What Causes Cardiovascular Disease?

In my opinion, there is no single cause of cardiovascular disease (CVD). It can be multi-factorial. Indeed, there are many theories out there and it’s likely a combination of insults explained in these theories that promote CVD. To understand CVD we need to start with the structure of the arterial walls. Essentially arteries are tubes with various layers coated by epithelial cells on the inside. It is recurring damage to these cells that lead to plaque formation. The plaques are composed of lipids, cholesterol, calcium, fibrous tissue such as collagen and smooth muscle cells, inflammatory cells such as macrophages and foam cells, clotting factors such as fibrin and even accumulated cellular waste products. As the plaques build up, they narrow the vessel and can eventually occlude it. Sometimes the fibrous cap of the plaque ruptures leading to total occlusion and a heart attack. Essentially, blood flow to parts of the heart stops and the tissue starts to die. But usually, occlusion happens over time. There are three major coronary arteries that supply the heart with blood. As a plaque gets bigger, the amount of maximal blood flow decreases such that pain with exertion is the first symptom of narrowing. Over time, the blood flow may become more restricted until pain at rest occurs. There are ways to re-open the vessels by placing stents in them. But if the plaques are in several arteries, one may need to get surgery to graft new vessels around the plaques and restore blood flow. This is called a Coronary Artery Bypass Grafting (CABG).

What is very concerning is that the rate of CVD over the last 100 years has grown enormously. It was practically unknown before 1900. Now, it is the leading cause of death in the United States. What is interesting is that cultures that have remained on their traditional diets have virtually no CVD. It is only with the introduction of a western diet that CVD begins to show itself. Thus, something in the western diet that has arisen and grown over the last 100 years must be the culprit. Of course, diet may not be the only cause. Smoking, air pollution and other toxins may contribute as well. The recognizable things that have increased in the western diet is the addition of seed oils, the amount of carbohydrates and sugars and the ultra processing of foods. The one thing that has significantly decreased in the American diet is saturated fat. When these factors are added to the diets of native populations all over the world, CVD increases.

But what is it about seed oils and sugars that lead to CVD? They increase the amount of inflammation, glycation products and oxidative damage in the body. Seed oils contain omega 6 fatty acids, particularly linoleic acid, that raises the amount of Arachadonic acid in the body which then leads to inflammatory products. Linoleic acid also interacts with the endocannabinoid system in the body to raise hunger, much like the THC in marijuana does. Sugars and carbohydrates raise insulin levels which put the body in an anabolic state, one of building and fat storage. Further, they glycate, or add sugar moieties, to molecules inducing oxidative stress and free radical damage...essentially causing generalized damage and inflammation. It also leads to metabolic syndrome, insulin resistance and eventually Diabetes.

Anything that damages the endothelial cells lining the arteries leads to a repair process. When cells are damaged there is an inflammatory response where certain immune cells show up. When the epithelial cells need to be repaired cholesterol and the shuttle that carries it, LDL, arrives on the scene. Because there is damage, clotting occurs and those products present as well. It’s like a construction zone to shore up, clean up and then repair the area. However, the damage has been done and is rarely as good as new. A plaque forms during this process as supplies needed for repair buildup and debris is cleared away.

What are the insults that can occur to the endothelial cells? The first is direct physical stress. The artery is a tube and subject to sheer stresses of the flow of blood. There is a hairy, gel-like structure called the glycocalyx that covers the endothelial cells and protects against these sheer stresses. It also forms a barrier controlling the flow of molecules and cells from the blood into the arterial wall. It’s has anti-adhesive properties keeping blood cells from sticking to the arterial walls which helps prevent blood clots and atherosclerosis. It protects against inflammation and controls the movement of fluids. It is very important in protecting our endothelial cells. Factors that injure the glycocalyx include inflammation, high intra-vascular pressure (hypertension), oxidative stress and reactive oxygen species, inflammatory cytokines, bacterial endotoxins, hyperglycemia (elevated blood glucose), smoking and pollution, and oxidized LDL. When the glycocalyx is injured, the endothelial cells become directly exposed to these same factors. It may be for only a short time, as the glycocalyx repairs itself. But repeated insults leave irreparable damage.

Most of the damage to our endothelial cells comes from dietary and environmental stresses - essentially, what we put into our body, either from ingestion, absorption through our skin or breathing.

