Despite their potential interest for clinical management, measurements of respiratory mechanics in patients with acute respiratory distress syndrome (ARDS) are seldom performed in routine practice. We introduced a systematic assessment of respiratory mechanics in our clinical practice. After the first year of clinical use, we retrospectively assessed whether these measurements had any influence on clinical management and physiological parameters associated with clinical outcomes by comparing their value before and after performing the test.The respiratory mechanics assessment constituted a set of bedside measurements to determine passive lung and chest wall mechanics, response to positive end-expiratory pressure, and alveolar derecruitment. It was obtained early after ARDS diagnosis. The results were provided to the clinical team to be used at their own discretion. We compared ventilator settings and physiological variables before and after the test. The physiological endpoints were oxygenation index, dead space, and plateau and driving pressures.Sixty-one consecutive patients with ARDS were enrolled. Esophageal pressure was measured in 53 patients (86.9%). In 41 patients (67.2%), ventilator settings were changed after the measurements, often by reducing positive end-expiratory pressure or by switching pressure-targeted mode to volume-targeted mode. Following changes, the oxygenation index, airway plateau, and driving pressures were significantly improved, whereas the dead-space fraction remained unchanged. The oxygenation index continued to improve in the next 48 h.Implementing a systematic respiratory mechanics test leads to frequent individual adaptations of ventilator settings and allows improvement in oxygenation indexes and reduction of the risk of overdistention at the same time.NCT02623192. Registered 30 July 2015).The present study involves data from our ongoing registry for respiratory mechanics  contains supplementary material, which is available to authorized users. Patients with acute respiratory distress syndrome (ARDS) present various degrees of impairment in respiratory mechanics and different physiological responses to a given level of positive end-expiratory pressure (PEEP). Applying the same ventilator regimen to every patient would be inadequate and at times can be potentially harmful. For example, the potential benefits of high PEEP in terms of oxygenation improvement and alveolar recruitment should be balanced against the risks induced by high pressures, such as hemodynamic impairment and overdistention. In other words, one needs to individualize the PEEP level by evaluating both its safety and its effectiveness for a specific patient . This reL), by a lack of standardized procedures, and by the challenges of integrating the results of these measurements into ventilatory management. Even worse, the most recent large observational studies on patients with ARDS showed that simple parameters such as plateau pressure (Pplat) were not measured in the majority of the patients [Despite their potential interest for clinical management, neither airway pressure (Paw)-based respiratory mechanics nor esophageal pressure (Pes)-based lung and chest wall mechanics are systematically assessed in routine practice. This discrepancy can be explained by technical issues  in obtaipatients .To improve the integration of respiratory mechanics measurement in our clinical practice, a group of physicians and respiratory therapists (RTs) at our institution introduced a respiratory mechanics test to systematically assess respiratory mechanics  for patients with ARDS and be implemented as a quality improvement (QI) program. The goal was to provide clinicians with relevant physiological assessment that could be helpful for clinical practice. Because the needs for adjusting ventilator settings can be very different, this program did not include clinical recommendations or specific guidelines associated with these measurements.Having implemented this systematic test in our clinical practice for 1 year, we retrospectively tried to assess if it had any impact. We looked for whether any changes in ventilatory settings were performed. We also assessed whether the observed changes modified physiological variables known to be associated with mortality, and we tried to understand whether the observed changes were consistent with the measurements.This is a retrospective study of the impact of a 1-year program (see below) with an aim of systematically evaluating respiratory mechanics in patients with ARDS by comparing the ventilator settings and relevant physiological variables before and after performing the measurements. The program was decided by the critical care department at a teaching hospital  and implemented in both the medical-surgical and the trauma-neurosurgical intensive care units (ICUs). Of note, the measurements are entered into a registry for future studies.To increase awareness and understanding of monitoring respiratory mechanics, education sessions consisting of lectures, bench and bedside hands-on sessions, and feedback rounds were provided to ICU clinicians. The education sessions were focused on explaining the importance of measuring respiratory mechanics, the technical approaches for measurements, the physiological and clinical meanings of the measured variables based on scientific evidence, and the limitations of those variables. We did not propose to use one single parameter on which to base changes of the ventilator settings; we proposed to incorporate multiple variables  into the global history of the patient and let the clinical team decide what was best for the patient.To standardize the procedures, we developed written protocols to guide esophageal catheter placement and the associated systematic measurements.To simplify the calculations, we developed a custom-programmed Portable Document Format form  to automatically calculate physiological parameters and generate a clinical report  was recruited voluntarily to facilitate implementing the test in four aspects:2/FiO2) was ≤200 mmHg. In the group of patients with mild ARDS , catheters were placed at the discretion of the clinical team. In the following cases, the clinical team discussed the benefits of doing the measurements on a case-by-case basis: (a) severe hemodynamic instability ; or (b) a known esophageal problem, active upper gastrointestinal bleeding, or any other contraindication to the insertion of a gastric tube.All patients admitted to the ICUs meeting the Berlin definition of ARDS  and receT) of 6 ml/kg of predicted body weight (PBW), a constant inspiratory flow of 50–60 L/minute, and 0.3-second pause at the end of inspiration. Respiratory rate (RR) was set to maintain a minute ventilation (VE) similar to premeasurement level. PEEP and the fraction of inspired oxygen (FiO2) were maintained at the clinically chosen level. Paw, airway flow, and airway volume were directly taken from the ventilator monitoring system. Pes was measured using a catheter with an air-filled balloon  with a pressure transducer connected to a bedside monitor . Measuring Pes was recommended as a component of the test for patients with a PaO2/FiO2 ratio ≤200 mmHg, but the decision of placing a catheter was left at the discretion of the clinicians. The validity of the Pes was confirmed using an occlusion test during spontaneous breathing (premeasurement) or a positive pressure occlusion test by manually compressing the thorax during passive breathing [T between the breaths with occlusion to the one without occlusion. Total positive end-expiratory pressure (PEEPtot), airway peak pressure (Ppeak), and airway Pplat were recorded. Intrinsic PEEP, Pdriv (Pplat − PEEPtot), respiratory system compliance, and resistance were then calculated automatically.Paw-based respiratory mechanics were measured by using end-expiratory and end-inspiratory occlusions for 1–2 seconds. The absence of leakage during an end-inspiratory occlusion was confirmed by the equivalence of expiratory VL,end-exp) and transpulmonary pressure at end inspiration , lung compliance, chest wall compliance, and the ratio of lung elastance to respiratory system elastance were calculated automatically. PL, unless specifically indicated such as elastance-derived transpulmonary plateau pressure, was calculated using direct measurement of Pes.Pes-based lung and chest wall mechanics  were mea2O (preferably 5 cmH2O) from the clinical PEEP level if the Pplat was <35 cmH2O (in the vast majority of the cases). PEEP was reduced by 3–5 cmH2O if the Pplat had reached 35 cmH2O or in the presence of poor hemodynamic tolerance. We report this procedure as an incremental PEEP trial. FiO2 was kept constant for comparing the change in PaO2/FiO2.Oxygenation and hemodynamic responses to PEEP were assessed by increasing PEEP by 3–5 cmH2O from a high to a low level for one breath. Because inspiratory VT was unchanged, the difference in expiratory VT values between the expired VT displayed immediately after decreasing PEEP and the breath before changing PEEP was referred to as the total change in lung volume from high to low PEEP. In parallel, the predicted change in lung volume was estimated by the product of respiratory system compliance at low PEEP (or zero PEEP) and the change in pressure . When the total change in lung volume was greater than this predicted value, the difference was taken as an estimate of derecruited lung volume (Vder). A high Vder  due to reducing PEEP suggested that the PEEP was effective in recruiting the lung (or in maintaining the lung recruited). The rationale for this approach was reported previously, although the current method was simplified to make its use feasible rapidly at the bedside [Alveolar derecruitment was estimated using a single-breath simplified decremental PEEP maneuver Fig.  performe bedside . Of noteEach patient enrolled underwent measurements of respiratory mechanics performed by one or two trained RTs and/or fellows (depending upon availability of clinicians) following a standardized protocol. More than 20 clinicians were considered as trained users. The patients were measured at the early stage of ARDS, and all of them were already deeply sedated and often paralyzed. Additional sedation with or without paralysis could be transiently necessary to suppress or minimize spontaneous breathing. This approach was accepted as part of our clinical practice to get reliable measurements of passive respiratory mechanics. Nevertheless, the decisions of deepening sedation and/or using paralysis for an individual patient were made at the discretion of the clinical team. The absence of spontaneous effort was confirmed by the absence of a negative Paw swing during a 3-second end-expiratory occlusion and by the presence of positive Pes swings during tidal breathing. Volume-controlled ventilation (VCV) was used during the measurements with a standardized tidal volume  were excluded from the study.2 × 100/PaO2) [2, whereas a high OI means that high delivered pressure and/or FiO2  is needed for each millimeter of mercury of PaO2. The dead-space fraction was calculated using the Enghoff modification of the Bohr equation with an estimation of resting energy expenditure using the Harris-Benedict equation and an assumption that the respiratory quotient equals 0.8. It is noteworthy that these two parameters, OI and dead-space fraction, were not directly given to clinicians. The Pdriv, calculated as the difference in Paw between a 1- to 2-second end-inspiratory occlusion  and an end-expiratory occlusion , was referred to as Pdriv in this study. For the purpose of our retrospective study, however, we found that the PEEPtot was not always assessed and documented by clinicians before or after the measurements and that the Pplat was sometimes estimated from the Ppeak in patients receiving pressure-controlled ventilation (PCV). The estimated Pdriv before and after the measurements could therefore slightly differ from the Pdriv during the measurements, and it was calculated as the difference between estimated Pplat and PEEP (not PEEPtot) and referred to as ∆P [We designed a statistical plan to decide a priori which variables we wanted to test. The first question was to determine the proportion of patients in whom ventilatory settings were changed after the measurements. We also wanted to determine if the changes were consistent with the measurements. The relevant endpoints were the effects of these changes on physiological parameters known to be associated with mortality, namely the oxygenation index (OI = mean Paw × FiO00/PaO2) , 8, the 00/PaO2) , Pplat, E  as a surrogate of dead space [We also calculated corrected VE and the O/SI before and after the measurements were compared. The O/SI was not provided to clinicians but was