Dare to Live

Chapter 1 What is arterial plaque, how does it form and why? Why do humans get plaque? What is plaque? What is it made of? Why does plaque form in some areas and not others? The answers to these questions may surprise you. The final question as to why some us get more arterial plaque than others is the summation of all the contributing risk factors I discuss in this book. Our understanding of atherosclerosis is still evolving and new risk factors continue to emerge. This is one reason why its is imperative to stay up to date if you are a doctor interested in preventive cardiology or if you are a patient keen on avoiding a heart attack. As I mentioned, atherosclerosis is a complex subject under continuous study by cardiology researchers. Plaque results from the process of atherosclerosis; and unchecked atherosclerosis often results in a heart attack. In the most basic terms, plaque is the body’s response to injury at the artery wall. We used to call the plaque in arteries a “callus” analogous to the thickening of the skin in response to mechanical friction and pressure. Injury comes in two types: mechanical and chemical. Mechanical injury includes arterial stretching caused by the effects of blood pressure on the artery wall and shear stress caused by the frictional forces of passing blood cells over the inner lining of an artery over a lifetime. Chemical injury includes factors such as oxidative stress (not enough antioxidants), dietary deficiencies, hormones imbalances, smoking, pollution, too much (or the wrong kind) of cholesterol, and lack of nitric oxide. The most common cause of a heart attack is plaque rupture. When plaque ruptures in a coronary artery, a clot may form and block blood flow to the heart. When plaque ruptures in the arteries feeding your brain, the clot can result in a stroke. Plaque is composed of lipids (fats and cholesterol), calcium, white blood cells, muscle cells, and connective tissue. It is metabolically active and can be hotter than surrounding tissues. White blood cells enter and modify the plaque by becoming part of its structure and by secreting enzymes that degrade the fibrous cap that covers the plaque. Plaque formation starts in early adulthood and progresses at varying rates depending on many factors. Generally, as plaque grows, more calcium accumulates within the plaque structure. Because cholesterol is a significant component of plaque, it became a major focus of drug research—to the detriment, I believe, of investigating other promoters of atherosclerosis. Though elevated cholesterol can accelerate atherosclerosis, is not the only cause of the problem. Some people with high cholesterol never get heart disease and others with normal cholesterol do. The reason for this is that not all cholesterol is the same. Plaque goes through many stages. Plaque usually progresses from being soft (and vulnerable to rupture) to a harder more relatively more stable stage. Because soft plaque is more unstable than hard plaque it is more dangerous. Mixed plaque contains soft and hard forms and is also likelier to rupture than hard plaque. Total plaque burden and rate of plaque growth also predict plaque rupture and heart attack risk regardless of plaque type. Plaque forms and becomes stable or unstable for complex reasons. The cells found in plaque— endothelial cells, smooth muscle cells, platelets (not a true cell), and white blood cells interact with their environment, such as during expansion and contraction of the blood vessel. The health of the blood vessel wall, the state of activation of the blood clotting mechanism, and inflammation are other interrelated processes that contribute to plaque formation. How Plaque Forms Exactly how and why plaque forms is still being researched. The “response-to-injury” theory is most widely accepted. The first step in this is endothelial injury. Normally the endothelium has a working defense system. When this defense system is compromised endothelial injury may ensue. Endothelial injury causes inflammation, and this attracts white blood cells which try to fix the damage. The endothelium is the layer of cells on the inside of the blood vessel that is in contact with the blood. Endothelial injury can be caused by oxidized low-density lipoprotein (LDL) cholesterol; infectious agents (viruses); toxins (heavy metals, cigarette smoke, pollution); elevated blood sugar; and metabolic by-products. Elevated levels of LDL cholesterol can overwhelm the endothelium’s defenses. If those defenses are inadequate or the LDL particles are too numerous, the LDL particle becomes oxidized and can cause a wide range of vessel wall dysfunctions that are associated with the development of atherosclerosis. We call this dysfunction Endothelial Dysfunction. Typical dysfunction includes impairments in relaxation/dilation of the artery, which elevates blood pressure and can further damage the blood vessel wall. These dysfunctions arise from the inability of a protective chemical called nitric oxide (NO) to do its job at maintaining a healthy vessel tone. The decrease in NO is associated with increased platelet stickiness and increased risk of clot formation, which can lead to heart attack and stroke. Furthermore, oxidized LDL can activate other inflammatory processes through acting on DNA. Oxidized LDL and inflammatory molecules can stimulate the DNA of the endothelial cell to produce more Toll like receptors (TLR). These receptors play a major role in activating the immune system by regulating production of immune system chemicals (chemokines and cytokines), which further promote atherosclerosis. Oxidation of LDL is common in smokers and people who have low antioxidant levels. This is why the role of antioxidants in heart disease has been a subject of continued research. Calcification The kind of plaque that shows up on a CT heart scan is calcified plaque. A heart scan is also called electron beam computed tomography (EBCT) or 64 slice cardiac CT. The calcium in the plaque is what the heart scan sees because the heart scan is really a fancy kind of x-ray and x-rays see calcium (think of bones). Calcification is the result of long-term inflammatory processes in the body and can occur in tendons, muscles, or any soft tissue or organ. Calcified plaque in arteries contributes to their hardening or stiffening. Calcification is an age-related process, so a limited amount is normal. Researchers are still studying why it occurs at all. Interestingly, some people who would appear to be high-risk have no calcified plaque in their coronary arteries. When I see this coupled with other risk factors I become concerned that the patient may have soft uncalcified plaque. I recommend a carotid media intima thickness (CMIT) test in these cases to determine if soft plaque is indeed beginning to form. Calcification involves vitamin D, vitamin K, phosphate, elevated serum calcium, genetic predisposition, and even blood pH. Elevated serum calcium (hypercalcemia) is usually the result of another condition such as hyperparathyroidism and needs to be evaluated by an endocrinologist. Calcium itself isn’t really the problem; its the underlying process that leads to the calcification can that is the problem, mainly inflammation. Patients on Coumadin, a common anticoagulant, have more coronary calcification that normal because this drug deactivates a protein that inhibits calcification (Schurgers, Cranenburg, & Vermeer, 2008). Coumadin also blocks vitamin K (Krueger, Westenfeld, Schurgers, & Brandenburg, 2009). Animal studies have shown that high doses of menaquinone, a type of vitamin K, can reverse calcification (Krueger, et al., 2009). We finally have some human trails proving this assumption, though more are needed. In 2000, researchers at Tufts University in cooperation with the US Department of Agriculture performed an intervention study on humans with coronary calcium as determined by a heart scan. In patients w