Cholesterol is a fatty substance that is essential for proper body functioning. But elevated blood levels of cholesterol increase the risk of coronary heart disease and heart attacks.
The government's National Cholesterol Education Program has estimated that at least 36 million people—about two thirds of them age 45 or older—have blood cholesterol levels high enough to merit treatment with cholesterol-lowering drugs. Yet only 12 to 15 million of them are currently taking such medication, and many (probably most) are taking too small a dose. The landmark Heart Protection Study, published in the Lancet in 2002, concluded that cholesterol-lowering drugs called statins can produce substantial benefits in a much wider range of high-risk people than had been previously thought—including people over age 70, women, and anyone with vascular disease or diabetes, regardless of whether they have high cholesterol levels.
- What is cholesterol?
- Why are blood levels of cholesterol important to heart health?
- What other fats in the blood are important to heart health?
- Should you have your cholesterol levels tested?
- Are your cholesterol levels too high?
- What lifestyle measures help control cholesterol?
- What medicines help control cholesterol?
Cholesterol is a white, waxy lipid (fat) that is present in the tissues of humans and other animals and, thus, in all foods from animal sources. Although cholesterol is essential for many bodily functions, it isn't an essential nutrient, meaning that the diet does not need to contain cholesterol to meet the body's requirements. The liver manufactures all the cholesterol that the body needs. Particles called lipoproteins, formed in the liver, transport cholesterol and other fats through the bloodstream. The three lipoproteins are named according to their density: very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Most cholesterol is transported by LDL.The liver secretes VLDL, which is converted to LDL in the bloodstream. The cholesterol on LDL is used to form membranes in cells throughout the body; deposits of LDL cholesterol in the arterial walls initiate the formation of plaques.
HDL also carries cholesterol in the blood; however, HDL has the beneficial capacity of picking up cholesterol from cells and atherosclerotic plaques and bringing it back to the liver for reprocessing or excretion. Therefore, HDL cholesterol is often referred to as "good" cholesterol, because it clears cholesterol from the arteries, while LDL cholesterol has been called "bad" because it deposits cholesterol in the arteries. Because elevated cholesterol levels contribute to the development of atherosclerosis, reducing cholesterol levels can help prevent coronary heart disease and heart attacks.
Why are blood levels of cholesterol important to heart health?
The blockage that ultimately triggers a heart attack is most often a blood clot that forms at a site where a coronary artery has developed atherosclerosis. This involves the formation of deposits called plaques within the walls of arteries. The plaques are composed of cholesterol-laden foam cells, smooth muscle cells, fibrous proteins, and calcium. As the plaques build up, the arterial walls thicken and narrow. Increased total and LDL cholesterol levels boost the risk of coronary heart disease by increasing the amount of cholesterol deposited within the walls of the arteries.
Symptoms of coronary heart disease, including angina, result when an advanced plaque narrows a coronary artery so much that it hinders blood flow to the heart. Plaque deposits also roughen arterial walls and make it easier for a blood clot to form along their surface. Complete blockage of a coronary artery by a clot can cause a heart attack. A portion of a clot can also break loose from its place of origin and cause a heart attack by lodging in a narrower section of the artery or in a smaller artery supplying blood to the heart.
What other fats in the blood are important to heart health?
High blood levels of fats known as triglycerides—which contribute to atherosclerosis—also are a risk factor for coronary heart disease. Like cholesterol, triglycerides are obtained from food and produced in the liver, and they are transported in the blood by lipoproteins, mostly VLDL.
High triglyceride levels pose a risk partly because elevations in triglycerides are commonly associated with low HDL cholesterol levels. However, research over the past decade indicates that elevated triglyceride levels are also an independent risk factor for coronary heart disease, although how they increase the risk isn't quite clear. One possible explanation is that elevations in blood triglycerides alter the size, density, and composition of LDL—changes that may promote atherosclerosis.
Should you have your cholesterol levels tested?
Cholesterol and triglycerides are fatty substances called lipids. Both are essential for proper body functioning, but elevated blood levels of these lipids increase the risk of coronary heart disease and heart attacks.
According to current guidelines from the National Cholesterol Education Program, everyone who is 20 years of age or older should have a blood test called a lipid profile (sometimes called a lipoprotein profile) at least once every five years.
This test, which measures blood levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, should be performed at your doctor's office. You will probably be asked to fast for at least 12 hours before the test, since what you eat can affect levels of blood triglycerides.
If fasting isn't possible, then only the values for total cholesterol and HDL cholesterol are obtained. If you are considered at low risk for coronary heart disease and the test results confirm this assumption, no further testing may be required. Otherwise, your doctor may ask you to return for a fasting lipid profile.
