Even though several mobile apps that can measure blood pressure have been developed, the data about the accuracy of these apps are limited.We assessed the accuracy of AlwaysBP (test) in blood pressure measurement compared with the standard, cuff-based, manual method of brachial blood pressure measurement (reference).AlwaysBP is a smartphone software that estimates systolic blood pressure (SBP) and diastolic blood pressure (DBP) based on pulse transit time (PTT). PTT was calculated with a finger photoplethysmogram and seismocardiogram using, respectively, the camera and inertial measurement unit sensor of a commercially available smartphone. After calculating PTT, SBP and DBP were estimated via the Bramwell-Hill and Moens-Korteweg equations. A calibration process was carried out 3 times for each participant to determine the input parameters of the equations. This study was conducted from March to August 2021 at Chungnam National University Sejong Hospital with 87 participants aged between 19 and 70 years who met specific conditions. The primary analysis aimed to evaluate the accuracy of the test method compared with the reference method for the entire study population. The secondary analysis was performed to confirm the stability of the test method for up to 4 weeks in 15 participants. At enrollment, gender, arm circumference, and blood pressure distribution were considered according to current guidelines.Among the 87 study participants, 45 (52%) individuals were male, and the average age was 35.6 (SD 10.4) years. Hypertension was diagnosed in 14 (16%) participants before this study. The mean test and reference SBPs were 120.0 (SD 18.8) and 118.7 (SD 20.2) mm Hg, respectively . The absolute differences between the test and reference SBPs were <5, <10, and <15 mm Hg in 57.5% (150/261), 84.3% (220/261 ), and 94.6% (247/261) of measurements. The mean test and reference DBPs were 80.1 (SD 12.6) and 81.1 (SD 14.4) mm Hg, respectively . The absolute differences between the test and reference DBPs were <5, <10, and <15 mm Hg in 75.5% (197/261), 93.9% (245/261), and 97.3% (254/261) of measurements, respectively. The secondary analysis showed that after 4 weeks, the differences between SBP and DBP were 0.1 (SD 8.8) and −2.4 (SD 7.6) mm Hg, respectively.AlwaysBP exhibited acceptable accuracy in SBP and DBP measurement compared with the standard measurement method, according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization protocol criteria. However, further validation studies with a specific validation protocol designed for cuffless blood pressure measuring devices are required to assess clinical accuracy. This technology can be easily applied in everyday life and may improve the general population’s awareness of hypertension, thus helping to control it. Hypertension is an established major risk factor for various cardiovascular diseases and mortality . SignifiTo improve the accessibility of blood pressure measurement, many new devices are being developed for this purpose that are comparable to the conventional, cuff-based, manual method or oscillometric blood pressure measurement devices. Cuffless devices include wristbands, rings, patch systems, and smartphone software; these devices have exhibited acceptable accuracy when compared with conventional blood pressure measurements -9. The pThe number of smartphone users has increased worldwide, and many people in high-income and low-income countries use them . Most smThis study was conducted at Chungnam National University Sejong Hospital from March 2021 to August 2021. The enrollment targeted adults aged between 19 and 70 years. Those who met the following conditions were excluded: (1) individuals who were unable to use the test or reference blood pressure measurement device for up to 30 minutes in a sitting position (2) and individuals who had a history of cardiac arrhythmias or peripheral vascular disease. We determined the number of participants according to a validation guideline, which states that at least 85 patients are required for an Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) validation study . At enroThe test device, AlwaysBP (Deepmedi Inc), is a smartphone software that estimates a person’s systolic blood pressure (SBP) and diastolic blood pressure (DBP) based on the PTT. The blood pressure estimation model was designed to include the following two steps: (1) calculation of the PTT by using seismocardiography and photoplethysmography via the test device and (2) input of the acquired PTT into the blood pressure estimating equations . PTT was0, and the average PP and MBP measured by cuff-based blood pressure measurement device were entered as PP0 and MBP0, respectively. The PTT value obtained from the third calibration was input as the PTT of the formulas, and SBP and DBP values were input as the SBP and DBP, respectively; moreover, the γ value was updated according to the results of the calculated equations  [0, PP0, and PTT0, respectively, and the γ obtained from the third calibration was used in the equations. This equation model was implemented in the AlwaysBP app and used to measure blood pressure at the initial visit and at follow-up. The test blood pressure measurement software was installed and used in a Galaxy S10 smartphone (Samsung Electronics) throughout this study. The test software has yet to be released on the app market for commercial use.To determine the input parameters of the equations, a calibration process was carried out 3 times for each participant . The PTT0 years) . After tThe basic demographics, including past medical history, comorbidities, and drug use, of the participants were assessed through an interview with the physician and recorded on a dedicated electronic case reporting form. The participants sat in a comfortable position for at least 5 minutes before measuring blood pressure. During the blood pressure measurement, the participant’s back and arms were supported, their left arm was placed at heart level, their legs were not crossed, and their feet were placed flat on the floor. Dialogue and other interferences were prohibited throughout the measurement. Calibration of the test device was performed just before the measurement of the blood pressure.The test blood pressure was defined as the blood pressure value measured by the test device (AlwaysBP), and the reference blood pressure was defined as the blood pressure value measured by the reference blood pressure device (InBody). The reference SBP and DBP were measured, using the participant’s left arm, by 2 trained nurses who were blind to each other’s readings. A double-headed stethoscope (Y-tube) was used for the simultaneous auscultation of the brachial pulse, and the blood pressures at the first and fifth Korotkoff sound were recorded as SBP and DBP, respectively. The average blood pressure values measured by the two observers were considered the reference blood pressures for the analysis. The test blood pressure was measured simultaneously with the reference blood pressure. The participant’s right hand held the test device, and the index finger was positioned to cover the camera lens on the back of the smartphone to obtain the finger photoplethysmography signal. Concomitantly, the seismocardiography signal was obtained by placing the front of the smartphone on the participant’s anterior chest wall. This position was maintained for 20 seconds, and if the participant’s position was inadequate for proceeding with the study or blood pressure measurement, the research personnel advised the participant to return to the correct position. If an error occurred because of the poor signal quality of the test blood pressure device resulting from the insufficient color change of the finger to red (a result of the LED light being below a predetermined threshold), blood pressure measurement was attempted again until the error did not occur.This study consisted of 2 parts . The priFor the primary analysis, blood pressure was measured 3 times for each participant after individualized calibration. Calibration was performed by entering the measured reference blood pressure value into the test device after applying the test and the reference devices at the same time. This process was performed 3 times consecutively, without a break. Afterward, 5 minutes of rest were allowed after completion of the calibration. Subsequently, blood pressure was measured 3 times per participant, with an interval of 5 minutes for resting. As a result, a total of 261 pairs of test-reference blood pressure sets from 87 participants were obtained for SBP and DBP, respectively.Blood pressure was measured and recorded weekly for 4 weeks in 15 participants who were initially enrolled in this study to investigate the stability of the test device over time. Blood pressure measurements performed during the follow-up were carried out identically to the initial blood pressure measurements, with the exception that no calibration was performed.P value and Pearson correlation coefficient (r) were calculated. Bland-Altman plots were generated to compare the distribution of differences in SBP and DBP between the test and reference devices. All reported P values were 2-sided, and significance was set at P<.05. All statistical analyses were performed by using R software .Baseline characteristics were expressed as percentages for categorical variables and as means with SDs for continuous variables. Differences between test and reference blood pressure values in the primary and secondary analyses were expressed as means and SDs. To evaluate the correlation between the test and reference blood pressures, the All participants participated voluntarily in this study and provided written informed consent. The study protocol was approved by the Institutional Review Committee of Chungnam National University Sejong Hospital . This study was conducted in accordance with the relevant guidelines and regulations.Among the 87 study participants, 45 (52%) individuals were male, and the average age was 35.6 (SD 10.4) years. The mean height and weight were 168.2 (SD 8.1) cm and 75.2 (SD 17.9) kg, respectively. Further, 14 (16%) participants were diagnosed with hypertension and were taking antihypertensive drugs prior to enrollment. The most used drug to manage hypertension was an angiotensin II receptor blocker. The mean screening SBP and DBP were 134.2 (SD 20.3) mm Hg and 82.8 (SD 15.2) mm Hg, respectively .The mean test SBP was 120.0 (SD 18.8) mm Hg, and the mean reference SBP was 118.7 (SD 20.2) mm Hg . The difP=.10) and −2.0 (SD 5.3) mm Hg (P=.01) for SBP and DBP, respectively. After 4 weeks, the differences between SBP and DBP were 0.1 (SD 8.8) mm Hg (P=.96) and −2.4 (SD 7.6) mm Hg (P=.04), respectively.This study assessed the accuracy of a smartphone-based blood pressure measurement software (AlwaysBP) compared with the standard, cuff-based, manual method of brachial blood pressure measurement. Our results revealed that the test device showed acceptable accuracy for both SBP and DBP, and the difference between the test and reference SBP values was stable over the 1-month follow-up. The DBP values of the study device were not stable for 1 month.The development of various cuffless blood pressure monitors has allowed for the measurement of blood pressure easily and comfortably. Such devices are expected to improve the penetration rate of blood pressure measurements, which is very important for lowering the rates of hypertension unawareness and uncontrolled hypertension after diagnosis. Several smart devices that can measure blood pressure without the use of a cuff have been developed. The most commercially available devices are smartwatch devices, which work mainly by acquiring photoplethysmography signals and estimating blood pressure via a machine learning algorithm based on these signals or PTT calculation ,9,15,16.In our study, the test device estimated SBP and DBP based on the PTT. The advantage of PTT-based blood pressure measurement over photoplethysmography analysis–based blood pressure estimation has not been elucidated fully. However, there is a huge body of evidence that PTT is associated with blood pressure -20. MoreThe existing blood pressure measuring devices requiring calibration also have limitations and therefore need to be improved. Changes in blood pressure within an individual are not usually considered in calibration and testing. Thus, there have been debates regarding the problems in validating cuffless blood pressure measuring devices that require calibration, because the time between calibration and testing is insufficient to account for individual differences in blood pressure . Our sysDue to the inherent features exhibited by cuffless blood pressure measuring devices, it is imperative to establish more specialized criteria for validating such products . The exiThis study had several limitations. First, it was conducted at a single center in Korea. The device algorithm was based on the Korean population during development, and this study was also conducted with Koreans. Second, although study participants were enrolled according to the AAMI/ESH/ISO protocol, we understand that this protocol should not be used for a cuffless device; therefore, further study is required with a validation protocol specifically designed for cuffless blood pressure devices. Third, both arms were used to detect test and reference blood pressure values simultaneously. Although participants with a history of peripheral vascular disease were not enrolled, the difference in reference blood pressures between both arms was not assessed prior to this study. Fourth, despite meeting the validation criteria suggested by the AAMI/ESH/ISO guidelines, our device’s accuracy may not be sufficient for populations with high DBPs, as shown by the study results. Fifth, our study primarily included young and healthy participants; thus, the accuracy and applicability of our device for older and comorbid populations may be limited. Sixth, our study did not include the average agreement between the two observers and the frequency of device errors; therefore, further study is required to assess the functional consistency and reliability of the AlwaysBP software. Lastly, our data did not include information regarding the skin pigmentation of participants, which can have effects on the signal to noise ratio. Although our study exclusively recruited individuals of East Asian ethnicity and used LED technology from smartphones to obtain high-quality photoplethysmography data from participants’ fingers, the influence of an individual’s skin pigmentation cannot be disregarded. Hence, an evaluation of the accuracy of the study device based on variations in skin pigmentation is necessary. Further investigations involving larger sample sizes with diverse comorbidities and skin colors are also required. Such additional studies should be conducted by an independent group for transparency and to mitigate potential bias .This study assessed the accuracy of the AlwaysBP smartphone software, which was used to estimate blood pressure in 87 study participants. The cuffless smartphone software showed acceptable accuracy for SBP and DBP when compared with the reference cuff-based manual blood pressure measurement method, according to the AAMI/ESH/ISO protocol criteria. However, we understand that this protocol was only designed to validate cuff-based blood pressure measuring devices. Therefore, further validation studies with a specific validation protocol designed for cuffless blood pressure measuring devices are required to assess clinical accuracy.The cuffless smartphone technology can be easily applied in everyday life, and it may improve the awareness and control of hypertension in the general population by enabling regular blood pressure monitoring, remote monitoring by health care providers, and programmed alerts and reminders for medication and measurement. Additionally, educational content can promote adherence to treatment plans and provide tips for managing hypertension.


