Atorvastatin reduces macrophage accumulation in atherosclerotic plaques: a comparison of a nonstatin-based regimen in patients undergoing carotid endarterectomy.
OBJECTIVE
The object of our study was to compare the effect of high-dose vs low-dose atorvastatin vs nonstatin-based treatment (cholestyramine plus sitosterol) on cell composition of carotid plaque.


METHODS
We recruited 60 hypercholesterolemic patients (total cholesterol, 5.83-7.64 mmol/L) eligible for carotid endarterectomy. Three months before surgery, patients were randomized into 3 groups (n=20) receiving atorvastatin 10 mg/day (AT-10) or atorvastatin 80 mg/day (AT-80) or cholestyramine 8 g/day plus sitosterol 2.5 g/day. Analysis of cell composition was performed on endarterectomy specimens.


RESULTS
The 3 treatments resulted in a significant reduction of total cholesterol and low-density lipoprotein cholesterol (LDL-C), although the decrease in total cholesterol and LDL-C was of smaller magnitude in the cholestyramine plus sitosterol group. The 3 regimens did not influence the levels of inflammatory markers (including high-sensitivity C-reactive protein). Macrophage content was significantly lower in the AT-10 group plaques compared to the cholestyramine plus sitosterol group. It was further reduced in the AT-80 group plaques. These differences were no longer significant after adjustment for changes in LDL-C. No difference in lymphocyte number was observed among treatments, whereas the content of smooth muscle cells was higher in the AT- 80 group. An inverse association was observed between LDL-C changes in the 3 groups and macrophage content in the plaques.


CONCLUSIONS
Short-term treatment with high-dose statin is superior to a nonstatin lipid-lowering regimen in reducing the macrophage cell content within atherosclerotic lesions, but this effect was determined by the degree of LDL-C-lowering.
Puato
Massimo
M
Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Padova, Medicina Interna I, Ospedale Ca' Foncello, Via Ospedale, 31100 Treviso, Italy.
Faggin
Elisabetta
E
Rattazzi
Marcello
M
Zambon
Alberto
A
Cipollone
Francesco
F
Grego
Franco
F
Ganassin
Lorenzo
L
Plebani
Mario
M
Mezzetti
Andrea
A
Pauletto
Paolo
P
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000008:administration & dosage*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology / Q000628:therapy; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D002792:Cholestyramine Resin / Q000008:administration & dosage*; D016894:Endarterectomy, Carotid; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000473:pathology / Q000628:therapy; D018655:Lymphocyte Count; D008264:Macrophages / Q000473:pathology*; D008297:Male; D011758:Pyrroles / Q000008:administration & dosage*; D012855:Sitosterols / Q000008:administration & dosage*
D000924:Anticholesteremic Agents; D015415:Biomarkers; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D011758:Pyrroles; D012855:Sitosterols; D002792:Cholestyramine Resin; C025473:gamma-sitosterol; D002097:C-Reactive Protein; D000069059:Atorvastatin