Unveiling the Role of the Most Impactful Cardiovascular Risk Locus through Haplotype Editing.

The 9p21.3 cardiovascular disease locus is the most influential common genetic risk factor for coronary artery disease (CAD), accounting for ∼10%-15% of disease in non-African populations. The ∼60 kb risk haplotype is human-specific and lacks coding genes, hindering efforts to decipher its function. Here, we produce induced pluripotent stem cells (iPSCs) from risk and non-risk individuals, delete each haplotype using genome editing, and generate vascular smooth muscle cells (VSMCs). Risk VSMCs exhibit globally altered transcriptional networks that intersect with previously identified CAD risk genes and pathways, concomitant with aberrant adhesion, contraction, and proliferation. Unexpectedly, deleting the risk haplotype rescues VSMC stability, while expressing the 9p21.3-associated long non-coding RNA ANRIL induces risk phenotypes in non-risk VSMCs. This study shows that the risk haplotype selectively predisposes VSMCs to adopt a cell state associated with CAD phenotypes, defines new VSMC-based networks of CAD risk genes, and establishes haplotype-edited iPSCs as powerful tools for functionally annotating the human genome.

Epithelial-like transport of mineral distinguishes bone formation from other connective tissues.

We review unique properties of bone formation including current understanding of mechanisms of bone mineral transport. We focus on formation only; mechanism of bone degradation is a separate topic not considered. Bone matrix is compared to other connective tissues composed mainly of the same proteins, but without the specialized mechanism for continuous transport and deposition of mineral. Indeed other connective tissues add mechanisms to prevent mineral formation. We start with the epithelial-like surfaces that mediate transport of phosphate to be incorporated into hydroxyapatite in bone, or in its ancestral tissue, the tooth. These include several phosphate producing or phosphate transport-related proteins with special expression in large quantities in bone, particularly in the bone-surface osteoblasts. In all connective tissues including bone, the proteins that constitute the protein matrix are mainly type I collagen and γ-carboxylate-containing small proteins in similar molar quantities to collagen. Specialized proteins that regulate connective tissue structure and formation are surprisingly similar in mineralized and non-mineralized tissues. While serum calcium and phosphate are adequate to precipitate mineral, specialized mechanisms normally prevent mineral formation except in bone, where continuous transport and deposition of mineral occurs.

Evaluation of Cerebrovascular Reactivity and Vessel Wall Imaging in Patients With Prior COVID-19: A Prospective Case-Control MRI Study.

BACKGROUND. SARS-CoV-2 infection is associated with acute stroke, possibly caused by viral tropism to the vascular endothelium. Whether cerebrovascular endothelial dysfunction and inflammation persist after acute infection is poorly understood. OBJECTIVE. The purposes of this study were to assess the association between prior SARS-CoV-2 infection and cerebrovascular reactivity (CVR) and vessel wall imaging (VWI) abnormalities and to explore the association between CVR impairment and post-COVID neurologic conditions. METHODS. This prospective study included 15 participants with prior SARS-CoV-2 infection (11 women, four men; mean age, 43 years; mean time since infection, 238 days; three with prior critical illness, 12 with prior mild illness; seven with post-COVID neurologic conditions) and 10 control participants who had never had SARS-CoV-2 infection (two women, two men; mean age, 44 years) from July 1, 2021, to February 9, 2022. Participants underwent research MRI that included arterial spin labeling perfusion imaging with acetazolamide stimulus to measure cerebral blood flow (CBF) and calculate CVR. Examinations also included VWI, performed with a contrast-enhanced black-blood 3D T1-weighted sequence. An age- and sex-adjusted linear model was used to assess associations between CVR and prior infection. A t test was used to assess associations between CVR and post-COVID neurologic conditions in participants with previous infection. A difference of proportions test was used to assess associations between VWI abnormalities and infection status. RESULTS. Mean whole-cortex CBF after acetazolamide administration was greater in participants without previous infection than in participants with previous infection (73.8 ± 13.2 [SD] vs 60.5 ± 15.8 mL/100 gm/min; p = .04). Whole-brain CVR was lower in participants with previous infection than those without previous infection (difference, -8.9 mL/100 g/min; p < .001); significantly lower CVR was also observed in participants with previous infection after exclusion of those with prior critical illness. Among participants with previous infection, CVR was lower in those with than those without post-COVID neurologic conditions, although this difference was not significant (16.9 vs 21.0 mL/100 g/min; p = .22). Six of 15 (40%) participants with previous infection versus 1 of 10 (10%) participants without previous infection had at least one VWI abnormality (p = .18). All VWI abnormalities were consistent with atherosclerosis. CONCLUSION. SARS-CoV-2 infection is associated with chronic impairment of CVR. The mechanism is unknown from this study. CLINICAL IMPACT. Future studies are needed to determine the clinical implications of SARS-CoV-2-associated CVR impairment.