Objectives: The study aimed to examine the association of three anemia-related biomarkers with the adequacy of peritoneal dialysis (PD) in patients with chronic kidney disease (CKD).Methods: This study included 127 PD patients. The total Kt/V urea (Kt/V) was calculated according to the Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines. All patients were classified into two groups based on Kt/V, viz., adequate (Kt/V ≥1.7) and inadequate (Kt/V <1.7) groups. Effect sizes are expressed as odds ratios (ORs) and 95% confidence interval (CI).Results: After adjusting for age, gender, hypertension, diabetes, and PD duration, 20 g/L increment in hemoglobin (Hgb) was observed to significantly reduce the risk of inadequate PD by 19% , 5 g/L increment in the mean corpuscular hemoglobin concentration (MCHC) by 7% , and 5% increment in transferrin saturation (TS) by 23% . The gender-specific nomogram model was constructed by incorporating three significant anemia-related biomarkers and convenient influencing factors, and the prediction accuracy was good (concordance index (C-index): 0.686 for men and 0.825 for women).Conclusion: Our findings indicate that the deterioration of three anemia-related biomarkers  can precipitate the development of inadequate PD in Chinese patients with CKD. Chronic kidney disease (CKD) is a chronic disorder of public health importance affecting approximately 1/10 of adults worldwide . EchoingIn patients with CKD, PD can meet the requirements of clearing uremic toxins and reaching an acid–base balance, as well as removing excess fluids . DialysiIt is widely recognized that renal anemia is a common complication of uremic patients, and patients with a lower Kt/V level require more erythropoietin to manage anemia. Several studies showed that patients with the total Kt/V level maintained below 1.70 as a lower level in hemoglobin indicated inadequate PD . In patiTo fill this gap in knowledge and produce more references for future studies, we aimed to examine whether anemia-related biomarkers, both individually and as a nomogram, can potentially predict the risk of inadequate PD in patients with CKD.The conduct of this study was reviewed and approved by the ethics committees of the Beijing Hospital of Traditional Chinese Medicine, conforming to the principles of the Declaration of Helsinki. All participants provided their informed consent prior to their participation in the study.All study participants were Chinese adults who had PD catheter placement and regularly visited the Department of Nephrology at the Beijing Hospital of Traditional Chinese Medicine. This is a retrospective study conducted from September 2017 to October 2022. For consistency, the most recent PD adequacy assessment was recorded from the study participants.Initially, 142 patients were recruited in this study, and 15 of them were excluded due to the following reasons: 1) being under hemodialysis or after kidney transplantation; 2) recently experiencing significant changes in their weight; 3) having PD-related peritonitis occurrence in the last 3 months; 4) being diagnosed with diabetic ketoacidosis, acute cardiovascular events, or other severe disorders, including tumors; 5) having no consultation records for 3 months. Finally, 127 eligible patients with complete data were analyzed in this study.In addition to the age and gender, the diagnoses of hypertension and diabetes mellitus were also performed at the time of enrollment. Hypertension was defined as having a systolic blood pressure value of ≥140 mmHg, diastolic blood pressure value of ≥90 mmHg, or the current use of antihypertensive agents . DiabeteThe collection of clinical biomarkers initiated from October 2022. Venous blood was taken in the fasting state. The total Kt/V value was calculated using the formula recommended in K/DOQI. Hemoglobin (Hgb) and the mean corpuscular hemoglobin concentration were measured using a hematology analyzer. Furthermore, the corresponding reference ranges used for Hgb were 115–150 g/L in women and 120–160 g/L in men. The MCHC was in a range of 316–354 g/L. Percentage of transferrin saturation was calculated by dividing serum iron by the total iron-binding capacity and multiplying the result by 100. TS ranged from 20% to 55%. Creatinine concentrations were determined by the enzymatic method, and urine microalbumin was determined by the immunoturbidimetric method. All assays were conducted at the Clinical Laboratory, Beijing Hospital of Traditional Chinese Medicine.Based on the ISPD and K/DOQI guidelines, participants were classified into two groups according to total Kt/V, viz., adequate (Kt/V ≥1.7) and inadequate (Kt/V <1.7) groups.2 tests for categorical variables and Wilcoxon rank-sum tests for continuous variables were used to assess the differences in demographic data and clinical biomarkers between the two groups.Normally distributed variables are expressed as the mean (standard deviation), skewed variables as the median (interquartile range), and categorical variables as the count (percent). The χa priori balanced in logistic regression analyses. The gender differed significantly between the two groups (p = 0.001) in an unadjusted model. Hypertension control was reported as the preserve of the residual kidney function, which had an impact on the calculation of total Kt/V  was also calculated for each model.The calibration capability was assessed using the −2 log likelihood ratio test, the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) to inspect how closely the prediction probability for the addition of significant anemia-related biomarkers reflected the actual observed risk and the global fit of the modified risk model. In addition, decision curve analysis reflects the net benefit of adding anemia-related biomarkers. In this curve, the The nomogram model was constructed using the “RMS” package in the R programming environment (version 3.5.2), and the predictive accuracy was reflected by the concordance index (C-index). Statistical power was calculated by using power and sample size calculations (PS) software version 3.0.7. Unless otherwise stated, STATA software version 16  was used for data cleaning and statistical analyses. Without prior notice, the statistical significance was set at a probability of less than 5%.p = 0.001). Distributions of age and PD duration, as well as percentages of hypertension and diabetes, were comparable. As for anemia-related biomarkers, only TS was significantly higher in cases than that in controls (p = 0.006).To facilitate clinical application, a nomogram model was constructed upon being stratified by gender, as illustrated in For example, assuming a woman aged 60 years old with diabetes mellitus and hypertension, PD for 3 years, Hgb of 90 g/L, MCHC of 315 g/L, TS of 15%, and her total points being 350, then the probability of experiencing inadequate PD was estimated to be nearly 90%.The aim of this retrospective study was to examine the prediction of anemia-related biomarkers for inadequate PD in patients with CKD. Our key findings are that the deterioration of three anemia-related biomarkers  can precipitate the development of inadequate PD in Chinese patients with CKD. To the best of our knowledge, this is, thus far, the first report that has evaluated the prediction of anemia-related biomarkers for inadequate PD among Chinese adults.Some studies have examined the association between anemia and PD adequacy, whereas the results of these studies are inconsistent and inconclusive. For instance, a randomized prospective cohort in Hong Kong showed that patients with their total Kt/V maintained below 1.70 had lower levels of Hgb and more severe anemia . A signiThe important finding of this study is that TS differed significantly between patients in the adequate and inadequate groups, which is rarely reported in the medical literature. This finding is biologically plausible. TS can reflect a soluble transferrin receptor, which is a biomarker of erythropoiesis and is often impaired in dialysis patients . There iBecause of the complicated profiles of inadequate PD in patients with CKD, the contribution of individual biomarkers may be small or dependent on the presence of other biomarkers. The majority of studies in this field focused on single biomarkers, while disregarding other relevant biomarkers and overlooking their joint contribution. In this study, we not only assessed the association of anemia-related biomarkers with inadequate PD individually but also jointly in the form of a nomogram. In view of the marked gender differences in the incidence of inadequate PD among patients with CKD, we separately constructed nomogram models for anemia-related biomarkers and the risk of substandard Kt/V by gender, and both models were featured through decent prediction accuracy. For practical reasons, these nomogram models can be routinely applied in clinical practice to facilitate clinical decision-making and the personalized management of PD.Several possible limitations should be acknowledged for this study. First, the cross-sectional data on this study preclude further comments on the cause–effect relationship between anemia-related biomarkers and Kt/V, and all study participants were recruited from one center, requiring further external validation. Second, some unmeasured characteristics of study subjects, such as dietary habits, might confound the association of anemia-related biomarkers with PD . Third, In spite of these limitations, our findings indicate the deterioration of three anemia-related biomarkers  can precipitate the development of inadequate PD in Chinese patients with CKD. Importantly, we have constructed a nomogram model based on anemia-related biomarkers for predicting inadequate PD, which can help provide evidence for medical decision-making and arguments for future research work on anemia as candidate monitors. Meanwhile, we hope that further investigations on the molecular mechanisms linking anemia-related biomarkers and PD inadequacy are warranted.


