About Cholesterol

It may surprise you to know that cholesterol itself isn't bad. In fact, cholesterol is just one of the many substances created and used by our bodies to keep us healthy. Some of the cholesterol we need is produced naturally (and can be affected by your family health history), while some of it comes from the food we eat. There are two types of cholesterol: good and bad. Its important to understand the difference, and to know the levels of good and bad cholesterol in your blood. Too much of one type or not enough of another can put you at risk for coronary heart disease, heart attack or stroke.

What is Cholesterol?

Cholesterol is a fatty substance (a lipid) that is an important part of the outer lining (membrane) of cells in the body of animals. Cholesterol is also found in the blood circulation of humans. The cholesterol in a person's blood originates from two major sources; dietary intake and liver production. Dietary cholesterol comes mainly from meat, poultry, fish, and dairy products. Organ meats, such as liver, are especially high in cholesterol content, while foods of plant origin contain no cholesterol. After a meal, cholesterol is absorbed by the intestines into the blood circulation and is then packaged inside a protein coat. This cholesterolprotein coat complex is called a chylomicron. The liver is capable of removing cholesterol from the blood circulation as well as manufacturing cholesterol and secreting cholesterol into the blood circulation. After a meal, the liver removes chylomicrons from the blood circulation. In between meals, the liver manufactures and secretes cholesterol back into the blood circulation.

The Two Sources of Cholesterol

What are LDL and HDL cholesterol?

LDL cholesterol is called "bad" cholesterol, because elevated levels of LDL cholesterol are associated with an increased risk of coronary heart disease. LDL lipoprotein deposits cholesterol on the artery walls, causing the formation of a hard, thick substance called cholesterol plaque. Over time, cholesterol plaque causes thickening of the artery walls and narrowing of the arteries, a process called atherosclerosis. HDL cholesterol is called the "good cholesterol" because HDL cholesterol particles prevent atherosclerosis by extracting cholesterol from the artery walls and disposing of them through the liver. Thus, high levels of LDL cholesterol and low levels of HDL cholesterol (high LDL/HDL ratios) are risk factors for atherosclerosis, while low levels of LDL cholesterol and high level of HDL cholesterol (low LDL/HDL ratios) are desirable. Total cholesterol is the sum of LDL (low density) cholesterol, HDL (high density) cholesterol, VLDL (very low density) cholesterol, and IDL (intermediate density) cholesterol. What determines the level of LDL cholesterol in the blood? The liver not only manufactures and secretes LDL cholesterol into the blood; it also removes LDL cholesterol from the blood. A high number of active LDL receptors on the liver surfaces is associated with the rapid removal of LDL cholesterol from the blood and low blood LDL cholesterol levels. A deficiency of LDL receptors is associated with high LDL cholesterol blood levels.

Both heredity and diet have a significant influence on a person's LDL, HDL and total cholesterol levels. For example, familial hypercholesterolemia (FH) is a common inherited disorder whose victims have a diminished number or nonexistent LDL receptors on the surface of liver cells. People with this disorder also tend to develop atherosclerosis and heart attacks during early adulthood. Diets that are high in saturated fats and cholesterol raise the levels of LDL cholesterol in the blood. Fats are classified as saturated or unsaturated (according to their chemical structure). Saturated fats are derived primarily from meat and dairy products and can raise blood cholesterol levels. Some vegetable oils made from coconut, palm, and cocoa are also high in saturated fats. Does lowering LDL cholesterol prevent heart attacks and strokes? Lowering LDL cholesterol is currently the primary focus in preventing atherosclerosis and heart attacks. Most doctors now believe that the benefits of lowering LDL cholesterol include:

Reducing or stopping the formation of new cholesterol plaques on the artery walls; Reducing existing cholesterol plaques on the artery walls; Widening narrowed arteries; Preventing the rupture of cholesterol plaques, which initiates blood clot formation; Decreasing the risk of heart attacks; and Decreasing the risk of strokes. The same measures that retard atherosclerosis in coronary arteries also benefit the carotid and cerebral arteries (arteries that deliver blood to the brain). How can LDL cholesterol levels be lowered? Therapeutic lifestyle changes to lower cholesterol Lowering LDL cholesterol involves losing excess weight, exercising regularly, and following a diet that is low in saturated fat and cholesterol. For more, please read the TLC, Therapeutic Lifestyle Changes article. Medications to lower cholesterol Medications are prescribed when lifestyle changes cannot reduce the LDL cholesterol to desired levels. The most effective and widely used medications to lower LDL cholesterol are called statins. Most of the large controlled trials that demonstrated the heart attack and stroke prevention benefits of lowering LDL cholesterol used one of the statins. Other medications used in lowering LDL cholesterol and in altering cholesterol profiles include nicotinic acid (niacin), fibrates such as gemfibrozil (Lopid), resins such as cholestyramine (Questran), and ezetimibe, Zetia. (An in-depth discussion of these

drugs is presented in this article starting at the heading: What are the statin drugs?)

