Predictions of hypertension were obtained using a logistic regression model, and predictions of LVMI were performed using regression models including (a) the wake systolic and diastolic BP indices, or (b) additionally including the standard deviation (SD) of wake SBP and DBP.R2 = 0.04). Among the individual variables studied, none were statistically significant. For prediction of LVMI, the SD of wake SBP and DBP were significantly associated with increased LVMI, but the wake SBP and DBP indices were not.With the change in 2022 to new ABPM guidelines from the AHA, comparing the old and new guidelines led to 70% of previous pre-hypertensive diagnoses now meeting criteria for diagnosis of hypertension, and a rise from 21% of the ABPMs meeting criteria for hypertension to 51% now meeting criteria. In a logistic regression model, prior patient data were not predictive of a diagnosis of hypertension from ABPM (Nagelkerke's In our patient population, the new ABPM guidelines led to a significant increase in diagnoses of hypertension. Prior patient data was not sufficient to predict a diagnosis of hypertension by ABPM, supporting the need for evaluation by ABPM as the gold standard. Our analysis of the relationship between ABPM readings and LVMI supports the hypothesis that BP variability contributes to increased LVMI. These data are consistent with growing evidence in the adult literature that BP variability detected by ABPM is associated with left-ventricular hypertrophy Cardiovascular disease is the leading cause of death worldwide and accounts for 1 in 3 deaths in the United States , 3. It iAAP CPG recommends ABPM should be performed to confirm the diagnosis of hypertension for patients with elevated BP for 1 year or more and patients with stage-1 HTN over 3 clinic visits. ABPM is more reliable and reproducible than clinic BP readings for the diagnosis of hypertension . SeveralThe main purpose of BP diagnostics is to establish effective control to prevent the development of target organ damage. Left-ventricular hypertrophy (LVH) is a marker of target organ damage associated with hypertension and is an independent risk factor for cardiovascular morbidity and mortality in adults. Because the incidence of cardiovascular disease (CVD) in children and adolescents is low, LVH is used a surrogate marker for the risk of CVD in children. Previous studies have found that the BP data from ABPM could predict LVH better than clinic BP readings , and incOther studies suggest that BP variability (BPV) may play a key role in LVH and decreased LV function –14. BPV In the present study, we collected data from the patients who were referred to our pediatric nephrology clinic at University Hospital System and the University of Texas Health Sciences Center at San Antonio for elevated blood pressure and underwent ABPM from 2015 to 2018.The goals of this study were to (1) Determine the effects of changes in the guidelines on ABPM diagnoses. (2) Determine whether findings of hypertension from 24-hour ABPM could be predicted from prior patient data, and (3) Determine whether ABPM data including the wake and sleep mean BP and BPV could predict left ventricular mass index (LVMI) in patients who obtained an echocardiogram (ECHO).This is a retrospective chart review. The patients enrolled were seen in our pediatric nephrology clinic for elevated blood pressure or hypertension and underwent a 24-hour ABPM from February 2015 to August 2018. Clinical data, including demographics, clinical presentation, medical history, comorbidities, ABPM results, family history, and laboratory values were obtained by chart review. Exclusion criteria included taking anti-hypertensive medications on initial ABPM and the following co-morbidities: chronic kidney disease, solid organ transplant, bone marrow transplant, congenital heart disease, malignancy, diabetes, and obstructive sleep apnea.The Space Labs 90217 monitor , validated in children, was used for all ABPM. The non-dominant arm was used, and patients were encouraged to attend school but avoid vigorous activity. Awake and sleep times were set according to patient report, and ABPM readings were taken every 20 min in the daytime and every 30 min at night. The adequacy of the ABPM study was determined by the interpreting physician at the time of ABPM evaluation according to AHA criteria, and the data were interpreted using American Heart Association (AHA) guidelines . RetrospThe office BP readings were taken when ABPM was placed in clinic. These readings were evaluated based on 2017 AAP clinical practice guidelines . BP percThe initial diagnosis of the ABPM study was done by 2014 AHA ABPM guidelines . Briefly2.7) to obtain the LVMI. LVMI was normalized by age-specific 95th percentile thresholds  was calculated by the Devereux et al. method . The lefresholds . LVH wasrcentile  for all https://www.jamovi.org.)Potential predictors of the binary outcome variable hypertension were analyzed individually using univariable logistic regression and simultaneously using multivariable logistic regression. The statistical significance of the effect of each predictor was evaluated by Wald tests, and the magnitude of the effect was expressed as the odds ratio and its 95% confidence limits. Potential predictors of LVMI were analyzed individually and simultaneously by linear regression, which was performed separately for index variables only and for index and SD variables together; the two different models were compared with ANOVA. All statistical analyses were conducted using R implemented in jamovi Version 2.3  failed ABPM. The average number of readings was 52, 69% of the readings were successful, and the average number of hours was 24. R2 = 0.04; χ2 = 6.56, df = 7, p = 0.47). Among the individual predictor variables, only male gender neared statistical significance (p = 0.09). Obesity and the family history of hypertension were not associated with hypertension in our cohort, although previous studies have found an association  of 11.0 g/m2.7. Fourteen of the 40 subjects were found to have LVH based on LVMI > 95th percentile . Their LVMI values varied between 25.0 and 79.7 g/m2R for Model 2 (0.2250) was higher than the value for Model 1 (0.0943), but the difference was not significant . However, univariable analyses showed that both the systolic SD and the diastolic SD were significantly associated with LVMI ), but the index variables were not  (2.7) vs. 38.50 ± 7.95 (g/m2.7), respectively.For our analysis, the LVMI value normalized by the 95th percentile  was used= 0.225) . LVMI diOur study presents data from a large cohort of children who were referred for elevated blood pressure to a single pediatric nephrology clinic and underwent ABPM. With the revised classification of ABPM in 2022 by the AHA, we found a significant increase in diagnoses of hypertension, including children previously diagnosed as either normal or pre-hypertension. This is expected, given lower thresholds for mean awake BP and mean sleep BP readings, particularly in tall males. This was found in our cohort. 70 percent of previously pre-hypertensive subjects were found to be hypertensive by 2022 ABPM guidelines, and 30 percent were found to be normotensive. These pre-HTN to normotensive subjects included a larger percentage of females and were shorter than the pre-HTN to hypertensive subjects.The study was focused on subjects without co-morbidities to identify primary hypertension and estimate the risk of target organ damage with the new ABPM criteria. Our results showed that the presence of sustained hypertension was not predicted by the patient data available prior to ABPM. We found that clinic BP readings were poorly correlated with the diagnosis of hypertension. All subjects were referred for elevated BP on multiple visits in clinic, but only 21% were found to have hypertension by ABPM at the time of diagnosis. Even under the new guidelines, only 51% were found to be hypertensive. Almost half of the subjects were found to have white-coat hypertension, which is consistent with other studies –24. Davi2.7, predicts a 3.3 times higher risk of a CV event (Why do clinic BP readings fail to predict the results of ABPM? One reason is that clinic BP data are seldom obtained in the recommended manner prior to referral for ABPM. Rea et al. found that only 2% of patients had followed the recommended steps from the 2017 AAP CPG for assessment of clinic BP readings, only 10% had a follow-up appointment, and 2% had recommended lab tests . ABPM isCV event . Our stuCV event , 30. BP CV event , 13, 31.CV event . Richey CV event . FurtherCV event . In combThe majority of our subjects with LVH were overweight or obese, and the total number of subjects was limited. For these reasons, the data were not sufficient to determine the relative effects of overweight/obesity vs. hypertension on LVMI. Previous studies showed that obesity and hypertension were both independently associated with LVH in children , 33.Although the present study included a large number of ABPM recordings, they are all from a single center and reflect the standard practice at one institution, so generalizability may be limited, and referral bias may be present. The demographics of our patient population were somewhat different from those of many other centers in the United States, including a majority of the subjects identifying as Hispanic/Latino. The diagnosis of OSA was excluded in this cohort. However, we did not screen all patients for OSA, and there is a potential for undiagnosed OSA in this population.We only used one office BP reading in this cohort, and the majority of the readings were obtained using oscillometric devices. Although auscultatory measurement is the gold standard, our clinic was not set up specifically for pediatric nephrology, and BP was not usually measured by auscultation. We did have previous blood pressure readings from prior to referral. However, the time differences between these were variable, and in many cases lifestyle modifications may have been initiated by the PCP while the subject was awaiting further evaluation. Also, we were unable to track how these previous BP readings were obtained, so these data appeared of limited value for our study. Echocardiograms were obtained by provider's discretion, not by a protocol or criteria, as most of the data were collected before the 2017 AAP Pediatric HTN guidelines, and the number of echo studies was limited. These factors may have limited our ability to discern the relationships between prior clinical data and the ABPM diagnosis, and between the ABPM data and LVMI.In our patient population, with the implementation of the new AHA ABPM criteria in 2022 we saw a rise in total diagnoses of hypertension in our patient population, with the most dramatic change being previously pre-hypertensive patients joining the hypertensive category. Prior patient data were not sufficient to predict a diagnosis of hypertension from ABPM, supporting the need for evaluation by ABPM as the gold standard. Our analysis of the relationship between ABPM readings and LVMI supports the hypothesis that systolic BP variability contributes to increased LVMI. These data are consistent with growing evidence in the adult literature that BP variability detected by ABPM is associated with left ventricular hypertrophy.


