Lipoproteins and homocyst(e)ine as risk factors for atherosclerosis: assessment and treatment.

Two new important independent risk factors for coronary artery disease (CAD) have been identified: lipoprotein (a) [Lp(a)] and homocyst(e)ine. Both are associated with increased frequency of cardiovascular events, both coronary and peripheral. Measurement of these two factors should be considered in patients with symptomatic CAD, stroke, a strong family history (but low other conventional risk factors); in first degree relatives of those with very high Lp(a) or homocyst(e)ine levels; and in other individuals in whom the need for an aggressive treatment of metabolic risk factors is indicated. While treatment of high serum Lp(a) with drugs is difficult it appears from the epidemiological or clinical evidence that the additional risk due to Lp(a) can be drastically lowered by decreasing the patient's low density lipoprotein (LDL) cholesterol levels to below 3 mmol/L. The treatment of increased homocyst(e)ine can be easily accomplished by vitamin B6 or folic acid administration. Various analyses describing the value of positive tests for diagnosis of atherosclerosis indicate that overall risk evaluated by computer models from Framingham data, use of total: high density lipoprotein (HDL) cholesterol ratio and/or the National Cholesterol Education Program (NCEP) II guidelines are the best predictors of future cardiovascular events. The strategic aim for treatment regimens should be threefold: lower serum LDL cholesterol levels; decrease serum triglycerides (and triglyceride-rich lipoproteins); and increase HDL cholesterol. Niacin and statin drugs are the most cost effective means to achieve the former and niacin and fibrates to achieve the latter goal. Where target LDL cholesterol levels can be achieved with less expensive statin preparations their use may be economically advantageous.