Differences in the Magnitude of Wave Reflection Account for Differential Effects of Amlodipine- Versus Atenolol-Based Regimens on Central Blood Pressure

Abstract

Antihypertensive agents may differ in their effects on central systolic blood pressure, and this may contribute to treatment-related differences in cardiovascular outcomes. In a substudy of the Anglo-Scandinavian Cardiac Outcome Trial, we investigated whether directly measured carotid systolic blood pressure differed between people randomized to amlodipine- and atenolol-based therapies and whether this is accounted for by differences in wave reflection patterns. Additional analysis was undertaken to establish whether differences in carotid systolic blood pressure predicted left ventricular mass, accounting for between-treatment differences in left ventricular mass index. Blood pressure and flow velocity were measured in the right carotid artery of 259 patients. Wave intensity analysis was used to separate and quantify forward and backward waves. Brachial blood pressure did not differ significantly between groups, but carotid systolic blood pressure (127 [12] versus 133 [15] mm Hg; P<0.001), the ratio of backward:forward pressure (0.48 [0.17] versus 0.53 [0.19]; P=0.01), and wave reflection index (19.8% [10.9%] versus 23.3% [13.3%]; P=0.02) were significantly lower in patients randomized to amlodipine-based therapy. Left ventricular mass index was also lower in this group, and adjustment for carotid blood pressure attenuated treatment differences to a greater extent than brachial blood pressure. Carotid systolic blood pressure was also a significant independent predictor of left ventricular mass index in a multivariate model. Carotid systolic blood pressure is lower in people randomized to amlodipine-based compared with atenolol-based treatment despite there being no significant difference in brachial blood pressure. This difference is attributable to a lesser magnitude of wave reflection in patients randomized to the amlodipine-based regimen.