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.

Quantitative EEG in obstructive sleep apnea syndrome: a review of the literature.

Obstructive sleep apnea syndrome (OSAS) is characterized by the recurrent cessation (apnea) or reduction (hypopnea) of airflow due to the partial or complete upper airway collapse during sleep. Respiratory disturbances causing sleep fragmentation and repetitive nocturnal hypoxia are responsible for a variety of nocturnal and daytime complaints of sleep apnea patients, such as snoring, daytime sleepiness, fatigue, or impaired cognitive functions. Different techniques, such as magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, are used to evaluate the structural and functional changes in OSAS patients. With quantitative electroencephalographic (qEEG) analysis, the possible existence of alterations in the brain electrical activity of OSAS patients can be investigated. We review the articles on qEEG results of sleep apnea patients and summarize the possible explanations of these qEEG measures. Finally, we review the impact of continuous positive airway pressure (CPAP) treatment on these alterations to assess whether CPAP use can eliminate alterations in the brain activity of OSAS patients.

The acute effects of alcohol on cerebral hemodynamic changes induced by the head-up tilt test in healthy subjects.

BACKGROUND: Alcohol is a known triggering factor for orthostatic dysfunction, increasing the risk of neurally-mediated syncope. Since orthostatic tolerance may be affected by both systemic and cerebral hemodynamic changes, our aim was to investigate the acute effects of alcohol on cerebral vasoreactivity measured during the head-up tilt (HUT) test in 20 healthy subjects. METHODS: Mean arterial blood pressure (mBP), heart rate, and flow parameters in both middle cerebral arteries (MCAs) were continuously recorded in the supine and during a 10-minute HUT positions before and after alcohol intake. RESULTS: The HUT test resulted in a more prominent decline of adjusted mBP at the level of MCAs (mBPMCA) and a significantly larger decrease of MCA mean flow velocities (MFVMCA) in the post-alcohol period than before alcohol intake. During the HUT phase, the relative decrease in MFVMCA was significantly smaller than the reduction in mBPMCA before drinking alcohol, while these changes were similar after alcohol ingestion. The cerebrovascular resistance index (CVRi) decreased during the HUT phase in the control period, however, it increased after alcohol intake. CONCLUSION: The similar decrease in mBPMCA and MFVMCA during orthostatic stress after alcohol ingestion together with the increased CVRi indicated the impairment of the compensatory vasodilation of cerebral resistance vessels, i.e. impaired cerebral autoregulation. These findings suggest that alcohol may contribute to impaired orthostatic tolerance not only by a hypotensive response but also by the alteration of cerebral blood flow regulation.

Mannose-Binding Lectin Levels and Carotid Intima-Media Thickness in Type 2 Diabetic Patients.

INTRODUCTION: Mannose-binding lectin (MBL) activates complement system and has been suggested to play a role in vascular complications in diabetics. Carotid intima-media thickness (cIMT) detects subclinical atherosclerosis. We evaluated the association of MBL and IMT in type 2 diabetic (T2DM) patients. METHODS: Serum MBL levels and cIMT were measured in a total of 103 diabetics and in 98 age-matched healthy controls. RESULTS: There was no significant difference in MBL level in T2DM versus controls. As expected, IMT was significantly higher in T2DM patients than in controls (P = 0.001). In T2DM, the lowest cIMT was seen in patients with normal MBL level (500-1000) while cIMT continuously increased with both high MBL and absolute MBL deficiency states. This was especially significant in high MBL versus normal MBL T2DM patients (P = 0.002). According to multiple regression analysis the main predictors of IMT in T2DM are age (P < 0.003), ApoA level (P = 0.023), and the MBL (P = 0.036). CONCLUSIONS: Our results suggest a dual role of MBL as a risk factor for cIMT in T2DM. MBL may also be used as a marker of macrovascular disease, as both low and high levels indicate the susceptibility for atherosclerosis in T2DM.

[Beneficial effect of continuous positive airway pressure therapy in obstructive sleep apnea syndrome]. / A légsínterápia jótékony hatásai obstruktív alvási apnoéban.

Continuous positive airway pressure therapy is an evidence based therapy of obstructive sleep apnea syndrome. The effective treatment of obstructive sleep apnea can decrease sympaticotonia and, consequently, blood pressure. Furthermore, it can improve inflammatory and metabolic parameters resulting in a decreased cardiovascular risk. This article summarizes the positive effects of continuous positive airway pressure therapy on cardiovascular risk factors in obstructive sleep apnea syndrome.

