Ambulatory 24-hour cardiac oxygen consumption and blood pressure-heart rate variability: effects of nebivolol and valsartan alone and in combination

Abstract

We compared an angiotensin receptor blocker (valsartan; VAL), a beta-blocker (nebivolol; NEB) and the combination of NEB/VAL with respect to 24-hour myocardial oxygen consumption (determined by 24-hour ambulatory heart rate-central systolic pressure product [ACRPP]) and its components. Subjects with hypertension (systolic blood pressure >140 or diastolic blood pressure >90; n = 26) were studied in a double-blinded, double-dummy, forced-titration, crossover design with 3 random-order experimental periods: VAL 320 mg, NEB 40 mg, and NEB/VAL 320/40 mg daily. After 4 weeks of each drug, ambulatory pulse wave analysis (MobilOGraph) was performed every 20 minutes for 24 hours. All three treatments resulted in nearly identical brachial and central systolic blood pressures. NEB alone or in combination with VAL resulted in lower ACRPP (by 11%-14%; P < .001 each) and heart rate (by 18%-20%; P < .001 each) compared with VAL, but stroke work (ACRPP per beat) was lower with VAL. Relative and adjusted variability (standard deviation and coefficient of variation) of heart rate were also lower with NEB and NEB/VAL than VAL. Results in African Americans, the majority subpopulation, were similar to those of the entire treatment group. We conclude that the rate-slowing effects of NEB cause ambulatory cardiac myocardial oxygen consumption to be lower with NEB monotherapy or NEB/VAL combination therapy than with VAL monotherapy. NEB/VAL is not superior to NEB alone in controlling heart rate, blood pressure, or ACRPP. Heart rate variability but not ACRPP variability is reduced by NEB or the combination NEB/VAL. There is no attenuation of beta-blocker-induced rate-slowing effects of in African Americans.

Keywords: Ambulatory blood pressure monitoring; angiotensin receptor blockers; beta blockers; central blood pressure; clinical trial; myocardial oxygen consumption; nebivolol; pulse wave analysis; rate-pressure product; valsartan.

Conflict of interest statement

Conflict of interest: none.

Copyright © 2015 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.

Study design. The forced-titration design is depicted in the upper panel, which also shows the timing of 24-hour ambulatory pulse wave monitoring. Subjects received half doses of each drug (160 mg valsartan or 20 mg ncbivolol daily) at the beginning and end of each treatment period. Possible randomization sequences are shown in the bottom panel.

Figure 2.

Ambulatory central rate-pressure product (ACRPP) by treatment and time period. The principal dependent variable (ACRPP) was lower on nebivolol or the combination than with valsartan.