Is 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%.