EFFECT OF APHERESIS OF LOW-DENSITY-LIPOPROTEIN ON PERIPHERAL VASCULAR-DISEASE IN HYPERCHOLESTEROLEMIC PATIENTS WITH CORONARY-ARTERY DISEASE

Background: Apheresis of low-density lipoprotein (LDL) is an effective lipid-lowering treatment in hypercholesterolemic patients who have co ronary artery disease and are refractory to drugs. More aggressive lip id-lowering therapy may further slow the progression of atherosclerosi s. Objective: To compare the effect of LDL apheresis and simvastatin t herapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease. Design: Open, randomized, single-cent er study. Setting: University hospital. Patients: 42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extens ive coronary atherosclerosis. Intervention: Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years. Measurements: Lipid and lipoprotein levels, changes in he modynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spect rum analysis of the femoral artery), and changes in the mean intima-me dia thickness of three carotid artery segments. Results: Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the aphere sis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastati n-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 m g/dL (change, -19%) in the former group and increased from 38.4 to 44. 5 mg/dL (change, 15%) in the latter group. In the apheresis group, the number of patients with hemodynamically significant stenoses in the a ortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thic kness decreased by a mean +/- SD of 0.05 +/- 0.34 mm in the apheresis group and increased by 0.06 +/- 0.38 mm in the simvastatin-only group (P < 0.001). According to multiple regression analysis, changes in apo lipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R(2) = 0.36); changes in lipopro tein(a) and apolipoprotein Al levels accounted for changes in the inti ma-media thickness of the carotid artery (R(2) = 0.49). Conclusions: A ggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an incr ease in the number of hemodynamically significant stenoses in the lowe r limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.