The Inverse Relation of HDL Anti-Oxidative Functionality with Serum Amyloid a is Lost in Metabolic Syndrome Subjects

Objective: Anti-oxidative properties of high density lipoproteins (HDL) are relevant for atheroprotection. HDL carry serum amyloid A (SAA), which may impair HDL functionality. We questioned whether HDL anti-oxidative capacity is determined by SAA. Design and Methods: Relationships of HDL anti-oxidative capacity (% inhibition of low density lipoprotein oxidation in vitro) with SAA were determined in 54 non-diabetic subjects without metabolic syndrome (MetS) and 68 subjects with MetS (including 51 subjects with Type 2 diabetes mellitus). Results: SAA levels were higher in MetS subjects, coinciding higher high sensitive C-reactive protein (hs-CRP) and lower HDL cholesterol and apolipoprotein (apo) A-I levels (P<0.001 for all). HDL anti-oxidative capacity was not different between subjects with and without MetS (P=0.76), but the HDL anti-oxidation index (HDL anti-oxidative capacity multiplied by individual HDL cholesterol concentrations), as a measure of global anti-oxidative functionality of HDL, was lower in Mets subjects (P<0.001). HDL anti-oxidative capacity was correlated inversely with SAA levels in subjects without MetS (r=-0.286, P=0.036). Notably, this relationship was independent of HDL cholesterol or apoA-I (P<0.05 for both). In contrast, no relation of HDL anti-oxidative capacity with SAA was observed in MetS subjects (r=0.032, P=0.80). The relationship of SAA with HDL anti-oxidative capacity was different in subjects with MetS compared to subjects without MetS (P=0.039 for the interaction between the presence of MetS and SAA on HDL anti-oxidative capacity) taking age and diabetes status into account. Conclusion: Higher SAA levels may impair HDL anti-oxidative functionality. The relationship of this physiologically relevant HDL functionality measure with circulating SAA levels is apparently disturbed in metabolic syndrome.