Altered irisin/BDNF axis parallels excessive daytime sleepiness in obstructive sleep apnea patients.

STUDY OBJECTIVES: Obstructive sleep apnea hypopnea syndrome (OSAHS) is a sleep-related breathing disorder, characterized by excessive daytime sleepiness (EDS), paralleled by intermittent collapse of the upper airway. EDS may be the symptom of OSAHS per se but may also be due to the alteration of central circadian regulation. Irisin is a putative myokine and has been shown to induce BDNF expression in several sites of the brain. BDNF is a key factor regulating photic entrainment and consequent circadian alignment and adaptation to the environment. Therefore, we hypothesized that EDS accompanying OSAHS is reflected by alteration of irisin/BDNF axis. METHODS: Case history, routine laboratory parameters, serum irisin and BDNF levels, polysomnographic measures and Epworth Sleepiness Scale questionnaire (ESS) were performed in a cohort of OSAHS patients (n = 69). Simple and then multiple linear regression was used to evaluate data. RESULTS: We found that EDS reflected by the ESS is associated with higher serum irisin and BDNF levels; ß: 1.53; CI: 0.35, 6.15; p = 0.012 and ß: 0.014; CI: 0.0.005, 0.023; p = 0.02, respectively. Furthermore, influence of irisin and BDNF was significant even if the model accounted for their interaction (p = 0.006 for the terms serum irisin, serum BDNF and their interaction). Furthermore, a concentration-dependent effect of both serum irisin and BDNF was evidenced with respect to their influence on the ESS. CONCLUSIONS: These results suggest that the irisin-BDNF axis influences subjective daytime sleepiness in OSAS patients reflected by the ESS. These results further imply the possible disruption of the circadian regulation in OSAHS. Future interventional studies are needed to confirm this observation.

Hypertension-induced subclinical vascular and cognitive changes are reversible-An observational cohort study.

Beside the well-known complications of poorly controlled, long-standing hypertension, milder abnormalities induced by early-stage hypertension have also been described. In our study, the authors examined the reversibility of changes induced by early-stage hypertension. The authors performed laboratory testing, ambulatory blood pressure monitoring, carotid intima-media thickness (IMT) measurement, evaluation of stiffness parameters, assessment of various cardiac and cerebral hemodynamic parameters during head-up tilt table (HUTT) testing, and neuropsychological examinations in 49 recently diagnosed hypertensive patients. Following baseline assessment, antihypertensive therapy was commenced. After one year of therapy, lower IMT values were found. Pulse wave velocity showed a borderline significant decrease. During HUTT, several hemodynamic parameters improved. The patients performed better on neuropsychological testing and reached significantly lower scores on questionnaires evaluating anxiety. The present study shows that early vascular changes and altered cognitive function observed in newly diagnosed hypertensive patients may improve with promptly initiated antihypertensive management.

[Complex non-invasive hemodynamic system for the evaluation of vascular status]. / Komplex, nem invazív mérorendszer a vascularis status vizsgálatára.

The vascular diseases (myocardial infarct, stroke, peripheral occlusive disease) have a common pathophysiological background, the arteriosclerosis, that impairs the autoregulation of cerebral vessels, decreases the endothelium mediated flow in the peripheral vessels. Therefore the assessment of the vascular damage or the follow-up of therapy need a complex and simultaneous approach. Currently the morphological and functional changes in the vascular system can be investigated with separated measuring systems, focusing either to cardiac or cerebral parameters (intermittent blood pressure measurement, ECG, cerebral blood flow by transcranial Doppler e.g.). Our purpose is to establish a complex non-invasive system for the simultaneous measurement and comparison of cardiac/cerebral/peripheral hemodynamics. The hemodynamic parameters in hypertensive patients are examined with transcranial Doppler and cardiac monitoring during tilt-table test. Intima-media thickness, flow-mediated dilatation in brachial artery, augmentation index and pulse wave velocity are also measured. The measurement will be repeated after 6 and 12 months follow-up. Our preliminary results are similar to those found in the literature, that proves the reliability of our complex noninvasive hemodynamic system. It is assumed, that 12 months antihypertensive therapies with ACE inhibitors, calcium antagonist etc. might result in different effects on different vascular parameters. Our system enables the individualization of antihypertensive therapy.

Quantitative morphological analysis of the motoneurons innervating muscles involved in tongue movements of the frog Rana esculenta.

We give an account of an effort to make quantitative morphological distinctions between motoneurons of the frog innervating functionally different groups of muscles involved in the movements of the tongue. The protractor, retractor, and inner muscles of the tongue were considered on the basis of their major action during the prey-catching behavior of the frog. Motoneurons were selectively labeled with cobalt lysin through the nerves of the individual muscles, and dendritic trees of successfully labeled neurons were reconstructed. Each motoneuron was characterized by 15 quantitative morphological parameters describing the size of the soma and dendritic tree and 12 orientation variables related to the shape and orientation of the dendritic field. The variables were subjected to multivariate discriminant analysis to find correlations between form and function of these motoneurons. According to the morphological parameters, the motoneurons were classified into three functionally different groups weighted by the shape of the perikaryon, mean diameter of stem dendrites, and mean length of dendritic segments. The most important orientation variables in the separation of three groups were the ellipses describing the shape of dendritic arborization in the horizontal, frontal, and sagittal planes of the brainstem. These findings indicate that characteristic geometry of the dendritic tree may have a preference for one array of fibers over another.

