ACE-INHIBITION BUT NOT ANGIOTENSIN-II ANTAGONISM REDUCES PLASMA-FIBRINOGEN AND INSULIN-RESISTANCE IN OVERWEIGHT HYPERTENSIVE PATIENTS

The aim of this study was to compare the effects of the angiotensin-co nverting enzyme (ACE) inhibitor perindopril and the angiotensin II ant agonist losartan on insulin sensitivity and plasma fibrinogen in overw eight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perind opril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen f or further 6 weeks. At the end of the placebo and of the treatment per iods, blood pressure was measured, plasma fibrinogen was evaluated, an d insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min o f clamp and total glucose requirement (TGR) were evaluated. Both perin dopril and losartan reduced SEP (by a mean of 20.2 mm Hg, p < 0.001 VS . placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DB P (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs, placebo respectively), with no difference between the two tr eatments. GIR was significantly increased by perindopril (+2.91 mg/min /kg, p = 0.042 vs. placebo), but not by losartan (+-0.28 mg/min/kg, NS ). TGR was not modified by losartan but was increased by perindopril ( +9.3 g, p = 0.042 vs, placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losarta n (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen wa s correlated with the increase in GIR (r = 0.39; p < 0.01). These find ings suggest that fibrinogen de crease produced by the ACE inhibitor i s related to its action on insulin sensitivity, which seems to be depe ndent not on angiotensin II blockade but rather on other mechanisms.