High Cholesterol
Introduction
With cholesterol testing at health fairs and drug stores, and with a breakdown of fat and cholesterol counts on all the packaged food we eat, you are probably well aware of the relationship between high cholesterol and heart disease. Yet, heart disease remains the leading cause of death in the United States; and you may not always eat the healthy, low-cholesterol diet that you should.
Because of the important relationship between high cholesterol and heart disease, all adults over the age of 20 years should have a fasting lipoprotein profile [a complete cholesterol profile--includes measuring total cholesterol, triglycerides, low-density lipoprotein(LDL) and high-density lipoprotein (HDL)] checked at least every 5 years. This should occur more often if a family history of coronary heart disease exists. Most children do not need to have their blood cholesterol level checked.
What is it?
Cholesterol is a soft, waxy, fat-like substance the body needs for cells to grow and regenerate. Cholesterol comes from two sources: your body and the foods you eat. The body makes its own cholesterol in the liver, and it only takes a small amount of cholesterol in the blood to meet your body's needs. However, because cholesterol can be found in foods such as red meats, whole milk dairy foods, and egg yolks, eating too much dietary cholesterol can make your blood cholesterol levels increase. Too much cholesterol circulating in the bloodstream is known as hypercholesterolemia.
Hypercholesterolemia increases the risk of heart disease because it can lead to atherosclerosis, a condition in which fat and cholesterol are deposited on the walls of the arteries. Atherosclerosis can occur in arteries throughout the body, including the coronary arteries (those feeding the heart). In time, narrowing or clogging of the coronary arteries by atherosclerosis can produce the signs and symptoms of heart disease, including angina (chest pain) and heart attacks.
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| When cholesterol builds up in arteries, it forms plaques which block blood flow and deny oxygen to the heart. |
There are a number of types of cholesterol:
- Low-density lipoproteins (LDLs) are often referred to as "bad cholesterol" because LDL cholesterol carries cholesterol to the body?s tissues, including the arteries. Elevated levels of LDLs can lead to heart disease.
- High-density lipoproteins (HDLs) are referred to as "good cholesterol" because HDL cholesterol carries cholesterol from the tissues to the liver for removal from the body. Elevated levels of HDLs can prevent heart disease.
- Triglycerides are a storage form of fat. Elevated levels of triglycerides may also increase the risk of heart disease.
What causes it?
Many factors appear to contribute to the development of high cholesterol:
- Heredity--Your genes partly influence how your body makes and handles cholesterol.
- Your diet--A high intake of saturated fat, dietary cholesterol, and excess calories can cause your cholesterol levels to increase. Being overweight can increase your LDL levels and decrease your HDL levels.
- Age and gender--Cholesterol levels begin to increase in both men and women beginning around 20 years of age. Premenopausal women usually have lower levels of cholesterol when compared with men of the same age. After menopause, a woman's LDL cholesterol level typically goes up, as does her risk for heart disease.
- Other medical conditions--Conditions such as diabetes, liver disease, thyroid disease, or kidney disease can cause elevated cholesterol.
- Lack of physical activity--Increased physical activity lowers LDL and raises HDL levels. Lack of exercise can cause the opposite.
High Cholesterol Leads to Heart Disease
Cholesterol is a lipid - or fat - that is created from other nutrients in the liver, and is also obtained from animal products in the diet (red meats, dairy products, etc.). Because cholesterol is a fat, it does not dissolve in the blood. Instead, it connects with proteins to form small globules known as lipoproteins. There are four types of lipoproteins: they are chylomicrons (pronounced: ki-low-my-krons), very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL).
Chylomicrons are the lipoproteins that transport fats that have been broken down in the gut after a meal, to tissues in the body where they are used and stored. These fats are known as triglycerides. VLDL transports triglycerides and cholesterol to similar sites where they are either used or stored. When chylomicrons and VLDL reach tissues, an enzyme splits off the fatty acids and glycerol, leaving the cholesterol. The remains of the chylomicrons continue to circulate in the blood until they reach the liver, where they are broken down. At the same time, the remains of the VLDLs are converted into LDLs and are also cleared from the circulation by the liver. Liver cells that break down LDLs are equipped with special receptors that attract LDL, removing it from the bloodstream, and breaking it down for use in the cells. Variations in these receptors are believed to play a role in the ability of an individual to remove "bad" cholesterol from their bodies. It has been found, for example, that patients with familial hypercholesterolemia (high cholesterol that is hereditary or ?runs in the family?) have defective LDL receptors. If too few receptors are present or if they operate abnormally, LDL levels build up in the blood.
Researchers have also found that a high fat diet not only increases the amount of fat in the bloodstream, but also causes the liver to reduce the number of LDL receptors. With fewer receptors taking in the LDLs, the levels of LDLs and total cholesterol (TC) in the blood increase.
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| Receptors on cell walls attract LDL cholesterol, remove it from the bloodstream, and convert it for use by the cells. If there are not enough receptors or if they do not operate properly, LDLs build up in the blood. |
While high blood triglyceride levels alone do not necessarily cause atherosclerosis, some lipoproteins that are rich in triglycerides also contain cholesterol. Furthermore, high triglycerides are often accompanied by other factors, like low HDL levels or a tendency toward diabetes. Therefore, high triglycerides may be a sign of a lipoprotein problem that contributes to heart disease.
HDL (sometimes referred to as the "good" cholesterol) plays a different role. It clears cholesterol from cells and helps transport it back to the liver. That is why low HDL levels are considered as important a risk factor for heart disease as high LDLs.
High levels of both LDLs and certain types of VLDLs increase the risk for coronary atherosclerosis. This is why LDL is called the "bad" cholesterol. Researchers believe that the reason these types of cholesterol play a role in building up plaque in the arteries is because of their size. These particular lipid globules are small, and when they come into contact with the cells lining the arteries, they are more easily trapped than larger globules. When cells in the artery wall absorb the cholesterol, they form a bump. This cholesterol-rich bump becomes covered by a hard-coated cap, creating what is called a plaque. Oxygenis also believed to be involved in this process. The LDL cholesterol globules are absorbed into the artery walls when they are oxidized. This is why some clinicians recommend the use of vitamins that prevent oxidation (antioxidants) to help decrease atherosclerosis, although the scientific evidence to support this is weak.
It appears that differences in the size of the LDL particles play an important part in predicting the risk of heart disease. In March, 1999, researchers at the University of Washington School of Public Health and Community Medicine reported studies showing that for every nanometer (a billionth of a meter, which is very, very tiny) decrease in low-density lipoprotein (LDL) particle diameter or size, heart disease risk increases from 30 to 230 percent, depending on the population studied.
Plaques come in
various sizes and shapes. Doctors used to believe that the largest plaques were
the most dangerous, and the ones most likely to cause total blockage of coronary
arteries. In fact, these plaques are most likely responsible for causing angina (chest pain).
This plaque buildup narrows the space in the coronary arteries through which
blood can flow, decreasing the supply of oxygen and nutrients to the heart. If
not enough oxygen-carrying blood can pass through the narrowed arteries to reach
the heart muscle, the heart responds with the pain that is called angina. The
pain usually happens with exercise or physical exertion when the heart needs more oxygen. It is
typically felt in the chest or sometimes in other places like the left arm and
shoulder. However, this same inadequate blood supply may cause no symptoms.
Small plaques,
that block less than half of the artery opening, are often invisible on many of
the tests doctors use to identify coronary heart disease. However, these small
plaques are now thought to be very unstable and more likely to rupture or burst.
The rough edge left over from this rupture attracts platelets and other clotting
factors to the site of the plaque causing a blood clot to form. If the blood clot totally blocks the artery,
it stops blood flow and a heart attack occurs. The muscle on the far side of the
blood clot does not get enough oxygen and begins to die. The damage can be
permanent and in some cases, deadly. Who has it? It is estimated that 100 million American adults have total blood cholesterol values of 200 mg/dL and higher--desirable total cholesterol levels are below 200 mg/dL. This desired level may be lower for those who have already had a heart attack or for those at risk for heart disease because they smoke, have hypertension, or have diabetes. There are about 13.2 million Americans with known coronary heart disease and about 8.7 million adults without formally diagnosed coronary heart disease. Interestingly, about 10% of adolescents age 12 through 19 have total blood cholesterol levels of greater than 200 mg/dL. This may be due to the increasing rates of obesity among children and adolescents. There is compelling evidence that the development of atherosclerosis begins in childhood and progresses slowly into adulthood.
The good news is that medications and healthier lifestyles are making a difference. Today, the number of Americans with a desirable blood cholesterol level (less than 200 mg/dL) has risen to over 51% and the average total cholesterol in this country has fallen from 220 mg/dL in the early 1960s to 203 mg/dL in 2002. But, we still have a long way to go.
