Brachial pressure-independent reduction in carotid stiffness after long-term angiotensin-converting enzyme inhibition in diabetic hypertensives.
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(-1)x10(-3); 4 mg: from 13.2+/-5.2 to 12.7+/-5.9 kPa(-1)x10(-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.
Tropeano
Anne-Isabelle
AI
Department of Pharmacology and INSERM U 652, Georges Pompidou European Hospital, Paris, France.
Boutouyrie
Pierre
P
Pannier
Bruno
B
Joannides
Robinson
R
Balkestein
Elisabeth
E
Katsahian
Sandrine
S
Laloux
Brigitte
B
Thuillez
Christian
C
Struijker-Boudier
Harry
H
Laurent
Stéphane
S
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001916:Brachial Artery; D002339:Carotid Arteries / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
D000806:Angiotensin-Converting Enzyme Inhibitors; D020913:Perindopril