TY - JOUR
T1 - Short-term fenofibrate treatment reduces elevated plasma Lp-PLA2 mass and sVCAM-1 levels in a subcohort of hypertriglyceridemic GOLDN participants
AU - Tsai, Alexander K.
AU - Steffen, Brian T.
AU - Ordovas, Jose M.
AU - Straka, Robert
AU - Zhou, Xia
AU - Hanson, Naomi Q.
AU - Arnett, Donna
AU - Tsai, Michael Y.
N1 - Funding Information:
Supported by National Heart, Lung, and Blood Institute Grant U01HL072524-04 .
PY - 2011/8
Y1 - 2011/8
N2 - High levels of lipoprotein-associated phospholipase A2 (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 mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA2 and sVCAM-1. Concentrations of Lp-PLA2 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-PLA2 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-PLA2 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-PLA2 and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA2 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-PLA2 concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
AB - High levels of lipoprotein-associated phospholipase A2 (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 mass, it is unclear whether fenofibrate reduces sVCAM-1 levels or whether an association exists between any changes observed in Lp-PLA2 and sVCAM-1. Concentrations of Lp-PLA2 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-PLA2 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-PLA2 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-PLA2 and sVCAM-1 at baseline or post-treatment. In conclusion, fenofibrate treatment in hypertriglyceridemic subjects reduced the levels of Lp-PLA2 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-PLA2 concentrations indicative of increased cardiovascular disease risk (>200 ng/mL).
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U2 - 10.1016/j.trsl.2011.01.014
DO - 10.1016/j.trsl.2011.01.014
M3 - Article
C2 - 21757154
AN - SCOPUS:79960316123
SN - 1931-5244
VL - 158
SP - 99
EP - 105
JO - Translational Research
JF - Translational Research
IS - 2
ER -
