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Women's Health and Fertility
Atherosclerosis and Coronary Artery Disease
Atherosclerosis is perhaps the single most deadly disease in North America, yet there is a good chance that most people, even those at high risk for heart disease, don't really understand how it develops. The fact is, long before any symptoms are clinically evident, atherosclerosis begins as a malfunction of specialized cells that line our arteries. Called endothelial cells, they are the key to atherosclerosis, and underlying endothelial dysfunction is the central feature of this dreaded disease.
Not every person who suffers from atherosclerosis has the risk factors we commonly associate with the disease, such as elevated cholesterol, but every single person with atherosclerosis has endothelial dysfunction. It is the uniting concept through which coronary artery disease must be understood. Atherosclerosis begins with inflammation and immune cell activation at the endothelial level, and they lead to endothelial dysfunction and eventually damage to the artery and formation of plaque. This process is hastened by high cholesterol, smoking, obesity, high blood pressure, and other risk factors for coronary heart disease.
In the world of conventional medicine, atherosclerosis is a widely misunderstood disease, perhaps because of a fundamental misconception about the nature of the arteries themselves. In this antiquated view, the arteries have been thought of as stiff pipes that gradually become clogged with excess cholesterol floating around the bloodstream. The solution recommended most often has been to reduce the dietary consumption of fats in order to lower levels of cholesterol, triglycerides, and low-density lipoprotein (LDL) in the blood. Conventional medicine's preferred method of reestablishing blood flow in clogged arteries is through surgery (coronary artery bypass graft surgery) or by insertion of catheters bearing tiny balloons that crush the plaque deposits against the arterial walls (angioplasty), followed by the implantation of tiny mesh tubes (stents) to keep the arteries open.
There are problems with this view, however. For one thing, the grafts used to reestablish blood flow can also develop atherosclerotic plaque deposits. The same was true for balloon angioplasty; in their early years, up to half of all angioplasty procedures “failed” when the arteries gradually closed again. Even today, with the use of improved stents, the failure rate is between 10 and 15 percent, and many people have to undergo repeat angioplasty or even surgery
Today, our understanding of atherosclerosis has literally redefined the disease. We now understand atherosclerosis as a chronic inflammatory disease that affects the way arteries function at the most basic level. Instead of viewing the arteries as pipes through which blood flows, we now understand that arteries are muscular organs that change and adapt to their environment and contract and expand in response to multiple factors, helping to raise and lower blood pressure and distribute blood throughout the body. Finally, we have begun to unravel the biochemical processes that underlie atherosclerosis.
This new understanding of atherosclerosis has yet to filter into mainstream medicine, but the most progressive and forward-thinking researchers are already developing novel ways to correct the endothelial dysfunction that underlies coronary heart disease. Life Extension Foundation is closely monitoring the state of research regarding this epidemic disease of normal aging.
Endothelial Dysfunction: Underlying Arterial Disease
The cause and progression of atherosclerosis are intimately related to the health of the inner arterial wall. Arteries are composed of three layers. The outer layer is mostly connective tissue and provides structure to the layers beneath. The middle layer is smooth muscle; it contracts and dilates to control blood flow and maintain blood pressure. The inner lining consists of a thin layer of endothelial cells (the endothelium) that provides a smooth, protective surface. Endothelial cells prevent toxic, blood-borne substances from penetrating the smooth muscle of the artery. They also respond to changes in blood pressure and release substances into the cells of the smooth muscle that help change the muscle tone of the artery. Furthermore, endothelial cells secrete chemicals that provoke a protective response in the artery after an injury. This protective response includes signaling smooth muscle cells and white blood cells to congregate at the site of an injury.
As we age, however, the endothelium becomes leaky, allowing lipids and toxins to penetrate the endothelial layer and enter the smooth muscle cells. As a result, smooth muscle cells gather at the site of the injury, and the artery loses some flexibility. In response, the endothelium signals white blood cells to congregate along the cell wall. These white blood cells produce pro-inflammatory substances, such as leukotrienes and prostaglandins, as well as damaging free radicals that attack the endothelium (Touyz RM 2005). Toxins soon begin to penetrate into the arterial wall, where lipids such as LDL, cholesterol, and triglycerides accumulate and become oxidized.
At this point, the atherosclerotic process has begun in earnest. In response to the oxidized lipids, the body mounts an intensive immune response that causes more white blood cells to attack the fats, producing more inflammation within the arterial wall. In an attempt to heal the injury, smooth muscle cells begin to produce collagen to form a cap over the injury site. The mixture of oxidized lipids, white blood cells, and smooth muscle cells forms a plaque deposit. Over time, calcium accumulates on the deposit and forms a brittle cap. If this calcified plaque ruptures, a blood clot can form, and the clot may result in a heart attack or stroke.
