Increased oxidized low density lipoprotein associated with high ceruloplasmin activity in patients with active acromegaly

P>Objective Active acromegaly is associated with increased mortality from cardiovascular causes. Several studies have shown increased atherogenic risk factors and biomarkers of inflammation and atherosclerosis in association with growth hormone excess. The aim of this study was to evaluate oxidized low density lipoprotein (oxLDL) levels and some modulators of LDL oxidative modification in patients with acromegaly. Design Open transversal study. Patients Fifteen patients with active acromegaly and 15 controls were studied. Measurements We evaluated the levels of oxLDL, thiobarbituric acid reactive substances (TBARS), ceruloplasmin, bilirubin, uric acid and total reactive antioxidant potential, and the activities of ceruloplasmin, myeloperoxidase, superoxide distmutase, paraoxonase 1, and platelet activating factor acethylhydrolase. Statistical analysis was performed including body mass index as a covariate or as a fixed variable. Results Patients with acromegaly showed significantly higher levels of oxLDL (120 +/- 19 vs. 86 +/- 20 U/l, P < 0 center dot 001) and endothelin (P < 0 center dot 05), increased ceruloplasmin activity (P < 0 center dot 01) and a trend towards higher values in TBARS concentration (P = 0 center dot 07) in comparison to healthy controls. OxLDL was positively associated with GH, IGF-I and its binding protein 3 (r = 0 center dot 63, P < 0 center dot 001; r = 0 center dot 53, P < 0 center dot 01; and r = 0 center dot 56, P < 0 center dot 01; respectively). OxLDL showed direct associations with endothelin-1 (r = 0 center dot 53, P < 0 center dot 01) and ceruloplasmin activity (r = 0 center dot 43, P < 0 center dot 05). The other parameters evaluated were similar in both groups. Conclusions The increase in plasma oxLDL levels, a direct marker of the plaque formation, could constitute a link between atherosclerosis and active acromegaly. LDL oxidation would not be the consequence of diminished antioxidant defences, but of an enhancement in prooxidant factors like ceruloplasmin.