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Background In maintenance hemodialysis patients, intradialytic hypotension (IDH) is a frequent complication that has been associated with poor clinical outcomes. Prediction of IDH may facilitate timely interventions and eventually reduce IDH rates. Methods We developed a machine learning model to predict IDH in in-center hemodialysis patients 15–75 min in advance. IDH was defined as systolic blood pressure (SBP) Results We utilized data from 693 patients who contributed 42 656 hemodialysis sessions and 355 693 intradialytic SBP measurements. IDH occurred in 16.2% of hemodialysis treatments. Our model predicted IDH 15–75 min in advance with an AUROC of 0.89. Top IDH predictors were the most recent intradialytic SBP and IDH rate, as well as mean nadir SBP of the previous 10 dialysis sessions. Conclusions Real-time prediction of IDH during an ongoing hemodialysis session is feasible and has a clinically actionable predictive performance. If and to what degree this predictive information facilitates the timely deployment of preventive interventions and translates into lower IDH rates and improved patient outcomes warrants prospective studies.

Introduction:Vasodilation can paradoxically increase arterial stiffness in older, hypertensive adults. This study modeled increasing smooth muscle tone as a therapeutic strategy to improve central arterial dysfunction in hypertension using participant-specific simulations.Methods:Participant-specific models of the carotid artery were parameterized from vascular ultrasound measures of nitroglycerin-induced vasodilation in 18 hypertensive veterans. The acute changes in carotid artery mechanics were simulated for changes of +/- 2, +/- 4, and +/- 6% in smooth muscle tone and +/- 5, +/- 10, and +/- 15 mmHg in mean arterial pressure (MAP). The chronic carotid artery adaptations were simulated based on the hypothesis that the carotid artery will remodel wall-cross sectional area to maintain mechanical homeostasis.Results:A 6% increase in smooth muscle tone acutely decreased carotid pulse wave velocity from 6.89 +/- 1.24 m/s to 5.83 +/- 1.73 m/s, and a 15 mmHg decrease in MAP decreased carotid pulse wave velocity to 6.17 +/- 1.23 m/s. A 6% increase in smooth muscle tone acutely decreased wall stress from 76.2 +/- 12.3 to 64.2 +/- 10.4 kPa, and a 15 mmHg decrease in MAP decreased wall stress to 60.6 +/- 10.7 kPa. A 6% increase in smooth muscle tone chronically decreased wall cross-sectional area from 18.3 +/- 5.4 to 15.2 +/- 4.9 mm(2,) and a 15 mmHg decrease in MAP decreased wall cross-sectional area to 14.3 +/- 4.6 mm(2).Conclusion:In participant-specific simulation, increasing smooth muscle tone can have a stronger or equivalent effect on carotid artery mechanics compared with decreasing blood pressure. Increasing central arterial smooth muscle tone may be a novel therapeutic target to improve central arterial dysfunction in older, hypertensive adults and should be a focus of future research.

Background: Diabetes is a risk factor for cognitive impairment, and disease duration is associated with geriatric decline and functional disabilities. Objective: This study aimed to examine the association of diabetes duration with domain-specific cognitive impairment in elderly. Methods: A total of 3,142 participants from the National Health and Nutrition Examination Survey (NHANES) from the period between 2011 and 2014 were included. We assessed cognitive function using the Digit Symbol Substitution Test (DSST), the CERAD Word Learning (CERAD-WL) test, the CERAD Delayed Recall (CERAD-DR) test and animal fluency (AF) test. Results: After adjusting for age, sex, race/ethnicity, education level, and annual household income, we found that diabetes with a duration longer than 20 years were at 3.32-fold increased risk of DSST impairment (OR = 3.32, 95% CI: 1.95 to 5.67), 1.72-fold increased risk of CERAD-WL impairment (OR = 1.72, 95% CI: 1.13 to 2.62), and 1.76-fold increased risk of AF impairment (OR = 1.76, 95% CI: 1.23 to 2.53), compared with those with no diabetes. Associations were generally stronger in women than in men. Participants with diabetes, who were diagnosed at 50–59 years old were at increased risk of DSST impairment, CERAD-WL impairment, CERAD-DR impairment, and AF impairment per 5 years longer duration of diabetes. Conclusion: Longer diabetes duration was associated with the increased risk of cognitive impairment, especially in processing speed and attention. The presence of chronic kidney disease was associated with the increased risk of DSST impairment.

Objective: The aim of this study was an assessment of post hoc associations among circadian rhythm parameters, physical activity (PA), and cardiometabolic risk factors in adults with obesity and prediabetes after 3 years of weight loss maintenance.Methods: Circadian rhythm parameters (continuous wrist-temperature measurements), PA, systolic and diastolic blood pressure (SBP, DBP), heart rate (HR), plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, remnant cholesterol, triacylglycerol, and C-reactive protein (CRP) concentrations were determined in 91 free-living participants (mean [SD], age = 56.6 [10] years; BMI = 28.2 [4.0]; homeostatic model assessment of insulin resistance [HOMA-IR] = 3.2 [3.1]) and in 38 participants in sedentary respiration chamber conditions (age = 56.6 [10] years; BMI = 28.5 [4.0]; HOMA-IR = 3.3 [1.4]). Associations of circadian rhythm parameters and PA with cardiometabolic risk factors were determined using factor analyses followed by Pearson correlations.Results: Values of cardiometabolic risk factors were similar, whereas circadian rhythm parameters and PA differed significantly (p Conclusions: In adults with obesity and prediabetes, parameters indicating a robust circadian rhythm were, independently of PA, associated with lower cardiometabolic risk and CRP. Only in free-living conditions, PA mediated the association of higher circadian stability with lower SBP.

