Chapter 2 - Life and Death of an Artery
Updated on February 1, 2003

How Arteries Develop

We begin life deep in our mother’s womb as a single fertilized cell. The cell quickly divides and multiplies into three layers. The outermost layer differentiates into our skin and sensory organs. The innermost layer becomes our digestive tract and our lungs. Sandwiched between these two layers is the mesoderm. As our embryonic body gradually grows, the mesoderm gives birth to blood vessels, connective tissue, bone, blood cells, muscles and many other internal organs. Blood vessels begin life as endothelial cells. As if by magic, these cells proliferate and form delicate tubes. The tubes burrow into every tissue of the body. Throughout our lives, the endothelial cells retain the ability to sprout new capillaries. No cell in our body is more than 50-100 micrometers (one millionth of a meter) from a capillary tube. An average animal cell is about 50 micrometers wide. Capillaries, the thinnest blood vessels, bring blood past every cell. Molecules pass to and fro in a never ending cycle of nourishment and cleansing. Thus, the body proper is linked through a vast river of blood with millions of tributaries.

By the time we are adults, the endothelium, which lines all of our blood vessels, has a surface area of 14,000 square feet, or the equivalent of six and a half tennis courts. With each heart beat, oxygenated blood surges through every organ, cascading down the pressure gradient created by the squeezing of our left ventricle. The blood flows first through large arteries, then the smaller branch arteries, then the smaller arterioles, and finally into the capillaries. The large arteries have circular smooth muscle cells wrapped around the endothelium. The muscle layer thins out as the arteries get smaller. In the capillaries, the only barrier between blood and tissue is the single layer of the endothelium.

The circulating blood flows past the endothelium in a never ending stream. In healthy arteries, the endothelium remains intact, a smooth, interlocking layer of cells. In diseased arteries, the endothelium becomes inflamed. White blood cells, the body’s intrepid warriors against a hostile environment, squeeze through spaces in the endothelium and enter the intima, just beyond. What causes this injury? Why are some of us protected? Why are others so susceptible? We are just beginning to unlock these secrets. In this book I will show you many of the factors that control this life and death process.

The Endothelium- Key to the Health of Your Artery

The diseased artery begins with a process called endothelial dysfunction. The endothelium, because of its strategic location, controls a host of key bodily functions. On the inner side of the endothelium is the blood. The endothelium, through chemical mediators, can initiate clot formation and inflammation, both intimately involved in atherosclerosis, heart attacks, strokes and other deadly arterial diseases. On the outer side of the endothelial cells are the vascular smooth muscle cells. Messages from the endothelium determine how permeable the artery wall is to substances in the blood. The endothelium can stimulate muscle cells to constrict or relax. The endothelium can also send out signals ordering the muscle cells to proliferate and become part of the plaque. As we shall see, the endothelium is the key to health and disease in the artery wall. Almost everything we do to achieve arterial health has its effect through the endothelium.

Our Paleolithic Heritage

Over long stretches of unmeasured time humans evolved to become supremely adept at survival. On the vast plains, in forests and jungles, our ancestors hunted wild animals and gathered wild fruits, vegetables, nuts and seeds. Over 100,000 generations, our genes evolved in response to the prehistoric environment. Then, 10,000 years (500 generations) ago, with the advent of agriculture, we began our transition to our current environment. But our genes are still optimally programmed for the conditions that existed prehistorically.

The cardiovascular system delivers oxygen, nutrients and molecular messengers to the tissues and removes wastes for transport to the lungs, kidneys or liver. What sort of environment is it programmed to live in? The Paleolithic environment provided a diet of fruits, vegetables, berries, nuts, fiber, fish, fowl and wild game. 20-40% of calories came from carbohydrates. But the carbohydrates were primarily fruits and vegetables carrying about 100 grams of fiber. Protein accounted for 20-35% of calories, mostly from lean sources of meat and fish and legumes. Fat provided 20-60% percent of calories. The ratio of omega-6 to omega-3 fatty acids was between 1:1 and 1:4. The diet was high in vitamins and minerals because of the freshness of the foods and the lack of cooking. Early humans consumed 7,000 mg of potassium and only 600 mg of sodium.

