Myocardial remodeling and fibroblast growth factor in patients with resistant hypertension

Aim. To study the prevalence and severity of left ventricular hypertrophy (LVH), its relationship with fibroblast growth factor (FGF23) in patients with resistant hypertension (RH) depending on the effectiveness of multiagent antihypertensive therapy.Material and methods. The study included 92 patients diagnosed with RH. All patients underwent 24-hour ambulatory blood pressure monitoring (ABPM), echocardiography, general laboratory tests, and the serum FGF23 level was determined.Results. According to ABPM results, patients were divided into following groups: 1st — controlled RH (n=44) and 2nd — uncontrolled (n=48) RH. The groups were comparable in sex, age, main clinical and anthropometric parameters. In group 2, the main parameters of ABPM were higher. There were no differences in general laboratory tests, In the group of uncontrolled RH, the level of FGF23 was higher — 11,7 [8,5; 15,4] pmol/ml vs 9,2 [7,1; 11,6] pmol/ml in the 1st group (p=0,0036). According to echocardiography, a comparable violation of left ventricular (LV) diastolic function, an increase in left atrial size, LV mass (LVM) and LVM index were found. In patients of the 2nd group, large values of interventricular septal thickness were revealed — 1,3 [1,2; 1,4] cm vs 1,2 [1,1; 1,3] cm in the 1st group (p=0, 0043) and relative LV wall thickness (LVWT) — 0,50 [0,48; 0,53] vs, 0,45 [0,43; 0,50] in the 1st group (p<0,0001). In the 1st and 2nd groups, concentric LVH was more common (18 (41%) patients in the 1st and 26 (54,1%) in the 2nd (p=0,044) groups) than eccentric LVH (15 (34,1%) and 13 (27,1%) patients in the 1st and 2nd groups, respectively). Correlation analysis revealed a positive relationship between pulse pressure and HTN duration (r=48, p=0,02) and FGF23 level (r=0,62, p=0,004). The LVM index was positively associated with the diastolic pressure-time index (BP) (r=51, p=0,02). A positive correlation was found between relative LVWT and pulse pressure (r=0,64, p=0,02) and a negative relationship with the duration of regular antihypertensive therapy (r=47, p=0,04), A strong relationship was found between LVEF and FGF23 levels (r=0,75, p=0,005).Conclusion. For patients with uncontrolled resistant hypertension, an increase in pulse pressure and myocardial remodeling in the form of concentric hypertrophy are more characteristic. FGF23 is significantly higher in uncontrolled RH and is positively associated with pulse pressure and relative LVWT

Prevalence of cardiac arrhythmias among patients undergoing chronic hemodialysis

Aim. To evaluate the prevalence of arrhythmias in patients undergoing chronic hemodialysis, to characterize the arrhythmia types in relation to the dialysis procedure and to determine their relationship with clinical findings and echocardiographic characteristics.Material and methods. The study involved 152 patients with kidney failure undergoing chronic hemodialysis. All patients underwent an assessment of dialysis parameters, collection of clinical data, and 48-hour Holter monitoring. In addition, 93 patients underwent an echocardiography with an assessment of left ventricular (LV) mass index, LV ejection fraction, left atrial (LA) volume index, E/e’, cardiac output and preload, which was defined as increased LV filling pressure (E/e’ >12) and LA enlargement (LA volume index >30 ml/m2).Results. Among the 152 examined patients, premature supraventricular and ventricular contractions (PVCs) were observed in almost all patients, while 41% had paroxysmal supraventricular tachycardia. Clinically significant arrhythmias included persistent atrial fibrillation (AF) in 8,6% of patients, paroxysmal AF in 3,9%, nonsustained ventricular tachycardia in 19,7%, bradycardia in 4,6%, second-degree atrioventricular block in 1,3% and third-degree atrioventricular block among 2,6%. PVCs were more common on dialysis days, while tachyarrhythmias were more common during dialysis and in the immediate post- dialysis period. Older age (odds ratio (OR) 10 years older, 1,53; 95% confidence interval (CI): 1,15-2,03; P=0,003), lower cardiac output (OR 1 L/min more, 0,66; 95% CI: 0,44-1,00; P=0,05) were independently associated with clinically relevant arrhythmias.Conclusion. In patients on chronic hemodialysis, older age, increased preload and lower cardiac output are independently associated with clinically relevant arrhythmias. In addition, a positive association between increased LV mass index and AF episodes has been demonstrated. Lower cardiac output had positive correlation with AF and ventricular arrhythmias

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

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

Enalapril and endothelial function in arterial hypertension patients of various age

