Effects of valsartan on fibrinolysis in hypertensive patients with metabolic syndrome - the KACT-MetS study -

Abstract

Background: The purpose of this study was to analyze the effect of valsartan on abnormal adipocyte metabolism and prothrombotic state in hypertensive patients with metabolic syndrome (MetS). Methods and Results: We conducted a multicenter, prospective, randomized, parallel-group controlled trial in 150 hypertensive patients with MetS. They were randomly assigned to receive either 80-160mg valsartan per day (valsartan group, n=79) or other conventional treatment without a renin-angiotensin system (RAS) inhibitor (non-RAS inhibitor group, n=71). After 1 year, there were no significant differences between the 2 groups in the changes in systolic and diastolic blood pressures (valsartan: 153±15/86±15 to 138±16/77±12mmHg; non-RAS inhibitor: 150±14/82±15 to 137±15/76±10mmHg). There was a significant difference in the change in the levels of plasminogen activator inhibitor-1 (PAI-1) between the 2 groups after 1 year (valsartan: 3.7±3.2ng/ml; non-RAS inhibitor: 5.8±3.3ng/ml, P=0.04). There was no significant difference between groups in the change in the concentration of adiponectin after 1 year (valsartan: 0.3±0.4μg/ml; non-RAS inhibitor: 0.9±0.4μg/ml, P=0.22). The animal study showed aortic PAI-1 protein expression was reduced in double knockout mice of angiotensin II type 1a receptor and apolipoprotein E (apoE) compared with the apoE knockout mice. Conclusions: Valsartan reduced plasma PAI-1 levels compared to non-RAS inhibitor in hypertensive patients with MetS, which suggests it may be useful for improving fibrinolytic function.