What are "normal" cholesterol blood levels? There are no established "normal" blood levels for total and LDL cholesterol. In most other blood tests in medicine, normal ranges can be set by taking measurements from large number of healthy subjects. For example, normal fasting blood sugar levels can be established by performing blood tests among healthy subjects without diabetes mellitus. If a patient's fasting blood glucose falls within this normal range, he/she most likely does not have diabetes mellitus, whereas if the patient's fasting blood sugar tests higher than the normal range, he/she probably has diabetes mellitus and further tests can be performed to confirm the diagnosis. Medications, such as insulin or oral diabetes medications can be prescribed to lower abnormally high blood sugar levels. Unfortunately, the normal range of LDL cholesterol among "healthy" adults (adults with no known coronary heart disease) in the United States may be too high. The atherosclerosis process may be quietly progressing in many healthy adults with average LDL cholesterol blood levels, putting them at risk of developing coronary heart diseases in the future.

What are the 2004 NCEP cholesterol treatment guidelines? After reviewing these large randomized cholesterol-lowering trials, The National Cholesterol Education Program (NCEP) expert panel published their new recommendations. The new NCEP recommendations, presented in the June, 2004 issue of Circulation, are: 1. The report advised physicians to consider more intensive LDL cholesterol-lowering for people at very high, high, and moderately high risk for a heart attack. These options include setting lower treatment goals for LDL cholesterol and initiating cholesterollowering drug therapy at lower LDL thresholds, as compared to ATP III guidelines published in 2001. For example, for patients with a very high risk of heart attacks, the LDL cholesterol treatment goal remains at <100mg/dl, but the report advised doctors to consider the option of lowering the LDL cholesterol (usually using a statin plus lifestyle changes) to < 70 mg/dl. 2. The report emphasized the importance of initiating therapeutic lifestyle changes (TLC) to modify lifestyle-related risk factors (obesity, physical inactivity, metabolic syndrome, high blood triglyceride levels and low HDL cholesterol levels). TLC Lifestyle

changes have the potential to reduce heart attack and stroke risks through several mechanisms beyond the lowering of LDL cholesterol. 3. When LDL-lowering medication is used for very high, high or moderately high risk patients, the report advises that the intensity of LDL-lowering drug therapy be sufficient to achieve at least a 30 to 40 percent reduction in LDL cholesterol levels. 4. When a very high or high risk patient also has high blood triglyceride or low HDL cholesterol levels, doctors may consider combining nicotinic acid or a fibrate with a statin. Nicotinic acid and fibrates are more effective than statins in lowering triglycerides and increasing HDL. 5. Age should not be a consideration since older persons also benefit from lowering LDL cholesterol. Thus, it is never too late or the patient too old to begin lifestyle changes and medications to lower LDL cholesterol. A word of caution is in order. Elderly patients are more likely to have liver and kidney dysfunction, and are also more likely to be on multiple medications some of which may interfere with the breakdown of cholesterol-lowering drugs such as statins. Thus lower dosing may be necessary to avoid adverse side effects. The 2004 NCEP treatment goals according to risk categories Risk category High risk Very high risk More intense LDL goal LDL goal option < 100 mg/dl < 100 mg/dl < 70 mg/dl Initiate TLC if LDL is: > 100 mg/dl > 100 mg/dl Consider drugs + TLC if LDL is: >100 mg/dl <100 mg/dl >130mg/dl, consider drug option if LDL is 100-129 mg/dl

Moderately <130 high risk (10 yr. risk mg/dl 10-20%) Moderate risk (10 yr. <130 risk mg/dl <10%) Lower risk <160 mg/dl