TRIB3 is closely related to insulin resistance, metabolic disorders and vascular diseases. Recently, it was reported that a 33 bp variable number of tandem repeats (VNTR) located in the TRIB3 promoter could considerably alter its transcriptional activity. Nonetheless, whether the shift of TRIB3 transcriptional activity has the effect of inducing diabetic vascular complications is still unclear. Therefore, in our study, we aimed to explore the relationship between the TRIB3 33bp VNTR and diabetic vascular complications. The TRIB3 33bp VNTR polymorphisms were determined by PCR and Sanger sequencing, a total of 798 eligible Chinese patients with type 2 diabetes (T2DM) were included in our study and then evaluated with clinical data. After adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes, we found that the high number of 33 bp tandem repeats (repeats>8) was significantly associated with an increase in the risk of cerebrovascular diseases compared with the low number of 33 bp tandem repeats (repeats≤6) in patients with T2DM. The intermediate number of 33bp tandem repeats (6 < repeat≤8) was markedly associated with a decreased risk of diabetic retinopathy compared with the low number of tandem repeats . Adjusting for gender, age and BMI, there was a significant difference in DBP levels among patients with the number of different 33 bp tandem repeats . Subgroup analysis found that TRIB3 VNTR was significantly correlated with the difference in systolic blood pressure (SBP) in T2DM patients taking ACEI/ARB drugs . Our results indicated that TRIB3 promoter 33bp VNTR is related to vascular diseases in T2DM patients, and may serve as a new biomarker for individualized prevention and therapy of T2DM.Previous studies have demonstrated that  Diabetes is a chronic disease caused by the interaction of genetic and environmental factors. According to the latest data on diabetes worldwide released by the IDF , from 20P1 allele of the IL-4 VNTR polymorphism were more likely to suffer from diabetic peripheral neuropathy , cardiovascular diseases in patients with diabetes predominantly include atherosclerotic cardiovascular disease (ASCVD) and heart failure . Diabeti2)) in T2DM patients without other factors causing kidney damage , triglyceride, total cholesterol, HDL-cholesterol, LDL-cholesterol. Disease histories include drinking history, smoking history, cerebrovascular history, cardiovascular history and macrovascular history. In addition, the use of insulin, insulin sensitizer, β-receptor blockers, α-glucosidase inhibitor, biguanides, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists, lipid-lowering drugs, calcium channel blockers, ACEI/ARB drugs and calcium dobesilate were also recorded. Among them, blood pressure, blood glucose, triglycerides, total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were regarded as important indicators. This study design was approved by the ethics committee in the Institute of clinical pharmacology, Central South University, and has been registered . The outline of the study protocol can be seen in This study was a retrospective study of T2DM patients in the Second Xiangya Hospital Affiliated to Central South University from 2017 to 2019. Subjects exclusion criteria were: patients who did not provide a blood sample, those who were not diagnosed with type 2 diabetes, those who refused to receive informed consent, and those who could not be genotyped in the TRIB3 promoter 33bp VNTR was genotyped. The template DNA concentration in each sample was detected by Nanodrop 2000 and then amplified by polymerase chain reaction. The reaction system included template DNA 1 μL, each 1 μL of 10 μM forward and reverse primers, High fidelity enzyme MIX 10 μL, ddH2O 7 μL, The final volume was 20 μL.Primer information: the forward primer sequence is 3′-GAGTCCGTGGCTGATGTCT-5′, and the reverse primer sequence is 3′-TACCTCGCCCCGTCGTTC-5’. The PCR reaction started at 94 °C for 5 min to denature the double-stranded DNA, followed by 35 consecutive cycles according to the three steps of denaturation at 94°C for 30s, annealing at 58°C for 30s and extension at 72°C for 30s, and finally extended at 72°C for 5 min. The length of the PCR products was shown in TRIB3 33bp tandem repeats in both alleles of participants , and then stored at -80°C.Next, the icipants .TRIB3 33bp tandem repeats in the sequencing results, combined with the results of previous studies on transcriptional activity, we divided patients into three groups based on the total number of TRIB3 33bp tandem repeats in both alleles: low number of 33bp tandem repeats (repeats≤6), intermediate number of 33bp tandem repeats (6 < repeats≤8) and high number of 33bp tandem repeats (repeats>8).According to the genotype frequency of the number of TRIB3 promoter 33bp VNTR and common complications of T2DM, logistic regression analysis was used to calculate the odds ratio (OR) and 95% confidence interval (CI) adjusting for age, gender, BMI, smoking history, drinking history and duration of diabetes. Effect size is obtained by estimating effect size in one-way ANOVA. In addition, the picture was made by the GraphPad Prism 8 program. p < 0.05 was regarded as significant results.We calculated the sample size using sample size calculations software (Version 3.0.43) based on gene frequencies and cardiovascular event rates. The experimental data were statistically analyzed by the IBM SPSS statistics 20 program, and the results were output by five statistical methods: t-test, cross table, chi-square test, one-way ANOVA and multinomial logistic regression analysis. When calculating the mean and standard deviation of the research results, it was corrected by adding gender, age and BMI to the covariates. In order to explore the relationship between TRIB3 33bp tandem repeats in each patient was measured to evaluate the relationship between TRIB3 promoter 33bp VNTR and the clinical characteristics of subjects. The average age of participants was 58.3 years, and the standard deviation was 11.6. In the history of smoking, the proportion of patients with smoking behavior and repeats≤6 accounted for 36.3%, the proportion of patients with 6 < repeats≤8 accounted for 35.6%, and the proportion of patients with repeats>8 accounted for 43.6%. Similarly, in the drinking history, subjects with low number of 33bp tandem repeats (repeats≤6) accounted for 32.6%, subjects with intermediate number of 33bp tandem repeats (6 < repeats≤8) accounted for 29.8%, and subjects with high number of 33bp tandem repeats (repeats>8)accounted for 27.3%. The disease histories of subjects showed that patients with repeats≤6 suffered from cerebrovascular disease and cardiovascular disease, accounting for 8.10 and 13.7% respectively, 12.2 and 8.3% of patients with repeats>6,≤8 suffered from cardiovascular disease and cerebrovascular disease respectively, while the ratio of patients with repeats>8 suffering from cardiovascular and cerebrovascular disease was 11:7. The baseline clinical characteristics of subjects were shown in TRIB3 promoter were shown in In this study, the clinical characteristics of Chinese T2DM patients such as gender, age, smoking history and drinking history were recorded, and the number of TRIB3 promoter 33bp VNTR and common complications of T2DM. Related data was shown in TRIB3 promoter was significantly correlated with the risk of cerebrovascular disease and diabetic retinopathy. Among them, the high number of 33bp tandem repeats (repeats>8) markedly increased the risk of cerebrovascular disease compared with the low number of 33bp tandem repeats (repeats≤6) . The intermediate number of 33bp tandem repeats (6 < repeats≤8) is considerably associated with a decreased risk of diabetic retinopathy compared with the low number of 33bp tandem repeats . However, there were no significant correlations between this VNTR and diabetic nephropathy, diabetic foot, and central obesity.Type 2 diabetes has many complications, and patients with T2DM have a higher risk of complications. Therefore, we studied the relationship between TRIB3 promoter 33bp VNTR and subjects’ blood pressure, blood lipid and blood glucose. The study showed that the 33bp VNTR was related to the blood pressure of patients, and there was a significant difference in diastolic blood pressure among patients with the total number of diverse TRIB3 33bp tandem repeats (p = 0.045). The diastolic blood pressure of patients with repeats≤6 was 81.6 ± 12.8 mmHg, that of patients with 6 < repeats≤8 was 79.8 ± 12.4 mmHg, and that of patients with repeats>8 was 78.7 ± 12.6 mmHg. However, there were no significant differences in glycosylated hemoglobin, systolic blood pressure, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and fasting blood glucose among the total number of distinct 33bp tandem repeats , the imbalance of TRIB3 upregulation-mediated signaling in pulmonary artery endothelial cells played a role in the occurrence and development of HPH  significantly increased the risk of cerebrovascular disease in patients with type 2 diabetes. Given the previous study AA genotype carriers have a better antihypertensive effect than AG/GG genotype carriers in receiving CCBs drugs, and the levels of DBP and MAP in patients decreased significantly. In contrast, among patients taking ARBs, patients with TRIB3AG/GG genotype received better antihypertensive treatment compared with AA genotype, in which the diastolic blood pressure changed significantly (TRIB3 rs6037475 CC genotype was associated with a significant reduction in DBP levels with the extension of treatment time in patients treated with felodipine (TRIB3 gene mutation can affect the efficacy of antihypertensive drugs on patients. We found that the TRIB3 promoter 33bp VNTR is significantly correlated with the level of SBP in patients taking ACEI/ARB drugs, which suggested that this VNTR may be involved in the regulatory pathway of ACEI/ARB drugs.ficantly . In addilodipine . TherefoTRIB3 promoter 33bp VNTR was found to be significantly associated with cerebrovascular disease in our findings, surprisingly, this VNTR was not significantly correlated with cardiovascular disease. Moreover, when exploring whether TRIB3 VNTR affected the blood pressure of patients taking antihypertensive drugs, we only discovered that variable numbers of tandem repeats were significantly associated with the systolic blood pressure of patients treated with ACEI/ARB medications, but not CCBs and beta-blockers. This may be due to the mechanism of action of ACEI/ARB drugs being different from that of CCBs and β-blockers, and the VNTR may only act on related proteins or genes involved in the activation pathway of ACEI/ARB drugs (The diabetic macrovascular disease includes cardiovascular disease, cerebrovascular disease, and peripheral arterial disease, all of which share similar pathogenesis and risk factors. Although the RB drugs .TRIB3 promoter 33bp VNTR was associated with T2DM complicated with cerebrovascular diseases and diabetic retinopathy, which means that this variable number of tandem repeats in TRIB3 promoter may be a new target for predicting T2DM patients with a high risk of vascular diseases in the future. So it has a certain reference value in individualized medication. Our research is a preliminary exploration. Further research is warranted to confirm whether TRIB3 VNTR affects blood pressure, the risk of diabetic cerebrovascular disease and diabetic retinopathy and its involvement in the ACEI/ARB pathway.Our exploratory study found that


