What Is Cholesterol? What Are Triglycerides?
Cholesterol and triglycerides are two forms of lipid, or fat. Both cholesterol and triglycerides are necessary for life itself. Cholesterol is necessary, among other things, for building cell membranes and for making several essential hormones. Triglycerides, which are chains of high-energy fatty acids, provide much of the energy needed for cells to function.
Where Do Cholesterol and Triglycerides Come From?
There are two sources for these lipids: diet and "endogenous" sources (that is, those manufactured within the body).
Dietary cholesterol and triglycerides mainly come from eating meats and dairy products. These dietary lipids are absorbed through the gut,and then are delivered through the bloodstream to the liver, where they are processed.
One of the main jobs of the liver is to make sure all the tissues of the body receive the cholesterol and triglycerides they need to function. Whenever possible (that is, for about 8 hours after a meal), the liver takes up dietary cholesterol and triglycerides from bloodstream. During times when dietary lipids are not available, the liver produces cholesterol and triglycerides itself.
The liver then packages the cholesterol and triglycerides, along with special proteins, into tiny spheres called lipoproteins. The lipoproteins are released into the circulation, and are delivered to the cells of the body. The cells remove the needed cholesterol and triglycerides from the lipoproteins, as they are needed.
What Are LDL and HDL?
LDL stands for "low density lipoprotein," and HDL for "high density lipoprotein." In the bloodstream, "bad" cholesterol is carried in LDL, and "good" cholesterol is carried in HDL. Most cholesterol in the blood is packaged as LDL. Only a relatively small proportion is from HDL cholesterol. Thus, the total cholesterol level in the blood usually reflects mainly the amount of LDL cholesterol that is present.
Why Are High LDL Cholesterol Levels Bad?
Elevated levels of LDL cholesterol have been strongly associated with an increased risk of heart attack and stroke. It appears that when LDL cholesterol levels are too high, the LDL lipoprotein tends to stick the lining of the blood vessels, which helps to stimulate atherosclerosis. So, an elevated LDL cholesterol level is a major risk factor for heart disease and stroke. This is why LDL cholesterol has been called "bad" cholesterol.
Why Is Some Cholesterol Called "Good" Cholesterol?
Much evidence now suggests that higher HDL cholesterol levels are associated with a lower risk of heart disease, and that low HDL cholesterol levels are associated with an increased risk of heart disease. Thus, HDL cholesterol appears to be "good."
Why is HDL cholesterol protective? It appears that the HDL lipoprotein "scours" the walls of blood vessels and cleans out excess cholesterol. The cholesterol present in HDL is (to a large extent) actually excess cholesterol that has just been removed from cells and blood vessel walls, and is being transported back to the liver for processing.
How Important Are Triglycerides?
While the association between triglycerides and the risk of heart disease has not been as clear as it is for cholesterol, in recent years, several studies have established that people with elevated levels of triglycerides are indeed at increased risk. Also, elevated triglyceride levels are very often strongly associated with other important risk factors, including low levels of HDH cholesterol, obesity, insulin resistance, diabetes, and a tendency toward excessive blood clotting.
Most of these risk factors associated with high triglyceride levels are part of condition called metabolic syndrome, a condition caused by excess weight and lack of exercise in people who are prone to develop insulin resistance. So, treating high triglyceride levels is most often not done in isolation, but requires treating the constellation of risk factors associated with metabolic syndrome.
What Can Cause High Cholesterol?
Elevated cholesterol levels can be caused by several factors, including heredity, poor diet, obesity, sedentary lifestyle, age, and gender (premenopausal women have lower cholesterol levels than men). Several medical conditions, including diabetes, hypothyroidism (low thyroid,) liver disease, AND chronic renal (kidney) failure, can also increase cholesterol levels. Drugs, such as steroids and progesterone, can do the same.
What Are "Desirable" Cholesterol Levels?
