Cholesterol's Effect on the Heart
Coronary artery disease, commonly known as heart disease, is the leading cause of death in the US and was responsible for nearly 530,000 deaths in 1999.
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| Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain. |
As many as half of these deaths may be attributed to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.
Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.
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Click the icon to see an image of the developmental process of atherosclerosis. |
The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:
- Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe, cases to heart attack.
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Click the icon to see an image of a heart attack. |
- Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.
This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, a synergistic phenomenon occurs whereby the whole is more dangerous than the sum of its individual risk factors.
The effects of cholesterol on the heart may involve more than just one the arteries. There is some evidence unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even inhibit the protection that aspirin provides for people with heart disease.
On an encouraging note, however, mortality rates associated with coronary artery disease have dropped by over one-half during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management. Only 40% of people with high cholesterol levels actually die of heart disease, however, and experts cannot yet define which people are most at risk from high cholesterol levels.
Effect of Total Cholesterol
Studies consistently report a higher risk for death from heart disease with high (200 and higher) total cholesterol levels. The higher the cholesterol the greater the risk. So, for example, according to a 2000 study, men with total cholesterol levels higher than 240 mg/dL have a risk that is 2.15 to 3.63 times that of those whose cholesterol is below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.
Low Density Lipoproteins (LDL), the "Bad" Cholesterol
The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with lowest LDL levels. Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, it can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response.
Oxidation. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules called oxygen-free radical, also called oxidants.
- When LDL collects on arterial walls these oxidants are released from the wall membranes.
- Oxidants are missing an electron and tend to bind with other molecules in the body, which is the process called oxidation.
- When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.
Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:
- White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies are now reporting that this enzyme may play a major role in the release of the plaque-forming inflammatory factors.)
- Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.
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Click the icon to see an image of the cut section of an artery. |
- Immune factors that increase the risk for blood clots are also mobilized.
- Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels, allowing blood to flow freely.
Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.
High Density Lipoproteins (HDL), the "Good" Cholesterol
HDL appears to benefit the body in two ways:
- It removes cholesterol from the walls of the arteries and returns it to the liver.
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Click the icon to see an image of the liver. |
- It helps prevent oxidation of LDL. In fact, it appears to have antioxidant properties on its own.
HDL then helps keep arteries open and reduces the risk for heart attack. High levels of high-density lipoprotein (HDL), above 60 mg/dL, may be as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.
Triglycerides
Evidence now suggests that triglycerides may be major troublemakers for the heart. Triglycerides appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.
The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. It is the mechanism responsible for type 2 diabetes and occurs in common forms of diabetes, and with or without diabetes, is now believed to be a major risk factor for heart disease regardless of the presence of diabetes.
Some evidence further suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.
Lipoprotein(a)
Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), or lp(a). This lipoprotein falls somewhere between HDL and LDL in density and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, however, few experts are recommending drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences. (Men may be protected by the male hormone testosterone.) High levels are almost nonexistent in Asians, while they have been observed in half of African American. Caucasians carry medium risk.
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