Cirrhosis causes alterations in the cardiovascular and autonomic nervous systems and leads to cirrhotic cardiomyopathy (CCM). CCM is defined as cardiac dysfunction characterized by an impaired systolic responsiveness to stress or exercise, and/or impaired diastolic function, as well as electrophysiological abnormalities, including chronotropic incompetence (CI), in the absence of other known cardiac disease. CI is a common feature of autonomic neuropathy in cirrhosis. The aim of the study is to assess the role of cardiac exercise stress test in the diagnosis of CCM.The analysis included 160 end-stage liver disease (ESLD) patients who underwent a cardiac exercise stress test prior to the orthotopic liver transplantation. CI was defined as the inability to achieve the heart rate reserve (HRR). Pertaining to the therapy with beta-blockers: 80% of HRR was achieved in patients not taking beta-blockers and 62% in patients taking beta-blockers.In the analyzed population, 68.8% of patients met the criteria for CI. CI was more frequent in the more severe ESLD (with a higher MELD score and in a higher Child-Pugh class). In comparison to the viral hepatitis and other etiologies of ESLD, patients with alcoholic cirrhosis had a significantly lower rest heart rate (HR), lower maximal HR, lower median achieved percentage of maximal predicted HR (MPHR), a smaller percentage of patients achieved ≥ 85% of MPHR and a lower heart rate reserve. No significant relationship between the survival of OLT recipients and presence of chronotropic incompetence regarding to class of Child-Pugh scale, MELD score and etiology of ESLD were found.The prevalence of CI is higher among liver transplant candidates than previously described. The altered chronotropic response may differ in regard to the severity of liver disease correlating with both the Child-Pugh and MELD scores, however CI does not seem to influence the long-term survival post OLT. Exercise stress test is a reliable, safe and useful tool for the diagnosis of CCM in liver transplant candidates and should be included in the standard cardiovascular assessment prior to OLT. Cirrhosis leads to cardiac and circulatory dysfunctions due to splanchnic arterial vasodilation. Initially, deterioration of the hemodynamic function is compensated by the development of a hyperkinetic circulation. Furthermore, the progression of liver disease and portal hypertension leads to progressive vasodilatation, which reduces the effective arterial blood volume and results in the activation of the sympathetic nervous system as well as the renin-angiotensin-aldosterone system (RAAS). These circulatory disturbances can lead to the dilatation of the left cardiac chambers and the development of functional changes in the heart .In 2005 the World Gastroenterology Organization proposed a working definition of cirrhotic cardiomyopathy (CCM), which is defined as a cardiac dysfunction with impaired contractile responsiveness to stress and/or altered diastolic relaxation with electrophysiological abnormalities in the absence of other known cardiac disease , 4. It sEnd-stage liver disease (ESLD), regardless of the etiology, is a leading indication for orthotopic liver transplantation (OLT) , 5. In tThis single-center retrospective analysis included 160 patients  diagnosed with ESLD, who were consulted by a designated cardiologist in our center and who underwent the OLT . As partThe exercise stress test was performed according to the Bruce protocol where the speed and gradient of the treadmill were raised every 3 minutes. A standard 12-lead electrocardiogram was performed before, during and after the stress test until the recovery of the heart rate. Blood pressure was measured before, every 3 minutes during the exercise test and after the recovery. The exercise tests were terminated due to the fatigue, chest pain, dyspnea, achievement of maximal predicted heart rate (MPHR) or on patient demand. Beta-blockers were not withdrawn prior to the exercise test.Blood samples were collected on the same day as the exercise stress test, for the calculation of the Model for End-Stage Liver Disease (MELD) score:The exercise stress test was diagnostic if the patient was able to achieve 85% of MPHR, which was calculated with a simple formula = 220—age. CI was defined as the inability to achieve the heart rate reserve (HRR). Pertaining to the therapy with beta-blockers: 80% of HRR was achieved in patients not taking beta-blockers and 62% in patients taking beta-blockers .Continuous variables of the baseline characteristics were summarized with mean values +/- SD for normally distributed variables and median values and interquartile range (IQR) for non-normally distributed variables. Frequencies and percentages were used for categorical variables. Comparisons were made using the chi-squared test for nominal variables. Unpaired t-tests were used for comparison of normally distributed continuous variables and the Mann-Whitney U-test for non-normally distributed data.The corresponding Kaplan–Meier curves for survival were also plotted and were compared using the log-rank test. Statistical significance for all analyses was determined as p<0.05. All analyses were carried out using the STATISTICA version 12 software.The mean age of the analyzed population was 49 ± 12.4 years old . The meaIn the study group, the mean duration of exercise was 396 ± 137 seconds. The median achieved metabolic equivalents of tasks (METs) were 7.95 (6.97–10.2), and the mean percentage of patients who achieved ≥7METs was 76.8%. Diminished physical capacity, defined as the achievement of 4 METs or less, was diagnosed in 1.25% of patients. No significant differences in the length of the exercise stress test and physical capacity parameters between classes and groups were observed in regards to the Child-Pugh classification and MELD scores. However, statistically significant differences in those parameters were observed between different etiologies of liver disease. Patients with alcoholic cirrhosis had significantly shorter time of exercise (360 (259–408) vs 389 (297–482) vs 436 (343–540), respectively, p = 0.02) and achieved lower METs scores (7.0 (5.5–8.2) vs 7.6 (6.9–10.2) vs 8.7 (7.0–10.2), respectively, p = 0.01) in comparison to the viral hepatitis and other etiologies. Moreover, the smallest percentage of patients suffering from alcoholic cirrhosis achieved ≥ 7 METs in the exercise test when compared to viral hepatitis or other etiologies .Patients diagnosed with encephalopathy had a significantly shorter time of exercise (301 (221–398) vs. 410 (304–540); p = 0.002), achieved lower METs (7.0 (5.5–8.0) vs. 8.2 (7.0–10.2); p = 0.008) and fewer of them achieved ≥ 7 METs during the exercise test .The chronotropic response of the analyzed population in regards to the severity and etiology of liver disease is presented in Tables Considerable differences in chronotropic response, depending on the MELD score, could also be observed . PatientChronotropic response differed significantly according to the etiology of ESLD . In compFurthermore, we noticed obvious consequences of beta-blocker usage, i.e. significantly lower rest HR, lower maximal HR, lower median achieved percentage of MPHR, lower percentage of patients who achieved ≥ 85% of MPHR and lower HRR. Moreover, chronotropic parameters differed significantly in regard to presence of CI . PatientThe Kaplan-Meier curves for survival of OLT recipients are plotted regarding to presence of CI and class of Child-Pugh scale , MELD scIn this study we report a relatively high prevalence of CI among liver transplant candidates, however it did not have a significant impact of their long-term survival post OLT , 7. The Several studies proposed the dobutamine stress echocardiographic examination (DSE) as a reliable method for the cardiovascular assessment of liver transplant candidates, which also enables the diagnosis of CI , 7. HoweThe pathophysiologic mechanisms of CI are associated with autonomic neuropathy , 11. In The prevalence of CI among liver transplant candidates seems to be higher than previously reported, but does not seem to influence the long-term survival after OLT. The altered chronotropic response may differ in regard to the severity of liver disease depending on both Child-Pugh and MELD scores. The exercise stress test is a reliable, safe and useful tool for the diagnosis of CCM in liver transplant candidates and should be included in the standard cardiovascular assessment prior to OLT. Diagnosis of CCM in patients qualified for liver transplantation will allow individual adaptations of the perioperative management and implementation of effective post-reperfusion prophylaxis and management of intraoperative hemodynamic disturbances by selecting appropriate pharmacological agents at adjusted doses, which will also prevent the excessive increase in blood pressure.Our study does not include information about the prevalence of PRS and in-hospital mortality of patients, due to the fact that there is no clear definition of PRS in the current literature, especially concerning the use of catecholamines prior to reperfusion. We are not able to confirm the exact percentage of patients with CCM, due to an unclear and unestablished definition. Moreover, data from the Cardiopulmonary Exercise Testing (CPET) and detailed analysis of the usage beta-blockers in that population of patients would add additional value to the study and should be concerned in further research on that topic.


