CLINICAL STUDY: ENDOTHELIAL FUNCTION
Improvement of coronary artery endothelial dysfunction with lipid-lowering therapy: heterogeneity of segmental response and correlation with plasma-oxidized low density lipoprotein
William F. Penny, MD, FACC*,
Ori Ben-Yehuda, MD ,
Kenji Kuroe, MA,
John Long, PhD* ,
Alan Bond, PhD* ,
Valmik Bhargava, PhD, FACC*,
Joseph F. Peterson, MD* ,
Martin McDaniel, BA,
Joseph Juliano, BS,
Joseph L. Witztum, MD,
John Ross, Jr., MD, FACC and
Kirk L. Peterson, MD, FACC
* University of California, San Diego, California, USA
Veterans Administration Medical Center, San Diego, California, USA
Manuscript received November 9, 1999;
revised manuscript received October 20, 2000,
accepted November 22, 2000.
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, 10–4M) 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 10–6M, 10–5M and 10–4M 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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Abbreviations and Acronyms
| | Ach | = acetylcholine | | Apo | = apolipoprotein | | eNOS | = endothelial nitric oxide synthase | | HDL | = high density lipoprotein | | HLM | = hierarchical linear model | | IgG | = immunoglobulin G | | IgM | = immunoglobulin M | | LDL | = low density lipoprotein | | LRfx | = lipid reduction effect | | MDA | = malondialdehyde | | NO | = nitric oxide | | ox-LDL | = oxidized low density lipoprotein |
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