Elevated LDL-C combined with hypertension worsens subclinical vascular impairment and cognitive function.

Hypertension and dyslipidemia belong to the most prevalent modifiable risk factors for cerebrovascular and cardiovascular diseases. Hereby, we aimed to examine the combined effects of newly diagnosed hypertension and hyperlipidemia on the characteristics of the arterial wall and on cognitive function. We examined 72 hypertensive and 85 apparently healthy individuals. Based on serum lipid levels, four subgroups were created ranging from normotensive-normolipidemic to hypertensive-hyperlipidemic subjects. Carotid intima-media thickness (IMT), arterial stiffness, and cognitive function were assessed. IMT of controls was the lowest, whereas that of patients with both risk factors the highest. Stiffness parameters increased when both risk factors were present, whereas subjects with only one risk factor exhibited intermediate values. Hypertensive patients performed worse when memory, attention, reaction time, and trait anxiety were assessed. Significant worsening of IMT, arterial stiffness, and sum of neuropsychological scores was observed along with increasing mean arterial pressure. Generally, hyperlipidemia combining with hypertension resulted in further worsening of all examined parameters. Subclinical changes of the vascular wall and cognitive performance are already present in recently diagnosed hypertensive patients. Combination of hyperlipidemia and hypertension results in more severe impairments, therefore, early and intensive treatment may be crucial to prevent further deterioration.

Anxiety, depression and autonomic nervous system dysfunction in hypertension.

OBJECTIVES: This study examined the relationship between autonomic nervous system dysfunction, anxiety and depression in untreated hypertension. PATIENTS AND METHODS: 86 newly diagnosed hypertensive patients and 98 healthy volunteers were included in the study. The psychological parameters were assessed with Spielberger State-Trait Anxiety Inventory and Beck Depression Inventory by a skilled psychologist. Autonomic parameters were examined during tilt table examination (10min lying position, 10min passive tilt). Heart rate variability (HRV) was calculated by autoregressive methods. Baroreflex sensitivity (BRS) was calculated by non-invasive sequence method from the recorded beat to beat blood pressure values and RR intervals. RESULTS: Significantly higher state (42.6±9.3 vs. 39.6±10.7 p=0.05) and trait (40.1±8.9 vs. 35.1±8.6, p<0.0001) anxiety scores were found in the hypertension group. There was no statistically significant difference in the depression level. LF-RRI (Low Frequency-RR interval) of HRV in passive tilt (377.3±430.6 vs. 494.1±547, p=0.049) and mean BRS slope (11.4±5.5 vs. 13.2±6.4, p=0.07) in lying position were lower in hypertensives. Trait anxiety score correlates significantly with sympatho/vagal balance (LF/HF-RRI) in passive tilt position (Spearman R=-0.286, p=0.01). CONCLUSIONS: Anxiety could play a more important role than depression in the development of hypertension. Altered autonomic control of the heart could be one of the pathophysiological links between hypertension and psychological factors.

Cerebro- and cardiovascular reactivity and neuropsychological performance in hypertensive patients.

BACKGROUND: Hypertensive (HT) patients are at higher risk of cognitive decline than normotensive individuals, because high blood pressure is a risk factor for mild cognitive deterioration. In this study cardio- and cerebrovascular reactivity along with cognitive performance was assessed on newly diagnosed HT patients. METHODS: Diagnosis of hypertension was based on international recommendations. None of the patients had diabetes, and all of them had normal cerebral CT scan. Eighty-one patients (43.5±10.2 years, male/female ratio: 42/39) were compared with 94 healthy controls (44±9.4 years, male/female ratio: 50/44). In both groups continuous, non-invasive and simultaneous monitoring of cerebral and cardiac hemodynamical parameters were recorded during head-up tilt table testing (HUTT). Reaction time, attention and memory skills, anxiety and depression rate were determined by neuropsychological tests. RESULTS: During HUTT significant differences were found in certain cardiovascular parameters (blood pressure, total peripheral resistance index, stroke index), but no differences were detected in cerebral blood flow velocity. While there was no significant difference in reaction time between the two groups, tests estimating short-term memory (Digit Span Test) differed significantly. Moreover, sum of standardized test scores was significantly lower, while anxiety level was significantly increased in HT patients compared to controls. CONCLUSION: Decrease in neuropsychological performance along with alterations of cardiovascular parameters is an early manifestation of hypertension. Aim for an early intervention and accurate treatment is crucial for preventing further impairments.