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.

[What pathomechanisms can lead to stroke in obstructive sleep apnea?]. / Milyen patomechanizmusok vezethetnek stroke-hoz obstruktív alvási apnoéban?

One of the less well-documented, potentially modifiable stroke risk factor is the obstructive sleep apnea. Obstructive sleep apnea increases cardiovascular morbidity and mortality, including stroke risk. The article summarizes the pathophysiological factors in sleep apnea syndrome which can increase stroke risk.

Anthracycline causes impaired vascular endothelial function and aortic stiffness in long term survivors of childhood cancer.

Vascular and endothelial functions were investigated in long term survivors of childhood cancer exposed to anthracycline treatment. We enrolled 96 long-term survivors (57 males and 39 females, mean age 14.9 ± 5.3 year) of different childhood cancers and 72 age-, sex-, bodyweight- and blood pressure matched controls (39 males and 33 females, mean age 13.7 ± 4.9 year). Aortic stiffness was characterized by echocardiography. Brachial artery endothelial function was assessed by flow-mediated dilatation (FMD%) and nitrate-mediated dilatation (NTG%). Results were compared between three subgroups: anthracycline treated, only chemotherapy treated and control subgroups. The cumulative anthracycline dose was less than 350 mg/m². The healthy control subgroup had a significantly greater FMD response (13.13 ± 2.40 %), and lower stiffness index (2.08 ± 0.6) than both the anthracycline (7.12 ± 6.28 % and 6.45 ± 3.25, respectively) and only chemotherapy treated (10.17 ± 4.23 % and 4.12 ± 2.32, respectively) subgroups. In the anthracycline treated subgroup a significantly (p < 0.01) lower FMD% response, and higher stiffness index were detected than in the only chemotherapy treated subgroup. Higher triglyceride level, higher cumulative anthracycline dose and lower age at the start of treatment were found to be associated independently with impairment of FMD% response and aortic stiffness. We found a significant negative correlation between FMD and aortic stiffness (p < 0.001) and a positive correlation between FMD and distensibility (p < 0.0001). Childhood cancer long term survivors exposed to anthracycline treatment exhibit a marked preclinical vasculopathy, characterized by endothelial dysfunction and increased arterial stiffness, contributing to a deteriorated cardiovascular function.

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.

Recurrent arterial thrombosis associated with the antithrombin basel variant and elevated lipoprotein(a) plasma level in an adolescent patient.

Both myocardial infarction and ischemic stroke are rare in the young. Yet a 15-year-old male patient suffered a myocardial infarction and later an ischemic stroke despite uninterrupted antiplatelet therapy. His medical history involved the surgical correction of an incomplete atrioventricular canal defect at the age of 13 years. No cardiovascular risk factors other than elevated lipoprotein(a) level could be identified. His antithrombin (AT) activity was decreased and DNA sequence analysis revealed heterozygosity for AT Basel (p.Pro41Leu), a variant with impaired heparin binding. This report supports a possible additional pathophysiological role for AT Basel and elevated lipoprotein(a) level in arterial thrombogenesis.

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.

The effect of sleep apnea on QT interval, QT dispersion, and arrhythmias.

BACKGROUND: QT interval (QT) and QT dispersion (QTd) are electrocardiograph (ECG) parameters for the evaluation of myocardial repolarization. The inhomogeneity of ventricular repolarization is associated with ventricular arrhythmias. An increased QT, QTd, and increased incidence of nocturnal cardiac rhythm disturbances have been described in patients with obstructive sleep apnea (OSA), while other investigators did not find a relationship between ventricular arrhythmias and OSA. HYPOTHESIS: The aim of this study was to examine the occurrence of ventricular arrhythmias and to measure QT parameters in patients with untreated OSA using an ambulatory Holter-ECG. METHODS: A total of 25 patients with untreated OSA were studied. After routine biochemical investigation and 2-dimensional, M-mode echocardiography, a 24-hour Holter-ECG was recorded to detect cardiac arrhythmias and QT parameters. QT parameters were measured by the QT Guard system. RESULTS: Only the QT interval increased significantly during the nighttime period (nocturnal QT interval: 423.1 +/- 34.6 ms, daytime QT interval: 381.6 +/- 33.8 ms, 24-hour QT interval: 394.7 +/- 31.1 ms). However, during the nighttime QT interval (422.8 +/- 14.9 ms), QTd (31.2 +/- 11.0 ms) and QT dispersion (30.5 +/- 10.2 ms) did not show any change compared to 24-hour (QTc interval: 423.7 +/- 14.2 ms, QTd: 28.8 +/- 9.4 ms, QTcd: 30.5 +/- 9.43 ms) and daytime levels (QTc interval: 423.9 +/- 14.3 ms, QTd: 27.3 +/- 10.7 ms, QTcd: 29.9 +/- 11.1 ms). None of the patients had ventricular arrhythmias. CONCLUSIONS: QTd and QTcd did not increase during the nighttime period. Our study did not show an increased risk of ventricular arrhythmias in this population during the monitoring period.

