High Cholesterol

Overview

Hypercholesterolemia, or high cholesterol, is a high level of cholesterol in the blood that can cause plaque to form and accumulate leading to blockages in the arteries (atherosclerosis), increasing the risk for heart attack, stroke, circulation problems, and death.

What Is Cholesterol?
Cholesterol is a soft, waxy fat particle (lipid) that circulates in the blood. It has several important functions in the body: it is a building block for all cell membranes and many sex hormones, and is the digestive substance released by the gall bladder.

The body produces cholesterol in the liver. The liver, in fact, produces almost all of the cholesterol the body needs. However, many popular foods contain cholesterol and the substances used to produce cholesterol particles, which can increase the amount of cholesterol in the blood.

Evidence that High Cholesterol Levels are Bad
Many studies have looked at the relationship between high cholesterol levels and heart attack and death. In one study of young men without known heart disease, cholesterol levels were measured and participants were followed for 6 years. During this time, researchers recorded heart attacks and deaths that occurred in the participants.

The higher the cholesterol level, the greater the risk for having a fatal heart attack. In fact, the risk for a fatal heart attack is about 5 times higher in those with a cholesterol level of 300 mg/dL or more than in those with a cholesterol level below 200 mg/dL.

The Framingham Heart Study is probably the most famous ongoing heart study in the world. Cholesterol levels, smoking habits, heart attack rates, and deaths in the population of an entire town have been recorded for over 40 years. After 30 years, over 85% of people with cholesterol levels of 180 mg/dL or less were still alive; almost 33% of those with cholesterol levels greater than 260 mg/dL had died.

There have been many studies examining the relationship between cholesterol levels and heart attacks and death. There is overwhelming evidence that high cholesterol levels increase the risk for heart attack, circulation problems in the legs, stroke, and death.

What Cholesterol Levels Require Treatment?
There is no formula to determine what level of cholesterol is considered "safe" and what level of cholesteral requires treatment. Cholesterol experts, including those who wrote the NCEP guidelines, have come up with general recommendations based on ongoing research.

The NCEP based its recommendations, in part, on the future risk for heart attack. This makes sense, because someone who has no risk factors for coronary artery disease or heart attack can tolerate a somewhat elevated cholesterol level. In someone with established coronary artery disease, the risks for heart attack (or additional heart attacks) and death are much higher, so even a mildly elevated cholesterol level must be aggressively treated.

NCEP recommendations are based on the LDL cholesterol level because it correlates best with risk for heart attack and death, and because treatment of the LDL level has been the focus of recent studies.

All these considerations make the recommendations a little complex. Fortunately, several general guidelines have emerged. Different physicians may suggest different levels at which therapy should be started, and different goals of therapy, so it is important to discuss your levels with your doctor.

Many physicians recommend that patients without known atherosclerosis should strive to lower their LDL cholesterol level if it is above 160-190 mg/dL. The more risk factors for coronary artery disease one has (e.g., diabetes, high blood pressure, cigarette smoking, history of premature heart disease in parents or brothers and sisters), the less tolerance there should be for high LDL levels. Most physicians agree that patients with known atherosclerosis whose LDL levels are above 100-130 mg/dL should be treated.

Target LDL Cholesterol Level
There is no golden number below which an LDL level is considered "safe." Target levels vary, depending on the individual. Again, one should discuss the goals of cholesterol therapy with one's physician. The following is presented only as a general discussion.

Many physicians follow the recommendations of the NCEP and establish a target LDL level below 130-160 mg/dL for patients without known atherosclerosis. For patients with no other cardiac risk factors (e.g., diabetes, high blood pressure, cigarette smoking, family history of premature heart disease), a level below 160 may be acceptable.

For those with multiple cardiac risk factors, a level below 130 mg/dL may be considered more desirable. For those who have atherosclerosis, many physicians believe LDL should be brought down to a level below 100 mg/dL, the target level set by the NCEP

Treatment

The treatment approach to abnormal lipid levels differs depending on which lipid is high. For the purposes of simplicity, the focus here is on management of a high LDL ("bad") cholesterol level.

There are basically two ways to lower LDL cholesterol: with medication (pharmacological therapy) and without medication (nonpharmacological therapy).

Nonpharmacological Therapy
Standard nonpharmacological therapy consists primarily of modifying eating and exercise habits. This therapy often modestly reduces LDL cholesterol but is not likely to lower the LDL cholesterol level by more than about 30 mg/dL.

When can nonpharmacological therapy be used?
For people without atherosclerosis and with modestly elevated LDL cholesterol levels, the urgency to treat with medication is not great. An initial 6-12 month trial of nonpharmacological therapy may be advised by some physicians. If the LDL cholesterol has fallen to an acceptable level within that time frame, the patient can continue with these interventions only. If the level remains high, however, drug therapy should be initiated.

Changing diet can decrease the cholesterol level by about 8%-14%, which may be enough to reach the target level in some cases. However, diet and other lifestyle modifications generally do not decrease LDL levels by more than 30 mg/dL. If your LDL level is notably elevated, you may want to discuss with your doctor the possibility of adding drug therapy to your treatment plan.

People with established atherosclerosis have the incentive to significantly lower their high LDL levels. Most practitioners agree that both drug therapy and lifestyle modifications are needed, particularly because there is such good evidence that medication significantly decreases the chances of having a future heart attack or stroke and increases the chances for living longer.