Little is known about the genetic determinants of medication use in preventing cardiometabolic diseases. Using the Finnish nationwide drug purchase registry with follow-up since 1995, we performed genome-wide association analyses of longitudinal patterns of medication use in hyperlipidemia, hypertension and type 2 diabetes in up to 193,933 individuals (55% women) in the FinnGen study. In meta-analyses of up to 567,671 individuals combining FinnGen with the Estonian Biobank and the UK Biobank, we discovered 333 independent loci (P –9) associated with medication use. Fine-mapping revealed 494 95% credible sets associated with the total number of medication purchases, changes in medication combinations or treatment discontinuation, including 46 credible sets in 40 loci not associated with the underlying treatment targets. The polygenic risk scores (PRS) for cardiometabolic risk factors were strongly associated with the medication-use behavior. A medication-use enhanced multitrait PRS for coronary artery disease matched the performance of a risk factor-based multitrait coronary artery disease PRS in an independent sample (UK Biobank, n = 343,676). In summary, we demonstrate medication-based strategies for identifying cardiometabolic risk loci and provide genome-wide tools for preventing cardiovascular diseases.

Background: Hyperuricemia may predispose to renal damage, but in end-stage renal disease lower uric acid concentrations have been associated with higher mortality. In experimental studies, uric acid has promoted renal fibrosis and inflammation, but some studies have shown nephroprotective effects probably due to alleviated oxidative stress. We studied the influence of moderate hyperuricemia on kidney morphology in 5/6 nephrectomized rats.Methods: Three weeks after subtotal nephrectomy or sham-operation, rats were put on 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Blood pressure was monitored using tail-cuff. At close of the study, blood, urine, and kidney samples were taken, and renal histology, mast cell count, and oxidative stress markers were determined. Kidney tissue inflammation and fibrosis were evaluated using RT‑PCR and immunohistochemistry.Results: Oxonic acid diet increased plasma uric acid levels by >80 µmol/l without influencing blood pressure. Creatinine clearance was reduced by ~60% in both remnant kidney groups, and by ~30% in hyperuricemic sham-operated rats. In remnant kidney rats with suppressed plasma renin activity, moderate hyperuricemia decreased glomerulosclerosis, tubulointerstitial damage, and kidney mast cell count, but did not influence the fibrosis marker collagen I mRNA content. In both hyperuricemic groups, the mast-cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue COX‑2 levels were decreased.Conclusions: Hyperuricemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately increased plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental chronic renal insufficiency.

Objectives This study investigates whether a citrus and pomegranate complex (CPC) improves physical fitness, mental well-being, and blood biomarkers for oxidative stress and endothelial function in healthy elderly. Design A randomized placebo-controlled cross-over trial. Participants The study included 36 healthy elderly aged 60–75 years old. Intervention and Measurements Participants received four weeks of CPC supplementation and performed the handgrip strength and senior fitness test. Quality of life (QOL) was assessed and blood samples were analyzed for oxidative stress and endothelial function markers. Results After four weeks of CPC supplementation, handgrip strength significantly improved (p=0.019), compared to placebo. Moreover, the thinking, memory, learning, and concentration facets were improved (p=0.042), compared to placebo, and plasma malondialdehyde decreased, compared to placebo (p=0.033). The intervention did not affect senior fitness and the other QOL domains and blood parameters. Conclusion Four weeks of daily CPC supplementation significantly improves handgrip strength and self-evaluated measures of psychological function in healthy older adults. Further research should focus on mechanisms associated with physical performance.

Background: Rescue treatment for delayed cerebral ischemia (DCI) after subarachnoid hemorrhage can include induced hypertension (iHTN) and, in refractory cases, endovascular approaches, of which selective, continuous intraarterial nimodipine (IAN) is one variant. The combination of iHTN and IAN can dramatically increase vasopressor demand. In case of unsustainable doses, iHTN is often prioritized over IAN. However, evidence in this regard is largely lacking. We investigated the effects of a classical (iHTN+IAN) and modified (IAN only ) treatment protocol for refractory DCI in an observational study. Methods: Rescue treatment for DCI was initiated with iHTN (target >180 mm Hg systolic) and escalated to IAN in refractory cases. Until July 2018, both iHTN and IAN were offered in cases refractory to iHTN alone. After protocol modification, iHTN target was preemptively lowered to >120 mm Hg when IAN was initiated (IAN only ). Primary outcome was noradrenaline demand. Secondary outcomes included noradrenaline-associated complications, brain tissue oxygenation, DCI-related infarction and favorable 6-month outcome (Glasgow Outcome Scale 4–5). Results: N=29 and n=20 patients were treated according to the classical and modified protocol, respectively. Protocol modification resulted in a significant reduction of noradrenaline demand (iHTN+IAN 0.70±0.54 µg/kg per minute and IAN only 0.26±0.20 µg/kg per minute, P P P =0.95). Incidence of DCI-related infarction (45.0% versus 41.1%, odds ratio, 1.16 [0.37–3.66]; P =0.80) and favorable clinical outcome (55.6% versus 40.0%, odds ratio, 1.88 [0.55–6.39]; P =0.32) were similar. Brain tissue oxygenation was significantly higher with IANonly (26.6±12.8, 39.6±15.4 mm Hg; P Conclusions: Assuming the potential of iHTN to be exhausted in case of refractory hypoperfusion, additional IAN may serve as a last-resort measure to bridge hypoperfusion in the DCI phase. With close monitoring, preemptive lowering of pressure target after induction of IAN may be a safe alternative to alleviate total noradrenaline load and potentially reduce complication rate.