What are the risk factors? A high fat diet, lack of exercise, and a family history of high cholesterol or heart disease will all increase your risk for high cholesterol and heart disease. If you have high cholesterol, the additional risk factors for developing heart disease include the following:
Additional Factors that May Increase Risk
Metabolic Syndrome, a collection of several health risks and problems, can place you at greater risk of developing heart disease, stroke, and diabetes. It is estimated that 1 in 5 Americans has metabolic syndrome, including 43.5% of people 60 to 70 years of age. Although the cause is unknown, researchers believe that it's related to many factors including diet, family history, and the amount of exercise a person gets. Diagnosis of this syndrome includes 3 or more of the following risk factors: People with established heart disease and metabolic syndrome are considered to be at ?highest risk? for heart problems. This risk is increased even more in people with diabetes. Many of these very high risk patients have a more aggressive LDL (bad cholesterol) goal of less than 70 mg/dL compared to less than 100 mg/dL to 160 mg/dL for healthy individuals.
What are the symptoms?
Before the onset of heart disease, high cholesterol does not usually produce symptoms in and of itself. Without obvious health effects or symptoms, the average person has a hard time making needed diet and exercise improvements. The following are signs or results of high cholesterol:
- Coronary heart disease
- Heart Attack or stroke
- Peripheral arterial disease (narrowing of the blood vessels that deliver oxygen-rich blood to the legs, abdomen, pelvis, arms or neck)
- Inflammation of the pancreas
But any heart patient will tell you, the time to make changes is long before chest pain hits. When "bad" cholesterol blocks arteries in a condition called atherosclerosis, the results can be debilitating and even fatal.
How is it treated?
Treatment of high cholesterol is aimed at lowering the low-density lipoproteins (LDL) or "bad cholesterol," lowering triglyceride levels, and increasing the high-density lipoproteins (HDL) or "good cholesterol." Decreasing total cholesterol by 10% can result in a 30% reduction in coronary heart disease incidence. For every 1% decrease in LDL (bad cholesterol levels), heart disease rates drop 2%. On the other hand, for every 1% decrease in HDL, there is a 2 to 3% increase in the risk of heart disease.
A low fat/low cholesterol diet and exercise are essential in helping to lower cholesterol and to maintain low cholesterol levels. While drug therapy is often needed to lower cholesterol, diet and exercise are additionally recommended to help the drug therapy lower and control cholesterol levels. Patients with established cardiac disease and multiple risk factors (metabolic syndrome, diabetes, or smoking) are sometimes given more intense lifestyle changes. To learn more about diet and exercise, click on the "Helping Yourself" section above.
The decision to start a patient with dietary therapy or drug therapy is usually based on a patient's LDL cholesterol levels, presence of heart disease, and risk factors. Your doctor should calculate your "10-year risk" (also known as a ?Framingham Risk?) for developing heart disease and use that risk estimation to decide if and when to start cholesterol-lowering therapy either through dietary modifications or medications.
Your goal LDL level will also depend on the above-mentioned factors. The following table illustrates guidelines that will aid your health care provider in making these decisions.
| Patient Category | LDL Level | LDL Goal |
| Without heart disease and with less than 2 risk factors | LDL greater than 160 mg/dL start diet therapy + exercise LDL greater than 190 mg/dL start drug therapy (160 to 189 mg/dL: LDL-lowering drug optional) |
less than 160 mg/dL |
| Without heart disease and with 2 or more risk factors with a 10- year risk less than 10%* | LDL greater than 130 mg/dL start diet therapy + exercise LDL greater than 160 mg/dL start drug therapy |
less than 130 mg/dL |
| Without heart disease and with 2 or more risk factors with a 10- year risk 10 to 20%* | LDL greater than 130 mg/dL start diet therapy + exercise LDL greater than 130 mg/dL start drug therapy (LDL 100 to 129 mg/dL: drug therapy optional) |
less than 130 mg/dL (optional goal: less than 100 mg/dL) |
| With heart disease | LDL greater than 100 mg/dL start diet therapy + exercise LDL greater than 100 mg/dL start drug therapy(LDL less than 100 mg/dL: drug therapy optional) |
less than 100 mg/dL(optional goal: less than 70 mg/dL**) |
| With Type 2 Diabetes Mellitus | LDL greater than 100 mg/dL start diet therapy + exercise LDL greater than 100 mg/dL start drug therapy(LDL less than 100 mg/dL: drug therapy optional) |
less than 100 mg/dL(optional goal: less than 70 mg/dL**) |
| *10-year risk calculators are available at on DrugDigest under the ?Interactive Tools? tab. **In patients that are ?very high risk? (those with established heart disease and multiple major risk factors including diabetes, metabolic syndrome, and current smokers), a more aggressive LDL goal of less than 70 mg/dL may be encouraged |
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For the initial drug treatment of hypercholesterolemia, HMG-CoA reductase inhibitors (also called "statins") are often used because of their effectiveness and low incidence of side effects. Currently, six statin drugs are available. The choice of which to use will depend on how much cholesterol reduction you need, doctor's preference, and prescription insurance benefits. Studies have shown that certain high risk patients, such as those with diabetes, benefit from cholesterol lowering therapy with statins. To learn more about how the statins compare to each other, visit our "Compare Drugs" section.
