Treatment of arterial hypertension with diuretics depending on patient’s salt sensitivity

Abstract

At present WHO considers arterial hypertension (AH) as the most frequent cause of death that can potentially be prevented. Timely diagnosis, preventive measures, and use of the adequate pharmacotherapy delays the progression of the disease, reduces the risk of complications, improves the quality of life and helps to maintain working capacity. The onset and progression of hypertension is associated with numerous risk factors, including environmental, genetic factors and the negative habits. The medical analytical literature provides evidence for the relationship between the amount of salt consumed and the hypotensive efficacy of diuretic drugs in patients with hypertension and genetic polymorphism. The objective: to study the effect of thiazide diuretics on the level of blood pressure depending on the Gly460Trp polymorphism of the ADD1 gene. Materials and methods. The study involved 120 patients of the Ukrainian population with a diagnosis of stage II hypertension (main group) and 112 apparently healthy individuals (control group). The method of Weinberger MN (1986) was used to determine the type of salt sensitivity. The Gly460Trp polymorphism of the ADD1 gene was determined by PCR. Patients of the main group were divided into two treatment groups: group I (60 people) received indapamide retard 1.5 mg daily, group II (60 people) – hydrochlorothiazide 25 mg daily. Results. Among 120 hypertensive patients, 75.8% were homozygotes for the G-allele, 21.7% – were heterozygotes and 2.5% – homozygotes for the T-allele. There were 2 times more sick carriers of the T-allele than healthy individuals (p˂0.05). In subgroup Ia (carriers of the GG genotype), the decrease in the level of mean daily SBP (ΔSBP) was 16.5 mmHg, among carriers of the T-allele – 49.8 mm Hg, in subgroup Ib – 12.6 and 26, 3 mm Hg respectively. The antihypertensive effect of treatment in carriers of the T-allele of group I was 2 times greater. In subgroup IIa (carriers of the GG genotype), the decrease in ΔSBP was 18.5 mmHg, and in carriers of the T-allele – 29.8 mm Hg. (p˂0.05). In subgroup IIb – 16.4 and 31.3 mm Hg. respectively. Therefore, the use of thiazide diuretics in carriers of T-allele gives the best hypotensive result and does not depend on salt sensitivity. Conclusion. Patients with hypertension have a significantly higher frequency of the T-allele G460T of the ADD1 gene compared to healthy individuals (12.5% vs 6.7%). The presence of the T-allele in the genotype of a patient with AH is a predictor of the successful use of thiazide diuretics.