Effect of intensive versus moderate lipid lowering on endothelial function and vascular responsiveness to angiotensin II in stable coronary artery disease.
Recent evidence has demonstrated that intensive lipid-lowering therapy with a high-dose statin provides significant clinical benefit beyond moderate lipid-lowering therapy. However, dose-dependent effects of short-term statin therapy on vascular function have not been demonstrated. We studied endothelial function and vascular responsiveness to angiotensin II in patients who had coronary artery diseased and were randomized to receive low- or high-dose atorvastatin (10 or 80 mg, respectively) or placebo. Internal thoracic artery segments were obtained during coronary bypass surgery and studied in vitro. Endothelium-dependent vasodilation was increased with atorvastatin therapy (p = 0.035) but was significantly increased further in patients who received 80 mg compared with those who received 10 mg of atorvastatin (p = 0.05). Endothelium improvement was accompanied by decreased vascular response to angiotensin II (p = 0.039). These findings suggest a mechanism for the clinical benefit of intensive lipid-lowering treatment in coronary heart disease.
van der Harst
Pim
P
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. p.van.der.harst@thorax.umcg,nl
Wagenaar
Lodewijk J
LJ
Buikema
Hendrik
H
Voors
Adriaan A
AA
Plokker
H W Thijs
HW
Morshuis
Wim J
WJ
Six
A Jacob
AJ
Boonstra
Piet W
PW
Nickenig
Georg
G
Wassmann
Sven
S
van Veldhuisen
Dirk J
DJ
van Gilst
Wiek H
WH
D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology*; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D001026:Coronary Artery Bypass; D003324:Coronary Artery Disease / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D066298:In Vitro Techniques; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000503:physiopathology; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011758:Pyrroles; D000804:Angiotensin II; D000069059:Atorvastatin