Integrative assessment of candidate gene polymorphisms distribution by forming a gene modification index in arterial hypertension with and without obesity: a new perspective in cardiology management

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V Bondar ◽  
K Chernyshova ◽  
H Chernyshova ◽  
S Kolomiiets ◽  
V Klochko ◽  
...  

Abstract   The concept of evolutionary accumulation of candidate gene polymorphisms in the realization of the hypertensive phenotype becomes promising in understanding of arterial hypertension (AH). A large amount of data about genetic polymorphisms in population have been accumulated and perspective approaches to their integrative assessment are being formulated for practical management. The purpose of the research was to analyze and compare the proportion of modified candidate genes (CG) in the group of hypertensive patients with and without obesity with the group of non-hypertensive patients by calculating the gene modification index (GMI) for the assessment of possible usage of genetic stratification in the management of AH. Methods 106 patients with AH and obesity (age 46.2 [24–72], m/f 79/27), (group 1), 96 hypertensive patients without obesity (age 48.3 [26–75], m/f 72/24), (group 2) and 98 non-hypertensive patients (age 41.6 [26–69], m/f 39/59), (group 3) (ESC/ISH 2018, WHO 1997) were examined. The analysis of polymorphisms of the following CG by PCR was perfomed: ADD1: 1378, AGT: 704, AGT: 521, AGTR1: 1166, AGTR2: 1675, CYP11B2: −344, GNB3: 825, NOS3: −786, NOS3: 894. The GMI which represents the percentage of “pathological” genotypes was formed and calculated by the formula: GMI = (N/13.5) × 100, where N is the sum of points of present GP (“pathological” homozygous was 1,5 points, heterozygous – 1 point, “normal” genotype – 0 points); 13.5 – maximum number of points. The GMI from 0 to 20% was considered as low genetic risk (GR), from 21 to 40% – moderate GR, from 41 to 70% – high GR, from 71 to 100% – very high GR. Results In patients with AH and obesity, a low GR was in 4 (3.8%), in the group of hypertensive patients without obesity – 13 (13.5%), in normotensive patients – in 81 (82.7%) (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.02). Moderate GR was observed in 21 (19.8%) patients of the 1st group, in 25 (26%) patients of the 2nd group and in 12 (12.2%) patients of the 3rd group (p1–3 = 0.07, p2–3 = 0.01, p1–2 = 0.02). 54 (50.9%) patients of group 1, 41 (42.7%) patients of group 2 and 5 (5.1%) of patients of group 3 had a high GR (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.08); a very high GR was in 27 (25.5%) patients of the 1st group, in 17 (17.8%) of the 2nd group and was absent in the patients of the 3rd group (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.02). The average GMI in group 1 was 66.2% [CI 95%, 20–78], in group 2 – 56.4% [CI 95%, 18–72], in group 3 – 22% [CI 95% 5–41], (p1–3 = 0.0001, p2–3 = 0.0001, p1–2 = 0.04). Conclusions It was revealed a strong significant predominance of the proportion of modified CG in hypertensive patients with and without obesity compared with non-hypertensive patients. There was a moderate significant difference between hypertensive patients, depending on the presence of obesity. Evaluation of GMI is a perspective direction in the diagnosis and prevention of AH and can be used in practical management. Funding Acknowledgement Type of funding source: None

2019 ◽  
Vol 23 (2) ◽  
pp. 277-282
Author(s):  
V. D. Nemtsova ◽  
I. A. Ilchenko ◽  
V. V. Zlatkina

