Influence of pharmacogenetically determined treatment on parameters of peripheral hemodynamics in patients with arterial hypertension

Abstract

Aim: To evaluate daily blood pressure monitoring (DBPM) data changes in patients with essential arterial hypertension (EAH) under the influence of pharmacogenetically determined treatment depending on genes polymorphisms of angiotensin-converting enzyme (ACE, I/D), angiotensin II fifirst type receptor (AGTR1, А1166С), endothelial NO-synthase (eNOS, T894G), peroxisome proliferators-activated receptor-γ2 (PPAR-γ2, Pro12Ala), β1-adrenergic receptor (ADRB1, Arg389Gly). Material and Methods: 249 patients with EAH І-ІІІ stages (48.2% – women, 51.8% – men, mean ages 50.5±10.4 years) and 50 practically healthy persons were observed. Alleles of polymorphic locus were assessed by polymerase chain reaction (PCR) based method. DBPM was performed according to standard protocol. Patients were split by genotypes and treatment type into 6 groups: 1st group: I-allele of ACE gene carriers (n=60) took Hydrochlorothiazide (HCTZ) and angiotensin II receptor blocker (ARB II); 2nd group: I/D-genotype carriers (n=34) took HCTZ+β1-adrenobloker (β1-АB); 3rd group: I/D-genotype carriers (n=50) took HCTZ+ACE-inhibitor (ACEI); 4th group: DD-genotype carriers (n=15) took calcium channels bloker (CCB)+ ARB II; 5th group: DD-genotype carriers (n=15) took CCB+β1-АB; 6th group: DD-genotype carriers (n=27) took CCB+ACEI. Treatment efficacy was analyzed according to European Guidelines (2007). Results: Pharmacogenetically determined treatment of EAH patients during 9-12 months caused daily, day, and night blood pressure (BP) decrease below the “threshold” level in 154 (76.6%) patients. That did not significantly differ from the frequency of “target” office BP achievement: 149 (74.1%). The number of patients with normal BP daily profile “dipper” increased reliably by 10.1% (р<0.001), with “non-dipper” and “night-peaker” patients amount diminishing (р<0.05). Longterm combined therapy caused achievement of “target” average daily BP24 (DBPM) depending on types of treatment combination: after HCTZ+ARB ІІ – in 55 (91.7%) patients; after HCTZ+β1-AB – in 25 (73.5%) persons; after HCTZ+ACEI – in 33 (66.0%) patients; after CCB+ARB II – in 11 (73.3%) persons, without a reliable difference between genotypes; after CCB+β1-AB – in 11 (73.3%) patients (easier in Ala-allele carriers of PPAR-γ2 gene, р=0.002); after CCB+ACEI – in 19 (70.4%) patients (easier in AlaAla-genotype carriers of PPAR-γ2 gene, р=0.007). Conclusions: Prescription of HCTZ+ARB II drugs combination is more effective in treatment of EAH І-allele carriers of ACE gene patients than HCTZ+β1-АB or HCTZ+ACEI – 91.7% vs 66.0 or 73.5%, accordingly (р<0.001); for DD-genotype carrier hypertensive patients the combination of CCB+ARB II and CCB+β1-АB is more effective than CCB+ACEI – 73.3% vs 70.4%, accordingly.