Renal denervation in resistant hypertension treatment.

BACKGROUND AND OBJECTIVES: Purpose of the study is the assessment of the effectiveness of renal denervation with different types of catheters, as well as its long-term effects, in the patients with resistant hypertension. MATERIALS AND METHODS: This single-center prospective study included 81 patients who underwent a renal denervation procedure using 2 types of catheters: monopolar and helical (Medtronic Inc., Minneapolis, Minnesota, the USA) between 2015 and 2018. Baseline demographics, clinical, functional and laboratory characteristics of the patients were assessed. A comparative analysis of the dynamics of office systolic and diastolic blood pressure during 5 years of follow-up was carried out. The Kaplan-Meier method was used to study the survival of the patients with resistant hypertension after renal denervation. RESULTS: A total of 81 patients with a mean age of 57.79 ± 9.87 years, of whom 37.04 % were men, were included in the 2-stage study (first stage using monopolar catheters and second stage using spiral catheters). At the time of inclusion, study participants were receiving an average of 4.5 ± 1.4 antihypertensive medications. In 36 (or 44.4 %), the procedure was performed using a monopolar catheter; in 45 (or 55.6 %), a spiral catheter was used. There were no statistically significant differences between the two groups of the patients. The analysis established statistically significant changes in the dynamics of office SBP and DBP (p < 0.001) assessed 1, 2, 3, 4, and 5 years after the renal denervation procedure. The analysis demonstrated a stability in the reduction of office SBP and DBP during the 5-year follow-up. The results of the study showed that the median survival time was 1061 days from the beginning of follow-up (95% CI: 728.03 to 1 393.97 days); the median survival time in the monopolar catheter group was 777 days (95% CI: 692.314 to 861.686) and in the spiral catheter group 1 294 days (95% CI: 713.079 to 1 874.921). FINDINGS: Our results demonstrated the efficiency and safety of renal denervation in both short-term and long-term follow-up using monopolar and spiral catheters in the treatment of uncontrolled hypertension with combined antihypertensive therapy. The most significant is the demonstrated stability of the effect after the procedure. In addition, the survival rate of the patients with resistant hypertension after the intervention has been carried out (Tab. 2, Fig. 3, Ref. 22).

Case-finding for alpha1-antitrypsin deficiency in Kazakh patients with COPD.

BACKGROUND: Alpha-1-antitrypsin deficiency (AATD) is an under-diagnosed condition in patients with chronic obstructive pulmonary disease (COPD). The aim of this study was to screen for AATD in Kazakh patients with COPD using dried blood spot specimens. METHODS: The alpha1-antitrypsin (AAT) concentration was determined by nephelometry, PCR was used to detect PiS and PiZ alleles; and isoelectric focusing was used to confirm questionable genotype results and detect rare AAT variants. RESULTS: To this aim, 187 Kazakh subjects with COPD were recruited. Blood samples were collected as dried blood spot. Genotyping of 187 samples revealed 3 (1.6%) PI*MZ and 1 (0.53%) PI*MS, Phenotyping identified also two sample (1.1%) with phenotype PiMI. Allelic frequencies of pathological mutations Z, S and I resulted 0.8%, 0.3%, 0.5%, respectively, in COPD Kazakh population. CONCLUSION: This study proved that AATD is present in the Kazakh population. These results support the general concept of targeted screening for AAT deficiency in countries like Kazakhstan, with a large population of COPD patients and low awareness among care-givers about this genetic condition.

Association Between the P2RY12 Receptor Gene Polymorphism and Aspirin Resistance in Patients with Coronary Artery Disease.

INTRODUCTION: Platelet activation and aggregation are key elements in the development of coronary atherosclerosis. Recent studies have shown that the two polymorphisms of platelet ADP receptor P2RY12 (haplotypes H2 and 34T) are associated with increased platelet aggregation and atherothrombotic risk. It was shown that these polymorphisms promote reduced body response to antiplatelet therapy. AIM: We investigated the association of P2RY12 gene polymorphisms with aspirin resistance in patients with coronary artery disease (CAD). METHODS: This case-control study included 100 cases with CAD (mean age 57.6 ± 2.8 years) treated in the cardiology department of the city hospital Semey, Kazakhstan, 90 of whom suffered from myocardial infarction. The control group (n = 100) were healthy people without a history of CAD, matched on sex and age. Genotyping of polymorphisms H1/H2 in P2RY12 gene was performed by PCR. Statistical analysis was performed using SPSS v.19.0. RESULTS: The distribution of H1/H2 genotypes P2RY12 was 42%, 34%, and 24%, respectively, in cases and 42%, 58%, and 0%, respectively, in controls. All allele frequencies were consistent with the Hardy Weinberg equilibrium (p = 0.0036 and p = 0.0001 in cases and controls, respectively). Genotype H2 was associated with risk of CAD with aspirin resistance (co-dominant model: OR = 3.75, 95% CI 0.14 - 99.88, p = 0.05 and dominant model: OR = 2.78, 95% CI 0.11 - 70.93, p = 0.05). We found significant differences in the distribution of the mutant genotype H2 between CAD patients with aspirin resistance and healthy controls (χ2 = 30.3, p < 0.05). CONCLUSION: We found an association of H2 haplotype in P2RY12 gene with aspirin resistance in patients with CAD. However, in order to obtain definitive conclusions about the role of genetic variants with the development of aspirin resistance in patients with CAD, there is a need for further research with a larger sample size as well as the use of selective thromboxane receptor antagonists for studying functional effects of genetic variants.

Association between C677T/MTHFR genotype and homocysteine concentration in a Kazakh population.

We recently suggested that due to insufficient intake of vegetables, low folate status and mild homocysteinemia might exist in the Kazakh population. To clarify the determinants of homocysteine concentrations among this population, we determined concentrations of serum folate, albumin, creatinine, vitamin B12, and the C677T/ MTHFR genotype in 110 Kazakh individuals and compared these with plasma total homocysteine. In Kazakh, after adjustment for age and sex, folate was correlated with plasma total homocysteine, whereas concentrations in those with the TT genotype was almost twice as high as in those with the CC and CT genotypes (19.7+/-1.8 micromol/L vs. 10.7+/-0.5 micromol/L, p<0.001). Our results suggest that the C677T/MTHFR genotype is associated with homocysteine concentrations in this population and this association might be affected by other factors, such as folate status.