Document Detail

Aggressive lipid-lowering is more effective than moderate lipid-lowering treatment in carotid plaque stabilization.
MedLine Citation:
PMID:  19837545     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: Atherosclerotic plaque stabilization is a promising strategy to prevent cerebrovascular events in patients with carotid atherosclerosis. Vascular calcification inhibitors, known osteopontin (OPN) and osteoprotegerin (OPG), have emerged as novel cardiovascular biomarkers. This open-label, prospective study aimed to examine whether aggressive lipid-lowering therapy with atorvastatin is more effective than moderate lipid-lowering in increasing carotid plaque echogenicity, assessed by Gray-Scale Median (GSM) score and suppressing serum OPN and OPG levels in patients with moderate carotid stenosis.
METHODS: One hundred forty patients (64 males, 76 females), aged 50 to 75 years, with carotid stenosis (North American Symptomatic Carotid Endarterectomy Trial [NASCET]: 30%-60% for symptomatic and 30%-70% for asymptomatic), but without indications for surgical intervention, were enrolled. Patients with coronary heart disease, renal failure, hypothyroidism, osteoporosis, and ongoing use of statins were excluded. Patients were randomly assigned to: Group A (N = 70): Moderate lipid-lowering therapy with low-dose of atorvastatin (10 mg-20 mg) to target LDL-C <100 mg/dL. Group B (N = 70): Aggressive lipid-lowering therapy with high-dose of atorvastatin (80 mg) to target LDL-C <70 mg/dL. Blood pressure, lipid and glycemic indexes, hsCRP, serum OPN, and OPG were measured at baseline and after 12 months as well as the GSM score. Independent samples t test, paired samples t test, Pearson correlation, and multiple regression analysis were used (P < .05).
RESULTS: There were no significant differences between groups at baseline. Three patients in group A experienced either cerebrovascular or cardiac ischemic attacks, while two patients in group B underwent coronary angioplasty during follow-up. Group B showed a more pronounced improvement in total cholesterol and LDL-cholesterol compared with group A (P < .05). Moreover, atorvastatin treatment suppressed serum hsCRP, OPN, and OPG levels from baseline in both groups (P < .001). Notably, aggressive treatment decreased OPN (P = .012) and OPG (P = .025) levels to a greater degree compared with moderate treatment. Similarly, GSM score was remarkably increased in both groups, but that augmentation was greater in group B (from 66.39 +/- 23.66 to 100.4 +/- 25.31) than in group A (from 64.4 +/- 23.62 to 85.39 +/- 20.21) (P = .024). No change in the degree of carotid stenosis was noted in both treatment arms. Importantly, the aforementioned reduction in OPN (r = -0.517, P = .024) and OPG (r = -0.312, P = .008) levels was inversely associated with GSM score changes in univariate and standard multiple regression analysis (R(2) = 0.411, P = .021).
CONCLUSIONS: Among patients with moderate carotid stenosis, an aggressive atorvastatin regimen enhanced carotid plaque echogenicity and reduced serum OPN and OPG levels to a greater extent than respective moderate atorvastatin therapy. Most importantly, those atorvastatin-induced effects were associated with OPN and OPG suppression in a dose-dependent manner.
Nikolaos P E Kadoglou; Nikolaos Sailer; Anestis Moumtzouoglou; Alkistis Kapelouzou; Thomas Gerasimidis; Christos D Liapis
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Publication Detail:
Type:  Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2009-10-17
Journal Detail:
Title:  Journal of vascular surgery     Volume:  51     ISSN:  1097-6809     ISO Abbreviation:  J. Vasc. Surg.     Publication Date:  2010 Jan 
Date Detail:
Created Date:  2010-02-01     Completed Date:  2010-02-23     Revised Date:  2012-10-03    
Medline Journal Info:
Nlm Unique ID:  8407742     Medline TA:  J Vasc Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  114-21     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
First Department of Internal Medicine, Hippokratio General Hospital of Thessaloniki, Thessaloniki, Greece.
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MeSH Terms
Biological Markers / blood
C-Reactive Protein / metabolism
Carotid Stenosis / blood,  complications,  drug therapy*,  ultrasonography
Cerebrovascular Disorders / etiology,  prevention & control
Cholesterol, LDL / blood
Dose-Response Relationship, Drug
Heptanoic Acids / administration & dosage*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage*
Middle Aged
Myocardial Ischemia / etiology,  prevention & control
Osteopontin / blood
Osteoprotegerin / blood
Prospective Studies
Pyrroles / administration & dosage*
Severity of Illness Index
Time Factors
Treatment Outcome
Ultrasonography, Doppler
Reg. No./Substance:
0/Biological Markers; 0/Cholesterol, LDL; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Osteoprotegerin; 0/Pyrroles; 0/SPP1 protein, human; 0/TNFRSF11B protein, human; 106441-73-0/Osteopontin; 110862-48-1/atorvastatin; 9007-41-4/C-Reactive Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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