Subclinical cardiac dysfunction in pediatric kidney transplant recipients identified by speckle-tracking echocardiography.

BACKGROUND: Kidney transplantation (KTx) improves prognosis in children with kidney failure; still, these patients are prone to cardiovascular damage due to multiple risk factors. Our aim was to assess myocardial structure and function in pediatric KTx by conventional and speckle-tracking echocardiography (STE) in association with established cardiovascular risk factors. METHODS: Forty-two KTx and 39 healthy age- and gender-matched children were evaluated. KTx recipients were further categorized according to the control of hypertension assessed by 24-h ambulatory blood pressure monitoring (ABPM). Subjects underwent pulse wave velocity (PWV) measurement, conventional echocardiography, and 2-dimensional STE. Left and right ventricular (LV, RV) global longitudinal strain (GLS), and LV circumferential strain (GCS) were measured. Glomerular filtration rate (eGFR) was calculated according to the Schwartz formula. RESULTS: KTx patients had increased blood pressure and arterial stiffness. LV ejection fraction (EF) was preserved along with elevated LV mass index (LVMi) while LVGLS was significantly lower, whereas LVGCS and RVGLS were increased in KTx. Uncontrolled hypertensives had lower LVGLS compared to those with controlled hypertension. Using multiple forward stepwise regression analysis, 24-h SBP and relative wall thickness (RWT) were independent determinants of LVMi, whereas antihypertensive therapy, eGFR, and HOMA-IR were independent determinants of LVGLS. CONCLUSIONS: Cardiac morphology and function show distinct changes after KTx. Along with comparable ventricular volumes, LV hypertrophy and subclinical myocardial dysfunction are present. Control of hypertension and kidney graft function are major factors of LV performance. STE may be useful to reveal early myocardial dysfunction in pediatric KTx. A higher resolution version of the Graphical abstract is available as Supplementary information.

Effects of acetazolamide on central blood pressure, peripheral blood pressure, and arterial distensibility at acute high altitude exposure.

AIMS: We assessed the haemodynamic changes induced by exposure to high altitude hypoxia and the effects on them of acetazolamide, a drug prescribed to prevent and treat mountain sickness. METHODS AND RESULTS: In 42 subjects (21 males, age 36.8 ± 8.9 years) randomized to double blind acetazolamide 250 mg b.i.d. or placebo, pulse wave velocity and pulse wave parameters were assessed (PulsePen) at baseline; after 2-day treatment at sea level; within 6 h and on 3rd day of exposure to high altitude. Exposure to high altitude significantly increased diastolic (P < 0.005) and mean blood pressure (BP) (P < 0.05, after prolonged exposure) in placebo but not in the acetazolamide group. Therefore, subjects on acetazolamide showed significantly lower values of diastolic (P < 0.005) and mean BP (P < 0.05) at altitude. Furthermore, they also showed significantly lower values of systolic BP (P < 0.05). Pulse wave velocity did not change at high altitude, while the augmentation index, normalized for a theoretical heart rate of 75 b.p.m., significantly increased (P < 0.05) under placebo, but not under acetazolamide. In a multivariate model, unadjusted augmentation index at high altitude was not affected by BP changes, while significant determinants were heart rate and gender. CONCLUSION: Acute exposure to high altitude induced a rise in brachial BP and changes in pulse waveform-derived parameters, independent from changes in mean BP and partly counteracted by treatment with acetazolamide. The impact of acetazolamide on the haemodynamic alterations induced by hypobaric hypoxia may be considered among the beneficial effects of this drug in subjects prone to mountain sickness. CLINICAL TRIAL REGISTRATION: EudraCT Number: 2010-019986-27.

A study protocol for evaluating aortic stiffness modifications in patients treated with endovascular aortic repair.

BACKGROUND: Arterial stiffness, particularly aortic stiffness (AoS), is associated with an increased risk of cardiovascular disease. Endovascular repair for abdominal (EVAR) and thoracic (TEVAR) aortic disease may increase AoS. This study protocol aims to assess changes in AoS before and after interventions for aortic disease. METHODS: Patients scheduled for EVAR or TEVAR during a three-year period will be enrolled. An indirect AoS indicator, carotid-to-femoral pulse wave velocity (cf-PWV) will be measured non-invasively using applanation tonometry and reported with others perioperative data before and after the endovascular treatment. Moreover, cardiological data will be collected through echocardiography. RESULTS: Fifty EVAR and 50 TEVAR will be enrolled. We will primarily analyze changes in cf-PWV. To ensure the reliability of our findings, we will also include supplementary data such as clinical information, morphological data, and functional echocardiographic data. CONCLUSIONS: By examining AoS modifications before and after endovascular aortic repair, this study aims to enhance our understanding of how arterial stiffness changes following endoprosthesis deployment. The findings from the applied protocol are expected to be informative for innovative graft designs with minimized mechanical mismatch with the aortic wall and with improved vascular hemodynamic, aligning with the current trend in improving patient outcomes. Moreover, understanding these modifications is important for predicting and improving long-term cardiovascular outcomes in patients undergoing such interventions.

Early wave reflection of carotid artery is associated with 18F-FDG PET hypometabolism in Alzheimer's brain areas of cognitively normal adults.

INTRODUCTION: Arterial stiffening likely plays a role in Alzheimer disease (AD) pathogenesis. The current study investigated whether inter-individual variations in arterial stiffness and pressure wave parameters were associated with 18F-FDG positron emission tomography (PET) metabolism in AD-associated brain areas throughout adulthood, independently of age and before the onset of any neuropsychological disorders. METHODS: A prospective, large age-range population of 67 patients (17 young, 16 middle-aged, and 34 older adults; 37 women) underwent a: brain 18F-FDG PET, blood pressure recording, and carotid/femoral pulse wave-based measurements, including the time-to-peak of the reflected backward carotid pulse wave (bT), on the same day. Multivariable and quantitative voxel-to-voxel analyses (P-voxel < 0.005, corrected for cluster volumes) were conducted to assess associations between vascular parameters and 18F-FDG PET metabolism in AD-associated brain areas. RESULTS: In the multivariable analysis, only increased age and decreased bT were independently associated with the decline of metabolic activity in AD-associated brain areas (P < 0.001). In the voxel-to-voxel analysis with age as a covariate, bT was strongly associated with the metabolic activity of 40 clusters in AD-associated brain areas (clusters cumulative volume: 63 cm3; T score max: 5.7). CONCLUSION: In a large age-range population of adult patients, who are still unaffected by neuropsychological disorders, an early reflected arterial pressure wave, as evidenced by a decreased bT value, is strongly associated with hypometabolic activity of AD-associated brain areas, independently of age.

Myocardial oxygen supply and demand imbalance predicts mortality in older nursing home residents: The PARTAGE study.

BACKGROUND: A mismatch between myocardial oxygen supply and demand is the most common cause of ischemic myocardial injury in older persons. The subendocardial viability ratio (SEVR) can usefully estimate the degree of myocardial perfusion relative to left-ventricular workload. The aim of the present study was to evaluate the ability of SEVR to predict long-term mortality in the older population. Additionally, we aimed to identify the SEVR cutoff value best predicting total mortality. METHODS: This is a multicenter, longitudinal study involving a large population of individuals older than 80 years living in nursing homes. Patients with cancer, severe dementia, and very low level of autonomy were excluded from the study. Participants were monitored for 10 years. Adverse outcomes were recorded every 3 months from inclusion to the end of the study. SEVR reflects the balance between subendocardial oxygen supply and demand, and was estimated non-invasively by analyzing the carotid pressure waveform recorded by applanation arterial tonometry. RESULTS: A total of 828 people were enrolled (mean age: 87.7 ± 4.7 years, 78% female). 735 patients died within 10 years and 24 were lost to follow-up. SEVR was inversely associated with mortality at univariate Cox-regression model (risk ratio, 0.683 per unit increase in SEVR; 95% confidence interval (CI) [0.502-0.930], p = 0.015) and in a model including age, sex, body mass index, Activity of Daily Living index and Mini-Mental State Examination score (risk ratio, 0.647; 95% CI [0.472-0.930]). The lowest tertile of SEVR was associated with higher 10-years total mortality than the middle (p < 0.001) and the highest (p < 0.004) tertile. A SEVR cutoff value of 83% was identified as the best predictor of total mortality. CONCLUSIONS: SEVR may be considered as a marker of "cardiovascular frailty." An accurate non-invasive estimation of SEVR could be a useful and independent parameter to assess survival probability in very old adults. TRIAL REGISTRATION: NCT00901355, registered on ClinicalTrials.gov website.

Developing technologies to assess vascular ageing: a roadmap from VascAgeNet.

