The Interplay of Dyslipidemia, Oxidative Stress, and Clinical Outcomes in Acute Ischemic Stroke Patients with and without Coronary Artery Disease.

We assessed lipid and lipoprotein profiles, along with oxidative stress (OS) parameters, in patients within the crucial 24 h period following an acute ischemic stroke (AIS), comparing those with and without coronary artery disease (CAD). We aimed to correlate these measures with clinical condition scales (NIHSS, mRS) post-AIS. This study included 27 AIS patients without CAD (AIS group) and 37 AIS patients with CAD (CAD-AIS group). Using polyacrylamide gel electrophoresis (Lipoprint system), we determined plasma LDL and HDL subfractions. Spectrophotometric methods were used to assess plasma antioxidant capacity, lipoperoxides, homocysteine (HC) levels, paraoxonase1, and catalase activities. We also measured urine isoprostanes and the activities of antioxidant enzymes (SOD, GPx) with commercial kits. CAD-AIS patients had notably higher HC levels, while there were no significant differences in lipoprotein subfractions and OS parameters between both groups. In the AIS group, mRS scores showed negative correlations with catalase, GPx activities, and total cholesterol. In the CAD-AIS group, atherogenic lipoproteins (IDLC, LDL2, LDL3-7) exhibited a significant positive correlation with mRS. This study underscores the role of dyslipidemia and OS in the development of AIS and CAD. It emphasizes the complex connections between specific biomarkers and post-stroke clinical outcomes. Our results suggest a significant impact of CAD treatment on lipid profile but not on homocysteine levels. The traditional narrative associating high cholesterol as the ultimate risk factor for cardiovascular diseases needs to be challenged, at least with respect to neurological outcomes. These insights may guide more targeted therapeutic approaches.

Endothelial Function in Patients with Multiple Sclerosis: The Role of GLP-1 Agonists, Lipoprotein Subfractions, and Redox Balance.

INTRODUCTION: Epidemiological studies have suggested an increased vascular risk in patients with multiple sclerosis (MS). There is increasing evidence of the beneficial effects of GLP-1 agonists (GLP-1a) in preventing vascular complications and slowing the progression of neurodegeneration. Our objective was to explore the changes in the endothelial function of MS patients after 12 months of GLP-1a therapy. We also explored the role of lipoprotein subfractions and the antioxidant capacity of plasma. METHODS: MS patients were enrolled in a prospective, unicentric study. GLP-1a (dulaglutide) was administered to 13 patients. The control population consisted of 12 subjects. Endothelial function was determined by peripheral arterial tonometry and expressed as reperfusion hyperemia index (RHI). Trolox equivalent antioxidant capacity (TEAC) was used to assess the total antioxidant capacity of the plasma. The levels of lipoprotein subfractions were evaluated. RESULTS: The GLP-1a group did not have a significant change in their RHIs after 12 months (2.1 ± 0.6 vs. 2.1 ± 0.7; p = 0.807). However, a significant increase in their TEACs was observed (4.1 ± 1.4 vs. 5.2 ± 0.5 mmol/L, p = 0.010). On the contrary, the subjects in the control group had a significant worsening of their RHIs (2.1 ± 0.5 vs. 1.8 ± 0.6; p = 0.030), without significant changes in their TEACs. Except for a significant decrease in very-low-density lipoprotein (VLDL) (30.8 ± 10.2 vs. 22.6 ± 8.3 mg/dL, p = 0.043), no other significant changes in the variables were observed in the control group. VLDL levels (beta = -0.637, p = 0.001), the use of GLP-1a therapy (beta = 0.560, p = 0.003), and small LDL (beta = 0.339, p = 0.043) were the only significant variables in the model that predicted the follow-up RHI. CONCLUSION: Our results suggest that the application of additional GLP-1a therapy may have atheroprotective and antioxidant effects in MS patients with high MS activity and thus may prospectively mitigate their vascular risk. However, the lipoprotein profile may also play an important role in the atherogenic risk of MS subjects.

