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Lipoprotein(a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary
V Schachinger1, M Halle, J Minners
1Department of Rehabilitation, Prevention and Sports Medicine, University Freiburg, Germany. schaechinger@em.uni-frankfurt.de
Insights
High lipoprotein(a) [Lp(a)] levels impair specific endothelium-dependent vasodilation, particularly receptor-mediated responses, potentially contributing to coronary artery disease pathogenesis.
Area of Science:
- Cardiovascular Medicine
- Endothelial Function Research
- Lipoprotein Metabolism
Background:
- Lipoprotein(a) [Lp(a)] is an established independent predictor of coronary artery disease (CAD) development and progression.
- Elevated Lp(a) levels are linked to impaired endothelium-dependent vasodilation in epicardial arteries.
Purpose of the Study:
- To investigate the impact of serum lipoprotein(a) [Lp(a)] levels on various endothelium-dependent vasodilator stimuli.
- To differentiate the effects of Lp(a) on distinct mechanisms of endothelium-dependent vasodilation.
Main Methods:
- Assessed vasomotor responses in 108 patients with angiographically normal or minimally diseased coronary vessels.
- Utilized acetylcholine, cold pressor testing, increased blood flow, and nitroglycerin as vasodilator stimuli.
- Analyzed responses based on Lp(a) serum levels, specifically comparing levels >= 30 mg/dl to < 30 mg/dl.
Main Results:
- Lp(a) levels >= 30 mg/dl were associated with enhanced vasoconstriction to acetylcholine (receptor-mediated) and cold pressor testing (receptor- and flow-mediated).
- No significant compromise was observed in strictly endothelium-dependent, non-receptor-mediated, flow-dependent dilation or endothelium-independent dilation (nitroglycerin).
- Multivariate analysis identified Lp(a) as an independent predictor of paradoxical vasoconstriction to acetylcholine and cold pressor testing.
Conclusions:
- High Lp(a) levels are associated with a selective impairment of vasodilator capacity mediated by receptor-dependent endothelial stimuli.
- This impaired coronary dilator capacity in elevated Lp(a) may contribute to myocardial ischemia pathogenesis, particularly under conditions involving receptor-mediated stimulation like sympathetic activation.
Objectives:
We investigated the influence of lipoprotein(a) [Lp(a)] serum levels on different endothelium-dependent vasodilator stimuli representing different mechanisms of endothelium-dependent vasodilation.
Background:
Lp(a) is an independent predictor for the development and progression of coronary artery disease. Impairment of endothelium-dependent vasodilation of epicardial arteries has been shown in patients with high levels of Lp(a).
Methods:
In 108 patients with angiographically normal or minimally diseased coronary vessels, vasomotor responses to acetylcholine, cold pressor testing, increased blood flow and nitroglycerin were assessed.
Results:
Lp(a) levels > or = 30 mg/dl were associated with significant dose-dependent enhancement of the vasoconstrictor response to acetylcholine [receptor-mediated vasodilation, p = 0.002; acetylcholine 10(-6) mol/liter, -29 +/- 21% vasoconstriction with Lp(a) levels > or = 30 mg/dl vs, -5.6 +/- 25% with Lp(a) levels < 30 mg/dl]. In addition, vasoconstrictor response to cold pressor test (receptor- and flow-mediated vasodilation) was significantly enhanced in patients with Lp(a) levels > or = 30 mg/dl (-13 +/- 12% vs. 1.2 +/- 16%, p = 0.005). In contrast, strictly endothelium-dependent, but non-receptor-mediated, flow-dependent dilation and endothelium-independent dilation with nitroglycerin were not compromised. Linear regression analysis revealed an inverse relation between Lp(a) and both acetylcholine-induced (r = -0.34, p = 0.0007) and cold pressor test-induced (r = -0.44, p = 0.0001) vasodilation. By multivariate analysis, Lp(a) was a strong and independent predictor of paradoxic vasoconstriction only in response to acetylcholine and cold pressor testing. Impairment of coronary blood flow increase in patients with Lp(a) levels > or = 30 mg/dl did not reach statistical significance.
Conclusions:
High Lp(a) levels are associated with a selective impairment of vasodilator capacity of receptor-mediated endothelial stimuli. Impaired dilator capacity of the coronary circulation associated with elevated Lp(a) levels may contribute to the pathogenesis of myocardial ischemia in response to trigger mechanisms involving receptor-mediated stimulation such as sympathetic activation.