on May 15, 2006
Published online before print May 15, 2006, doi: 10.1161/01.HYP.0000224283.76347.8c
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Submitted on February 9, 2006
From the Department of Pharmacology and INSERM U 652 (A.-I.T., P.B., B.L., S.L.), Georges Pompidou European Hospital, Paris, France; Department of Pharmacology (A.-I.T.), Henri Mondor Hospital, Paris, France; Department of Cardiology and INSERM U 652 (B.P.), Manhes Hospital, Fleury-Merogis, France; Department of Pharmacology and INSERM U 644 (R.J., C.T.), Bois-Guillaume Hospital, Rouen, France; Department of Pharmacology (E.B., H.S.-B.), Cardiovascular Research Institute, Maastricht, The Netherlands; and the Department of Biostatistics and INSERM U 644 (S.K.), Saint-Louis Hospital, Paris, France. * To whom correspondence should be addressed. E-mail: stephane.laurent{at}egp.ap-hop-paris.fr.
Abstract--Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressure-independent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63±7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg: from 13.1±5.9 to 16.0±6.7 kPa-1x10-3; 4 mg: from 13.2±5.2 to 12.7±5.9 kPa-1x10-3; ANOVA, dose-period interaction, P<0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.
Revised on March 9, 2006
Brachial Pressure-Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives
Anne-Isabelle Tropeano;
Key words: carotid arteries • elasticity • diabetes mellitus • hypertension • angiotensin-converting enzyme
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