Association between cognitive impairment and the disability in people with multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) may be present in people with multiple sclerosis (PwMS) in different stages of the disease, as well as in PwMS with various degrees of disability. This study aimed to investigate cognitive decline over a period of 12 months and to examine an association between cognition and the disability in PwMS, also over a period of 12 months. METHODS: The Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) battery was used, containing the Symbol Digit Modalities Test (SDMT), the Categorical Verbal Learning Test (CVLT), and the Brief Visuospatial Memory Test-Revised (BVMT-R). The Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9-HPT) were used to assess the degree of disability. For the analysis of cognitive decline over the period of 12 months, Wilcoxon signed-rank test (paired sample t-test) was used. For the correlation between cognition and disability, Spearman's correlation test was used. RESULTS: We observed statistically meaningful difference only in one measure of cognition (CVLT), not the other two (SDMT and BVMT-R). SDMT significantly correlated with methods assessing the degree of disability in both time points. In the second examination, we observed a correlation between BICAMS and 9-HPT. Similarly, SDMT and BVMT-R also correlated with EDSS. CONCLUSION: To investigate the cognitive decline in PwMS, a longer period of time probably should have been chosen. EDSS is commonly used to monitor disease progression, but it does not include the evaluation of various parameters, such as cognition or upper limb function. Its use with the 9-HPT and cognitive tests may represent a more reliable and comprehensive assessment of a patient's clinical condition.

Lipoprotein Subfractions Associated with Endothelial Function in Previously Healthy Subjects with Newly Diagnosed Sleep Apnea-A Pilot Study.

BACKGROUND: Obstructive sleep apnea (OSA) activates several pathophysiological mechanisms which can lead to the development of vascular diseases. Endothelial dysfunction (ED) is an initial step in the development of atherosclerosis. The association between ED and OSA has been described in several studies, even in previously healthy subjects. High-density lipoproteins (HDL) were generally considered to be atheroprotective, and low-density lipoprotein (LDL) to be an atherogenic component of lipoproteins. However, recent findings suggest a pro-atherogenic role of small HDL subfractions (8-10) and LDL subfractions (3-7). This study aimed to evaluate the relationship between endothelial function and lipid subfractions in previously healthy OSA subjects. MATERIAL AND METHODS: We prospectively enrolled 205 subjects with sleep monitoring. Plasma levels of triacylglycerols, total cholesterol, LDL, HDL, and their subfractions were assessed. Endothelial function was determined using peripheral arterial tonometry, and reperfusion hyperemia index (RHI) was assessed. RESULTS: Plasma levels of small and intermediate HDL subfractions have statistically significant pro-atherogenic correlations with endothelial function (p = 0.015 and p = 0.019). In other lipoprotein levels, no other significant correlation was found with RHI. In stepwise multiple linear regression analysis, small HDL (beta = -0.507, p = 0.032) was the only significant contributor in the model predicting RHI. CONCLUSIONS: In our studied sample, a pro-atherogenic role of small HDL subfractions in previously healthy subjects with moderate-to-severe OSA was proven.

No Difference in Sleep Desaturations Severity between Patients with Wake-Up and Non-Wake-Up Stroke: A PRESS Study Results.

BACKGROUND: Wake-up stroke (WUS) is a certain type of ischemic stroke in which a patient wakes up with a new neurological deficit due to cerebral ischemia. Sleep-disordered breathing is an independent risk factor for stroke, but the role of nocturnal oxygen desaturation in the pathophysiology of WUS is still insufficiently explored. According to several studies, patients with WUS have a significantly more severe sleep apnea syndrome and lower mean blood oxygen saturation. This study aimed to assess the severity of nocturnal desaturations in acute WUS and non-WUS patients using nocturnal pulse oximetry. MATERIAL AND METHODS: The cohort of 225 consecutive patients with neuroimaging-verified acute cerebral ischemia was prospectively enrolled. For further analyses, 213 subjects with known WUS/non-WUS status were selected (111 males and 102 females, average age 70.4 ±12.9, median baseline NIHSS = 5, median baseline mRS = 3). Patients were divided into the WUS group (n = 45) and the non-WUS group (n = 168). Overnight pulse oximetry was performed within 7 days of the stroke onset and data of both of the studied groups were compared. RESULTS: We found oxygen desaturation index (ODI) in the WUS group was 14.5 vs. 16.6 (p = 0.728) in the non-WUS group, basal O2 saturation was 92.2% vs. 92.5% (p = 0.475), average low O2 saturation was 90.3% vs. 89.6% (p = 0.375), minimal O2 saturation was 79.5% vs. 80.6% (p = 0.563), and time with O2 saturation <90% (T90) was 4.4% vs. 4.7% (p = 0.729). CONCLUSIONS: In the studied sample, monitored respiratory parameters including ODI, basal O2 saturation, average low O2 saturation, minimal O2 saturation, and T90 did not significantly differ between groups of WUS and non-WUS patients.