<100 mg/dl

> 130 mg/dl

> 130 mg/dl

>160 mg/dl >190 mg/dl, consider drug optional if LDL is 160-189 mg/dl

> 160 mg/dl

High risk patients are those who already have coronary heart disease (such as a prior heart attack), diabetes mellitus, abdominal aortic aneurysm, or those who already have atherosclerosis of the arteries to the brain and extremities (such as patients with strokes, TIA's (mini-strokes), and peripheral vascular diseases). High risk patients

also include those with 2 or more risk factors (e.g., smoking, hypertension, or a family history of early heart attacks) that places them at a greater than 20 percent chance of having a heart attack within 10 years. (A person's chance of having a heart attack can be calculated by using the Framingham Heart Study Score Sheets, at http://nhlbi.nih.gov/about/framingham/riskabs.htm). Very high -risk patients are those who have coronary heart disease in addition to having either multiple risk factors (especially diabetes), or severe and poorly controlled risk factors (such as continued smoking), or metabolic syndrome (a constellation of risk factors associated with obesity, including high triglycerides and low HDL). Patients hospitalized for acute coronary syndromes are also at very high risk. Moderately high risk patients are those who have neither coronary heart disease nor diabetes mellitus, but have multiple (2 or more) risk factors for coronary heart disease that put them at a 10 to 20 percent risk of heart attack within 10 years. (Use the Framingham Heart Study Score Sheets, at http://nhlbi.nih.gov/about/framingham/riskabs,htm to calculate the 10 year risk.) Moderate risk patients are those who have neither CHD nor diabetes mellitus, but have 2 or more risk factors for coronary heart disease that put them at a <10% risk of heart attack within 10 years. Lower risk patients are those with 0 to 1 risk factor for coronary heart disease.

Why is HDL the good cholesterol? HDL is the good cholesterol because it protects the arteries from the atherosclerosis process. HDL cholesterol extracts cholesterol particles from the artery walls and transports them to the liver to be disposed through the bile. It also interferes with the accumulation of LDL cholesterol particles in the artery walls. The risk of atherosclerosis and heart attacks in both men and is strongly related to HDL cholesterol levels. Low levels of HDL cholesterol are linked to a higher risk, whereas high HDL cholesterol levels are associated with a lower risk. Very low and very high HDL cholesterol levels can run in families. Families with low HDL cholesterol levels have a higher incidence of heart attacks than the general population, while families with high HDL cholesterol levels tend to live longer with a lower frequency of heart attacks. Like LDL cholesterol, life style factors and other conditions influence HDL cholesterol levels. HDL cholesterol levels are lower in persons who smoke cigarettes, eat a lot of sweets, are overweight and inactive, and in patients with type II diabetes mellitus.

HDL cholesterol is higher in people who are lean, exercise regularly, and do not smoke cigarettes. Estrogen increases a person's HDL cholesterol, which explains why women generally have higher HDL levels than men do. For individuals with low HDL cholesterol levels, a high total or LDL cholesterol blood level further increases the incidence of atherosclerosis and heart attacks. Therefore, the combination of high levels of total and LDL cholesterol with low levels of HDL cholesterol is undesirable whereas the combination of low levels of total and LDL cholesterol and high levels of HDL cholesterol is favorable.

What are LDL/HDL and total/HDL ratios? The total cholesterol to HDL cholesterol ratio (total chol/HDL) is a number that is helpful in estimating the risk of developing atherosclerosis. The number is obtained by dividing total cholesterol by HDL cholesterol. (High ratios indicate a higher risk of heart attacks, whereas low ratios indicate a lower risk). High total cholesterol and low HDL cholesterol increases the ratio and is undesirable. Conversely, high HDL cholesterol and low total cholesterol lowers the ratio and is desirable. An average ratio would be about 4.5. Ideally, one should strive for ratios of 2 or 3 (less than 4).

What are the treatment guidelines for low HDL cholesterol? In clinical trials involving lowering LDL cholesterol, scientists also studied the effect of HDL cholesterol on atherosclerosis and heart attack rates. They found that even small increases in HDL cholesterol could reduce the frequency of heart attacks. For each 1 mg/dl increase in HDL cholesterol, there is a 2 to 4% reduction in the risk of coronary heart disease. Although there are no formal NCEP (please see discussion above) target treatment levels of HDL cholesterol, an HDL level of <40 mg/dl is considered undesirable and measures should be taken to increase it.

How can levels of HDL cholesterol be raised? The first step in increasing HDL cholesterol levels (and decreasing LDL/HDL ratios) is therapeutic life style changes. When these modifications are insufficient, medications are used. In prescribing medications or medication combinations, doctors have to take into account medication side effects as well as the presence or absence of other abnormalities in cholesterol profiles.

