NO activity in familial combined hyperlipidemia: potential role of cholesterol remnants.
OBJECTIVE
Patients with familial combined hyperlipidemia (FCH) have an increased cardiovascular mortality despite only moderate elevations of LDL-cholesterol. Since endothelial NO release is intimately involved in the anti-atherosclerotic effects of the endothelium, we studied the effect of short-term lipid-lowering therapy on NO-mediated vasodilatation in patients with FCH. In view of only moderate LDL elevations, we evaluated whether alterations in other lipid fractions upon therapy correlated to changes in NO-mediated vasodilatation.


METHODS
NO activity was assessed by serotonin-induced, nitric oxide-mediated increase in forearm blood flow (FBF). Measurements were performed 2 weeks off and 4 weeks on lipid-lowering therapy in 12 FCH patients using forearm venous occlusion plethysmography. Control experiments were performed in 12 healthy subjects.


RESULTS
Serotonin-induced vasodilatation was impaired in FCH patients (FBF (unit ml/100 ml forearm tissue/min) from 3.0 (0.3) to 4.8 (0.4)) compared to controls (FBF from 2.9 (0.3) to 6.5 (0.6); p < 0.05 vs. FCH). FBF response to serotonin improved significantly upon lipid-lowering therapy (from 3.0 (0.3) to 5.7 (0.5); p < 0.05 treated vs. untreated). The level of improvement in endothelial function was significantly correlated to the absolute reduction of intermediate density lipoproteins upon lipid-lowering therapy (r = -0.64; p < 0.05), whereas it did not correlate to changes in VLDL- or LDL-cholesterol, nor to Lp(a).


CONCLUSIONS
Patients with familial combined hyperlipidemia have impaired NO-mediated vasodilatation, that responds rapidly to lipid lowering medication, and may be related to changes in intermediate density lipoproteins.
Stroes
E
E
Department of Nephrology and Hypertension, University Hospital Utrecht, The Netherlands.
de Bruin
T
T
de Valk
H
H
Erkelens
W
W
Banga
J D
JD
van Rijn
H
H
Koomans
H
H
Rabelink
T
T
D000328:Adult; D001120:Arginine; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside; D012039:Regional Blood Flow / Q000187:drug effects; D012701:Serotonin; D019821:Simvastatin / Q000627:therapeutic use; D014664:Vasodilation / Q000187:drug effects
D000960:Hypolipidemic Agents; D008074:Lipoproteins; D009599:Nitroprusside; D009569:Nitric Oxide; D012701:Serotonin; D001120:Arginine; D002784:Cholesterol; D019821:Simvastatin