title: Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants.
abstract: High levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA(2) has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA(2) mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA(2) and sVCAM-1. Concentrations of Lp-PLA(2) mass and sVCAM-1 levels were measured in plasma at baseline and after 3 weeks of fenofibrate treatment (160 mg/d) in 96 hypertriglyceridemic participants of the Genetics of Lipid-lowering Drugs and Diet Network study. Lp-PLA(2) and sVCAM-1 were stratified by tertiles as determined by baseline levels of the respective target. Fenofibrate treatment resulted in a 30.1% mean increase in Lp-PLA(2) mass (P = 0.0003) and a 14.7% mean increase in sVCAM-1 levels (P = 0.0096) but only in tertile1 of either target. In contrast, Lp-PLA(2) mass was reduced by 35.3% (P < 0.0001) in tertile 3. Soluble VCAM-1 levels were significantly reduced by 7.74% (P = 0.0109) and 17.2% (P < 0.0001) in tertiles 2 and 3, respectively. No associations were observed between Lp-PLA(2) and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA(2) mass and sVCAM-1, but only in those with elevated baseline levels of these biomarkers. The greatest reductions in Lp-PLA(2) levels were observed in individuals with Lp-PLA(2) concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
authors.affiliation: Department of Laboratory Medicine & Pathology, University of Minnesota, Minneapolis, MN 55455-0392, USA. tsaix001@umn.edu
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Tsai
authors.forename: Brian T
authors.initials: BT
authors.lastname: Steffen
authors.forename: Jose M
authors.initials: JM
authors.lastname: Ordovas
authors.forename: Robert
authors.initials: R
authors.lastname: Straka
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.forename: Naomi Q
authors.initials: NQ
authors.lastname: Hanson
authors.forename: Donna
authors.initials: D
authors.lastname: Arnett
authors.forename: Michael Y
authors.initials: MY
authors.lastname: Tsai
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood*; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
chemical_list: D000960:Hypolipidemic Agents; D019010:Vascular Cell Adhesion Molecule-1; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D011345:Fenofibrate