calculated for the study.The denominator can be referred to as the “cost” of mechanical ventilation, whereas the numerator is the “benefit.” Therefore, a low O/SI suggests a low “benefit-to-cost ratio” of mechanical ventilation; that is, the benefit was achieved by paying a relatively high cost, whereas a high O/SI suggests a high benefit-to-cost ratio. Both the corrected VE and Pplat) before and after measurements . We used the ABGs that were closest to the time of measurements but at least 1 h away from the measurements, as well as the corresponding ventilator settings and respiratory parameters. (Also refer to the discussion.) Detailed physiological variables obtained during the measurements were also collected.We collected information by reviewing the clinical charts for patients’ demographic, physiological, and radiographic characteristics; ARDS risk factors; coexisting conditions; ventilator settings; arterial blood gas (ABG) analysis; and documented respiratory parameters , 62 patients were enrolled and had measurements performed  and unchanged in the others. Changes included switching pressure-targeted mode to volume-targeted mode in 19 patients (31.1%), reducing peak inspiratory pressure in 4 patients who were receiving pressure-targeted mode, decreasing PEEP in 22 patients, and increasing PEEP in 9 patients , whereas the mean Paw increased from 18 ± 3 cmH2O to 21 ± 3 cmH2O (P < 0.0005). In patients whose PEEP was decreased, the PaO2/FiO2 remained stable , whereas the mean Paw decreased from 20 ± 4 cmH2O to 16 ± 4 cmH2O (P < 0.0005) .A major change observed concerned the individualization of PEEP, as depicted in Fig. P < 0.0005). We reasoned that the O/SI, similarly to OI, may be more meaningful than oxygenation itself regarding clinical outcome.The changes in ventilator settings, especially a frequent reduction in PEEP level, eventually led to lower airway Pplat and Pdriv, and at the same time to improvements in oxygenation, OI, and O/SI Table . This reWe decided to focus our comparison of the physiological variables at 1 h after the measurements to better ensure that the adjustments of ventilator settings and the physiological impact were likely secondary to the measurements. Later, the ventilation mode can be switched to partial assist mode. Also, comparing mean Paw  or Pdriv in pressure-target mode becomes challenging once the patient recovers spontaneous breathing effort.P = 0.016) than at 1 h after the measurements. Of note, 16 and 21 patients  had spontaneous effort, defined as actual RR exceeding preset RR or receiving partial support mode, – at 24 and 48 h.We, however, also reviewed data at 24 h and 48 h. The improvements in physiological variables were consistent, indicated by the progressively lower OI at 24 and 48 h  on the ventilator settings, interactions were frequent at the beginning of the project, and it is difficult to ascertain their exact influence. These interactions were meant to overcome the technical and knowledge barriers to measurement and interpretation of respiratory mechanics in clinical practice.A respiratory mechanics test can be embedded in clinical practice and provides physiological parameters for clinicians. It leads to individualization of ventilator settings in patients with ARDS that improved physiological endpoints known to be associated with clinical outcomes, and it allowed reduction in the pressures needed to maintain oxygenation.Additional file 1:Figure S1 Patient flowchart. Table S1 Spearman correlation between measurements and the clinical changes in PEEP*. Table S2 Response standardized by ΔPEEP level and clinical adjustments of PEEP*. Table S3 Arterial pH, bicarbonate, and vital signs before and after the measurements (N = 61)*. Table S4 The detailed number of measurements for Table Appendix S1 Sample of the custom-programmed PDF with data obtained in a real case. Appendix S2  Sample of a clinical report automatically generated by the custom-programmed PDF. (DOCX 741 kb)Statistical analysis. Additional file 2:Ethics approval letter. Ethic approval by the research ethics board (REB#16-095) of St. Michael’s Hospital . (PDF 307 kb)


Since both, hypotension and hypertension, can potentially impair the function of vital organs such as heart, brain, or kidneys, monitoring of arterial blood pressure (BP) is a mainstay of hemodynamic monitoring in acutely or critically ill patients. Arterial BP can either be obtained invasively via an arterial catheter or non-invasively. Non-invasive BP measurement provides either intermittent or continuous readings. Most commonly, an occluding upper arm cuff is used for intermittent non-invasive monitoring. BP values are then obtained either manually  or automatically . For continuous non-invasive BP monitoring, the volume clamp method or arterial applanation tonometry can be used. Both techniques enable the arterial waveform and BP values to be obtained continuously. This article describes the different techniques for non-invasive BP measurement, their advantages and limitations, and their clinical applicability. Monitoring of arterial blood pressure (BP) is a mainstay of hemodynamic monitoring in acutely or critically ill patients. Close monitoring of BP is of great importance to detect and treat hypotension and hypertension early. Both, hypotension and hypertension can impair the function of vital organs, such as the brain , the heaThe direct measurement of BP via arterial cannulation is regarded as the clinical reference method (criterion standard). In clinical routine, it is commonly performed during high-risk surgery and in intensive care medicine. The cannulation of an artery, however, can be time-consuming, needs to be done by a trained operator, and is associated—although very rarely —with potThere are several ways to non-invasively measure BP. Monitoring techniques can be classified according to their ability to measure BP intermittently or continuously Figure . In thisFor intermittent BP measurement, an air-filled occluding cuff can be used that enables BP to be measured either manually or automatically. For all occluding cuffs, the right size is critical for valid measurement . Manual With the palpatory method, an inflatable cuff is wrapped around the upper arm of a patient. The manometer connected to the cuff by a tube shows the pressure applied. The physician feels the radial pulse, inflates the cuff until the brachial artery collapses, and there is no blood flow any more. The pressure at which a pulse can be detected again while deflating the cuff corresponds to the systolic arterial pressure of the patient. This method does not need a stethoscope or any other specific skills or equipment and can also be performed in a noisy environment. However, it only provides the systolic arterial pressure. The auscultatory method is performed in a similar way; after inflation of the cuff to a pressure above the systolic pressure , the typical Korotkoff sounds can be detected by a stethoscope applied distal of the upper arm cuff during slow deflation. The onset of the sounds corresponds to the patients’ systolic arterial pressure, the last sound at decreasing cuff pressure equals the patients’ diastolic arterial pressure. The advantage of this technique is that it provides the diastolic arterial pressure value, disadvantages include the need for training how to correctly apply this technique and the need of a stethoscope and a quiet environment.An automated method to measure BP with the help of an occluding cuff employs the oscillometric technique. The cuff is inflated to a preset value automatically. Then, the pressure is gradually being reduced. The pressure wave causes oscillations in the vessel, which can be detected by the cuff. Mean arterial pressure corresponds to the maximum of oscillations ; an algoThe intermittent nature of BP measurements provided by all the techniques described earlier is a disadvantage they all have in common.During the recent years, continuous non-invasive BP monitoring techniques became available that enable a real-time BP curve and numerical BP values to be assessed (just with direct BP measurement).The continuous non-invasive measurement principles are based on either one of two different techniques, namely arterial applanation tonometry or the volume clamp method. Arterial applanation tonometry is based on the work of Pressman and Newgard , who fouThe second technique for non-invasive continuous BP measurement is called volume clamp method (or vascular unloading technology) based on the work by Penaz et al. . The BP The continuous non-invasive devices are all sensitive to patient movement; therefore, monitoring of the conscious patient is possible but measurement results need to be checked for plausibility. In case of severe vasoconstriction, peripheral vascular disease, or distorted fingers due to arthritis, clinical experience has shown that it may be difficult to obtain a valid waveform using finger cuffs. Some patients report discomfort from the congestion in venous return from the fingertip where the cuff is place. For this reason, manufacturers recommend to change the cuff to another finger after a certain period of monitoring. In addition, compared to conventional intermittent devices for BP measurement, continuous BP monitoring is relatively expensive.Most clinicians ask themselves, whether the non-invasively obtained BP curve shows the “real” BP. Therefore, it is inevitable to discuss the measurement performance in terms of accuracy and precision of the various non-invasive devices. The pressure measured within an artery by means of arterial cannulation is regarded as the reference method of BP measurement. In the absence of direct BP measurement, the auscultatory method with a mercury column is regarded as the “gold standard.” However, as Alpert and colleagues  point ouThe reliability of non-invasive intermittent BP measurement in patients with arrhythmia has been questioned . Two stuFor all non-invasive devices that measure BP continuously, numerous validation studies exist –36. Kim In the end, the operator has to know about the limitations and pitfalls of any BP measuring technique, both non-invasive and invasive, to select the optimal technology for BP monitoring for the individual patient.The BP monitoring that we use for the individual patient needs to be tailored to the needs of the patients and the clinical setting.For critically ill patients in the ICU, non-invasive BP monitoring is unlikely to play a big role in the foreseeable future. Although some researchers see the age of total non-invasive BP monitoring dawning , in our In the emergency department, it is crucial to identify hemodynamic instability early. Intermittent BP monitoring, however, often is set at quite long intervals  resulting in missing or only delayed detection of hypotension. There are studies that point out the advantage of continuous monitoring in terms early recognition of deterioration of the patient’s hemodynamic status , 40.For patients undergoing surgical procedures, the appropriate method of BP monitoring needs to be identified considering perioperative cardiovascular risk stratification. There are different types of hypotension during general anesthesia and surgery, e.g., post-induction hypotension, early intraoperative hypotension, and late intraoperative hypotension with different risk factors . There iIn the perioperative setting, the likelihood for intraoperative hypotension and the patient’s risk to develop hypoperfusion-induced organ failure should lead to the choice of which BP monitoring to use Figure . We recoBlood pressure monitoring needs to be tailored to the individual patient. In stable, low-risk patients, intermittent oscillometric BP measurements are usually sufficient. Patients who are at risk for hemodynamic instability should be monitored by continuous BP measurement. Whether continuous non-invasive BP monitoring can improve patient outcome in certain patient collectives or clinical settings  is the subject of the current clinical research. In critically ill patients, we still recommend the continuous invasive BP monitoring with an arterial catheter.All authors listed, have made a substantial, direct and intellectual contribution to the work, and approved it for publication.AM has no conflict of interest. BS collaborates with Pulsion Medical Systems SE  as a member of the medical advisory board and received honoraria for giving lectures and refunds of travel expenses from Pulsion Medical Systems SE. BS received research support from Edwards Lifesciences . BS received institutional research grants, unrestricted research grants, and refunds of travel expenses from Tensys Medical Inc. . BS received honoraria for giving lectures and refunds of travel expenses from CNSystems Medizintechnik AG .