A mathematical model for biomechanical behavior of the aortic arch.

The aortic arch plays a significant role in homeostatic mechanisms to retain blood pressure at stable balance in the cardiovascular system. Therefore, the objective is to estimate and identify cardiovascular illness imposed by the abnormal blood hemodynamic domain. In this regard, hemodynamic forces are monitored by the baroreflex of the artery wall. Therefore, these receptors quickly detect the abnormal stress magnitudes in the aortic arterial wall. The present study presents a 3D aortic arch model extracted by a Computerized tomography scan. Also, the numerical solution was carried out by ANSYS 2020 R1 in view of Fluid-Structure Interaction After that, we found wall shear stress (WSS), pressure, and velocity in the fluid domain. Also, the normal stress was analyzed to determine the aortic arch baroreflex location in the solid range. In this regard, higher WSS values are measured at the supra-aortic branches going out the aortic arch that reached 42.5 Pa. Also, higher normal stress happened at the aortic root and the supra-aortic branches and reached approximately 200 kPa at peak systole.

Membrane Permeability Is Required for the Vasodilatory Effect of Carbonic Anhydrase Inhibitors in Porcine Retinal Arteries.

It has been demonstrated previously that a variety of carbonic anhydrase inhibitors (CAIs) can induce vasodilation in pre-contracted retinal arteriolar segments although with different efficacy and potency. Since the CAIs tested so far are able to permeate cell membranes and inhibit both intracellular and extracellular isoforms of the enzyme, it is not clear whether extra- or intracellular isoforms or mechanisms are mediating their vasodilatory effects. By means of small wire myography, we have tested the effects of four new CAIs on wall tension in pre-contracted retinal arteriolar segments that demonstrably do not enter cell membranes but have high affinity to both cytosolic and membrane-bound isoforms of CA. At concentrations between 10-6 M to 10-3 M, none of the four membrane impermeant CAIs had any significant effect on arteriolar wall tension, while the membrane permeant CAI benzolamide (10-3 M) fully dilated all arteriolar segments tested. This suggests that CAI act as vasodilators through cellular mechanisms located in the cytoplasm of vascular cells.

Wave propagation through a viscous fluid-filled elastic tube under initial pressure: theoretical and biophysical model.

The velocity of propagation of pulse waves through the arteries is one of the indicators of the health of the cardiovascular system. By measuring the pulse wave velocity, cardiologists estimate the elasticity of the blood vessel walls and the changes that occur with aging. When the Moens-Korteweg equation is used in analysis, it leads to an erroneous assessment. This paper presents the solution of Navier-Stokes equations for propagation of pulse waves through an elastic tube filled with viscous fluid under initial pressure. The equation for pulse wave velocity depending on viscosity, density and initial fluid pressure, density and elasticity of the wall and geometry of the tube is derived. The results of the equation were compared with experimental results measured using a biophysical model of the cardiovascular system.

Early Alterations of Intra-Mural Elastic Lamellae Revealed by Synchrotron X-ray Micro-CT Exploration of Diabetic Aortas.