Regular aerobic exercise, loss of excess weight (fat), and cessation of smoking cigarettes will increase HDL cholesterol levels. Regular alcohol consumption (such as one drink a day) will also raise HDL cholesterol. Because of other adverse health consequences of excessive alcohol consumption, alcohol is not recommended as a standard treatment for low HDL cholesterol. Medications that are effective in increasing HDL cholesterol include nicotinic acid (niacin), gemfibrozil (Lopid), estrogen, and to a much lesser extent, the statin drugs (discussed below). A newer medicine, fenofibrate (Tricor) has shown much promise in selectively increasing HDL levels and reducing serum triglycerides.

What are triglycerides, chylomicrons, and VLDL? Triglyceride is a fatty substance that is composed of three fatty acids. Like cholesterol, triglyceride in the blood either comes from the diet or the liver. Also, like cholesterol, triglyceride cannot dissolve and circulate in the blood without combining with a lipoprotein. Thus, after a meal, the triglyceride and cholesterol that are absorbed into the intestines are packaged into round particles called chylomicrons before they are released into the blood circulation. A chylomicron is a collection of cholesterol and triglyceride that is surrounded by a lipoprotein outer coat. (Chylomicrons contain 90% triglyceride and 10% cholesterol.) The liver removes triglyceride and chylomicrons from the blood, and it synthesizes and packages triglyceride into VLDL (very low-density lipoprotein) particles and releases them back into the blood circulation.

Do high triglyceride levels cause atherosclerosis? Whether elevated triglyceride levels in the blood lead to atherosclerosis and heart attacks is controversial. While most doctors now believe that an abnormally high triglyceride level is a risk factor for atherosclerosis, it is difficult to conclusively prove that elevated triglyceride by itself can cause atherosclerosis. However, it is increasingly recognized that elevated triglyceride is often associated with other conditions that increase the risk of atherosclerosis, including obesity, low levels of HDL- cholesterol, insulin resistance and poorly controlled diabetes mellitus, and small, dense LDL cholesterol particles.

What are the causes of elevated triglyceride levels? In some people, abnormally high triglyceride levels (hypertriglyceridemia) are inherited. Examples of inherited hypertriglyceridemia disorders include mixed hypertriglyceridemia, familial hypertriglyceridemia, and familial dysbetalipoproteinemia. Hypertriglyceridemia can often be caused by non-genetic factors such as obesity, excessive alcohol intake, diabetes mellitus, kidney disease, and estrogen- containing medications such as birth control pills.

How can elevated blood triglyceride levels be treated? The first step in treating hypertriglyceridemia is a low fat diet with a limited amount of sweets, regular aerobic exercise, loss of excess weight, reduction of alcohol consumption, and stopping cigarette smoking. In patients with diabetes mellitus, meticulous control of elevated blood glucose is also important. When medications are necessary, fibrates (such as Lopid), nicotinic acid, and statin medications can be used. Lopid not only decreases triglyceride levels but also increases HDL cholesterol levels and LDL cholesterol particle size. Nicotinic acid lowers triglyceride levels, increases HDL cholesterol levels and the size of LDL cholesterol particles, as well as lowers the levels of Lp (a) cholesterol. The statin drugs have been found effective in decreasing triglyceride as well as LDL cholesterol levels and, to a lesser extent, in elevating HDL cholesterol levels. A relatively new medicine, fenofibrate (Tricor), shows promise as an effective agent in lowering serum triglyceride levels as well as raising HDL levels, particularly in patients who have had suboptimal responses to Lopid. In some patients, a combination of Lopid or Tricor with adjunctive statin therapy (see below) may be prescribed. While this combination is often effective in patients with complex lipid disorders, the potential for side effects may be increased and such patients should be under strict medical supervision.

What are lipid-altering medications? Lipid altering medications are used in lowering blood levels of undesirable lipids such as LDL cholesterol and triglycerides and increasing blood levels of desirable lipids such as HDL cholesterol. Several classes of medications are available in the United States, including HMG CoA reductase inhibitors (statins), nicotinic acid, fibric acid derivatives, and medications that decrease intestinal cholesterol absorption (bile acid sequestrants and cholesterol absorption inhibitors). Some of these medications are primarily useful in lowering LDL cholesterol, others in lowering triglycerides, and some

in elevating HDL cholesterol. Medications also can be combined to more aggressively lower LDL, as well as in lowering LDL and increasing HDL at the same time. Lipid altering medications commonly used in the United States Medication examples Pravachol, Mevacor, Lipitor, Lescol, Crestor, Zocor Effects on blood lipids Most effective in lowering LDL, mildly effective in increasing HDL, mildly effective in lowering triglycerides Most effective in increasing HDL, effective in lowering triglycerides, mildly to modestly effective in lowering LDL Most effective in lowering triglycerides, effective in increasing HDL, minimally effective in lowering LDL Mildly to modestly effective in lowering LDL, no effect on HDL and triglycerides Mildly to modestly effective in lowering LDL, no effect on HDL and triglycerides Effective in lowering LDL and triglycerides and increasing HDL Synergistic in lowering LDL and effective in lowering LDL with low doses of each ingredient

