Brachial Pressure–Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 48; no. 1; pp. 80 - 86
• Main Authors: Tropeano, Anne-Isabelle, Boutouyrie, Pierre, Pannier, Bruno, Joannides, Robinson, Balkestein, Elisabeth, Katsahian, Sandrine, Laloux, Brigitte, Thuillez, Christian, Struijker-Boudier, Harry, Laurent, Stéphane
• Format: Journal Article
• Language: English
• Published: United States American Heart Association, Inc 01.07.2006
• Subjects: Angiotensin-Converting Enzyme Inhibitors - pharmacology; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Blood Pressure - drug effects; Brachial Artery; Carotid Arteries - drug effects; Carotid Arteries - pathology; Carotid Arteries - physiopathology; Diabetes Complications - pathology; Diabetes Complications - physiopathology; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - pathology; Diabetes Mellitus, Type 2 - physiopathology; Dose-Response Relationship, Drug; Female; Humans; Hypertension - complications; Hypertension - drug therapy; Hypertension - pathology; Hypertension - physiopathology; Male; Middle Aged; Perindopril - pharmacology; Perindopril - therapeutic use; Single-Blind Method; Tunica Intima - pathology; Tunica Media - pathology
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000224283.76347.8c

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 mgfrom 13.1±5.9 to 16.0±6.7 kPa×10; 4 mgfrom 13.2±5.2 to 12.7±5.9 kPa×10; 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.