Dizziness is a common chief complaint of patients presenting to the Emergency Department (ED). Physicians must quickly and accurately identify patients whose etiology is most likely ischemia. Additional tools are available, but often require further training (vestibular testing) or are costly and not always readily available (magnetic resonance imaging (MRI)). This study evaluates the ability of a routine history and simple physical examination to correctly identify dizzy patients with posterior circulation ischemia, and the added utility of CT angiography (CTA).We performed a retrospective analysis of all individuals presenting to the ED with a reported chief complaint of dizziness. Neurology was consulted and CTA ordered at the discretion of the ED provider. Demographic, medical, and radiographic variables were evaluated along with final diagnosis. Multivariable logistic regression and ROC analysis were used to determine factors associated with ischemia, the sensitivity of vascular risk factors and focal exam findings in predicting ischemia, and the additional benefit, if any, of CTA.p < 0.0001), systolic blood pressure , and focal exam findings  were most significantly associated with ischemia in multivariable modeling. When age, race, sex, presence of vascular risk factors, and focal neurologic findings were entered into ROC analysis, the AUC for correctly identifying posterior circulation ischemia was 0.90. In the subset of patients who underwent CTA (n = 87), the AUC did not improve .One thousand two-hundred sixteen individuals meeting inclusion criteria presented to the ED over a 2 year period and were included in analysis. One hundred (8.2 %) were diagnosed with posterior circulation ischemia. For the entire cohort, age (OR 1.4 per 10 years, A vascular risk assessment and neurological examination are adequate for risk stratification of ischemia in the dizzy patient and should remain the standard evaluation. Dizziness is one of the most common complaints of individuals presenting to the Emergency Department (ED). In the United States alone, there are approximately 7.5 million cases each year . SubjectEvaluation of dizziness is typically based on clinical suspicion and available resources. Currently, no clear practice guidelines exist , 5. PrioAlong with the physical examination, neuroimaging can be a useful tool for risk stratification in those for whom the diagnosis is not immediately clear; though a noncontrast head CT has been shown to be low yield in prior studies , 15. MagThis study was performed to determine the ability of a standard vascular risk factor assessment and simple neurologic screen to identify patients with dizziness secondary to ischemia, and subsequently the added utility of CTA for risk stratification in individuals with diagnostic uncertainty. Results may lead not only to improved risk assessment, but a significant savings in healthcare costs.This study was approved by the Johns Hopkins University School of Medicine Institutional Review Board. A retrospective chart review was performed for all adults  presenting to the Johns Hopkins Bayview Medical Center ED, an urban tertiary referral center, from January 2012 through December 2013 whose chief complaint within the electronic medical record (EMR) on presentation to the ED was: dizziness, vertigo, or imbalance. The EMR was further reviewed to ensure accuracy of the search results, and data were collected regarding patient demographics ; medical variables (admission systolic and diastolic blood pressure (mmHg), use of antiplatelet and/or anticoagulant medications, history (by patient report) of: diabetes mellitus, coronary artery disease (CAD), hypertension, hyperlipidemia, and tobacco use); physical exam findings ; laboratory tests (white blood cell count (WBC), hematocrit; erythrocyte sedimentation rate (ESR), glycosylated hemoglobin (HgbA1c), troponin, low-density lipoprotein (LDL), international normalized ratio (INR), serum sodium, blood urea nitrogen, creatinine, glucose); neuroimaging ; and final diagnosis. The cause of dizziness was determined by review of the completed work-up  and discharge summary. The primary outcome of interest was posterior circulation ischemia (stroke or transient ischemic attack (TIA)). Neurology was consulted at the discretion of the ED physician. Stroke was adjudicated from the EMR according to discharge diagnosis and confirmed with neuroimaging results. Posterior circulation stroke was defined by a hyperintensity on diffusion-weighted MRI or hypodensity on head CT located in the vascular territories fed by the vertebrobasilar system  that corresponded to presenting symptoms. TIA was determined by the primary neurology team caring for the patient (discharge diagnosis) and defined as a transient deficit most likely due to an underlying vascular cause without lasting evidence on neuroimaging. No intracerebral hemorrhages were included. Charts and neuroimaging were reviewed independently by two separate reviewers with 20 % overlap of cases.A subset of patients underwent CTA as part of their diagnostic work-up based on the discretion of the treating ED and Neurology teams. The characteristics of this subgroup are detailed in our t-tests (for continuous variables) and chi square tests/Fisher’s exact tests . The primary objective was to determine factors associated with posterior circulation ischemia in patients presenting to the Emergency Department with dizziness and the ability of a basic vascular risk assessment and neurologic screen to identify individuals with posterior circulation ischemia. A secondary aim was to determine the added utility of CTA for those patients thought to require additional imaging. For the primary analysis, covariates significant in univariate analysis (p < 0.05), or those thought a priori to be of potential clinical significance, were entered into a multivariable logistic regression analysis of the entire population, with posterior circulation ischemia (stroke or TIA) as the dependent variable. To determine the added benefit of CTA, subsequent models were generated including only patients who underwent CTA. A receiver operating characteristic (ROC) analysis was performed comparing the area under the curve (AUC) using vascular risk factors and clinical exam with and without inclusion of CTA findings, along with sensitivity/specificity analyses.Analyses were performed using Stata SE version 13 . Univariate analyses were performed using Student’s paired n = 53), leaving 1,216 patients for final analysis. Eighty-seven underwent CTA as part of their work-up and were included in the secondary analysis. Inter-rater agreement was 99 % for review of both the EMR and neuroimaging results.One thousand two hundred sixty-nine patients aged 18 years or greater were identified by their electronic medical record as potential subjects. Patients were excluded from further analysis if they left the ED without evaluation/laboratory tests (n = 66): 71 % benign paroxysmal positional vertigo/vestibular neuritis, 18 % vestibular migraine, and 11 % vertigo.The overall age of the cohort was 56 years (+/−19). Forty-two percent were male and 31 % were black. The average systolic blood pressure was 137 mmHg (+/−26). Sixteen percent of the cohort had coronary artery disease; 63 % hypertension; 26 % diabetes; 41 % hyperlipidemia; and 49 % were previous or active smokers. Fifteen percent were noted to have double vision; 8 % dysarthria; 8 % a facial droop; and 18 % unilateral motor/sensory deficits. One hundred (8.2 %) were diagnosed with posterior circulation ischemia (stroke = 71 or TIA = 29). Forty-five percent of strokes were located in the pons, 30 % the cerebellum, 13 % occipital lobe or thalamus (PCA territory), 8 % medulla, and 4 % midbrain. The most common other discharge diagnoses included: dehydration/orthostatic hypotension, arrhythmia, anemia, hyper/hypoglycemia, and systemic illness such as myocardial infarction or GI illness. Only five percent of the non-ischemic diagnoses were neurological (p = 0.005), older age (p < 0.0001), and elevated systolic blood pressure (p < 0.0001) were associated with posterior circulation ischemia in univariate analysis (Table p = 0.062), hypertension (p = 0.001), hyperlipidemia (p = 0.002), and history of smoking (p = 0.004). The presence of focal neurologic deficits including: dysarthria (p < 0.0001), facial droop (p < 0.0001), and unilateral weakness or numbness (p < 0.0001) was also associated with ischemia.Male sex , systolic blood pressure , and focal exam findings  remained significantly associated with posterior circulation ischemia in the overall population in multivariable models  were entered into multivariable regression analysis. Race was also included given the high suspicion it may also be clinically relevant. Individual risk factors and exam findings were condensed into single variables for simplification and to decrease the number of variables within the model. Advanced age . A history of diabetes, hypertension, and CAD alone were not significantly associated with patients undergoing further risk assessment with CTA. Overall results for factors associated with ischemia were similar within the subgroup who underwent CTA (n = 87) (Table p = 0.003). “Any calcium” on CTA was not a significant predictor of ischemia when the model was fully-adjusted (p = 0.38). Only the presence of calcium within the distal internal carotid artery (ICA) was associated with ischemia  in multivariable modeling.Eighty-seven patients underwent CTA for additional risk assessment. These patients were more likely to be older, white, male, and smokers; with neck pain; focal findings on exam; and higher blood pressures, glucose, HbA1c and LDL values  Table , though n = 87). The AUC for these same variables without adding CTA to the model was 0.78. The AUC did not change when any calcium on CTA (AUC = 0.78) or calcification of the distal ICA (AUC = 0.78) was added to the model  predicting ischemic stroke was 0.90. The positive predictive value of the model was 57 % and the negative predictive value was 94 %. To evaluate the added benefit of CTA in predicting ischemia, we looked specifically at the cohort who underwent additional neuroimaging , are chosen to undergo additional imaging. Our study is consistent with other published literature , 9, 26 aIn patients presenting to the ED with subjective dizziness, performing a careful history of vascular risk factors and basic neurological assessment looking for focal deficits  will correctly identify most individuals presenting with dizziness secondary to ischemia. In addition, the absence of these findings indicates the likelihood of ischemia is probably low. The presence of calcification within the cervical and intracranial vessels on CTA can be associated with posterior circulation ischemia, but in our population did not add significant utility above clinical acumen. A vascular risk assessment and neurological examination are adequate for risk stratification of ischemia in the dizzy patient and should remain the standard evaluation.