Diabetes is a major concern of our society as it affects one person out of 11 around the world. Elastic fiber alterations due to diabetes increase the stiffness of large arteries, but the structural effects of these alterations are poorly known. To address this issue, we used synchrotron X-ray microcomputed tomography with in-line phase contrast to image in three dimensions C57Bl6J (control) and db/db (diabetic) mice with a resolution of 650 nm/voxel and a field size of 1.3 mm3. Having previously shown in younger WT and db/db mouse cohorts that elastic lamellae contain an internal supporting lattice, here we show that in older db/db mice the elastic lamellae lose this scaffold. We coupled this label-free method with automated image analysis to demonstrate that the elastic lamellae from the arterial wall are structurally altered and become 11% smoother (286,665 measurements). This alteration suggests a link between the loss of the 3D lattice-like network and the waviness of the elastic lamellae. Therefore, waviness measurement appears to be a measurable elasticity indicator and the 3D lattice-like network appears to be at the origin of the existence of this waviness. Both could be suitable indicators of the overall elasticity of the aorta.

High-Intensity Endurance and Strength Training in Water Polo Olympic Team Players: Impact on Arterial Wall Properties.

INTRODUCTION: Regular physical activity is recommended to minimize health risk. However, the upper intensity threshold associated with the best health outcomes is difficult to be determined. Water polo (WP) Olympic athletes present unique characteristics such as high-intensity exercise, long training sessions, and a combination of endurance and strength training. Therefore, we examined in which way the long-term, intense, mixed endurance and strength training affects the peripheral and central hemodynamics. METHODS: The study population consisted of 20 WP Olympic team players, 20 matched recreationally active (RA) subjects, and 20 sedentary control subjects (Cl). Reflected waves were assessed with the augmentation index (AIx), central aortic stiffness with pulse wave velocity (PWV), and endothelial function with flow-mediated dilation (FMD). RESULTS: Amongst Cl subjects, RA subjects, and WP players, there was no difference in age (p = 0.33) as well as in brachial systolic pressure (p = 0.52), while there was a stepwise decrease in aortic systolic pressure (116 ± 16 mm Hg vs. 107 ± 14 mm Hg vs. 106 ± 6 mm Hg, p = 0.03). There was also a stepwise improvement in AIx (-4.22 ± 9.97% vs. -6.97 ± 11.28% vs. -12.14 ± 6.62%, p = 0.03) and FMD (6.61 ± 1.78% vs. 7.78 ± 1.98% vs. 8.3 ± 2.05%, p = 0.04) according to the intensity of exercise, with WP players having lower AIx and higher FMD compared to RA subjects and Cl subjects. No difference was found in PWV (Cl: 5.88 ± 0.72 m/s vs. RA: 6.04 ± 0.75 m/s vs. WP: 5.97 ± 1.09 m/s, p = 0.82) among the three studied groups. CONCLUSIONS: Young WP Olympic team players depict improved arterial wall properties and endothelial function compared to RA and Cl subjects.

Roles of Nuclear Receptors in Vascular Calcification.

Vascular calcification is defined as an inappropriate accumulation of calcium depots occurring in soft tissues, including the vascular wall. Growing evidence suggests that vascular calcification is an actively regulated process, sharing similar mechanisms with bone formation, implicating both inhibitory and inducible factors, mediated by osteoclast-like and osteoblast-like cells, respectively. This process, which occurs in nearly all the arterial beds and in both the medial and intimal layers, mainly involves vascular smooth muscle cells. In the vascular wall, calcification can have different clinical consequences, depending on the pattern, localization and nature of calcium deposition. Nuclear receptors are transcription factors widely expressed, activated by specific ligands that control the expression of target genes involved in a multitude of pathophysiological processes, including metabolism, cancer, inflammation and cell differentiation. Some of them act as drug targets. In this review we describe and discuss the role of different nuclear receptors in the control of vascular calcification.

Correlations between Retinal Arterial Morphometric Parameters and Neurodegeneration in Patients with Type 2 Diabetes Mellitus with No or Mild Diabetic Retinopathy.