Due to the growing number of patients with age-related diseases, the aim of the study was to investigate in the changes of aging rate (AR) in patients with comorbid course of arterial hypertension (H), type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SH) and to study the features of these changes depending on hormonal imbalance. 118 patients (63 women and 55 men, average age — 53.6±4.3 years) were divided into 3 groups: group 1 (n=37) with isolated H; group 2 (n=42) — with H and T2DM; group 3 (n=39) — with H, T2DM and SH. The investigation program included: measurement of anthropometric parameters (blood pressure, height, body weight (BW), body mass index (BMI)), carbohydrate and thyroid metabolism using standard methods, biological age (BA) by V.P. Voitenko et al. Statistical processing was performed using the Statistica for Windows 8.0 software package. When evaluating AR, physiological aging was found in 8 patients (21.6%) of group 1, in 4 (9.5%) patients of group 2 and 3 (7.7%) of patients in group 3. In the overwhelming majority of the examined patients, premature aging (PA) was noted, however, the acceleration of PA between patients of groups 2 and 3 was not differ significantly (p>0.05). The increase in AR in group 2 patients was accompanied by an increase in BA by 7.2 years, in 3 group patients — by 7.3 years compared with their chronological age. A correlation analysis revealed a positive relationship between BMI and coefficient of aging rate (CAR) (r=0.679; p<0.05); BMI and BA (r=0.562; p<0.05) and CAR and the TSH level (r=0.050; p=0.388) in the 3rd group. Thus, the presence of hypertension and comorbid endocrinopathies — T2DM and SH significantly increases the AR and when assessing the effect of endocrine disorders, the presence of T2DM is more important than SH.


2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett

Abstract Background Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission. Methods In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous glucose monitoring, 24-h blood-pressure- and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 h) than Group-2 patients (0.2 ± 0.3 per 24 h), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 h). Plasma norepinephrine and mean arterial blood pressure were higher Group-1 and Group-3 patients than in control patients of Group 2. At discharge, the daily cumulative insulin dose was reduced in Group-1 (− 18.4 ± 24.9 units) and in Group-3 patients (− 18.6 ± 22.7 units), but remained unchanged in Group-2 control patients (− 2.9 ± 15.6 units). Conclusions An association between hypoglycemic events and uncontrolled hypertension was found in this study.


1998 ◽  
Vol 274 (4) ◽  
pp. H1113-H1120 ◽  
Author(s):  
Michael R. Ujhelyi ◽  
J. Jason Sims ◽  
Allison Winecoff Miller

This study assessed the effect of low (10 mg ⋅ kg−1 ⋅ h−1) and very high (18 mg ⋅ kg−1 ⋅ h−1) doses of lidocaine on defibrillation energy requirements (DER) to relate changes in indexes of sodium-channel blockade with changes in DER values using a dose-response study design. In group 1 (control; n = 6 pigs), DER values were determined at baseline and during treatment with 5% dextrose in water (D5W) and with D5W added to D5W. In group 2 ( n = 7), DER values were determined at baseline and during treatment with low-dose lidocaine followed by high-dose lidocaine. In group 3 ( n = 3), DER values were determined at baseline and high-dose lidocaine. Group 3 controlled for the order of lidocaine treatment with the addition of high-dose lidocaine after baseline. DER values in group 1 did not change during D5W. In group 2, low-dose lidocaine increased DER values by 51% ( P = 0.01), whereas high-dose lidocaine added to low-dose lidocaine reduced DER values back to within 6% of baseline values ( P = 0.02, low dose vs. high dose). DER values during high-dose lidocaine in group 3 also remained near baseline values (16.2 ± 2.7 to 12.9 ± 2.7 J), demonstrating that treatment order had no impact on group 2. Progressive sodium-channel blockade was evident as incremental reduction in ventricular conduction velocity as the lidocaine dose increased. Lidocaine also significantly increased ventricular fibrillation cycle length as the lidocaine dose increased. However, the greatest increase in DER occurred when ventricular fibrillation cycle length was minimally affected, demonstrating a negative correlation ( P = 0.04). In summary, lidocaine has an inverted U-shaped DER dose-response curve. At very high lidocaine doses, DER values are similar to baseline and tend to decrease rather than increase. Increased refractoriness during ventricular fibrillation may be the electrophysiological mechanism by which high-dose lidocaine limits the adverse effects that low-dose lidocaine has on DER values. However, there is a possibility that an unidentified action of lidocaine is responsible for these effects.


