Dénes Páll

Effect of a Novel Free Radical Scavenger, Edaravone (MCI-186), on Acute Brain Infarction

Edaravone, a novel free radical scavenger, demonstrates neuroprotective effects by inhibiting vascular endothelial cell injury and ameliorating neuronal damage in ischemic brain models. The present study was undertaken to verify its therapeutic efficacy following acute ischemic stroke. We performed a multicenter, randomized, placebo-controlled, double-blind study on acute ischemic stroke patients commencing within 72 h of onset. Edaravone was infused at a dose of 30 mg, twice a day, for 14 days. At discharge within 3 months or at 3 months after onset, the functional outcome was evaluated using the modified Rankin Scale. Two hundred and fifty-two patients were initially enrolled. Of these, 125 were allocated to the edaravone group and 125 to the placebo group for analysis. Two patients were excluded because of subarachnoid hemorrhage and disseminated intravascular coagulation. A significant improvement in functional outcome was observed in the edaravone group as evaluated by the modified Rankin Scale (p = 0.0382). Edaravone represents a neuroprotective agent which is potentially useful for treating acute ischemic stroke, since it can exert significant effects on functional outcome as compared with placebo.

2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

Increased common carotid artery intima media thickness in adolescent hypertension: Results from the Debrecen Hypertension Study

Background: The aim of the present work was to investigate intima media thickness (IMT) in healthy and in hypertensive adolescents and its influencing factors. Methods: 103 hypertensive and 58 healthy adolescents were studied. IMT was measured in the common carotid artery using B-mode ultrasonography. Additionally, laboratory parameters (blood glucose, cholesterol, triglycerides, HDL- and LDL-cholesterols) and left ventricular mass indices were obtained. Results: IMT in the common carotid artery was higher in hypertensive adolescents (means ± SD: 0.55 ± 0.11 mm) than in healthy control subjects (0.48 ± 0.08 mm, p < 0.001). Similarly, a higher left ventricular mass index was measured in hypertensive (103.2 ± 30.6 g/m2) than in healthy teenagers (91.1 ± 25.2 g/m2, p < 0.001). In general, IMT in adolescents was associated with age, weight, body mass index, left ventricular mass index and average systolic and diastolic blood pressure values of the subjects. By assessing the multivariate association between IMT and other factors, intima-media thickness was only associated with age and left ventricular mass index of the hypertensive subjects and was independent from all the investigated factors in normotensive controls. Conclusions: Our data suggest an ongoing target-organ damage in adolescent hypertension. These patients need to be subjected to early diagnostic methods, treatment and a regular follow-up, in order to avoid severe clinical manifestations of secondary target-organ damage due to hypertension.

Blood pressure distribution in a Hungarian adolescent population: comparison with normal values in the USA.

Objectives To describe the blood pressure characteristics and distribution of all adolescent high school students (aged 15–18 years) in Debrecen (total population 230 000), Hungary. To define threshold values for normal blood pressure by age-, sex- and height-specific groups. To compare our data with results from a USA meta-analysis, which forms the basis of current guidelines. Participants and methods All young people attending high school in Debrecen (final sample n = 10 359) participated in the study. After they had rested for 10 min, three blood pressure measurements were taken from the right upper arm, separated by 5 min intervals. All measurements were obtained by a validated, automated, digital Omron M4 device. Results The 50th, 90th and 95th percentile values of blood pressure were defined by dividing the adolescent population into age-, sex- and height-specific subgroups. In comparison with USA guidelines, in our sample the systolic blood pressure of boys in the different subgroups was 6–11 mmHg greater, whereas this difference was less marked for girls (1–5 mmHg). There were no marked differences in diastolic blood pressure, but our values were slightly lower. Conclusions Our findings demonstrate the influence of geographical and ethnic variations on blood pressure. Acceptance and use of non-population-specific blood pressure distributions may lead to under- or overdiagnosis of adolescent hypertension. The use of geographically more relevant data should be encouraged.

New developments in the pathogenesis of obesity-induced hypertension

Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.

Cerebrovascular Reactivity in Hypertensive and Healthy Adolescents: TCD With Vasodilatory Challenge

Background. Adolescent hypertension predicts hypertension and increased cardiovascular morbidity in adulthood. The aim of the present work was to test whether cerebrovascular reactivity to CO2 is altered among hypertensive adolescents. Methods. From the population‐based cohort of the Debrecen Hypertension Study, 113 hypertensive and 58 normotensive adolescents underwent transcranial Doppler measurements at rest and after 30 seconds of breath holding. Results. Systolic, mean, and diastolic blood flow velocities were higher among hypertensive individuals at rest. Taking the absolute blood flow velocity parameters into account, after breath holding, only the pulsatility index was significantly higher in the hypertensive group. The percentage change of the different blood flow parameters showed less intensive change in hypertensive teenagers. Conclusion. Cerebral vasoreactivity is decreased among hypertensive individuals as compared to healthy controls.

