Document Detail

Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein.
MedLine Citation:
PMID:  11693750     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: This study assessed coronary artery endothelial function in patients with hypercholesterolemia before and after lipid lowering, using quantitative angiography to examine the acetylcholine (Ach) response along the entire analyzable vessel. BACKGROUND: Lipid lowering reverses endothelial dysfunction, but whether improvement occurs only in some segments and not others has not been established. Statistical correlation of improvement with specific lipid moieties remains undefined. METHODS: Quantitative angiography was performed after Ach (10(-6), 10(-5), 10(-4) M) in 29 patients with coronary atherosclerosis before and 18 +/- 5.2 months after lipid-lowering treatment (statins, bile sequestrant resins). Standard lipid moieties and markers of oxidized low density lipoprotein (LDL) (immunoglobulin G and M autoantibody titers to malondialdehyde-LDL, E06 epitope) were measured serially. RESULTS: Pre-treatment of the vessel diameters at control and with 10(-6)M, 10(-5) M and 10(-4) M Ach were 2.108 +/- 0.085, 2.086 +/- 0.087, 2.069 +/- 0.084 and 1.963 +/- 0.097 mm (M +/- SE), respectively, and increased at follow-up to 2.139 +/- 0.094, 2.119 +/- 0.086, 2.127 +/- 0.084 and 2.080 +/- 0.085 mm (p < 0.0001). Improvement in the most constricted and modest declination in the more dilated segments were observed. Change in the E06 and Apolipoprotein A-1 titers correlated with improved vasomotion (p = 0.027 and 0.005, respectively). The pre- and post-treatment levels of the E06 epitope, as well as the post-treatment IgM autoantibody titer to MDA-low density lipoprotein, also correlated (p < 0.028, < 0.001 and p < 0.004, respectively). CONCLUSIONS: Drug treatment reverses endothelial dysfunction, but the effect is heterogeneous. Most coronary segments show enhancement, while others show declination of dilation, underscoring the importance of assessing the entire analyzable artery. Improvement in vasomotion correlates most significantly with markers of plasma-oxidized low-density lipoprotein.
W F Penny; O Ben-Yehuda; K Kuroe; J Long; A Bond; V Bhargava; J F Peterson; M McDaniel; J Juliano; J L Witztum; J Ross; K L Peterson
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  37     ISSN:  0735-1097     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2001 Mar 
Date Detail:
Created Date:  2001-11-05     Completed Date:  2001-12-04     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  766-74     Citation Subset:  AIM; IM    
University of California, San Diego, USA.
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MeSH Terms
Acetylcholine / pharmacology
Cholesterol, LDL / blood*
Coronary Angiography
Coronary Vessels / physiopathology*
Endothelium, Vascular / drug effects*
Hypercholesterolemia / blood,  physiopathology*
Middle Aged
Vasodilation / drug effects
Vasodilator Agents / pharmacology
Grant Support
Reg. No./Substance:
0/Cholesterol, LDL; 0/Vasodilator Agents; 51-84-3/Acetylcholine
Comment In:
J Am Coll Cardiol. 2001 Dec;38(7):2136-7   [PMID:  11738332 ]

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