A hydroxymethylglutaryl coenzyme A reductase inhibitor improves endothelial function within 7 days in patients with chronic hemodialysis.
BACKGROUND
Atherosclerosis-related diseases are leading causes of morbidity among patients undergoing hemodialysis. The effects of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) on the endothelial function of hemodialyzed patients are not known.


RESULTS
For 16 weeks, we prescribed simvastatin (low dose: 5 mg or moderate dose: 10 mg) to 28 patients (low dose: n=14, 61.2 ± 8.6 years, moderate dose: n=14, 60.8 ± 10.2 years) and chose 9 patients (61.5 ± 5.2 years) without prescriptions as controls. We compared the effects of statin on lipids, flow-mediated endothelium-dependent and nitroglycerin-induced endothelium-independent dilatation (%FMD, %NTD), and markers of oxidant stress and atherosclerosis. Serum HDL-cholesterol and triglycerides did not change significantly in any of the three groups; however, LDL-cholesterol was decreased at 16 weeks in both simvastatin groups. The %FMD and plasma NOx increased at 1 and 16 weeks in both statin groups, but not in the control group (P<0.01). The %NTD did not change. Oxidized LDL, VCAM-1, and 8-isoprostane decreased significantly after 16 weeks in both statin groups; however, TNF-α and interleukin 6 did not change. In the control group, no significant changes in these parameters were observed. Multiple regression analyses showed that the (short) period of hemodialysis and (young) age are significant factors associated with %FMD improvement.


CONCLUSIONS
A statin improved impaired endothelial function in the arteries of chronic dialysis patients, in part by enhancing NO bioavailability within one week. Improved endothelial function is in line with the anti-atherosclerotic effects observed in patients undergoing chronic hemodialysis.
Kishimoto
Noriaki
N
Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Hayashi
Toshio
T
Sakuma
Ichiro
I
Kano-Hayashi
Hatsuyo
H
Tsunekawa
Taku
T
Osawa
Masako
M
Ina
Kouichiro
K
Iguchi
Akihisa
A
D000368:Aged; D001916:Brachial Artery / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000639:trends; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors