From Department of Medicine IV (S.J., M.S., M.L., H.W., G.W., R.E.S.),
University of Erlangen-Nürnberg, Klinikum Nürnberg-Süd,
Nürnberg, Germany, and Department of Clinical Chemistry and Laboratory
Medicine (G.S.), University of Regensburg, Germany.
Background—Impaired
endothelium-dependent vasodilation is an early sign of
atherosclerosis in hypercholesterolemic
patients. We hypothesized that lipid-lowering therapy can improve
endothelial function and that this effect is mainly
mediated by increased bioavailability of nitric oxide (NO).
Methods and Results—In a randomized, double-blind,
placebo-controlled trial, we studied 29 patients (age, 50±12 years)
with hypercholesterolemia (LDL
cholesterol
Conclusions—Lipid-lowering therapy with fluvastatin
can improve disturbed endothelial function in
hypercholesterolemic patients compared with placebo.
This improvement is mediated by increased bioavailability of NO.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Increased Bioavailability of Nitric Oxide After Lipid-Lowering Therapy in Hypercholesterolemic Patients
A Randomized, Placebo-Controlled, Double-blind Study
160 mg/dL) randomly assigned to receive
either fluvastatin (40 mg twice daily; 17 patients) or
placebo (12 patients). Forearm blood flow was measured by
plethysmography before and after 24 weeks of treatment.
Endothelium-dependent vasodilation was assessed by
intra-arterial infusion of acetylcholine (ACh; 3, 12, 24,
and 48 µg/min) and basal NO synthesis rate by
intra-arterial infusion of
NG-monomethyl-L-arginine
(L-NMMA; 1, 2, and 4 µmol/min). Simultaneous
intra-arterial infusion of L-NMMA (4 µmol/min) and
ACh (12, 24, and 48 µg/min) was used to test whether any increase in
endothelium-dependent vasodilation after lipid-lowering
therapy could be blocked by this NO synthase inhibitor.
Endothelium-dependent vasodilation improved
significantly after 24 weeks of lipid-lowering therapy compared with
before therapy (ACh 24 µg/min: 240±34% before versus 347±50%
after therapy; P
0.01) and placebo (changes between
after and before therapy with ACh 24 µg/min: 108±39% for
fluvastatin versus -26±32% for placebo;
P0.05). This improvement in
endothelium-dependent vasodilation could be blocked by
simultaneous administration of L-NMMA (ACh 24 µg/min plus
L-NMMA 4 µmol/min: 170±69% before versus 219±47% after
treatment; P=NS).
Key Words: atherosclerosis • endothelium • blood flow • hypercholesterolemia • nitric oxide • vasodilation
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