Fenofibrate improves endothelial function and decreases thrombin-activatable fibrinolysis inhibitor concentration in metabolic syndrome

Abstract

Procoagulant state, inflammation, and endothelial dysfunction have been documented in metabolic syndrome. Endothelial dysfunction is a strong predictor of cardiovascular events. Studies on the association of thrombin-activatable fibrinolysis inhibitor and thrombosis are still controversial, but substantial evidence suggests that increased thrombin-activatable fibrinolysis inhibitor or thrombin-activatable fibrinolysis inhibits or protects against arterial thrombosis. This study aimed to assess concomitantly the effects of fenofibrate therapy on thrombin-activatable fibrinolysis inhibitor concentrations and endothelial functions in patients with metabolic syndrome. Twenty-five patients (16 women; mean age 50.4 +/- 7.0) were enrolled in the study. Plasma thrombin-activatable fibrinolysis inhibitor, C-reactive protein, and fibrinogen levels were measured before fenofibrate administration and after 8 weeks of fenofibrate treatment. Endothelial function was assessed by endothelial-dependent flow-mediated dilatation from brachial artery. Pretreatment (baseline) thrombin-activatable fibrinolysis inhibitor level was 52.3 (1.2-119.7) decreasing to 7.7 (0.9-51.2; P < 0.001) after 8 weeks of fibrate treatment. Endothelial functions, which were measured with flow-mediated dilatation, were significantly improved after treatment (mean flow-mediated dilatation was 6.76 +/- 2.21 at baseline and 10.66 +/- 1.17% after 8 week of fenofibrate treatment, P < 0.001). Fenofibrate decreases thrombin-activatable fibrinolysis inhibitor levels and improves endothelial function in metabolic syndrome and, thus, suggests a potential for protection against cardiovascular effects. Further studies are warranted to confirm the effects of fibrates on thrombin-activatable fibrinolysis inhibitor and for conclusive evidence on the association between thrombin-activatable fibrinolysis inhibitor and thrombosis.

Fenofibrate improves endothelial function and plasma myeloperoxidase in patients with type 2 diabetes mellitus: an open-label interventional study

“…This finding is consistent with other studies that have shown significantly improved FMD response to hyperemia in patients with metabolic syndrome or hypertriglyceridemia following 6–8 weeks of fenofibrate administration [28-30]. A similar effect, partially related to enhanced reduction in LDL-cholesterol and apoB-100 concentrations, has been shown in T2DM patients treated with statins [31].…”

Evidence of direct smooth muscle relaxant effects of the fibrate gemfibrozil

“…It is not likely the inner endothelial cell layer, even though longstanding fibrate therapy in both dyslipidemic and diabetic patients has been shown to protect it (Kovacs et al, 2005;Otsuki et al, 2005;Kilicarslan et al, 2008). In the present study, experimental removal of the endothelium did not abolish gemfibrozil's vasorelaxant effects.…”

Targeting Dyslipidemia in the Metabolic Syndrome: An Update

“…A recent study showed that the -1131T>C polymorphism of the apoA5 gene is responsible for the response to fibrate treatment in subjects with the MetS [62]. In addition to their effect on the dyslipidemia, fibrates decrease thrombinactivatable fibrinolysis inhibitor levels and improve endothelial function in the MetS [63]. Fibrate treatment also reduces the production of postprandial inflammatory cytokines and hepatic-synthesized inflammatory proteins (monohydroxy fatty acids, lipopolysaccharide activated monocyte chemotactic protein-1, macrophage inflammatory protein-1alpha and interleukin-1beta) [64,65].…”