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. 2011 Aug;158(2):99-105.
doi: 10.1016/j.trsl.2011.01.014. Epub 2011 Feb 26.

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

Alexander K Tsai  1 , Brian T Steffen, Jose M Ordovas, Robert Straka, Xia Zhou, Naomi Q Hanson, Donna Arnett, Michael Y Tsai
Affiliations

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

Alexander K Tsai et al. Transl Res. 2011 Aug.

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).

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Figures

Figure 1
Figure 1
A. Mean Lp-PLA2 levels at baseline and following 3 weeks of fenofibrate treatment (160 mg/d) are shown in a sub-cohort of the GOLDN study. Results are divided into tertiles determined by baseline values of Lp-PLA2. In tertile 1, a significant 30.1% increase was found between baseline (89.48 ± 3.2 ng/mL) and post-treatment (128.06 ± 9.83 ng/mL) values (p=0.0003). No differences were observed in tertile 2. In tertile 3, mean baseline Lp-PLA2 levels of 288.94 ± 12.77 ng/mL significantly decreased 35.3% to 193.69 ± 8.26 ng/mL following treatment (p<0.0001). (B) Mean VCAM-1 levels are shown at baseline and following 3 weeks of fenofibrate treatment (160 mg/d) in a sub-cohort of the GOLDN study. Results are stratified into tertiles determined by baseline values of VCAM-1. In tertile 1, a significant increase was observed between baseline (494.48 ± 11.67 pg/mL) and post-treatment (579.69 ± 42.38 pg/mL) values (p=0.0096). In tertile 2, mean baseline VCAM-1 levels of 660.32 ± 8.56 pg/mL decreased 7.74% to 609.18 ± 18.77 pg/mL following treatment (p=0.0109). In tertile 3, mean baseline VCAM-1 levels of 922.69 ± 26.8 pg/mL significantly decreased 17.2% to 763.68 ± 35.34 pg/mL following treatment (p<0.0001). Values are expressed as mean ±SEM * P value < 0.05 for t-test comparing pre- and post-treatment values.
Figure 2
Figure 2
Scatterplots showing the correlation between: (A) the change in LpPLA2 mass and the change in VCAM-1 levels following 3 weeks of fenofibrate treatment (corr=0.04281, p=0.6804); (B) the change in ox-LDL levels and the change in LpPLA2 mass following 3 weeks of fenofibrate treatment (corr=−0.16477, p=0.1086); (C) basleine ox-LDL levels vs. baseline LpPLA2 mass (corr = −0.23540, p=0.0210).
Figure 2
Figure 2
Scatterplots showing the correlation between: (A) the change in LpPLA2 mass and the change in VCAM-1 levels following 3 weeks of fenofibrate treatment (corr=0.04281, p=0.6804); (B) the change in ox-LDL levels and the change in LpPLA2 mass following 3 weeks of fenofibrate treatment (corr=−0.16477, p=0.1086); (C) basleine ox-LDL levels vs. baseline LpPLA2 mass (corr = −0.23540, p=0.0210).
Figure 2
Figure 2
Scatterplots showing the correlation between: (A) the change in LpPLA2 mass and the change in VCAM-1 levels following 3 weeks of fenofibrate treatment (corr=0.04281, p=0.6804); (B) the change in ox-LDL levels and the change in LpPLA2 mass following 3 weeks of fenofibrate treatment (corr=−0.16477, p=0.1086); (C) basleine ox-LDL levels vs. baseline LpPLA2 mass (corr = −0.23540, p=0.0210).
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