Are Angiotensin Converting Enzyme Inhibitors a New Therapeutic Option in Hypercholesterolaemia?

Abstract

Endothelial function has been shown to be defective in hyperlipidaemic patients, and animal studies have suggested that Angiotensin Converting Enzyme (ACE) Inhibitors may prevent arterial damage. In order to see if this also occurs in man, we studied the effect of six months treatment with lisinopril on endothelial function in a group of hypercholesterolaemic patients. METHODS and RESULTS: 40 patients were recruited. Forearm Despite a normal cardiac response to ere was a fall in BP. The failure to increase calf vascular resistance due to the action of insulin on skeletal muscle vasculature may be responsible for postprandial hypotension in the elderly after HC.blood flow via venous occlusion plethysmography was assessed in response to Acetylcholine, and Sodium Nitroprusside. Subjects were then randomised in a double blind fashion to receive either Lisinopril 20mg/day (n=20). or placebo (n=20) for six months. Plethsymography was then repeated. Baseline variables between groups were comparable. Lisinopril group: Blood pressure fell significantly, systolic 145k4 vs. 12854 (P<O.OOl), diastolic 84f2 vs. 7 4 s mmHg (P<O.OOI). An improvement was found in the vasodilatory response (expressed as the ratio of the infusedkontrol arm) to Acetylcholine e.g. 3.33S.3 @re) w. 4.45-4.48 (posr) Jbr 3Opg/nil (Pc0.03) and also for Nitroprusside e.g. 3.0dO.2(pre) vs. 3.86_M.3(posf) at 3.2pg/m/ Placebo group: Vasodilatation deteriorated non significantly in response to Acetylcholine, Nitroprusside responses were unchanged. CONCLUSION: The data presented suggest that long term Lisinopril therapy has a beneficial effect on arterial function in hyperlipidaemics. This may be due to reductions in Angiotensin I1 which can promote the generation of superoxide anions these can then degrade Nitric Oxide. Further work should now investigate whether ACE Inhibitors are beneficial in reducing mortality and morbidity in hypercholesterolaemia. (P<O.OI).Postprandial hypotension is common in the elderly, particularly after high carbohydrate (HC). The mechanisms underlying this fall in blood pressure (BP) are unclear, after high fat (HF) when BP is well maintained there is an increase in calf vascular resistance (CVR) not seen after HC. Insulin (I) a vasodilator of skeletal muscle vasculature may be responsible for this failure of vasoconstriction, leading to PP hypotension. We measured the cardiovascular (CV) responses to a HF meal when accompanied by a euglycaemic I infusion reproducing the plasma profile seen after HC, and compared the responses to those occurring after HC and HF in 10 healthy elderly subjects (8 male, mean age 7 1.4f2.2). Fasted baseline measurements of heart rate (HR), BP, cardiac output (CO) using Doppler ultrasound and calf blood flow (CBF) using venous occlusion plethysmography were taken. These were repeated after eating on 2 occasions, a HF meal one being accompanied by the I infusion (HFI). On a third occasion a HC meal was eaten. Table. CV variables before and after the 3 meals.Data expressed as mean k SEM, * denotes p<0.05.