Bezafibrate improves hypertension and insulin sensitivity in humans

Abstract

We examined cellular membrane fatty acid composition and insulin sensitivity in patients with mild essential hypertension and hyperlipidemia, and investigated whether bezafibrate, a lipid-lowering drug, could improve elevated blood pressure and insulin sensitivity in these subjects by ameliorating cellular membrane fatty acid composition. Twenty-seven subjects were recruited. Twelve men with mild essential hypertension [systolic blood pressure (SBP) between 140 mmHg and 160 mmHg] and hypertriglyceridemia (plasma triglyceride concentration over 150 mg/dl) were designated the HL group. Fifteen men with mild essential hypertension and normotriglyceridemia (plasma triglyceride concentration below 150 mg/dl) were designated the NL group. Subjects in the HL group were given bezafibrate 400 mg/dl and those in the NL group were given placebo for 3 months. Bezafibrate significantly reduced SBP (140±2.6 to 131.8±2.6 mmHg, mean±SEM), diastolic blood pressure (DBP) (87.8±2.0 to 82.8±2.6 mmHg), fasting plasma triglyceride concentration (225.5±23.5 to 102.9±10.9 mg/dl), fasting plasma insulin concentration (9.6±0.8 to 7.1±0.8 μU/ml), and homeostasis model assessment scores (HOMA-R, 2.4±0.2 to 1.7±0.2), and significantly improved the insulin sensitivity index (56.0±3.0 to 70.7±4.8 mg·l2/mmol·mU·min) in the HL group. Regarding erythrocyte membrane fatty acid composition, bezafibrate reduced the percentages of saturated fatty acids (SFA) and increased the percentage of polyunsaturated fatty acids (PUFA). Plasma triglyceride concentrations were positively correlated with HOMA-R (r=0.50, p<0.01) and SFA (r=0.39, p<0.05), and negatively correlated with PUFA (r= -0.45, p<0.05) before administration of placebo or bezafibrate. In conclusion, an improvement of hyperlipidemia by bezafibrate may be attributed to reduction of blood pressure and amelioration of insulin sensitivity. Abnormalities in membrane lipid composition may play an important role in these metabolic disorders.