Vascular ageing is the deterioration of arterial structure and function which occurs naturally with age, and which can be accelerated with disease. Measurements of vascular ageing are emerging as markers of cardiovascular risk, with potential applications in disease diagnosis and prognosis, and for guiding treatments. However, vascular ageing is not yet routinely assessed in clinical practice. A key step towards this is the development of technologies to assess vascular ageing. In this Roadmap, experts discuss several aspects of this process, including: measurement technologies; the development pipeline; clinical applications; and future research directions. The Roadmap summarises the state of the art, outlines the major challenges to overcome, and identifies potential future research directions to address these challenges.

ABCA1-dependent serum cholesterol efflux capacity inversely correlates with pulse wave velocity in healthy subjects.

The capacity of HDL to induce cell cholesterol efflux is considered one of its main antiatherogenic properties. Little is known about the impact of such HDL function on vascular physiology. We investigated the relationship between ABCA1-dependent serum cholesterol efflux capacity (CEC), an HDL functionality indicator, and pulse wave velocity (PWV), an indicator of arterial stiffness. Serum of 167 healthy subjects was used to conduct CEC measurement, and carotid-femoral PWV was measured with a high-fidelity tonometer. J774 macrophages, labeled with [(3)H]cholesterol and stimulated to express ABCA1, were exposed to sera; the difference between cholesterol efflux from stimulated and unstimulated cells provided specific ABCA1-mediated CEC. PWV is inversely correlated with ABCA1-dependent CEC (r = -0.183; P = 0.018). Moreover, controlling for age, sex, body mass index, mean arterial pressure, serum LDL, HDL-cholesterol, and fasting plasma glucose, PWV displays a significant negative regression on ABCA1-dependent CEC (ß = -0.204; 95% confidence interval, -0.371 to -0.037). The finding that ABCA1-dependent CEC, but not serum HDL cholesterol level (r = -0.002; P = 0.985), is a significant predictor of PWV in healthy subjects points to the relevance of HDL function in vascular physiology and arterial stiffness prevention.

Paricalcitol and cardiorenal outcome: from the IMPACT study to clinical practice.

Chronic kidney disease mineral bone disorders (CKD-MBD) encompass laboratory, vascular and bone abnormalities that might portend a poor prognosis in CKD. In spite of a great effort in elucidating the CKD-MBD natural history and pathogenesis, the underlying mechanisms are still largely unknown. However, a deficit in vitamin D is commonly reported as one of the first steps in CKD-MBD, and numerous epidemiological studies have associated serum vitamin D levels with different markers of cardiovascular disease and the risk of death in different populations. We herein summarize current evidence that links vitamin D deficiency to an adverse outcome and the results of the most recent clinical trials that have investigated the impact of paricalcitol supplementation on hard outcome in CKD patients.

Does it make sense to measure only the brachial blood pressure?

The significant reduction in cardiovascular mortality in the second half of the 20th century, due to an effective battle against high blood pressure, may be considered one of the greatest medical success stories of the past century. However, several epidemiological and clinical studies have recently highlighted that the single acquisition of blood pressure values at brachial level is inadequate to accurately predict the cardiovascular risk of patients with high blood pressure values. Furthermore, some studies suggest the importance of central systolic blood pressure and central pulse pressure (central systolic blood pressure - diastolic blood pressure) as cardiovascular prognostic factors. Central systolic blood pressure and central pulse pressure are able to evaluate the real pressure load imposed on the left ventricle much better than peripheral systolic blood pressure and peripheral pulse pressure. Moreover, the disappearance of the blood pressure amplification phenomenon (i.e. the difference between peripheral and central systolic blood pressure) is a significant predictor of all-cause (including cardiovascular) mortality, independent of age and other standard confounding factors. Thus, the measurement of central arterial pressure provides more precise information on the cardiovascular risk than brachial artery blood pressure measurement.

Assessment and interpretation of blood pressure variability in a clinical setting.

Blood pressure (BP) is characterized by marked fluctuations occurring within the 24 h as a result of complex interactions between behavioral, environmental, humoral, and neural central or reflex influences. Significant BP variations also occur over more prolonged periods of time (i.e. between days, weeks, months, seasons and even years), not as a random phenomenon but as a result of several interacting factors yet not completely identified. Depending on the method and time interval considered for measurement, the clinical significance and prognostic implications of different types of BP variability (BPV) may substantially differ. Either in the short or in the long term, BPV has been associated with development, progression and severity of cardiac, vascular and renal organ damage and with an increased risk of cardiovascular events and mortality, independently adding to cardiovascular risk, over and above the contribution of elevated mean BP levels. The present paper provides a review on the main methods currently employed for assessment of BPV as well as on the mechanisms, clinical interpretation and prognostic significance of different types of BPV, addressing the question on whether BPV should be a target for antihypertensive treatment for the current prevention of cardiovascular disease.

