Long-term effects of pravastatin and fosinopril on peripheral endothelial function in albuminuric subjects.
The purpose of this double-blind, randomized, placebo-controlled trial was to determine the long-term effects of pravastatin and fosinopril treatment on peripheral endothelial function in subjects with albuminuria. Subjects (mean age 51 years, 63% male) were randomized to pravastatin 40 mg or matching placebo and to fosinopril 20mg or matching placebo. Using high resolution ultrasound, flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NID) was assessed at baseline and after 4 years of treatment in a total of 276 subjects. At baseline, mean+/-standard error FMD was 4.73+/-0.49% and NID was 10.86+/-0.67%. Pravastatin significantly reduced total cholesterol and LDL cholesterol (p<0.01) and randomization to pravastatin was associated with a non-significant improvement of 18.9% in FMD (+0.80+/-0.95, p=0.09), without a significant change in NID. Interestingly, pravastatin significantly increased FMD by 34.9% in men (+1.23, p=0.04), but only 1.1% in women (+0.06, p=0.95). Fosinopril was not associated with a change in FMD or NID despite significantly decreasing urinary albumin excretion, systolic and diastolic blood pressure (all p<0.01). In conclusion, after 4 years of follow-up, pravastatin treatment tended to increase FMD and this effect was predominantly present in men. Fosinopril treatment did not modify FMD during long-term follow-up.
Asselbergs
Folkert W
FW
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands. Electronic address: fwasselbergs@hotmail.com.
van der Harst
Pim
P
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
van Roon
Arie M
AM
Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
Hillege
Hans L
HL
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands.
de Jong
Paul E
PE
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
Gans
Reinold O B
ROB
Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
Smit
Andries J
AJ
Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
van Gilst
Wiek H
WH
Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands; Department of Clinical Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
D000328:Adult; D000419:Albuminuria / Q000188:drug therapy*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001916:Brachial Artery / Q000187:drug effects / Q000503:physiopathology; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D017328:Fosinopril / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017035:Pravastatin; D017328:Fosinopril