BACKGROUND: Handheld vital microscopy allows direct observation of red blood cells within the sublingual microcirculation. Automated analysis allows quantifying microcirculatory tissue perfusion variables - including tissue red blood cell perfusion (tRBCp), a functional variable integrating microcirculatory convection and diffusion capacities.OBJECTIVE: We aimed to describe baseline microcirculatory tissue perfusion in patients presenting for elective noncardiac surgery and test that microcirculatory tissue perfusion is preserved during elective general anaesthesia for noncardiac surgery.DESIGN: Prospective observational study.SETTING: University Medical Center Hamburg-Eppendorf, Hamburg, Germany.PATIENTS: 120 elective noncardiac surgery patients (major abdominal, orthopaedic or trauma and minor urologic surgery) and 40 young healthy volunteers.MAIN OUTCOME MEASURES: We measured sublingual microcirculation using incident dark field imaging with automated analysis at baseline before induction of general anaesthesia, under general anaesthesia before surgical incision and every 30 min during surgery. We used incident the dark field imaging technology with a validated automated analysis software.RESULTS: A total of 3687 microcirculation video sequences were analysed. Microcirculatory tissue perfusion variables varied substantially between individuals - but ranges were similar between patients and volunteers. Under general anaesthesia before surgical incision, there were no important changes in tRBCp, functional capillary density and capillary haematocrit compared with preinduction baseline. However, total vessel density was higher and red blood cell velocity and the proportion of perfused vessels were lower under general anaesthesia. There were no important changes in any microcirculatory tissue perfusion variables during surgery.CONCLUSION: In patients presenting for elective noncardiac surgery, baseline microcirculatory tissue perfusion variables vary substantially between individuals - but ranges are similar to those in young healthy volunteers. Microcirculatory tissue perfusion is preserved during general anaesthesia and noncardiac surgery - when macrocirculatory haemodynamics are maintained.

Funder: Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DIfE) (3440), PURPOSE: In several studies, exploratory dietary patterns (DP), derived by principal component analysis, were inversely or positively associated with incident type 2 diabetes (T2D). However, findings remained study-specific, inconsistent and rarely replicated. This study aimed to investigate the associations between DPs and T2D in multiple cohorts across the world. METHODS: This federated meta-analysis of individual participant data was based on 25 prospective cohort studies from 5 continents including a total of 390,664 participants with a follow-up for T2D (3.8-25.0 years). After data harmonization across cohorts we evaluated 15 previously identified T2D-related DPs for association with incident T2D estimating pooled incidence rate ratios (IRR) and confidence intervals (CI) by Piecewise Poisson regression and random-effects meta-analysis. RESULTS: 29,386 participants developed T2D during follow-up. Five DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, were associated with higher incidence of T2D. The strongest association was observed for a DP comprising these food groups besides others (IRRpooled per 1 SD = 1.104, 95% CI 1.059-1.151). Although heterogeneity was present (I2 = 85%), IRR exceeded 1 in 18 of the 20 meta-analyzed studies. Original DPs associated with lower T2D risk were not confirmed. Instead, a healthy DP (HDP1) was associated with higher T2D risk (IRRpooled per 1 SD = 1.057, 95% CI 1.027-1.088). CONCLUSION: Our findings from various cohorts revealed positive associations for several DPs, characterized by higher intake of red meat, processed meat, French fries and refined grains, adding to the evidence-base that links DPs to higher T2D risk. However, no inverse DP-T2D associations were confirmed.

As opposed to arterial distension in the radial plane, longitudinal wall motion (LWM) is a multiphasic and bidirectional displacement of the arterial wall in the anterograde (i.e., in the direction of blood flow) and retrograde (i.e., opposing direction of blood flow) directions. Although initially disregarded as imaging artifact, LWM has been consistently reported in ultrasound investigations in the past decade and is reproducible beat-to-beat, albeit with large interindividual variability across healthy and diseased populations. Emerging literature has sought to examine the mechanistic control of LWM to explain the shape and variability of the motion pattern but lacks considerations for key foundational vascular principles at the level of the arterial wall ultrastructure. The purpose of this review is to summarize the potential factors that underpin the causes and control of arterial LWM, spanning considerations from the arterial extracellular matrix to systems-level integrative theories. First, an overview of LWM and relevant aspects wall composition will be discussed, including major features of the multiphasic pattern, arterial wall extracellular components, tunica fiber orientations, and arterial longitudinal prestretch. Second, current theories on the systems-level physiological mechanisms driving LWM will be discussed in the context of available evidence including experimental human research, porcine studies, and mathematical models. Throughout, we discuss implications of these observations with suggestions for future priority research areas.

As opposed to arterial distension in the radial plane, longitudinal wall motion (LWM) is a multiphasic and bidirectional displacement of the arterial wall in the anterograde (i.e., in the direction of blood flow) and retrograde (i.e., opposing direction of blood flow) directions. While initially disregarded as imaging artifact, LWM has been consistently reported in ultrasound investigations in the last decade and is reproducible beat-to-beat, albeit with large inter-individual variability across healthy and diseased populations. Emerging literature has sought to examine the mechanistic control of LWM to explain the shape and variability of the motion pattern but lacks considerations for key foundational vascular principles at the level of the arterial wall ultrastructure. The purpose of this review is to summarize the potential factors that underpin the causes and control of arterial LWM, spanning considerations from the arterial extracellular matrix to systems-level integrative theories. First, an overview of LWM and relevant aspects wall composition will be discussed, including major features of the multiphasic pattern, arterial wall extracellular components, tunica fiber orientations, and arterial longitudinal pre-stretch. Second, current theories on the systems-level physiological mechanisms driving LWM will be discussed in the context of available evidence including experimental human research, porcine studies, and mathematical models. Throughout, we discuss implications of these observations with suggestions for future priority research areas.

