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Rapid effect of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibition on coronary endothelial function
Sven Wassmann1, Anna Faul, Benno Hennen
1Medizinische Klinik und Poliklinik, Innere Medizin III, Universitätskliniken des Saarlandes, D-66421 Homburg/Saar, Germany.
Insights
A single dose of pravastatin improved coronary artery function within 24 hours in patients with endothelial dysfunction. This statin therapy enhanced endothelium-dependent vasomotion without significantly altering cholesterol levels.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Endothelial Function
Background:
- Statins reduce cardiovascular events in hypercholesterolemic patients.
- The rapid effects of statins on coronary vasculature in patients with endothelial dysfunction are not well understood.
Purpose of the Study:
- To investigate whether statins can improve coronary endothelial function within 24 hours of administration in patients with endothelial dysfunction.
Main Methods:
- A randomized, double-blind, placebo-controlled trial involving 27 patients with stable angina.
- Coronary endothelial function was assessed using quantitative coronary angiography and acetylcholine infusion before and 24 hours after a single 40 mg dose of pravastatin or placebo.
- Coronary blood flow reserve was measured using Doppler velocimetry during adenosine infusion.
Main Results:
- Single-dose pravastatin significantly attenuated acetylcholine-induced vasoconstriction (P<0.05) within 24 hours, indicating improved endothelial function.
- The placebo group showed no significant change in acetylcholine-mediated vasoconstriction.
- Neither pravastatin nor placebo altered the response to nitroglycerin, coronary blood flow reserve, or serum lipid/hs-CRP levels within 24 hours.
Conclusions:
- Pravastatin treatment rapidly improves endothelium-dependent coronary vasomotion within 24 hours.
- These beneficial effects occur independently of significant changes in blood lipid levels or cholesterol.
- Statins offer early functional benefits to the coronary vasculature in patients with endothelial dysfunction.
Abstract:
Treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) decreases cardiovascular event rates in hypercholesterolemic patients. Whether statins exert effects within 24 hours on the coronary vasculature in patients with endothelial dysfunction has not been elucidated. Twenty-seven patients with stable angina pectoris and average low-density lipoprotein cholesterol concentrations of 138+/-9 mg/dL at baseline were allocated to treatment with placebo (14 patients) or 40 mg/d pravastatin (13 patients) in a randomized, double-blind, prospective trial. Coronary endothelial function was assessed before and 24 hours after single treatment by quantitative coronary angiography during intracoronary infusion of nitroglycerin or increasing concentrations of acetylcholine (0.01, 0.1, and 1 micromol/L). Coronary blood flow reserve was measured by Doppler velocimetry during adenosine infusion. Intracoronary acetylcholine infusion induced abnormal vasoconstriction in both groups before treatment, indicating coronary endothelial dysfunction. Treatment with a single oral 40-mg dose of pravastatin significantly attenuated acetylcholine-mediated vasoconstriction after 24 hours (mean+/-SE decrease in luminal diameter before and after treatment: 0.01 micromol/L, 6.1+/-2.2% versus 3.0+/-1.2%; 0.1 micromol/L, 15.6+/-2.6% versus 7.4+/-1.8%; P<0.05; 1 micromol/L, 22.9+/-2.9% versus 13.2+/-2.6%; P<0.05). There was no significant difference in the response to acetylcholine in the placebo group (8.1+/-2.4% versus 9.7+/-2.4%, 16.1+/-2.9% versus 16.8+/-3.2%, and 21.4+/-3.9% versus 23.3+/-4.2%). The response to nitroglycerin infusion was not altered in both groups. Increase in coronary blood flow in response to adenosine and coronary flow reserve remained unchanged during placebo and statin treatment. Serum concentrations of blood lipids and high-sensitive C-reactive protein were not significantly altered after 24 hours in response to placebo or pravastatin therapy. Statin treatment improves endothelium-dependent coronary vasomotion within 24 hours in the absence of significant cholesterol reduction. The full text of this article is available online at http://www.circresaha.org.