Effects of Eplerenone on Left Ventricular Hypertrophy in Patients With Resistant Hypertension and Obstructive Sleep Apnoea

125 patients (78 men and 47 women) aged 18 - 65 years, with diagnosed resistant hypertension and moderate or severe OSA were included in the study, which was conducted in years 2014-2017 in the Department of Hypertension, Angiology and Internal Medicine and the Department of Pulmonology, Allergology and Respiratory Oncology at the University of Medical Sciences in Poznan, Poland. 23 patients did not complete the study because they did not meet the inclusion criteria (10 patients) and did not follow the recommendations (13 patients). 102 patients were randomized to two groups. In Group A, 50mg Eplerenone was administered orally once a day additionally for standard antihypertensive therapy. In Group B, standard antihypertensive therapy was not changed for 6 months of follow-up. RAH was recognized when in spite of the use of at least 3 antihypertensive agents (including a diuretic) in maximum doses, it was impossible to achieve the target values of BP (< 140/90 mmHg). The patients were taking on average 3,93 antihypertensive medications including diuretics (100% of patients), angiotensin-converting enzyme inhibitors (54% of patients), angiotensin II receptor antagonists (45.2% of patients), calcium antagonists (83.9% of patients), β-blockers (77.4% of patients), and α-blockers (22.6% of patients). The permission no. 565/14 to conduct the study was granted by the Ethics Committee of the University of Medical Sciences in Poznan. All patients gave an informed and written consent to participation in the study. Blood pressure measurements In all patients, during each visit, BP measurements were performed three times at rest in supine position, in standard conditions, using an upper arm blood pressure monitor BP monitor (Omron 705IT, Omron Healthcare, Kyoto, Japan). Ambulatory 24-hours BP automated monitoring (ABPM) was performed using a 24-hour ambulatory peripheral BP monitor TM2430 (A&D Medical, San Jose, California, United States). The frequency of measurements was every 15 minutes between 7:00 and 22:00 and every 30 minutes between 22:00 and 7:00.

Neck circumference measurement The neck circumference was measured in the midway of the neck, between the mid-cervical spine and mid-anterior neck, in standing position, with a flexible no-stretchable plastic tape, and approximated to the nearest 0.1 cm.

Echocardiographic examination

All patients underwent complete transthoracic echocardiographic study with Vivid S6 (GE Medical System, Tirat Carmel, Israel) with a 1,5 - 3,6 megahertz cardiac sector probe. A standard M-mode, two-dimensional and Doppler echocardiographic examination was performed according to the guidelines of American Society of Echocardiography. Three consecutive cycles were averaged for every parameter. The same experienced cardiologist who was blinded to the presence or absence of OSA performed all echocardiographic examinations. Left ventricular end-diastolic diameter (LVED), thickness of intraventricular septum at end diastole (IVS), left ventricular posterior wall at end diastole (LVPW) and left ventricular mass (LVM) were measured according to American Society of Echocardiography recommendations. The LVH was defined as the IVS or the LVPW>12 mm. The left ventricular mass was calculated using a simple and anatomically validated formula:

LVM = 0.8 × 1.04 [(IVS + LVED + LVPW) 3 - LVED 3] + 0.6 LVM was calculated as corrected for height and LVM index (LVMI). The relative wall thickness (RWT) was calculated as (2× LVPW)/LVEDD, for which the normal limit is <0.42. Based on LVMI and RWT, the LV geometry was classified as normal (LVMI <115 g/m2 in men, <95 g/m2 in women and RWT <0.42), concentric remodeling (normal LVMI <115 g/m2 in men, <95 g/m2 in women and increased RWT >0.42), concentric hypertrophy (LVMI >115 g/m2 in men, >95 g/m2 in women and increased RWT >0.42) or eccentric hypertrophy (LVMI >115 g/m2 in men, >95g/m2 in women and normal RWT <0.42).