2014 ◽  
Vol 2014 ◽  
pp. 1-19 ◽  
Author(s):  
Cheuk-Kwan Sun ◽  
Yen-Yi Zhen ◽  
Hung-I Lu ◽  
Pei-Hsun Sung ◽  
Li-Teh Chang ◽  
...  

We tested the hypothesis that Lipofectamine siRNA delivery to deplete transient receptor potential cation channel (TRPC) 1 protein expression can suppress hypoxia-induced pulmonary arterial hypertension (PAH) in mice. Adult male C57BL/6 mice were equally divided into group 1 (normal controls), group 2 (hypoxia), and group 3 (hypoxia + siRNA TRPC1). By day 28, right ventricular systolic pressure (RVSP), number of muscularized arteries, right ventricle (RV), and lung weights were increased in group 2 than in group 1 and reduced in group 3 compared with group 2. Pulmonary crowded score showed similar pattern, whereas number of alveolar sacs exhibited an opposite pattern compared to that of RVSP in all groups. Protein expressions of TRPCs, HIF-1α, Ku-70, apoptosis, and fibrosis and pulmonary mRNA expressions of inflammatory markers were similar pattern, whereas protein expressions of antifibrosis and VEGF were opposite to the pattern of RVSP. Cellular markers of pulmonary DNA damage, repair, and smooth muscle proliferation exhibited a pattern similar to that of RVSP. The mRNA expressions of proapoptotic and hypertrophy biomarkers displayed a similar pattern, whereas sarcomere length showed an opposite pattern compared to that of RVSP in all groups. Lipofectamine siRNA delivery effectively reduced TRPC1 expression, thereby attenuating PAH-associated RV and pulmonary arteriolar remodeling.


2020 ◽  
Author(s):  
Abimbola Abobarin-Adeagbo ◽  
Andreas Wienke ◽  
Matthias Girndt ◽  
Rainer U. Pliquett

Abstract Background: Aim of this study is to investigate a possible association of hypoglycemic episodes and arterial hypertension. We hypothesize that hospitalized insulin-treated diabetes patients with hypertensive crisis have more hypoglycemic episodes than their counterparts without hypertensive crisis on admission.Methods: In a prospective, observational cohort study, 65 insulin-treated diabetes patients (type 1, type 2, type 3c) were included in Group 1, when a hypertensive crisis was present, as control patients in Group 2 without hypertensive crisis or hypoglycemia, in Group 3, when a symptomatic hypoglycemia was present on admission. All patients were subjected to open-label continuous flash glucose monitoring, to 24-hour blood-pressure and Holter electrocardiogram recordings, and to laboratory tests including plasma catecholamines. Results: 53 patients, thereof 19 Group-1, 19 Group-2, 15 Group-3 patients, completed this study. Group-1 patients had the highest maximum systolic blood pressure, a higher daily cumulative insulin dose at admission, a higher body-mass index, and a higher plasma norepinephrine than control patients of Group 2. Group-3 patients had more documented hypoglycemic episodes (0.8 ± 0.5 per 24 hours) than Group-2 patients (0.2 ± 0.3 per 24 hours), however, they were not different to the ones in Group-1 patients (0.4 ± 0.4 per 24 hours). Plasma norepinephrine and mean arterial blood pressure were not different between Group-1 and Group-3 patients, though higher than in Group-2 patients. At discharge, the daily cumulative insulin dose was reduced in Group-1 (-18.4 ± 24.9 units) and Group-3 patients (-18.6 ± 22.7 units), but remained unchanged in Group-2 patients (-2.9 ± 15.6 units).Conclusions: An association between hypoglycemic events and uncontrolled hypertension was found in this study.