In patients with chronic kidney disease, metabolic syndrome has been demonstrated to be the culprit behind diverse complications. Adiponectin is known to have anti-atherogenic and cardio-protective effects. Meanwhile, the relationship between adiponectin and metabolic syndrome in patients with chronic kidney disease has not been clarified. The aim of this study was to elucidate the relationship between adiponectin level and metabolic syndrome in patients with chronic kidney disease.The KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease is a cohort study that enrolled subjects with chronic kidney disease throughout South Korea. From February 2011 to July 2014, data were collected from 1332 patients with chronic kidney disease.P < 0.001) after adjustment for multiple confounding factors.The mean age of the patients was 53.5 years and 803 patients (60.7%) were men. The median adiponectin level was 10.7 μg/mL and 585 (44.3%) patients had metabolic syndrome. In multiple linear regression analysis, log adiponectin was positively associated with high-density lipoprotein cholesterol levels (β = 0.006), whereas it was negatively associated with serum albumin (β = −0.284), triglyceride (log β = −0.288), high sensitivity C-reactive protein (log β = −0.058) levels and estimated glomerular filtration rate (β = −0.005). Multiple logistic regression analysis indicated that low adiponectin level was independently associated with a higher risk of metabolic syndrome (per 1 μg/mL increase; odds ratio = 0.953, 95% confidence interval = 0.898–0.970, Hypoadiponectinemia is independently associated with the presence of metabolic syndrome in patients with chronic kidney disease. Metabolic syndrome is defined as the aggregation of non-traditional risk factors, including central obesity, hypertension, hyperglycemia, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-C) . The cliAdiponectin, which is released from adipocytes , is knowTherefore, the aim of this study is to clarify the determinant factors of adiponectin level, and elucidate the relationship between adiponectin level and metabolic syndrome in patients with chronic kidney disease.The study has a cross-sectional design, using the database system of the KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD), a nationwide multicenter prospective cohort including chronic kidney disease stage 1–5 pre-dialysis patients from February 2011 to July 2014. KNOW-CKD was implemented to investigate the pathophysiologic mechanisms of renal or cardiovascular outcomes in Korean chronic kidney disease populations. The detailed design and methods of the KNOW-CKD were previously published . Among 1All data analyzed in this study were collected at the time of enrollment. The demographic data were collected by experienced doctors and nurses from the study subjects. Body mass index was calculated as weight in kilograms divided by the square of height in meters , and theA total 10 mL of whole blood was collected using a serum separation tube (SST) and centrifuged within 1 h after collection for the separation of serum prior to delivery to the central laboratory  for measuring creatinine. Laboratory data included complete blood cell counts, glucose, uric acid, blood urea nitrogen, serum creatinine, calcium and phosphate, lipid profiles, serum albumin, and high sensitivity C-reactive protein (hs-CRP) level at the central laboratory. Serum creatinine was measured by an IDMS-traceable method. Calcium levels were corrected by using the serum albumin level. Another 15 mL of the first-voided urine was also collected to analyze urinary levels of albumin and creatinine at the central laboratory. Albuminuria was determined by urinary albumin-to-creatinine ratio (UACR) from spot urine samples, and eGFR was calculated using the four-variable modification of diet in renal disease (MDRD) equation including age, sex, race, and serum creatinine level . Plasma The harmonizing definition  bases tht test or the Mann–Whitney U-test was used for continuous variables and the Chi-square test for categorical variables. Univariate and multiple linear regression analyses were performed to determine independent factors associated with adiponectin level. Regarding the distribution of variables, adiponectin level, triglyceride, hs-CRP, and UACR were transformed to natural logarithm values for linear regression analysis. The independent predictive role of adiponectin level for the presence of metabolic syndrome was confirmed by multiple logistic regression analysis, which included significant variables in the comparison of baseline characteristics according to the presence of metabolic syndrome and multiple linear regression analysis. For further investigation beyond multiple logistic regression analysis, a cubic spline model was developed to illustrate systemic relations between adiponectin level and the risk of metabolic syndrome. We also conducted baseline subgroup analyses stratified by cause of chronic kidney disease, sex, age, diabetes mellitus, body mass index, UACR, eGFR, statin use, and angiotensin II receptor blocker (ARB). The trend for the mean adiponectin level across the numbers of metabolic syndrome components was verified by the trend test. Statistical analysis was performed with IBM SPSS Statistics for Windows version 23.0 . P values less than 0.05 were considered significant.Continuous variables were represented by using mean ± standard deviation or the median (interquartile range), while categorical variables were represented as the number of subjects (percentage). Normality of distribution was ascertained by the Kolmogorov–Smirnov test. To compare differences between patients with and without metabolic syndrome, Student’s 2, and the median adiponectin level was 10.7 (6.2–17.8) μg/mL. Metabolic syndrome was present in 585 (44.3%) patients. Patients were divided into 2 groups according to the presence of metabolic syndrome. UACR [208 (45–533) vs. 398 (113–1557) mg/g Cr] and hs-CRP [0.05 (0.02–0.18) vs. 0.12 (0.04–0.34) mg/dL] were higher, while eGFR (53.7 ± 30.9 vs. 43.8 ± 27.3 mL/min/1.73 m2) and adiponectin level [12.5 (7.1–19.6) vs. 8.6 (5.3–14.9) μg/mL] were significantly lower in the metabolic syndrome group compared to the non-metabolic syndrome group.The baseline characteristics are shown in Table Crude prevalence rates of metabolic syndrome, based on the combination of chronic kidney disease stages and quartilized adiponectin levels, are shown in Fig. 2, β = −0.066), and fibrate (β = −0.509) were negatively related with statistical significance.Univariate linear regression analysis was performed to determine the relationship between clinical and biochemical variables and the adiponectin level Table . In the 2, β = −0.056), and fibrate use (β = −0.358) were independently related to adiponectin level.To further clarify the independent association of adiponectin level with clinical and biochemical variables, multiple linear regression analysis was performed with the variables that had significant differences in the comparison of baseline characteristics according to the presence of metabolic syndrome and univariate linear regression analysis. In the analysis, waist circumference (β = −0.020), hemoglobin (β = −0.069), serum albumin (β = −0.326), triglyceride , HDL-C , hs-CRP , eGFR  = 0.942 (0.911–0.974), P < 0.001] or non-diabetic  nephropathy after adjustment for multiple confounding variables. For a more specific explanation of non-diabetic groups, hypertensive and glomerulonephritis groups still showed independent association between high adiponectin levels and presence of metabolic syndrome, while polycystic kidney disease group did not show any significance in the full adjustment model  1 and 2 in the intra-renal arterioles, endothelium, podocytes, mesangial cells of the glomerulus, and proximal tubular cells . In expeFrom the clinical aspect, a landmark study showed that high adiponectin levels are associated with a lower risk of myocardial infarction in men , and thiNevertheless, the present analysis indicates that adiponectin level was independently associated with the risk of metabolic syndrome in chronic kidney disease patients after adjustment for confounding factors including eGFR and UACR. Adiponectin is secreted from visceral fat. Therefore, a strong relationship between adiponectin level and metabolic components including triglycerides, HDL-C, and waist measurements might overwhelm the association with renal function. In particular, waist enlargement is the second-most common metabolic syndrome component, followed by glucose. In this analysis, the relationship between adiponectin level and the risk of metabolic syndrome would mostly be influenced by the prevalence of larger-waist subjects. In obese subjects, adiponectin levels were lower despite the fact that adipose tissue is its source . In addiIn the end, we found several results. First, serum albumin levels were significantly and independently associated with adiponectin levels in our analysis. In fact, this clear finding has already been reported in several previous investigations , 34, andSeveral limitations of our study must be acknowledged. First, the study was performed with an analysis of cross-sectional data, the causative role of adiponectin on development of metabolic syndrome is still inconclusive. Thus, given the differences in overall outcome between previous studies, further research with a prospective design in this area should be prioritized. Second, in the course of defining metabolic syndrome, the waist circumference was evaluated using Asian criteria. Although there is controversy about defining the waist criteria in metabolic syndrome diagnosis, the Korean Diabetes Association presented Korean waist criteria, which is the same as the Asian criteria in the harmonizing definition. Third, the genetic polymorphism of adiponectin levels was also reported , thus thIn conclusion, low adiponectin levels were independently associated with the presence of metabolic syndrome in chronic kidney disease patients. The relationship showed linearity throughout the categorical adiponectin levels. A strategy to modulate serum adiponectin might be helpful to improve metabolic derangements in patients with chronic kidney disease.