Microcirculatory and Rheological Adaptive Mechanisms at High Altitude in European Lowlander Hikers and Nepalese Highlanders.

BACKGROUND: Physical activity at high-altitudes is increasingly widespread, both for tourist trekking and for the growing tendency to carry out sports and training activities at high-altitudes. Acute exposure to this hypobaric-hypoxic condition induces several complex adaptive mechanisms involving the cardiovascular, respiratory and endocrine systems. A lack of these adaptive mechanisms in microcirculation may cause the onset of symptoms of acute mountain sickness, a frequent disturbance after acute exposure at high altitudes. The aim of our study was to evaluate the microcirculatory adaptive mechanisms at different altitudes, from 1350 to 5050 m a.s.l., during a scientific expedition in the Himalayas. METHODS: The main haematological parameters, blood viscosity and erythrocyte deformability were assessed at different altitudes on eight European lowlanders and on a group of eleven Nepalese highlanders. The microcirculation network was evaluated in vivo by conjunctival and periungual biomicroscopy. RESULTS: Europeans showed a progressive and significant reduction of blood filterability and an increase of whole blood viscosity which correlate with the increase of altitude (p < 0.02). In the Nepalese highlanders, haemorheological changes were already present at their residence altitude, 3400 m a.s.l. (p < 0.001 vs. Europeans). With the increase in altitude, a massive interstitial oedema appeared in all participants, associated with erythrocyte aggregation phenomena and slowing of the flow rate in the microcirculation. CONCLUSIONS: High altitude causes important and significant microcirculatory adaptations. These changes in microcirculation induced by hypobaric-hypoxic conditions should be considered when planning training and physical activity at altitude.

Wall Properties of Elastic and Muscular Arteries in Children and Adolescents at Increased Cardiovascular Risk.

BACKGROUND: Pulse wave velocity (PWV) assessment represents a simple method to estimate arterial distensibility. At present, carotid-femoral PWV (cf-PWV) is considered the gold standard method in the non-invasive evaluation of the elastic properties of the aorta. On the other hand, the mechanical properties of muscular arteries can be evaluated on the axillo-brachial-radia axis by estimating the carotid-radial PWV (cr-PWV). While a number of studies have addressed these issues in adults, limited information is available on the respective features of cf-PWV and cr-PWV and on their modulating factors in children and adolescents at increased cardiovascular risk. METHODS: The mechanical properties of the predominantly elastic (aorta) and muscular (axillo-brachial-radial axis) arteries were evaluated in a pediatric population characterized by either elevated blood pressure (BP) or excess body weight, and the main factors affecting cf-PWV and cr-PWV values in these individuals were investigated. RESULTS: 443 children and adolescents (median age 11.5 years, 43.3% females) were enrolled; 25% had BP values >90th percentile and 81% were excess weight. The cf-PWV values were significantly lower than the cr-PWV values: median (Q1-Q3) = 4.8 m/s (4.3-5.5) and 5.8 m/s (5.0-6.5), respectively (p < 0.001). The pubertal development (p < 0.03), systolic BP and diastolic BP z-scores (p = 0.002), heart rate (p < 0.001), and waist-to-height ratio (p < 0.005) were significantly associated with cf-PWV values. No significant association was found between BMI z-score and cf-PWV. Predictors of high cf-PWV (>95th percentile) were the heart rate (OR 1.07, 95%CI 1.04-1.10, p < 0.001) and waist-to-height ratio (OR 1.06, 95%CI 1.0-1.13, p = 0.04). The variables significantly related with cr-PWV values were diastolic BP z-score (p = 0.001), heart rate (p < 0.01), and HOMA index (p < 0.02). No significant association was found between the cr-PWV and BMI z-score or waist-to-height ratio. CONCLUSIONS: Systolic and diastolic BP values and central obesity are associated with aortic stiffness in a population of children and adolescents at increased cardiovascular risk. In contrast, diastolic BP, heart rate, and levels of insulin resistance appear to be related to distensibility of the upper limb vascular district.