The cardiovascular system of our ancestors also evolved to handle dehydration, rapid bursts of energy for fight or flight situations, bleeding and infections. The sympathetic nervous system, through the action of neurotransmitters, primes the body for heightened activity and potential injury. The neurotransmitter noradrenaline speeds up the heart and constricts blood vessels. Noradrenaline is also released into the blood stream from the adrenal gland, along with adrenaline. Both make platelets more likely to clump together and initiate clot formation. Stimulation of the sympathetic nervous system and the adrenal gland also acts on the immune system to stimulate an inflammatory response. Our bodies are supremely primed to respond to potential blood loss and potential infection from wounds. Stress mediators also signal the kidneys to release substances that raise blood pressure and promote sodium retention, in case of sudden blood loss.

In our society, the diet is high in refined carbohydrates, saturated fats, and oxidized fats. It is low in fiber, vitamins and minerals, monounsaturated fats and omega-3 fatty acids. The combination of high calorie foods and sedentary habits means we consume more calories than we burn. The stress we experience tends to be chronic rather than acute. We sit in traffic, are time-pressured, have little control over our environment, and are forced to suppress hostile or fearful emotions.

How do our blood vessels respond to our modern environment? Let’s take a look at the artery wall as we age:

Birth to Fifteen Years Old

During our first decade of life the artery wall already shows signs of damage. Children under the age of ten have what are called fatty streaks. These thin lesions contain inflammatory cells. No one knows exactly why these lesions form. The artery wall becomes inflamed and permeable to LDL cholesterol and white blood cells. The LDL is altered through oxidation to become oxidized LDL. The oxidized LDL gets “eaten” by white blood cells called macrophages. The macrophages swell into foam cells, so called because the oxidized LDL gives them a foamy appearance under the microscope. These very early lesions most probably develop as a response to the diet.

Fifteen to Thirty-Four Years Old

In 1985 a study was published called the PDAY study (Pathobiogical Determinants of Atherosclerosis in Youth). Autopsies were performed on 3,000 young people who died in accidents. The study showed that all teenagers had fatty streaks somewhere in their arteries. Youths in their twenties had raised lesions, thicker than fatty streaks. These lesions have more cholesterol in them and more inflammatory cells. By the time they reached their thirties, one in ten of these young people already had advanced lesions with large lipid cores surrounded by fibrous tissue. Eight out of ten of those with advanced lesions were smokers. Other risk factors for more advanced lesions were obesity and high blood pressure.

Thirty-Five to Fifty Years Old

Plaque continues to form in new areas of the arteries. Plaque becomes more diffuse. It spreads down the arteries, creating more and more danger zones where clot can form. We begin to see the complex lesions that have broken through the wall and attracted platelets. The artery wall starts to resemble a combat zone, reflecting years of assault by the inflammatory machinery of the body.

Beyond Fifty

Plaque first forms in the aorta. Then it attacks the coronary arteries of the heart. Then it creeps into branch arteries of the aorta. These branch arteries distribute blood to the brain, the legs and all the other tissues of the body. Once we reach our fifties, rates of heart attacks start to climb because the quantity of plaque in some arteries reaches a critical mass. Also, the body’s ability to fight chronic stress and chronic inflammation starts to diminish. Many chronic diseases begin to become more prevalent. Of course, not everyone develops plaque at the same rate. EBCT scanning perfectly identifies how much plaque each of us has. Since men and women develop plaque at different rates, EBCT scanning shows higher plaque burdens in men than women at all ages. The calcium that collects in the plaque becomes visible to EBCT when its volume reaches the size that can be seen with special computer workstations. The smallest visible speck of calcium is about the size of a grain of sand.

Arteries with high plaque burdens are very prone to a process called plaque rupture or plaque erosion. An area of plaque in the wall of an artery is separated from the endothelium by a layer of fibrous connective tissue. Inflammation can break down this fibrous tissue, which provides structural support, and initiate a catastrophic break in the endothelium that leads to sudden clot formation. The clot may enlarge to the point where it occludes the artery, or it may break away and block the artery further downstream. These events are called heart attacks if the artery feeds the heart (coronary artery) or strokes if the artery feeds the brain (usually a carotid artery).

A fifty year old man who never smoked has a ten year risk of dying from a heart attack of 1% (one per hundred). By the age of seventy, his risk is 9% (nine per hundred). By the age of 80, the risk is 20% (twenty per hundred). For male smokers of the same age the risks are 3%, 14% and 30%. For women non-smokers the numbers are 0.4%, 5% and 15%, while for women smokers the risks are 1%, 9% and 26%. These are average numbers. Half the population will have lower risk and half the population will have higher risk. The risk is directly proportional to the plaque burden, which can be accurately determined by EBCT.