There has been the introduction and increasing consumption of seed oils (thank you Proctor and Gamble for creating Crisco), the increase in sugars, particularly fructose, and the processing of our food. We have also reduced the amount of fatty meat and total saturated fats that we eat. Another change is the availability of fruits and vegetables virtually all year round. One might think that eating fruits year-round might be a good thing. However, the size and structure of fruits have changed since our ancestral times. Fruit has fructose, a particular kind of sugar that has been linked to diabetes, obesity and CVD. There is a theory that eating fruits at the beginning of fall gave us an evolutionary advantage because it caused us to store fat for the cold periods [See my section on fructose and uric acid]. Yes, fruits can make us fat.

The first theory to explain heart disease was championed by Ansel Keys. The “Diet-Heart Hypothesis” claims that eating saturated fat raises cholesterol which then leads to CVD. There are several issues with this hypothesis. The first is that it was based on “The Seven Countries Study” which actually had data from 22 countries but Keys chose only seven that fit his hypothesis. Further studies to confirm this hypothesis never supported it. One was delayed in publishing for 16 years and anther was never published...until a scientist went in and found the data in the researcher’s basement and presented it. Both contradicted the Diet Heart Hypothesis [see below].

The Minnesota Coronary Survey: This was the largest test of the diet-heart hypothesis, involving 9,057 men and women over 4.5 years. The study compared a diet with 18% saturated fat against a control diet with 9% saturated fat. Despite the significant difference in saturated fat intake, the researchers did not find any reduction in cardiovascular events, cardiovascular deaths, or total mortality. Although the study was funded by the National Institutes of Health (NIH), the results were not published for 16 years after the principal investigator, Ivan Frantz, had retired. Frantz reportedly stated that there was nothing wrong with the study; they were just disappointed with the outcome

The Sydney Diet Heart Study (SDHS): This randomized controlled trial, conducted from 1966 to 1973, was not fully reported initially. When the previously unpublished data were recovered and published in 2013, it showed that replacing saturated fat with vegetable oil rich in linoleic acid significantly increased the risks of death from coronary heart disease and all causes, despite lowering serum cholesterol. This finding directly contradicted the traditional diet-heart hypothesis.

Another issue is that Homo sapiens, and our precursors, have been eating saturated fats for millennia, yet, it is now in the late 20th century that somehow it has become bad for us? Unfortunately, the FDA dietary guidelines were constructed from the Diet-Heart Hypothesis theory and it has been used since. Americans HAVE lowered saturated fat from their diet and CVD has still risen.

So if saturated fat is not leading to CVD, what is? I would argue that the best evidence points to the rise in seed oils and sugars in our diet. Let’s examine seed oils first.

In the early 1900’s Proctor and Gamble made the first seed oil for mass consumption called Crisco. It was made from cottonseed oil and was highly processed. The first attempt to use seed oils resulted in products that tasted horrible and went rancid quickly. But this new product looked like tallow and was marketed as new and glamorous. It was a success and now Americans use seed oils as their primary cooking source. And it is inescapable. It is in almost every food, especially processed ones. See my section on seed oils to discover how detrimental they are.

The other is the rise of sugars and carbohydrates in our diet. If one is told to decrease fats, particularly saturated fats, then one must increase the other macronutrients in one’s diet to compensate. Thus, carbohydrates and proteins must go up. And since a lot of proteins such as meats, contain fats then it must be carbs that increase the most.

Processed foods have been labeled by the food industry as a cheap and easy way to get the nutrients we need. But they are calorically high in sugars and seed oils. Some are “fortified” with vitamins and minerals. But generally, they are nutrient poor lacking the right proteins and fats. Being high in sugar, they raise insulin and lead to metabolic syndrome and diabetes. And this leads to a whole host of issues, such as chronic inflammation, glycation and oxidation in our bodies. For example, inflammation damages the glycocalyx, the protective barrier in our arteries, leading to endothelial cell damage. There is the oxidized LDL theory of CVD where normal LDL, which is not damaging to endothelial cells, get oxidized and THEN are damaging. But LDL, in and of itself, is not bad for you. It is the presence of inflammation and oxidative products brought on by our diet that damages them. Thus, drugs to reduce LDL are really a crapshoot. If you have bad LDL, you are lowering both good and bad LDL. And LDL is a necessary lipoprotein developed over millennia of evolution. We could not exist without it. Yet the pharmaceutical companies continue to tell us it is good for us to lower our lipoproteins (“cholesterol”). The drug Repatha has been shown to lower LDL to a level of 30 mg/mL. Yet studies have shown that this does not impact CVD and is actually detrimental. This is an example of treating the symptoms rather than the root cause.