Cortical spreading edema in persistent visual migraine aura.

We present imaging evidence of the spreading of cortical edema with reversibly restricted water diffusion from the left occipital to the temporoparietal cortex in persistent visual migraine aura in a 58-year-old man. The right-sided visual field defect lasting for 15 days was associated with discoupling of glucose metabolism and blood flow and the decreased apparent diffusion coefficient also suggested cytotoxic edema. At 8 weeks no signs were present, and magnetic resonance imaging became normal; therefore, long-lasting restricted cortical water diffusion, even if coupled with hypometabolism and edema, can be reversible in persistent visual migraine aura.

Calcium distribution in the vessel wall and intima-media thickness of the human carotid arteries.

Increased common carotid artery (CCA) intima-media thickness (IMT) measured by B-mode ultrasound is an early marker of the atherosclerotic process. Arterial calcification is not clearly understood. Using the particle-induced X-ray emission (PIXE) method, we have looked for the location in the artery wall where calcium accumulated in the early phase of atherosclerosis. Twelve segments of CCAs of deceased stroke patients were investigated. In-vivo, carotid duplex ultrasound was performed with bilateral CCA IMT measurement at plaque-free sections. During autopsy, segments of carotid arteries were collected and filled under pressure with a stained histologic embedding material. The frozen arteries were cut into 60-microm-thick slices. Calcium distribution maps from the segments of arteries were determined by PIXE method. IMT measured by ultrasound and calcium distribution maps measured by PIXE were compared. In our cross-sectional study, using the PIXE analysis and ultrasound images, we could demonstrate early calcium accumulation in the media layer. Our results have also shown a significant relationship between calcium content of distributional maps measured by PIXE analysis and corresponding IMT on B-mode ultrasound images of human CCAs.

Serum asymmetric dimethylarginine negatively correlates with intima-media thickness in early-onset atherosclerosis.

BACKGROUND: Asymmetric dimethylarginine (ADMA) assumes a significant role in atherosclerosis by inhibiting the endothelial nitric oxide synthase (eNOS). Moreover, ADMA inhibits the inducible NOS (iNOS), the isoform that triggers atherosclerosis via peroxynitrite formation. Therefore, we investigated whether ADMA is a risk or protective factor in the atherosclerotic process. Intima-media thickness (IMT) of the common carotid artery, a surrogate for vascular diseases, was chosen as the outcome variable of interest. METHODS: Sixty patients younger than 55 years having at least 30% stenosis of the internal carotid artery and 30 age- and gender-matched controls were recruited at a community-based neurosonological laboratory. We investigated relatively young patients to circumvent the confounding effect age has in the development of atherosclerosis. RESULTS: The IMT showed a negative correlation with ADMA upon analysis of the pooled data (Spearman correlation coefficient -0.300, p = 0.0041) and the atherosclerotic stratum (Spearman correlation coefficient -0.323, p = 0.012). A multiple linear regression model containing all determinant factors of IMT previously identified by simple regression was used to further quantify the relationship between IMT and ADMA. The negative association between IMT and ADMA remained statistically significant (beta: -0.510, CI: -0.894, -0.127; p = 0.010), furthermore it was even stronger in the atherosclerotic stratum (beta: -0.67, CI: -1.16, -0.18; p = 0.008). CONCLUSIONS: A minimal increase in ADMA concentration may be protective by inhibiting iNOS but not eNOS in states where iNOS is induced, e.g. inflammation accompanying atherosclerosis.