2021 ◽  
Vol 20 (Supplement_1) ◽  
Author(s):  
R Sharafutdinova ◽  
VI Ruzov ◽  
VA Razin ◽  
RH Gimaev ◽  
LT Nizamova

Abstract Funding Acknowledgements Type of funding sources: None. Aim of study. To study spontaneous platelet aggregation in patients with arterial hypertension with different functional classes (FC) of CHF with preserved systolic function not taking antiplatelet therapy. Material and Methods 51 patients with AH with different types of CHF, mean age 55.4 ± 5.9 years, with preserved left ventricular systolic function according to ECHO-CS were studied. The patients were divided into 4 groups depending on FC of CHF: Group 1 - 0 FC of CHF (n = 11), Group 2 - 1 FC of CHF (n = 13), Group 3 - 2 FC of CHF (n = 14), and Group 4 - 3 FC of CHF (n = 13). Spontaneous platelet aggregation was determined on a KFK-2MP photoelectrocolorimeter (Russia). Results. During the study, the spontaneous platelet aggregation was 1.08 ± 0.31 in patients with CHF class 0 (1 gr), and 1.22 ± 0.25 in patients with CHF class 1, with no statistical difference in comparison with 1 gr (p = 0.233). In group 3 (2FC CHF), spontaneous platelet aggregation was 1.33 ± 0.27, with a statistically significant difference with spontaneous platelet aggregation in patients with type 0 (p = 0.042), but with group 2 (1FC CHF), no statistically significant difference was found (p = 0.281). Spontaneous platelet aggregation in group 4 (3FC CHF) was 1,62 + 0,32, with statistically significant difference in comparison with all groups, so with group 1 - p &lt; 0,001, with group 2 - p = 0,016 and with group 3 - p = 0,017. Conclusion. Patients with arterial hypertension with preserved systolic function showed an increase in spontaneous platelet aggregation with increasing functional class of CHF, and the most significant increase in platelet aggregation was seen in patients with class 3 CHF.


2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Marina Shargorodsky

The present study was designed to determine the effect of different doses of the angiotensin II receptor blocker, candesartan, on circulating adiponectin and leptin levels as well as plasma leptin adiponectin ratio (LAR) in hypertensive patients with multiple cardiovascular risk factors. 69 hypertensive patients were randomized to 3 groups: group 1 included patients treated with high doses of Candesartan (32mg), group 2 included patients treated with conventional doses of Candesartan (16mg), group 3 included patients that received antihypertensive treatment other that ARBs or ACEIs. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, CRP, aldosterone, renin,HOMA-IR, leptin , adiponectin and LAR. Baseline adiponectin, leptin and LAR levels did not differ significantly between the three groups. After six months of treatment LAR was significantly higher in group 3 than group 1 (p=0.007) or group 2 (p=0.023). Marginal across-group differences were detected for post-treatment circulating adiponectin level (p=0.064). Univariate GLM analysis of posttreatment LAR detected significant by-group differences even after adjustment for age, sex, baseline values of LAR and blood pressure. In this model, group was the only significant predictor of LAR after controlling for these variables. Treatment with high doses of angiotensin II receptor blocker, candesartan, is associated with significantly reduced LAR and marginally increased circulating adiponectin levels in hypertensive patients with multiple cardiovascular risk factors.


2019 ◽  
pp. 112067211988039 ◽  
Author(s):  
Simone Donati ◽  
Andrea Maria Maresca ◽  
Jennifer Cattaneo ◽  
Alessandra Grossi ◽  
Marco Mazzola ◽  
...  