In my opinion, the drivers for CVD are diet, particularly the Standard American Diet, and smoking of any kind. The Inuit which live in the polar regions had virtually no CVD or chronic illnesses. The Maasai in Africa had a diet comprised of mostly meat and cow’s milk. However, both were not immune to the spreading western diet and for the Maasai, more than 50% of their diet is now comprised of plant foods and both groups rates of CVD and diabetes have increased.

So what is in the western or standard American diet (SAD) that is causing CVD? It is seed oils high in Linoleic acid (an inflammatory Omega-6 fatty acid), the high amount of carbohydrates (particularly fructose) and the ultra-processing of foods. But one may ask, what about saturated fats, cholesterol and LDL? The Diet-Heart Hypothesis introduced by Ansel Keys has been debunked. Saturated fat is GOOD for you! Cholesterol is a molecule that is absolutely necessary for proper cellular function. LDL is a lipoprotein that is needed to carry fat soluble molecules around the body. It is not damaging until it becomes oxidized and/or glycated. The SAD causes chronic inflammation, hunger (lack of satiety), oxidation and glycation. These lead to diabetes, obesity, chronic renal insufficiency, polyneuropathy, dementia, gastrointestinal issues such as Crohn’s disease and Ulcerative Colitis, skin issues, peripheral vascular disease and CVD. The fact that cancer rates have risen dramatically over the last 100 years and are hitting younger age groups may be attributed to the SAD as well.

Right now, in the US, we are treating the symptoms of the SAD rather than correcting the root cause. We take pills for diabetes, hypertension, cholesterol (which is a scam, see my section on that) and now obesity. Shouldn’t we focus on why we have to do that? My guess is that Big Pharma, Big Food, Big Agra and Big sugar are making a lot of money off of our poor health and dietary patterns. And they influence government officials and those on the committee making our dietary guidelines.

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Ravnskov U, Diamond DM, Hama R, et al. Lack of an association or an inverse association between low-density-lipoprotein cholesterol and mortality in the elderly: a systematic review. BMJ Open 2016;6(6):e010401; doi: 10.1136/bmjopen-2015-010401.

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Siri-Tarino PW, Sun Q, Hu FB, et al. Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease. Am J Clin Nutr 2010;91(3):535–546; doi: 10.3945/ajcn.2009.27725.

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The Glycocalyx

Nieuwdorp M, Haeften TW van, Gouverneur MCLG, et al. Loss of Endothelial Glycocalyx During Acute Hyperglycemia Coincides With Endothelial Dysfunction and Coagulation Activation In Vivo. Diabetes 2006;55(2):480–486; doi: 10.2337/diabetes.55.02.06.db05-1103.

This is a 150-year detective story with a cast of unrecognized heroes who may, finally, become known for their work on the true causes of heart disease. Exploring the truth about cholesterol—the apparently tried, and convicted, cause of millions of deaths from heart disease—with billions spent each year on lowering cholesterol with diet and drugs.

Is it possible that our villain was simply left holding the gun whilst the true culprits ran and hid? Have they escaped our clutches?

Dr. Kendrick also introduces us to a range of other lesser known characters in this tale of selective reporting, data manipulation, and intrigue. The true story of heart disease is out there, and the evidence has been brought together here—a scientific mystery for our time that is ready to unfold.

Atherosclerotic Plaques

Stent Placement in an Atherosclerotic Plaque

The Maasai of Kenya: the consequences of an epidemiological transition D. Lund Christensen. Unit of International Health, University of Copenhagen, Copenhagen, Denmark

Cardiovascular Disease Susceptibility and Resistance in Circumpolar Inuit Populations Maria Tvermosegaard MD a b, Inger K. Dahl-Petersen MSc, PhD a, Nina Odgaard Nielsen MSc, PhD a, Peter Bjerregaard MD, DrMSc a c, Marit Eika Jørgensen MD, PhD

Mialon M, Serodio PM, Crosbie E, et al. Conflicts of interest for members of the US 2020 dietary guidelines advisory committee. Public Heal Nutr 2022;27(1):e69; doi: 10.1017/s1368980022000672.