Elevated white blood cell count, CRP and fibrinogen levels are not associated with increased anti-endothelial and anti-ox-LDL antibody, MCP-1, and RANTES levels in early onset occlusive carotid artery disease.

BACKGROUND: Inflammatory processes have importance in atherosclerosis. We evaluated if subjects below 55 years of age with occlusive carotid artery disease have higher serum levels of antibodies against oxidized LDL and endothelial cells and the chemokines MCP-1 and RANTES than age matched subjects without atherosclerosis. METHODS AND RESULTS: Sixty patients with occlusive carotid artery disease (stenosis or occlusion) and 30 age-matched controls participated in the study. We measured the degree of carotid artery stenosis and intima-media thickness (IMT) by duplex ultrasound. White blood cell count (WBC), C-reactive protein (CRP), and fibrinogen levels were significantly higher in patients (means+/-SD: 7.5+/-1.8 vs. 6.1+/-1.1 G/L, p<0.001; 7.7+/-20.7 vs. 2.5+/-1.9 mg/L, p=0.015; and 3.7+/-0.9 vs. 3.1+/-0.5 g/L, p<0.001, respectively). Antibody levels against oxidized LDL and endothelial cells (21.1+/-22.9 and 19.9+/-15.3 EU/mL, p=0.6; and 19+/-15 vs. 20+/-9 U/mL, p=0.07) and RANTES and MCP-1 levels (72.4+/-32.3 vs. 73.8+/-27.3 ng/mL, p=0.7; and 468+/-1041 vs. 318+/-131 pg/mL, p=0.7) did not differ significantly between patients and controls and did not correlate with IMT. CONCLUSIONS: Higher levels of WBC, CRP, and fibrinogen suggest an ongoing inflammation in early-onset carotid atherosclerosis, but increased IMT is not associated by the elevation of serum levels of chemokines and antibodies evaluated in this study.

Serum levels of platelet released CD40 ligand are increased in early onset occlusive carotid artery disease.

OBJECTIVE: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40-CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age-matched controls. METHODS: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age-matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima-media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean +/- SD. RESULTS: Mean age was 50.9 +/- 3.5 and 50.1 +/- 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 +/- 0.14 vs. 0.78 +/-0.12 mm, p=0.0003). Serum levels of sCD40L were significantly higher (6.9 +/- 5 vs. 4.5 +/- 3.0 ng/mL, p=0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 +/- 56.9 vs. 79.3 +/- 18.7 pg/mL, p=0.34). IMT did not correlate with sCD40L or sCD40 levels (R=-0.03, p=0.77; and R=0.109, p=0.308, respectively). CONCLUSIONS: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.

[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.

Changes of cerebral hemodynamics in hypertensives during physical exercise.

BACKGROUND AND PURPOSE: Previously, 30 untreated hypertensive patients were investigated by transcranial Doppler (TCD) monitoring during physical exercise, and changes of hemodynamic parameters were compared with those of age matched healthy subjects. After 3-year antihypertensive (AHT) treatment, these hypertensives were investigated again. The aim of this study was to compare the cerebral hemodynamic changes in the regularly treated and noncompliant (untreated) hypertensives during ergometer cycling. METHODS: Nineteen of 30 previously untreated hypertensive patients could be investigated again using the same method as before. Eleven were regularly treated (treated hypertensive [T-HT] group), and 8 did not take their AHT medications due to lack of compliance (noncompliant hypertensive [NC-HT] group). Blood pressure, heart rate, end-tidal CO2 (etCO2; Capnogard capnograph), and bilateral middle cerebral artery mean blood flow velocity (MV) were continuously monitored during ergometer cycling according to the World Health Organization protocol. Values of 2-minute loading were analyzed. RESULTS: Median loading time did not differ significantly between the T-HT and NC-HT groups. After 2 minutes of cycling in treated patients, the ratio of MV and etCO changes (DeltaMV/DeltaetCO2) showed similar values as before therapy (P = .38), whereas in noncompliant patients, a further worsening of the ratio of DeltaMV/DeltaetCO2 could be observed (P = .04). CONCLUSION: The decrease of arteriolar vasodilation (ie, the ratio of DeltaMV/DeltaetCO2) could be demonstrated in the NC-HT group after 3 years. TCD combined with ergometer cycling is a useful method for evaluation of cerebral hemodynamic changes after AHT therapy.