Background: Cerebral blood flow (CBF) is believed to be relatively constant within an upper and lower blood pressure limit. Different methods are available to monitor CBF autoregulation during surgery. This study aims to critically analyze the application of the cerebral oxygenation index (COx), one of the commonly used techniques, using a reference to data from a series of clinical registrations. Method: CBF was monitored using near-infrared spectroscopy, while cerebral blood pressure was estimated by recordings obtained from either the radial or femoral artery in 10 patients undergoing cardiopulmonary bypass. The association between CBF and blood pressure was calculated as a moving continuous correlation coefficient. A COx index > 0.4 was regarded as a sign of abnormal cerebral autoregulation (CA). Recordings were examined to discuss reliability measures and clinical feasibility of the measurements, followed by interpretation of individual results, identification of possible pitfalls, and suggestions of alternative methods. Results and Conclusion: Monitoring of CA during cardiopulmonary bypass is intriguing and complex. A series of challenges and limitations should be considered before introducing this method into clinical practice. Cerebral complications after cardiac surgery have a multifaceted background, often with serious consequences for the patient . One risThe brain represents about 2–3% of the total body mass. Despite its relatively small weight it still receives approximately 15% of the systemic blood flow. This disproportionally high CBF is explained by a high cerebral metabolically activity requiring about 20% of available circulating oxygen . As cereClinically suitable methods to monitor cerebral autoregulation (CA) emerged during the mid-1990s . The useThe present study aims to critically analyze and discuss the reliability and validity of the COx index as a measure of CA, where the properties of the COx index were illustrated using data from a series of patients undergoing cardiopulmonary bypass (CPB).n = 12) requiring deep hypothermic circulatory arrest were however excluded. The remaining cohort (n = 10) formed the final dataset. Descriptive characteristics are listed in This study was based on data from patients admitted for cardiac surgery at the Heart Centre of Umeå University Hospital between August 2019 and March 2020. The cohort comprised a subset of 22 patients selected at the discretion of the anesthesiologist as suitable for online monitoring of the regional cerebral oxygen saturation. Patients . Patient consent was waived.CPB was conducted in a standard fashion maintaining MAP > 50 mmHg, mixed venous oxygen saturation > 70%, non-pulsatile roller pump perfusion , and membrane oxygenation. Normocapnia (5–6 kPa) and normal arterial oxygen tension (15–20 kPa) were aimed for and verified by intermittent blood gas analyses.Patient monitoring included at least one arterial blood pressure preferably from the radial artery, central venous pressure via the internal jugular vein, 5-lead electrocardiography, peripheral oxygen saturation, and nasal and/or bladder temperature. Induction of anesthesia was performed using propofol and fentanyl combined with rocuronium for skeletal muscle relaxation. Sevoflurane was used to maintain anesthesia throughout the intraoperative period. Blood pressure was controlled by norephedrine or intermittent boluses of phenylephrine.TM  monitor measures the regional cerebral oxygen balance (rSO2) in the prefrontal cortex by emitting infrared light at 730 nm and 810 nm captured by photodetector sensors placed on the left and right side of the forehead. The degree of light absorption at the specified frequencies translates to the actual hemoglobin oxygen saturation level in the arterial, capillary, and venous compartments, where the contribution from the venous saturation is approximately 75%  and the mean value (MV) (2 (4%) by more than 300% based on the interpatient overall median values  at this level indicates a weak association, where the degree of explanation (r2) equals just 16%. From a statistical viewpoint, there is room for a significant degree of uncertainty. Increasing the COx threshold above the 0.4 level would probably increase the sensitivity, but at the same time significantly decrease the success rate, when loss of CA is detected. Where the balance between the magnitude of COx and the success rate is optimal is yet to be defined. The influence of a constantly high rSO2 is of interest. It may explain, why only a few patients demonstrated abnormal CA.On the critical evaluation of the threshold for the COx index, which is typically set to >0.4 , 33, it The COx threshold >0.4 to define impaired CA has become more of a gold standard . Howeverper se does not say anything about its relation to the actual blood flow unless vascular resistance is known.The systemic blood flow is established by the pressure wave generated by cardiac muscle contractions. The pressure build-up within the left and right ventricle during systole is continuous until it overtakes the backpressure on the other side of the opening aortic and pulmonary valve. The ejected stroke volume will elevate the systemic and pulmonary blood pressure at two completely different levels directly related to the vascular resistance in the respective circulatory beds. Of note is that the cardiac output will still be the same within both vascular beds, despite these key differences . The relThis reasoning can be applied in the process of CPB. The main objective in this context is to establish and maintain adequate systemic blood flow traditionally based on a fixed index related to the patient’s body surface area  or more The systemic blood flow delivered from the heart-lung machine will be distributed in a hierarchical manner to all organs and vascular beds . With reMuch of our understanding regarding how CBF control is from the seminal publication by Lassen in 1959 .Even if systemic blood flow and blood pressure are essential in relation to CBF control, other equally essential regulatory mechanisms are also involved, such as neurovascular coupling , cerebroP = 0.044). The magnitude of these COx indices is however very low, which generally would not indicate disturbed CA. Hori and co-workers showed how a blood pressure below the lower limit of preserved CA observed in the intensive care unit was positively correlated with the release of the brain-specific injury biomarker glial fibrillary acidic protein (GFAP) [The amount of evidence showing an absolute association between results from monitoring the COx index and clinical outcomes is limited. Brown and colleagues assessed CA by means of transcranial Doppler in a group of cardiac surgical patients requiring the use of CPB . A totaln (GFAP) . Of noten (GFAP) . Using a, if MAP drops below the targeted limit, the COx registration should signal, and additionally verify that CA is restored by blood pressure adjustments. To the best of our knowledge, no such verification publication exists. Until then, we believe that the information obtained from the COx index should be thoroughly scrutinized before introduction into clinical practice.Monitoring the CA by measuring the correlation between CBF and MAP is intriguing. The method aims to identify a blood pressure limit at which MAP and CBF become correlated. Numerous publications verify that this is possible and more importantly that the information can be used to protect patient groups against a variety of different adverse complications. The key question is whether this blood pressure limit really is a reliable marker of CA? To answer this question, we need investigations to verify that the blood pressure limit can be used to successfully tailor and maintain CA in real-time, i.e.


Objectives: To establish an individualized nomogram to predict the probability of drug-induced liver injury (DILI) in tuberculosis patients receiving anti-tuberculosis treatment.Methods: The clinical information of patients admitted to a tertiary hospital between January 2010 and December 2022 was retrospectively reviewed from the clinical records. Patients with baseline liver diseases (hepatis B or C infection and fatty liver) or taking liver protective drugs were excluded. The maximum values in liver function test within 180 days after anti-tuberculosis treatment were collected to determine the occurrence of DILI. The candidate variables used for establishing prediction model in this study were the last results within the 30 days before the treatment onset. The final variables were included after univariate and multivariate logistic regression analyses and applied to establish the nomogram model. The discrimination power and prediction accuracy of the prediction model were assessed using the area under the receiver operating characteristic (AUC) curve and a calibration chart. The clinical effectiveness was assessed via decision curve analysis (DCA). The established model was validated in two validation groups.Results: A total of 1979 patients with 25 variables were enrolled in this study, and the incidence of DILI was 4.2% (n = 83). The patients with complete variables were divided into training group , validation group I (n = 492) and validation group II (n = 264). Five variables were independent factors for DILI and included in the final prediction model presented as nomogram: age , total bilirubin ≥17.1 μmol/L , uric acid , neutrophil count  and alcohol consumption . The AUCs of the prediction model in the training group, validation group I and validation group II were 0.833, 0.668, and 0.753, respectively. The p-values of calibration charts in the three groups were 0.800, 0.996, and 0.853. The DCA curves of the prediction model were above the two extreme curves.Conclusion: The nomogram model in this study could effectively predict the DILI risk among patients under anti-tuberculosis drug treatment. Mycobacterium tuberculosis (MTB) is the pathogen that causes tuberculosis (TB) in humans and constitutes a great threat to global public health. The World Health Organization (WHO) reported that approximately 10.6 million people fell ill due to TB in 2021 worldwide, and this number is 4.4% higher than that in 2020 : the patients who were diagnosed with tuberculosis infection and started their anti-TB drug treatment between January 2010 and December 2022. The database was constructed based on the clinical records from patients who were admitted to Affiliated Dongyang Hospital of Wenzhou Medical University. Exclusion criteria: the patients who took liver protective drugs for treatment or prophylaxis based on the drug usage record; the patients who were accompanied by HIV infection and liver cancer. The baseline liver diseases including hepatitis caused by HBV or HCV  and fatty liver  were determined based on the extracted information from clinical record database.The definition criteria list for DILI induced by anti-TB treatment included  a clear p < 0.05). The linear relationship between the continual variables and logitp was tested using the Box-Tidwell function. If, a linear relationship was absent (p < 0.05), and the variable was converted into categorical variables based on the normal range. The presence of multicollinearity among the involved variables was defined as variance inflation factors (VIFs) larger than 10, and thus these variables were excluded in further analysis. Second, multivariate analysis and stepwise regression were used to identify variables significantly related to DILI. Based on the finally involved variables, a second validation group  was extracted from the population, excluding those had been enrolled in training group and validation group I. The discriminative ability of logistic regression model was assessed based on the area under the receiver operating characteristic (ROC) curve (AUC), model calibration was evaluated using the Hosmer–Lemeshow statistic  and the net benefit in clinical was evaluated by decision curve analysis (DCA). The prediction power of established model was further validated in two validation groups  and R 4.2.1 software for Windows were used for statistical analysis. Continuous variables were expressed as median with the corresponding interquartile range, and were compared using either Student’s A total of 4,715 patients under anti-TB drug treatment were initially included in this study . 2,259 pp < 0.05, p > 0.05). Seven variables were converted into categorical variables, including globulin, indirect bilirubin, total bilirubin, direct bilirubin, absolute value of monocyte, aspartate aminotransferase and alanine aminotransferase due to no linearity to logitp , elevated total bilirubin , neutrophil count , and alcohol consumption . Conversely, uric acid  was the protective parameter against the development of DILI  were significantly related to DILI by stepwise regression . Accordi of DILI .p-value of 0.800 based on the Hosmer & Lemeshow test  was extracted from the 1979 patients with complete information on final five variables after excluding those involved in training group and validation group I. Fourteen variables showed significant differences between training group and validation group II . The eston curve .Based on the established logistic regression model, a nomogram for presenting the significance of involved variables for predicting the risk of DILI among the patients was established . IndividDILI in patients receiving anti-TB agents can interrupt the therapy process, and identification of associated risk factors can help clinical staff to take preventive measures against it. Here, a nomogram model was established based on five clinical parameters  assessed before the treatment onset. This model could predict the DILI risk in patients receiving first-line anti-TB agents who did not take any hepatoprotectants, and has a good discrimination power.A 6-month regimen is recommended by WHO composing of four first-line anti-TB agents  for patients with TB . The regIn this study, five objective parameters were involved in the prediction model, and these parameters can be easily obtained in clinical practice before the anti-tuberculosis treatment. Elevated levels of total bilirubin might be associated with metabolism dysfunction in liver, eventually increasing the DILI risk once the treatment starts. As the sum of indirect bilirubin and direct bilirubin, the increased total bilirubin might be the results of reduced uptake ability by the liver and weakened excretion by the kidney. In this study, the kidney related variable creatinine was comparable between patients with DILI and without DILI, indicating for key role of liver dysfunction in elevated total bilirubin instead of kidney impairment. Though other studies have indicated the significance of ALT and AST levels for predicting DILI, these two variables were not the significant factors in this study . The incAlthough several studies on DILI risk factors have been conducted, these studies involved limited numbers of patients and mostly focused on screening for risk factors . Our nomThere were some limitations in this study. Despite the large sample size, all the patients were from a single center, and thus the prediction power of established model need be validated in other regions. The duration between the treatment onset and DILI occurrence was not available from the database. Several parameters were not available for some of the involved patients due to the retrospective nature of the study, resulting in the exclusion of more than 50% of the patients. In addition, the treatment duration and accumulative drug dosage were not available from the database.TB patients frequently suffer from DILI after receiving first-line anti-TB agents, though they were not accompanied by liver-related diseases before treatment, including HBV infection, fatty liver and liver cancers. A nomogram model based on five variables before anti-TB treatment  can predict future DILI with a good discriminative power. This prediction model based on these easily accessible parameters can help clinical staff to evaluate the DILI risk before the treatment and take active intervenes to prevent the occurrence of DILI in patients with high risk.


The effect of inverse inspiration:expiration (I:E) ratio on functional residual capacity (FRC) during pneumoperitoneum is unclear. We hypothesised that volume-targeted pressure-controlled inverse ratio ventilation (vtPC-IRV) would increase FRC by increasing the level of auto-PEEP in low respiratory compliance situations.2O; (2) IRV2, I:E ratio of 2:1 and BAP off; (3) IRV3, I:E ratio of 3:1 and BAP off; and (4) IRV4, I:E ratio of 4:1 and BAP off. The changes in FRC were identified and compared among these settings.During robot-assisted laparoscopic radical prostatectomy, 20 obese patients were sequentially ventilated with four different settings for 30 min in each setting: (1) control, I:E ratio of 1:2 and baseline airway pressure (BAP) of 5 cm HP=0.006). Shunt and physiological dead space were significantly lower in all IRV groups than in the control group; however, there were no significant differences among the IRV groups.The FRC significantly increased as the I:E ratio increased. The FRC values expressed as median (inter-quartile range) during control, IRV2, IRV3, and IRV4 were 1149 (898–1386), 1485 (1018–1717), 1602 (1209–1775), and 1757 (1337–1955) ml, respectively. Auto-PEEP increased significantly as the I:E ratio increased and correlated with FRC (rho=0.303; vtPC-IRV with shortened expiratory time and increased auto-PEEP effectively increases FRC during robot-assisted laparoscopic radical prostatectomy in obese patients. FRC increases progressively as the I:E ratio increases from 1:2 to 4:1; however, an I:E ratio higher than 2:1 does not further improve the dead space.UMIN000038989. However, VDphys increases with time, suggesting that atelectasis develops with time during surgery. FRC, auto-PEEP, or total PEEP were not measured in those studies. No previous studies have investigated the effect of inverse inspiration:expiration (I:E) ratio with short expiratory time on FRC during pneumoperitoneum in the Trendelenburg position. Thus, we aimed to evaluate the FRC with various I:E ratios of vtPC-IRV in obese patients undergoing robot-assisted laparoscopic radical prostatectomy.We previously reported that the physiological dead space  on 15 April 2019 (No. 18–194). It was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000038989). Written informed consent was obtained from all participants.