Does Lipoprotein(a) Impair Endothelial Function?

Objectives. This study was undertaken to test the hypothesis that lipoprotein(a) [Lp(a)] impairs endothelial function. Background. Elevated Lp(a) plasma levels have been demonstrated to be associated with an increased risk of coronary heart disease. In atherosclerosis, endothelial dysfunction is kno...

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Bibliographic Details
Published in:Journal of the American College of Cardiology 1998-02, Vol.31 (2), p.359-365
Main Authors: Schlaich, Markus P, John, Stefan, Langenfeld, Matthias R.W, Lackner, Karl J, Schmitz, Gerd, Schmieder, Roland E
Format: Article
Language:English
Subjects:
Acetylcholine - administration & dosage
Acetylcholine - pharmacology
Adult
Arteriosclerosis - physiopathology
Atherosclerosis (general aspects, experimental research)
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Cholesterol, HDL - blood
Cholesterol, LDL - blood
Coronary Disease - etiology
Endothelium, Vascular - drug effects
Endothelium, Vascular - physiopathology
Enzyme Inhibitors - administration & dosage
Enzyme Inhibitors - pharmacology
Female
Forearm - blood supply
Humans
Immunoelectrophoresis
Infusions, Intra-Arterial
Lipoprotein(a) - blood
Lipoprotein(a) - physiology
Male
Medical sciences
Middle Aged
Nitric Oxide - metabolism
Nitric Oxide - pharmacology
Nitric Oxide Synthase - antagonists & inhibitors
Nitroprusside - administration & dosage
Nitroprusside - pharmacology
omega-N-Methylarginine - administration & dosage
omega-N-Methylarginine - pharmacology
Plethysmography
Regional Blood Flow - drug effects
Regression Analysis
Risk Factors
Vasoconstrictor Agents - administration & dosage
Vasoconstrictor Agents - pharmacology
Vasodilation - drug effects
Vasodilator Agents - pharmacology
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Summary:Objectives. This study was undertaken to test the hypothesis that lipoprotein(a) [Lp(a)] impairs endothelial function. Background. Elevated Lp(a) plasma levels have been demonstrated to be associated with an increased risk of coronary heart disease. In atherosclerosis, endothelial dysfunction is known to be an early indicator of vascular changes. However, the effect of Lp(a) on nitric oxide (NO)-dependent vasodilator response has not yet been determined. We therefore examined the influence of Lp(a) on basal and stimulated NO-mediated vasodilator response in the forearm vascular bed. Methods. Strain gauge plethysmography was used to measure changes in forearm blood flow produced by intraarterial infusion of increasing doses of acetylcholine (3, 12, 24 and 48 μg/min), sodium nitroprusside (200, 800 and 3,200 ng/min) and N-monomethyl l-arginine (l-NMMA) (1, 2 and 4 μmol/min) in 57 white subjects (mean age ± SD 37 ± 14 years). Lp(a) plasma concentrations were determined by rocket immunoelectrophoresis. Results. Endothelium-dependent vasodilation tested by intraarterial acetylcholine and endothelium-independent vascular relaxation tested by intraarterial sodium nitroprusside were not correlated with Lp(a). Similarly, no significant differences in forearm blood flow changes were observed when patients were classified into tertiles according to their individual Lp(a) concentration. In contrast, changes in forearm blood flow after intraarterial l-NMMA indicating basal production and release of NO differed significantly among tertiles. Patients in the highest Lp(a) tertile (49.2 ± 20.3 mg/dl) had a much greater vasoconstrictive response to l-NMMA than patients in the lowest Lp(a) tertile (4.8 ± 2.5 mg/dl): 2 μmol/min of l-NMMA, −23.6 ± 22.5% vs. −10.4 ± 9.1% (p < 0.02); 4 μmol/min of l-NMMA, −27.8 ± 10.3% vs. −17.6 ± 9.9% (p < 0.03). Lp(a) plasma level consistently correlated negatively with the forearm blood flow responses to 4 μmol/min of intraarterial l-NMMA (r = −0.38, p < 0.01). Multiple stepwise regression analysis of variables, including total and high and low density lipoprotein cholesterol, further confirmed that plasma Lp(a) remained a significant independent determinant of forearm blood flow changes in response to l-NMMA (p < 0.02). Conclusions. The endothelium-dependent vasoconstrictive response to l-NMMA was enhanced in subjects with relatively high Lp(a) plasma levels, suggesting an increased basal production and release of NO. This response seemed to
ISSN:0735-1097
1558-3597
DOI:10.1016/S0735-1097(97)00497-X