Statin therapy improves brachial artery vasodilator function in patients with Type 1 diabetes and microalbuminuria.
OBJECTIVE
Type 1 diabetes mellitus patients with microalbuminuria have endothelial dysfunction associated with the degree of albuminuria but not with LDL-cholesterol levels. Lipid-lowering agents such as statins may still be of benefit as they can correct endothelial dysfunction by both lipid and non-lipid mechanisms. We therefore examined the effects of atorvastatin on brachial artery endothelial dysfunction in these patients.


METHODS
In a double-blind, randomized crossover study, 16 Type 1 diabetes mellitus patients with microalbuminuria received 6 weeks of atorvastatin 40 mg/day or placebo, separated by a 4-week washout. Brachial artery, endothelium-dependent, flow-mediated dilatation (FMD) and endothelium-independent, glyceryl trinitrate-mediated dilatation (GTNMD) were measured.


RESULTS
Compared with placebo, atorvastatin produced a significant decrease in apolipoprotein B (34.2%), LDL-cholesterol (44.1%) (all P < 0.001), and oxidized-LDL (35.7%, P = 0.03). There was a non-significant increase in plasma cGMP (P = 0.13) on atorvastatin. FMD and GTNMD increased significantly on atorvastatin (FMD: atorvastatin +1.8 +/- 0.4%; placebo +0.2 +/- 0.4%, P = 0.007); (GTNMD: atorvastatin +1.3 +/- 0.9%; placebo -1.2 +/- 0.6%, P = 0.04). An increase in cGMP was independently correlated with an increase in FMD on atorvastatin (adjusted (R2) 0.41, P = 0.02).


CONCLUSIONS
Atorvastatin improves endothelium-dependent and independent vasodilator function of the brachial artery in Type 1 diabetes mellitus patients with microalbuminuria. This may relate to pleiotropic effects of statins, in particular reduced oxidative stress and increased availability of nitric oxide.
Dogra
G K
GK
School of Medicine and Pharmacology, Royal Perth Hospital Unit, Western Australian Heart Research Institute, University of Western Australia, Perth, Western Australia. sdogra@cyllene.uwa.edu.au
Watts
G F
GF
Chan
D C
DC
Stanton
K
K
D000293:Adolescent; D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D001055:Apolipoproteins B / Q000032:analysis; D000069059:Atorvastatin; D001916:Brachial Artery / Q000503:physiopathology*; D008078:Cholesterol, LDL / Q000097:blood; D018592:Cross-Over Studies; D006152:Cyclic GMP / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin; D011758:Pyrroles / Q000627:therapeutic use*; D012039:Regional Blood Flow; D018709:Statistics, Nonparametric; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents
D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011758:Pyrroles; D014665:Vasodilator Agents; C099252:oxidized low density lipoprotein; D000069059:Atorvastatin; D005996:Nitroglycerin; D006152:Cyclic GMP