BackgroundPressure ulcers (PUs) occur when the skin covering a weight-bearing part of the body is compressed for a long time between bone, any other part of the body, bed, chair, or any other hard surface. This study aimed to determine the prevalence of pressure ulcers at a tertiary care hospital in all specialty departments including COVID-19.MethodsA retrospective study was conducted at North West General Hospital and Research Center, Peshawar, Pakistan. After obtaining ethical approval, data were obtained from the hospital database from July 2020 to June 2021. The keywords “bed sore,” “pressure sore,” and “pressure ulcer” were used to search for relevant cases, and patient demographics, including age and gender, site of pressure ulcer, stage of pressure ulcer, whether the pressure ulcer was single or multiple, length of stay at the hospital, and specialty department, were collected.ResultsIn total, 99 patients met the inclusion criteria, of which 65 (65.7%) were males, while 34 (34.3%) were females. The age of the patients ranged from 15 to 92 years, with a mean age of 59.93 years. Of the patients, 87 (87.9%) had acquired only a single pressure ulcer. Stage 2 pressure ulcers were the most documented, making up 43.1% of the total cases reported, while stage 4 cases were only 3.3%. The sites most frequently affected by pressure ulcers were the gluteal and sacral regions, accounting for 34.4% and 30.3%, respectively. The incidence of pressure ulcers was the highest in the COVID-19 ward, i.e., 25.3%, followed by the neurosurgery ward with a 20.2% incidence.ConclusionPressure ulcers occur frequently in almost all the specialty departments of a healthcare setting, especially in COVID-19 and neurosurgery wards, and impose significant physical, psychological, and financial burdens. The prevention of pressure ulcers is the best approach to avert patients and their families from all the burdens associated with pressure ulcers. Pressure ulcers (PUs) previously known as decubitus ulcers and informally called bedsores are caused by intense and/or prolonged pressure or in combination with shear usually in areas of the body where there are bony prominences . They ocThe incidence of PUs in the United States and Canada is between 5% and 32% . In the Evidence-based studies to prevent and treat PUs have led us to design guidebooks, but unfortunately, they are not adequately used in clinical practices . One reaThis study is part of a patient safety and quality improvement project by the authors that compares the prevalence of pressure ulcers pre- and post-intervention using a pressure ulcer prevention tool from the Agency for Healthcare Research and Quality . The proStudy setting and designA retrospective survey was conducted at North West General Hospital and Research Center, Peshawar, Pakistan, to determine and compare the occurrence of pressure ulcers in the different specialty wards at the facility. The facility is a private sector tertiary care hospital that caters to the healthcare needs of more than 1000 patients daily. Patients are received from all over Pakistan, especially from the Khyber Pakhtunkhwa region and Afghanistan.Ethical approvalEthical approval for the study was granted by the Institutional Review and Ethics Board of North West General Hospital and Research Center after approval of the project proposal. The approval is registered under reference ID IREB/EAC/04 in the institution records.Inclusion and exclusion criteriaThose patients who were admitted to the facility in the past one year for at least three days and had acquired pressure ulcers during their stay ) were included in the study. Patients with incomplete data were excluded from the study.Data collection and analysisData were collected from the hospital database of the patients’ physicians and nursing notes at the Management and Information Section (MIS) of the facility. The keywords “bed sore,” “pressure sore,” and “pressure ulcer” were used to search for relevant cases, and patient demographics, including age and gender, site of PU, stage of PU, whether the PU was single or multiple, length of stay at the hospital, and specialty department, were collected. The data of 18,579 patients from July 2020 to June 2021 were obtained, of which 99 patients were identified who met the inclusion criteria. Eight such patients who were admitted to the Accident and Emergency department with existing PUs were excluded from the study. Multiple PUs were counted as separate cases in the stage and anatomical location variables only. Data were exported to SPSS version 21 , analyzed, and formatted into tables.After retrieving and reviewing the data collected, 99 patients were identified who met the inclusion criteria. Regarding gender, 65 (65.7%) patients were males, while 34 (34.3%) were females. The age of the patients ranged from 15 to 92 years, with a mean age of 59.93 years. Six (6%) patients were under the age of 30, 22 (22.2%) were between 30 and 50 years of age, the highest number of patients (43 (43.4%)) were in the age group of 51-70 years, and 28 (28.2%) were older than 70 years.A total of 122 cases of hospital-acquired pressure ulcers (HAPUs) were reported. Of the patients, 87 (87.9%) had acquired only a single PU. Stage 2 PUs were the most documented, making up 43.1% of the total cases reported, while stage 4 cases were only 3.3%. The sites most frequently affected by HAPUs, identified and documented by the attending physicians and nurses, were the gluteal and sacral regions, accounting for 34.4% and 30.3%, respectively. Conversely, the elbows and trochanters were the least affected of all the areas of the body, which were six cases (4.9%) each (Table The length of stay had an indirect relation to the number of patients. Thirty-three (33.3%) patients stayed at the hospital for less than 10 days; on the contrary, only 12 (12.1%) patients had a stay of longer than 40 days. The incidence of PUs was the highest in the COVID-19 ward, i.e., 25.3%, followed by the neurosurgery ward with 20.2% incidence. In contrast, the orthopedic ward had only one case of PU reported  in the facility and the shortage of staff in the COVID-19 ward may also have added to the incidence of PUs. The neurosurgery ward had the second most reported cases of PUs, which supports the findings of studies previously conducted on patients with spinal cord injury and other neurotrauma . The leaPUs remain a problem for all healthcare facilities, and because they can occur during short stays, prevention is very important. Studies show that reduced activity is the most significant risk factor for PUs ,22. OtheSpecific risk factors need to be determined in prospective studies. Rather than focusing on the treatment of PUs, which costs huge amounts, preventive measures should be encouraged and taught in all healthcare settings and the community. Certified wound care nurses should be hired or trained, who would implement the already introduced policies and pressure ulcer prevention protocols of the facility. PU care plans should be developed, and immobilized patients should be regularly assessed for the risk factors of PUs. The Wound, Ostomy, and Continence Nurses Society (WOCN) recommends minimizing/eliminating pressure, friction, and shear, regular positioning, prophylactic dressings in at-risk patients, and using incontinence skin barriers such as creams, ointments, and film-forming protectants in addition to optimum nutrition .This study has not taken into account the deep tissue pressure injuries of patients with COVID-19 that mostly occur while the patients are in the prone position. This is a limitation of the study, and prospective studies need to be conducted that will consider the aforementioned aspect of hospital-acquired pressure ulcers.This study on the prevalence of PUs leads us to the conclusion that PUs occur in all specialty departments of a healthcare setting, especially in COVID-19 and neurosurgery wards. PUs impose significant physical, psychological, and financial burdens not only on patients but also on their relatives and caregivers. Given the current evidence, the prevention of pressure ulcers by methods including repositioning, optimizing the nutrition, and moisturizing the skin seems the most appropriate approach to prevent patients and their families from all the burdens associated with pressure ulcers.


ABL was evaluated by liquid chromatography, mass spectrometry. ABL was significantly higher in patients vs. controls, mean (range): 1.7 (0.7–3) µmol/L vs. controls 0.6 (0.4–0.8) µmol/L (+180%) p < 0.001. While A1R and A2AR production did not differ in patients and controls, we found an over-production of A2BR in patients: 1.70  vs. controls = 1.03 (0.70–1.40), mean + 65% (p < 0.001). A2BR production with a cut off of 1.3 arbitrary units, gives a good sensitivity and specificity for the diagnosis. Production measurement of A2BR on monocytes and ABL could help in the diagnosis, especially in atypical or with poor symptoms.Fibromuscular dysplasia (FMD) is a non-inflammatory vascular disease that is characterized by unexplained systemic hypertension occurring in young people, associated with arterial stenosis, aneurysm rupture, intracranial/renal infarction, and stroke. Although the gold standard for the diagnosis remains catheter-angiography, biological markers would be helpful due to the delay from first symptom to diagnosis. Adenosine is an ATP derivative, that may be implicated in FMD pathophysiology. We hypothesized that changes in adenosine blood level (ABL) and production of adenosine receptors may be associated with FMD. Using peripheral blood mononuclear cells, we evaluated A Fibromuscular dysplasia (FMD) is an idiopathic systemic vascular disease, affecting mostly middle-aged women (mean age at diagnosis 46–53 years) and accounting for 10% to 20% of the cases of renal artery stenosis .High level of nuclei progesterone receptors in dysplasic renal arteries of FMD was reported, suggesting that progesterone may play a role in the disease and could partly explain the sex ratio . FinallyRecently a possible implication of the adenosinergic system has been advocated .Adenosine is a ubiquitous nucleoside that mainly comes from the dephosphorylation of ATP. While a part of adenosine metabolism is associated with the methionine cycle.Adenosine release occurs more particularly during ischemia, hypoxia, or inflammation ,12.1R, A2AR, A2BR, and A3R [1R leads mostly to vasoconstriction [2AR [2BR [V, KATP channels [1R can induce vasoconstriction via a direct (cAMP independent) effect and the activation a protein kinase C (PKC) [Adenosine strongly impacts the vascular tone via its 4 G-coupled membrane receptors named A and A3R . While ttriction , the vasion [2AR ,15 and A2AR [2BR . The vaschannels . Convers C (PKC) . It was  C (PKC) . The relIn FMD the vascular flow is disturbed in the affected areas notably with a decrease in renal perfusion, accounting for hypertension. Thus, the decrease in blood flow with a relative ischemia may activate the adenosinergic system to improve blood flow as it was described in coronary artery disease .We hypothesized that the adenosinergic system may be disturbed in this affection.The aim of this study was to evaluate adenosine blood level, and adenosine receptors production by FMD patient peripheral blood mononuclear cells (PBMC), these cells being a good model for the evaluation of the adenosinergic system in cardiovascular diseases ,21,22.Adult patients with multifocal FMD (diagnosed using CT scan or duplex ultrasound) were included according to current criteria ,3. ContrPatients aged between 18 to 80 years.Patients with multifocal FMD of a renal or cervical artery with typical aspect “ string of beads “ appearance.Patients willing to participate in the study.We included (between October 2020 and November 2021), 67 patients diagnosed with multifocal fibromuscular dysplasia (FMD group) in our center of competence for rare vascular diseases  and 40 controls. The patients included were all referred to our center of vascular medicine and arterial hypertension. Criteria were as follows:Subjects aged between 18 to 80 years.Subjects without history of personal or familial fibromuscular dysplasia.Subjects without story of cardiovascular disease or inflammatory process.Subjects free from medical treatment.Subjects willing to participate in the study.Patients less than 18 or more than 80 years of age.Renal failure with GFR < 30 mL/min.Pregnant women.Patients with symptomatic atheromatous cardiovascular disease.Patient with inflammatory or chronic disease.Patient with a history of cancer or active cancer.Patient refusing to participate in the study.Whole blood was collected using finger puncture followed by deposit of a drop of blood (20 μL) on a blotting paper (Whatman 903 protein saver cards™) and dried over night at room temperature to obtain dried blood spot. Then, the blot spots were stored at room ambiance in a dried room, until analysis. Adenosine dosages were carried out in series of 10 patients and 5 controls.The method has been previously described . BrieflyAfter extraction, adenosine concentration was measured by LC-MS/MS as previously described . Samples2AR expressed at the surface, mirrors that of A2AR associated with cardiovascular tissues [g, 30 min) within 2 h of collection. After centrifugation, mononuclear cells were collected from the plasma/Ficoll interface and washed twice with phosphate buffered solution. The cell pellet was stored at −80 °C until used for Western blot