What lifestyle changes can bring about lower LDL cholesterol levels?
Several are commonly accepted as positively impacting elevated cholesterol levels:

• Diet. Minimize excess cholesterol and fat intake, especially saturated fat. These fats raise cholesterol levels more than any other substances. Cholesterol and saturated fats are found primarily in foods derived from animals, such as meats and dairy products. Unwanted cholesterol and fats lurk in many foods that might never be suspected of having high amounts of these substances. Here are some dietary guidelines for reducing cholesterol and fat consumption:

1. Eat lean fish, poultry, and meat. Remove the skin from chicken and trim the fat from beef before cooking.

2. Avoid eating commercially prepared and processed food (cakes, cookies, etc.)

3. Increase the relative amount of fruits, vegetables, breads, cereals, rice, legumes, and pasta.

4. Use skim or 1% milk.

5. Avoid breaded fried foods.

6. Eat no more than 2 egg yolks (or whole eggs) per week.

7. Use cooking oils that are high in unsaturated fat (e.g., corn, olive, canola, safflower oils)

8. Use soft margarines. They contain less saturated fat.

• Weight loss. Losing modest amounts of weight (even only 5-10 lbs.) can double the reduction in LDL levels achieved through an improved diet. Weight loss should be achieved gradually by modestly decreasing calorie intake and increasing exercise.
• Exercise. Exercise can decrease LDL levels and increase HDL levels to some extent. For example, taking a brisk 30-minute walk or a low-level jaunt on a treadmill 3-4 times a week is likely to positively impact the cholesterol profile. Patients with chest pain and/or known or suspected heart disease should talk to their doctors before beginning any exercise program.

Pharmacological (Drug) Therapy
The introduction of HMG-CoA reductase inhibitors (or statins) significantly advanced the treatment of hypercholesterolemia. Statins lower LDL cholesterol levels by 20%-40%. At maximum doses, they lower LDL levels by an amazing 40%-50%. They provide the added benefit of modestly increasing HDL ("good") cholesterol levels, usually by about 5%-10%.

These agents are usually well tolerated, have few side effects, and need to be taken only once or twice a day. Because the body produces cholesterol primarily during the night, most of these medicines should be taken after dinner or during the evening. A high dose can be split and taken once in the morning and once in the evening.

Should patients already taking one of the older types of cholesterol-lowering medications switch to a statin? Several things should be kept in mind. First, some people are possibly being treated with a different type of medication because the primary lipid problem may not be a high LDL level but some other abnormality, such as a markedly high triglyceride level.

Second, if treatment with an older type of medication is working well and the patient is satisfied, there's no reason to change. However, if the person doesn't take the medication regularly because it's hard to remember to take several doses every day, because it has unpleasant side effects, or because it has failed to lower the LDL to an acceptable level, it may be worthwhile to discuss switching to one of the statins with a physician.

Statins. Commonly prescribed statins include: atorvastatin (Lipitor®), cerivastatin (Baycol®), fluvastatin (Lescol®), lovastatin (Mevacol), pravastatin (Pravachol®), and simvastatin (Zocor®).

There are two rare but potential side effects associated with these medications. The first, mild inflammation of the liver, can be detected by simple blood tests (liver function tests, or LFTs). The tests are usually performed once or twice during the first several months of therapy and then periodically (e.g., twice a year) thereafter. The second very rare side effect is muscle inflammation, soreness, pain, and weakness. Because this occurs so rarely, no routine testing is performed. However, a patient who develops diffuse muscle pain or weakness should speak with his or her doctor.

Occasionally, even with high-dose statin therapy, the LDL level may not decrease sufficiently. In this case, another cholesterol-lowering medication may be added.

Other medications. These medications, when combined with a statin, may help lower cholesterol to an acceptable level. Patients should be aware that using the combination may increase the risk for liver and/or muscle inflammation. These drugs include: cholestyramine (LoCHOLEST®, Questran®), colestipol (Colestid®), fenofibrate (Tricor®), fluvastatin (Lescol®), gemfibrozzil (Lopid®), and niacin (Niacinol®, Niacor®, Nicolar®, Slo-Niacin®).

Alternative Treatment

Most alternative medicines and therapies have not been subjected to scientific investigation, making it hard to assess their effectiveness. Some objective information, however, has emerged.

• Garlic. The medicinal properties of garlic (used by the Babylonians and other ancient peoples in their medicines) continue to be debated. The debate has instigated a number of studies examining garlic's effect on cholesterol levels. When combined, the results of some of the earlier studies suggest that garlic may lower total cholesterol levels by an average of about 9%. However, some of the recent, more well-designed studies (in which half of the group was treated with garlic and the other half with a placebo) have found no beneficial effect produced by garlic on either total cholesterol or LDL levels. What can be concluded from this? The best that can be said, from a scientific point of view, is that garlic may at most have a modest effect on cholesterol levels but should not be used instead of other interventions.
• Oat bran. Oat bran mania swept across the United States a decade ago. Research (including one report published in the New England Journal of Medicine) found that oat bran, per se, had little impact on cholesterol levels. Rather, any beneficial effects were attributable to the fact that people were eating more oat bran and less fat.
• Cholesterol-lowering margarine. The Food and Drug Administration (FDA) recently approved two of these products, Benecol® and Take Control®, for marketing. These margarines contain plant-derived substances that can decrease the absorption of cholesterol in the digestive tract. They modestly reduce cholesterol by about 7%-10%. They should not be used instead of drug therapy but can be added to a treatment plan for hypercholesterolemia.