Hospital length of stay (LOS) has recently been receiving increasing attention as a marker of medical resource consumption. Identifying predictors of longer LOS can better equip doctors to counsel patients and facilitate more efficient patient flow and utilization of medical resources. The objective of this study was to identify pre- and intra-operative risk factors for postoperative hospital LOS in patients who had undergone radical prostatectomy in China.We retrospectively analyzed data of 793 eligible patients with prostate cancer who had undergone radical prostatectomy in our institution between January 2011 and March 2016. Relevant preoperative variables, including patient characteristics, medical comorbidities, prostate cancer disease-specific variables, urinary tract symptoms, preoperative laboratory values, and intraoperative variables including operation type, operation duration, and blood loss, were analyzed. The outcome was postoperative length of stay which was calculated as the time from the date of operation to the date of discharge. Multiple linear regression analysis was used to identify predictors of this outcome.The mean postoperative LOS was 11.7 days (±4.6 days) and the median 10 days . According to univariate and multivariate analysis, operation type (open or laparoscopic), blood loss, Gleason score (≥8) and preoperative laboratory values of white blood count (WBC) were found to be the main explanatory predictors of postoperative LOS of patients with prostate cancer in our institution. Additionally, open surgery was the strongest significant predictor of longer LOS according to the standardized coefficients in this model.Our findings indicate that significant predictors of longer postoperative LOS in patients who have undergone radical prostatectomy in China include both preoperative variables of Gleason score, WBC and intraoperative variables of operation type (open or laparoscopic), blood loss. To shorten hospital LOS in patients with prostate cancer and optimize utilization of Chinese medical resources, efforts should be made to improve the intraoperative process and reduce the prevalence of preoperative risk factors. Prostate cancer is the commonest cancer in men  and radiNumerous risk factors are associated with prolonged LOS, including preoperative and intraoperative factors and postoperative complications . StudiesElucidating risk factors that are significantly associated with LOS may help physicians to identify patients at greater risk for prolonged LOS and thus provide more appropriate counseling , as wellBetween January 2011 and March 2016, 836 consecutive patients with localized prostate cancer underwent radical prostatectomy and were discharged from our institution. Only patients with the pathological diagnosis of prostatic adenocarcinoma were included in this study, those with sarcoma of the prostate being excluded. Patients who had undergone transurethral resection of the prostate or another operation for concomitant diseases during the period of hospitalization were also excluded. Additionally, patients for whom equal to or more than three study variables were unavailable were also excluded from the final analysis. All patients’ data were extracted by a trained clinical reviewer from electronic medical records maintained in a secure clinical database at our institution. After applying inclusion and exclusion criteria, 793 inpatients were included in the final analysis. The flowchart of screening for eligibility for the study is shown in Fig. The primary outcome variable was postoperative LOS in days, which was calculated from the date of operation to the date of discharge. Because the data of LOS in days were not normally distributed, these data were subjected to reciprocal transformation to meet the model assumption of a normal distribution. The reciprocally transformed LOS was then used as the dependent variable in the subsequent multiple linear regression analysis.9/L) (WBC), neutrophil count (%), hemoglobin, hematocrit, platelet count (× 109/L), albumin, glutamic-pyruvic transaminase (GPT), serum total bilirubin, creatinine, serum potassium, serum calcium, and blood glucose. Intraoperative variables, including operation duration (h), blood loss (L), and operation type were collected from operation notes and operation logs. The type of surgery performed  was selected by each patient after discussion with the surgeon.In this study, 32 variables were assessed. Preoperative variables included patient characteristics, comorbidities, prostate cancer disease-specific variables, urinary tract symptoms, and preoperative laboratory values. Patient characteristics assessed included age, body mass index (BMI), marital status, smoking and drinking status, and family history of prostate cancer. Comorbidities, including hypertension requiring medication; diabetes requiring either oral medication or insulin injections or both; and history of cardiovascular and cerebrovascular disease were combined into one variable because of the small positive sample size. History of cardiovascular and cerebrovascular disease was treated as a dichotomous variable and defined as positive in the presence of a history of myocardial infarction, coronary artery disease before or after coronary stent implantation, arrhythmia, transient ischemic attack, or cerebrovascular accident such as cerebral embolism, cerebral thrombosis, or cerebral hemorrhage. The above information was abstracted from preoperative medical records. Inclusion of the disease-specific variable of prostate specific antigen (PSA) was considered essential; the most recent PSA value prior to surgery was used in the analysis. Biopsy Gleason scores were acquired from prostate biopsy reports. Prostate volume was calculated by using the following formula: transverse diameter × vertical diameter × longitudinal diameter × π/6; the diameters were measured by color ultrasound. Urinary tract symptoms, including dysuria, pain or burning on urination, frequent urination, urgent urination, and hematuria, were assessed as dichotomous variables and abstracted from medical records of symptoms reported by patients. Preoperative laboratory values closest to the day of surgery were also recorded, including white blood count  in the univariate analysis were included in the subsequent multiple linear regression analysis by using stepwise selection methods. P < 0.05 was set as the criterion for inclusion of a variable in the final model. There were missing data in the variables of BMI, Prostate volume and Operation duration, while the extent of cases with one or two missing variables in the 793 patients was less than 3% and there were no statistically difference in LOS between cases with versus without missing data. Missing data were imputed by mean substitution and were included in the data analysis. All statistical analyses were performed using SPSS software .Continuous data are presented as mean ± standard deviation or median (interquartile range) and categorical data as frequency and percentage. Correlations between each variable and LOS were tested by univariate analysis, including the Mann–Whitney U test for variables with two subgroups, Kruskal–Wallis test for variables with multiple subgroups and Spearman correlation analysis for continuous variables. Variables that were found to be significantly associated with LOS , with 191 patients’ (24.1%) value being in the high-risk range (PSA > 20 ng/mL). As to type of surgery, 325 patients (41.0%) had undergone ORP, 257 (32.4%) LRP, and 211 (26.6%) RARP. The mean operation time (hours) was 3.0 ± 0.9 h. Details of patient characteristics and pre- and intra-operative variables are listed in Table The mean postoperative LOS for the entire sample was 11.7 days (± 4.6 days), and the median 10 days . Both some pre- and intra-operative variables were associated with longer postoperative LOS; namely, the prostate cancer disease-specific variables of preoperative PSA value and biopsy Gleason score, urinary tract symptoms of dysuria, preoperative laboratory values for WBC, platelet count, serum calcium and blood glucose, and intraoperative variables of operation type, and blood loss. However, patient age was not a risk factor for longer LOS. Additionally, the intraoperative variable of operation duration was not found to be significantly associated with longer postoperative LOS. The same results were obtained when reciprocal-transformed LOS was subjected to univariate analysis.Table Table The expected increasing numbers of patients with prostate cancer will inevitably increase the demand for access to hospitalization; it is therefore important to optimize medical resource utilization in an attempt to meet this demand. Hospital LOS, an important indicator of resource utilization, has been increasingly investigated in the face of limited medical resources and increasing pressure for cost containment , 7, 15. In our study, the median postoperative LOS of our patient cohort was 10 days, which is much longer than that reported from Western countries, where the median postoperative LOS after radical prostatectomy is reportedly only one day , 14. ThiBeing one of the main treatments for clinically localized prostate cancer, three types of radical prostatectomy are available in our institution, namely open, laparoscopic, and robotic prostatectomy. Many previous studies comparing operative outcomes of the three types of surgery, have reported that minimally invasive (laparoscopic or robotic) surgery is associated with a significantly shorter LOS than open surgery –28. Our We also found the intraoperative variable of blood loss to be an important predictor of longer LOS after radical prostatectomy. This result is consistent with previous studies , 14 thatIn one previous study , the disStudies investigating predictors of LOS in other surgical disciplines have also highlighted that preoperative laboratory values such as low hematocrit, high creatinine, or low albumin are significant indicators of prolonged LOS , 14, 34.2 value in the final regression model was 0.205; such a small R2 value suggests that postoperative variables such as complications may play major roles in postoperative LOS. Previous studies have reported strong associations between postoperative adverse events and prolonged LOS [We here identified several important predictors of longer LOS for post-prostatectomy patients with prostate cancer in China. In particular, we added the disease-specific variable of Gleason score as a risk factor for longer LOS. However, several limitations of our study should be noted. First, it was a retrospective analysis and data were collected from a single institution in Zhejiang, China, thus limiting the generalizability of these finding to other countries or even other institutions in China. Second, we only analyzed preoperative and intraoperative variables and the Rnged LOS . Hence, Elucidating the risk factors for longer LOS will enable better patient counseling and more efficient management of medical resources. In our study, we found that both some preoperative and intraoperative variables are significant predictors of longer postoperative LOS after radical prostatectomy in China. Measures should be taken to improve intraoperative procedures and reduce the prevalence of preoperative risk factors without sacrificing the quality of medical care with the aim of shortening hospital LOS and improving the efficiency of utilization of Chinese medical resources.