analysis.PBMCs were chosen because pharmacological profile of their A tissues ,21,22. P1R, A2AR, and A2BR expressions of PBMCs were determined by Western blot using Adonis, an agonist-like monoclonal antibody to human A2AR [1R , and a goat polyclonal antibody to human A2BR . PBMC pellets (0.25 × 106 cells) were solubilized using lysis buffer and sonication. Samples were then submitted to standard 12% polyacrylamide gel electrophoresis under reducing conditions before transferring to a polyvinylidene difluoride membrane. The filters were then incubated with Adonis (1 µg/mL) or A1R or A2BR antibodies (0.25 µg/mL). Blots were revealed by phosphatase alkaline-labeled antispecies as second antibodies and adapted colorimetric substrate. Each band corresponding to the adenosine receptors  was submitted to densitometry analysis using the Image J 1.42q software . Results were expressed in arbitrary units (AU), defined as the ratio of pixels generated by the adenosine receptor band to pixels generated by the background signal, as previously described [The procedure for Western blotting has been described ,26,27,28p-values < 0.05 were considered statistically significant. Quantitative and qualitative variables were compared using Mann–Whitney U tests, Chi-square test, or Fisher’s exact test, as appropriate. Qualitative variables were reported as median with minimal and maximal range (min-max range). Diagnostic test accuracy of adenosine blood level and A2AB receptor expression in PBMCs for fibromuscular dysplasia was assessed by receiver operating characteristic (ROC) curves and area under the receiver operating characteristic (AUROC). AUROC from 0.9 to 1 was considered as excellent accuracy, 0.8 to 0.9 as good, 0.7 to 0.8 as good, 0.6 to 0.7 as good, and <0.6 as insufficient. The Youden index was assessed for all point of ROC curves (sensitivity + specificity − 1) and the optimal threshold was determined by the maximum value of the Youden index. We hypothesized that a variation of at least 50% in ABL and receptor expression level will have physiological consequences. In this perspective, a number of 50–60 patients vs. 40 controls appears sufficient.Statistical analyses were performed using GraphPad Prism program version 8.4.3. All statistical tests were two-sided and p = 0.73) and sex ratio (p = 0.97).A total of 67 patients, mean age and range 55 (29–77) years, and 40 controls 56 (37–70) years were included. Clinical characteristics of patients are given in ABL was significantly higher in patients vs. controls see .n = 25) vs. no smokers (n = 42) 1.85 µM vs. 1.7 µM, p = 0.8.Finally, while smoking may alter nucleosides metabolism in vitro (29), no difference appeared when considering current smokers (1R or A2AR production in patients vs. controls: A1R (A.U.): Patients = 0.97 (0.78–1.20) vs. Controls = 0.90 (0.80–1.15) (p = 0.17). A2AR: Patients = 1.30 (0.90–1.80) vs. Controls = 1.29 (0.90–1.50) (p = 0.06);While no significant difference occurred concerning A2BR (A.U) production level compared with controls: 1.70 (0.90–2.40) vs. Controls = 1.03 (0.70–1.40), mean + 65% (p < 0.001) see Patients exhibit a higher AWhile cigarettes smoking may modify nucleotides metabolism , no diff1R: 0.9 AU vs. 0.98 p = 0.5; A2AR: 1.3AU vs. 1.3AU p = 0.49; A2B: 1.7 AU vs. 1.85AU, p = 0.5. There was no significant difference between women and men patients in ABL: median 1.7 vs. 1.9 p = 0.3 and in receptors expression: A1R: 0.9 vs. 1, p = 0.08; A2AR = 1.3 vs. 1.4 p = 0.052; A2BR: 1.7 vs. 1.8 p = 0.07. No difference appears between women and men in controls (data not shown). Finally, a correlation was found between ABL and A2B receptor expression  curves show a good sensitivity/specificity ratio for ABL > 0.85 µmol/L see A. For A23 AU see B. Finall1R or A2AR expression was found in patients with FMD, we report here an overexpression of A2B receptors in PBMC in a context of high ABL. Abnormalities in ABL and adenosine receptors expression have been reported in some cardiovascular diseases. Thus, high ABL have been found in chronic cardiac failure  [2B production participates in the AF process or if conversely it is an adaptive mechanism that remains unknown. Whatever, in AF patients, the overproduction of A2BR, while significantly remained weak, around 15%. In this study, we described an overproduction of 65% in mean associated with a high ABL level, +180% compared with controls. ROC curves indicate a good predictive value for the A2BR production with a cut-off 1.23 associated with a good sensitivity of A2BR overproduction. Similar data have previously been reported in a pilot study including a weak number of FMD patients that did not permit to establish ROC curves [The main result of this study is that while no significant modifications in Are CCF, ,31), in , in 1R ore CCF, ,33), whi, whi1R opatients ,33 or dupatients . Interesposition , the incion (AF) . HoweverC curves . 2A and A2B receptors are implicated in the control of blood flow via the regulation of vascular tone and muscle cell proliferation [2BR [2BR leads to inhibition of vascular smooth muscle cell proliferation [2BR inhibits smooth muscle cell proliferation mediated by B-Myb regulation of the A2BR [Both Aferation ,38. Vascion [2BR ,40. Indeferation ,40. In vthe A2BR .2BR protects against experimental vascular injury. Thus, A2B-deficient mice (KO) enhances post injury neo-intima formation in the vasculature in an experimental model of femoral injury [2BR have the lower affinity for adenosine and thus can be activated only in the case of high adenosine extra cellular level, like in the present study.Activation of Al injury . Interesl injury . Among aFMD is associated with ischemia in a lot of territories including renal arteries , coronar2B low affinity receptors. A2 adenosine receptor subtypes have been described as sensors of tissue damage and their activation leads to anti-inflammatory properties more particularly in vessels. Activation of A2AR and A2BR leads to the inhibition of pro-inflammatory cytokine release [2BR may have antifibrotic effects [2BR remains controversial [2BR by high extracellular adenosine level may promote myocytes apoptosis in the vascular walls [Ischemia promotes adenosine release, explaining the very high ABL (until 3 µM in some patients). This increase is sufficient to activate A release  and inhi release . Activat effects , howeveroversial . The incoversial . In the oversial . Indeed,ar walls .2B receptor expression is probably a consequence of the disease rather than a cause. Indeed, there is no evidence for a difference in expression of adenosine receptors pending on sex. In this study, no significant difference in ABL or in receptors expression was found between women and men in both patients and controls. The ischemia in arterial territories leads to the release in adenosine that in turn up-regulates A2B receptors which have low affinity [2 receptors. Note that while not significant there is a trend in an increase in A2AR production in FMD patients (p = 0.06).The well-known presence of a sex ratio in FMD  indicateaffinity . This co2B receptors has been reported on monocytes in response to parasite [2BR, a mechanism by which macrophages can be deactivated [Outside the cardiovascular system, an up-regulation of Aparasite  and in cparasite . Gamma ictivated .2B receptors could help in the diagnosis of FMD. A larger number of patients may be needed to establish ROC curves with sufficient sensitivity and specificity.Although involving a limited number of patients, our study seems to indicate that the expression level of A2B receptor modulating agents could be used in the treatment of the condition. We only evaluated the level of expression but not the function  by mononuclear cells. We therefore cannot know whether produced in abundance these receptors are functional. Here too lies the limit of our study. However, our study originally falls more within the development of new markers. Our study does not allow us to conclude whether AWe cannot exclude the presence of asymptomatic FMD in the control group. However, the prevalence of FMD in France is less than 1/259 . Thus, tFinally, we cannot exclude, in FMD patients, abnormal activities of enzymes that metabolize adenosine. 5′-nucleotidases activities may be higher or adenosine deaminase activity lower. Perhaps rate of erythrocyte ATP degradation into AMP is higher in patients. The answer to these questions needs further investigations.2B overproduction and high ABL are associated with FMD outside an inflammatory context. Thus, expression measurement of A2BR and ABL could help in the diagnosis, in particular, in especially atypical forms or those with very few clinical signs. This is all the more so since, apart from cancers, a such hyperexpression of A2B receptors has been rarely mentioned. However, if the overproduction of A2B in FMD participate into the disease progression or if it is an adaptive mechanism needs further investigations.We found that A


In these patients, the log-TMAO level was positively associated with log-CRP  and negatively associated with eGFR . In conclusion, our study revealed a positive association between serum TMAO level and MetS among patients with CAD.Trimethylamine N-oxide (TMAO) is a gut microbial metabolite that affects atherogenesis and glucose dysregulation. The purpose of this study was to look at the link between blood TMAO levels and metabolic syndrome (MetS) in individuals with coronary artery disease (CAD). Blood samples were obtained in fasting status, and serum TMAO level was quantified by high-performance liquid chromatography–mass spectrometry. MetS and its components were defined according to the International Diabetes Federation diagnostic criteria. Of 92 enrolled patients, 51 (55.4%) had MetS. Patients with MetS had a greater proportion of hypertension and diabetes mellitus, higher body weight, waist circumference, body mass index, systolic blood pressure, fasting glucose, triglycerides, blood urea nitrogen, creatinine, C-reactive protein (CRP), insulin level, homeostasis model assessment of insulin resistance, and TMAO level. Multivariable logistic regression models revealed that TMAO level (odds ratio: 1.036, 95% confidence interval: 1.005–1.067,  Metabolic syndrome (MetS), which is a constellation of insulin resistance, hyperglycemia, hyperlipidemia, and hypertension, was reported to have a worldwide prevalence of 10–40% and to predispose to type 2 diabetes and cardiovascular disease . Model 1 was adjusted for the MetS components, such as waist circumference, DM, hypertension, fasting glucose, TG, and HDL-C. Model 1 showed a 3.3% increase in the risk of MetS  for every 1-μg/L increase in TMAO level. In addition to the variables in model 1, other variables that were significant for MetS  were included in model 2. Model 2 showed a 4.3% increase in the risk of MetS  for every 1-μg/L increase in TMAO level. The result above suggested that TMAO had a positive association with MetS in patients with CAD after adjusting for significant confounders. According to the ROC curve, the optimal cutoff serum value of TMAO for predicting MetS in patients with CAD was 106.69 g/L, with an area under the ROC curve of 0.832 , a sensitivity of 86.3 percent, and a specificity of 68.3 percent ; waist circumference ; SBP ; log-BUN ; log-creatinine ; log-CRP  and was negatively correlated with eGFR   and eGFR  were independently and significantly associated with log-TMAO levels.Simple multivariate linear analyses positively correlated log-TMAO level with hypertension (= 0.003) . In a muThis study on patients with CAD found that the fasting TMAO level was positively associated with MetS. In addition, log-TMAO level was positively associated with log-CRP level and negatively associated with eGFR.Beyond the connection between atherosclerosis and poor cardiovascular outcomes, increasing evidence suggested that gut microbiota is crucial in glucose hemostasis . A recenSeveral reports revealed that TMAO could alter lipid homeostasis. First, TMAO was shown to promote foam cell formation by upregulating macrophage scavenger receptors . Second,Regarding the last two components of MetS, there is limited literature on the correlation of TMAO with hypertension and obesity. In one rat study, TMAO prolonged the angiotensin II ability to elevate blood pressure, which is the crucial component of the renin-angiotensin system . In one Several confounders could alter serum TMAO levels, and one of the most important is renal function. TMAO is cleared by the kidney and excreted unchanged through the urine. Nearly 95% of TMAO is excreted in the urine within one day . CurrentThe intestinal microbiota plays a pivotal role in cardiovascular diseases and vascular aging ,29. WithThe cross-sectional design of this study, as well as the small number of patients included, and a post-hoc analysis noted the power is 0.655, were limitations of this work. Only the correlation of TMAO with MetS was provided instead of causality. There was no diet pattern evaluation or microbiome analysis of the subjects to prevent synthesis differences. In addition, the discrepancies in sex, CRP level, estrogen concentration, and inflammation severity may have confounded the TMAO levels. The highly positive correlation between serum TMAO and urine TMAO suggests that urine TMAO has the potential to serve as clinical applicability in the future . MoreoveIn conclusion, serum fasting TMAO level was positively associated with MetS, CRP level, and eGFR in patients with CAD.


