AimsTo investigate the effect of antihypertensive therapy on ventricular-arterial mechanics, coupling, and efficiency in early-stage hypertension.Methods and resultsWe studied 527 participants from two clinical trials assessing the effect of blood pressure lowering on diastolic function. Participants were aged ≥45 years with early-stage hypertension, no heart failure, ejection fraction (EF) ≥50%, and diastolic dysfunction using Doppler echocardiography. Effective arterial afterload and its components were assessed along with measures of left ventricular (LV) structure and function prior to and after 24-38 weeks of antihypertensive therapy. Systolic blood pressure decreased from 154 ± 18 to 137 ± 15 mmHg at follow-up. Blood pressure reduction was associated with decreases in ventricular and arterial stiffness, improvements in systemic arterial compliance and resistance, enhanced LV ejection, and reduction in cardiac work (all P < 0.001). Changes in Ea/Ees ratio were inversely correlated with those in EF (r = -0.25; P < 0.001), stroke work index (r = -0.13; P = 0.007), and LV efficiency (r = -0.98; P < 0.001); and directly related to changes in mitral E/e′ (r = 0.12; P = 0.01). Adjusting for age and blood pressure change, women and obese individuals had less enhancement in ventricular-arterial coupling and efficiency compared with men and non-obese individuals (P = 0.04 and 0.007, respectively).ConclusionAntihypertensive therapy reduces arterial and ventricular stiffness, enhances ventricular-arterial coupling, reduces cardiac work, and improves LV efficiency, systolic, and diastolic function. Attenuated responses in women and among obese subjects suggest that structure-function changes may be less reversible in these groups, possibly explaining their greater susceptibility to ultimately develop heart failure. © 2012 Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2012. For permissions please email: journals.permissions@oup. com.