How Plaque Develops

As arteries age, their integrity is challenged. As we have seen, the wall can begin to suffer early in life. Plaque build-up gradually accumulates, spreading relentlessly if unchecked. By the time we reach forty, many people have advanced lesions just waiting to break down and cause blood vessel closures, which can have catastrophic consequences for the heart or the brain. Why do we develop plaque, and how can we arrest the process?

Plaque, or atherosclerosis, is a disease that involves several stages. The first stage is called endothelial injury. The endothelium is the single layer of cells directly in contact with blood as it flows through the arteries. Every small stress to our cells produces substances called reactive oxygen species, or free radicals. These molecules are constantly being generated. Even the process of energy production within the cell produces free radicals. Free radicals have an unpaired electron that attacks nearby molecules to find another electron. Free radicals can damage the cell membrane as well as cell DNA. Our cells produce antioxidants to neutralize free radicals. We also consume antioxidants in foods.

When free radicals attack the endothelium they cause an injury. This injury elicits an inflammatory response. The inflammatory cells are marshaled to help repair the injury. When the injury is prolonged or repetitive, endothelial dysfunction develops. Endothelial dysfunction is the underlying condition that leads both to atherosclerosis and hypertension, or high blood pressure. Endothelial dysfunction means the endothelium cannot normally dilate, and tends to remain constricted. The same process that causes constriction also causes chronic inflammation. Inflammatory cells move into the artery wall. The inflamed artery wall thickens as the inflammatory cells multiply and become engorged with LDL cholesterol that has been damaged by free radicals (oxidized LDL). Inflammation causes the smooth muscle cells in the wall to migrate and proliferate, adding more size to the plaque. Eventually, over many years, the inflammatory cells filled with oxidized LDL cholesterol burst open and form a lipid core, which is a large pool of lipids surrounded by smooth muscle cells, more inflammatory cells and connective, or scar tissue. The connective tissue can strengthen the plaque by preventing it from breaking through the endothelium. But inflammation can weaken the plaque by breaking down the connective tissue. When enough connective tissue breaks down, the lipid core ruptures through the endothelium to form an unstable plaque. The unstable plaque attracts platelets and clot-forming molecules. The clot can narrow or close the artery. When this happens, the muscle of the heart or the cells of the brain are at risk of death, because both the heart and the brain are the most metabolically active tissues in the body. Brain tissue in particular cannot survive without a constant flow of blood. Heart muscle can last longer, but even a transient decrease in blood flow can provoke dangerous rhythm disturbances in the electrical activity of the heart. Blood flow interruption also prevents heart muscle from functioning normally. Cardiac output goes down, causing an even greater decrease in blood flow the muscle, and setting up a vicious cycle.

The lifelong process of plaque build-up depends upon a chronic excess of free radicals and a chronic state of artery wall inflammation. Since free radicals are always being produced, an excess develops when there is an antioxidant deficit. A lack of sufficient antioxidants in the diet, coupled with dietary promoters of oxidation and inflammation, can lead to chronic oxidative stress due to chronically elevated levels of free radicals.

Stress and inflammation initiate plaque, and oxidized LDL fuels plaque growth. Our genes respond to stress by directing protein synthesis to restore cellular health. Since our genes developed to promote survival in the Paleolithic environment, they are not as adept at meeting the challenges imposed by chronic oxidative stress and chronic inflammation. A brief episode of oxidative stress induces genes to direct the synthesis of more antioxidants. Prolonged oxidative stress eventually overwhelms the cell’s ability to restore equilibrium. People who are more susceptible to plaque generally have genes that are least able to cope with chronic oxidative stress and inflammation.

Restoring and Maintaining Healthy Arteries

Being 3D Healthy means identifying your risks, setting your goals and following a program to achieve those goals. Lifestyle changes are the foundation of 3D Health, because they promote cellular equilibrium. Lifestyle choices profoundly influence the balance between free radicals and antioxidants, between acute and chronic inflammation, between artery dilation and constriction and between clot promotion and clot inhibition. I never recommend medications without first initiating appropriate lifestyle changes. Medications may lower cholesterol or blood pressure, but if the conditions promoting endothelial dysfunction are not treated, the arterial disease will continue to progress. 3D Health restores cellular equilibrium, thereby correcting the biological markers identified as plaque promoters. But before we discuss the different stages of 3D Health, lets look a little more closely at the key predictor of your risk- EBCT scanning.