Vasoactive endothelial function (EF) was assessed in 48 patients with arterial hypertension (AH) (18 participants under 60 years, 30 patients older than 60). Enalapril ("Enam", Dr Reddy's, India) effects on EFwere studied. AH patients were characterized by impaired vasoactive EF, correlating with age. In older patients, endothelial reaction to nitroglycerin was also disturbed. Three-month "Enam" therapy was associated with EF normalization. In blood pressure-normalizing doses, "Enam "facilitated improvement of initially impaired endothelial cells' sensitivity to shear stress

Arterial hypertension features in the elderly and their correction

Aim. To study vasomotor endothelial function (EF) in the elderly patients with arterial hypertension (AH), during its pharmaceutical correction. Material and methods. In total, 66 individuals aged over 60 years, with isolated systolic and systole-diastolic AH (ISAH, SDAH) were examined. All patients underwent 24-hour blood pressure monitoring (BMP), ultrasound assessment of EF and intima-media thickness (IMT), endotelin-1 level (ET-1) measurement, and lipid profile assessment. All participants received Nifecard® XL (Lek, Slovenia), for 6 months. Results. In ISAH patients, endothelial reaction to reactive hyperemia was significantly weaker than that in SDAH participants. AH patients had insufficient brachial artery vasodilatation in nitroglycerin test, as well as increased ET-1 levels. Maximal ET-1 levels were registered in SDAH individuals. After six-month Nifecard® ХL treatment, vascular EF substantially improved. According to 24-hour BPM data, BP circadian rhythm disturbances were quite common, being observed in 80% of ISAH patients, and 44.4% of SDAH subjects. During 6-month therapy, Nifecard® ХL demonstrated high antihypertensive activity: BP circadian rhythm normalized, number of patients with normal circadian rhythms doubled, and number of patients with unsatisfactory nighttime BP decrease, or nighttime AH, decreased. Conclusion: EF normalization and target BP level achievement are the main tasks of AH treatment. Long-acting, extended-release calcium antagonists are effective in the elderly patients

Evaluation of Drug Therapy and Adherence to It in Patients after Acute Coronary Syndrome in Real Clinical Practice (Results of One Year Observation)

Aim. To study the prescribed drug therapy, as well as adherence to it in patients with acute coronary syndrome (ACS) in real clinical practice within a year after the index event. Material and methods. The study included 327 patients who were in hospital treatment with ACS: 199 patients (60.9%) with unstable angina (UA) and 128 (39.1%) – with acute myocardial infarction (AMI). The prescribed treatment and adherence to therapy were evaluated within 12 months after the coronary event. Therapy prescribed to patients was compared with current clinical guidelines for the treatment of patients with ACS. Results. 67% of patients completed the clinical study Adherence to prescribed medication within 12 months after ACS was maximal for ACE inhibitors/angiotensin receptor blockers (83.6%), dual antiplatelet therapy (79.9%) and β-blockers (78.1%), and minimal for lipid-lowering drugs (statins; 61.6%). A significant decrease in adherence was revealed in 6 and 12 months from the initiation of therapy. Significantly higher level of adherence to DAT was found in patients with AMI compared with patients with UA (p&lt;0.05). When analyzing the frequency of occurrence of endpoints, it was found that patients who did not adhere to treatment significantly more often had hospitalizations due to UA (15.1% vs 7.4%; p&lt;0.05), AMI (16.9% vs 8.1%; p&lt;0.05), death from cardiovascular causes (13% vs 10.4%; p&lt;0.05). Conclusion. Therapy prescribed at the outpatient stage in patients with ACS in the Rostov Region corresponds to the modern clinical recommendations. Six months after hospital discharge adherence to drug therapy in patients is reduced, which requires more careful outpatient monitoring during this period. In patients who are not adherent to treatment, cardiovascular complications are significantly more frequent

PHARMACEUTICAL CORRECTION OF VASCULAR DISTURBANCES IN PATIENTS WITH ARTERIAL HYPERTENSION

Aim: To study vascular stiffness and elasticity, microcirculation (MC) parameters, and mildronate effects in patients with arterial hypertension (AH). Material and methods. The study included 99 patients with Stage I-II AH (mean age 63,2+2,6 years). Pulse wave velocity was assessed by volume sphygmography (Poly-Spectre system, Neuro-Soft). MC parameters were assessed with a computerised Doppler ultrasound device (Minimax-Doppler-K). After a wash-out period, the participants were randomised into 2 groups. Group I received enalapril (Renipril, Pharmstandard; 10 mg/d) and mildronate (0,25 g twice a day). Group II was administered Renipril (10 mg/d) only. Results. After 12 weeks of the treatment, blood pressure (BP) levels were significantly reduced. In Group I, a significant increase in mean linear blood flow velocity after occlusion test, as well as in volume blood flow velocity, was observed, compared to the baseline. In 66% of the patients, blood flow velocity after occlusion test was increased by at least 20%. Conclusion. Adding mildronate to the standard antihypertensive therapy with ACE inhibitors facilitates faster normalisation of vascular function