Adherence to positive airway pressure therapy initiated in the early subacute phase of ischemic stroke: a PRESS study follow-up.

BACKGROUND: Sleep-disordered breathing (SDB) is frequent in stroke patients and negatively affects stroke outcomes. Positive airway pressure (PAP) is the standard first-line treatment for patients with moderate-to-severe SDB. Despite a strong link between PAP adherence and therapeutic response, rates of post-stroke PAP adherence remain underexplored. Our study aimed to determine PAP adherence in patients undergoing comprehensive sleep apnea assessment and in-lab PAP titration in the early subacute phase of stroke. METHODS: In-hospital screening pulse oximetry was performed in consecutive patients with imaging-confirmed acute ischemic stroke. Subjects with desaturation index ≥ 15.3/h were selected as PAP candidates, and polysomnography was recommended. In a sleep laboratory setting, subjects underwent a diagnostic night followed by a titration night, and PAP therapy was initiated in subjects with apnea-hypopnea index ≥ 15/h. Adherence to PAP therapy was assessed at a 6-month follow-up visit. RESULTS: Of 225 consecutive patients with acute ischemic stroke, 116 were PAP candidates and 52 were able to undergo polysomnography. PAP therapy was initiated in 35 subjects. At a 6-month follow-up visit, out of 34 stroke survivors, PAP adherence (PAP use of > 4 h per night) was present in 47%. Except for the significantly lower minimal nocturnal O2 saturation determined from the polysomnography (74.6 ± 11.7% vs. 81.8 ± 5.2%, p = 0.025), no other significant difference in characteristics of the groups with PAP adherence and PAP non-adherence was found. CONCLUSIONS: Less than half of the stroke subjects remained adherent to PAP therapy at 6 months post-PAP initiation. Special attention to support adaptation and adherence to PAP treatment is needed in this group of patients.

Real-world operation of multiple sclerosis centres in Central-Eastern European countries covering 107 million inhabitants.

BACKGROUND: In 2018 multiple sclerosis (MS) care unit (MSCU) recommendations were defined. Nevertheless, the information on MS care, and whether MS centres fulfil the international recommendation is limited. Thus our objectives were to assess whether centres meet the MSCU recommendations and gain a comprehensive overview of MS care in Central-Eastern European countries. METHODS: A self-report questionnaire assessing aspects of the MSCU recommendations, disease-modifying therapy (DMT) and registry use and the patient number was assembled and sent to nine Central-Eastern European countries. Furthermore, one Danish and one German centre were contacted as a reference. RESULTS: In 9/9 countries, MS care was pursued in centres by MS neurologists and MS nurses. In Austria and the Czech Republic, management of MS was conducted under strict regulations displaying a referral centre system, fundamentally similar to but independent of the MSCU criteria. Several centres fulfilled all aspects of the MSCU criteria, while others had similar insufficiencies consisting of a speech therapist, continence, pain and spasticity specialist, neuro-ophthalmologist, and oto-neurologist. In 9/9 countries, DMTs were reimbursed. However, some centres did not provide every available DMT. A national registry was available in 4/9 countries with mandatory registry use only in Austria and the Czech Republic. CONCLUSION: In countries where MSCU recommendations are not fulfilled, a strictly regulated centre system similar to the Austrian and Czech model with a registry-based quality control might ensure appropriate care for people with MS.

Treatment with Cladribine Tablets Beyond Year 4: A Position Statement by Southeast European Multiple Sclerosis Centers.

Based on the results of the pivotal CLARITY study, cladribine tablets were approved for use in the European Union in 2017 as a high-efficacy therapy for highly active relapsing-remitting multiple sclerosis (MS). Cladribine tablets are used as an induction therapy: half of the total dose is given in year 1 and the other half in year 2. In the CLARITY Extension trials, repeating the dose routinely in years 3 and 4, was not associated with significantly improved disease control. However, there is very limited evidence on how to manage people with MS (pwMS) beyond year 4, which is increasingly important because more and more patients are now ≥ 4 years after cladribine treatment. Overall, postapproval data show that treatment with two cladribine cycles effectively controls disease activity in the long term. However, there is general agreement that some pwMS with suboptimal response could benefit from retreatment. This study reviews the practical aspects of using cladribine tablets, summarizes the evidence from clinical trials and real-world studies on the safety and efficacy of cladribine, and proposes a treatment algorithm developed by expert consensus for pwMS previously treated with cladribine. In brief, we propose that additional courses of cladribine tablets should be considered in patients with minimal (no relapses, 1-2 new lesions) or moderate (1 relapse, 3-4 new lesions) disease activity, while significant disease activity (> 1 relapse, > 3 new lesions) or progression should warrant a switch to another high-efficacy treatment (HET). More evidence is needed to improve the treatment guidelines for pwMS who previously received cladribine.

Factor XIa inhibition with asundexian after acute non-cardioembolic ischaemic stroke (PACIFIC-Stroke): an international, randomised, double-blind, placebo-controlled, phase 2b trial.

BACKGROUND: Asundexian (Bayer AG, Leverkusen, Germany), an oral small molecule factor XIa (FXIa) inhibitor, might prevent thrombosis without increasing bleeding. Asundexian's effect for secondary prevention of recurrent stroke is unknown. METHODS: In this randomised, double-blind, placebo-controlled, phase 2b dose-finding trial (PACIFIC-Stroke), patients with acute (within 48 h) non-cardioembolic ischaemic stroke were recruited from 196 hospitals in 23 countries. Patients were eligible if they were aged 45 years or older, to be treated with antiplatelet therapy, and able to have a baseline MRI (either before or within 72 h of randomisation). Eligible participants were randomly assigned (1:1:1:1), using an interactive web-based response system and stratified according to anticipated antiplatelet therapy (single vs dual), to once daily oral asundexian (BAY 2433334) 10 mg, 20 mg, or 50 mg, or placebo in addition to usual antiplatelet therapy, and were followed up during treatment for 26-52 weeks. Brain MRIs were obtained at study entry and at 26 weeks or as soon as possible after treatment discontinuation. The primary efficacy outcome was the dose-response effect on the composite of incident MRI-detected covert brain infarcts and recurrent symptomatic ischaemic stroke at or before 26 weeks after randomisation. The primary safety outcome was major or clinically relevant non-major bleeding as defined by International Society on Thrombosis and Haemostasis criteria. The efficacy outcome was assessed in all participants assigned to treatment, and the safety outcome was assessed in all participants who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT04304508, and is now complete. FINDINGS: Between June 15, 2020, and July 22, 2021, 1880 patients were screened and 1808 participants were randomly assigned to asundexian 10 mg (n=455), 20 mg (n=450), or 50 mg (n=447), or placebo (n=456). Mean age was 67 years (SD 10) and 615 (34%) participants were women, 1193 (66%) were men, 1505 (83%) were White, and 268 (15%) were Asian. The mean time from index stroke to randomisation was 36 h (SD 10) and median baseline National Institutes of Health Stroke Scale score was 2·0 (IQR 1·0-4·0). 783 (43%) participants received dual antiplatelet treatment for a mean duration of 70·1 days (SD 113·4) after randomisation. At 26 weeks, the primary efficacy outcome was observed in 87 (19%) of 456 participants in the placebo group versus 86 (19%) of 455 in the asundexian 10 mg group (crude incidence ratio 0·99 [90% CI 0·79-1·24]), 99 (22%) of 450 in the asundexian 20 mg group (1·15 [0·93-1·43]), and 90 (20%) of 447 in the asundexian 50 mg group (1·06 [0·85-1·32]; t statistic -0·68; p=0·80). The primary safety outcome was observed in 11 (2%) of 452 participants in the placebo group versus 19 (4%) of 445 in the asundexian 10 mg group, 14 (3%) of 446 in the asundexian 20 mg group, and 19 (4%) of 443 in the asundexian 50 mg group (all asundexian doses pooled vs placebo hazard ratio 1·57 [90% CI 0·91-2·71]). INTERPRETATION: In this phase 2b trial, FXIa inhibition with asundexian did not reduce the composite of covert brain infarction or ischaemic stroke and did not increase the composite of major or clinically relevant non-major bleeding compared with placebo in patients with acute, non-cardioembolic ischaemic stroke. FUNDING: Bayer AG.

Impairment of endothelial function in Parkinson's disease.