Polyphenols have gained significant attention in protecting several chronic diseases, such as cardiovascular diseases (CVDs). Accumulating evidence indicates that polyphenols have potential protective roles for various CVDs. Hypertension (HTN) is among the hazardous CVDs accounting for nearly 8.5 million deaths worldwide. HTN is a complex and multifactorial disease and a combination of genetic susceptibility and environmental factors play major roles in its development. However, the underlying regulatory mechanisms are still elusive. Polyphenols have shown to cause favourable and beneficial effects in the management of HTN. Noncoding RNAs (ncRNAs) as influential mediators in modulating the biological properties of polyphenols, have shown significant footprints in CVDs. ncRNAs control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct link with blood pressure (BP) regulation is highly probable. Recent evidence suggests that a number of ncRNAs, including main small ncRNAs, microRNAs (miRNAs) and long ncRNAs (lncRNAs), play crucial roles with respect to the antihypertensive effects of polyphenols. Indeed, targeting lncRNAs by polyphenols will be a novel and promising strategy in the management of HTN. Herein, we reviewed the effects of polyphenols in HTN. Additionally, we emphasized on the potential effects of polyphenols on regulations of main ncRNAs, which imply the role of polyphenols in regulating ncRNAs in order to exert protective effects and thus proposing them as new targets for HTN treatment. Polyphenols have gained significant attention in protecting several chronic diseases, such as cardiovascular diseases (CVDs). Accumulating evidence indicates that polyphenols have potential protective roles for various CVDs. Hypertension (HTN) is among the hazardous CVDs accounting for nearly 8.5 million deaths worldwide. HTN is a complex and multifactorial disease and a combination of genetic susceptibility and environmental factors play major roles in its development. However, the underlying regulatory mechanisms are still elusive. Polyphenols have shown to cause favourable and beneficial effects in the management of HTN. Noncoding RNAs (ncRNAs) as influential mediators in modulating the biological properties of polyphenols, have shown significant footprints in CVDs. ncRNAs control basic functions in virtually all cell types relevant to the cardiovascular system and, thus, a direct link with blood pressure (BP) regulation is highly probable. Recent evidence suggests that a number of ncRNAs, including main small ncRNAs, microRNAs (miRNAs) and long ncRNAs (lncRNAs), play crucial roles with respect to the antihypertensive effects of polyphenols. Indeed, targeting lncRNAs by polyphenols will be a novel and promising strategy in the management of HTN. Herein, we reviewed the effects of polyphenols in HTN. Additionally, we emphasized on the potential effects of polyphenols on regulations of main ncRNAs, which imply the role of polyphenols in regulating ncRNAs in order to exert protective effects and thus proposing them as new targets for HTN treatment.

Aims This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. Methods and results EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Self-reported physical activity was summarized using the Cambridge physical activity index (inactive, moderately inactive, moderately active, and active). Participants were categorized into sub-groups based on the presence or the absence of the following risk factors: obesity (body mass index ≥30 kg/m2), hypercholesterolaemia (total cholesterol ≥6.2 mmol/L), history of diabetes, hypertension (self-reported or ≥140/90 mmHg), and current smoking. Prentice-weighted Cox regression was used to assess the association between physical activity and incident CHD events (non-fatal and fatal). Compared to inactive participants without the respective CHD risk factor (referent), excess CHD risk was highest in physically inactive and lowest in moderately active participants with CHD risk factors. Corresponding excess CHD risk estimates amongst those with obesity were 47% [95% confidence interval (CI) 32–64%] and 21% (95%CI 2–44%), with hypercholesterolaemia were 80% (95%CI 55–108%) and 48% (95%CI 22–81%), with hypertension were 80% (95%CI 65–96%) and 49% (95%CI 28–74%), with diabetes were 142% (95%CI 63–260%), and 100% (95%CI 32–204%), and amongst smokers were 152% (95%CI 122–186%) and 109% (95%CI 74–150%). Conclusions In people with CHD risk factors, moderate physical activity, equivalent to 40 mins of walking per day, attenuates but does not completely offset CHD risk.

Renovascular hypertension is defined as the reduction in renal perfusion resulting in sustained hypertension. This study aims to investigate the possible effects of myrtle leaf extract (Myrtus communis L.) on, heart, kidney and aorta tissues in the experimental renovascular hypertension (RVH). 32 male Wistar Albino rats were divided into four groups as control, hypertension, hypertension+ramipril, and hypertension+myrtle leaf extract treatment groups. RVH model was induced by Goldblatt\"s 2-kidney 1-clip method. 12 weeks later than the treatment blood pressures were recorded and oxidant and antioxidant parameters, tissue factor activity, and histological analysis were determined in the kidney, heart, and aortic tissues. The blood pressure levels of the hypertension group significantly increased compared to the control group. Administration of myrtle leaf extract and ramipril significantly decreased the increased blood pressure. In the hypertension group, oxidative damage increased in the kidney, heart, and aorta tissues. In the histological evaluation of tissues in RVH, heart muscle fibres degenerated. Bowman capsule and glomeruli dilated and tubules damaged in the kidney. Myrtle leaf extract administration regenerated the damages and degenerations. The administration of myrtle leaf extract restored the impaired oxidant-antioxidant balance in the heart, kidney and aorta tissues of hypertensive rats. Myrtle leaf extract can be considered as an alternative antihypertensive treatment target in the prevention of oxidative stress-induced damage in renovascular hypertension.