Is newborn telomere length (TL) associated with blood pressure in childhood?In this birth cohort study including 485 newborns, participants with a longer birth TL had a significantly lower diastolic and mean arterial pressure at the age of 4 to 6 years. Furthermore, longer newborn TL was significantly associated with lower odds of having high childhood blood pressure.These results suggest that TL at birth associates with early life vascular health and that newborn TL may be a programmed molecular mediator containing genetic and prenatal environmental exposure information contributing to vascular health later in life. This cohort study of Belgian mother-child pairs examines the association of newborn telomere length with blood pressure in childhood. Adult telomere length (TL) is a biological marker of aging associated with vascular health. TL at birth is associated with later life TL and may contain early biological information of later life cardiovascular health and disease.To evaluate whether newborn TL is associated with early life blood pressure differences in childhood.This cohort study was part of the ENVIRONAGE  study, a birth cohort of Belgian mother-child pairs with recruitment at birth and a median follow-up of 4.5 years conducted between October 2014 and July 2021. Participants included for analysis provided full data for evaluation at follow-up visit. Data analysis was conducted between August and September 2021.Cord blood and placental average relative TL were measured at birth using quantitative polymerase chain reaction (qPCR). Systolic, diastolic, and mean arterial pressure (MAP) were evaluated at follow-up. High childhood blood pressure  was defined following the 2017 American Academy of Pediatrics guidelines. Multivariable adjusted linear and logistic regression models were used to associate newborn TL and blood pressure indicators in childhood.This study included 485 newborn children (52.8% girls) with a mean (SD) age of 4.6 (0.4) years at the follow-up visit. Newborn TL was associated with lower blood pressure in childhood. A 1-IQR increase in cord blood TL was associated with a –1.54 mm Hg  lower diastolic blood pressure and –1.18 mm Hg  lower MAP. No association was observed with systolic blood pressure. Furthermore, a 1-IQR increase in cord blood TL was associated with lower odds of having high blood pressure at the age of 4 to 6 years . In placenta, a 1-IQR increase in TL was associated with a –0.96 mm Hg  lower diastolic, –0.88 mm Hg  lower MAP, and a lower adjusted OR of 0.69  for having a high blood pressure in childhood.In this prospective birth cohort study, variation in early life blood pressure at school-age was associated with TL at birth. Cardiovascular health may to some extent be programmed at birth, and these results suggest that TL entails a biological mechanism in this programming. Blood pressure substantially rises with aging across the life span. Blood pressure tracks from childhood to adolescence and adulthood, and high blood pressure is associated with cardiovascular disease in later life.3 Telomere length (TL) is considered a biological indicator of age that relates to cardiovascular disease (CVD) and mortality in adult humans, independent of chronological age.4 The telomere biological system is an important molecular mechanism that may be causally related to cardiovascular aging,5 an effect supported by experimental6 and human population-based studies.7 Dysfunctional telomere-related senescence of the vascular wall and impaired endothelial functioning may explain why a shortened TL is observed in hypertensive individuals.9Telomeres are nucleoprotein complexes capping the end of our chromosomes that shorten due to cell division and advancing age.10 Furthermore, TL tracks over different age segments in life,12 showing that TL-related health conditions observed later in life may find their origin at birth to some extent. This highlights telomeres as an important molecular explanation in the fetal programming of health and disease hypothesis.13 Recent advances have been made to understand this wide variation of TL at birth, with a main focus on prenatal environmental and lifestyle factors,17 although the consequences of this early variation in relation to later life (cardiovascular) health outcomes are underexplored. The first evidence of newborn TL and later life cardiovascular health showed that after a 40-year follow-up in 144 individuals a short birth TL is associated with an increased risk of projected atherosclerotic lesions by the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) score.18 Further preliminary evidence by Kaali and colleagues19 suggests that cord blood TL may relate to systolic blood pressure (SBP) in children at the age of 4 years (in a cohort with 97 children). To our knowledge, no large population-based studies have been evaluating the correlation of newborn TL with childhood blood pressure measures as a major adult risk factor for CVD. Therefore, we studied whether newborn TL is associated with blood pressure measures in childhood as phenotypical indicators of early cardiovascular aging. Cord blood and placental TL at birth were studied in the ENVIRONAGE birth cohort in relation to blood pressure indicators  in early childhood .At birth, TL is highly variable and strongly projects towards later life TL.STROBE) guidelines.The ongoing ENVIRONAGE study was initiated in 2010 in Limburg, Belgium. Mother-newborn pairs are recruited at birth and are invited for a follow-up around the age of 4 years . The stu20 for maternal age, parity, sex, gestational age, and birth weight, but did slightly differ in maternal education and newborn ethnicity . A total of 553 child-mother pairs (54.5%) were followed-up, of whom 485 children had a blood pressure measurement and TL at birth and formed the basis population of the current analysis. The studied ENVIRONAGE population is demographically comparable with the not-analyzed fraction of the cohort and representative of the reproductive segment of the population at large21 coding: low when no diploma was obtained, middle when a secondary school diploma was obtained, and high when a high school or university diploma was obtained), smoking , and newborn ethnicity  was collected.At birth, information on gestational age , birth weight (in grams), maternal prepregnancy body mass index , and history of gestational hypertension and preeclampsia are collected from medical records. Via questionnaires filled out by the mothers in the maternity ward, information on maternal age, education  during the follow-up period was collected . Based on the date of follow-up, a seasonal scale was calculated .At follow-up visits conducted between 4 and 6 years later, body anthropometrics of the children including height (to the nearest centimeter) and weight (to the nearest 0.1 kg) were measured. BMI and childhood overweight (including obesity) were defined using age- and sex-specific BMI cut-offs according to the International Obesity Task Force.23 After 5 minutes of rest in the supine position, a trained observer obtained 5 consecutive readings of the SBP and DBP at 1-minute intervals. Mean SBP and DBP were based on the mean of the last 3 readings. MAP was calculated as DBP plus one-third of pulse pressure (the difference between SBP and DBP).Child and maternal blood pressure were measured with an automated upper-arm blood pressure monitor (Omron Corporation) equipped with a cuff adapted to the arm size of children. Measurements were performed by a standardized method, as described by the European Society of Hypertension.24 Information on sample collection, processing, DNA extraction, DNA quantification and integrity evaluation, quantitative polymerase chain reaction (qPCR) details, and quality controls are provided in eMethods 1 in the 25 The inter-assay ICC was 0.94  and the intra-assay ICC was 0.95 .Placental and cord blood TL were measured as described previously.P value <.05 was considered statistically significant. Participants’ characteristics were presented as means (with SDs) or frequency. Pearson correlations and single and multivariable-adjusted linear and logistic regression models were applied.All data management and statistical analyses were done using SAS version 9.4 . All performed statistical tests were 2-sided and a In a first step, the association between cord blood and placenta TL (independent variables) and SBP, DBP, and MAP (dependent variables) in children ages 4 to 6 years were analyzed using separate linear regression models . First, we adjusted our models for a priori selected prenatal and perinatal covariates that may be associated with both the dependent and independent variables, including newborn sex, ethnicity, gestational age, birth weight, maternal age, maternal prepregnancy BMI, maternal education, maternal smoking during pregnancy, and maternal gestational hypertension and preeclampsia. Second, we further adjusted for postnatal factors between ages 4 and 6 years, including child age, child weight, child height, and household smoke exposure during childhood. To evaluate the robustness of our models we stratified our models for sex, excluded preterm births  and children who were overweight . Furthermore, we adjusted the models for child BMI instead of child weight and height, adjusted for date and season of the follow-up, and additionally adjusted the model for the corresponding maternal blood pressure indicator. Estimates are presented as the difference in blood pressure for a 1-IQR increase in cord blood or placental TL.26 recommend using US reference values. Therefore, we used the 2017 American Academy of Pediatrics (AAP) guidelines for defining high blood pressure.27 Age-, sex-, and height-specific BP percentiles were calculated for SBP and DBP and referred to as high when above the 90th percentile  .Of the 485 ENVIRONAGE participants included in analysis, newborns had a mean (SD) gestational age of 39.1 (1.6) weeks and a birth weight of 3393 (490) grams; 256 (52.8%) were girls, and 26 (5.4%) were of non-European ethnicity . Mothersr = –0.13; P = .003 and r = –0.12; P = .009) and MAP , but not with SBP (P < .001) and –1.18 mm Hg  lower DBP and MAP, respectively, at the age of 4 to 6 years. Longer cord blood TL was not associated with SBP . A 1-IQR increase in placental TL was associated with a –0.96 mm Hg  and –0.88 mm Hg  lower DBP and MAP, respectively. Longer placental TL was not associated with lower SBP . Comparable regression estimates were observed when stratifying for boys and girls, or when excluding preterm births or children that were overweight (eTable 3 in the Cord blood and placenta TL were negatively correlated with DBP (with SBP . These awith SBP . In thesP = .03) and a 1-IQR increase placental TL was associated with a lower adjusted OR of 0.69 .While accounting for all aforementioned covariates, newborns with longer TL (both cord blood and placenta) showed lower odds of having a high blood pressure  in childhood . A 1-IQRThe core finding of this study was that newborn TL was associated with blood pressure indicators early in life. Children born with longer TL  displayed a lower diastolic blood pressure and MAP at the age of 4 to 6 years. This shows the potential of TL at birth