Whether elevated beat-to-beat blood pressure variability (BPV) has an influence on vascular elasticity is confounded and poorly understood. This study hypothesized that the increased BPV could have an adverse effect on the vascular elasticity, as estimated by total arterial compliance (TAC), independent of blood pressure (BP) values. Beat-to-beat BP and TAC were measured in 81 hypertensive patients  and in 80 normal adults (control population). Beat-to-beat BPV was assessed by standard deviation (SD), average real variability (ARV), residual standard deviation (RSD) and variation independent of mean (VIM). In experimental population, systolic BPV (SBPV) showed a significant correlation with TAC ; similarly, SD, RSD and VIM of diastolic BP (DBP) also showed explicit correlation with TAC . However, in the control population, neither SBPV nor diastolic BPV (DBPV) showed a significant correlation with TAC. Furthermore, in the experimental population, VIM of systolic BP (SBP) was also a determinant of TAC  independent of average SBP, DBP, age and body mass index. In conclusion, these data imply that beat-to-beat BPV, especially SBPV, shows an independent correlation with vascular elasticity in hypertensive population. Although high blood pressure (BP) values have been considered to evoke the adverse influence of the CVD, increasing evidence shows that the increased BP variability (BPV) is also associated with the development of the CVD2. Short-term BPV, which includes 24-h BPV and beat-to-beat BPV, has been confirmed as a risk factor of CVD events6. Upon most occasions, the standard deviation (SD) of the BP measurements is used as the clinical evaluation of short-term BPV2. However, SD is limited to estimate the BPV in multivariate module, because SD only reflects the global fluctuation of the BP values around the mean level and does not take the order of BP measurements into account9. To overcome these drawbacks of the SD, some novel parameters have been proposed to estimate BPV. These novel parameters include average real variability (ARV), residual standard deviation (RSD) and variation independent of mean (VIM). ARV takes the sequence of BP measurements into account7. RSD can reflect the underlying trend between BP values and time8. VIM is transformed by the SD, and it can exclude the impact of mean BP levels9.Cardiovascular disease (CVD) remains the number one cause of death globally; almost 17.5 million people died from CVD in 2012, accounting for 31% of all global deaths, and the number may reach up to 23.3 million by 203010. Vascular damage accompanies elevated arterial stiffness and reduced arterial elasticity. Total arterial compliance (TAC) is an evaluation of the arterial compliance in the entire arterial tree11, and it reflects the elastic property of the vascular system14. Furthermore, TAC plays an important role in the biomechanics and homeostasis10, and it is the main determinant of cardiac afterload, left ventricular function and arterio-ventricular coupling19. The decreased TAC represents the reduction of the vascular elasticity. And reduced TAC is considered as the optimal clinical index of damaged pulsatile arterial function and signals the early vascular damage20. Recently, some studies have manifested that 24-h BPV shows significant association with vascular damage23. Although beat-to-beat BPV is considered more precise than 24-h BPV to evaluate the short-term BPV6, the association between beat-to-beat BPV and vascular damage is non-significant6.The vascular damage increases CVD risk, and it occurs before any clinical feature of the CVDThe aim of this study was to explore the influence of beat-to-beat BPV on vascular elasticity, estimated by TAC, in hypertensive population. In this study, we measured the beat-to-beat BP parameters and TAC by noninvasive method in hypertensive population and normal population. We used the hypertensive subjects as experimental group and used the normal subjects as a control group.The study protocol was designed according to the principles of the Declaration of Helsinki and then was approved by the Clinical Ethics Committee of the Second People’s Hospital of Shenzhen, China. The experimental data were available. All subjects volunteered to participate in this study, and the written informed consent forms were obtained from each subject before the experiment. And all of data were available. The study population included two separate populations, an “experimental population” of hypertensive patients and a “control population” of normal adults. The latter data analysis was utilized to confirm the findings obtained in the experimental population. The experimental population consisted of 81 hypertensive patients with an age range of 29–75 years . All of the hypertensive patients fulfilled the following inclusion criteria: (a) SBP larger than 140 mmHg or DBP larger than 90 mmHg; (b) no history of diabetes mellitus, dyslipidemia; (c) no clinical or laboratory evidence of heart failure, coronary artery disease, cerebrovascular disease. With the objective of confirming the findings of the experimental population, we included another completely independent population of 80 normal adults . All of control subjects met following inclusion criteria: (a) no history of hypertension, and SBP smaller than 140 mmHg and DBP smaller than 90 mmHg; (b) no history of diabetes mellitus, dyslipidemia; (c) no clinical or laboratory evidence of heart failure, coronary artery disease, cerebrovascular disease; (d) no history of drug abuse. Both the experimental subjects and the control subjects were recruited in the Second People’s Hospital of Shenzhen, Shenzhen, China from April to December 2014.24. And the correct arterial diameter is maintained by Physiocal algorithm25. While, the Modelflow method is utilized to measure stroke volume26. In the Modelflow method, a non-linear three-element model, representing three major characteristics of aortic input impedance, is utilized to calculate the stroke volume precisely26. All subjects were instructed to lie in the supine position on a single bed quietly when the cardiovascular signals were measured. The procedure of cardiovascular signals measurement lasted ten minutes. Moreover, body weight and height were measured with the subjects without shoes and in light clothing. And body mass index (BMI) was estimated by the ratio of weight (kg) to the height square (m2). Caffeine, smoking and alcohol use was also recorded. All the subjects were asked to refrain from caffeine, cigarette, alcohol, or severe physical activities for 3 ~ 4 hours prior to the experiment.All of the subjects underwent clinical examination in the two populations. In both of the populations, cardiovascular signals of the patients were recorded by Finometer® MIDI  and were stored in a personal computer with a BeatScope® Easy software . And these cardiovascular signals mainly included beat-to-beat BP, ECG and stroke volume. In the Finometer® MIDI, the beat-to-beat BP is recorded by volume-clamp method, which is kept the arterial diameter constant with a cuff wraps around the finger1, × 2, …, Xn denoted a set of BP measurement values; y = kxp through a plot of SD BP (y-axis) against mean BP (x-axis).Because SD of the BP values had some disadvantages, such as only exhibiting the distribution of BP measurements around the mean levels and not accounting for the time sequence of BP recordings, it was limited to assess the BPV only using the SD of BP values. To overcome these limitations, we added the ARV, RSD and VIM to evaluate the beat-to-beat BPV besides SD. These parameters were calculated using the following formulas:28. Chemla et al.15 studied the estimation of TAC in human at rest, and they demonstrated that the stroke volume/pulse-pressure method (SV/PP) was a reliable method to assess TAC. Moreover, Haluska et al.29 compared the pulse-pressure method (PPM), area method (AM) and SV/PP to evaluate TAC; and they found that each of the approaches showed significant correlation with each other; and SV/PP and PPM were more robust than the AM. In addition, Simone et al.16 used SV/PP to evaluate TAC, and they demonstrated that SV/PP was a predictor of cardiovascular morbid events independent of age and LV mass index in arterial hypertension; Wohlfahrt et al.17 also used SV/PP to estimate TAC, and they found that chronic changes TAC were differentially correlated with age-related LV stiffening and chamber remodelling. In this study, SV/PP was utilized to assess the TAC. We measured stroke volume, beat-to-beat SBP and beat-to-beat DBP, and the pulse-pressure (PP) was the beat-to-beat SBP minus the beat-to-beat DBP.It is lack of a ‘gold standard’ to assess TAC. Some noninvasive approaches have been used to estimate TAC, and they derived from the Windkessel modelThe Statistical Package for the Social Sciences (SPSS) 19.0  was used for statistical analysis. Continuous variables were tested to detect substantial deviations from normality by computing the Kolmogorov-Smirnov Z, and the assumption of satisfactory normal distribution was met for all of the examined variables. Descriptive statistics were presented as mean ± SD. Independent-sample T test was used to test the difference of parameters in the two groups. Bivariate correlation analysis was used to investigate the bivariate associations. Multivariate linear regression analysis  were used to elucidate the independent determinants of TAC. P < 0.05 was considered statistically significant.Demographic data of the experimental population and control population was listed in Table Table The Pearson’s correlations of TAC with anthropometric measures values, HR values, PP and stroke volume, were shown in Table Table The independent relationships between BPV and TAC were examined in stepwise multiple linear regression models in hypertensive population. Before building the model, the test for multicollinearity among the tested variables was performed; and the variance inflation factor (VIF) was less than 5; that is to say, there is no multicollinearity among these tested variables. As Table In this study, our results provided unequivocal evidence of the association between vascular elasticity, as evaluated by TAC, and different parameters of beat-to-beat BPV, especially the beat-to-beat SBPV, in hypertensive population. Whereas, the correlation of vascular elasticity with beat-to-beat BPV was not significant in normal population. The evidence suggested that the elevated beat-to-beat BPV had an influence on the vascular elasticity and marked the early vascular damage in hypertensive patients.The results of our study have some potential clinical implications. Our results showed that the correlation between reduced TAC and elevated beat-to-beat BPV, especially the beat-to-beat SBPV, was significant independent of average BP in hypertensive population. For hypertensive patients, although the reduction in average BP by treatment is important, the decreasing BPV may be also important for preventing cardiovascular morbidity and mortality. Moreover, the elevated BPV may be also an underlying mark of premature vascular lesions.22; the increased BPV values might be a new determinant of the development target-organ damage, especially vascular damage. BPV was regarded as an intricate interaction between intrinsic cardiovascular control mechanism and external environmental stimuli. The beat-to-beat BPV mainly reflected the influences of central sympathetic drive, arterial or cardiopulmonary reflex, humoral, rheological, behavioural and emotional factors, activity and sleep5. Few previous studies investigated the target-organ damage correlated with beat-to-beat BPV. Parati et al.30 measured 24-hour beat-to-beat BP in intra-arterial method and assessed target-organ damage in 108 untreated hypertensive subjects; they used SD of beat-to-beat BP to estimate the beat-to-beat BPV; and they manifested that the severity of target-organ damage increased with the elevated mean BP and BPV in nearly any level of the 24-hour beat-to-beat BP. Veerman et al.31 measured 20 minutes beat-to-beat BP in 33 untreated hypertensive subjects by Finapres Model 5; and they measured the left ventricular mass index (LVMI) and urinary albumin-to-creatinine ratio to assess the target-organ damage; LVMI was utilized to evaluate the cardiac organ damage, and the urinary albumin-to-creatinine ratio was a surrogate marker for renal organ damage; in their results, they found urinary albumin-to-creatinine ratio was associated with beat-to-beat DBPV significantly; however, neither SBPV or DBPV was correlated with LVMI remarkably. However, there were some drawbacks of those studies. Parati et al.30 only used SD of BP values to evaluate the BPV, and the study subject of Veerman et al.31 was quite small. Furthermore, Wei et al.6 also explored the correlation between beat-to-beat SBPV and target-organ damage; they measured 10 minutes beat-to-beat BP in 256 untreated hypertensive subjects with Finometer device; they also measured LVMI, urinary albumin-to-creatinine ratio and pulse wave velocity (PWV) to assess the target-organ damage; PWV was used to estimate the arterial stiffness ; ARV, VIM and the difference between maximum and minimum BP (MMD) were used to estimated the BPV; and then they demonstrated that LVMI increased with the three indices of SBPV, and the urinary albumin-to-creatinine ratio only increased with MMD of SBP, while, none of the three indices of SBPV was associated with PWV significantly. In our study, we used TAC to evaluate the vascular elasticity and utilized SD, ARV, RSD and VIM of beat-to-beat BP values to assess the beat-to-beat BPV. And we demonstrated that all of the four indices of SBPV were associated with vascular elasticity; in addition, SD, RSD and VIM of DBP were also correlated with TAC in bivariate correlation analysis; whereas, in multivariate linear regression analysis, only