodium, and the water follows. This is especially true because elevated levels of insulin increase the number of aquaporins within the renal pelvis. These can be thought of as small floodgates that allow water to be reabsorbed into the body. Insulin opens them up. So hyperinsulinemia can cause high blood pressure and it can also cause dyslipedemia (high blood cholesterol levels) by increasing the amount of cholesterol your liver makes, which is specifically VLDL. Remember those guys? They are the ones that get deposited on the arterial walls. These aren’t my facts; they are the reviews and conclusions of many doctors who submit this stuff to peer-reviewed journals. So we can tell hyperinsulinemia is a bad mother.

But wait, there’s more….

In July of 1989 in the Archives of Internal Medicine Dr. Norman Kaplan wrote a ground breaking piece titled “The Deadly Quartet” and since it went into print, it has not been challenged, rebuked, or rebutted. Dr. Kaplan referred to this “quartet” as hypertriglyceridemia, hypertension, glucose intolerance, and central obesity. A similar paper has also been published by Dr. Gerald Reaven calling these four pathologies “Syndrome X”. At the center of the quartet was hyperinsulinemia. Dr. Kaplan reviewed many studies, and came to the conclusion that hyperinsulinemia was the root cause of high triglycerides, high blood pressure, glucose intolerance, and central obesity. Let me say that again, hyperinsulinemia is the root cause of all four of those problems! The big four are merely correlates of hyperinsulinemia. This means that not all of the big four may be present with hyperinsulinemia, but if any one or two are there, then there is a pretty good chance that hyperinsulinemia is also present. We also have to think that where there is smoke there is fire. If hyperinsulinemia is present, and we know if can cause one or all of the big four, then the chances of elevated levels of any of the big four are pretty good, even if they are not disease causing at that point.

But wait, there’s more….

Glucose intolerance is a pretty close relative of hyperinsulinemia. Not being able to tolerate glucose and having high levels of insulin go hand in hand. The Whitehall Study done by the University of London measured the glucose tolerance of a large group of both diabetic and non-diabetic adults. They classified them as diabetic, glucose intolerant, or healthy based on certain lab values and then followed these subjects for 33 years to see if they died from heart disease or lived a healthy life. The diabetic subjects were 3.7 times as likely to succumb to heart disease as the glucose intolerant or normal patients. That was expected, however. The borderline glucose intolerant and borderline healthy subjects (between 86 ng/dl and 95 ng/dl- the lab values used to designate this particular range) were only slightly better off, being only 3 times as likely to die from heart disease in 33 years. The optimal range ended up being 75ng/dl to 85ng/dl. This is considered normal to low by most labs, but these people had the lowest heart disease mortality among the subjects. Just to clarify how this test works, the subjects take a standard dose of glucose usually in the form of a sugary drink. Then at timed intervals there blood is drawn and blood sugar is measured. The more insulin resistant someone is, the higher their blood sugar will be after this test. So if a person is healthy, their blood sugar will be normal (lower) when the blood is drawn. So these subjects would have lower amounts of blood sugar floating around normally, lower insulin, and thus lower oxidative stress on the tissues, including the vascular system. Another interesting twist was that there were no differences statistically between the groups (diabetic, glucose intolerant, and normal) in their cholesterol levels (LDL and Total Cholesterol to HDL ratio). This means that having higher or lower cholesterol levels did not cause or prevent their mortality due to heart disease.

Moving right along, there has been a big push to lower fat intake, lower cholesterol intake, cholesterol levels, and to especially exile saturated fats to be “heart healthy”. A study published in The Journal of Clinical Nutrition entitled “Dietary Fats, Carbohydrates, and Progression of Coronary Atherosclerosis in Postmenopausal Women” followed 235 women with coronary artery narrowing as determined via angiography for 3 years. The women also reported their diets to the directors of the study. Those women with increase saturated fats in their diets had increase HDL cholesterol (good), lower total cholesterol (good), and lower total cholesterol to HDL ratio (very good). Their atheroslecrotic plaques did not grow and narrowing did not increase either. The researchers claimed these women now had a “better risk factor profile” than the other women. The other women ate more polyunsaturated fats and carbohydrates and had increased size of their plaques, and increased narrowing.