Acute stroke is associated with high morbidity and mortality. In the last decades, new therapies have been investigated with the aim of improving clinical outcomes in the acute phase post stroke onset. However, despite such advances, a large number of patients do not demonstrate improvement, furthermore, some unfortunately deteriorate. Thus, there is a need for additional treatments targeted to the individual patient. A potential therapeutic target is interventions to optimize cerebral perfusion guided by cerebral hemodynamic parameters such as dynamic cerebral autoregulation (dCA). This narrative led to the development of the INFOMATAS (Identifying New targets FOr Management And Therapy in Acute Stroke) project, designed to foster interventions directed towards understanding and improving hemodynamic aspects of the cerebral circulation in acute cerebrovascular disease states. This comprehensive review aims to summarize relevant studies on assessing dCA in patients suffering acute ischemic stroke, intracerebral haemorrhage, and subarachnoid haemorrhage. The review will provide to the reader the most consistent findings, the inconsistent findings which still need to be explored further and discuss the main limitations of these studies. This will allow for the creation of a research agenda for the use of bedside dCA information for prognostication and targeted perfusion interventions.

Objectives Excessive left ventricular mass (LVM) results in inefficient LV work with energy waste leading to a negative prognostic effect. We aimed at investigating the presence of inappropriate LVM and calculating the myocardial mechano-energetic efficiency index (MEEi) in former pre-eclamptic (PE) women (with or without HELLP syndrome) compared to women who experienced HELLP syndrome without PE. Study design: In this cross-sectional study, women with a history of normotensive HELLP (n=32), PE without HELLP (n=59), and PE with HELLP (n=101) underwent echocardiography as part of the clinical CV work-up after their complicated pregnancies from 6 months to 4 years postpartum. We excluded women with comorbidities, including chronic hypertension, hypercholesterolemia, and obesity. Main outcome measures: LVM excess was calculated as the ratio between observed LVM and predicted LVM (by sex, stroke work and height), while MEEi was considered as the ratio between stroke work and “double product” (to approximate energy consumption), indexed to LVM. Results LV hypertrophy was present in 8-14% and concentric remodeling in 31-42% of women, without intergroup difference. LVM was inappropriate in one-third of normotensive former HELLP and in about one-half of PE with or without HELLP, with no difference among groups. Accordingly, without nominal difference, MEEi showed a tendency towards lower values in former pre-eclamptic individuals. Conclusions Women with a history of HELLP syndrome, independently from the presence/absence of PE, showed inappropriate LVM in the first 4 years after delivery, which may partially explain the elevated CV risk in these women compared to the general female population.

Mortality in children with kidney failure is higher in girls than boys with cardiovascular complications representing the most common causes of death. Pulse wave velocity (PWV), a measure of vascular stiffness, predicts cardiovascular mortality in adults. Here, PWV in children with kidney failure undergoing kidney replacement therapy was investigated to determine sex differences and potential contributing factors. Two-hundred thirty-five children (80 girls; 34%) undergoing transplantation (150 pre-emptive, 85 with prior dialysis) having at least one PWV measurement pre-and/or post-transplantation from a prospective cohort were analyzed. Longitudinal analyses (median/maximum followup time of 6/9 years) were performed for PWV z-scores (PWVz) using linear mixed regression models and further stratified by the categories of time: pre-kidney replacement therapy and post-transplantation. PWVz significantly increased by 0.094 per year and was significantly higher in girls (PWVz + 0.295) compared to boys, independent of the underlying kidney disease. During pre-kidney replacement therapy, an average estimated GFR decline of 4 ml/min/1.73 m(2) per year was associated with a PWVz increase of 0.16 in girls only. Higher diastolic blood pressure and low density lipoprotein were independently associated with higher PWVz during pre-kidney replacement therapy in both sexes. In girls post-transplantation, an estimated GFR decline of 4ml/min/1.73m(2) per year pre-kidney replacement therapy and a longer time (over 12 months) to transplantation were significantly associated with higher PWVz of 0.22 and of 0.57, respectively. PWVz increased further after transplantation and was positively associated with time on dialysis and diastolic blood pressure in both sexes. Thus, our findings demonstrate that girls with advanced chronic kidney disease are more susceptible to develop vascular stiffening compared to boys, this difference persist after transplantation and might contribute to higher mortality rates seen in girls with kidney failure., German Federal Ministry of Education and Research [01EO0802]; European Renal Association -European Dialysis and Transplant Association; Roche Organ Transplant Research Foundation [365520785], This study was made possible by grants from the German Federal Ministry of Education and Research (#01EO0802), the European Renal Association -European Dialysis and Transplant Association (www.eraedta.org), and Roche Organ Transplant Research Foundation (#365520785). Several coauthors are members of the European Rare Kidney Disease Reference Network (ERKNet). This study has been presented as an abstract at the TTS (The Transplantation Society) 2020 Virtual Congress on September 14, 2020.