VIM of SBP was associated with TAC independent of SBP, DBP, age and BMI in hypertensive population.Although the level of high BP values had been confirmed as an important predictor of target-organ damage, which mainly included vascular, cardio, renal organ damage, over the past years34. SD mainly reflected the dispersion of BP measurements around the mean value without taking accounting of the time series of the BP recordings7; moreover, as SD mainly reflected the dispersion of BP recordings around the mean value, it could be influenced by the mean BP9. To overcome these deficiencies of the SD, we used ARV, RSD and VIM besides SD to estimate BPV in this study. As the ARV was calculated by the average level of absolute differences of consecutive measurements, it took the time series of BP measurements into account and it was also less sensitive to relatively low frequency sampling of non-invasive monitoring7. RSD was the square root of the total squared differences of data points from a linear regression of blood pressure values against time8. When the BP fluctuation had an underlying trend over time, especially the relationship between BP and time was approximately linear, RSD was more suitable than SD to estimate the extent of variability. VIM was a transformation of SD that was defined to be uncorrelated with mean levels for all individuals in the cohort9. Using VIM as an index of variability might help to overcome some of the difficulties associated with mean BP levels. In other words, the VIM could eliminate the confounding interference of the mean BP values. Indeed, in multivariate linear regression analysis, our result authentically showed that the VIM of SBP was correlated with TAC independent of SBP values in hypertensive population.Our results also provided the methodology to quantify the BPV and its prognostic significance. It was crucial to use proper parameters to assess BPV. Some previous studies used different parameters to evaluate the BPV, and found the BPV were controversial to predict risk of CVDet al.2 found that arterial stiffness together with stroke volume determined the enhancement of pulse pressure; in return, increased BP evoked a passive augment of in arterial stiffness through the recruitment of collagen fibers in the wall. And the TAC was the inverse of arterial stiffness. These explained that the correlation of TAC with SPBV was closer than DBPV.In addition, some other interesting results in this study deserve discussion. Our results showed that SBP and all of the indices of SBPV in the hypertensive population were larger than the values in the normal population significantly. However, DBP and all the indices of DBPV in the hypertensive population were not significantly different from the values in the normal population. Similarly, HR parameters in the hypertensive population were also not significantly different from the values in the normal population. Furthermore, the TAC in the hypertensive subjects was smaller than the values in the normal subjects remarkably. And the closer correlation was found between SBPV and TAC. Schillaci 29. In the three-element Windkessel model, it assumed that the heart follows Poiseuille’s Law and the ratio of pressure to volume in the chamber was constant14. When the structural changes existed in some disease states, this presumption might not be valid. However, the addition of more elements evoked the increase in variance, but could not improve the accuracy. In addition, the calculation of SV/PP was used peripheral PP instead of central PP to estimate the TAC15. In patients with no or minor amplification of pulse pressure from aorta to periphery, this approximation could be accurate; nevertheless, for patients with subjects exhibiting physiological pulse wave amplification, it might underestimate the TAC. To improve the sensitivity and specificity of TAC estimation, the definition of TAC should have a consensus. Moreover, Heitmar et al.14 suggested that some additional parameters, such as arterial pulse pressure waveform, be added to analyze the TAC.Notwithstanding the novelty of our results, we should interpret the limitations of our study. In this study, SV/PP was used to assess TAC. This method was based on a three-element Windkessel modelIn addition, this study was a cross-sectional study. Considering the cross-sectional nature of the present study, we could not deduce the existence of any causal link between beat-to-beat BPV and TAC. In other words, increased beat-to-beat BPV might evoke the reduction of the TAC or versa. Larger longitudinal studies were needed to evaluate the prognostic implications of beat-to-beat BPV on TAC in a hypertensive population. Furthermore, the sample size of the current study was relatively small. The relatively small sample size might have some influences on the results. Lastly, the age range of the hypertensive population and normal population was relatively large, and it might also affect the accuracy of the results.In the present study, we studied the influence of beat-to-beat BP parameters on the vascular elasticity in hypertensive population. Our results showed that the beat-to-beat BPV, especially the beat-to-beat SBPV, was an independent determinant of vascular elasticity. As the reduced vascular elasticity respected the alterations of structural and functional vascular properties, the beat-to-beat BPV might have an impact on structural and functional vascular properties in hypertensive population.Dataset 1Dataset 2


To determine the relationship between central blood pressure (CBP) indices and mild cognitive impairment (MCI) in adults over the age of 50.A cross-sectional study conducted using a non-invasive SphygmoCor XCEL device. CBP indices and brachial blood pressure were measured in 50 inpatients and outpatients. MCI was assessed using the Montreal Cognitive Assessment (MoCA) instrument and by the European Consortium Criteria (ECC).p = 0.04) and language (p = 0.02), and between pulse pressure amplification (PPA) and language (p = 0.03).Seventy-six percent of subjects had hypertension, and 52% were diagnosed as having MCI using the ECC. No significant association was found between any of the measured blood pressure variables and global cognition. A significant relationship was observed between augmentation index (AI) and abnormal clock-drawing (CBP indices like AI and PPA, which are markers of vascular stiffness, are associated with poor executive function and language cognitive domain deficits. High blood pressure may exert negative effects on the brain and contribute to cognitive decline. Hypertension is seen in 7% of adults aged 18–39 years, 33% of adults aged 40–59 years and 55% of Medicare beneficiaries . A numbeAlthough blood pressure is typically measured peripherally over the brachial artery, central blood pressure (CBP) measurements, including aortic blood pressure, have shown stronger associations with end-organ damage and may be of greater clinical use. CBP can be measured non-invasively using validated cuff- based techniques. Recent studies indicate that the interaction of vascular stiffness and wave dynamics in the large arteries is an important mediator of blood pressure elevation with aging. Pressure waves travelling from the left ventricle to the aorta and subsequently to the peripheral arteries are reflected at the arterial junction, resulting in wave retropulsion, which augments pressure in the aortic root. A recent, prospective, observational study showed a temporal relationship between vascular stiffness, blood pressure elevation and progression to hypertension .Arterial stiffness of the large vessels influences the pumping of blood from the heart and is an independent predictor of future cardiovascular events beyond blood pressure alone. Arterial stiffness measures both structural  and dynamic arterial components . Different blood pressure indices are used to measure arterial stiffness ) and its associated hemodynamic sequelae with wave reflections (Pulse Pressure Amplification(PPA) and Augmentation Index(AI)). These blood pressure indices improve incremental cardiovascular risk stratification and prediction of future CV outcomes . cfPWV iThe association of CBP indices and cognitive decline has not been widely studied. Therefore, the objective of this study was to determine the relationship between central blood pressure (CBP) indices and the cognitive function of adults over the age of 50 years. This study may give further insights into the association between blood pressure and cognitive deterioration.In this cross-sectional study, using a non-invasive SphygmoCor XCEL device , CBP indices  and traditional brachial blood pressure (BBP) were measured in 50 inpatients and outpatients at the University of Alberta Hospital and Kaye Edmonton Clinic. Non-English speaking subjects and those with a history of dementia, blindness, depression, anxiety, mental illness, substance abuse and chronic pain were excluded. Subjects were also excluded when they were medically unstable or terminally ill, under isolation precautions or unable to give informed consent. Data on demographic variables and vascular risk factors including hypertension, diabetes and hyperlipidemia was obtained. Information on history of transient ischemic attacks (TIA’s), strokes and anti-hypertensive medications was also obtained.Blood pressure measurements were obtained after patients had been resting in a supine position for at least 10 min. Both brachial and central BP indices were measured at the beginning and again at the end of the assessment, with each brachial BP measurement resulting from the average of two back-to-back readings. Central BP indices were generated non-invasively from a brachial artery waveform using the generalized transfer function of the Sphygmocor XCEL software. Pulse wave velocity was calculated using the same device, by measurement of the distance and pulse transit time between the carotid and femoral arteries .Cognitive testing was done using MoCA  and EuroDescriptive statistics was performed on all demographic and clinical parameters. The prevalence of cognitive impairment was calculated. Baseline patient characteristics were reported as percentages for categorical variables and means and standard deviations for continuous ones. Logistic regression models were constructed to examine the independent association between peripheral or central BP with the MoCA score  as well as the individual cognitive domains , and the ECC diagnosis of MCI (present or absent) separately. All statistical analyses were performed using SPSS, with two-sided p-values with statistical significance set at 0.05.Ethics approval was obtained from the University of Alberta Research Ethics Board. Written informed consent was obtained from all the participants in the study.2, with 56% being female, 76% having hypertension, and 42% being smokers (Table The average age (± SD) of the subjects was 70 ± 12 years and the average body mass index was 29 ± 6 kg/mp = 0.04) and language . As shown in Table p = 0.03).Fifty-two percent of patients were diagnosed as having MCI using the ECC. No significant relationship was seen between any of the measured blood pressure variables  and MCI. Mean blood pressures levels between normal and abnormal clock drawing and language domains are shown in Table Measurements of blood pressure indices were generally reliable, with good intra-rater reliability indicated by the intra-class correlation coefficients ranging from 0.92 to 0.97 Table .Table 4IHypertension is the most important modifiable risk factor for the development and progression of cognitive decline. Cognitive impairment can range from simple memory loss to deficits in executive function, manifesting as difficulties with planning and organizing tasks, managing time, self-care, and decreased processing speed . In the The clinical evaluation of arterial stiffness and its pulsatile hemodynamics is complex. A few studies have shown a relationship between CBP parameters such as PP and PWV and indices of cognitive function –26. AmonTsao et al. in their study showed similar results to our study in that cfPWV was not associated with cognitive decline . This laA strength of this study is its use of the MoCA for cognitive assessment, which is a more sensitive test for assessing mild cognitive impairment than the Mini-Mental State Examination (MMSE), and which also incorporates an assessment of executive function. We also employed the standardized Consortium Criteria for the diagnosis of MCI. To our knowledge, this is the first study to show an association between high AI and abnormal language and executive function.Limitations of this study include its cross-sectional nature, which shows only association and not causation, and the small sample size. We did not calculate the sample size. However, we observed significant relationships between two independent variables (augmentation index and pulse pressure amplification) and two aspects of cognition (clock-drawing and language). Although there was a relationship between these variables and the primary end-point of the study (presence or absence of mild cognitive impairment), it did not reach statistical significance. In addition, as expected augmentation index (mean ± SD) was higher in those with MCI (MCI present 26.27 ± 13.81vs MCI absent 23.40 ± 12.28), and pulse pressure amplification was to be lower in those with MCI (MCI present 1.34 ± 0.13 vs MCI absent 1.37 ± 0.14) indicating that our data fit the experimental model.Results from this study suggests that CBP indices like AI and PPA, which are markers of vascular stiffness, wave dynamics and augmentation pressure are associated with possible poor executive function and language cognitive domain deficits. These CBP indices may be sensitive indicators of cognitive decline. Future large studies are needed to clarify the effect of CBP indices on cognitive aging.