Medication class

statins

Nicotinic acid (Niacin)

Niacin, Niaspan, SloNiacin

Fibric acid

Lopid, Tricor

Bile acid sequestrants Cholesterol absorption inhibitors

Questran, Welchol, Colestid Zetia

Combining Advicor nicotinic acid with (lovastatin+niaspan) statin Combining a statin with an absorption inhibitor Vytorin (Zocor + Zetia)

What are the statin drugs? The statins are the most widely used, and also the most powerful medications for lowering LDL cholesterol. Numerous large, randomized, double-blind, placebo-controlled, , clinical trials (controlled trials) have shown that statins reduce heart attacks (and strokes) and improve survival. Statins are well tolerated with low side effect rates when used long term. Statins not only lower blood LDL cholesterol levels, they also modestly increase HDL cholesterol levels and modestly decrease triglyceride levels. The statins that are now on pharmacy shelves in the

U.S. (putting the generic name first followed by the brand name in parentheses) are:

rosuvastatin ( Crestor) fluvastatin sodium (Lescol) made by Novartis atorvastatin calcium (Lipitor) made by Parke-Davis and Pfizer lovastatin (Mevacor) made by Merck pravastatin sodium (Pravachol) made by Bristol-Myers Squibb simvastatin (Zocor) made by Merck

Studies have consistently shown that lowering LDL cholesterol with diet and statins reduces the risk of a second heart attack. The prevention of recurrent heart attacks in patients who have already suffered a heart attack is called secondary prevention. Studies have also demonstrated that reducing LDL cholesterol with lifestyle changes and statins reduces the risk of having the first heart attack. Prevention of heart attacks in those who have never had a heart attack is called primary prevention. Studies have also confirmed that reducing LDL cholesterol benefits both men and women, and the elderly. For more, please read our article on Statins. How do doctors select statin drugs? Which statin to use is an individualized decision. There are several considerations in choosing a statin:

In patients who need intense LDL cholesterol-lowering, it is more appropriate to use one of the more potent statins, such as atorvastatin (Lipitor) or rosuvastatin (Crestor). Sometimes a statin may need to be combined with another medication such as cholestyramine (Questran), ezetimibe (Zetia) or nicotinic acid, in order to achieve the LDL cholesterol goals. In patients with chronic liver disease who need statin treatment, it is important to completely abstain from alcohol and use either pravastatin (Pravachol) or rosuvastatin (Crestor) in low doses. (Pravastatin and rosuvastatin are safer to use in patients with liver disease.) If LDL cholesterol goals cannot be attained with low doses of either of these two statins, cholestyramine (Questran) or ezetimibe (Zetia) can be added. In patients who develop muscle aches or muscle damage with a statin, it may be appropriate to try another statin, such as pravastatin (Pravachol), that probably has less of a muscle toxic effect than the other statins. In patients who are at risk of developing muscle injury (for example a patient who is already

taking gemfibrozil), pravastatin (Pravachol) would also be a suitable statin to use. Atorvastatin (Lipitor) and fluvastatin (Lescol) do not require dose adjustments in patients with kidney diseases.

What is nicotinic acid (niacin)? Nicotinic acid (niacin) is a B vitamin. An average American diet contains 15-30 mg of niacin per day. However, in treating blood cholesterol and triglyceride disorders, high doses (1-3 grams a day) of nicotinic acid are necessary. Nicotinic acid is available in several preparations that include immediate release niacin, sustained release prescription brand Niaspan, and over- the- counter (OTC) sustained release niacin. OTC preparations are not federally regulated, and some OTC preparations may have no active ingredient. Thus, they would be ineffective in either lowering LDL or raising HDL cholesterol. Some formulations of OTC sustained release niacin have been associated with liver toxicity and rare cases of fulminant (usually fatal without liver transplantation) hepatitis have been reported. The prescription brand sustained release Niaspan has been found in clinical trials to cause only minor elevations in blood liver enzymes without causing significant liver disease. Nicotinic acid is most effective in increasing HDL cholesterol and it is also modestly effective in lowering LDL cholesterol, Lp(a) cholesterol, and triglyceride levels (see below). Nicotinic acid is most suited for individuals whose only problem is low HDL cholesterol. Nicotinic acid used alone can raise HDL cholesterol levels by 30% or more. Nicotinic acid is not as effective as a statin in lowering LDL cholesterol levels. Therefore, when low HDL cholesterol is accompanied by high LDL cholesterol, most doctors use a statin to decrease the LDL cholesterol first. If necessary, nicotinic acid can be added to a statin to further raise HDL cholesterol levels. Advicor is a combination product approved for use in the United States. It is a combination of sustained release niacin with lovastatin. Advicor is useful in patients who need to both significantly lower their LDL cholesterol and increase HDL cholesterol. For more, please read our article on Nicotinic acid.