Introduction: Sleep-disordered breathing (SDB) is present in 21-74% of all patients with atrial fibrillation (AF). Treatment of SDB by positive airway pressure may help to prevent recurrence of AF after electrical cardioversion and help to improve AF ablation success rates in non-randomized studies.Areas covered: In this review, the current understanding of the atrial arrhythmogenic pathophysiology of SDB is summarized, and diagnostic and therapeutic challenges in AF patients are discussed. Current international recommendations are presented, and a comprehensive literature search is undertaken.Expert opinion: AF patients with SDB rarely report SDB-related symptoms such as daytime sleepiness. Therefore, systematic home sleep testing evaluation should be considered for all patients eligible for rhythm control strategy. A close interdisciplinary collaboration between the electrophysiologist/cardiologist, nurses and sleep-specialists are required for the management of SDB in AF patients. An arrhythmia-orientated assessment of SDB may better quantify SDB-related AF risk in an individual patient and may help to better guide targeted and personalized SDB treatment in AF patients as a component of rhythm and symptom control strategies. Finally, randomized controlled trials are needed to confirm the relationship between SDB and AF, and the benefits of routine testing and treatment of SDB in AF patients.

The opinion on the mechanisms underlying the pathogenesis of preeclampsia still divides scientists and clinicians. This common complication of pregnancy has long been viewed as a disorder linked primarily to placental dysfunction, which is caused by abnormal trophoblast invasion, however, evidence from the previous two decades has triggered and supported a major shift in viewing preeclampsia as a condition that is caused by inherent maternal cardiovascular dysfunction, perhaps entirely independent of the placenta. In fact, abnormalities in the arterial and cardiac functions are evident from the early subclinical stages of preeclampsia and even before conception. Moving away from simply observing the peripheral blood pressure changes, studies on the central hemodynamics reveal two different mechanisms of cardiovascular dysfunction thought to be reflective of the early-onset and late-onset phenotypes of preeclampsia. More recent evidence identified that the underlying cardiovascular dysfunction in these phenotypes can be categorized according to the presence of coexisting fetal growth restriction instead of according to the gestational period at onset, the former being far more common at early gestational ages. The purpose of this review is to summarize the hemodynamic research observations for the two phenotypes of preeclampsia. We delineate the physiological hemodynamic changes that occur in normal pregnancy and those that are observed with the pathologic processes associated with preeclampsia. From this, we propose how the two phenotypes of preeclampsia could be managed to mitigate or redress the hemodynamic dysfunction, and we consider the implications for future research based on the current evidence. Maternal hemodynamic modifications throughout pregnancy can be recorded with simple-to-use, noninvasive devices in obstetrical settings, which require only basic training. This review includes a brief overview of the methodologies and techniques used to study hemodynamics and arterial function, specifically the noninvasive techniques that have been utilized in preeclampsia research.

Introduction: Sleep-disordered breathing (SDB) is present in 21–74% of all patients with atrial fibrillation (AF). Treatment of SDB by positive airway pressure may help to prevent recurrence of AF after electrical cardioversion and help to improve AF ablation success rates in non-randomized studies. Areas covered: In this review, the current understanding of the atrial arrhythmogenic pathophysiology of SDB is summarized, and diagnostic and therapeutic challenges in AF patients are discussed. Current international recommendations are presented, and a comprehensive literature search is undertaken. Expert opinion: AF patients with SDB rarely report SDB-related symptoms such as daytime sleepiness. Therefore, systematic home sleep testing evaluation should be considered for all patients eligible for rhythm control strategy. A close interdisciplinary collaboration between the electrophysiologist/cardiologist, nurses and sleep-specialists are required for the management of SDB in AF patients. An arrhythmia-orientated assessment of SDB may better quantify SDB-related AF risk in an individual patient and may help to better guide targeted and personalized SDB treatment in AF patients as a component of rhythm and symptom control strategies. Finally, randomized controlled trials are needed to confirm the relationship between SDB and AF, and the benefits of routine testing and treatment of SDB in AF patients.

Background Post-transplantation diabetes mellitus (PTDM) is a major clinical problem in kidney transplant recipients (KTRs). Diuretic-induced hyperglycaemia and diabetes have been described in the general population. We aimed to investigate whether diuretics also increase PTDM risk in KTRs. Methods We included 486 stable outpatient KTRs (with a functioning graft ≥1 year) without diabetes from a prospective cohort study. Participants were classified as diuretic users and non-users based on their medication use verified by medical records. Results At the baseline study, 168 (35%) KTRs used a diuretic (thiazide, n = 74; loop diuretic, n = 76; others, n = 18) and 318 KTRs did not use a diuretic. After 5.2 years [interquartile range (IQR) 4.0‒5.9] of follow up, 54 (11%) KTRs developed PTDM. In Cox regression analyses, diuretic use was associated with incident PTDM, independent of age, sex, fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) {hazard ratio [HR] 3.28 [95% confidence interval (CI) 1.84–5.83]; P Conclusions This study demonstrates that diuretics overall are associated with an increased risk of developing PTDM in KTRs, independent of established risk factors for PTDM development. The association was present for both thiazide and loop diuretics.