Reactive oxygen species and lipid peroxidation are important factors that contribute to the development of age-related cataract. The study included 130 patients with age-related cataract, 69 of whom were diagnosed with hypertension (HT), 20 with hypertension and type 2 diabetes mellitus (DM), and 41 had no accompanying condition. The following parameters were measured in the serum of the examinees: products of lipid peroxidation malondialdehyde (MDA) and lipofuscin-like fluorophores (LLF), activity of prooxidative enzymes xanthine oxidase (XO) and myeloperoxidase (MPO), antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx), the concentration of thiol groups, and the ferric reducing activity of plasma. The activity of prooxidative enzymes XO and MPO was higher in the plasma of patients with HT  and with HT and DM  compared to patients with age-related cataract . Our research has shown that patients with age-related cataract and hypertension were exposed to increased oxidative damage of biomolecules, based on the increased plasma LLF and MDA content and decreased levels of thiol groups. Oxidative changes of biomolecules in these patients were associated with increased activity of the XO, MPO, and GPx enzymes and a lower extracellular SOD activity and total ferric reductive ability of plasma. Oxidative modifications of various biomolecules constantly occur in tissues throughout an individual's life, but in patients with age-related cataract (ARC), oxidative modifications of proteins and lipids are obvious and a dominant metabolic feature and pathological substrate of disease . The dev2•−), which is the main ROS within vasculature. NO is a potent vasodilator substance and its diminished availability upon reaction with O2•− causes increased resistance of arterioles, eventually leading to the development of hypertension  are implicated in vascular redox signaling, regulation of vascular tone, and remodeling of blood vessel walls. Conversely, increased presence of oxidants resulting in oxidative stress probably contributes to endothelial dysfunction and the development of hypertension . In endortension .+ as an electron acceptor in the course of conversion of hypoxanthine and xanthine to uric acid. However, limited proteolysis, oxidation of critical thiol-groups, or hypoxic conditions can induce the conversion of the enzyme to the oxidase form  has received special attention in past years. In physiological conditions, this xanthine-degrading enzyme exists as a dehydrogenase, utilizing NADase form . Both xaIt has been previously demonstrated that XO-derived oxidants have a strong impact on arteriolar tone and blood pressure in spontaneously hypertensive animals , and thaThis study included 130 patients with ARC, scheduled for cataract surgery in the Department for Ophthalmology, Health Center Kosovska Mitrovica, Serbia. Of all included patients, 41 had ARC only, 69 had ARC and hypertension, and 20 patients had ARC, HT, and type 2 DM. The study protocol was approved by the Ethics Committee of the Medical Faculty in accordance with the Helsinki Declaration. Informed consent was obtained from all individual participants included in the study. Patients with hypertension were identified by blood pressure of more than 140/90 mmHg. Their blood pressure was recorded by an auscultatory method using a sphygmomanometer.g for 10 min at 4°C, serum or plasma samples were separated, and aliquoted samples were immediately stored at –80°C. All chemicals used in this study were of analytical grade.Venous blood was collected after an overnight fasting into tubes containing solid dipotassium EDTA or into plain tubes. The tubes were centrifuged at 1351 2.Serum lipid profile, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TAG) were measured using commercial enzymatic kits  by automated analyzer . Low-density lipoprotein (LDL)-cholesterol was derived according to the Friedewald's equation. Concentration of glycated hemoglobin A1C (HbA1C) was assessed by turbidimetric inhibition immunoassay. Body mass index (BMI) was calculated as the ratio between body weight in kg and the square of body height in mThe concentration of malondialdehyde (MDA), which is a relatively stable lipid peroxidation marker, was measured by a method according to Ledwozyw et al.  on a SafXO activity was measured by spectrophotometry based on the change in absorbance at 290 nm, at the conversion of xanthine to uric acid  . Plasma Activity of SOD was measured by the method of Misra and Fridovich  based on–). The absorbance was read at 412 nm on the Safas UV/VIS spectrophotometer. The ferric reducing/antioxidant power assay (FRAP) is a colorimetric method for testing the ability of ferric reductive plasma, where at low pH, Fe+3-TPTZ reduces to Fe+2-TPTZ giving a blue color with maximum absorbance at 593 nm (The concentration of serum -SH groups was measured with Ellman's reagent (DTNB) . Proteint 593 nm .t-test for two independent samples and the single-factor ANOVA with the post hoc Tukey's test. The method used for dependence analysis was the Pearson linear correlation coefficient. Hypotheses were tested at the level of statistical significance  of 0.01 and 0.05. The software program SPSS Statistics 22 (USA) was used for statistical analysis of the results.Descriptive statistical methods, methods for testing statistical hypotheses, and methods for testing dependence were used for the analysis of primary data. Descriptive statistical methods used were the following: measure of central tendency (arithmetic mean), measure of variability (standard deviation), and relative numbers. The methods used for testing statistical hypotheses were the Demographic and clinical characteristics and biochemical indicators of lipids and glycemic status in the examined patients are presented in The activity of oxidant enzymes XO  and MPO  in the serum of patients with age-related cataract was significantly lower compared to patients with age-related cataract and HT  and patients with HT and DM . Also, there was a significant difference between the activities of both oxidant enzymes in the serum of patients with a HT and patients with HT and DM (P<0.01).Significantly lower activity of antioxidant enzymes SOD and GPx was measured in patients with HT and DM compared to patients with only ARC.The plasma of patients diagnosed with HT and DM in addition to ARC showed the lowest ferric reductive ability (575.9±67.6 μmol/L) compared to the patients with ARC and HT (613.9±43.9 μmol/L) and those with age-related cataract .The highest concentration of sulfhydryl groups was measured in the plasma of normotensive ARC patients (501.4±45.6 μmol/L) compared to patients with HT (400.6±34.6 μmol/L) and those with HT and DM .There was a significant positive correlation between plasma concentration of lipofuscin-like fluorophores (RFU/mL) and GPx activity (U/L) , between the concentration of LLF (RFU/mL) and XO activity , and between the concentration of MDA (µmol/L) and GPx activity .A significant correlation between the LLF and MPO  of how hypertension enhances cataractogenesis is yet to be established, constantly increased blood pressure is often associated with systemic inflammation, dysregulation of glycemic control, dys- and hyperlipidemia, obesity, and oxidative stress . AccordiIn the study of Khan et al., enzymatic as well as non-enzymatic antioxidants were depleted in hypertension , while iWe have previously shown that increased XO expression may intensify oxidative stress at both lens and systemic levels, probably contributing to earlier development of ARC in diabetic subjects . Our cur2•− and H2O2, depending on whether the substrate is xanthine or hypoxanthine. In circulation, XO can also produce ROS, thereby imposing injury to vascular endothelial and other cells in close proximity, for example adhered neutrophils. The reaction between O2•− and NO yields peroxynitrite, which is a powerful oxidant involved in nitration of tyrosine residues in proteins, also reported in hypertension and cardiovascular diseases (Human endothelial cells contain cytoplasmic and membrane-bound XO, capable of producing Odiseases . In addidiseases . Moreovediseases , and thadiseases .2•− than normal (Increased XO activity was probably affected by the presence of hyperlipidemia and hypercholesterolemia in our study. In fact, the ARC with hypertension group had significantly higher concentrations of triglycerides, total cholesterol, and LDL-cholesterol levels than those with ARC only. Hypercholesterolemia is often associated with local hypoxia of the blood vessel walls, favoring the conversion of endothelial xanthine dehydrogenase to XO form. Also, hyperlipidemia and hypercholesterolemia can alter the function and/or expression of glycosaminoglycan XO receptors thereby enhancing accumulation of XO within the vascular wall. A study by Ohara et al. showed that blood vessels of cholesterol-rich diet fed animals produced three times more On normal , while in normal .2•− could have some impact on activation of phagocytes and the release of MPO into extracellular space. It was previously demonstrated that O2•− has an important role in regulation of MPO catalytic cycles, as it allows uninterrupted development of the chlorinating MPO cycle, thus intensifying oxidative damage (Previous studies have demonstrated that XO can also act as a modulator of innate immune response through induction of pro-inflammatory cytokine synthesis and activation of neutrophils and macrophages, contributing to atherosclerosis development . Upon ace damage . MPO-dere damage . AccordiResults of our current study indicated that hypertension was associated with increased systemic activity of pro-oxidant enzymes XO and MPO in patients with ARC. We have also shown that endogenous antioxidant defense mechanisms were dysregulated in ARC patients with hypertension, as plasma GPx was upregulated, while the other antioxidants, including total thiol groups, SOD and FRAP, were significantly reduced. These results indicate that hypertension promoted oxidative stress in ARC patients. In such conditions, the supply of antioxidants and vitamins to eye tissues may be insufficient to protect the eye lens from further oxidative modifications, thus contributing to the development of ARC.