What are fibric acid derivatives (fibrates)? Fibric acid derivatives (fibrates) are effective medications in lowering blood triglyceride levels. Fibrates lower blood triglyceride levels by inhibiting the liver production of VLDL (the triglyceride-rich lip-protein fraction), and by speeding up the removal of triglycerides from the blood. Fibrates are also modestly effective in increasing blood HDL cholesterol levels. However, fibrates are not effective in

lowering LDL cholesterol. Examples of fibrates available in the United Sates include Gemfibrozil (Lopid) and fenofibrate (Tricor). Very high triglyceride levels (usually > 1000 mg/dl) can cause pancreatitis (inflammation of the pancreas that can result in a serious an illness with severe abdominal pain). By lowering the blood triglycerides, fibrates are used to prevent pancreatitis. Fibrates are not effective in lowering LDL cholesterol and cannot be used alone in lowering LDL cholesterol levels. However, when a high risk patient (see NCEP recommendations above) also has high blood triglyceride or low HDL cholesterol levels, doctors may consider combining a fibrate, such as fenofibrate (Tricor), with a statin. Such a combination will not only lower the LDL cholesterol, but will also lower blood triglycerides and increase HDL cholesterol levels. Fibrates have also been used alone to prevent heart attacks especially in patients with elevated blood triglycerides and low HDL cholesterol levels. In one large study, gemfibrozil decreased the risk of heart attacks but did not affect the overall survival of persons with high cholesterol levels. For more, please read our article on Fibrates.

What are bile acid sequestrants? Bile acid sequestrants such as Cholestyramine (Questran), colestipol (Colestid), and colesevelam (Welchol) are medications for lowering LDL cholesterol. Bile acid sequestrants bind bile acids in the intestine and cause more of the bile acids to be excreted in the stool. This reduces the amount of bile acids returning to the liver and forces the liver to produce more bile acids to replace the bile acids lost in the stool. In order to produce more bile acids, the liver converts more cholesterol into bile acids, which lowers the level of cholesterol in the blood. Bile acid sequestrants have modest LDL cholesterol-lowering effects. Low doses (for example 8 gram/day of Cholestyramine) can lower LDL cholesterol by 10%-15 %. But even high doses (24 gram/day of cholestyramine) can only lower LDL cholesterol by approximately 25%. Therefore, bile acid sequestrants used alone are not as effective as statins in lowering LDL cholesterol. However, bile acid sequestrants are most useful in combining with a statin or niacin to aggressively lower LDL cholesterol levels. The statin-bile acid sequestrant combination can lower LDL cholesterol levels by approximately 50%, lower than a statin alone. A statinniacin combination can substantially reduce LDL cholesterol and elevate HDL cholesterol. For more, please read our article on Bile Acid Sequestrants.

