Document Detail


Low-density lipoprotein lowering does not improve calf muscle perfusion, energetics, or exercise performance in peripheral arterial disease.
MedLine Citation:
PMID:  21867844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: We hypothesized that low-density lipoprotein (LDL) reduction regardless of mechanism would improve calf muscle perfusion, energetics, or walking performance in peripheral arterial disease (PAD) as measured by magnetic resonance imaging and magnetic resonance spectroscopy.
BACKGROUND: Statins improve cardiovascular outcome in PAD, and some studies suggest improved walking performance.
METHODS: Sixty-eight patients with mild to moderate symptomatic PAD (age 65 ± 11 years; ankle-brachial index [ABI] 0.69 ± 0.14) were studied at baseline and annually for 2 years after beginning simvastatin 40 mg (n = 20) or simvastatin 40 mg/ezetimibe 10 mg (n = 18) if statin naïve, or ezetimibe 10 mg (n = 30) if taking a statin. Phosphocreatine recovery time was measured by (31)P magnetic resonance spectroscopy immediately after symptom-limited calf exercise on a 1.5-T scanner. Calf perfusion was measured using first-pass contrast-enhanced magnetic resonance imaging with 0.1 mM/kg gadolinium at peak exercise. Gadolinium-enhanced magnetic resonance angiography was graded. A 6-min walk and a standardized graded Skinner-Gardner exercise treadmill test with peak Vo(2) were performed. A repeated-measures model compared changes over time.
RESULTS: LDL reduction from baseline to year 2 was greater in the simvastatin 40 mg/ezetimibe 10 mg group (116 ± 42 mg/dl to 56 ± 21 mg/dl) than in the simvastatin 40 mg group (129 ± 40 mg/dl to 90 ± 30 mg/dl, p < 0.01). LDL also decreased in the ezetimibe 10 mg group (102 ± 28 mg/dl to 79 ± 27 mg/dl, p < 0.01). Despite this, there was no difference in perfusion, metabolism, or exercise parameters between groups or over time. Resting ABI did improve over time in the ezetimibe 10 mg group and the entire study group of patients.
CONCLUSIONS: Despite effective LDL reduction in PAD, neither tissue perfusion, metabolism, nor exercise parameters improved, although rest ABI did. Thus, LDL lowering does not improve calf muscle physiology or functional capacity in PAD. (Comprehensive Magnetic Resonance of Peripheral Arterial Disease; NCT00587678).
Authors:
Amy M West; Justin D Anderson; Frederick H Epstein; Craig H Meyer; Hongkun Wang; Klaus D Hagspiel; Stuart S Berr; Nancy L Harthun; Arthur L Weltman; Joseph M Dimaria; Jennifer R Hunter; John M Christopher; Christopher M Kramer
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  58     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-08-26     Completed Date:  2011-10-24     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1068-76     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00587678
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MeSH Terms
Descriptor/Qualifier:
Aged
Anticholesteremic Agents / pharmacology,  therapeutic use*
Azetidines / pharmacology,  therapeutic use*
Cholesterol, LDL / blood
Energy Metabolism
Exercise Test
Exercise Tolerance / drug effects
Female
Humans
Leg / blood supply*
Magnetic Resonance Angiography
Magnetic Resonance Spectroscopy
Male
Middle Aged
Muscle, Skeletal / blood supply,  metabolism
Peripheral Arterial Disease / blood,  drug therapy*
Phosphocreatine / metabolism
Simvastatin / pharmacology,  therapeutic use*
Grant Support
ID/Acronym/Agency:
M01RR000847/RR/NCRR NIH HHS; R01 HL075792/HL/NHLBI NIH HHS; R01 HL075792/HL/NHLBI NIH HHS; T32 EB003841/EB/NIBIB NIH HHS; T32 EB003841/EB/NIBIB NIH HHS
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Azetidines; 0/Cholesterol, LDL; 020IUV4N33/Phosphocreatine; 163222-33-1/ezetimibe; AGG2FN16EV/Simvastatin
Comments/Corrections
Comment In:
J Am Coll Cardiol. 2011 Aug 30;58(10):1077-9   [PMID:  21867845 ]

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