Volume of the proximal half of the thoracic aorta is the most comprehensive FDG-PET/CT indicator of arterial aging throughout adulthood.

INTRODUCTION: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) features of the proximal and more elastic half of the thoracic aorta are known to correlate with aorta stiffness in older populations. This prospective study aimed to analyze the changes in these FDG-PET/CT features between young, middle-aged, and older adults, and investigate associations with arterial stiffness and blood pressure (BP). METHODS: Young (< 40 years), middle-aged (40-to-60 years), and older (> 60 years) adults, who underwent an FDG-PET/CT, were prospectively recruited. FDG-PET/CT features of the proximal half of the thoracic aorta were analyzed relative to the age categories, BP and carotid-femoral pulse wave velocity (PWV), a reference indicator of aorta stiffness. RESULTS: We included 79 patients (38 women; 22 young, 19 middle-aged, and 38 older adults). An increase in age category was associated with increases in mean standardized uptake values (SUVs) of blood and aorta and most significantly in aorta SUV heterogeneity, represented by SUV standard deviation (SUV-SD), aorta calcification volume, and the aorta volume indexed to body surface area. However, this indexed aorta volume was the sole variable: (i) exhibiting a stepwise increase from young (median: 25 cm3/m2 [interquartile range: 20-28 cm3/m2]), to middle-aged (41 [30-48] cm3/m2, p < 0.001 vs. Young), and older (62 [44-70] cm3/m2, p < 0.001 vs. middle-age) adults, and (ii) selected in the multivariate predictions of systolic, diastolic, and pulse BP. Indexed aorta volume was also a multivariate predictor of PWV but in association with SUV-SD and hypertension. CONCLUSION: In a population of patients referred to an FDG-PET/CT investigation, the indexed volume of the proximal and more elastic half of the thoracic aorta is the most comprehensive indicator of arterial aging. This imaging parameter exhibits a stepwise increase from young to middle-aged and older adults, is strongly linked to inter-individual changes in both arterial stiffness and BP, and thus, could help assess the early phases of arterial aging. Trial registration ClinicalTrial.gov, NCT03345290. Registered 17 November 2017, https://clinicaltrials.gov/ct2/show/NCT03345290?term=NCT03345290&draw=2&rank=1.

Marfan Syndrome: Enhanced Diagnostic Tools and Follow-up Management Strategies.

Marfan syndrome (MFS) is a rare inherited autosomic disorder, which encompasses a variety of systemic manifestations caused by mutations in the Fibrillin-1 encoding gene (FBN1). Cardinal clinical phenotypes of MFS are highly variable in terms of severity, and commonly involve cardiovascular, ocular, and musculoskeletal systems with a wide range of manifestations, such as ascending aorta aneurysms and dissection, mitral valve prolapse, ectopia lentis and long bone overgrowth, respectively. Of note, an accurate and prompt diagnosis is pivotal in order to provide the best treatment to the patients as early as possible. To date, the diagnosis of the syndrome has relied upon a systemic score calculation as well as DNA mutation identification. The aim of this review is to summarize the latest MFS evidence regarding the definition, differences and similarities with other connective tissue pathologies with severe systemic phenotypes (e.g., Autosomal dominant Weill-Marchesani syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome) and clinical assessment. In this regard, the management of MFS requires a multidisciplinary team in order to accurately control the evolution of the most severe and potentially life-threatening complications. Based on recent findings in the literature and our clinical experience, we propose a multidisciplinary approach involving specialists in different clinical fields (i.e., cardiologists, surgeons, ophthalmologists, orthopedics, pneumologists, neurologists, endocrinologists, geneticists, and psychologists) to comprehensively characterize, treat, and manage MFS patients with a personalized medicine approach.

Blood pressure variability: methodological aspects, clinical relevance and practical indications for management - a European Society of Hypertension position paper ∗.

