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Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental
W F Penny1, O Ben-Yehuda, K Kuroe
1University of California, San Diego, USA.
Insights
Lipid-lowering therapy improves coronary artery endothelial function, but the effects are heterogeneous across vessel segments. Improvements in vasomotion correlate with reduced markers of oxidized low-density lipoprotein (LDL).
Area of Science:
- Cardiovascular Medicine
- Endocrinology
- Pharmacology
Background:
- Endothelial dysfunction is a hallmark of hypercholesterolemia.
- Lipid-lowering treatments are known to improve endothelial function.
- The segmental variability and specific lipid correlates of this improvement are not well-defined.
Purpose of the Study:
- To assess coronary artery endothelial function in hypercholesterolemic patients before and after lipid-lowering therapy.
- To evaluate the acetylcholine (Ach)-induced response across the entire analyzable coronary artery.
- To determine the correlation between lipid moieties, oxidized LDL markers, and endothelial function improvement.
Main Methods:
- Quantitative angiography was used to measure coronary artery diameter changes in response to Ach (10^-6 to 10^-4 M).
- 29 patients with coronary atherosclerosis underwent assessment before and after 18 months of lipid-lowering treatment (statins, bile sequestrant resins).
- Serial measurements included standard lipids and autoantibody titers against malondialdehyde-LDL (MDA-LDL) and the E06 epitope.
Main Results:
- Lipid-lowering treatment significantly improved coronary vasomotion (p < 0.0001).
- Observed improvements were heterogeneous, with enhanced dilation in some segments and decreased dilation in others.
- Improvement in vasomotion correlated significantly with changes in E06 and Apolipoprotein A-1 titers, and with markers of oxidized LDL.
Conclusions:
- Drug-induced reversal of endothelial dysfunction is heterogeneous across coronary artery segments.
- Assessing the entire analyzable artery is crucial for understanding treatment effects.
- Improved vasomotion is most strongly associated with reduced plasma-oxidized low-density lipoprotein levels.
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.
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