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

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

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

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

Arterial hypertension management in pregnancy

Arterial hypertension (AH) in pregnancy is a heterogeneous pathology. It includes chronic AH (secondary AH and essential AH) which has been observed before pregnancy; gestational AH which develops approximately after 20 weeks of pregnancy and disappearing within 42 days after childbirth; pre-eclampsia (gestosis) which is a combination of AH and proteinuria; and unclassified AH which is diagnosed when blood pressure (BP) is first measured after 20 weeks of pregnancy, and elevated BP, with or without systemic signs and symptoms, is detected. AH in pregnancy increases the risk of complications both for the mother and the child, which points to the need for its active diagnostics and monitoring of the status of target organs and feto-placental complex. Pharmacotherapy of AH in pregnancy is based on the balance of its effectiveness and safety. Therefore, the first-choice medications are methyldopa, dihydropyridine calcium antagonists (nifedipine SR), and cardio-selective beta-blockers. AH in pregnancy is a risk factor of cardiovascular disease across life course stages in women

Place of magnesium drugs in pregnant women with cardiovascular disease

By now there is a substantial evidence on the role of magnesium deficiency, which can occur during pregnancy even in healthy women in case of its insufficient intake through food, in the deterioration of the clinical condition and obstetric complications, especially in patients with cardiovascular disease. Therefore, complex preventive therapy which apart from treatment of hypertension and autonomic dysfunction with mitral valve prolapse, includes oral organic magnesium formulations (lactate, citrate, pidolate) in combination with pyridoxine to replenish magnesium deficiency in these patients has a pronounced positive effect both on the mother, the fetus, and the course of pregnancy

UTILIZING ENOXAPARIN IN THE MANAGEMENT OF ACUTE CORONARY SYNDROME

Anticoagulant therapy is widely used in all forms of acute coronary syndrome (ACS) to inhibit the formation of thrombin and/or to inhibit its activity to reduce the risk of thrombotic events (both in primary percutaneous coronary intervention and in the absence of revascularization). Of the entire range of anticoagulants offered by the domestic and foreign pharmaceutical industry, a limited number of drugs of this group are used in the treatment of ACS, in particular, unfractionated heparin and low molecular weight heparin – enoxaparin.Enoxaparin has a safety profile and clinical efficacy at least comparable to that of unfractionated heparin, and at the same time has a number of obvious advantages, such as a simpler protocol of administration and dosing, does not require routine monitoring of the parameters of the blood coagulation system. In patients with ACS with ST-segment elevation the routine administration of enoxaparin should be considered as an alternative to the standard regimen of unfractionated heparin therapy. In patients with ACS without ST-segment elevation enoxaparin should be used when fondaparinux is unavailable

Metabolic syndrome and correction methods in pregnancy

The article is devoted to management of pregnant patients with obesity. Fat metabolism disorders are known to contribute to the development of gestational hypertension, preeclampsia, intrauterine hypoxia and fetal macrosomia, birth defects and other complications, including in the newborn. Hypertension plays an important role in the pathogenesis of those complications in pregnant women with obesity. Hypertension is at the same time a result of metabolic disorder and an exacerbating factor which adversely impacts the course and outcome of pregnancy. The article tells about rational combination therapy of hypertension during pregnancy

Clinical efficacy of low-dose combination of bisoprolol and hydrochlorothiazide for the treatment of postmenopausal women with hypertension and thyroid pathology

The study covered 140 women aged 45-60 (median age: 50 ± 7,2 years) in postmenopausal period the majority of who had stage II hypertension (120 women) and 20 were apparently healthy (control group). The function of the thyroid gland was examined; 78 patients were diagnosed with hypothyroidism, 30 with hyperthyroidism and 12 with euthyroidism. Evaluation of the size of β-adrenoceptors in erythrocyte membranes (β-APM) through the unique research method revealed a wide range of β-APM measures; all the patients were diagnosed with hypersympathicotonia. After the examination, treatment with Lodoz (bisoprolol 5 mg and hydrochlorothiazide 6.25 mg) once daily in the morning was initiated. Blood pressure and overall well-being of patients were checked once a week; if monotherapy with Lodoz proved to be ineffective, bisoprolol 5 mg in the evening was prescribed additionally; in case of failure to achieve required anti-hypertensive effect in patients, they were prescribed with enalapril 10-20 mg per day. 80 patients with hypertension taking Lodoz (5 of those in combination with bisoprolol) and 20 patients taking enalapril completed the treatment. After 12 weeks of antihypertensive therapy all patients who completed the study underwent 24-hour blood pressure monitoring; the results showed a good antihypertensive effect of Lodoz. No side-effects attributed to the therapy were observed