Blood pressure is not a static parameter, but rather undergoes continuous fluctuations over time, as a result of the interaction between environmental and behavioural factors on one side and intrinsic cardiovascular regulatory mechanisms on the other side. Increased blood pressure variability (BPV) may indicate an impaired cardiovascular regulation and may represent a cardiovascular risk factor itself, having been associated with increased all-cause and cardiovascular mortality, stroke, coronary artery disease, heart failure, end-stage renal disease, and dementia incidence. Nonetheless, BPV was considered only a research issue in previous hypertension management guidelines, because the available evidence on its clinical relevance presents several gaps and is based on heterogeneous studies with limited standardization of methods for BPV assessment. The aim of this position paper, with contributions from members of the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability and from a number of international experts, is to summarize the available evidence in the field of BPV assessment methodology and clinical applications and to provide practical indications on how to measure and interpret BPV in research and clinical settings based on currently available data. Pending issues and clinical and methodological recommendations supported by available evidence are also reported. The information provided by this paper should contribute to a better standardization of future studies on BPV, but should also provide clinicians with some indications on how BPV can be managed based on currently available data.

Non-Invasive Assessment of Arterial Stiffness: Pulse Wave Velocity, Pulse Wave Analysis and Carotid Cross-Sectional Distensibility: Comparison between Methods.

Background: The stiffening of large elastic arteries is currently estimated in research and clinical practice by propagative and non-propagative models, as well as parameters derived from aortic pulse waveform analysis. Methods: Common carotid compliance and distensibility were measured by simultaneously recording the diameter and pressure changes during the cardiac cycle. The aortic and upper arm arterial distensibility was estimated by measuring carotid−femoral and carotid−radial pulse wave velocity (PWV), respectively. The augmentation index and blood pressure amplification were derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the common carotid artery. Results: 75 volunteers were enrolled in this study (50 females, average age 53.5 years). A significant inverse correlation was found between carotid distensibility and carotid−femoral PWV (r = −0.75; p < 0.001), augmentation index (r = −0.63; p < 0.001) and central pulse pressure (r = −0.59; p < 0.001). A strong correlation was found also between the total slope of the diameter/pressure rate carotid curves and aortic distensibility, quantified from the inverse of the square of carotid−femoral PWV (r = 0.67). No correlation was found between carotid distensibility and carotid−radial PWV. Conclusions: This study showed a close correlation between carotid−femoral PWV, evaluating aortic stiffness by using the propagative method, and local carotid cross-sectional distensibility.

Uric acid and arterial stiffness in children and adolescents: Role of insulin resistance and blood pressure.

Several studies describe the association between serum uric acid (SUA) and arterial stiffness in adults. Uric acid contributes through several mechanisms to the increase in blood pressure (BP) and adversely affects the insulin signaling pathway. Moreover, SUA predict the development of hypertension and insulin resistance up to type 2 diabetes. Early arterial stiffening, estimated by carotid-femoral pulse wave velocity (PWV), may already be present in pediatric age. Aim of our study was to investigate the relationship between SUA and PWV in a pediatric population and its interaction with insulin resistance and BP. In 322 children and adolescents (56.2% male, mean age 11.3 [SD 2.8] years), we measured weight, height, waist circumference, BP and PWV. We also assayed SUA and estimated glomerular filtration rate (eGFR) and calculated HOMA-index as a marker of insulin resistance. Simple and multiple regression analyses were performed to assess variables associated with PWV. Mediation models were applied to identify the direct and indirect effects of individual variables on PWV. On univariate analysis, age (p < 0.001), waist circumference-to-height ratio (p = 0.036), systolic and diastolic BP (SBP and DBP) z-score (p < 0.001), heart rate (p = 0.028), SUA (p = 0.002), HOMA-index (p < 0.001), and eGFR (p = 0.014) were significantly associated with PWV. The multiple regression model showed that only age (p = 0.028), SBP z-score (p = 0.006), and heart rate (p = 0.001) were significantly associated with PWV. The results were superimposable when the DBP z-score replaced the SBP z-score in the model. Mediation models showed that the effect of eGFR on PWV was fully mediated by SUA (p = 0.015) and that the effect of SUA on PWV was totally mediated by HOMA-index (p < 0.001). Both SUA (p < 0.01) and HOMA-index (p < 0.01) had a significant association with higher SBP (DBP) z-scores. The double mediation model including both BP and HOMA-index showed that the SUA effect on PWV was totally mediated by both variables (p = 0.005, for HOMA-index, p = 0.004, for SBP z-score and p = 0.007, for combined effect). The results were superimposable when the DBP z-score replaced the SBP z-score in the model. In conclusion, insulin resistance and BP are both important mediators of the association between SUA and vascular stiffness in pediatric age.

Interactions Between Brain 18F-FDG PET Metabolism and Hemodynamic Parameters at Different Ages of Life: Results From a Prospective Cross-Sectional Study.

