Cholesterol Particle Size

LDL patterns A and B refer to the size of LDL cholesterol particles in the blood. Some doctors believe that small LDL cholesterol particles in the blood may pose a greater risk for developing atherosclerosis and heart attacks than the absolute level of LDL cholesterol in the blood. The size of LDL cholesterol particles is primarily inherited. A special blood test called polyacrylamide gradient gel electrophoresis can measure particle size and determine whether a person has blood cholesterol LDL pattern A or LDL pattern B.

Persons with LDL cholesterol pattern A have large, buoyant LDL cholesterol particles. Individuals with pattern A are more likely to have normal blood levels of LDL cholesterol, HDL cholesterol, and triglycerides. Pattern A is usually not associated with an increased likelihood of atherosclerosis.

Persons with LDL cholesterol pattern B have predominantly small and dense LDL cholesterol particles. Pattern B is frequently associated with low HDL cholesterol levels, elevated triglyceride levels, and the tendency to develop high blood sugar levels and type II diabetes mellitus.

Individuals with pattern B are also more likely to develop high blood triglyceride levels after a fatty meal (postprandial hyperlipidemia). Pattern B is associated with accelerated atherosclerosis and a 3 to 5- fold increase in heart attack risk. Pattern B is believed to be the most important cause of atherosclerosis in people with normal or near normal total and LDL cholesterol levels.

Some scientists believe that the smaller LDL particles are more dangerous than the larger ones because they can more easily squeeze through the tiny gaps between the cells in the endothelium to reach inside the artery walls. The endothelium is a thin layer of cells which covers the inner wall of the arteries. The cells making up the endothelium have tiny gaps between them. Others postulate that the smaller LDL cholesterol particles are more easily oxidized. Oxidation of cholesterol is significant in the formation of cholesterol plaques.

How can LDL cholesterol size be enlarged?

Even though LDL cholesterol particle size is mainly genetically inherited, individuals who have small LDL particles (pattern B) can increase their particle size through diet, exercise, and medications.

Diets that are low in saturated fat and cholesterol, regular aerobic exercise, and loss of excess body fat have been determined to decrease the number of small LDL particles and increase the number of large LDL particles in the blood. In other words, lifestyle modifications can change pattern B to pattern A.

When lifestyle changes alone are unsuccessful, medications can be used. Even though the statin medications (discussed above) are effective in lowering the absolute levels of LDL cholesterol, they appear to have a limited effect on LDL cholesterol size pattern. Medications such as nicotinic acid (niacin) and gemfibrozil (Lopid) have been found effective in many instances in increasing the size of LDL cholesterol particles.

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%.

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