OBJECTIVE: There are conflicting data regarding the relationship between Parkinson's disease (PD) and the atherosclerotic process. This study aimed to compare endothelial function in patients with PD and matched controls. In PD subjects, we searched for factors contributing to endothelial dysfunction as well. Traditional vascular risk factors, PD characteristics, and PD medication were considered. RESULTS: We prospectively enrolled 41 patients with PD and 41 controls matched for age, sex, body mass index, and vascular risk factors. Endothelial function (EF) was assessed using peripheral arterial tonometry (EndoPAT 2000 device) and expressed as reperfusion hyperemia index (RHI). Clinical characteristics including PD medication were recorded. RHI was non-significantly lower in the PD group than in controls (1.8 ± 0.5 vs. 1.9 ± 0.5, p = 0.478). In PD patients, in linear regression analysis, smoking (beta = -0.453, p = 0.008) and use of dopamine agonists (beta = -0.365, p = 0.030) were significant contributors in a model predicting RHI. Despite non-significant differences in endothelial dysfunction between PD patients and controls, our results suggest an association between smoking, dopamine agonists, and impaired EF in PD patients. The small sample size, as well as the absence of an extended search for traditional and non-traditional vascular risk factors, are the most important factors limiting the interpretation of the current results.

Cognition in Patients with Sleep-Disordered Breathing: Can Obstructive and Central Apneic Pauses Play a Different Role in Cognitive Impairment?

BACKGROUND: There are increasing data linking sleep apnea with cognitive impairment. We aimed to clarify the relationship between sleep-disordered breathing (SDB) and cognition. Detailed attention was assigned to the potential role of central versus obstructive apneic pauses in cognitive impairment. METHODS: Patients with suspected SDB were prospectively enrolled, and a complex sleep study was performed that included overnight polysomnography. A revised version of Addenbrooke's Cognitive Examination (ACE-R) was used to assess cognition, evaluating overall cognition and individual subdomains. RESULTS: A total number of 101 participants were included in the study. In multivariate binary logistic regression analysis, obstructive apnea index ([OAI], 95% CI: 1.009-1.057, p = 0.008) was the only significant contributor to the model predicting attention deficit. The proportion of N1 stage of NREM sleep was the only significant contributor to the model predicting impaired verbal fluency (95% CI: 1.004-1.081, p = 0.029). No significant differences in sleep-related indices were observed in the remaining ACE-R subdomains. CONCLUSION: Except for verbal fluency and attention, we failed to find any significant association of sleep-related indices with the impairment in different cognitive subdomains. Our data suggest that impairment observed in verbal fluency is associated with a higher proportion of shallow NREM sleep, and attention deficit is associated with higher OAI. Obstructive respiratory episodes seem to play a more important role in cognitive impairment when compared to central ones.

Effects of Short- and Long-Term Aerobic-Strength Training and Determinants of Walking Speed in the Elderly.

BACKGROUND/AIMS: Walking speed (WS) is an objective measure of physical capacity and a modifiable risk factor of morbidity and mortality in the elderly. In this study, we (i) determined effects of 3-month supervised aerobic-strength training on WS, muscle strength, and habitual physical activity; (ii) evaluated capacity of long-term (21 months) training to sustain higher WS; and (iii) identified determinants of WS in the elderly. METHODS: Volunteers (F 48/M 14, 68.4 ± 7.1 years) completed either 3-month aerobic-strength (3 × 1 h/week, n = 48) or stretching (active control, n = 14) intervention (study A). Thirty-one individuals (F 24/M 7) from study A continued in supervised aerobic-strength training (2 × 1 h/week, 21 months) and 6 (F 5/M 1) became nonexercising controls. RESULTS: Three-month aerobic-strength training increased preferred and maximal WS (10-m walk test, p < 0.01), muscle strength (p < 0.01) and torque (p < 0.01) at knee extension, and 24-h habitual physical activity (p < 0.001), while stretching increased only preferred WS (p < 0.03). Effect of training on maximal WS was most prominent in individuals with baseline WS between 1.85 and 2.30 m·s-1. Maximal WS measured before intervention correlated negatively with age (r = -0.339, p = 0.007), but this correlation was weakened by the intervention (r = -0.238, p = 0.06). WS progressively increased within the first 9 months of aerobic-strength training (p < 0.001) and remained elevated during 21-month intervention (p < 0.01). Cerebellar gray matter volume (MRI) was positively associated with maximal (r = 0.54; p < 0.0001) but not preferred WS and explained >26% of its variability, while age had only minor effect. CONCLUSIONS: Supervised aerobic-strength training increased WS, strength, and dynamics of voluntary knee extension as well as habitual physical activity in older individuals. Favorable changes in WS were sustainable over the 21-month period by a lower dose of aerobic-strength training. Training effects on WS were not limited by age, and cerebellar cortex volume was the key determinant of WS.

The impact of sleep apnea syndrome on the altered lipid metabolism and the redox balance.

BACKGROUND: Obstructive sleep apnea (OSA) is a disorder with a significant risk for cardiovascular diseases. Dyslipidemia and redox imbalance belong to potential mechanisms linking OSA with the development of vascular diseases. The main aim of this study was the evaluation of the presence of lipid abnormalities in OSA patients, focusing on small dense low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subfractions and determination of the redox imbalance by evaluating the marker of oxidative damage to plasma lipids - lipoperoxides. METHODS: The study included 15 male subjects with polysomnographically confirmed OSA and 16 male healthy controls. Plasma levels of total cholesterol, LDL and HDL and their subfractions, triacylglycerols and lipoperoxides were determined in all study individuals. Plasma LDL and HDL subfractions were separated by the Lipoprint system which is a polyacrylamide gel electrophoresis. Lipoperoxide levels were determined spectrophotometrically. RESULTS: OSA patients had significantly higher triacylglycerols, total cholesterol and LDL-cholesterol compared to healthy controls. HDL cholesterol was not significantly different. Of the LDL and HDL subfractions, OSA patients had significantly lower levels of atheroprotective LDL1 and large HDL subfractions and significantly higher levels of atherogenic small dense LDL3-7 and HDL8-10 subfractions. Lipoperoxide levels in patients with OSA were significantly elevated compared to healthy individuals. CONCLUSION: The lipoprotein pro-atherogenic phenotype was found in individuals with OSA characterized by increased levels of atherogenic lipoprotein subfractions and reduced levels of atheroprotective subfractions. In addition, a plasma redox imbalance was found in patients with OSA compared to controls by detecting higher oxidative damage to lipids. Abnormalities in lipoprotein levels in patients with OSA, as well as the redox imbalance, could lead to an acceleration of the atherosclerotic process in predisposed individuals and thus represent a significant risk factor for vasular diseases.

Mood disorders in patients with hypersomnia: comparison of sleep-related breathing disorders versus narcolepsy.

BACKGROUND: Anxiety and depression are common comorbidities of excessive daytime sleepiness (EDS). Sleep-related breathing disorders (SBD) and central disorders of hypersomnolence (like narcolepsy [NA]) are the most frequent causes of EDS. This study aimed to evaluate mood disorders in NA patients compared to the subjects with EDS due to SBD (SBD-EDS). METHODS: In a retrospective analysis, subjects with NA and SBD-EDS were compared. All subjects underwent overnight polysomnography. NA patients underwent also multiple sleep latency test. Epworth sleepiness scale (ESS), Pittsburgh Sleep Quality Index (PSQI), Becks questionnaire, and Zung depression scale were used to assess EDS, sleep quality, anxiety, and depression, respectively. RESULTS: We enrolled 24 NA and 41 SBD-EDS subjects. Values of PSQI and Zung scale were significantly worse in the SBD-EDS group than in NA patients (8.34±3.84 vs. 6.83±2.25, p=0.04; 46.86±12.69 vs. 40.81±11.27, p=0.03, respectively). Anxiety was significantly more frequent in SBD-EDS subjects compared to NA (63.4% vs. 37.5%, p=0.04). Out of all observed sleep-related indices, PSQI was the only factor, that significantly correlated with the measures of anxiety in both groups (NA: r=0.65, p=0.001; SBD-EDS: r=0.45, p=0.003) and with the measures of depression in NA subjects (r=0.51, p=0.01). In SBD-EDS group, measures of depression significantly correlated with PSQI (r=0.46, p=0.002), oxygen desaturation index (r=0.35, p=0.03), and ESS (r=0.5, p=0.001). CONCLUSION: Compared to NA, our results suggest significantly worse measures of depression and a significantly higher frequency of anxiety in the SBD-EDS population. Measures of anxiety and depression significantly correlated with quality of sleep in both groups.

Cardiac autonomic function in patients with early multiple sclerosis.

PURPOSE: Cardiac autonomic dysfunction has been reported in patients with long-standing multiple sclerosis (MS); however, data in early disease are limited. The present study was aimed at evaluating cardiac autonomic function in patients with early MS in the context of white matter metabolic status, which could potentially affect functions of the autonomic brain centers. METHODS: Cardiac sympathetic and baroreflex cardiovagal responses to the Valsalva maneuver, orthostatic test, and the Stroop test were evaluated in 16 early, treatment-naïve patients with relapsing-remitting MS, and in 14 healthy participants. Proton magnetic resonance spectroscopic imaging (MRSI) of the brain was performed in eight of these MS patients and in eight controls. RESULTS: Valsalva maneuver outcomes were comparable between patients and controls. At baseline, norepinephrine levels were lower (p = 0.027) in MS patients compared to controls. The patients had higher heart rate (p = 0.034) and lower stroke volume (p = 0.008), but similar blood pressure, cardiac output and norepinephrine increments from baseline to 2 min of the orthostatic test compared to controls. MS patients and controls did not differ in responses to the Stroop test. MRSI showed lower total N-acetylaspartate/total creatine (p = 0.038) and higher myo-inositol/total creatine (p = 0.013) in MS lesions compared to non-lesional white matter. CONCLUSION: Our results show normal cardiac sympathetic and baroreflex cardiovagal function in MS patients with relapsing-remitting MS with lesions at the post-acute/early resolving stage. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov under the Identifier: NCT03052595 and complies with the STROBE checklist for cohort, case-control, and cross-sectional studies.

Association of lipoprotein levels with sleep apnea: role of autonomic dysfunction.

Objectives. Although multiple mechanisms, including autonomic dysfunction, seem to link sleep-disordered breathing (SDB) with dyslipidemia in animal studies, the data in clinical studies are limited. The aim of this study was to explore the association of lipoprotein levels with SDB measures in healthy habitual snorers. We supposed that autonomic dysfunction is the linking mechanism.Methods. We enrolled 110 previously healthy subjects with complaints of habitual snoring. To assess SDB, polysomnography was performed. Blood samples for the analysis of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG) were obtained in a fasting condition after the polysomnography. Baroreflex sensitivity (BRS) was used to assess the autonomic dysfunction.Results. In stepwise multiple linear regression analysis, minimal nocturnal blood oxygen saturation (beta=-0.240, p=0.020) and neck circumference (beta=0.224, p=0.03) were the only significant contributors in model predicting TG. SDB measures were not identified as significant contributors in models predicting TC, LDL, and HDL. We failed to find any significant difference in BRS in SDB subjects when compared according to the presence or absence of hypercholesterolemia/ hypertriglyceridemia. In SDB subjects, the area under the curve in a receiver operating curve to predict hypercholesterolemia and hypertriglyceridemia by BRS was 0.468 (95% CI: 0.328-0.608) and 0.425 (95% CI: 0.304-0.546), respectively.Conclusions. Our results suggest that minimal nocturnal blood oxygen saturation is significant contributor in model predicting TG. No significant decrease in BRS was found in SDB subjects with hypercholesterolemia and hypertriglyceridemia. In SDB subjects, the role of autonomic dys-function in the development of dyslipidemia remains controversial.

Sleep apnea prediction in acute ischemic stroke (SLAPS score): a derivation study.

BACKGROUND: Despite its high prevalence and negative impact, sleep-disordered breathing (SDB) remain commonly underdiagnosed and undertreated in stroke subjects. Multiple stroke comorbidities and risk factors, including obesity, hypertension, diabetes mellitus, ischemic heart disease, atrial fibrillation, and heart failure (H.F.) have been associated with SDB. This study aimed to examine associations of clinical and demographic characteristics with moderate-to-severe SDB (msSDB) in stroke patients and to develop a predictive score. METHODS: Consecutive patients with ischemic stroke were enrolled in an open, prospective study. SDB was assessed using standard polysomnography. Clinical and demographic characteristics, as well as findings from echocardiography, entered the analysis. Multivariate logistic regression models were used to examine the associations with msSDB. Based on the results, an original score to predict msSDB was proposed and tested. RESULTS: 120 patients with acute ischemic stroke (mean age: 64.0 ± 12.2 years, median NIHSS: 4) were included. Body-mass index (BMI), wake-up stroke onset (WUS), and diastolic dysfunction were independently associated with msSDB. A score allocating 1 point for BMI≥25 kg/m2 and <30 kg/m2, 2 points for BMI≥30 kg/m2, 1 point for WUS and 1 point for diastolic dysfunction resulted in an area under the curve of 0.81 (95% CI 0.71-0.90, p<0.001), sensitivity 82.9%, specificity 71.9% to identify stroke patients with msSDB. CONCLUSIONS: BMI, WUS, and diastolic dysfunction were associated with msSDB. A simple score might help to identify acute stroke patients with msSDB, who are usual candidates for positive airway pressure therapy.