Total cholesterol: Desirable blood levels for total cholesterol are below 200 mg/dL. Levels between 200 and 239 are considered "borderline." Levels above 240 are considered high.
LDL cholesterol: Optimal LDL levels are less than 100 mg/dL. Near optimal levels are between 100 and 129. Levels between 130 and 159 are considered "borderline;" levels between 160 and 189 are considered "high;" and levels of 190 and above are considered "very high."
HDL cholesterol: In general, the higher the HDL cholesterol levels the better. HDL levels below 41 mg/dL are considered too low.
Who Needs To Be Treated For Elevated Cholesterol?
While various professional groups have offered guidelines for treating cholesterol, most American physicians follow the current recommendations from the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III, or ATP III). The ATP III guidelines recommend making treatment decisions according to two considerations:
Additional risk factors that modify cholesterol goals:
- cigarette smoking
- diabetes
- hypertension -- blood pressure greater than 140/90
- blood pressure medication
- low HDL cholesterol
- family history of premature heart disease (close male relative with heart disease before age 55, or close female relative with heart disease before age 65)
- age greater than 45 in men, or greater than 55 in women
- an estimated 10-year risk of heart attack of 20% or higher, calculated using a formula derived from the Framingham study. NIH Online Version of the 10-year Risk Calculator
Formal guidelines like the ATP III recommendations usually stress lifestyle changes as the primary method of reducing elevated cholesterol and triglyceride levels. These lifestyle changes primarily consist of diet, exercise, and weight loss.
Recommended dietary changes include incorporating low total fat, low saturated fat, low dietary cholesterol, and increased starch and fiber. Physical activity should ideally consist of at least 20 minutes of aerobic exercise, three to five times per week, but in fact any increase in physical activity is helpful. Patients who are obese can often significantly reduce their LDL cholesterol and triglyceride levels by losing weight.
Cholesterol levels should be re-measured 3-6 months after undertaking these lifestyle-based efforts at improving lipid levels. If lipid levels are still not satisfactory, drug therapy should then be considered.
What Drugs Are Used to Treat Cholesterol and Triglycerides?
Drugs used to treat cholesterol and triglyceride levels fall into five major categories:
Bile acid binding resins: Cholestyramine prevents the cholesterol in bile (the digestive product secreted from the gallbladder) from being reabsorbed into the bloodstream in the gut, so the cholesterol is excreted in the stool. Side effects include intestinal gas and gallstones, which significantly limits their usefulness. Cholestyramine can also cause a decrease in the absorption of other drugs you may be taking, as well as certain vitamin deficiencies. In addition, cholestyramine can can occasionally cause an increase in triglyceride levels.
Niacin: Niacin is one of the B vitamins. When used in large doses and in the correct form, it can significantly reduce LDL cholesterol and increase HDL cholesterol. Its major side effects include skin flushing and severe itching, along with gastrointestinal disturbances; it can cause liver disease in some formulations. Nicacin is very effective, but because of side effects, it often tends to be poorly tolerated. Using niacin appropriately and safely to treat lipid levels can be tricky and potentially dangerous, and in general should be done under a doctor's supervision.
Fibric acid derivatives: The chief benefits of the fibric acid derivatives, gemfibrozil and clofibrate, are that they can lower triglyceride levels and (very modestly) increase HDL cholesterol levels. Their ability to reduce LDL cholesterol is much more modest. Their side effects include nausea, vomiting, abdominal pain and gallstones. The frequency of these side effects often limit their usefulness.
Ezitimibe: Ezitimibe is a unique anti-cholesterol drug that works by reducing the absorption of dietary cholesterol by the gut. Ezitimibe is marketed as Zetia, and in combination with a statin drug as Vytorin. Ezitimibe significantly reduces LDL cholesterol levels. However, this drug has been the subject of much controversy since 2008, when the ENHANCE trial suggested that (despite the successful reduction in cholesterol with ezitimibe), patients treated with this drug may have had more rapid progression of atherosclerosis. It is currently used by most doctors only when adequate cholesterol levels cannot be achieved with other measures.
