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Context:Plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) predicts incident cardiovascular disease and is associated preferentially with negatively charged apolipoprotein B-containing lipoproteins. The plasma cholesteryl ester transfer (CET) process, which contributes to low high-density lipoprotein cholesterol and small, dense low-density lipoproteins, is affected by the composition and concentration of apolipoprotein B-containing cholesteryl ester acceptor lipoproteins.Objective:We tested relationships of CET with Lp-PLA2 in subjects with and without metabolic syndrome (MetS).Design and Setting:In 68 subjects with MetS and 74 subjects without MetS, plasma Lp-PLA2 mass, cholesterol esterification (EST), lecithin:cholesterol acyltransferase (LCAT) activity level, CET, CET protein (CETP) mass, and lipoproteins were measured.Results:EST, LCAT activity, CET (P < 0.001 for all), and CETP (P = 0.030) were increased, and Lp-PLA2 was decreased (P = 0.043) in MetS. CET was correlated positively with Lp-PLA2 in subjects with and without MetS (P < 0.05 for both). EST and LCAT activity were unrelated to Lp-PLA2, despite a positive correlation between EST and CET (P < 0.001). After controlling for age, sex, and diabetes status, CET was determined by Lp-PLA2 in the whole group (β = 0.245; P < 0.001), and in subjects with (β = 0.304; P = 0.001) and without MetS (β = 0.244; P = 0.006) separately, independently of triglycerides and CETP.Conclusions:Plasma CET is related to Lp-PLA2 in subjects with and without MetS. The process of CET, but not EST, may be influenced by Lp-PLA2. These findings provide a rationale to evaluate whether maneuvers that inhibit Lp-PLA2 will reduce CET, and vice versa to document effects of CETP inhibition on Lp-PLA2.

Objective Plasma lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) levels predict incident cardiovascular disease, impacting Lp-PLA 2 as an emerging therapeutic target. We determined Lp-PLA 2 responses to statin and fibrate administration in type 2 diabetes mellitus, and assessed relationships of changes in Lp-PLA 2 with subclinical inflammation and lipoprotein characteristics. Methods A placebo-controlled cross-over study (three 8-week treatment periods with simvastatin (40 mg daily), bezafibrate (400 mg daily) and their combination) was carried out in 14 male type 2 diabetic patients. Plasma Lp-PLA 2 mass was measured by turbidimetric immunoassay. Results Plasma Lp-PLA 2 decreased (− 21 ± 4%) in response to simvastatin ( p 2 during combined treatment (− 17 ± 3%, p 2 changes during the 3 active lipid lowering treatment periods were related positively to baseline levels of high sensitive C-reactive protein, non-HDL cholesterol, triglycerides, the total cholesterol/HDL cholesterol ratio and less LDL electronegativity ( p p 2 ( p 2 responses correlated inversely with changes in non-HDL cholesterol, triglycerides and the total cholesterol/HDL cholesterol ratio during treatment ( p p Conclusions In type 2 diabetes mellitus, plasma Lp-PLA 2 is likely to be lowered by statin treatment only. Enhanced subclinical inflammation and more severe dyslipidemia may predict diminished LpPLA 2 responses during lipid lowering treatment, which in turn appear to be quantitatively dissociated from decreases in apolipoprotein B lipoproteins. Conventional lipid lowering treatment may be insufficient for optimal LpPLA 2 lowering in diabetes mellitus.