as a biologically relevant parameter to monitor healthy vs unhealthy aging trajectories.28 Experimental studies show that dysfunctional telomeres relate to dilated cardiomyopathy, ventricular wall remodelling,6 and endothelial cell senescence in atherosclerosis.29 Telomere shortening is observed in human vascular endothelial cells in areas of high hemodynamic stress compared with endothelial cells in the vascular system with low hemodynamic stress.30 Vascular smooth muscle cells in atherosclerotic plaques show shorter telomeres than in normal vessels.31 These observations suggest that telomere biology and cardiac-specific cell aging in cells factor into blood pressure control. Furthermore, genome-wide association studies of adult leukocyte TL (LTL) identified 7 single-nucleotide variations  linked with LTL that mutually project towards an increased risk for coronary artery disease.7Telomeres contain thousands of tandem repeated TTAGGG sequences that get lost after each cell division due to incomplete DNA replication. TL represents the replicative history of cells and when telomeres critically shorten or become dysfunctional, cellular senescence is induced.32 average LTL may provide some information about an individual’s tissue and cell-specific average telomeric state. We show that TL in both cord blood leukocytes and placental cells is associated with blood pressure in early childhood. Whether cord blood TL or placental TL also reflects cardiac cell- and tissue-specific telomere shortening at birth or later life is unknown. Previous research showed that shorter cord telomeres tend to be associated with a higher PDAY score approximately 42 years later in life, but no association with hypertension and blood pressure was observed.18 A study including 97 children showed an inverse association between cord blood mononuclear cell TL and SBP in boys after a median follow-up of 4 years, but no association with DBP was observed.19 We show associations with DBP and MAP, but associations with SBP were not observed with cord blood TL. Why an association with DBP and not with SBP was observed is still unclear. Differences in SBP and DBP variability may be different in children than in adults. In addition, DBP is a major contributor in secondary hypertension in children, especially in children aged under 6 years.35 This indicates the potential important role of DBP very early in life. The importance of elevated childhood blood pressure is further evident from a recent meta-analysis including 39 714 children  that showed that a 1-SD increase in both childhood SBP and DBP results in 71%  and 57%  higher risk for hypertension in adulthood .36 Furthermore, as blood pressure from childhood onwards tracks over time,1 it has been shown that elevated childhood blood pressure relates to intermediate markers of cardiovascular disease including increased pulse wave velocity, increased intima-media thickness, and left ventricular hypertrophy.37 Although the observed associations appear to be small, a population-wide reduction in diastolic pressure by approximately 1 mm Hg is likely to result in a 7% decrease in coronary heart disease and a 10% decrease in stroke later in life,38 showing the clinical relevance of a 0.96 to 1.54 mm Hg change in diastolic pressure observed in our study.Leukocyte TL is commonly used in epidemiological settings, and may be an overall indicator of the telomeric state of an individual. Because of the high intra-individual synchrony and shortening rate in TL between different tissues in adulthood,10 and is associated with blood pressure later in life, our results may give further interpretations to observations that link adult LTL with hypertension9 and increased risks for CVD,4 in which a part of these observations may be traced back to birth. TL at birth is highly variable,39 and understanding the reason for the variation in TL among individuals is crucial for differentiating between causal pathways vs reactive pathways or consequences. As we found out that TL at birth associates with blood pressure at the age of 4 to 6 years, we might think that besides consequential changes, fetal programming may also play a role, but this should be further evaluated. TL, established during gestational life and continuously modified thereafter, might include a signature of inheritance as well as the effects of the intrauterine and extrauterine environments. Therefore TL at birth may be an important biological mediator between genetics, prenatal environmental risk factors, and later life cardiovascular events, and which could provide important insights into the fetal programming of disease hypothesis as postulated by Barker.41 Besides Barker, Brenner42 can be considered as one of the founding fathers of the developmental origin of health and disease hypothesis. He offers a possible explanation for the inverse association between blood pressure and fetal growth by the number of nephrons a person is born with, in which telomeres may have a role in renal growth and function and therefore would associate with later life hypertension.43 We acknowledge however that large follow-up studies from birth onwards are needed  to further show the potential involvement of early TL and telomere attrition in these observations.As TL tracks from birth to later lifeOur study has important strengths, including its relatively large sample size. Furthermore, in children and older people alike, blood pressure variability, the white-coat effect, and observer bias limit the reliability of office measurements. Automated techniques of blood pressure measurement may overcome these limitations. We used standardized conditions and multiple automated blood pressure readings that are characterized by high reproducibility and are not subject to digit preference or observer bias. We show consistent findings between blood pressure indicators and TL measured in 2 tissues collected at birth.44 and alter the risks for cardiovascular diseases. Therefore, whether initial TL is also related to hard cardiovascular disease end points and target organ damage later in life is unknown. To address this latter question, long-term follow-up studies are needed. Second, whether TL measured in cord blood and placenta also reflects cardiac tissue- and cell telomere-aging at birth or later in life is unknown. Mean relative cord blood and placental TL as measured in this study was more a systemic indicator of an individual’s telomeric state, and observations made here need to be interpreted within a population-based perspective and not from an individual-based perspective. Furthermore, indications of telomere integrity, telomere dysfunctionalities, telomere damage, or the amount of critically short telomeres that are specific to tissues or cells besides average TL may relate more strongly to specific telomere-related diseases.46 Therefore average TL is more likely an overall health and disease-susceptibility indicator rather than it is a disease-specific indicator. Third, as newborn TL is associated with parental TL,39 the contribution of parental TL in the observed associations may warrant further evaluation. Nevertheless, newborn TL contains parental inherited features and nongenetic information that contributes to the observed associations with blood pressure. Finally, our population showed a relatively high prevalence of children with elevated blood pressure according to the 2017 AAP guidelines, which is in line with previous observations.47 This is due to the stringent guidelines as a purpose for early detection, potential intervention, and follow-up recommendations when blood pressure is measured on a single day. In this regard, we acknowledge that actual hypertension diagnosis in young children requires repeated blood pressure monitoring over time.Our study also had several limitations. First, although blood pressure tracks over time, individual lifestyle factors and interventions over the life course can change blood pressures later in lifeIn this prospective cohort study, newborn TL was associated with blood pressure indicators in children aged 4 to 6 years. TL at birth may be an important early biological marker that links prenatal genetic and nongenetic risk factors with later life health conditions, as in line with the fetal programming of health and disease theory. Additional long-term longitudinal studies with repeated blood pressure measurements over childhood and early adulthood are needed to further examine the role of TL at birth and cardiovascular health trajectories and later life CVD risk. Understanding gene-environmental factors contributing to the initial setting of TL may expand our understanding of the early development of cardiovascular changes.


Beetroot juice (BRJ) improves peripheral endothelial function and vascular compliance, likely due to increased nitric oxide bioavailability. It is unknown if BRJ alters cerebrovascular function and cardiovagal baroreflex control in healthy individuals.We tested the hypotheses that BRJ consumption improves cerebral autoregulation (CA) and cardiovagal baroreflex sensitivity (cBRS) during lower-body negative pressure (LBNP).2  during a 5 min baseline and throughout LBNP to attenuate reductions in end-tidal CO2 tension (PETCO2). O-LBNP was conducted at ∼0.02 Hz for six cycles (−70 mmHg), followed by a 3-min recovery before S-LBNP (−40 mmHg) for 7 min. Beat-to-beat middle cerebral artery blood velocity (MCAv)  and blood pressure were continuously recorded. CA was assessed using transfer function analysis to calculate coherence, gain, and phase in the very-low-frequency  and low-frequency bands . cBRS was calculated using the sequence method. Comparisons between POST vs. PRE are reported as mean ± SD.Thirteen healthy adults  performed oscillatory (O-LBNP) and static LBNP (S-LBNP) before (PRE) and 3 h after consuming 500 mL of BRJ (POST). Participants inhaled 3% COVLF was greater at POST , but phaseVLF (P = 0.17) and gainVLF (P = 0.69) were not different. CoherenceLF and phaseLF were not different, but gainLF was lower at POST . During S-LBNP, CA was not different in the VLF or LF bands . Up-cBRS and Down-cBRS were not different during both LBNP protocols.During O-LBNP, coherenceThese preliminary data indicate that CA and cBRS during LBNP in healthy, young adults is largely unaffected by an acute bolus of BRJ. Reducti memory)  and Alzh memory) . Cardiov memory) , increas memory) , and red memory) .via dietary nitrate supplementation alter blood pressure control, and in turn alter the regulation of cerebral blood flow due to integrative mechanisms.Endogenous nitric oxide production can be supplemented with dietary nitrates to increase its bioavailability . Dietaryvia anaerobic bacteria and is further reduced to nitric oxide in the stomach before entering the bloodstream (Beetroot juice (BRJ) is a popular nitric oxide supplement due to its high inorganic nitrate profile. When BRJ is ingested, nitrate is broken down to nitrite in the oral cavity odstream . Acute Bodstream . Improveodstream , but theodstream . Simultaodstream . MaintaiThe purpose of the present study was to determine if acute BRJ consumption alters cBRS and CA. We tested the hypotheses that a single bolus of BRJ would acutely increase dynamic and