Statins: The statin drugs inhibit the liver enzyme HMG-CoA reductase, which significantly reduces the production of cholesterol by the liver. These drugs almost always produce a substantial reduction in LDL cholesterol, with a modest decrease in triglycerides, and a modest increase in HDL cholesterol. They tend to be well-tolerated in general, but can cause elevations in liver enzymes, and a muscle disorder which can be severe in rare cases. The muscle disorder (myopathy) is particularly likely when statins are used in combination with gemfibrozil.
Finally, there are some non-prescription approaches to reducing cholesterol that may sometimes be effective.
Of all these drug choices, the statins are not only generally more effective than drugs in other categories, they also tend to be much better tolerated. Furthermore, evidence is accumulating that the aggressive use of statins can slow the progression of coronary artery disease, and can stabilize coronary artery plaques (which can reduce the risk of acute coronary syndrome (ACS)).
Treating Abnormal Lipids - Summary
The most common approach to the treatment of abnormal lipid levels can be summarized as follows: First, dietary changes, weight loss, and exercise are tried. If that fails (human nature being what it is), then most doctors will try statins. If statins fail, or if they are not tolerated, an agent from another class of the lipid-lowering drugs can be tried.
http://heartdisease.about.com/cs/cholesterol/a/choltri.htm
Based on these two items (i.e., lipid levels and presence of additional risk factors) treatment is recommended as follows:
For those with 0 - 1 risk factors:The target LDL level is 160 mg/dL or lower. If the LDL level is greater than 159, lifestyle changes should be initiated to reduce cholesterol levels. If the LDL level is greater than 189, drug treatment should be strongly considered.
For those with 2 or more risk factors:The target LDL level is 130 mg/dL or lower. If the LDL level is greater than 129, lifestyle changes should be initiated. Drug therapy should be strongly considered for LDL levels above 159.
If heart disease is already present, or the calculated 10-year risk of heart attack is greater than 20%, or if diabetes is present: The target LDL level is 100 mg/dL or lower. If the LDL level is greater than 100, lifestyle changes should be initiated. If the LDL level is greater than 129, drug treatment should be strongly considered.
What About Treatment for High Triglycerides?
The latest guidelines recommend treating patients who have elevated triglyceride levels. The decision to treat is generally based on the triglyceride levels themselves. Normal triglyceride levels are less than 150 mg/dL. Borderline high levels are 150-199 mg/dl. High levels are 200-499 mg/dL, and very high triglyceride levels are greater than 500 mg/dL.
Most people with elevated triglyceride levels have metabolic syndrome (or diabetes), so the foundation of therapy is lifestyle modification, specifically, weight loss and exercise. Drug therapy is often required, however, if triglyceride levels are in the "very high" range.
What Other "Special Circumstances" Deserve Attention?
Patients with very high LDL cholesterol levels (greater than 189 mg/dL): These patients often have a genetic form of lipid disorder. Not only do they have a high risk of premature heart disease without aggressive therapy, but their family members should ALSO be screened for elevated cholesterol levels; those with high cholesterol levels also need to be treated.
Patients with low HDL cholesterol levels (less than 40 mg/dL): The latest guidelines recognize low HDL levels as a strong independent risk factor for coronary artery disease. Many of patients with low HDL will have diabetes or metabolic syndrome. They are often overweight and physically inactive. Other causes of low HDL levels are smoking, very high carbohydrate diets (greater than 60% of calories accounted for by carbohydrates), and drugs (such as steroids and progesterone). Treatment low HDL levels is usually aimed at weight reduction, smoking cessation, exercise, and controlling other risk factors (such as hypertension, LDL cholesterol, and triglycerides). Therapy with niacin may also increase HDL levels.
How Are Elevated Cholesterol and Triglycerides Treated?