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

• Compared with ARBs, beta–blockers reduce heart rate and 24–hour myocardial oxygen consumption.
• Ambulatory systolic blood pressure control is similar between beta–blocker and angiotensin receptor blocker.
• Beta–blockers lower the relative and absolute variability of heart rate and rate–pressure product.
• Rate slowing and reduced 24–hour myocardial oxygen consumption are present in whites and African Americans.

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.