But wait, there’s more….

One of the biggest atherosclerosis studies ever done recently pulled a John Kerry and flip-flopped! The Framingham Heart study is one of the longest running heart, atherosclerosis, and cardiovascular disease studies that’s ever been done. In 1970, the director of the study wrote a brief review saying that people who had high blood cholesterol levels were at a high risk of atherosclerosis. He also said that because of the high cholesterol and fat content in the arterial plaques that high cholesterol levels in the diet and fat were one of the big causes of atherosclerosis. These are almost direct quotes, but as you can see he seems pretty sure of himself.

In 1992, the new director of the Framingham Study, Dr. William Castelli said in the Archives of Internal Medicine:

“In subsequent follow ups in metabolic ward-type studies higher saturated fat intake, higher cholesterol intake, and a higher calorie diet resulted in lower cholesterol levels”

Dr. Kannel wrote in the American Journal of Cardiology:

”It is not possible to select a critical lipid value that separates potential cardiovascular disease candidates from the rest of the population.”

In lay terms this means that it is impossible to set a value for total cholesterol or LDL cholesterol that separates those that are at risk for heart disease and those that aren’t. Dr Kannel went on to say that reducing fat in the diet gives us slightly lower LDL values, but drastically reduces HDL (the good stuff) values concurrently. In his opinion the best cholesterol related predictor of heart disease and atherosclerosis was the Total Cholesterol to HDL cholesterol ratio, even though he admitted this was a fairly weak correlate to heart disease in the grand scheme of things. His main point was that we want a relatively high HDL number, to get make our ratio better. Saturated fats anyone?

Uh oh.

So what can we do? There is so much information out there, and it seems as though every reporter, diet guru, or person hocking their get fit fast book is blubbering out the same mis-information. If we look at what relatively low carbohydrate diets have shown clinically we can get some answers.

To be fair, not every low carbohydrate diet it the Atkin’s diet. In fact, Atkin’s can be considered a ketogenic diet because it doesn’t allow much fruit or vegetables. But if we limit carbs to only fruit or vegetable sources, and increase fat accordingly, while eating enough protein, maybe even slightly more (not unlimited amounts), we are pretty close to a ketogenic diet and may even dip into ketosis depending on how much veggies and fruit are being eaten. Let’s see what happens.

A paper written for the Rejuvenation Research journal entitled ”Effect of Short Term Ketogenic Diet on Redox Status of Human Blood” the low carbohydrate diet increased total antioxidant status, uric acid levels, sulfhyldryl group content, and catalase and super oxide dimutase levels were unchanged. Antioxidants are good for us because they bind to free radicals and render them harmless. This lowers overall oxidative stress by reducing the amount of free radicals roaming about. So raising total antioxidant status in the blood is a good thing. Uric acid scavenges free radicals and prevents oxidative stress, so more of that is good news as well. Sulfhyldryl groups are also known as glutathione, which is an antioxidant made within the mitochondria (the engines within your cells). Increased glutathione is a good thing because it prevents the mitochondria from releasing free radicals when they make energy. It is also important that your body is making these things and you’re not just taking them from supplements, drinks, and pills containing antioxidants such as vitamin E and others. The problem is that these orally taken antioxidants never make it to the mitochondria, which is where we really need them. Also it is a good sign that catalase and super oxide dimutase levels remained unchanged when this diet was being eaten. These two substances are markers of oxidative stress, so if they had went up then we know the diet induced more oxidative stress and so the increased antioxidant activity would have all been a wash.
In conclusion, we just want to avoid inflammation, hyperinsulinemia, and eat a good diet that’s low in starch and sugar. The rest is up to you to get your learn on and find some answers to the questions that are plaguing you!