−2 aged 40–75 yr with ASA physical status score 1–2, scheduled to undergo robot-assisted laparoscopic radical prostatectomy. The exclusion criteria were ASA physical status of 3–5, a history of asthma, pulmonary emphysema, pneumothorax, or lung surgery. The patients were enrolled between 15 June 2019 and 30 July 2020.The study included patients with BMI >25 kg m2 analysis. Continuous radial arterial pressure, cardiac index, and stroke volume variation (SVV) were monitored using a Vigileo system with a Flo-Trac sensor . Mainstream CO2 and flow sensors were attached to the proximal end of the tracheal tube to enable volumetric capnography . Anaesthesia was induced by administering i.v. propofol 1–3 mg kg−1 and fentanyl 2–4 μg kg−1. Tracheal intubation was performed after the administration of rocuronium 0.8–1.0 mg kg−1. Anaesthesia was maintained by total intravenous administration of propofol 100–200 μg kg−1 min−1 and remifentanil 0.2–0.3 μg kg−1 min−1. Intermittent intravenous injections of rocuronium 0.1–0.2 mg kg−1 and fentanyl 1–2 μg kg−1 were administered, as needed.Routine patient monitoring included ECG, pulse oximetry, noninvasive arterial blood pressure measurement, and inspired and expired CO2 pneumoperitoneum at 12 mm Hg, the patients' lungs were sequentially ventilated using four different settings for 30 min each: control, IRV2, IRV3, and IRV4 settings. Each ventilator setting included the volume targeted pressure control (expressed as ‘pressure control ventilation-volume guarantee’ in Engström Carestation™) mode, in which the airway pressure was adjusted to achieve a target tidal volume. The target tidal volume was adjusted with the plateau pressures permitted to increase to an upper limit of 30 cm H2O. The initial fraction of inspiratory oxygen (FiO2) was 0.5, and the ventilatory frequency was set at 12 bpm. The target tidal volume and ventilatory frequency remained constant throughout the study providing there were no respiratory complications. For the control setting, the I:E ratio was 1:2, and the baseline airway pressure . In IRV3, the I:E ratio was 3:1 and BAP was off. In IRV4, the I:E ratio was 4:1 and BAP was off.After the induction of anaesthesia, we ventilated the patients' lungs using a ventilator  that measures FRC and auto-PEEP. After positioning in the 25–30° Trendelenburg position and CO2O, peripheral oxygen saturation was allowed to drop to 93%, whereas end-tidal carbon dioxide (ETCO2) was permitted to increase to 60 mm Hg. When any of these predetermined limits were exceeded, the study was halted, and the ventilator setting was changed to an I:E ratio of 1:1, increasing the ventilatory frequency and FiO2 and increasing or decreasing the tidal volume.Auto-PEEP was allowed to increase to 10 cm H−1 of Ringer's acetate solution or hydroxyethyl starch if the SVV exceeded 15%.The MAP was maintained >70 mm Hg using IV ephedrine (4–8 mg). An intravenous fluid challenge was provided with 10 ml kgi’ in Engström Carestation™) and total PEEP were calculated as follows: total PEEP=auto-PEEP+PEEP. Static compliance (Cstat) was calculated as Cstat=VTI −1, where VTI is the inspired tidal volume and Pplat is the plateau pressure.The primary outcome measure was FRC measured using the oxygen wash-in and wash-out methods provided within the ventilator (Engström Carestation™). The International Organization for Standardization (ISO) redefined the baseline and PEEP terminology.phys) is a functional evaluation of the difference in the partial pressure of CO2 between the arterial blood and mixed expired gas [VDphys=VTE･(Paco2–PEco2)･Paco2−1], where VTE is the expired tidal volume and Peco2 is the mixed expired gas partial pressure of CO2, representing the overall CO2 elimination efficiency of the respiratory and circulatory dynamics. Using the volumetric capnography theory (see Supplementary data), VDphys was divided into airway dead space (VDaw), alveolar dead space , and shunt dead space (VDshunt)   is a functional evaluation of the difference in CO2 partial pressure between the alveolar and mixed expired gas, representing V̇A/Q̇>1 mismatch. VDalv, calculated as VDresp–VDaw, is a functional evaluation of the relative hyperinflation in the alveolar units, representing intra-alveolar V̇A/Q̇>1 mismatch. VDshunt, calculated as VDphys–VDresp or VDphys–VDaw–VDalv, represented functional evaluation of relative hyperperfusion and the difference in CO2 partial pressure between the pulmonary artery and mixed expired gas, representing V̇A/Q̇<1 mismatch.Physiological dead space (VDVDshunt) . VDaw isaw change represented extra-alveolar V̇A/Q̇=∞ mismatch derived from airway space volume change. Plateau-dependent VDaw change represented extra-alveolar V̇A/Q̇=∞ mismatch caused by gas diffusion in the airway. Plateau-dependent VDalv change represented intra-alveolar V̇A/Q̇>1 mismatch caused by hyperinflation with circulatory suppression. The plateau-independent VDalv change represented intra-alveolar V̇A/Q̇=∞ mismatch such as pulmonary infarction. Plateau-dependent VDshunt change represented intra-alveolar V̇A/Q̇<1 mismatch caused by heterogeneous expansion disorders. Plateau-independent VDshunt change represented intra-alveolar V̇A/Q̇=0 mismatch caused by atelectasis and extra-alveolar V̇A/Q̇=0 mismatch caused by an extra-alveolar shunt . Non-parametric data distribution was assumed owing to the small number of patients included in this study, and the descriptive parameters were generally expressed as median (inter-quartile range [IQR]).The sample size was calculated based on previous data1, % predicted), target tidal volume, BAP, and I:E ratio. Spearman's rank correlation was used to assess the relationship between the variables. All statistical analyses were performed using R© version 3.5.2 . Statistical significance was set at P<0.05.The Friedman test followed by the Wilcoxon signed-rank test with Bonferroni correction were used to identify the changes and differences in respiratory and haemodynamic variables among the ventilator settings. Multiple regression analysis was used to identify the influence of various factors on the primary outcome measure. The dependent variable was FRC, and the independent variables were selected from patient characteristics and ventilator settings based on clinical prediction. We eliminated the calculated or estimated variables from the potential independent factors. The selected independent variables were BMI, FVC (% predicted), forced expiratory volume in 1 s , I:E ratio (P=0.001), and target tidal volume (P<0.001) were independently associated with FRC . However, other factors, including %predicted FVC, %predicted FEV1, or BAP, were not. Spearman's rank correlation showed that FRC values were correlated with auto-PEEP, static compliance, Pao2/FIO2, VDshunt, and VDphys, but not with total PEEP , auto-PEEP reached 9 cm H2O during the IRV4 settings with FRC of 1752 ml compared with 1157 ml at the control settings.There were no respiratory complications during the perioperative period with auto-PEEP, peripheral oxygen saturation, and EThe effect of an inverse I:E ratio on FRC during pneumoperitoneum remains unclear. We found that the larger the I:E ratio with vtPC-IRV, the higher was the FRC. Furthermore, the I:E ratio – but not BAP – was an independent predictor of FRC. FRC was correlated with auto-PEEP but not with PEEP or total PEEP.2O with an I:E ratio of 1:2 effectively improved FRC and respiratory mechanics in non-obese patients. However, the effects of high BAP were diminished in patients with obesity during general anaesthesia with neuromuscular blocking agents.2O did not prevent FRC decreases.2O increased end-expiratory lung volume and improved Pao2/FIO2 in obese patients during elective laparoscopic surgery.Tan and colleagues2 pneumoperitoneum in the Trendelenburg position. Therefore, it was difficult to increase FRC because of the low levels of BAP with a long expiratory time (I:E ratio of 1:2), in the same way as previously reported. Thus, our results suggest that short expiratory time with IRV accompanied by increased auto-PEEP would effectively increase FRC under such conditions with a low static compliance. However, although increased FRC may prevent atelectasis, it has a potential risk of hyperinflation of the normal alveoli and circulatory compromise.In our study, patients with obesity must have had low static compliance during COA/Q̇<1) in the impaired alveolar unit and may redistribute the inflated gas toward the healthy alveolar unit excessively, causing relative hyperinflation (V̇A/Q̇>1). Similar to lung recruitment manoeuvres, PC-IRV can decrease pulmonary blood flow to the ventilated alveoli, inducing relative hyperinflation (V̇A/Q̇>1). Moreover, it is likely to redistribute the pulmonary blood flow toward the non-ventilated alveoli, promoting relative hyperperfusion (V̇A/Q̇<1).Atelectasis may obstruct alveolar expansion, inducing relative hyperperfusion  may contribute to reduced FRC and induce atelectasis. Furthermore, increasing FRC by BAP under long expiration time (I:E ratio of 1:2) with low respiratory compliance is difficult. IRV with a short expiratory time and high auto-PEEP even with low respiratory compliance effectively increases FRC. However, IRV is not commonly used or safe. It needs an anaesthesia ventilator equipped with an expiratory flow-time wave monitor to avoid lung hyperinflation, adequate haemodynamic management, moderate muscle relaxation, and the expertise of an anaesthesiologist. Therefore, IRV with an I:E ratio of 3:1–4:1 is not recommended. However, a short expiratory time with IRV would enhance the BAP effect of increasing FRC in situations with low static compliance. We believe that vtPC-IRV with an I:E ratio of 1:1–2:1 and a BAP of 5–7 cm H2O is a safe and practical open-lung approach ventilation strategy in situations with low static compliance, which may provide sufficient total PEEP and appropriate inflation of the slow opening alveolar components.Earlier studies showed that the higher the BAP, the higher was the FRCphys and VDshunt increased within 2 h intraoperatively, and atelectasis probably developed in ventilator conditions with an I:E ratio of 1:2 or 2:1, suggesting that FRC may decrease, and the dead space components may increase with time. Therefore, it is conceivable that our findings of IRV acutely increasing FRC and decreasing VDphys and VDshunt were attributable to ventilator settings, rather than time-dependent changes.In this study, the ventilator settings were sequentially changed at intervals of 30 min, and the measurements were obtained at the end of each setting. As the sequence was not randomised, the results might be influenced by time-dependent changes or trends in respiratory status during the 2-h intervention period. We cannot rule out this possibility. However,,Atelectasis likely develops heterogeneously within hours; however, we only measured acute changes in the respiratory and circulatory status in each 30-min period of ventilator setting. Changes over a longer period or the actual degree of atelectasis were not evaluated. Further studies evaluating the development of atelectasis using electrical impedance tomography, a useful tool for evaluating the heterogeneous development of atelectasis over time,vtPC-IRV with short expiratory time and high auto-PEEP effectively increases FRC during robot-assisted laparoscopic radical prostatectomy in patients with obesity. The higher FRC is observed with larger I:E ratio in vtPC-IRV. Furthermore, vtPC-IRV decreases the shunt and physiological dead space, indicating that vtPC-IRV can be used as an open-lung approach ventilation strategy in cases of low respiratory compliance. However, an I:E ratio of more than 2:1 does not improve dead space further, suggesting that using an I:E ratio of more than 2:1 is not required under these conditions.Study design: GH, TA.Data acquisition: GH, YY, HO, MS, KM.Data analysis: GH.Drafting of the article: GH, TA.All authors interpreted the data and approved the final version of the manuscript.The authors received no specific funding for this work.The authors declare that they have no conflicts of interest.