Background and Objectives: In patients with diabetes mellitus (DM), the neural retina is starting to degenerate before the development of vascular lesions. Our purpose was to investigate the correlation between the retinal arterial morphometric parameters and structural neurodegeneration in patients with type 2 DM with no or mild diabetic retinopathy (DR). Materials and Methods: This is a prospective study including 53 eyes of patients with type 2 DM and 32 eyes of healthy controls. Based on SD-OCT (spectral domain-optical coherence tomography) images, using a micro-densitometry method, we measured the outer and luminal diameter of retinal arteries and calculated the AWT (arterial wall thickness), WLR (wall-to-lumen ratio), and WCSA (wall cross-sectional area). GCL (ganglion cell layer) and RNFL (retinal nerve fiber layer) thickness were analyzed in correlation with the retinal arterial morphometric parameters mentioned above. Results: GCL was thinner in the inner quadrants in the NDR (no DR) group compared to controls (p < 0.05). RAOD (retinal artery outer diameter), RALD (retinal artery lumen diameter), AWT, WLR, and WCSA were similar between groups. A regression model considering age, gender, duration of DM, and HbA1C was carried out. Central GCL thickness was correlated positively with RAOD (coefficient 0.360 per µm, p = 0.011), RALD (coefficient 0.283 per µm, p = 0.050), AWT (coefficient 0.304 per µm, p = 0.029), and WCSA (coefficient 3.90 per µm, p = 0.005). Duration of DM was positively correlated with WCSA (coefficient 0.311 per one year duration of diabetes, p = 0.043). Conclusions: Significant GCL thinning in the inner quadrants preceded the morphological retinal arterial morphometric changes, supporting the neurodegeneration as primary pathogenic mechanism in DR.

Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

The possibility that oxidative stress promotes degradation of the extracellular matrix and a relationship between intraluminal thrombus (ILT) thickness and proteolytic activity within the abdominal aortic aneurysm (AAA) wall has been suggested. In the present study, the hypothesis that thin ILT is correlated with an increase in oxidative stress-related enzymes and matrix metalloproteinase-9 (MMP-9) expression within the human AAA wall was investigated. We also studied the antioxidant activity of superoxide dismutases, catalase, glutathione peroxidase, glutathione reductase, and thioredoxin within the full-thickness AAA wall and through fluoroimmunohistochemical staining of catalase and MMP-9 expression within the inner and outer media, in relation to ILT thickness. Reactive oxygen species control the degradation and remodeling of the extracellular matrix by up-regulating proteolytic enzymes, such as MMPs. Results showed that oxidative stress and proteolytic enzyme expression were simultaneously, significantly higher within thin thrombus (≤10 mm)-covered aneurysm wall when compared with the wall covered by thick thrombus (≥25 mm). These findings provide the first demonstration, to our knowledge, of a causative link between oxidative stress instigating proteolytic enzyme expression at the tissue level and human AAA development. Presence of a thin circumferential thrombus should always be considered as a risk factor for the greatest increase in aneurysm growth rate and rupture, giving an indication for surgery timing.-Wiernicki, I., Parafiniuk, M., Kolasa-Wolosiuk, A., Gutowska, I., Kazimierczak, A., Clark, J., Baranowska-Bosiacka, I., Szumilowicz, P., Gutowski, P. Relationship between aortic wall oxidative stress/proteolytic enzyme expression and intraluminal thrombus thickness indicates a novel pathomechanism in the progression of human abdominal aortic aneurysm.

Persistent arterial wall inflammation in patients with elevated lipoprotein(a) despite strong low-density lipoprotein cholesterol reduction by proprotein convertase subtilisin/kexin type 9 antibody treatment.