What is ezetimibe (Zetia)? Ezetimibe lowers blood cholesterol by blocking the absorption of cholesterol, including dietary cholesterol, from the intestines. It does not affect, however, the absorption of triglycerides or fat-soluble vitamins. Ezetimibe was approved by the FDA in October, 2002. Ezetimibe can be used alone or together with a statin drug. Ezetimibe used alone is modestly effective in lowering LDL cholesterol. At a dose of 10 mg/day it can reduce LDL cholesterol by approximately 17%. When used with a statin, it can reduce LDL cholesterol level further than a statin alone. However, there is insufficient scientific data to determine whether a statin-ezetimibe combination actually further reduces heart attack or stroke risks. A new combination drug, Vytorin, is available and combines 10 mg of Zetia with 20, 40, or 80 mg of Zocor. Ezetimibe is probably most useful in avoiding having to use high doses of a statin to achieve the 2004 NCEP LDL cholesterol targets in certain patients. Using lower doses of a statin probably reduces the risk of muscle injury. A statin-ezetimibe combination may also be helpful in treating patients with very high LDL cholesterol who cannot attain LDL cholesterol targets even with maximal doses of statins. Ezetimibe can be taken with or without food and at the same time as statin drugs. Ezetimibe is well-tolerated. The overall rate of side effects with ezetimibe in clinical studies was similar to that reported with a placebo (an inactive sugar pill). Diarrhea, abdominal pain, back pain, joint pain, and sinusitis were the most commonly reported side effects, occurring in 1 in every 25 to 30 patients. s lowering LDL cholesterol enough? Unfortunately, the prevention and treatment of atherosclerosis are more complicated than just lowering LDL cholesterol levels. LDL cholesterol reduction is only half of the battle against atherosclerosis. Individuals who have normal or only mildly elevated LDL cholesterol levels can still develop atherosclerosis and heart attacks even in the absence of other risk factors such as cigarette smoking, high blood pressure, and diabetes mellitus. Additionally, successfully lowering elevated LDL cholesterol levels cannot always prevent atherosclerosis and heart attacks. In many clinical trials to lower LDL cholesterol, there were patients who adhered to their assigned diets, faithfully took their cholesterol-lowering medications, and successfully lowered their LDL cholesterol to target levels, yet still suffered progressive atherosclerosis and heart attacks. It is clear that while lowering LDL cholesterol below NCEP target levels is an important step, there are other factors involved.

What is lipoprotein (a), (Lp(a)) cholesterol? Lipoprotein (a) (Lp(a)) is an LDL cholesterol particle that is attached to a special protein called apo(a). In large part, a person's level of Lp(a) in the blood is genetically inherited. Elevated levels of Lp(a) (higher than 20 mg/dl to 30 mg/dl) in the blood are linked to a greater likelihood of atherosclerosis and heart attacks in both men and women. The risk is even more significant if the Lp(a) cholesterol elevation is accompanied by high LDL/HDL ratios. Certain diseases are associated with elevated Lp(a) levels. Patients on chronic kidney dialysis and those with nephrotic syndromes (kidney diseases that cause leakage of blood proteins into the urine) tend to have high levels of Lp(a). There are many theories as to how Lp(a) causes atherosclerosis although exactly how Lp(a) accumulates cholesterol plaques on the artery walls has not been well defined. Clinical trials conclusively proving that lowering Lp(a) reduces atherosclerosis and the risk of heart attacks have not been conducted. Currently, there is no international standard for determining Lp(a) cholesterol levels and commercial sources of Lp(a) testing may not have the same accuracy as research laboratories. Therefore, specifically measuring and treating elevated Lp(a) cholesterol levels are not widely performed in this country.

How can Lp(a) cholesterol levels be reduced? Most lipid-lowering medications such as statins, Lopid, and cholestyramine have a limited effect in lowering Lp(a) cholesterol levels. Estrogen has been shown to lower Lp(a) cholesterol levels by approximately 20% in women with elevated Lp(a) cholesterol. Estrogen can also increase HDL cholesterol levels when given to postmenopausal women. Additionally, nicotinic acid (Niacin or Niaspan) in high doses has been found to be effective in lowering Lp(a) cholesterol levels by approximately 30%.

Learn Your Levels

The American Heart Association endorses the National Cholesterol Education Program (NCEP) guidelines for detection of high cholesterol: Everyone age 20 and older should have a fasting "lipoprotein profile" every five years. This test is done after a nine- to 12-hour fast without food, liquids or pills. It gives information about total cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. If you are not fasting when the test is done, your doctor won't be able to get an accurate lipid profile and may need to test you again. Be sure to review your test results with your doctor so you can understand and follow your treatment plan. What Your Cholesterol Levels Mean Your test report will show your cholesterol levels in milligrams per deciliter of blood (mg/dL). To determine how your cholesterol levels affect your risk of heart disease, your doctor will also take into account other risk factors such as age, family history, smoking and high blood pressure. A complete fasting lipoprotein profile will show:

Your Your Your Your

total blood (or serum) cholesterol level HDL (good) cholesterol level LDL (bad) cholesterol level triglyceride level

Your Total Blood (or Serum) Cholesterol Level Less than 200 mg/dL: Desirable If your LDL, HDL and triglyceride levels are also at desirable levels and you have no other risk factors for heart disease, total blood cholesterol below