To retrospectively investigate the hemodynamic stresses in initiating aneurysm formation on major cerebral arterial bifurcations with computational fluid dynamics (CFD) analysis.The cerebral 3D angiographic data of major cerebral arterial bifurcations of the internal carotid, middle cerebral, anterior cerebral, and basilar arteries in 80 patients harboring bifurcation aneurysms and 80 control subjects with no aneurysms were retrospectively collected for the CFD analysis of hemodynamic stresses associated with aneurysm formation.P < 0.001) correlated with the age. At the center of direct flow impingement (CDFI) on the bifurcation wall, total pressure was the highest but dropped rapidly toward the branches. Wall shear stress, dynamic pressure, strain rate, and vorticity were lowest at the CDFI but they increased quickly toward the branches. The bifurcation angle was significantly (P < 0.001) enlarged in patients with bifurcation aneurysms than those without them, for all major arterial bifurcations. Most aneurysms leaned toward the smaller arterial branch or the arterial branch that formed a smaller angle with the parent artery, where the hemodynamic stresses increased significantly (P < 0.05), compared with those on the contralateral arterial branch forming a larger angle with the parent artery. Following the aneurysm development, all the hemodynamic stresses on the aneurysm dome decreased significantly (P < 0.001) compared with those at the initiation site on the bifurcation wall after virtual aneurysm removal. With the decrease of bifurcation angles, all the hemodynamic stresses decreased.Bifurcation angles at major bifurcations in all patients were significantly positively (The formation of intracranial aneurysms on major intracranial arterial bifurcations is significantly associated with locally abnormally augmented hemodynamic stresses, which must be reduced. Cerebral aneurysms are not uniformly distributed in the cerebrovascular tree even though some risk factors, including family history, smoking, and hypertension, exist for aneurysm formation, which impact cerebral arteries as a whole . CerebraThis retrospective one-center study was conducted from March 2016 to February 2021 in our hospital, and informed consent was waived by the ethics committee of our hospital because of the study's retrospective design. The datasets of consecutive patients with 3D digital subtraction angiography (DSA) were retrospectively included. All clear 3D imaging data of big vascular bifurcations were included, and patients with unclear imaging datasets were excluded.3, and a blood viscosity of 3.5 cP . Surface smoothing, virtual removal, and reconstruction of the aneurysm and arteries were conducted using the Meshlab software  . Polyhedf 3.5 cP  were useThe parent artery diameter was measured at the midway point between the bifurcation apex and the last branching point on the parent artery . The dauWhen comparing the hemodynamic stresses before and after aneurysm development, the virtual aneurysm removal technique, similar to the approach used by Gao et al.  and Mantt-test after confirming the normal distribution of the data. The statistical significance was defined as P < 0.05.The statistical analysis was conducted using JMP software . The correlation of parameters was assessed by multivariable analyses using the least squares linear regression approach, and the comparison between different groups was made by conducting Student's n = 20), middle cerebral artery , internal carotid artery , and basilar artery  bifurcations, were randomly selected for CFD analysis, with 43 women and 37 men aged 26–92 years (mean 55.8 ± 10.6). Twenty aneurysms were randomly selected for each major arterial bifurcation. The patients exhibited clinical symptoms, including subarachnoid hemorrhage, double vision, headache, face numbness, confusion, and other non-specific symptoms . Twenty subjects without cerebral arterial stenosis or intracranial aneurysms were randomly recruited into the control group for each big intracranial arterial bifurcation for comparison with the aneurysm group, including 39 women and 41 men aged 22–81 years (mean 52.2 ± 9.1). The patients' gender, age, aneurysm status, and clinical symptoms were collected. No significant (P > 0.05) differences were found in the mean age or gender component between the aneurysm and control groups.Eighty patients with intracranial aneurysms on big arterial bifurcations, including the ACA  positively correlated with age. The mean bifurcation angle was significantly (P < 0.001) greater in patients with than in those without bifurcation aneurysms . The lateral angle formed between the parent and either branching artery was significantly (P < 0.05) smaller in bifurcations with aneurysms than in bifurcations without aneurysms. Of the 80 bifurcation aneurysms, 68 (85%) aneurysms were deviated toward the branching artery, forming a smaller angle with the parent artery  on the aneurysm dome compared with those on the aneurysm initiation site , implying that aneurysm formation was to relieve the energy effect on the arterial bifurcation wall at the aneurysm initiation location.Analysis of the hemodynamic forces on the aneurysm dome and initiation site after virtual aneurysm removal ; Table 1P < 0.01, P < 0.01, P < 0.05, and P < 0.05, respectively) greater than those at Peak 2 . Moreover, the distance from Peak 1 to the direct impingement center was significantly greater than that from Peak 2 to the direct impingement center   .P < 0.001) difference was found between lines 3 and 5 in terms of dynamic pressure (189.6 ± 4.8 Pa vs. 134.8 ± 6.0 Pa), total pressure (311.5 ± 4.7 Pa vs. 386.0 ± 6.4 Pa), vorticity , WSS (24.6 ± 0.5 Pa vs. 18.4 ± 0.4 Pa), and strain rate , with the total pressure significantly greater on line 5 than on line 3 but the dynamic pressure, WSS, vorticity, and strain rate all significantly smaller on line 5 than on line 3. Significant differences were observed between lines 2 and 6 or between lines 1 and 7 . Moreover, the dynamic and total pressure, WSS, vorticity, and strain rate on line 3  were all significantly greater than those on line 2  (P < 0.001)  but the least dynamic pressure (44.9 ± 7.4 Pa), vorticity , WSS (9.7 ± 0.9 Pa), and strain rate  . From tr< 0.001) .P < 0.001) greater in the arterial branch that formed a smaller angle with the parent artery than the other arterial branch  to the location where the flow was parallel (laminar) to the bilateral daughter arterial wall was termed D, which indicated the acceleration area. Ds was from the direct impingement center to the point the flow became laminar on the branching artery that formed a smaller angle with the parent artery, and Di was from the direct impinging center to where the flow became laminar on the other arterial branch that formed a larger angle with the parent artery . Blood fThe analysis of patients with different BA bifurcation angles  after virtual aneurysm removal demonstrated that, with the narrowing of bifurcation angles, all the hemodynamic parameters decreased, the profiles of the parameters became narrowed, and the direct flow impingement region shrank, with the hemodynamic stresses focusing more on the bifurcation wall , 5. As tThe risk factors for intracranial aneurysm formation, including age, gender, hypertension, and hemodynamic stresses, all contribute to the initiation and growth of intracranial aneurysms , 15, andP < 0.001), whereas the angle between the arterial branch and the parent artery in patients with bifurcation aneurysms was significantly (P < 0.05) smaller than that in patients without aneurysms. Our findings were similar to one study (P < 0.05) increased compared with those at Peak 2 on the arterial branch that formed a larger angle with the parent artery. This may indicate that, on entering the arterial branch that formed a narrower angle with the parent artery, the blood flow greatly enhanced the hemodynamic stresses to damage the vessel wall at the peak site of the stresses for inducing an aneurysm. At the direct flow impingement center where the flow direction was perpendicular to the bifurcation wall, the total pressure reached the maximum, whereas the dynamic pressure, WSS, vorticity, and strain rate dropped to their lowest points. Low WSS only enhanced endothelial hyperplasia   , 3. ThisP < 0.001) compared with those on line 2, which probably suggests that the hemodynamic forces depicted by line 3 at Peak 1 on the arterial branch that formed a narrower angle with the parent artery are significant enough to trigger an aneurysm  lower than those at the aneurysm-triggering location. In the analysis of line-sampled hemodynamic stresses, the total pressure, dynamic pressure, strain rate, vorticity, and WSS on the aneurysm dome were very low, which suggests that aneurysm development involves the release of the local abnormally increased hemodynamic forces at the aneurysm-triggering location (P < 0.001). This suggests that vascular protrusion and aneurysm development involve the release of high local hemodynamic forces, including total pressure, dynamic pressures, and WSS.In the analysis of the hemodynamic forces on the major artery bifurcations before and after virtual aneurysm removal, the hemodynamic forces on the aneurysm dome were significantly  positive correlation with the patient's age, indicating that the arterial bifurcation angle increases with age. Moreover, the arterial bifurcation angle was significantly (P < 0.001) wider in patients with aneurysms than those without bifurcation aneurysms. Cerebral aneurysms tend to occur in patients at ~50 years of age  account for over 25% of all intracranial aneurysms . The ACAOur study, different from other studies –36, inveThis study had some limitations. In the blood flow simulation for CFD analysis, we used the flow inlet parameters of 0.1 m/s for velocity and 0 for pressure at the outlet for simulation in the intracranial arteries. If the inlet was at the beginning of ICA, internal carotid artery; BA, basilar artery, this inflow value of 0.1 m/s may not be sufficient for reflecting the actual value. However, the CFD study aimed to reach statistically significant values and differences, and in this aspect, we did reach a significant difference in patients with and without bifurcation aneurysms or in patients with narrowed or widened bifurcation angles. Moreover, real arteries are elastic and pulsate during systole, and in our study, we used rigid non-slip walls for CFD simulation, which is also a relative limitation when interpreting the data from CFD models.In summary, the hemodynamic stresses in the acceleration region near the direct flow impingement center at major arterial bifurcations were all increased on the arterial vessel that formed a narrower angle with the parent artery, probably triggering an aneurysm to release the local abnormally increased hemodynamic stresses induced by the direct impingement of blood flow.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Ethical review and approval was not required for the study on human participants in accordance with the local legislation and institutional requirements. Written informed consent from the patients/participants or patients/participants' legal guardian/next of kin was not required to participate in this study in accordance with the national legislation and the institutional requirements.HG: Data curation, Formal analysis, Funding acquisition, Investigation, Validation, Visualization, Writing—original draft. J-FL: Data curation, Investigation, Methodology, Supervision, Validation, Visualization, Writing—review and editing. C-HL: Conceptualization, Formal analysis, Investigation, Methodology, Project administration, Supervision, Validation, Writing—review and editing. J-WW: Data curation, Investigation, Methodology, Resources, Validation, Visualization, Writing—review and editing. HL: Data curation, Investigation, Methodology, Resources, Supervision, Validation, Visualization, Writing—review and editing. B-LG: Conceptualization, Data curation, Formal analysis, Investigation, Supervision, Validation, Visualization, Writing—review and editing.


