Effects of rosuvastatin on endothelial function in patients with familial combined hyperlipidaemia (FCH).
OBJECTIVE
Although several studies have reported a positive effect of statins on endothelial vasoreactivity, most studies performed in subjects with type 2 diabetes mellitus report no effect at all. This lack of effect may be related to the existence of insulin resistance, or to insufficient lowering of atherogenic (apo)lipoproteins. Therefore, we tested in this study whether treatment of insulin resistant familial combined hyperlipidaemia (FCH) patients with a high dose (40 mg/day) of the potent rosuvastatin was able to improve endothelial function, without necessarily improving insulin sensitivity.


METHODS
In a double-blind randomised crossover study, 18 subjects with FCH (without evident cardiovascular disease, mean [standard deviation] age 54 [7] years) underwent a 4-week run-in period after which they were randomised to treatment with placebo once daily for 12 weeks, followed by rosuvastatin 40 mg/day for 12 weeks or vice versa. Endothelial function was determined after 8 and 12 weeks of both treatment periods, respectively, by measurement of flow-mediated vasodilation (FMD) using high-resolution ultrasound and by measurement of vasodilator response to intrabrachial acetylcholine (Ach) by venous occlusion plethysmography (forearm blood flow [FBF]).


RESULTS
Plasma levels of lipids, (apo)lipoproteins and high-sensitivity C-reactive protein (hsCRP) improved significantly after rosuvastatin therapy compared to placebo. However, rosuvastatin had no effect on homeostasis model assessment (HOMA)-indices or on vasodilator responses to intra-brachial acetylcholine-infusion (FBF-ratio increased from a mean of 1.28 [SD: 0.46] to 5.82 [3.44] after rosuvastatin and from 1.33 [0.67] to 5.99 [3.89] after placebo, p = 0.35). Endothelium-dependent FMD was also unchanged (1.6% [3.1%] vs. 3.2% [3.5]%, p = 0.56 rosuvastatin vs. placebo, respectively).


CONCLUSIONS
In patients with FCH, a 12-week treatment of rosuvastatin 40 mg/day did not improve endothelial function (either in large conduit vessels or in resistance vessels), despite significant improvements in plasma lipids, (apo)lipoproteins. and low-grade inflammation.
ter Avest
Ewoud
E
Department of Medicine, Division of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Abbink
Evertine J
EJ
Holewijn
Suzanne
S
de Graaf
Jacqueline
J
Tack
Cees J
CJ
Stalenhoef
Anton F H
AF
D000328:Adult; D000368:Aged; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006950:Hyperlipidemia, Familial Combined / Q000188:drug therapy* / Q000503:physiopathology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D010919:Placebos; D010991:Plethysmography; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation
D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010919:Placebos; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium