Effect of a 3-year therapy with the 3-hydroxy-3-methylglutaryl coenzyme a reductase-inhibitor fluvastatin on endothelial function and distensibility of large arteries in hypercholesterolemic renal transplant recipient.
BACKGROUND
In patients after renal transplantation functional arterial vessel wall properties are impaired. Whether 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have a sustained effect on endothelial function and arterial distensibility in patients after renal transplantation is not clear. The authors studied the effects of a long-term therapy with fluvastatin on large artery distensibility and flow-mediated vasodilation (FMD) in hypercholesterolemic patients after renal transplantation in a prospective, blinded, and randomized trial.


METHODS
Twenty-six patients who had undergone renal transplantation were assigned randomly to either fluvastatin, 40 mg/d (n = 13) or placebo (n = 13) and underwent follow-up for 3 years. At baseline and after 6, 12, and 36 months of treatment, carotid and brachial artery distensibility, endothelium-dependent FMD, and nitroglycerine-induced vasodilation (NMD) of the brachial artery were measured by a echo-tracking device.


RESULTS
A significant decrease in total and low-density cholesterol was observed after 6, 12, and 36 months in patients treated with fluvastatin but not in the placebo group. FMD increased with fluvastatin from 4.6 +/- 2% to 12.4 +/- 2% after 12 months; this improvement was sustained with 13.4 +/- 3% after 36 months (P < 0.05). However, placebo did not alter FMD (P < 0.001 for trend difference between groups by analysis of covariance). Endothelium-independent NMD was similar in both groups at baseline and during therapy. Neither carotid nor brachial artery distensibility coefficients were altered by either treatment.


CONCLUSIONS
HMG-CoA reductase inhibitor therapy over 3 years results in a significant and sustained improvement of endothelial function in hypercholesterolemic patients after renal transplantation. However, this is not accompanied by a beneficial effect on impaired large artery distensibility even after long-term therapy with fluvastatin.
Kosch
Markus
M
Department of Internal Medicine D, University of Münster, Münster, Germany. koschm@uni-muenster.de
Barenbrock
Michael
M
Suwelack
Barbara
B
Schaefer
Roland M
RM
Rahn
Karl-Heinz
KH
Hausberg
Martin
M
D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001916:Brachial Artery / Q000502:physiology; D017536:Carotid Artery, Common / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D014664:Vasodilation / Q000187:drug effects*
D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D000077340:Fluvastatin