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 coronary artery disease and are refractory to drugs. More aggressive lipid-lowering therapy may further slow the progression of atherosclerosis.


OBJECTIVE
To compare the effect of LDL apheresis and simvastatin therapy with the effect of simvastatin therapy alone on the progression of peripheral vascular disease.


METHODS
Open, randomized, single-center study.


METHODS
University hospital.


METHODS
42 men with primary hypercholesterolemia (total cholesterol level > 8.0 mmol/L) and extensive coronary atherosclerosis.


METHODS
Biweekly apheresis of LDL plus simvastatin, 40 mg/d (n = 21), or simvastatin, 40 mg/d (n = 21), for 2 years.


METHODS
Lipid and lipoprotein levels, changes in hemodynamically significant stenoses in the aortotibial tract (measured by ankle:arm systolic blood pressure ratio combined with Doppler spectrum analysis of the femoral artery), and changes in the mean intima-media thickness of three carotid artery segments.


RESULTS
Mean baseline LDL cholesterol levels decreased from 7.8 to 3.0 mmol/L in the apheresis and simvastatin group and from 7.9 to 4.1 mmol/L in the simvastatin-only group; mean lipoprotein(a) levels decreased from 57.0 to 44.5 mg/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 aortotibial tract decreased from 9 to 7; in the simvastatin-only group, the number increased from 6 to 13 (P = 0.002). Mean intima-media thickness 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 apolipoprotein B, total cholesterol, and lipoprotein(a) levels accounted for changes in the aortotibial tract (R2 = 0.36); changes in lipoprotein(a) and apolipoprotein A1 levels accounted for changes in the intima-media thickness of the carotid artery (R2 = 0.49).


CONCLUSIONS
Aggressive lipid lowering with simvastatin and LDL apheresis decreased the intima-media thickness of the carotid artery and prevented an increase in the number of hemodynamically significant stenoses in the lower limbs. Therapy with simvastatin alone did not prevent progression of carotid or aortotibial vascular disease.
Kroon
A A
AA
University Hospital Nijmegen, The Netherlands.
van Asten
W N
WN
Stalenhoef
A F
AF
D000328:Adult; D000368:Aged; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001781:Blood Component Removal; D008078:Cholesterol, LDL / Q000378:metabolism*; D003131:Combined Modality Therapy; D003324:Coronary Artery Disease / Q000097:blood / Q000150:complications* / Q000628:therapy; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006439:Hemodynamics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000628:therapy*; D008148:Lovastatin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000097:blood / Q000150:complications / Q000628:therapy*; D019821:Simvastatin
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D004791:Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008148:Lovastatin; D019821:Simvastatin