Arterial wave reflection during antihypertensive therapy with barnidipine: a 6-month, open-label study using an integrated cardiovascular ultrasound approach in patients with newly diagnosed hypertension.
BACKGROUND
Increased central aortic pressure resulting from large artery stiffening and increased wave reflection is associated with higher hypertension-related morbidity.


OBJECTIVE
The goal of this study was to evaluate the effects of a vasodilator-based therapy with the calcium channel blocker barnidipine on arterial stiffness, wave reflection, and left ventricular (LV) performance using an integrated cardiovascular ultrasound approach (including wave intensity analysis).


METHODS
Newly diagnosed, previously untreated patients with grade 1 or 2 essential hypertension (systolic blood pressure [BP] > or =140 and <180 mm Hg, and/or diastolic BP > or =90 and <110 mm Hg), and with no signs of clinical cardiovascular disease, were eligible for study. Carotid artery mechanics were investigated at baseline and after 3 and 6 months of barnidipine therapy (10-20 mg once daily, according to an open-label design) using a double-beam carotid ultrasound technique. This provided a simultaneous recording of diameter-derived pressure and flow velocity signals and allowed analysis of wave intensity. Indices of local arterial stiffness and wave reflection, as well as separated forward and backward pressure waves, were estimated. LV geometry, mass, and systolic and diastolic performance were also assessed using Doppler echocardiography. All ultrasound examinations and readings were performed by investigators blinded to patient demographics and treatment phase. Normotensive control subjects (office BP <140/90 mm Hg) were included as a reference group.


RESULTS
Twenty-one white, treatment-naive patients with hypertension (mean [SD] age, 58 [8] years; 14 males; mean body mass index, 27 [5] kg/m(2); mean BP, 159 [14]/96 [5] mm Hg) were enrolled. Twenty normotensive subjects comprised the control group. Compared with the control subjects, patients with hypertension had a higher mean augmentation index ([AIx] 22.0% [7.0%] vs 13.1% [5.2%]; P < 0.01), Peterson's pressure-strain elastic modulus (175 [49] vs 126 [41] kPa; P < 0.01), and forward and backward pressure waves (137 [17] vs 108 [7] mm Hg [P < 0.001] and 21 [6] vs 17 [5] mm Hg [P < 0.05], respectively) at baseline. After 6 months of barnidipine treatment, mean office BP in the patients with hypertension decreased from 159 (14)/96 (5) mm Hg at baseline to 138 (16)/81 (9) mm Hg (P < 0.001) due to a significant reduction in forward and backward pressure waves, and AIx decreased to 17.0% (8.0%) (P < 0.01); there were no significant changes in indices of intrinsic arterial stiffness. A significant direct relationship between AIx and pulse pressure (r = 0.45 [P < 0.05]) was observed at baseline in hypertensive patients but not after therapy (r = 0.26 [P = NS]). Mean stress-adjusted LV midwall shortening increased from 110% (17%) at baseline to 118% (13%) at 6 months (P < 0.05), which was comparable to baseline values in the control subjects (119% [10%]).


CONCLUSIONS
In these middle-aged patients with newly diagnosed mild to moderate hypertension, vasodilator therapy with barnidipine reduced central BP by a parallel reduction of forward and backward pressure waves, together with a later arrival of the reflected waves, with no significant changes in intrinsic arterial stiffness.
Palombo
Carlo
C
Department of Internal Medicine, University of Pisa, Pisa, Italy. carlo.palombo@med.unipi.it
Malshi
Emona
E
Morizzo
Carmela
C
Rakebrandt
Frank
F
Corretti
Valentina
V
Santini
Francesca
F
Fraser
Alan G
AG
Kozakova
Michaela
M
D000368:Aged; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D015150:Echocardiography, Doppler; D004548:Elasticity; D005260:Female; D006801:Humans; D006973:Hypertension / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D012720:Severity of Illness Index; D013997:Time Factors; D016896:Treatment Outcome; D018615:Ultrasonography, Doppler, Color; D016277:Ventricular Function, Left / Q000187:drug effects
D002121:Calcium Channel Blockers; C050699:mepirodipine; D009543:Nifedipine