Differential Effects of Chronic Oral Antihypertensive Therapies on Systemic Arterial Circulation and Ventricular Energetics in African-American Patients
Authors: Cholley Bernard P. , Shroff Sanjeev G. , Sandelski Joanne , Korcarz Claudia , Balasia Beth A. , Jain Shelly , Berger David S. , Murphy Michael B. , Marcus Richard H. , Lang Roberto M. 
Published: June 2012

Background
A comprehensive evaluation of arterial load characteristics and left ventricular energetics in systemic hypertension has been limited by the need for invasive techniques to access instantaneous aortic pressure and flow. As a consequence of this methodological limitation, no data exist on the effects of long-term antihypertensive therapy on global arterial impedance properties and indexes of myocardial oxygen consumption (MV̇
o
2
). Using recently validated noninvasive techniques, we compared in hypertensive patients the effects of chronic oral treatment with ramipril, nifedipine, and atenolol on arterial impedance and mechanical power dissipation as well as indexes of MV̇
o
2
.

Methods and Results
Sixteen African-American subjects with systemic hypertension were studied with a randomized, double-blind, crossover protocol. Instantaneous central aortic pressure and flow, from which arterial load characteristics can be derived, were estimated from calibrated subclavian pulse tracings (SPTs) and continuous-wave aortic Doppler velocity in conjunction with two-dimensional (2D) echocardiographic measurements of the aortic annulus, respectively. To derive ventricular wall stress and indexes of MV̇
o
2
, left ventricular short- (M-mode) and long-axis (2D echo) images were acquired simultaneously with SPTs. Data were collected at the end of a 2-week washout period (predrug control) and after 6 weeks of treatment with each agent. Although all three agents reduced diastolic blood pressure to the same extent, different effects on mean and systolic pressures and vascular impedance properties were noted. Nifedipine reduced total peripheral resistance (TPR; 1744±398 versus 1290±215 dyne-s/cm
5
) and increased arterial compliance (AC
L
; 1.234±0.253 versus 1.776±0.415 mL/mm Hg). This improvement in arterial compliance was not entirely accounted for by the reduction in distending pressure. Ramipril also decreased TPR (1740±292 versus 1437±290 dyne-s/cm
5
) and increased AC
L
(1.214±0.190 versus 1.569±0.424 mL/mm Hg), but with this agent, the change in arterial compliance was explained solely on the basis of a reduction in distending pressure. Atenolol, in contrast, did not affect either TPR or AC
L
. In agreement with the compliance results, nifedipine and ramipril significantly lowered the first two harmonics of the impedance spectrum, but atenolol did not. None of these agents resulted in a significant change in characteristic impedance or in the relative amplitude of the reflected pressure wave. Total vascular mechanical power and percent of oscillatory power remained unaltered with all antihypertensive treatments. Only ramipril and nifedipine reduced the integral of both meridional and circumferential systolic wall stresses, indicating that MV̇
o
2
per beat was reduced with these agents. Stress-time index, a measure of MV̇
o
2
per unit time, decreased significantly with ramipril but not with nifedipine because of an increase in heart rate noted in 10 of 16 patients (mean increase, 10 beats per minute). Thus, a reduction in MV̇
o
2
coupled with unchanged total vascular mechanical power suggests improved efficiency of ventriculoarterial coupling with ramipril and with nifedipine in the subset of patients in whom heart rate remained unchanged. In contrast, there was no evidence of a reduction in wall stress, stress integral, or stress-time index with atenolol.

Conclusions
The noninvasive methodology used in this study constitutes a new tool for serial and simultaneous evaluation of arterial hemodynamics and left ventricular energetics in systemic hypertension. In this study, we demonstrate the differential effects of chronic antihypertensive therapies on systemic arterial circulation and indexes of MV̇
o
2
in African-American subjects. Consideration of drug-induced differential responses of arterial load and indexes of MV̇
o
2
with each drug may provide a more physiological approach to the treatment of systemic hypertension in individual patients.