Assessment of target-organ damage in adolescent white-coat and sustained hypertensives

Aims and scope The aim of the present study was to assess whether a difference exists between intima–media thickness and the left ventricular mass index in healthy nonhypertensive, white-coat hypertensive and sustained hypertensive adolescents. Patients and methods Fifty-nine normotensive and 120 hypertensive adolescents were enrolled in our study. Hypertensive patients were classified into white-coat hypertension (WCH) and sustained hypertension groups based on 24-h ambulatory blood pressure measurements. Both normotensive and hypertensive individuals underwent routine laboratory tests, intima–media thickness measurements on the common carotid arteries and transthoracic echocardiography to measure the left ventricular mass index (LVMI). Results Intima–media thickness was higher both in WCH and sustained hypertension compared with healthy normotensive individuals (controls: 0.048 ± 0.01 cm, WCH: 0.056 ± 0.01 cm, sustained hypertension: 0.054 ± 0.012 cm, both P < 0.001 compared with controls, nonsignificant difference between the two hypertensive groups). There was no difference between the LVMI of control individuals and WCH (LVMI: 35.5 ± 10.3 g/m2.7 and 37.7 ± 11.2 g/m2.7 respectively, P = 0.87). LVMI in sustained hypertension group (LVMI: 44.1 ± 14.1 g/m2.7) was significantly higher both compared with WCH (P < 0.05), and healthy adolescents (P < 0.001). Conclusion Target-organ damage develops in a stepwise fashion in adolescent hypertension. An increased intima–media thickness can be demonstrated not only in the sustained but also in the white-coat form of adolescent hypertension.

Impaired cerebral vasoreactivity in white coat hypertensive adolescents

Background and purpose:  Although its incidence is not high, adolescent hypertension may predict hypertension and increased cardiovascular risk in adulthood. Therefore, the aim of the present study was to assess whether cerebrovascular reactivity is altered in adolescent white coat and sustained hypertensive patients compared to healthy teenagers.

Altered signal pathway in angiotensin II-stimulated neutrophils of patients with hypercholesterolaemia

Angiotensin II (AII) in 1-10 nM concentrations has an in vivo immunostimulating effect on human neutrophils. The release of superoxide anions and leukotrienes (LTs) is significantly increased by 10 nM AII-stimulated neutrophils of patients with hypercholesterolaemia (HCH). These oxidizing agents may be involved in the damage of vessel walls, i.e., in atherosclerotic plaque formation. To clarify the receptor types and signal pathways in neutrophils of healthy controls and patients, inositol trisphosphate (IP(3)) production and Ca(2+) signalling were studied. Neutrophils were pretreated before AII stimulation with different inhibitory drugs. In control cells, the stimulation occurred predominantly through pertussis toxin-sensitive, type angiotensin 1 receptors. This induced IP(3) production and Ca(2+) signalling from intracellular pools. In neutrophils of hypercholesterolaemic patients, the enhanced release of oxidizing agents was dependent more on type angiotensin 2 than type angiotensin 1 receptors. After stimulation, there was no IP(3) production detected. The Ca(2+) signalling was lower than in control cells and was dependent on extracellular Ca(2+).

Hyperventilation-induced cerebrovascular reactivity among hypertensive and healthy adolescents

Background: It is known that cerebral vasoreactivity is altered in adult arterial hypertension but no information is available about cerebral arteriolar function in hypertensive adolescents. Therefore, the aim of the present work was to assess cerebral vasoreactivity responses in adolescent hypertension. Methods: 113 hypertensive and 58 normotensive adolescents were assessed with transcranial Doppler sonography by using voluntary hyperventilation (HV) as vasoconstrictory stimulus. Absolute blood flow velocities (systolic, mean and diastolic) and pulsatility indices (PIs) at rest and after HV, as well as percentage change of the blood flow velocities after HV were compared among the groups. Results: Blood flow velocities at rest were significantly higher in hypertensive individuals, while PIs were similar in the two groups. After HV, all blood flow velocity parameters were higher among hypertensive teenagers than in healthy controls, while PIs did not differ between the two groups. Taking the relative changes after HV into account, it was found that HV induced a more pronounced change of the systolic and mean blood flow velocities of the control subjects than in hypertensive adolescents. Conclusions: Cerebrovascular reactivity to hypocapnia is decreased in hypertensive adolescents as compared to healthy teenagers. Further studies are needed to clarify the clinical significance of altered cerebral microvascular function in adolescent hypertension.