Your doctor will use the test results—along with the presence of other coronary heart disease risk factors (such as age, family history of premature heart disease, cigarette smoking, blood pressure, and diabetes)—to estimate your risk. If your total cholesterol, LDL cholesterol, or triglyceride levels are elevated (or if your HDL level is too low), your doctor will determine the most effective risk reduction measures for you to take.
These could involve changes in your diet, increasing physical activity, quitting smoking, moderating alcohol intake, taking medication, or a combination of these measures.
Are your cholesterol levels too high?
Increased total and LDL cholesterol levels boost the risk of coronary heart disease (CHD) by increasing the amount of cholesterol deposited within the walls of the arteries. The National Cholesterol Education Program guidelines recommend that total cholesterol levels be kept below 200 mg/dL to reduce risk.
The target for LDL cholesterol depends on how many of the following risk factors are present:
- cigarette smoking;
- high blood pressure (140/90 mm Hg or higher) or use of blood-pressure-lowering medication;
- HDL cholesterol level below 40 mg/dL;
- family history of a premature CHD event (under 55 years old in men, under 65 in women) in a first-degree relative; and
- older age (45 years or older in men, 55 or older in women).
For people with none or one of these risk factors, LDL cholesterol levels should be less than 160 mg/dL. In individuals who do not have known cardiovascular disease or diabetes but have two or more of these risk factors, LDL cholesterol levels should be kept below 130 mg/dL. In all people with known cardiovascular disease or diabetes, LDL cholesterol levels should be lowered to less than 100 mg/dL, with an optional goal of less than 70 mg/dL.
A low HDL cholesterol level (less than 40 mg/dL) is considered a risk factor for CHD. In fact, a total blood cholesterol level of 200 mg/dL or lower—the level considered desirable—may still be associated with an increased risk of CHD if HDL cholesterol levels are below 40 mg/dL, particularly in women. A high level of HDL cholesterol (60 mg/dL or higher), however, is considered protective against CHD and cancels out the effects of one other CHD risk factor (such as increased age) when determining one's total number of risk factors.
Triglyceride levels between 150 mg/dL and 199 mg/dL are considered borderline, and levels between 200 mg/dL and 500 m/dL are high. Levels greater than 500 mg/dL are very high. About 35 percent of men and 24 percent of women are thought to have triglyceride levels above 150 mg/dL. The CHD risk of elevated triglycerides is especially great when combined with low levels of HDL cholesterol and small, dense LDL particles. This pattern is common in people who are obese or have diabetes or pre-diabetes. Elevated triglycerides also impart high risk when associated with a high ratio of LDL to HDL cholesterol or when due to one of two inherited conditions—familial combined hyperlipidemia or dysbetalipoproteinemia. Both of these disorders cause high blood cholesterol and/or high blood triglyceride levels.
Size and density of LDL particles can also affect CHD risk. LDL particles vary in size and density to produce two patterns: A and B. People with pattern A have mostly large LDL particles, while people with pattern B have a predominance of small, dense particles. Pattern B patients have a higher risk of CHD than pattern A patients. The majority of people with triglyceride levels above 150 mg/dL have pattern B. Men are more likely than women to have pattern B, which may be genetic or develop as a result of elevated triglycerides or diabetes.
The reason for the increased risk of CHD with pattern B is that smaller LDL particles enter the arterial wall more easily and are more prone to oxidation than larger LDL particles. However, the presence of mostly small LDL particles is often linked to higher triglyceride and lower HDL cholesterol levels, as well as to a greater number of LDL particles, and this combination may have a more important effect on CHD risk than particle size alone.
High levels of lipoprotein(a), also known as Lp(a), are another risk factor for CHD. The structure of Lp(a) is similar to LDL, except that it contains another protein called apo(a), which resembles the blood protein plasminogen. Plasminogen is converted into the enzyme plasmin, which plays a role in eliminating arterial blockage by breaking down fibrin, a major component of blood clots.
Two explanations have been proposed for why Lp(a) increases the risk of CHD. First, because of the similarity of apo(a) to plasminogen, Lp(a) might interfere with the conversion of plasminogen to plasmin, thus promoting the persistence of blood clots by reducing the beneficial action of plasmin. Second, like LDL, Lp(a) can deposit in arterial walls and contribute to plaque formation.
What lifestyle measures help control cholesterol?
Several lifestyle measures can help you lower your risk of coronary heart disease and heart attack by controlling your cholesterol levels. Even when these measures are not completely effective themselves, and medication is required to lower cholesterol to acceptable levels, they may allow a patient to take smaller amounts of medication (which in turn can reduce the risk of side effects). This section discusses blood lipid levels and:
The average American diet contains about 35 percent to 40percent of calories from fat. Not all of this fat is bad—in fact, some types of fat have a beneficial effect on blood lipids and may lower the risk of developing coronary heart disease or dying of it. But the prevalent type of fat in the American diet is saturated fat, the major dietary factor that raises blood cholesterol levels. In fact, saturated fat has a bigger impact on blood cholesterol levels than dietary cholesterol itself. Saturated fat includes mostanimal and dairy fats and some oils, such as palm and coconut oils. The simplest dietary measure to lower the risk of CHD and heart attack is limiting saturated-fat intake. The 2001 National Cholesterol Education Program guidelines recommend reducing total fat to between 25percent and 35percent of total calories and limiting the intake of saturated fat to less than 10percent of total calories in order to reduce blood cholesterol levels—specifically LDL cholesterol.