Introduction: Inflammation is highly prevalent among patients with end-stage kidney disease and is associated with adverse outcomes. We aimed to investigate longitudinal changes in inflammatory markers in a diverse international incident hemodialysis patient population.Methods: The MONitoring Dialysis Outcomes (MONDO) Consortium encompasses hemodialysis data-bases from 31 countries in Europe, North America, South America, and Asia. The MONDO database was queried for inflammatory markers (total white blood cell count [WBC], neutrophil count, lymphocyte count, serum albumin, and C-reactive protein [CRP]) and hemoglobin levels in incident hemodialysis patients. Laboratory parameters were measured every month. Patients were stratified by survival time (#6 months, >6 to 12 months, >12 to 18 months, >18 to 24 months, >24 to 30 months, >30 to 36 months, and >36 months) following dialysis initiation. We used cubic B-spline basis function to evaluate temporal changes in inflammatory parameters in relationship with patient survival. Results: We studied 18,726 incident hemodialysis patients. Their age at dialysis initiation was 71.3 +/- 11.9 years; 10,802 (58%) were males. Within the first 6 months, 2068 (11%) patients died, and 12,295 patients (67%) survived >36 months (survivor cohort). Hemodialysis patients who died showed a distinct biphasic pattern of change in inflammatory markers where an initial decline of inflammation was followed by a rapid rise that was consistently evident approximately 6 months before death. This pattern was similar in all patients who died and was consistent across the survival time intervals. In contrast, in the survivor cohort, we observed initial decline of inflammation followed by sustained low levels of inflammatory biomarkers.Conclusion: Our international study of incident hemodialysis patients highlights a temporal relationship between serial measurements of inflammatory markers and patient survival. This finding may inform the development of prognostic models, such as the integration of dynamic changes in inflammatory markers for individual risk profiling and guiding preventive and therapeutic interventions.

l-Citrulline may improve non-invasive vascular function and cardiometabolic risk markers through increases in l-arginine bioavailability and nitric oxide synthesis. A meta-analysis of randomised controlled trials (RCT) was performed to examine longer-term and postprandial effects of l-citrulline supplementation and watermelon consumption on these markers for CVD in adults. Summary estimates of weighted mean differences in vascular function and cardiometabolic risk markers with accompanying 95 % CI were calculated using random or fixed-effect meta-analyses. Seventeen RCT were included involving an l-citrulline intervention, of which six studied postprandial and twelve longer-term effects. Five studies investigated longer-term effects of watermelon consumption and five assessed effects during the postprandial phase. Longer-term l-citrulline supplementation improved brachial artery flow-mediated vasodilation (FMD) by 0·9 %-point (95 % CI 0·7, 1·1, P < 0·001). Longer-term watermelon consumption improved pulse wave velocity by 0·9 m/s (95 % CI 0·1, 1·5, P < 0·001), while effects on FMD were not studied. No postprandial effects on vascular function markers were found. Postprandial glucose concentrations decreased by 0·6 mmol/l (95 % CI 0·4, 0·7, P < 0·001) following watermelon consumption, but no other longer-term or postprandial effects were observed on cardiometabolic risk markers. To conclude, longer-term l-citrulline supplementation and watermelon consumption may improve vascular function, suggesting a potential mechanism by which increased l-citrulline intake beneficially affects cardiovascular health outcomes in adults. No effects on postprandial vascular function markers were found, while more research is needed to investigate the effects of l-citrulline and watermelon on risk markers related to cardiometabolic health.

Chronic kidney disease (CKD) is becoming one of the world’s most prevalent noncommunicable chronic diseases. The World Health Organization projects CKD to become the 5th most common chronic disease in 2040. Causes of CKD are multifactorial and diverse, but early-stage symptoms are often few and silent. Progression rates are highly variable, but patients encounter both an increased risk for end-stage kidney disease (ESKD) as well as increased cardiovascular risk. End-stage kidney disease incidence is generally low, but every single case carries a significant burden of illness and healthcare costs, making prevention by early intervention both desirable and worthwhile. This review focuses on the prevalence, diagnosis, and causes of CKD. In addition, we discuss the developments in the general treatment of CKD, with particular attention to what can be initiated in general practice. With the addition of recent landmark findings and the expansion of the indication for using sodium–glucose cotransporter 2 inhibitors, there are now new effective treatments to add to standard therapy. This will also be relevant for primary care physicians as many patients with CKD have their family physician as their primary health care professional handling kidney function preservation. In the future, more precise and less invasive diagnostic methods may not only improve the determination of the underlying cause of CKD but may also carry information regarding which treatment to use (i.e. personalized medicine). This could lead to a reduced number of preventive treatments per individual, while at the same time improving the prognosis. This review summarizes ongoing efforts in this area.

Background: Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity. Methods: Using a high-throughput array platform for DNA methylome profiling, we conducted a case-control epigenome-wide association study on early-life exposure to Chinese famine in 79 adults born during 1959–1961 and compared to 105 unexposed subjects born 1963–1964. Results: The single CpG site analysis of whole epigenome revealed a predominant pattern of decreased DNA methylation levels associated with fetal exposure to famine. Four CpG sites were detected with p < 1e-06 (linked to EHMT1, CNR1, UBXN7 and ESM1 genes), 16 CpGs detected with 1e-06 < p < 1e-05 and 157 CpGs with 1e-05 < p < 1e-04, with a predominant pattern of hypomethylation. Functional annotation to genes and their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders and metabolism. Multiple sites analysis detected two top-rank differentially methylated regions harboring RNF39 on chromosome 6 and PTPRN2 on chromosome 7, both showing epigenetic association with stress-related conditions. Conclusion: Early-life exposure to famine could mediate DNA methylation regulations that persist into adulthood with broad impacts in the activities of genes and biological pathways. Results from this study provide new clues to the epigenetic embedding of early-life adversity and its impacts on adult health.

Pulse wave velocity, a common metric of arterial stiffness, is an established predictor for cardiovascular events and mortality. However, its intrinsic pressure-dependency complicates the discrimination of acute and chronic impacts of increased blood pressure on arterial stiffness. Cardio-ankle vascular index (CAVI) represented a significant step towards the development of a pressure-independent arterial stiffness metric. However, some potential limitations of CAVI might render this arterial stiffness metric less pressure-independent than originally thought. For this reason, we later introduced CAVI(0). Nevertheless, advantages of one approach over the other are left debated. This review aims to shed light on the pressure (in)dependency of both CAVI and CAVI(0). By critically reviewing results from studies reporting both CAVI and CAVI(0) and using simple analytical methods, we show that CAVI(0) may enhance the pressure-independent assessment of arterial stiffness, especially in the presence of large inter-individual differences in blood pressure.