Conclusion: A decrease in the FT3/FT4 is an independent predictor of DKD occurrence in patients with T2DM.Objective: This study aims to explore the correlation between the free-triiodothyronine (FT3)-to-free-thyroxine (FT4) ratio (FT3/FT4) and diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus (T2DM). Methods: This study retrospectively analyzed 1729 patients with T2DM hospitalized in the Department of Endocrinology, Peking University International Hospital, from January 2017 to August 2021, including 1075 males and 654 females. In accordance with the FT3/FT4, the patients were divided into three groups. Results: (1) The levels of glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG) and postprandial blood glucose (PBG) among the three groups were significantly different, with the low FT3/FT4 group having the highest HbA1c, FBG and PBG among the three groups (F = 39.39,  In recent times, due to the advancement of the economy and people’s lifestyles, there has been a gradual rise in the prevalence of type 2 diabetes mellitus (T2DM). According to the International Diabetes Federation, there are approximately 422 million people with DM worldwide . End-staEarlier research has established a strong association between thyroid hormone (TH) and DM, as well as its associated complications. The association between thyroid dysfunction and microvascular complications in diabetic patients can be attributed to multiple factors including metabolic disorders, acid–base imbalances and tissue hypoxia caused by hyperglycemia, which can inhibit the activity of type 1 deiodinase and reduce the conversion of T4 to T3 in peripheral tissues ,6. PostmCompared with healthy people, the prevalence of thyroid disease in DM patients is higher; in particular, the prevalence of hypothyroidism in DM patients is higher than in healthy people . Recent The study was approved by the Ethics Committee of Peking University International Hospital and was conducted in accordance with the ethics standards of institutional and national research committees and the 1964 Helsinki Declaration and its later amendments or comparable ethics standards. As the study involved the retrospective analysis of clinical data, the requirement for written informed consent was waived. The number of the ethics approval is 2022-KY-0030-01. The clinical trial register number is ChiTR1800014785.The present study conducted a retrospective analysis of a total of 1729 patients diagnosed with T2DM who were admitted to the Department of Endocrinology at Peking University International Hospital from January 2017 to August 2021. The study population comprised 1075 males and 654 females, with an average age of 54.67 ± 13.65 years. All participants in this study were diagnosed with diabetes according to the diagnostic criteria for diabetes established by the World Health Organization (WHO) in 1999 . The cri2) = weight (kg)/body height2 (m2); WHR = waist circumference (cm)/hip circumference (cm).A retrospective analysis was conducted on the data of 1729 patients, and their general characteristics such as sex, age, height, weight, waist circumference, hip circumference, systolic blood pressure (SBP), diastolic blood pressure (DBP), diabetic duration and complications of diabetes were recorded in detail. BMI and WHR were calculated using the following formulae: BMI , fasting blood glucose (FBG), postprandial blood glucose (PBG), triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum creatinine (sCr), uric acid (UA), free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH) and the ratio of FT3 to FT4 (FT3/FT4). The PBG were tested for 2 h after ingesting 75 g of glucose during oral glucose tolerance tests. The participants were asked to provide urine samples for three consecutive mornings. The samples were used to measure urinary microalbuminuria, urinary creatinine and urinary-albuminuria-to-creatinine ratio (UACR) using the immunoturbidimetric method in our laboratory.Glomerular filtration rates (eGFRs) were calculated based on the sCr of the study subjects. Calculation formulae are as follows:Male:Female:−1·(1.73 m2)−1 for more than 3 months; or (3) renal biopsy consistent with the pathological changes in DKD.According to the Chinese Guidelines for the prevention and treatment of diabetes kidney disease , DKD canIn this study, a total of 384 patients with T2DM met the criteria for a DKD diagnosis. Out of these patients, 369 underwent renal biopsy, resulting in a renal biopsy rate of 96.09%. The others met the criteria: UACR ≥ 30 mg/g in at least two out of three tests, after excluding any interfering factors.n = 575 cases; the medium group (FT3/FT4 0.25–0.29): n = 577 cases; and the high group (FT3/FT4 > 0.29): n = 577 cases.The patients in the study were categorized into three groups based on their FT3/FT4 levels. These groups were identified as the low group (FT3/FT4 < 0.25): 2 test. Unconditional logistic regression models were used for univariate and multivariate analysis of the factors, and OR and its 95% CI were calculated. The receiver-operating-characteristic curves (ROC) were plotted and the area under the ROC curve (AUC) was calculated. All statistical tests were two-sided, and p < 0.05 was considered statistically significant.The statistical analysis was performed using the SPSS Version 22.0 software . Normality analysis was performed using the Kolmogorov–Smirnov test. The variables that followed normal distribution were presented as mean ± standard deviation. The comparison of continuous variables among the three groups was done using one-way analysis of variance (ANOVA), while the comparison between the two groups was done using the least-significant-difference (LSD) method. The comparison of counting data was done using the χp < 0.01). Additionally, the proportion of male patients was the highest in the high FT3/FT4 group (p < 0.01). The low FT3/FT4 group had the longest diabetic duration, while the high FT3/FT4 group had the shortest diabetic duration (p < 0.01). The UACR and eGFR levels among the three groups were significantly different, with the low FT3/FT4 group having the highest UACR and lowest eGFR levels (p = 0.02). The HbA1c, FBG and PBG levels among the three groups were significantly different, with the low FT3/FT4 group having the highest HbA1c, FBG and PBG levels . In addition, the proportion of DKD was the highest in the low FT3/FT4 group and the lowest in the high FT3/FT4 group (p < 0.01). The SBP, DBP, UA, TC, TG, LDL-C and HDL-C levels were not significantly different among the three groups (p > 0.05) (The low FT3/FT4 group had the highest average age and the lowest BMI compared to the other two groups ( > 0.05) .p = 0.03; r = −0.13, p < 0.01; r = −0.07, p < 0.01, respectively) and positive correlation of eGFR with FT4, FT3 and FT3/FT4   .Using DKD as the dependent variable and TH as the independent variable, a univariate logistic regression model was established. The results revealed that even after adjusting for factors such as age, BMI, sex, diabetic duration, blood pressur, and blood lipid and HbA1c levels, low levels of FT3/FT4 and low FT3 remained independent risk factors for DKD .The model to predict the risk of DKD using three variables, namely, FT3, FT4 and FT3/FT4, showed that the AUC of the models ranked FT3/FT4 (0.65) > FT3 (0.61) > FT4 (0.57). “Cut-off” is the value corresponding to the highest diagnostic accuracy of the variable for DKD. The corresponding cut-off points for FT4, FT3, and FT3/FT4 were 15.95 pmol/L, 4.85 pmol/L and 0.29 pmol/L, respectively .The multivariate predictive model was established with DKD as the dependent variable, and using indices of significant differences in univariate logistic analysis including sex, age, BMI, diabetic duration, blood pressure, HbA1c and FT3/FT4 as independent variables. The regression equation is logit (DKD) = −4.75 − 10.04 ×FT3/FT4 − 0.24 × Sex + 0.01 × Age + 0.02 × Diabetic duration + 0.02 × SBP + 0.07 × BMI + 0.18 × HbA1c. The AUC was 0.71 , the specificity was 56.75%, the sensitivity was 73.39% and the accuracy was 70.89%. The multivariate predictive model was established with DKD as the dependent variable, and using indices of significant differences in univariate logistic analysis including sex, age, BMI, diabetic duration, blood pressure, HbA1c and as independent variables. The regression equation is logit (DKD) = −8.02796 − 0.10217 × Sex + 0.01339 × Age + 0.02537 × Diabetic duration + 0.01901 × SBP + 0.05798 × BMI + 0.22655 × HbA1c. The AUC was 0.68 , the specificity was 72.07%, the sensitivity was 55.83% and the accuracy was 67.94% .DKD is a chronic condition resulting from diabetes and is considered one of the primary microvascular complications of the disease. It is estimated to occur in 20–40% of diabetic patients and is the leading cause of renal failure in this population. If DKD progresses to an advanced stage, it can cause permanent damage to renal function, leading to ESRD. This is a significant cause of mortality and cardiovascular events in patients with T2DM. Therefore, identifying the risk factors associated with DKD can provide valuable clinical information for preventing and treating the condition, ultimately leading to improved outcomes for individuals with T2DM.The association between thyroid dysfunction and microvascular complications in diabetic patients can be attributed to multiple factors. These factors include the following: (1) metabolic disorders, acid–base imbalances and tissue hypoxia caused by hyperglycemia, which can inhibit the activity of type 1 deiodinase and reduce the conversion of T4 to T3 in peripheral tissues ,15. It hIn a retrospective study involving 2832 participants in China, after propensity-score-matching (PSM) analyses, the results indicate that high concentrations of serum FT3 were associated with the significantly reduced risk of having moderate-risk to very-high-risk DKD stages . In our There are three types of deiodinase enzymes in peripheral tissues that regulate thyroid hormone metabolism: type 1, type 2 and type 3. Type 1 exists in the plasma membrane of the liver, kidney, thyroid and pituitary gland, and can deiodinize the inner and outer rings of T4 simultaneously; type 2 has the ability to deiodinize the outer ring to transform T4 into T3; and type 3 inactivates T4 and T3 via iodization of the internal ring . In periIn this study, it was found that there was no significant correlation between TSH and DKD in the univariate logistic regression analysis. This is different from previous studies, which have shown that the TSH levels in patients with DKD are significantly higher than in those without DKD in patients with T2DM . The disIn addition, the results of this study showed that age, male gender, diabetic duration, HbA1c levels and high blood pressure were also risk factors for DKD, which is consistent with previous research ,33,34. FThere are some limitations in our study. First, since it was a retrospective study, we lacked data on certain indicators; for example, some inflammatory factors and the status of deiodinase 2 were not detected. Future studies are needed to investigate whether regulation of thyroid function can improve the prognosis of DKD, and prospective studies are required to explore the underlying mechanism and pathway of the relationship between FT3/FT4 and DKD. Second, the subjects of this study were all inpatients, which may not fully represent the correlation between TH and DKD in outpatients with T2DM. Moreover, since the data were collected during hospitalization, the results of eGFR, TH and other indicators were tested only once, which may have resulted in some degree of error. Finally, maybe due to the limitation of the study sample size, the ROC results need to be further improved. Nevertheless, the current research on the relationship between FT3/FT4 and DKD is limited, and our findings are only a preliminary exploration. In future studies, we will further expand the sample size and conduct multicenter studies to improve the research results of this study.In conclusion, this study found that patients with T2DM and normal thyroid function who had low levels of FT3/FT4 had a significantly higher incidence of DKD. After adjusting for age, sex, diabetic duration, blood pressure and levels of blood lipid and blood glucose, low levels of FT3 and FT3/FT4 remained independent risk factors for DKD. These findings may be useful in predicting DKD in patients with T2DM.


