CHOLESTEROL AND ITS TREATMENT

Heart attacks are the leading cause of death in our society. Heart attacks occur when a complex process called atherosclerosis leads to damage of the lining of the blood vessels. This in turn leads to “plaque” formation and obstruction of blood flow through the vessel. The traditional risk factors for heart attacks include abnormal lipids, smoking, diabetes, hypertension, male gender, and family history. One of the main preventative measures is treatment of abnormal lipid profiles.

Cholesterol and triglycerides are two forms of lipids or fats. Cholesterol is necessary for building cell membranes and making several essential hormones. Triglycerides are chains of high energy fatty acids which provide most of the energy needed for cells to function.

Cholesterol and triglycerides come from two sources: diet and endogenous (manufactured within the body-usually within the liver). Dietary cholesterol and triglycerides come mainly from eating animal products and saturated fat. Once eaten, the dietary lipids are absorbed through the gut and then delivered through the bloodstream to the liver where they undergo processing. In the liver, the cholesterol and triglycerides are packaged into tiny spheres called lipoproteins. These lipoproteins are released into the circulation and delivered to the cells of the body. The lipoproteins most commonly discussed are LDL “low density lipoprotein” and HDL “high density lipoprotein.” We commonly refer to the LDL cholesterol as the “bad cholesterol” and the HDL cholesterol as the “good cholesterol.” With increasing elevation of LDL cholesterol, either alone or in combination with other risk factors, oxidation may occur. Change in the size of the LDL cholesterol proteins may then follow. This oxidized, or abnormally shaped LDL, can lead to damage of the blood vessels. The “Teflon” coating of the blood vessel walls subsequently becomes damaged by this abnormal LDL cholesterol. The HDL is felt to be protective and reduced levels of HDL lead to loss of protection of the blood vessel lining and further damage.

Triglycerides have been a problematic component of the lipid profile. It is presently felt that triglycerides acting alone or particularly in conjunction with low HDL can lead to damage of the blood vessel lining. Particularly in diabetics or those with the disorder known as the metabolic syndrome, elevated triglycerides are a worrisome risk factor. Again, triglycerides in the bloodstream are derived from fats eaten in foods or made in the body from other energy sources like carbohydrates. Calories ingested in a meal that are not used immediately by tissues are converted into triglycerides and transported to fat cells to be stored.

Most emphasis for treatment is currently placed on the LDL cholesterol. Achieving a goal of less than 130 is recommended in almost all individuals. In those with significant risk factors, an LDL level of less than 100 is advised. In very high risk individuals, particularly those who have had bypass surgery, coronary stents, or diabetes, an LDL level of 70 or less is desirable. In regards to triglycerides, a reasonable goal is a level less than 150. However, this is not easily obtainable particularly in individuals with diabetes. The goal for the HDL in most individuals is in excess of 40 and ideally greater than 50. This level is difficult to achieve with medications currently available.

Once lipid panels are measured, either prior to or in conjunction with medical therapy, some lifestyle changes are warranted. However, it is important to realize that it is very difficult to lower LDL cholesterol significantly by dietary measures alone. Current recommendations include weight loss with particular emphasis on reducing the amount of saturated fat and cholesterol content within the diet. Oil, such as Canola or olive, is preferred to saturated fats like butter. Physical activity most days of the week along with modest alcohol intake may also decrease the triglyceride levels as well as increase the HDL levels. Reduction in the amount of fat consumed from animal sources is also beneficial.

“Statins” have been very effective in reducing LDL cholesterol. In fact, these were the first drugs to show decrease in cardiovascular mortality as well as all-cause mortality. This means that in patients at risk, statin drugs improve their overall outlook and decrease their risk of death compared to those patients who do not take statins. Statins have become the mainstay treatment for individuals with coronary artery disease, strokes, and diabetes. They work by inhibiting a key enzyme in the manufacturing of cholesterol in the liver. Some of the older agents were shown to decrease the cholesterol levels by twenty to thirty percent; however, newer agents will decrease LDL cholesterol by an excess of fifty percent. In general, the statin drugs are safe with a low incidence of side effects. However, certain individuals have been troubled by muscle aches and in a very small proportion there is a risk for elevation of liver enzymes. With prudent use of these drugs, however, the side effects can be minimized.

Niacin has been a long-standing drug used in the treatment of hypercholesterolemia. Its mechanism is not entirely clear, but it has been shown to reduce triglycerides and LDL cholesterol while raising the HDL cholesterol. The fibrate drugs act by lowering the triglycerides and again by raising the HDL level. These drugs include Gemfibrozil or Lopid, and fenofibrilates like Tricor. They are useful in patients who tend to have very elevated triglycerides and low HDL. They have also fallen out of favor due to studies indicating minimal benefit unless very high levels are present. Zetia is a newer drug which blocks the intestinal reabsorption of cholesterol. Its main use has been in combination with statins to obtain a further twenty percent or so reduction in the LDL cholesterol. Further studies are ongoing to see if outcomes are similar for the LDL reduction seen with Zetia.

One of the weaknesses in the treatment of abnormal lipids has been the inability of any of the drugs to raise the HDL significantly. The statin drugs, niacin and Gemfibrozil, raise HDL only modestly. In addition, there is a slight rising of the HDL with alcohol intake and exercise. There are new drugs being investigated which hopefully will raise the HDL dramatically, and cause a reduction in cardiovascular events.

The lipid profile is usually obtained in a near fasting state and consists of the total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides. Other lipoprotein particles can be measured through specialized lab services. These can sometimes be beneficial in tailoring the drug therapy to the individual patients. In most individuals, however, the traditional cholesterol panel is helpful and used serially. Depending on the patient’s risk factor profile, previous history of cardiovascular events, and lipid results, decisions are made regarding therapy. In most patients, a statin agent is started and in many individuals a second agent is required in order to achieve the recommended goals. Liver tests are measured periodically to make sure there are no significant elevations. As mentioned above, in some patients, muscle aches may occur. This is often treated by reduction in the present statin agent or switching to another drug within the same class.

New advances in preventive medicine are occurring rapidly in the field of cardiology. The treatment of cholesterol and triglycerides will continue to evolve. It is one piece of the pie in the prevention of car¬diovascular events, the others being prevention of blood clotting or thrombosis and hypertension. Hopefully, we are moving toward the day when we can tailor drugs to the individual patient’s profile, reducing both the risk of complications and increasing the effect of the therapy.