ЭНДОТЕЛИЙ – ОРГАН-МИШЕНЬ ТЕРАПЕВТИЧЕСКОГО ВОЗДЕЙСТВИЯ У ЖЕНЩИН С АРТЕРИАЛЬНОЙ ГИПЕРТОНИЕЙ НА ФОНЕ ЭСТРОГЕНОВОГО ДЕФИЦИТА

Purpose. To study the endothelial function in the onset of arterial hypertension (AH) in perimenopausal women and to evaluate the possibility of the influence of antihypertensive therapy on endothelial dysfunction.Materials and methods. The study included 81 patients with essential hypertension (EH) I–II stage of 1–2 degrees and 23 healthy perimenopausal women. The level of estradiol and follicle stimulating hormone (FSH) were analyzed. Endothelial function was assessed by endothelium-dependent (EDVD), endothelium-independent (ENVD) vasodilation of the brachial artery and laboratory markers.Results. Regardless of the AH stage and degree 50 % of patients had endothelial dysfunction by EDVD / ENVD and vasoconstriction endothelial markers (endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA)) were increased. 12 weeks of treatment showed a statically significant reduction (p<0,05) in the concentration of ET-1 and ADMA, and increasing NO production (p<0,05) in all patients with hypertension.Conclusion. Perimenopausal women with EH regardless of the stage and degree blood pressure had a violation of EDVD/ ENVD and a change of endothelial markers. Monotherapy blockers of the renin-angiotensin-aldosterone system (RAAS) showed blood pressure normalisation and endothelial function improvement in most women with AH stage I-II and 1 degree, with 2 degree required a combination therapy with the addition of bisoprolol and low doses of hydrochlorothiazide to RAAS.Цель. Изучить функциональное состояние эндотелия у женщин с дебютом артериальной гипертонии (АГ) в перименопаузальном периоде и возможность влияния на эндотелиальную дисфункцию современной антигипертензивной терапии.Материалы и методы. В исследование включены 81 пациентка с гипертонической болезнью (ГБ) I–II стадии 1–2-й степени и 23 практически здоровые женщины в перименопаузе. Исследовали уровень эстрадиола и фолликулостимулирующего гормона (ФСГ). Функцию эндотелия оценивали по эндотелий-зависимой (ЭЗВД), эндотелий-независимой (ЭНВД) вазодилатации плечевой артерии и лабораторным маркерам.Результаты. Независимо от стадии ГБ и степени АГ, у 50 % пациенток была выявлена дисфункция эндотелия по ЭЗВД/ ЭНВД, а также отмечено повышение эндотелиальных маркеров вазоконстрикции – эндотелина-1 (ЭТ-1), асимметричного диметиларгинина (АДМА). Через 12 недель лечения отмечено достоверное снижение концентрации ЭТ-1 и АДМА и повышение продукции NO у всех пациенток с АГ.Заключение. У женщин в физиологической перименопаузе, независимо от стадии ГБ и степени повышения АД, отмечалось нарушение ЭЗВД и ЭНВД, а также изменение эндотелиальных маркеров. У пациенток с ГБ I–II стадии 1-й степени для нормализации АД и улучшения функционального состояния эндотелия в большинстве случаев была достаточна монотерапия блокаторами ренин-ангиотензин-альдостероновой системы (РААС), при 2-й степени требовалась комбинированная терапия РААС с добавлением бисопролола в сочетании с низкими дозами гидрохлортиазида

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

THE PLACE OF FOSINOPRIL IN EVIDENCE-BASED TREATMENT OF PATIENTS WITH ARTERIAL HYPERTENSION

Cardiovascular diseases (CVD) remain the main cause of mortality in the world. [1] At the same time, arterial hypertension (AH) is one of the most common CV pathologies, which, according to foreign researchers, affects about 30–45% of the general population [2] and about 40–47% of the population according to Russian studies. [3] The experts forecast that by 2030 the prevalence of hypertension will increase by approximately 10%. [4

Functional status of sympathetic-adrenal system and kidneys in perimenopausal women with arterial hypertension treated with antihypertensive therapy

84 women in perimenopause confirmed by medical history and hormonal status tests participated in the study; control group consisted of 64 patients with first or second degree hypertension and 20 apparently healthy women. Daily monitoring included blood pressure control, assessment of the functional status of sympathetic-adrenal system by the size of β-adrenoreceptors in erythrocyte membranes, test for microalbiminuria and glomerular filtration rate using Cockcroft-Gault formula. Group 1 included patients with first degree hypertension (23 women) which received losartan 50-100 mg/d monotherapy (Losarel, Sаndоz); group 2 patients (43 women) with second degree hypertension received combination therapy: losartan 100 mg/d and Lodoz (bisoporol 5 mg + hydrochlorothiazide 6.25 mg). Treatment lasted 12 weeks; patients were examined before inclusion in the study and after the study. Reduction in blood pressure to the target level was registered in all patients. There were no side or adverse effects. Initially elevated levels of β-adrenoreceptors in erythrocyte membranes significantly decreased in both groups, as a result of improved functional status of sympathetic-adrenal system. Renal excretion of nitrogen evaluated by glomerular filtration rate was not impaired; microalbiminuria increased manifold compared to reference values. After 12 weeks of treatment, microalbiminuria decreased in patients of all groups as a result of nephroprotective effect of antyheprtensive drug therapy

Pages of the History of Russian Medicine: Academician of the Russian Academy of Sciences, Doctor of Medical Sciences, Professor Alexey Petrovich Golikov – Doctor, Scientist, Citizen (to the 100th Anniversary of His Birth)

The main stages of the creative path of the scientist with a world-famous, professor, the Honored Worker of Science of the Russian Federation, Academician of the Russian Academy of Sciences Alexey Petrovich Golikov are presented in the article