AIMS: Subjects with lipoprotein(a) [Lp(a)] elevation have increased arterial wall inflammation and cardiovascular risk. In patients at increased cardiovascular risk, arterial wall inflammation is reduced following lipid-lowering therapy by statin treatment or lipoprotein apheresis. However, it is unknown whether lipid-lowering treatment in elevated Lp(a) subjects alters arterial wall inflammation. We evaluated whether evolocumab, which lowers both low-density lipoprotein cholesterol (LDL-C) and Lp(a), attenuates arterial wall inflammation in patients with elevated Lp(a). METHODS AND RESULTS: In this multicentre, randomized, double-blind, placebo-controlled study, 129 patients {median [interquartile range (IQR)]: age 60.0 [54.0-67.0] years, Lp(a) 200.0 [155.5-301.5] nmol/L [80.0 (62.5-121.0) mg/dL]; mean [standard deviation (SD)] LDL-C 3.7 [1.0] mmol/L [144.0 (39.7) mg/dL]; National Cholesterol Education Program high risk, 25.6%} were randomized to monthly subcutaneous evolocumab 420 mg or placebo. Compared with placebo, evolocumab reduced LDL-C by 60.7% [95% confidence interval (CI) 65.8-55.5] and Lp(a) by 13.9% (95% CI 19.3-8.5). Among evolocumab-treated patients, the Week 16 mean (SD) LDL-C level was 1.6 (0.7) mmol/L [60.1 (28.1) mg/dL], and the median (IQR) Lp(a) level was 188.0 (140.0-268.0) nmol/L [75.2 (56.0-107.2) mg/dL]. Arterial wall inflammation [most diseased segment target-to-background ratio (MDS TBR)] in the index vessel (left carotid, right carotid, or thoracic aorta) was assessed by 18F-fluoro-deoxyglucose positron-emission tomography/computed tomography. Week 16 index vessel MDS TBR was not significantly altered with evolocumab (-8.3%) vs. placebo (-5.3%) [treatment difference -3.0% (95% CI -7.4% to 1.4%); P = 0.18]. CONCLUSION: Evolocumab treatment in patients with median baseline Lp(a) 200.0 nmol/L led to a large reduction in LDL-C and a small reduction in Lp(a), resulting in persistent elevated Lp(a) levels. The latter may have contributed to the unaltered arterial wall inflammation.

Echo-tracking evaluation of changes in common carotid artery wall elasticity after smoking cessation.

The aim of this study was to explore changes in the common carotid arterial wall elasticity after smoking cessation. Carotid artery ultrasonographic examination was performed in 136 patients, then 1 or 2 years after smoking cessation. We used echo-tracking (ET) to measure stiffness index (ß), pressure-strain elasticity modulus (Ep), arterial compliance (AC), augmentation index (AI), and local pulse wave velocity (PWVß). Patients were divided into four groups based on whether or not they successfully stopped smoking (groups M and N, respectively) and whether (groups M2 and N2, respectively) or not (groups M1 and N1, respectively) they showed comorbidities. In group M1, ß, Ep and PWVß were lower at 1 year than before smoking cessation, while AC and AI did not change. At 2 years, ß, Ep, PWVß, and AC, but not AI, improved further. In group M2, ß, Ep, and PWVß decreased at 2 years, whereas AC and AI did not change. In groups N1 and N2, none of the variables changed significantly. ET can be used quantitatively to evaluate the impact of smoking cessation on the elasticity of the common carotid artery wall.

Development and maturation of the fibrous components of the arterial roots in the mouse heart.

The arterial roots are important transitional regions of the heart, connecting the intrapericardial components of the aortic and pulmonary trunks with their ventricular outlets. They house the arterial (semilunar) valves and, in the case of the aorta, are the points of coronary arterial attachment. Moreover, because of the semilunar attachments of the valve leaflets, the arterial roots span the anatomic ventriculo-arterial junction. By virtue of this arrangement, the interleaflet triangles, despite being fibrous, are found on the ventricular aspect of the root and located within the left ventricular cavity. Malformations and diseases of the aortic root are common and serious. Despite the mouse being the animal model of choice for studying cardiac development, few studies have examined the structure of their arterial roots. As a consequence, our understanding of their formation and maturation is incomplete. We set out to clarify the anatomical and histological features of the mouse arterial roots, particularly focusing on their walls and the points of attachment of the valve leaflets. We then sought to determine the embryonic lineage relationships between these tissues, as a forerunner to understanding how they form and mature over time. Using histological stains and immunohistochemistry, we show that the walls of the mouse arterial roots show a gradual transition, with smooth muscle cells (SMC) forming the bulk of wall at the most distal points of attachments of the valve leaflets, while being entirely fibrous at their base. Although the interleaflet triangles lie within the ventricular chambers, we show that they are histologically indistinguishable from the arterial sinus walls until the end of gestation. Differences become apparent after birth, and are only completed by postnatal day 21. Using Cre-lox-based lineage tracing technology to label progenitor populations, we show that the SMC and fibrous tissue within the walls of the mature arterial roots share a common origin from the second heart field (SHF) and exclude trans-differentiation of myocardium as a source for the interleaflet triangle fibrous tissues. Moreover, we show that the attachment points of the leaflets to the walls, like the leaflets themselves, are derived from the outflow cushions, having contributions from both SHF-derived endothelial cells and neural crest cells. Our data thus show that the arterial roots in the mouse heart are similar to the features described in the human heart. They provide a framework for understanding complex lesions and diseases affecting the aortic root.