Obstructive sleep apnea and hypertension: the role of gut microbiome.

Obstructive sleep apnea is common disorder affecting approximately one quarter of the common population. Prevalence is even higher in a population with increased vascular risk. Obstructive sleep apnea is a significant risk factor for hypertension, with approximately 50% of obstructive sleep apnea patients suffering hypertension. While the relationship between sleep apnea and hypertension has been firmly established, mechanisms linking these disorders are still poorly understood. Importance of sympathetic nervous system and renin-angiotensin-aldosterone system hyperactivity as well as endothelial dysfunction is suspected. There is increasing evidence supporting gut dysbiosis as one of the underlying mechanisms. Current article describes possible mechanisms linking obstructive sleep apnea with the development of hypertension. The role of gut microbiota in this process is discussed more closely.

Heart rate entropy is associated with mortality after intracereberal hemorrhage.

BACKGROUND: Autonomic nervous system changes have been associated with outcome after intracerebral hemorrhage (ICH) previously. We aimed to investigate the association of heart rate entropy (HRE) with mortality after ICH. METHODS: Sample HRE, heart rate variability and baroreflex sensitivity were examined in consecutive ICH patients. Hematoma volume, intraventricular hemorrhage, infratentorial origin, consciousness impairment and age were combined into standard ICH score. RESULTS: In 47 patients suffering ICH (mean age 61 years, median hemorrhage volume 38 mL) the areas under the curve (AUC) for mortality were 0.86, 0.83, 0.76, 0.74, 0.72 and 0.7 for HRE, ICH-score, normalized low frequency powers, low frequency/high frequency powers ratio, normalized high frequency powers and BRS, respectively. HRE and ICH score were associated with mortality independently (adjusted odd ratio (aOR) 0.09, 95% confidence interval (CI) 0.1-0.8, p = .03 and aOR 2.6, CI 1.03-6.6, p = .04). Combining ICH score with HRE into a novel score resulted in an AUC of 0.94, CI 0.88-0.99, p < .001. CONCLUSION: Compared to several autonomic markers HRE seems to bear the largest amount of information on death probability after ICH. Moreover, HRE may predict mortality comparable to ICH score. Combining HRE with ICH score may increase the predictive performance for mortality after ICH.

Allelic Distribution of Genes for Apolipoprotein E and MTHFR in Patients with Alzheimer's Disease and Their Epistatic Interaction.

BACKGROUND: Genetic risk factors play an important role in the pathogenesis of Alzheimer's disease (AD). However, the gene-gene interaction (epistasis) between specific allelic variants is only partially understood. OBJECTIVE: In our study, we examined the presence of the ɛ4 allele of apolipoprotein E (APOE) and the presence of C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in patients with AD and controls. We also evaluated the epistatic interaction between MTHFR and the APOE variants. METHODS: A total of 564 patients with AD and 534 cognitively unimpaired age-matched controls were involved in the study. RESULTS: The presence of the ɛ4 allele of APOE increases the risk of developing AD in a dose-dependent manner (OR 32.7: homozygotes, 15.6: homozygotes + heterozygotes, 14.3: heterozygotes). The combination of genotypes also increases the risk of developing AD in a dose-dependent manner: OR 18.3 (APOE 4/X and 4/4 + CT rs1801133), OR 19.4 (APOE 4/X and 4/4 + CT rs1801133 + AC rs1801131), OR 22.4 (APOE 4/X and 4/4 + TT rs1801133), and OR 21.2 (APOE 4/X and 4/4 + CC rs1801131). Homozygotes for variant alleles of MTHFR as well as patients with AD had significantly higher levels of homocysteine than homozygotes for standard alleles or controls. CONCLUSION: Homozygotes for APOE4 and carriers of APOE4 with TT genotype of rs1801133 were found to be at the highest risk of developing AD. These findings suggest that the epistatic interaction of specific gene variants can have a significant effect on the development of AD.