static CA and reduce cardiovagal-baroreflex sensitivity during oscillatory and static LBNP in healthy, young adults. These LBNP protocols are experimental models used to examine the dynamic and static components of cerebral blood flow regulation and autonomic control of blood pressure.2; 5 women) completed the study. All participants were fully informed of the experimental procedures prior to providing written, informed consent. Participants were excluded from the study if they self-reported to use tobacco or medications known to affect blood pressure or the autonomic nervous system ; had a pre-existing autonomic, cardiovascular, metabolic, respiratory, or endocrine disorder; major depression; were pregnant or breastfeeding. Women were tested during the first 10 days of their self-identified menstruation  to control for the menstrual cycle  and static lower body negative pressure (Static-LBNP) before and 3 h after BRJ consumption to allow for plasma nitrite levels to peak . Partici2 that can be observed during LBNP, participants inhaled a mild hypercapnic gas  during baseline and throughout the duration of testing. Our lab has previously demonstrated that LBNP set to −40 mmHg for 5 min reduces PETCO2 by 5 ± 3 mmHg in healthy, young adults . Participants were then instrumented with physiological monitoring equipment. Then, after >10 min of supine rest, 5 min of baseline data were recorded before initiating the LBNP protocols. To attenuate reductions in PETCOg adults , which lof ≥0.05 , thus weFollowing the 5-min baseline, the Oscillatory-LBNP protocol commenced. Oscillatory-LBNP was conducted at a frequency of ∼0.02 Hz, which consisted of 30 s on (−70 mmHg) and 30 s off (0 mmHg) for a total of six cycles. Then, a 3-min recovery period was allotted before the Static-LBNP protocol commenced. Static-LBNP consisted of −40 mmHg for a total of 7 min to assess static CA . Upon coThe LBNP protocols had pre-defined termination endpoints, including (a) Sustained systolic blood pressure (SBP) <80 mmHg with a precipitous decrease in heart rate; (b) If participants self-reported any symptoms of pre-syncope ; or (c) Upon participant request . All parvia a refractometer . Heart rate was continuously measured using 3-lead electrocardiogram . Beat-to-beat blood pressure was non-invasively measured using finger photoplethysmography on the left hand (middle finger) at heart level. Finger blood pressure was calibrated to brachial artery blood pressure in the supine position using the return-to-flow module . Blood pressure was confirmed intermittently throughout the protocol using auscultation of the right brachial artery . End-tidal CO2 tension (PETCO2) was continuously measured to estimate arterial CO2, from a mouthpiece using capnography while the nose was occluded with a nose clip . Left middle cerebral artery blood velocity (MCAv) was continuously measured using a 2 MHz probe  with insonation techniques outlined by Height was measured with a stadiometer . Nude body weight was measured on an electronic scale to the nearest 0.01 kg in a private bathroom. Urine specific gravity was measured 2 (62.5 Hz), and MCAv (1000 Hz) were continuously recorded using a data acquisition system . Stroke volume was estimated using Modelflow (Heart rate (1000 Hz), blood pressure (62.5 Hz), PETCOodelflow . Cardiacvia transfer function analysis . Please refer to the examples of typical tracings for oscillatory-LBNP and Static-LBNP protocols in n = 1 ; Static-LBNP; n = 3 ]  and 30 s off (0 mmHg) (∼0.02 Hz). This interval time was selected due to the cerebral vasculature’s ability to dampen changes in arterial pressure that occur slower than ∼30 s (0.03 Hz) . Static 1 male)] . One addR2 value calculated from individual linear regression analyses between SBP and RRI was ≥0.85  during Oscillatory-LBNP (∼6 min) and Static-LBNP (7 min). The ECG and beat-to-beat blood pressure waveforms were visually inspected for artifact and ectopic beats (none were identified). cBRS was calculated using the sequence method . Four suas ≥0.85 . The timas ≥0.85 . Sequencpost hoc analyses to determine where differences occurred. Within LBNP protocols, we used two-tailed paired t-tests to determine if indices of dynamic CA and cBRS differed between PRE-BRJ and POST-BRJ. Lastly, Cohen’s d effect sizes were calculated for CA and cBRS between PRE-BRJ and POST-BRJ within each LBNP protocol (d = 0.0–0.1), small (d = 0.2–0.4), intermediate (d = 0.5–0.7), and large (d = 0.8 and above) . We used linear mixed-effects models to compare absolute mean values during Oscillatory-LBNP at PRE-BRJ and POST-BRJ. Linear mixed-effects models were also used to compare absolute mean values during Static-LBNP at PRE-BRJ and POST-BRJ. No statistical comparisons were made between LBNP protocols. If a linear mixed-effects model revealed a significant interaction or main effect , we usedprotocol . Cohen’sd above) . StatistP = 0.017), but multiple comparisons did not reveal significant differences (P = 0.002), with multiple comparisons identifying that stroke volume was lower POST-BRJ at interval 4 of −70 mmHg in (P = 0.042) (P = 0.008), cardiac output was not different between PRE-BRJ and POST-BRJ during Oscillatory-LBNP   . Despiteory-LBNP . Mean arory-LBNP . CVCi wa= 0.023) .P = 0.008, d = 1.268). However, coherence was not different between PRE-BRJ and POST-BRJ in the LF (P = 0.510) or HF band (P = 0.137). Phase was not different between PRE-BRJ and POST-BRJ in any frequency band . Gain was lower at POST-BRJ in the LF band (0.07–0.20 Hz) vs. PRE-BRJ (P = 0.049). Gain was not different between PRE-BRJ and POST-BRJ in the VLF (P = 0.669) or HF band (P = 0.352).Indices of dynamic CA during Oscillatory-LBNP are presented in P ≥ 0.212). RRI was greater at PRE-BRJ vs. POST-BRJ (P = 0.025). Up-cBRS (P = 0.600) and Down-cBRS (P = 0.511) were not different between PRE-BRJ and POST-BRJ.Blood pressure and cBRS data during Oscillatory-LBNP are presented in P = 0.011) and minute 3 (P = 0.038) of Static-LBNP , LF (0.07–0.20 Hz) , or HF band (0.20–0.50 Hz) . There was an intermediate effect size for phase in the LF band (d = 0.660).Indices of static CA during Static-LBNP are presented in P ≥ 0.718). RRI (P = 0.066), Up-cBRS (P = 0.122), and Down-cBRS (P = 0.118) during S-LBNP were not different between PRE-BRJ vs. POST-BRJ.Blood pressure and cBRS data during Static-LBNP are presented in We investigated the acute effects of BRJ on CA and cBRS during oscillatory and static LBNP challenges in healthy, young adults. Our primary findings are that 3 h following the consumption of 500 mL of BRJ: (1) indices of dynamic CA are altered during blood pressure oscillations induced at ∼0.02 Hz, but not during a static hypotensive stimulus, and (2) cardiovagal baroreflex sensitivity is not altered during an oscillatory or static hypotensive stimulus.Beetroot juice did not alter mean arterial pressure during supine rest. Blood pressure has previously been shown to decrease following acute and chronic dietary nitrate supplementation (primarily BRJ), with more pronounced reductions observed in systolic vs. diastolic blood pressure . However2 and blood pressure were also not influenced by BRJ. Currently, there is a paucity of investigations in healthy, young adults regarding the acute effects of dietary nitrates on cerebral artery blood velocity and blood flow. A diet high in nitrates increased cerebral perfusion to the frontal lobe, but did not alter global cerebral perfusion in older adults , as MCAv was lower throughout oscillatory LBNP. Despite no statistical differences in the mean arterial pressure and MCAv responses to oscillatory LBNP, there were differences in some transfer function analysis indices of dynamic CA. In the VLF band, coherence was greater following BRJ  at PRE-BRJ and ∼5 mmHg (range: 0 to −13 mmHg) at POST-BRJ. The wide range at pre-BRJ was contributed by one male participant that exhibited large reductions in blood pressure at minute 5 and 6 at −40 mmHg before LBNP was terminated due to experiencing relative bradycardia associated with a decreasing blood pressure. Interestingly, this participant tolerated static LBNP following BRJ. Regardless, mean arterial pressure throughout the 7 min of LBNP was not different between pre and post-BRJ . We obse of LBNP . More prnd women . Despitengestion . These mPOST-BRJ . EvidencPOST-BRJ . It is dP = 0.07) were similar to the oscillatory LBNP responses. Yet, blood pressure and cBRS during the static LBNP protocols were not different between conditions  following BRJ ingestion in healthy, young adults. Contrary to our hypothesis, we observed no change in Up-Up or Down-Down cBRS after BRJ during static or oscillatory LBNP. During oscillatory LBNP, we observed no change in blood pressure between conditions, but RRIs decreased from pre to post-BRJ . Althougnditions . Althougnditions , whereasnditions  and 6-danditions . Our fin2 content  to the inspirate in an attempt to attenuate reductions in PETCO2 during LBNP protocols. The mild hypercapnic gas was inhaled for 5 min of supine baseline to allow for a new stable PETCO2 and baseline to be achieved prior to LBNP initiation. It has previously been reported that hypercapnia impairs dynamic CA, but this has been shown when PETCO2 is 5 mmHg greater than resting baseline (2 increased PETCO2 by ∼3 mmHg (PRE-BRJ) and ∼4 mmHg (POST-BRJ) from room air supine rest. We speculate that CA was not impaired due to the modest increases in PETCO2 that likely did not alter MCA diameter . Daily fluctuations in CA are poorly understood, but it appears that spontaneous autoregulation remains stable during the daytime hours (8 am–8 pm) in healthy individuals (There are several methodological considerations that should be taken into account when interpreting our data. First, we removed the transcranial Doppler ultrasound probe between testing sessions. This may alter the signal between testing time points. However, we utilized standard insonation techniques set forth by  content , which cbaseline . On averdiameter , but we ividuals . All of ividuals . It is cividuals . Howeverividuals . Fan et In summary, during an oscillatory blood pressure challenge, we observed an increase in VLF coherence, which may indicate a stronger linear relation between blood pressure and middle MCAv following BRJ ingestion. However, transfer gain and phase were not altered within this frequency band, indicating that there was no change in cerebral autoregulatory capacity. After BRJ, we did observe a slight reduction in LF gain during Oscillatory-LBNP. It is unclear if this is indicative of improved dynamic CA since the blood pressure oscillations were induced at a very low frequency. Indices of CA did not change during constant LBNP which indicates that static CA is not acutely altered with BRJ. Lastly, BRJ did not alter cBRS during dynamic and static LBNP in healthy, young adults. Therefore, a single 500 mL bolus of BRJ does not appear to acutely improve dynamic or static CA or cBRS during LBNP in healthy, young adults.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Review Board at the University at Buffalo. The patients/participants provided their written informed consent to participate in this study.All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.