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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, OBESITY, CARDIOVASCULAR HEALTH AND GENOMICS

Location: Boston, Massachusetts

Title: Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants)

Author
item Tsai, Alexander
item Steffen, Brian
item Ordovas, Jose
item Straka, Robert
item Zhou, Xia
item Hanson, Naomi
item Arnett, Donna
item Tsai, Michael

Submitted to: Translational Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/27/2011
Publication Date: 8/1/2011
Citation: Tsai, A.K., Steffen, B.T., Ordovas, J.M., Straka, R.J., Zhou, X., Hanson, N.Q., Arnett, D.K., Tsai, M.Y. 2011. Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants. Translational Research. 58(2):99-105.

Interpretive Summary: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an enzyme that in humans is encoded by the PLA2G7 gene. In the blood it travels mainly with low-density lipoprotein (LDL) and it is produced by inflammatory cells and hydrolyzes oxidized phospholipids in LDL. High levels of Lp-PLA2 are associated with inflammation, atherosclerosis, and coronary heart disease events. In addition, Lp-PLA2 has been linked to classical markers of endothelial activation, including soluble vascular cell adhesion molecule-1 (sVCAM-1). Although treatment with fenofibrate reduces Lp-PLA2, it is unclear whether fenofibrate reduces sVCAM-1 levels Concentrations of Lp-PLA2 and sVCAM-1 were measured in plasma at before and after 3 weeks of fenofibrate treatment in 96 hypertriglyceridemic (HTG) participants of the Genetics of Lipid-lowering Drugs and Diet Network study. Fenofibrate treatment resulted in approximately 30% increase in Lp-PLA2 and approximately 15% increase in sVCAM-1 levels but only in those with low baseline levels of either target. In contrast, Lp-PLA2 was reduced by approximately 35% in those with high baseline levels. VCAM-1 levels were significantly reduced by approximately 8% and 17% in those with medium and high levels, respectively. In conclusion, fenofibrate treatment in HTG reduced the levels of Lp-PLA2 and sVCAM-1, but only in those with elevated baseline levels of these biomarkers and therefore, at high cardiovascular risk.

Technical 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 less than 0.0001) in tertile 3. Soluble VCAM-1 levels were significantly reduced by 7.74% (P = 0.0109) and 17.2% (P less than 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 (greater than 200 ng/mL).

Last Modified: 8/24/2016
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