The guidelines also recommend limiting dietary cholesterol to less than 300 mg per day. But if LDL cholesterol levels remain high, saturated fat should be further restricted to less than 7percent of calories, and cholesterol to less than 200 mg per day.
When fat is consumed, monounsaturated fats should be chosen whenever possible.Olive and canola oils, almonds, and avocados contain large amounts of monounsaturated fat. Polyunsaturated fats—found in safflower, sunflower, and corn oils—also lower LDL cholesterol levels.
Omega-3 fatty acids, another type of polyunsaturated fat, seem to have cardioprotective benefits beyond LDL cholesterol lowering. Of the three types of omega-3 fatty acids, two are found only infish (particularly fatty fish. These can reduce the tendency for blood to clot, decrease the risk of arrhythmias (abnormal heart rhythms), and lower triglyceride levels. The American Heart Association recommends consuming at least two servings of fish per week to benefit from the cardioprotective effects of omega-3 fatty acids.
Just as with saturated fats, people should minimize their intake of trans fats, such as margarine or partially hydrogenated oils. Indeed, the Institute of Medicine, a branch of the National Academy of Sciences, recommends that trans fat consumption be as low as possible.
Experts recommend that adults consume at least 25 to 30 grams of dietary fiber each day. Fiber is an indigestible component of many foods, primarily grains, legumes, fruits, and vegetables. Fiber comes in two forms: soluble, the type in oatmeal that gets sticky when wet, and insoluble, the spongelike version in bran and in fruit and vegetable skins that absorbs water and helps to prevent constipation. Both types of fiber are important, but soluble fiber is especially effective in lowering blood cholesterol levels.
Food containing soluble fiber—such as oats, oat bran, barley, legumes, dried plums (prunes), apples, carrots, and grapefruits—should be included in the diet each day.
Just how soluble fiber reduces cholesterol levels is unclear. Researchers theorize that it works in much the same way as a class of lipid-lowering drugs called bile acid sequestrants. Normally, bile acids are reabsorbed from the intestine and returned to the liver for reprocessing. Bile acid sequestrants bind bile acids in the intestine and remove them in the stool. As a result, the liver converts more cholesterol to bile acids and removes more LDL from the blood by developing more LDL receptors on its surface.
Just how soluble fiber reduces cholesterol levels is unclear. Researchers theorize that it works in much the same way as a class of lipid-lowering drugs called bile acid sequestrants. Normally, bile acids are reabsorbed from the intestine and returned to the liver for reprocessing. Bile acid sequestrants bind bile acids in the intestine and remove them in the stool. As a result, the liver converts more cholesterol to bile acids and removes more LDL from the blood by developing more LDL receptors on its surface.
Soy products may also lower blood cholesterol levels. An analysis of 38 studies in which soy protein replaced animal protein in people's diets found that eating an average of 47 grams (about 10 ounces) of soy protein per day lowered levels of total cholesterol by about 9percent, LDL cholesterol by 13percent, and triglycerides by 11percent. The substitution of unsaturated for saturated fat (38percent of the calories in soybeans come from fat, mostly unsaturated) may account for some of this benefit.
But soy also contains phytochemicals (plant chemicals)—isoflavones, in particular—that may contribute to the cholesterol-lowering effect. Isoflavones are estrogenlike compounds present in soy foods such astofu and soy milk; estrogen lowers LDL cholesterol and boosts HDL cholesterol levels.
Weight loss is the most effective way to lower elevated triglyceride levels. It also helps to raise HDL cholesterol levels.
What medicines help control cholesterol?
The benefits of reducing total and LDL cholesterol levels with medication (below and chart on lipid-lowering drugs) have been clearly demonstrated by a number of well-designed studies. Recently, results from the Heart Protection Study, which examined the effects of long-term therapy with simvastatin, a type of statin drug, in more than 20,500 people, found that statin therapy reduced the incidence of heart attacks and strokes by about one third. Statins were effective not only in people with existing heart disease but also in people at high risk for heart attack, including those with diabetes, peripheral arterial disease, or a history of stroke. Moreover, people with pretreatment LDL cholesterol levels within the normal range—or even less than 100 mg/dL—benefited from statin therapy.