200 mg/dL puts you at relatively low risk of coronary heart disease. Even with a low risk, however, its still smart to eat a heart-healthy diet, get regular physical activity and avoid tobacco smoke. Have your cholesterol levels checked every five years or as your doctor recommends. 200239 mg/dL: Borderline-High Risk If your total cholesterol falls between 200 and 239 mg/dL, your doctor will evaluate your levels of LDL (bad) cholesterol, HDL (good) cholesterol and triglycerides. It's possible to have borderline-high total cholesterol numbers with normal levels of LDL (bad) cholesterol balanced by high HDL (good) cholesterol. Work with your doctor to create a prevention and treatment plan that's right for you. Make lifestyle changes, including eating a heart-healthy diet, getting regular physical activity and avoiding tobacco smoke. Depending on your LDL (bad) cholesterol levels and your other risk factors, you may also need medication. Ask your doctor how often you should have your cholesterol rechecked. 240 mg/dL and over: High Risk People who have a total cholesterol level of 240 mg/dL or more typically have twice the risk of coronary heart disease as people whose cholesterol level is desirable (200 mg/dL). If your test didnt show your LDL cholesterol, HDL cholesterol and triglycerides, your doctor should order a fasting profile. Work with your doctor to create a prevention and treatment plan that's right for you. Whether or not you need cholesterol-regulating medication, make lifestyle changes, including eating a heart-healthy diet, getting regular physical activity and avoiding tobacco smoke. Your HDL (Good) Cholesterol Level With HDL (good) cholesterol, higher levels are better. Low HDL cholesterol (less than 40 mg/dL for men, less than 50 mg/dL for women) puts you at higher risk for heart disease. In the average man, HDL cholesterol levels range from 40 to 50 mg/dL. In the average woman, they range from 50 to 60 mg/dL. An HDL cholesterol of 60 mg/dL or higher gives some protection against heart disease. Smoking, being overweight and being sedentary can all result in lower HDL cholesterol. To raise your HDL level, avoid tobacco smoke, maintain a healthy weight and get at least 3060 minutes of physical activity more days than not. People with high blood triglycerides usually also have lower HDL cholesterol and a higher risk of heart attack and stroke. Progesterone,

anabolic steroids and male sex hormones (testosterone) also lower HDL cholesterol levels. Female sex hormones raise HDL cholesterol levels.

Your LDL (Bad) Cholesterol Level The lower your LDL cholesterol, the lower your risk of heart attack and stroke. In fact, it's a better gauge of risk than total blood cholesterol. In general, LDL levels fall into these categories: LDL Cholesterol Levels Less than 100 mg/dL 100 to 129 mg/dL 130 to 159 mg/dL 160 to 189 mg/dL 190 mg/dL and above Optimal Near Optimal/ Above Optimal Borderline High High Very High

Your other risk factors for heart disease and stroke help determine what your LDL level should be, as well as the appropriate treatment for you. A healthy level for you may not be healthy for your friend or neighbor. Discuss your levels and your treatment options with your doctor to get the plan that works for you. The Cholesterol Heart Profilers is a great starting point for learning about prevention and treatment options for your specific cholesterol levels. This free, confidential online service creates a printable report with the key information you need to fully understand your cholesterol levels, health risks and treatment options. You'll get a personalized cardiovascular disease risk profile, along with a summary of treatment options, potential side effects, success rates and a list of relevant medical journal articles and research studies, all summarized in plain English. Your Triglyceride Level Triglyceride is a form of fat. People with high triglycerides often have a high total cholesterol level, including high LDL (bad) cholesterol and low HDL (good) cholesterol levels. Your triglyceride level will fall into one of these categories:

Normal: less than 150 mg/dL Borderline-High: 150199 mg/dL High: 200499 mg/dL Very High: 500 mg/dL

Many people have high triglyceride levels due to being overweight/obese, physical inactivity, cigarette smoking, excess alcohol consumption and/or a diet very high in carbohydrates (60 percent of more of calories). High triglycerides are a lifestyle-related risk factor; however, underlying diseases or genetic disorders can be the cause. The main therapy to reduce triglyceride levels is to change your lifestyle. This means control your weight, eat a heart-healthy diet, get regular physical activity, avoid tobacco smoke, limit alcohol to one drink per day for women or two drinks per day for men and limit beverages and foods with added sugars. Visit your healthcare provider to create an action plan that will incorporate all these lifestyle changes. Sometimes, medication is needed in addition to a healthy diet and lifestyle. A triglyceride level of 150 mg/dL or higher is one of the risk factors of metabolic syndrome. Metabolic syndrome increases the risk for heart disease and other disorders, including diabetes.