CIBERDEM (Ministerio de Economía, Industria y Competitividad-ISCIII), Ministerio de Sanidad, Servicios Sociales e Igualdad-ISCIII, Instituto de Salud Carlos III (PI17/02136, PI20/01322), European Regional Development Fund (ERDF) “A way to build Europe”. Ayudas a la investigación SED 2020., Doulatram-Gamgaram, V., Valdés, S., Maldonado-Araque, C., Lago-Sampedro, A., Badía-Guillén, R., García-Escobar, E., García-Serrano, S., García-Vivanco, M., Garrido, J.L., Theobald, M.R., Gil, V., Martín-Llorente, F., Calle-Pascual, A., Bordiu, E., Castaño, L., Delgado, E., Franch-Nadal, J., Chaves, F.J., Montanya, E., Galán-García, J.L., Aguilera-Venegas, G., Soriguer, F., Rojo-Martínez, G.

Skeletal muscle mass losses with age are associated with negative health consequences, including an increased risk of developing metabolic disease and the loss of independence. Athletes adopt numerous nutritional strategies to maximize the benefits of exercise training and enhance recovery in pursuit of improving skeletal muscle quality, mass, or function. Importantly, many of the principles applied to enhance skeletal muscle health in athletes may be applicable to support active aging and prevent sarcopenia in the healthy (non-clinical) aging population. Here, we discuss the anabolic properties of protein supplementation in addition to ingredients that may enhance the anabolic effects of protein (e.g. omega 3 s, creatine, inorganic nitrate) in older persons. We conclude that nutritional strategies used in pursuit of performance enhancement in athletes are often applicable to improve skeletal muscle health in the healthy older population when implemented as part of a healthy active lifestyle. Further research is required to elucidate the mechanisms by which these nutrients may induce favourable changes in skeletal muscle and to determine the appropriate dosing and timing of nutrient intakes to support active aging.

There is strong evidence that sex chromosomes and sex hormones influence blood pressure (BP) regulation, distribution of cardiovascular (CV) risk factors and co-morbidities differentially in females and males with essential arterial hypertension. The risk for CV disease increases at a lower BP level in females than in males, suggesting that sex-specific thresholds for diagnosis of hypertension may be reasonable. However, due to paucity of data, in particularly from specifically designed clinical trials, it is not yet known whether hypertension should be differently managed in females and males, including treatment goals and choice and dosages of antihypertensive drugs. Accordingly, this consensus document was conceived to provide a comprehensive overview of current knowledge on sex differences in essential hypertension including BP development over the life course, development of hypertension, pathophysiologic mechanisms regulating BP, interaction of BP with CV risk factors and co-morbidities, hypertension-mediated organ damage in the heart and the arteries, impact on incident CV disease, and differences in the effect of antihypertensive treatment. The consensus document also highlights areas where focused research is needed to advance sex-specific prevention and management of hypertension. ispartof: EUROPEAN HEART JOURNAL vol:43 issue:46 pages:4777-4788 ispartof: location:England status: published

BackgroundSystemic hypoperfusion plays a pivotal role in the pathogenesis of primary open-angle glaucoma (POAG). Extreme dips in mean arterial pressure (MAP) due to high 24-h variability are associated with POAG, however, whether this is driven by diurnal or nocturnal dips remains undocumented. We aimed this study to investigate the association of POAG damage with variability and dips in the diurnal and nocturnal MAP.MethodsWe conducted a retrospective longitudinal study that included 110 POAG patients who underwent 24-h ambulatory blood pressure monitoring. Our outcomes included (i) functional [visual field defects expressed as mean deviation (MD)] and (ii) structural (optic disc cupping obtained from cup-to-disc ratio) glaucoma damage. MAP variability independent of the mean (VIMmap) was computed for diurnal and nocturnal MAP. Dips were the five diurnal and three nocturnal lowest drops in MAP. We also calculated the night-to-day ratio. We applied mixed models to evaluate the progression of visual field defects and optic disc cupping in relation to diurnal and nocturnal MAP measures.ResultsThe mean age was 64.0 y (53% women). The median follow-up was 9 years. In adjusted mixed models, functional progression of glaucoma damage was associated with VIMmap (−2.57 dB change in MD per every 3 mmHg increase in VIMmap; P < 0.001) and diurnal MAP dips (changes in the MD ranged from −2.56 to −3.19 dB; P < 0.001). Every 5 mmHg decrease in the nocturnal MAP level was associated with −1.14 dB changes in MD [95% confidence interval (CI), −1.90 to −0.40] and 0.01 larger optic disc cupping (95% CI, 0.01–0.02). Lower night-to-day ratio was also related to both outcomes (P ≤ 0.012). Functional glaucoma damage worsened if nocturnal hypotension was combined with high variability or extreme dips in the diurnal MAP (P ≤ 0.022).ConclusionProgression of glaucoma damage in POAG associates with high variability and extreme dips in the diurnal MAP. Structural glaucoma damage seems more vulnerable to nocturnal hypotension. Ambulatory blood pressure monitoring allows the assessment of sporadic diurnal and persistent nocturnal hypotension episodes. These phenotypes might offer an opportunity to improve the risk-stratification of open-angle glaucoma (OAG).