Five classes of lipid-lowering medications are available:
- Statins (HMG-CoA reductase inhibitors)
- Bile acid sequestrants
- Nicotinic acid, or niacin
- Fibrates
- Cholesterol absorption inhibitors
- Stanols and sterols
Statins (HMG-CoA reductase inhibitors)
About 9 percent of the cholesterol-lowering drugs taken by Americans are statins. The drugs in this class are associated with few side effects and are the most effective drugs for lowering total and LDL cholesterol levels and for reducing the risk of heart attack. Statins also help lower the risk of stroke and, in people with coronary heart disease, the need for bypass surgery and angioplasty.
The statins include atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), and rosuvastatin (Crestor). Lovastatin, the only statin available as a generic, is also available in combination with extended-release niacin and is sold under the brand name Advicor. In addition, the FDA recently approved a pill called Caduet, which combines atorvastatin and the blood pressure-lowering drug amlodipine, for the treatment of elevated cholesterol levels in people who also have hypertension. And more recently the FDA approved Vytorin, a pill containing both simvastatin and the cholesterol absorption inhibitor ezetimibe.
Statins produce about a 25 percent to 55 percent reduction in levels of LDL cholesterol, a 5percent to 15 percent increase in HDL cholesterol levels, and a 10 percent to 25 percent reduction in triglyceride levels. The relative efficacy of the statins for lowering LDL cholesterol and triglyceride levels is as follows: rosuvastatin has the most potent effect, followed by atorvastatin, simvastatin, pravastatin, lovastatin, and fluvastatin. The ability to lower LDL cholesterol levels is usually the most important factor to consider when choosing a statin, but other considerations include a patient's level of coronary heart disease risk, differences in side effects, drug interactions, cost, results of clinical trials, and the time of day a dose should be taken.
Side effects are uncommon, occurring in only 1 percent to 2 percent of people. For more on side effects.
The bile acid sequestrants, cholestyramine (Questran) and colestipol (Colestid), have proven long-term safety and effectiveness. A newer sequestrant called colesevelam (Wel-Chol) became available in 2000. Sequestrants effectively lower LDL cholesterol levels, especially when taken in combination with statins or niacin. A number of studies have shown that such combinations slow the progression—or even cause modest regression—of plaques. Bile acid sequestrants can modestly raise triglyceride levels, however. Rarely, bile acid sequestrants can also interfere with the absorption of folic acid. Taking the sequestrants at the proper times is important to avoid interfering with the absorption of other drugs.
Large doses of this B vitamin are the most effective therapy for raising HDL cholesterol levels. Niacin can also lower triglyceride and LDL cholesterol levels but frequently causes adverse effects, especially when dosages higher than 2 grams a day are taken. Although niacin is available over the counter, all preparations should be used under a doctor's supervision.
Skin flushing and itching are common but not dangerous. Extended-release niacin (Niaspan) causes less flushing than immediate-release niacin (Niacor) and has the added advantage of once-daily dosing at bedtime, rather than three times a day with meals.
The fibrates, fenofibrate (Lofibra, Tricor) and gemfibrozil (Lopid), are the treatment of choice for those with markedly increased blood triglyceride levels. But any reduction in triglycerides with fibrates may be accompanied by a slight rise in LDL cholesterol. When this problem occurs, the addition of a statin can improve LDL cholesterol levels but may cause muscle inflammation in about 1 percent of people. (The problem is more common with gemfibrozil than with fenofibrate.) Muscle inflammation is reversible, but both drugs must be promptly discontinued, since persistent, severe muscle inflammation can cause kidney failure.
Cholesterol absorption inhibitors
An inhibitor of cholesterol absorption is the newest type of lipid-lowering medication. As the name implies, these drugs work by blocking the intestinal absorption of cholesterol from the diet and bile acids. Ezetimibe (Zetia) is the first and only drug to be approved in this class. The drug lowers LDL cholesterol levels by about 15percent, and when used in combination with a statin, LDL levels may be reduced by up to 55percent.
In 1999, the FDA approved cholesterol-lowering food additives called stanols and sterols, which help lower cholesterol levels by blocking the absorption of cholesterol in the small intestine. So far these substances have been added to margarines (Benecol, Take Control, and SmartBalance OmegaPlus) and orange juice (Minute Maid Premium Heart Wise). The margarines can reduce LDL cholesterol levels by 7 percent to 14 percent when used daily for a year or longer in combination with a low-saturated-fat, low-cholesterol diet and regular exercise. In a recent study, sterol-fortified orange juice reduced LDL cholesterol by 12 percent when participants drank two 8-ounce glasses each day with meals for eight weeks.
Don't forget that stanol- and sterol-fortified foods contain calories and can cause weight gain when consumed in large quantities or in addition to the usual diet.
Content excerpted from the Johns Hopkins White Paper on Heart Attack Prevention.