Brain 18F-FDG PET imaging is useful to characterize accelerated brain aging at a pre-symptomatic stage. This study aims to examine the interactions between brain glycolytic metabolism and hemodynamic parameters in different age groups. Methods: A total of 72 patients (from 23 to 88 years of age, 38 women) without any cerebral diseases but with available cardiac, arterial peripheral, and central blood pressure measurements as well as arterial stiffness parameters obtained from brachial pressure and applanation tonometry and a brain 18F-FDG PET scan were prospectively included into this study. Quantitative voxel-to-voxel analyses were carried out to test for negative associations between brain glycolytic metabolism and individual hemodynamic parameters (p-voxel of <0.001 for the whole population and <0.005 for age groups). Results: The heart rate parameter of the whole population showed the most extensive associations with brain metabolism (15,857 mm3, T-score: 5.1), predominantly affecting the frontal and temporal regions (69% of the volume). Heart rate for the younger age group, systolic and pulse pressure for the 41-60-year-old group, and diastolic pressure for the older group were most extensively associated with brain metabolism and mainly involved the fronto-temporal lobes (respective involvement of 52.8%, 60.9%, and 65.5%) which are also the regions implicated in accelerated brain aging. Conclusion: This cross-sectional prospective study identified extensive associations between cerebral metabolism and hemodynamic parameters, indicating common aging mechanisms. Heart rate throughout adult life, systolic and pulse pressure parameters around middle age, and diastolic pressure parameters in older patients, suggest the existence of potentially therapeutic targets to prevent accelerated brain aging.

Haemodynamic Adaptive Mechanisms at High Altitude: Comparison between European Lowlanders and Nepalese Highlanders.

Background: Exposure to high altitudes determines several adaptive mechanisms affecting in a complex way the whole cardiovascular, respiratory, endocrine systems because of the hypobaric hypoxic condition. The aim of our study was to evaluate the circulatory adaptive mechanisms at high altitudes, during a scientific expedition in the Himalayas. Methods: Arterial distensibility was assessed measuring carotid-radial and carotid-femoral pulse wave velocity. Tests were carried out at several altitudes, from 1350 to 5050 m above sea level, on 8 lowlander European researchers and 11 highlander Nepalese porters. Results: In Europeans, systolic blood pressure and pulse pressure increased slightly but significantly with altitude (p < 0.05 and p < 0.001, respectively). Norepinephrine showed a significant increase after the lowlanders had spent some time at high altitude (p < 0.001). With increasing altitude, a progressive increase in carotid-radial and carotid-femoral pulse wave velocity values was observed in lowlanders, showing a particularly significant increase (p < 0.001) after staying at high altitude (carotid-radial pulse wave velocity, median value (interquartile range) from 9.2 (7.9−10.0) to 11.2 (10.9−11.8) m/s and carotid-femoral pulse wave velocity from 8.5 (7.9−9.0) to 11.3 (10.9−11.8) m/s). At high altitudes (3400 and 5050 m above sea level), no significant differences were observed between highlanders and lowlanders in hemodynamic parameters (blood pressure, carotid-radial and carotid-femoral pulse wave velocity). Conclusions: The progressive arterial stiffening with altitude observed in European lowlanders could explain the increase in systolic and pulse pressure values observed at high altitudes in this ethnic group. Further studies are needed to evaluate the role of aortic stiffening in the pathogenesis of acute mountain sickness.

Arterial Stiffness in Thyroid and Parathyroid Disease: A Review of Clinical Studies.

Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid and parathyroid diseases are endocrine diseases with a relevant cardiovascular burden. The objective of this review was to consider the relationship between arterial stiffness and thyroid and parathyroid diseases in human clinical studies. We performed a systematic literature review of articles published in PubMed/MEDLINE from inception to December 2021, restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and thyroid and parathyroid diseases. For each selected article, data on arterial stiffness were extracted and factors that may have an impact on arterial stiffness were identified. We considered 24 papers concerning hypothyroidism, 9 hyperthyroidism and 16 primary hyperparathyroidism and hypoparathyroidism. Most studies evidenced an increase in arterial stiffness biomarkers in hypothyroidism, hyperthyroidism and primary hyperparathyroidism, even in subclinical and mild forms, although heterogeneity of measurement methods and of study designs prevented a definitive conclusion, suggesting that the assessment of arterial stiffness may be considered in the clinical evaluation of cardiovascular risk in these diseases.