Effects of Antihypertensive and Hypolipidemic Drugs on Plasma and High-Density Lipoprotein-Associated Platelet Activating Factor-Acetylhydrolase Activity

Abstract

Background: Human plasma platelet activating factor acetylhydrolase (PAF-AH) is a phospholipase A2 primarily associated with low-density lipoprotein (LDL). PAF-AH activity has also been found on high-density lipoprotein (HDL). Most of the clinical studies that have investigated the plasma levels of PAF-AH activity in cardiovascular disease have involved patients who were under treatment with various drugs, such as antihypertensive or hypolipidemic agents. However, the influence of these drugs on the enzyme activity has not been adequately studied. Material and Methods: We evaluated the effects of representative antihypertensive and hypolipidemic drugs on the total plasma, as well as on the HDL-associated PAF-AH activity, in 121 patients with essential hypertension and in 90 patients with dyslipidemias of type IIA or type IIB. Serum lipids and enzymatic activities were determined at baseline and after 3 months of treatment. Results: The administration of lacidipine (4 mg, n = 21), valsartan (80 mg, n = 26), indapamide (2.5 mg, n = 20), benazepril (20 mg, n = 20), or atenolol (50 mg, n = 34) did not affect either the total plasma- or the HDL-associated PAF-AH activity. In contrast, treatment with fluvastatin (40 mg, n = 50) or ciprofibrate (100 mg, n = 40) reduced by 25% plasma PAF-AH activity ( P < .001) associated with a decrease in serum levels of total cholesterol and LDL-cholesterol ( P < .001). Furthermore, ciprofibrate induced an increase by 26% in HDL-associated PAF-AH activity ( P = .004) along with an increase in serum HDL-cholesterol levels ( P = .02). Conclusions: Among all types of drugs studied, only those that significantly affect lipid metabolism, such as statins and fibrates, significantly influence PAF-AH activity in human plasma.