Metabolic effects of ramipril and indapamide in hypertensive patients with non-alcoholic fatty liver disease

Abstract

Objective. To assess the effects of combined antihypertensive therapy with ramipril and indapamide on insulin resistance, carbohydrate, lipid and purine metabolism, as well as the structure and function of the liver in hypertensive patients with non-alcoholic fatty liver disease (NAFLD).Design and methods. In a pre-post study, we included 30 patients with hypertension (HTN) 1–2 degrees in combination with NAFLD (Fatty Liver Index (FLI) > 60) aged 45 to 65 years. Patients discontinued antihypertensive therapy 5–7 days before the initial examination. After that one of the fixed combinations of ramipril (2,5/5 mg/day) and indapamide (0,625/1,25 mg) were prescribed along with the lifestyle and weight reduction recommendations (the Mediterranean type of diet, a decrease in calorie intake by 500–1000 kcal from baseline, and physical aerobic exercise at least 150 minutes per week). All patients underwent clinical examination, measurement of office blood pressure (BP), ambulatory BP monitoring (ABPM), anthropometric parameters, assessment of the visceral obesity index (VAI), anthropometric parameters, VAI, the degree of adipose tissue dysfunction (ATD), the percentage of visceral and subcutaneous fat by the bioelectrical impedance method. We also assessed lipid, carbohydrate, purine metabolism and the structural and functional state of the liver before and after the treatment.Results. After 24-week therapy with a fixed combination of ramipril and indapamide (average dosage of 4,04 ± 1,24 and 1,01 ± 0,31 mg, respectively) HTN patients with NAFLD achieved target BP. There was a decrease in both office systolic BP (SBP) (p < 0,001) and office diastolic BP (DBP) (p = 0,007) in 100 % of patients, as well as in ABPM indices. We observed a decrease in waist and hip circumferences (p ≤ 0,001 and p ≤ 0,001, respectively), the proportion of subcutaneous (p = 0,0134) and visceral (p = 0,002) fat. The number of patients with normal ATD increased (p = 0,030), while the proportion of patients with dysfunction decreased (p = 0,039). There was also a significant increase in high-density lipoprotein cholesterol (p = 0,027) and a decrease in insulin resistance (p = 0,002) and metabolic index (p = 0,030). We also found an improvement in carbohydrate metabolism with no change in purine metabolism. There was a favorable effect on the liver structure and function, and the number of patients with high alaninaminotransferase > 40 U/L decreased (5 (16,7 %) vs 0, p = 0,026).Conclusions. Twenty-fourweek treatment with a fixed combination of ramipril and indapamide, together with recommendations for lifestyle changes and weight loss, led to a significant decrease in BP levels, the severity of insulin resistance, and visceral obesity. In addition, the treatment had a beneficial effect on the parameters of carbohydrate and lipid metabolism, as well as liver structure and function (decreased severity of steatosis and fibrosis).