Dose-Dependent Arterial Destiffening and Inward Remodeling After Olmesartan in Hypertensives With Metabolic Syndrome

Abstract

Whether angiotensin receptor blockers can dose-dependently remodel the arterial wall during long-term treatment has been largely debated. In this phase III, multicenter, randomized, double-blind, parallel-group study, 133 subjects with hypertension and metabolic syndrome were assigned to olmesartan, either 20 mg (n=44), 40 mg (n=42), or 80 mg (n=47) once a day, according to a force titration design during a 1-year period. Office blood pressure, 24-hour blood pressure, aortic stiffness (carotid-femoral pulse wave velocity), and carotid parameters were measured at baseline, 24 weeks, and 52 weeks. Pulse wave velocity significantly decreased ( P <0.001) with time in each group, with no significant time–dose interaction, despite a tendency ( P =0.0685) for a smaller effect of 20 mg, compared with 40 and 80 mg at week 52. When the 40 and 80 mg doses were combined (40/80 mg versus 20 mg), a significant blood pressure–independent reduction in pulse wave velocity (−0.61 m/s) was observed at week 52 ( P =0.0066), whereas the nonadjusted reduction was −1.31 m/s ( P <0.0001). By contrast, after 20 mg, the blood pressure–independent reduction in pulse wave velocity was not significant. Patients receiving the highest dose of olmesartan (40 and 80 mg) had an inward carotid remodeling and were shifted toward a lower elastic modulus at a given circumferential wall stress, indicating an improvement in the intrinsic elastic properties of the carotid artery wall material. These data suggest that 40 and 80 mg olmesartan were able to significantly remodel and destiffen the arterial wall material during long-term treatment, partly independently of blood pressure, compared with 20 mg.