All the processes described above, in which the inner arterial wall is damaged and normal endothelial function is compromised, are collectively referred to as endothelial dysfunction. Evidence of endothelial dysfunction can even be found in adolescents who are genetically prone to atherosclerosis. While this process occurs naturally to some degree in all people, it is aggravated by the traditional risk factors for heart disease, such as smoking and obesity (two of the leading modifiable risk factors for coronary artery disease). The following are additional risk factors:
- Elevated LDL cholesterol . LDL is dangerous because it can penetrate the endothelial wall and contribute to the creation of lipid foam, which forms the core of a plaque deposit. Oxidized LDL cholesterol also triggers within the endothelium an inflammatory process that accelerates atherosclerosis.
- Hypertension . High blood pressure is known to aggravate endothelial dysfunction, and leading researchers have identified the endothelium as an “end organ” for damage caused by high blood pressure. Many studies have shown that high blood pressure is dangerous, and Life Extension suggests a target optimal blood pressure of 119/75 mmHg (or lower).
- C-reactive protein . Inflammation is central to the endothelial dysfunction that underlies coronary artery disease. One good way to measure inflammation is through levels of C-reactive protein (CRP). Studies have shown that higher levels of CRP increase the risk of stroke, heart attack, and peripheral vascular disease (Rifai N 2001; Rifai N et al 2001). Stroke patients with the highest CRP levels (greater than 33 mg/L) are two to three times more likely to die or experience a new vascular event within a year than are patients with low levels (less than 5 mg/L) (Di Napoli M et al 2001).
- Metabolic syndrome and diabetes . Metabolic syndrome is a cluster of abnormalities that, when they occur in the same person, dramatically elevate the risk of heart disease. These abnormalities include elevated triglyceride levels, insulin resistance, abdominal obesity, elevated blood pressure, and low high-density lipoprotein (HDL). According to recent data, this condition affects about 20 percent of adult Americans. Diabetes is also a significant risk factor for coronary artery disease. High circulating levels of blood glucose (and insulin) cause microvascular damage that accelerates the atherosclerotic process, partly by accelerating endothelial dysfunction (Beckman JA et al 2002).
- Homocysteine . High homocysteine levels contribute to inflammation and the production of free radicals that attack endothelial cells and raise thrombotic risk (Riba R et al 2004). Mild elevations in serum homocysteine (homocysteinemia) can be caused by nutrient deficiencies, including deficiencies in folate and vitamin B12. The Life Extension Foundation identified the role of homocysteine in cardiovascular disease in its November 1981 issue of Life Extension magazine. Life Extension's position has been confirmed by numerous studies showing that homocysteine, like cholesterol, is strongly associated with risk of heart disease (Haynes WG 2002; Guilland JC et al 2003).
- Elevated fibrinogen . Fibrinogen is involved in the blood clotting process. When a blood clot forms, fibrinogen is converted to fibrin, which forms the structural matrix of a blood clot (Koenig W 1999). Fibrinogen also facilitates platelet adherence to endothelial cells (Massberg S et al 1999). People with high levels of fibrinogen are more than twice as likely to die of a heart attack or stroke as people with normal fibrinogen levels (Wilhelmsen L et al 1984; Packard CJ et al 2000). This risk goes up even more in the presence of hypertension (Bots ML et al 2002).
Atherosclerosis: Not Just a Man's Disease
For years, many people believed that atherosclerosis primarily affected men. In reality, however, heart disease is the leading killer of women in the North America. Atherosclerosis tends to affect men and women differently and at different times in their lives. Before menopause, women suffer less from heart disease than men of comparable age. After menopause, however, the gap closes with age until eventually women become more likely than men to suffer from heart disease (Sans S et al 1997; LaRosa JC 1992).
Heart disease in women is often undiagnosed because its symptoms are often different from the symptoms men experience. Women are less likely to suffer from the chest pain traditionally associated with coronary artery disease in men (McSweeney JC et al 2003), and their heart attacks tend to be atypical (Sannito N et al 2002). Among women, the pain associated with reduced blood flow (ischemia) may be felt in the upper abdomen or back instead of the chest, and the symptoms of an actual heart attack (myocardial infarction) may also be different from those typically experienced by men.
The issue of women and heart disease is further complicated by conflicting messages about hormone replacement therapy sent by conventional medical research. For many years, doctors prescribed conventional hormone replacement therapy to reduce the risk of heart disease among menopausal women. In recent years, however, the wisdom of this approach has been called into question. Two arms of the large Women's Health Initiative study were stopped early when researchers discovered that women on conventional hormone replacement therapy were at a higher risk for coronary artery disease, heart attack, stroke, and breast cancer than other women. As a result of these findings, which were reported around the world, many women stopped using hormone replacement therapy, despite the possible benefits of estrogen therapy in reducing cardiovascular risk (Rosano GM et al 2003; Benagiano G et al 2004). Unfortunately, this study examined women using conjugated equine estrogens, which are estrogens derived from the urine of pregnant mares (Rossouw JE et al 2002).
resource: Life Extensions
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