Other drug classes that may be used to treat hypercholesterolemia include bile acid resins, nicotinic acid, fibric acid derivatives, and cholesterol absorption inhibitors. Some of these drugs can be used in combination if a further reduction in cholesterol is needed.
If you specifically have elevated triglyceride levels, a fibric acid derivative or niacin may be most effective for you. Both medications work by decreasing the liver's production of triglycerides. Additionally, fibric acid derivatives (or "fibrates") such as gemfibrozil also increase HDL-C (good cholesterol) production.
Bile acid resins are mainly used in young adults with hypercholesterolemia or in combination with another cholesterol-lowering medication. These drugs interact with several medications including carbamazepine, gemfibrozil, and thyroid medication as well as several blood pressure medicines and antibiotics. These medications should be administered at least 1 to 4 hours before or 4 to 6 hours after these cholesterol lowering agents. Please evaluate your medication list on our Drug Interaction Checker.
Cholesterol absorption inhibitors are a new class of cholesterol lowering agents and work together with statins to lower cholesterol. This class of drugs works to lower blood cholesterol levels by absorbing excess cholesterol (from foods) in the intestines and thus blocking cholesterol's entry into the bloodstream. In a study published by the Mayo Clinic in May 2005, it was found that the addition of Zetia (a cholesterol absorption inhibitor) to statin therapy may cause a further reduction in a patient?s cholesterol levels. It is thought that this reduction may be the result of the two drugs working together but at different areas of the cholesterol production pathway. In fact, one pharmacy manufacturer combined Zetia with a commonly used statin known as Zocor. This combination product is called Vytorin. However, as with any medications it is recommended that you ask your doctor if this drug or combination of drugs is appropriate for you.
To learn more about these drug classes, click on the links below.
Helping Yourself
One way to have more control over your cholesterol is to know your score. Most people leave it up to their doctor to check their cholesterol but there are devices you can buy that will allow you to measure your cholesterol at home. There are currently two machines available to test cholesterol levels at home. The CholesTrak Home Cholesterol Test requires one to two drops of blood from your fingertip and takes 10 to 12 seconds to determine your total cholesterol. The BioSafe Cholesterol Test is also available, and it provides a total cholesterol reading as well as HDL and LDL levels. Performing this test requires three drops of blood to be placed on a special collection card and mailed to a certified laboratory for analysis. The results are returned to the patient or health care provider.
The guidelines used to treat high cholesterol recommend "Therapeutic Lifestyle Changes" (TLC) to reduce the risk of coronary heart disease. These TLC changes include:
- Reduced intake of saturated fats and cholesterol
- Therapeutic dietary options that can help reduce the amount of bad cholesterol (LDL) in your blood
- Weight reduction
- Increased regular exercise
Diet and exercise are key. To keep your cholesterol levels from going up in the first place, eat a healthy diet--low in saturated fat and cholesterol and filled with fresh fruits and vegetables, and exercise regularly, most days of the week. Losing weight if you are overweight or obese is also recommended.
The TLC Diet consists of:
- Saturated fat: Less than 7% of total calories
- Polyunsaturated fat: Up to 10% of total calories
- Monounsaturated fat: Up to 20% of total calories
- Total fat: 25 to 35% of total calories
- Carbohydrate: 50 to 60% of total calories
- Fiber: 20 to 30 grams per day
- Protein: Approximately 15% of total calories
- Cholesterol: Less than 200 mg/day
- Total calories: Just enough to achieve or maintain a healthy weight and reduce your blood cholesterol level (Ask your doctor or registered dietician for your reasonable calorie level.)
