title: Lipoprotein(a) selectively impairs receptor-mediated endothelial vasodilator function of the human coronary circulation.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Rehabilitation, Prevention and Sports Medicine, University Freiburg, Germany. schaechinger@em.uni-frankfurt.de
authors.forename: V
authors.initials: V
authors.lastname: Schachinger
authors.forename: M
authors.initials: M
authors.lastname: Halle
authors.forename: J
authors.initials: J
authors.lastname: Minners
authors.forename: A
authors.initials: A
authors.lastname: Berg
authors.forename: A M
authors.initials: AM
authors.lastname: Zeiher
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000187:drug effects*; D003327:Coronary Disease / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006801:Humans; D016014:Linear Models; D017270:Lipoprotein(a) / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017202:Myocardial Ischemia / Q000209:etiology; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D017270:Lipoprotein(a); D014665:Vasodilator Agents; D005996:Nitroglycerin; D000109:Acetylcholine