Pulse wave velocity is used to diagnose central arterial stiffness (CAS) andquantify healthy vascular aging (HVA).To evaluate the CAS and HVA in elderly patients with systemic blood pressurelevels classified as optimal/normal.A total of 102 patients without comorbidities and with systolic pressure (SP)< 120 mmHg and diastolic pressure (DP) < 80 mmHg were selected fromthe EVOPIU database . The carotid-femoral pulse wave velocity (c-fPWV) and thecentral and peripheral pressures were evaluated in all patients. Thepatients were divided into four groups: G1: , G2 ,G3 , and G4 .In our sample, 56.7% of patients had c-fPWV ≥ 7.6 m/s. The central systolicpressure in G1 [99 (10) mmHg] was lower than that found in the other threegroups .Older people with optimal arterial blood pressure do not necessarily have HVAand could have c-fPWV values close to the limits established for CASdiagnosis. Systemic arterial hypertension (SAH) is the most prevalent disease amongelderly individuals. The global prevalence of hypertension in the elderly isestimated to be approximately 1 billion individuals.Aging is one of the most important causes of central arterial stiffness (CAS) inelderly individuals. Central vessel stiffness is a risk factor for cardiovascularmorbidity and mortalitySystolic Blood Pressure Intervention Trial  showedthat systolic pressures (SP) < 120 mmHg and diastolic pressures (DP) < 80 mmHgin elderly patients reduced cardiovascular risk by 25%, with lower rates of fataland nonfatal events and death from any etiology. The SPRINT results have changed the pressure targets in treatinghypertension worldwide. The Brazilian Guidelines for Arterial Hypertension began toclassify patients as having optimal pressure with SP less than 120 mmHg and DP lessthan 80 mmHg, while the American Guideline for the Prevention, Detection,Evaluation, and Management of High Blood Pressure in Adults classifiedthe same systemic blood pressure (SBP) levels as normal.The . Measurement of CAS by pulse wave velocity (PWV) has been suggested as anadditional test to calculate cardiovascular risk in hypertensive patients and for adapting therapeutic strategies. However, routine measurement of PWV is not practical and is not recommendedfor routine practice. On the other hand, PWV may be considered a physiologicalmethod for quantifying healthy arterial aging (HVA). The prevalence, correlates, and prognosis of HVA in elderly are incompletelyunderstood. Our study aimed to verify HAV and CAS in elderly patients with systemicblood pressure (SBP) levels classified as optimal/normal.It has long been thought that hypertension leads to a thickening and stiffening ofcentral arteries , whereas more recent evidencesuggests that stiffening precedes hypertension . The EVOPIU database consists of 1,204 patients over 60 years of age, withbiannual clinical and laboratory examinations. The carotid-femoral wave velocity(c-fPWV) was measured each visit. The EVOPIU study lasted 48 months (from 2014 to2018).The present study is a cross-sectional analysis for CAS evaluation in elderlypatients classified as having optimal pressure from the database Study of Pulse WaveSpeed in Elderly in Urban Area in Brazil (EVOPIU) and normal blood pressure according to the American Guidelines for Hypertension. Both cutoffs are SP < 120 mmHg and DP < 80 mmHg.The inclusion criteria were patients who presented at the initial EVOPIU visitwith optimal systemic blood pressure levels according to the BrazilianGuidelines for Arterial Hypertension 2020Patients with diabetes mellitus (DM), diagnosed by fasting glucose > 100 mg/dLor < 100 mg/dL while taking oral hypoglycaemic agents and/or insulin, and allpatients with systemic blood pressure (SBP) above 120/80 mmHg were excluded fromthe study.According to inclusion and exclusion criteria, 102 patients were selected for thepresent study, representing 8.6% of the database. All patients underwentapplanation tonometry to evaluate c-fPWV and were subsequently classifiedaccording to the values obtained for c-fPWV and whether or not they were usingantihypertensive drugs.. For diagnosis of CAS, we used cut-off values of Mendonça et al., whocalculated the values of c-fPWV for hypertensive and normotensive elderly in Brazil.We defined HVA as individuals having c-fPWV of < 7.6 m/s, optimal or normalblood pressures, and no additional cardiovascular risk factorIntelli Sense OmronHem®, Brazil). The values used are the arithmetic mean of the threemeasurements in mmHg. The cuffs of the devices were calibrated and adapted tothe circumference of the arms of the participants. Serum levels of uric acid,urea, and creatinine, blood glucose, and lipid profile were assessed usingcolorimetric methods , whereashematological examination was performed with a Sysmex® XED-2100 . Glomerular filtration rate (eGFR) was estimate by the CKD-EPI equation.The patients were divided into four groups: G1 (n = 19), without antihypertensivedrugs and c-fPWV < 7.6 m/s; G2 (n = 26), without antihypertensive drugs andc-fPWV ≥ 7.6 m/s; G3 (n = 25), using antihypertensive drugs and c-fPWV < 7.6m/s; and G4 (n = 32), using antihypertensive drugs and c-fPWV ≥ 7.6 m/s . Brachia® XCELdevice, model EM4C , which measured: the central andperipheral systolic  and diastolic pressure , pulse pressure, mean arterial pressure , amplification of arterial pulsepressure (AP), augmentation index (Aix %), heart rate (HR) and c-fPWV (m/s).Applanation tonometry (AT) was performed with the SphygmoCorSimple frequency descriptive analyses were performed for the variables, withmeasures of central tendency (mean and median) and variability (standarddeviation and interquartile range). Data were collected in electronicspreadsheets, and statistical tests were performed using Stata software version17.After analyzing the assumptions of normality by the Shapiro-Wilk test, ANOVAtests were applied for the parametric variables and Kruskal-Wallis tests wereapplied for the nonparametric variables. The c-fPWV values were adjusted forsex, age, and bMAP (c-fPWV adj.) (m/s). A value of p < 0.05 was considered anindication of statistical significance.The clinical and laboratory characteristics of the evaluated patients are shown inP< 0.05), and thebody mass index (BMI) did not differ among groups. There were no differences amonggroups for blood glucose, hemoglobin, hematocrit, uric acid, triglycerides,cholesterol, and HDL values. The serum creatinine values differed in all groups andwere higher in G4.The mean age of the patients was 67.8 ± 6.5 years. The median age was similar amongthe groups. Regarding sex, 70.6% of the patients were women, a similar percentage ineach of the four groups. There was a statistically significant difference in thebody weight among groups, being higher in G4  and similar with G3. The adjusted c-fPWV in G2and G4 were similar. G1 and G2 did not use antihypertensive while G3 and G4 usedthem regularly. The correlations between c-fPWV, bSP, cSP, bPP, and cPP werecalculated, and the following results were obtained: c-fPWV and bSP , c-fPWV and cSP , c-fPWVand bPP , c-fPWV and cPP . The correlation between c-fPWV and bPS is shownin The adjusted c-fPWV in G1 was 6.7 ± 0.31 m/s and was lower than groups G2 and G4, no comorbidities, and with c-fPWV within the parameters considered goodvascular health (G1). The elderly individuals in this group did not have DM or othercomorbidities and did not use antihypertensive medications. Group G2  showed an increase in c-fPWV at levelscompatible with the cut-off of CAS diagnosis for hypertensive patientsP< 0.05. The treatment did not seemto normalize c-fPWV in all hypertensive patients or the efficacy of hypotensivedrugs on the stiffness of the arterial wall was not yet evidenced in G4.The antihypertensive drugs used by G3 and G4 and c-fPWV are shown in  studied the arterial stiffness of hypertensive patients with and without DMin patients aged 45 to 97 years and found a positive correlation between SAH and theseverity of arterial vessel thickening. The authors found that patients withuncontrolled SAH had higher arterial stiffness than those with controlled SAH.However, our data showed that elderly patients, even those with OP, had c-fPWV atthe limits of CAS . Qu, Zhang, and Zhu recommends assessing subclinical damage in target organs only in hypertensivepatients. The present study demonstrates that, despite OP, the c-fPWV values may behigh and exceed the limits defined for HVA . Some antihypertensives, such as spironolactone, calcium channel blockers, and inhibitors of the renin-angiotensin system, may reduce CAS regardless ofSBP decrease or its hypotensive associations related to the reduction of CAS regardless of SBP levels.Our data indicate that OP in elderly individuals does not necessarily mean compliantcentral arterial vessels or HVA. However, the Consensus of the European Society ofHypertension/European Society of Cardiologyet al., the authors concluded that patients with good vascular health are moreprotected against occasional SBP elevations than other groups without theseconditions. In our study, it is important to note that c-fPWV was correlated withbrachial and central systolic pressures, while pulse pressures were not correlated.In elderly individuals, bSP and bPP are related to CAS; however, bPP was not correlated with c-fPWV in elderly individuals with OP.There is a possibility that this relationship becomes evident with higher SBPlevels. Vatner et al. demonstrated that arterial stiffness is linearly related to age, both innormotensive and severely hypertensive individuals. Safar et al. showed that the slopes of these linear relationships are not different; inother words, arterial stiffness increase in normotensive individuals in the same wayas in hypertensive individuals. In a study by Freitas . The serum creatinine levels of G4 differed from those of the other groups(CAS plays an important role in increasing microvascular pulsatility with consequentglomerular injuryr groups. G4 had The present was cross-sectional study, with the limitations inherent to this typeof design. The small number of patients in certain groups may not be allow dataextrapolation to larger populations. The study did not analyze the duration ofarterial hypertension and the consequent increase in arterial stiffness and didnot evaluate the effect of hypotensive drugs on c-fPWV. Under these conditions,some patients with c-fPWV within normal parameters could present only oneevolutionary phase of the disease.Older people with optimal pressure do not necessarily have HVA and may have c-fPWVvalues close to the limits established for CAS diagnosis.