The recommendations for cholesterol and sodium are the same for everyone on the TLC Diet. You should eat less than 200 mg of cholesterol a day and no more than 2400 mg of sodium a day.
Changing your diet may be difficult or inconvenient but not changing it can be more problematic and even life threatening in the long run.
More than 75 percent of people who have high cholesterol can control it with diet, exercise, and weight loss. However, 25 percent will need drug therapy to lower their cholesterol levels to the desirable range. These people will typically need to take cholesterol-lowering drugs regularly for the rest of their lives. Since the major risk from high cholesterol is heart disease, it is very important for people with high cholesterol to also reduce their risk by:
- Stopping smoking
- Exercise and weight loss
- Appropriate treatment for high blood pressure and diabetes if present
What is on the horizon?
As awareness of the health risks of too much fat and cholesterol in the body increases, the demand for medications that can lower levels of cholesterol and fats is expected to grow. Scientists continue to search for natural cholesterol-lowering substances. In addition to research on the efficacy of oat bran in reducing lipid levels in the blood, scientists have found evidence of cholesterol-lowering properties in various berries. In Israel, scientists are investigating the properties of a substance called glabridin, which is found in the roots of licorice and anise plants. This substance appears to inhibit the oxidation of LDL-cholesterol, which is a factor in the build-up of arterial plaque. The licorice or anise plant grows mainly in East Asian countries, including Mongolia and Vietnam. In these countries, chewing licorice root is a common practice and atherosclerosis is less common.
As in other medical fields, exciting research is exploring the genetic roots of hypercholesterolemia. With growing knowledge of both the chemistry of lipids in general, and cholesterol production in particular, scientists are unraveling the genes involved in lipid chemistry in the body. They are also studying genetic alterations that either protect individuals from hypercholesterolemia or make them more vulnerable. This kind of research may eventually yield medications that are even more effective than those that are currently in use and are more precisely targeted to the biochemistry of the condition.
Researchers have found, for example, that some patients do not respond to statins, the most widely used cholesterol medication. They believe that genetic variations appear to make some individuals more responsive and others less so. In the future, patients may be genetically assessed so that they can be prescribed the particular cholesterol-lowering medication that best fits their genetic profile.
In another recent paper, researchers in Sweden reported finding a gene variant that helps keep bad cholesterol at bay and may reduce heart disease risk by 50%. In a study of 184 healthy men, the research group found that a variation in gene that codes for the microsomal triglyceride transfer protein (MTP) was linked to low levels of LDL-cholesterol. The gene for MTP provides the blueprint for production of the protein that helps assemble LDL. Individuals who carry two copies of the variant form of the gene had LDL cholesterol levels 22% lower than did those who had one copy or no copies of the variant.
Although the MTP gene was first characterized in 1993, this is the first report of a common genetic variant within the gene. Individuals with the variant produce extra MTP, which results in reduced production of very-low-density lipoprotein (VLDL). Some drug companies have already begun looking at MTP inhibitors to help lower LDL.
In April 1999, Canadian scientists reported findings that give a clearer understanding of how HDL cholesterol helps prevent heart disease. The scientists found that a particular enzyme that is bound to HDL acts as a powerful antioxidant within blood vessels. This enzyme is called lecithin-cholesterol acetyltransferase (LCAT). While scientists are still studying exactly how LCAT prevents oxidation, they hope that in the future they may be able to enhance the antioxidant activity of LCAT in the body. In addition to its involvement in heart disease, oxidative damage is also thought to be a causative agent in the development of cancer.
In July 2003, researchers reported that they have identified a thyroid hormone kind of molecule that may be able to help people lose weight and lower cholesterol. The molecule that they have identified has been doing just that in laboratory animals. The hormone helps reduce weight by increasing the body's metabolic rate (the rate at which the body breaks down food and uses it for energy), which also helps keep blood cholesterol low. But thyroid hormone can also have potential dangerous side effects, the most worrisome of which is an increased heart rate. The aim of this research is to produce a drug that gives the benefits of thyroid hormone without the side effects. Their effort is based on the relatively new knowledge that there are two kinds of receptors that receive the hormone and pass its signal to the body. Researchers are now working to verify these findings.
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High Cholesterol Health Condition Last Updated: July 2007
Note: The above information is intended to supplement, not substitute for, the expertise and judgment of your physician, pharmacist, or other healthcare professional. It is not intended to diagnose a health condition, but it can be used as a guide to help you decide if you should seek professional treatment or to help you learn more about your condition once it has been diagnosed.