Cardiac and haemodynamic influence on carotid artery longitudinal wall motion.

NEW FINDINGS: What is the central question of this study? Carotid artery longitudinal wall motion (CALM) is a bidirectional forward and backward motion of the arterial wall; however, there is no evidence in humans for what controls CALM despite proposals for pulse pressure, left ventricular motion and shear rate. What is the main finding and its importance? Carotid artery longitudinal wall motion responses were heterogeneous when manipulating sympathetic activation and endothelium-independent vasodilatation, leading to non-significant group responses. However, individual CALM responses were associated with left ventricular rotation and shear rate. These findings are important when interpreting changes in CALM in humans with acute or chronic experimental designs. Carotid artery longitudinal wall motion (CALM) has recently attracted interest as an indicator of arterial health; however, the regulation of CALM is poorly understood. We conducted a series of studies aimed at manipulating pulse pressure (PP), left ventricular (LV) motion and carotid shear rate, which have been previously suggested to regulate various components of CALM pattern and magnitude. To determine the regulatory influences on CALM, 15 healthy men (22 ± 2 years old) were exposed to three acute interventions: the serial subtraction test (SST); the cold pressor test (CPT); and exposure to sublingual nitroglycerine (NTG). The SST elicited increases in PP (P < 0.01), apical LV rotation (P < 0.01) and carotid shear rate (P < 0.01), with no changes in CALM (P > 0.05). Likewise, the CPT elicited increases in PP (P = 0.01), basal LV rotation (P = 0.04) and carotid shear rate (P = 0.01), with no changes in CALM (P > 0.05). Conversely, exposure to NTG elicited no change in PP (P = 0.22), basal (P = 0.65) or apical LV rotation (P = 0.45), but did decrease carotid shear rate (P < 0.01), without altering CALM (P > 0.05). Considerable individual variability in CALM responses prompted further analyses where all three interventions were pooled for change scores. Changes in LV basal rotation were related to changes in systolic retrograde CALM (B = -0.025, P = 0.03), whereas changes in carotid shear rate were related to changes in diastolic CALM displacement (B = 0.0009, P = 0.01). The interventions were underpinned by relationships between CALM and both LV basal rotation and local shear rate at the individual level, indicating that cardiac and haemodynamic factors may influence CALM in humans.

MRI-based detection of renal artery abnormalities related to renal denervation by catheter-based radiofrequency ablation in drug resistant hypertensive patients.

