Cholesterol's Effect on the Heart
Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.
As many as half of these deaths were probably due 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.
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.
- 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, the risk is compounded.
The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.
On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.
Effect of Total Cholesterol
Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was 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 the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.
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, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or 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, a 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 report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
- Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.
- 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 and allow blood to flow freely.
High Density Lipoproteins (HDL), the "Good" Cholesterol
High density lipoprotein (HDL) appears to benefit the body in two ways:
- It removes cholesterol from the walls of the arteries and returns it to the liver.
- It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.
HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly 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
Triglycerides are major troublemakers for the heart. They 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. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.
Some evidence also 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), also known as 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, few experts recommend 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.
