GENDER DIFFERENCES IN ANTIHYPERTENSIVE EFFICIENCY OF COMBINATION PHARMACOTHERAPY IN PATIENTS WITH RESISTANT HYPERTENSION AND ABDOMINAL OBESITY IN RELATION TO SALT SENSITIVITY

Objective. To estimate the effectiveness of combination antihypertensive therapy, including the direct renin inhibitor aliskiren, in resistant hypertension (RHTN) and abdominal obesity (AO) according to gender and salt sensitivity.

Design and methods. The study included 161 patients with RHTN and AO, 78 (48.4 %) men and 83 (51.6 %) women. All patients at baseline and after 48 weeks of therapy as well as clinical and anthropometric study, electrocardiography and ambulatory blood pressure monitoring (ABPM) («Petr Telegin» BPLab Vasotens, Russia). Based on the V. I. Kharchenko’s test, all patients were divided into 4 groups: group 1 m (n = 38) and 1 w (n = 42) — «salt sensitive» men and women, and group 2 m (n = 40) and 2 w (n = 41) — «salt resistant» men and women. All patients received combination therapy: enalapril (renitek 20 mg/day, MSD, Switzerland),  amlodipine (normodipin 10 mg/day, Gedeon Richter, Hungary), hydrochlorothiazide (hydrochlorothiazide 12.5 mg/day, Gedeon Richter, Hungary) and direct renin inhibitor aliskiren (rasilez 150 mg/day, Novartis, Switzerland). After 3 weeks, aliskiren dose was increased up to 300 mg/day in case of low efficiency, followed by the repeated evaluation 3 weeks later. The data were processed using nonparametric statistics (Statistica 6.1, StatSoft Inc, USA). results. After 6 weeks of antihypertensive therapy including aliskiren (daily dose of 150/300 mg), target blood pressure (BP) < 140/90 mm Hg was detected in 31 (81.6 %) men and 32 (76 %) women in salt sensitive group, and in 31 (77.5 %) men and 39 (95.1 %) women in salt resistant group. Target BP < 140/90 mm Hg was registered more frequently among salt resistant women compared to salt resistant men (p = 0.02) and salt sensitive women (p = 0.01). All treatment groups showed a significant decrease in office systolic (SBP) and diastolic BP (DBP), and heart rate. Regardless of salt sensitivity and gender, there was a significant positive changes of ABPM indicators after 48 weeks of treatment. However, in salt sensitive men and women, the change in ABPM parameters was comparable, while salt resistant women showed more marked changes in comparison with salt resistant men positive, including changes in 24-mean and daily values of SBP and DBP, SBP and DBP time index and variability during the day, as well as the time and the speed of morning surge in SBP and DBP. After 48 weeks of therapy, «dipper» BP profile was found in 17 (54.8 %) of 31 men and 17 (53.1 %) of 32 women in the salt sensitive group. In salt resistance group, «dipper» type was more prevalent among women than among men (51.3 and 35.5 %, respectively, p = 0.048). conclusions.

Results of the study demonstrated a significant efficiency of aliskiren as part of combination antihypertensive therapy in both men and women with RHTN and AO regardless of salt sensitivity. At the same time, in salt sensitive men and women antihypertensive effects of aliskiren were comparable regardless of gender, whereas among salt resistant patients women showed higher benefit compared to men.

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