OBJECTIVES: Endovascular renal denervation (RDN) using catheter-based radiofrequency (RF) ablation has emerged as a potential treatment option for drug-resistant hypertension. Its efficacy is currently under debate. We aimed to evaluate the capability of contrast-enhanced magnetic resonance imaging (MRI) to assess the effects of RDN on the renal arterial wall in patients presenting with drug-resistant hypertension. METHODS: Patients were included prospectively following institutional review board approval and written informed consent. Renal arteries were imaged using a two-dimensional T1-weighted TSE sequence pre- and post-administration of a gadolinium-based contrast agent, before (D0), 2 days (D2) and 6 months (M6) after RDN. Mean enhancement of the wall (mENH) and mean wall thickness (mWT) were compared across time using an ANOVA with repeated measures and post-hoc paired t-test. RESULTS: Follow-up was completed for 23 patients (median age, 57 years; 16 men). The mENH at D2 (96.3 ± 36.0 %) was significantly higher than at D0 (61.1 ± 26.3%, p < 0.001) and M6 (66.1±22.7%, p < 0.001). Similarly, mWT was significantly higher at D2 (3.1 ± 0.4 m) than at D0 (2.7 ± 0.4mm, p < 0.001) and M6 (2.9 ± 0. 5 mm, p = 0.002). CONCLUSIONS: MRI demonstrated abnormalities of the arterial wall 2 days after RDN that had resolved at 6 months. KEY POINTS: • Contrast-enhanced MRI provides anatomic evidence of renal artery RF ablation • Temperature increase related to RF ablation induces transient arterial wall inflammation • Morphological effects observed 2 days post RF ablation are not visible after 6 months.

Effect of Mild Hypocapnia on Critical Closing Pressure and Other Mechanoelastic Parameters of the Cerebrospinal System.

OBJECTIVE: Brain arterial critical closing pressure (CrCP) has been studied in several diseases such as traumatic brain injury (TBI), subarachnoid haemorrhage, hydrocephalus, and in various physiological scenarios: intracranial hypertension, decreased cerebral perfusion pressure, hypercapnia, etc. Little or nothing so far has been demonstrated to characterise change in CrCP during mild hypocapnia. METHOD: We retrospectively analysed recordings of intracranial pressure (ICP), arterial blood pressure (ABP) and blood flow velocity from 27 severe TBI patients (mean 39.5 ± 3.4 years, 6 women) in whom a ventilation increase (20% increase in respiratory minute volume) was performed over 50 min as part of a standard clinical CO2 reactivity test. CrCP was calculated using the Windkessel model of cerebral arterial flow. Arteriolar wall tension (WT) was calculated as a difference between CrCP and ICP. The compartmental compliances arterial (C a ) and cerebrospinal fluid space (C i ) were also evaluated. RESULTS: During hypocapnia, ICP decreased from 17±6.8 to 13.2±6.6 mmHg (p < 0.000001). Wall tension increased from 14.5 ± 9.9 to 21.7±9.1 mmHg (p < 0.0002). CrCP, being a sum of WT + ICP, changed significantly from 31.5 ± 11.9 mmHg to 34.9±11.1 mmHg (p < 0.002), and the closing margin (ABP-CrCP) remained constant at an average value of 60 mmHg. C a decreased significantly during hypocapnia by 30% (p < 0.00001) and C i increased by 26% (p < 0.003). CONCLUSION: During hypocapnia in TBI patients, ICP decreases and WT increases. CrCP increases slightly as the rise in wall tension outweighs the decrease in ICP. The closing margin remained unchanged, suggesting that the risk of hypocapnia-induced ischemia might not be increased.

Cardiac amyloidosis is associated with increased aortic stiffness.

OBJECTIVE: Cardiac amyloidosis (CA) is as an infiltrative disorder primarily caused by extracellular tissue deposition of amyloid fibrils in the myocardial interstitium. The current study was designed to test whether alterations in ascending aortic elastic properties could be detected by echocardiography in CA patients, and to compare their results to controls. PATIENTS AND METHODS: We included 19 CA patients from which CA proved to be AL amyloidosis in 17 cases and transthyretin (TTR) amyloidosis in 2 cases. Their results were compared to 20 age-, gender-, and risk factor-matched controls. RESULTS: There was significantly greater interventricular septum and left ventricular (LV) posterior wall thickness, lower LV ejection fraction and greater E/A in CA patients than in controls, suggesting systolic, and diastolic dysfunction. CA patients also showed significantly reduced aortic strain and pulsatile change in aortic diameter, and increased aortic stiffness index. CONCLUSION: These results suggest increased aortic stiffness in CA patients.

[Informativity of Indicators of the Arterial Wall Stiffness for Screening Studies].

