Organoprotective properties of combination therapy with ramipril and indapamide in hypertensive patients with non-alcoholic fatty liver disease

Abstract

Objective. To assess the effect of combined antihypertensive therapy with ramipril and indapamide on the structural and functional state of the heart, blood vessels, kidneys, autonomic nervous system and liver in hypertensive patients with non-alcoholic fatty liver disease (NAFLD). Design and methods. We performed a prospective controlled study including 30 patients with hypertension (HTN) stages I–II, 1–2 degrees with NAFLD (fatty liver index (FLI) > 60) aged 45 to 65 years. Five-seven days before the initial examination, patients discontinued antihypertensive drugs, after the washout period one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg) was prescribed depending on the required dosage and recommendations on lifestyle changes and weight loss were given. Clinical examination, measurement of “office” blood pressure (BP), ambulatory BP monitoring (ABPM), central aortic pressure (CAP), pulse wave velocity (PWV), echocardiography and heart rate variability assessment were performed. The functional state of the kidneys and the structural and functional state of the liver were also assessed before and after treatment. Results. After 24-week therapy with a fixed combination of ramipril and indapamide (an average dosage 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively) target BP levels was achieved. According to ABPM, both daytime and nocturnal systolic BP (SBP) and diastolic BP (DBP) decreased. In addition, CAP (SBPao, DBPa) and augmentation index decreased. There was also a decrease in the stiffness of the arterial wall in muscle-type vessels (PWVm) (p = 0,0166) and in the number of patients with paradoxical test (p = 0,0320). There was a significant increase in creatinine clearance (Cockroft–Gault) after treatment (p = 0,0439) with no increase in glomerular filtration rate (CKD-EPI) (p = 0,1617). There was a significant change in the structural and functional indicators of the heart: increased left ventricular (LV) ejection fraction (p = 0,0398), decreased LV posterior wall thickness (p = 0,0457), LV end-systolic diameter (p = 0,0286), relative wall thickness (p = 0,0419) and LV myocardial mass index (p = 0,0002). There was a decrease in SDNN < 50 (p < 0,0001) and increase in RMSSD (p < 0,0001), which indicates a decrease in the sympathetic activity and an increase in parasympathetic regulation. Also the number of patients with normotonic type of autonomic reactivity in the orthostatic test increased after treatment (12 (24,0%) vs 19 (63,3%), p = 0,0456). The liver function and structure also improved showing decrease in total bilirubin (p = 0,0038) and gamma-glutamyltransferase (p = 0,0498), as well as the indices of liver steatosis (p = 0,0278) and fibrosis (p = 0,0166). Conclusions. Thus, combined antihypertensive therapy with ramipril and indapamide is well tolerated by patients, highly effective and demonstrates organoprotective properties regarding the heart, blood vessels, kidneys, autonomic nervous system and liver.