Effect of Fluvastatin and Valsartan, Alone and in Combination, on Postprandial Vascular Inflammation and Fibrinolytic Activity in Patients With Essential Hypertension

Abstract

Postprandial hypertriglyceridemia is associated with a series of atherogenic abnormalities, including a prothrombotic state and inflammation. Hypertensive patients have exaggerated postprandial triglyceride response. The benefit of combined treatment of statin and angiotensin II type 1 receptor blocker (ARB) has been demonstrated in diabetic patients. The aim of this investigation was to explore the effect of a statin, fluvastatin, and the ARB valsartan, alone and in combination, on fibrinolytic activity and inflammation after a high-fat meal in patients with essential hypertension (EHP). A total of 53 EHP patients were studied. The concentrations of plasma lipid profiles, soluble P-selectin, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type I (PAI-1) antigens were measured in fasting state and at 4 hours after a single high-fat meal (800 calories; 50 g fat). Patients randomly accepted placebo, fluvastatin 40 mg/day, valsartan 80 mg/day, or both for 1 week. Then a high-fat meal and assay of plasma samples were repeated. The postprandial plasma triglyceride, soluble P-selectin, PAI-1, and t-PA antigen concentrations significantly increased after a high-fat meal. Postprandial plasma concentration of triglyceride was significantly correlated with that of soluble P-selectin and PAI-1 antigen, respectively (P<0.001). The postprandial increase in plasma P-selectin, PAI-1, and t-PA antigen levels was attenuated by 1-week fluvastatin-alone and valsartan-alone treatments; their combination is more effective on both fasting and postprandial P-selectin, plasma PAI-1, and t-PA antigen levels. The improvement of these plasma variables was not significantly related to the changes of plasma lipids and blood pressure. In conclusion, postprandial hypertriglyceridemia induces postprandial fibrinolytic dysfunction and vascular inflammation in patients with essential hypertension after a high-fat meal. Short-term combined treatment with fluvastatin and valsartan more effectively inhibits this postprandial atherogenic change in plasma than monotherapy.