OBJECTIVE: comparative assessment of informativity of parameters of arterial wall stiffness - the cardio-ankle vascular index (CAVI), the augmentation index (AI) - for solution of problems of screening patients being under threat of realization of complex impact of metabolic syndrome (MS) and elevated vessel wall stiffness, both creators and markers of high risk of severe cardiovascular complications. MATERIALS AND METHODS: We examined mining industry employees (n=206) with cardiac risk factors (arterial hypertension, abdominal obesity, and smoking). Comparative group comprised 75 employees of the same enterprise without above-mentioned risk factors. Studies of arterial wall stiffness included determination of CAVI and AI. The sensitivity, specifcity and accuracy of the screening method were calculated. RESULTS: CAVI and AI parameters had different sensitivity, specifcity and accuracy for identifying patients at risk of cardiovascular complications. AI was 2 times more sensitive than CAVI during examination of patients with only clinical and anamnestic cardiovascular risk markers and patients with clinical-anamnestic and laboratory risk markers. Specifcity of AI was lower than specifcity of CAVI and atained only 34.4% in patients with clinical-anamnestic and laboratory risk factors. At the same time, specifcity of CAVI in these patients reached 86.2%. Accuracy of AI for screening study was 1.4 times higher than that of CAVI in patients with only clinical-anamnestic risk markers, and 1.6 times higher in patients with both clinical-anamnestic and laboratory risk markers. Moreover, after comparing patient groups with individually high and normal CAVI and AI, we found the differences in metabolic laboratory risk factors (glucose, total cholesterol, triglycerides and the Atherogenic Index) only for AI. CONCLUSION: Parameters of arterial stiffness have different informative value for screening of patients with clinical-anamnestic or laboratory risk factors. AI compared with CAVI is 2 times more sensitive and 1.6 times more accurate but has lower specifcity for risk factor screening among patients being under threat of realization of complex impact of MS and elevated vessel wall stiffness.

[Early Markers of Cardiovascular Risk in Women With Hereditary Burdening by Cardiovascular Diseases].

PURPOSE: to identify early markers of development of cardiovascular diseases (CVD) in women. MATERIALS AND METHODS: Female firstdegree relatives from 39 families formed 2 groups: families (n=19) containing mothers with arterial hypertension (AH) (group 1) and healthy daughters (group 1a); families (n=20) containing practically heathy mothers (group 2) and healthy daughters (group 2a). We assessed data of anamnesis, including registration of cardiovascular risk factors, and family history of CVD. Examination included registration of anthropometric parameters, automatic and manual measurement of intima-media thickness (IMT) and resistance indexes of brachiocephalic arteries (BCA). We also determined cardio-ankle vascular index (CAVI), ankle-brachial index (ABI), and measured magnitude of ß-adrenoreception of membranes (ß-ARM) of erythrocytes in micro-quantities of venous blood. RESULTS: Mothers in both groups of families had excessive body mass or obesity. Mothers of group 1 had more pronounced signs of abdominal obesity (AO). They also had abnormalities of IMT and sings of subclinical atherosclerosis of BCA. CAVI in this group was significantly higher than in group 2. In group 1a median BMI (25.5 kg/m2) and waist/hip ratio were significantly higher than in group 2a. Daughters of group 1a contrary to group 2a had abnormalities of vascular wall: increased automatically measured IMT of carotid arteries and elevated CAVI. Arterial pressure and heart rate (HR) in group 1a were within limits of physiological norm but significantly higher than in group 2a. All included women had elevated ß-ARM values but in group 1a this parameter was significantly higher than in group 2a and moderately correlated with HR. CONCLUSIONS: Risk factors of CVD development in women are AH, AO, high activity of the sympathoadrenal system. These factors provoke changes of vascular wall (elevation of its stiffness and early subclinical atherosclerosis). In daughters of mothers with AH important prognostic components of CVD risk in addition to family history of CVD are AO, systolic blood pressure (BP) >120 mm Hg, diastolic BP >78 mm Hg, HR approaching upper limit of physiological norm, and high CAVI (indicator of vascular wall stiffness).