(Circulation. 2000;102:820.)
© 2000 American Heart Association, Inc.
Editorial |
Cardiovascular Benefit of Cholesterol-Lowering Therapy
Does Improved Endothelial Vasodilator Function Matter?
From the Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
Correspondence to Richard O. Cannon III, MD, National Institutes of Health, Bldg 10, Room 7B15, 10 Center Dr MSC-1650, Bethesda, MD 20892-1650. E-mail cannonr@nih.gov
Key Words: Editorials • cholesterol • vasodilation • endothelium • statins
Lipid-lowering therapy with HMG-CoA reductase inhibitors (statins) has been shown in large clinical trials to reduce cardiovascular morbidity and mortality in otherwise healthy hypercholesterolemic subjects and in patients with coronary artery disease. The magnitude of risk reduction is greatest in individuals with the highest pretreatment cholesterol levels, although those with mild elevation in LDL cholesterol may also benefit from statin therapy. Because angiographic trials with lipid-lowering therapy have shown little reduction in atherosclerotic plaque size, alternate mechanisms of therapeutic benefit to the arterial wall have been proposed, the most testable of which is improvement in endothelial vasodilator function.
Endothelial Vasodilator Function Testing, Myocardial Ischemia, and Cardiovascular Risk
The endothelium maintains a nonthrombogenic
surface for blood flow, prevents platelet and leukocyte adhesion to
the vessel surface, modulates cellular composition of the
arterial wall, and promotes dilator tone of arteries and
veins, homeostatic properties regulated in part by the local synthesis
of nitric oxide. Several groups have shown that
endothelial release of nitric oxide is reduced or
absent in patients with atherosclerosis, as well as in
patients with risk factors for atherosclerosis,
including hypercholesterolemia. Thus,
acetylcholine, the agonist used in Furchgott and Zawadzki’s
experiments that showed release of relaxant factor from the
endothelium,1 commonly constricts
coronary arteries of patients with
atherosclerosis at doses that dilate arteries of
patients whose coronary angiograms appear normal, especially if
they are free of risk factors for
atherosclerosis.2 3 Consistent
with the notion that an important mechanism of
cardiovascular risk reduction with statin therapy is
improvement in nitric oxide–regulated endothelial
function, several groups have shown that statin
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