Introduction: To evaluate retinal microvasculature modifications by means of optical coherence tomography angiography in human subjects diagnosed with arterial hypertension and to assess potential clinical relevance for early diagnosis. Methods: A cross-sectional study of 30 subjects affected by arterial hypertension compared to a matched cohort of healthy patients was conducted. Patients were evaluated by the Outpatient Clinic for Hypertension and the Retina Center, University of Insubria, Varese, Italy. Patients were divided into three groups: Group 1—healthy subjects, Group 2—patients first diagnosed with hypertension, and Group 3—patients with treated hypertension. Optical coherence tomography angiography was performed applying different analysis protocols for macula and optic disk, using an AngioVue OCTA System on an Optovue device. Morphological data were compared to and correlated with clinical vascular parameters, to evaluate preclinical microvascular damage. Results: A significant reduction in deep vascular layer density (Group 1: 59.2% ± 1.5% standard deviation; Group 2: 59.2% ± 2.2% standard deviation; Group 3: 57.8% ± 2.6% standard deviation; p < 0.05) as well as an enlargement of the deep foveal avascular zone area (Group 1: 0.34 ± 0.09 mm2; Group 2: 0.36 ± 0.07 mm2; Group 3: 0.39 ± 0.1 mm2; p < 0.05) was measured in patients with first diagnosed hypertension and in treated patients compared to healthy subjects. We also observed a significant decrease in mean foveal choroidal thickness in affected patients compared to controls (Group 1: 319.68 ± 61.72 µm standard deviation; Group 2: 251.04 ± 63.1 µm standard deviation; Group 3: 262.65 ± 51.08 µm standard deviation; p < 0.05). Our preliminary data did not show a significant correlation with microalbuminuria levels. Discussion: Retinal vascular density showed pathological modifications between healthy subjects and hypertensive patients. These preliminary findings suggest that optical coherence tomography angiography may identify pathological markers of an early hypertensive damage and help monitor disease progression with potential therapeutic advantages.


2011 ◽  
Vol 493-494 ◽  
pp. 366-369
Author(s):  
Hironobu Oonishi ◽  
Hiroyuki Oonishi Jr. ◽  
Shigekazu Mizokawa ◽  
Hirotsugu Ohashi ◽  
Masaru Ueno ◽  
...  

To improve the fixation of bone and bone cement in THA we used Interface Bioactive Bone Cement technique (IBBC) since 1982. For prostheses 28 mm-alumina head with polyethylene socket (Kyocera Co.) were used. In IBBC not-resorbable pure crystalline HA granules (0.3– 0.5 mm) were smeared on the bone surface in one to three layers just before packing bone cement. Group 1: IBBC was used in six joints in 1982. Group 2: In 25 patients, conventional bone cement technique (non-IBBC) in the one hip (in 1985 to 1986) and IBBC technique in the other hip (in 1986) were performed in the same patients. Group 3: In 65 patients (71 joints) IBBC were performed. Neither radiolucent line nor osteolysis appeared in all case in group 1. In group 2 in Non-IBBC the appearance rate of radiolucent line and osteolysis were rather high, however in IBBC they were extremely low. In Non-IBBC loosening were seen in 5 joints in the acetabulum and in 2 joints in the femur. However, in IBBC there was no loosening. In group 3 the radiolucent line and the osteolysis appeared extremely low. There was no loosening. In Non-IBBC the appearance rate of radiolucent line and the osteolysis was very high and the rate of loosening was 20%. However, in IBBC, radiolucent line and osteolysis will be prevented eternally.


2011 ◽  
Vol 17 (5) ◽  
pp. 460-466 ◽  
Author(s):  
B. L. Multanovsky ◽  
S. A. Lenig

Objective. To compare parameters of 24-hour blood pressure (BP) monitoring in young men with normal, high normal BP and arterial hypertension 1 degree. Design and methods. 102 men (group 1 — 32 subjects with optimal and normal BP, group 2 — 34 subjects with high normal BP, group 3 — 36 men with 1 degree hypertension) underwent 24-hour BP monitoring, and parameters of BP loading and BP changes during the day night were assessed. Results. To a considerable extent subjects with high normal BP demonstrated hypertension at 24-hour BP monitoring, and are characterized by higher «loading pressure» and higher morning BP elevation compared to those with normal and optimal BP; in the group with higher BP the number of patients with normal night profile of BP decreases. Conclusions. Our data confirm that 24-hour BP monitoring should be performed in all patients with high normal BP, and the latest should be considered a group of a higher cardiovascular risk. The disorders of daily BP profile become more profound as arterial hypertension develops.


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