The purpose of this study was to assess the effects of age, body condition score (BCS) and muscle condition score (MCS) on indirect radial and coccygeal Doppler systolic arterial blood pressure (SAP) measurements in dogs.Sixty-two privately-owned dogs were enrolled between June and July 2016. The BCS and MCS were determined by two investigators. Blood pressure was measured per published guidelines and using headphones, and the order of measurement site was randomized. Dogs were positioned in right lateral recumbency for radial measurements and sternal recumbency or standing for coccygeal measurements. Associations between SAP and other variables were assessed by correlation coefficients and analysis of covariance.r = 0.45, P < 0.01). Radial SAP measurements were higher than coccygeal SAP measurements , but discordance occurred in both directions. No difference was observed between the first measurement taken, the average of measurements 2–6, or the average of all 6 measurements for either the radial  or coccygeal  site. Associations were not found between SAP measurements for either site and age, weight, BCS, MCS, anxiety score, or cuff size. Heart rate decreased significantly from the start of acclimation to the end of the first data collection series regardless of site (P < 0.01).Radial and coccygeal SAP measurements were moderately correlated (Initial measurement site can be based on patient and operator preference given lack of associations with patient variables, but the same site should be used for serial SAP measurements given discordant results between sites. Due to the lack of overt clinical signs directly attributable to systemic hypertension, it is considered one of the most under-diagnosed systemic illnesses in companion animals . ProlongHypotension requiring vasopressor therapy is associated with a 3.4-fold increase in the risk of death in dogs with sepsis . HypotenAlthough direct arterial measurement of blood pressure remains the gold standard, the pain and specialized equipment associated with this method limits its use in a clinical setting . FurtherThe purpose of this study was to assess the impacts of BCS and MCS on correlations between indirect radial and coccygeal SAP measurements taken using the Doppler method in privately-owned dogs. Secondary objectives of the study were to assess for associations between SAP measurement results and anxiety score, cuff size, and heart rate and to compare time required for collection of a complete series of readings at each site.This study was conducted at the University of Tennessee’s Veterinary Medical Center and was approved by the Institutional Animal Care and Use Committee of the University of Tennessee, Knoxville (protocol number 2426).Between June and July 2016, privately-owned dogs were enrolled in the study based on initial BCS determination assigned by one investigator (APM) using a 5-point scale . An enroPrivately-owned dogs from the veterinary teaching hospital population as well as those belonging to faculty, staff, and students were recruited. Informed consent was obtained for each dog prior to enrollment. Prior to data collection, owners were asked to provide information regarding any known medical conditions and/or current medications. Dogs that did not have a tail, had been anesthetized within the previous 12 hrs, or became fractious or intolerant of manipulation were excluded from the study. Participants diagnosed with local or systemic diseases were not excluded, nor were those dogs receiving medications, consistent with previous studies . ImmediaAll investigators that completed BCS and MCS scoring received training in BCS and MCS assignment from a board-certified veterinary nutritionist prior to the start of data collection. Investigators independently assigned a BCS and MCS to each participant using a 5-point scale and a 4-point scale, respectively . The inihttps://www.random.org, accessed May 15 2016), a randomization table was generated to determine the initial site of SAP measurement  for the target number of participants for each BCS category. Based on the initial BCS assigned, dogs were allocated into measurement groups using the next available assignment in the randomization table. If a participant was excluded from the study after assignment in the randomization table, its name was crossed out once on the table and that randomization assignment was recycled for the next participant.Using a randomized number generator  and Doppler unit with probe  for every SAP measurement, the cuff was inflated to approximately 20 mmHg above the point at which blood flow was no longer audible. Air was slowly and completely released from the cuff, and the pressure at which flow was first heard was recorded as the SAP. The process was repeated until 6 consistent readings were obtained. Heart rates at the beginning and end of each pressure series were recorded using Doppler ultrasonic pulse detection. Headphones were worn by the investigator for the entire duration that the Doppler was turned on to limit the potential of noise from the machine to contribute to ‘white coat’ effects. An anxiety score (ranging from 0 to 3) was assigned to the participant after completion of data collection , the animal was placed in left lateral recumbency and the right antebrachium was used. For coccygeal SAP measurements, the dog was allowed to either stand or lay in sternal recumbency. Ultrasonic coupling gel was applied to the concave side of a flat infant Doppler probe, which was then positioned perpendicular over the artery. Using the same sphygmomanometer . Interclass correlation coefficients (weighted κ) were calculated for inter-rater reliability for BCS and MCS scores assigned by two investigators , after which the mean of the 2 scores was used for all further analyses. Mean SAP measurements greater than 150 mmHg were considered consistent with hypertension, based on previous guidelines . Mean SAPearson product moment correlation coefficients were calculated to assess correlations between the average of BP 2–6 for the radial and coccygeal sites, as well as between the average of BP 2–6 for each site and possible covariates . Regression analysis was used to determine variance inflation factors to assess for collinearity between possible covariates .P < 0.05 was considered significant.A mixed effects crossover design and corresponding ANCOVA was performed to determine if mean BP 2–6 differed between radial and coccygeal measurement sites and to assess whether the washout period between treatment sites was adequate. Period and Site were included as fixed effects. Age, weight, average heart rate, BCS, MCS, anxiety score, time required to complete the measurement series, and cuff size as a percentage of appendage circumference were initially included as covariates in the analysis. Dog nested within sequence was included as a random effect. A compound symmetry variance/covariance structure was incorporated into the model to account for constant covariates. Backwards variable selection was performed on the full model to determine which covariates explain significant variability in mean BP 2–6. Factors included in the final model were period, site, and average heart rate. The Shapiro–Wilk test of normality of the residuals was evaluated to ensure the assumptions of the statistical method had been met. Commercial statistical software packages MedCalc , SAS  and SPSS  were used for all analyses. n = 5) or unavailability of one of two investigators  to assign a BCS/MCS prior to subject discharge (n = 3). Initial BCS categorization for the 62 dogs that completed the study was BCS 1: two dogs, BCS 2: six dogs, BCS 3: 20 dogs, BCS 4: 20 dogs, and BCS 5: 14 dogs. Age, sex distribution, weight, anxiety score, mean BCS and MCS for measurements assigned by DIM and JCW, and mean radial and coccygeal SAP measurements are presented in n = 24), with three or less each of 29 breeds. The complete list of breeds and the number of dogs representative of those breeds are provided in P < 0.01) and κ = 0.57 (P < 0.01), respectively.Seventy dogs were enrolled in the study, of which eight were excluded due to intolerance of manipulation or SAP measurement at either the radial or coccygeal artery (P < 0.01) at each site. For the radial site, heart rate values ranged from 104 bpm (range: 68–180) at the beginning of the acclimation period to 93 bpm (range: 54–162) at the end of the procedure. Post-hoc tests indicated that radial heart rate values were significantly different at the beginning of the acclimation period when compared to heart rates at the three other time points (P < 0.01). For the coccygeal site, heart rate ranged from 104 bpm (range: 60–180) at the beginning of the acclimation period to 93 bpm (range: 60–162) at the end of the measurement period. Although there was a significant difference in heart rate during the acclimation period (P < 0.01), this difference was not evident across all time points based on post-hoc analysis. Interestingly, there was no significant difference between the first blood pressure taken, the average of BP 2–6, or the average of all six measurements for either the radial  or coccygeal  site. There was also no difference in the time required for collection of the complete SAP measurement series for the two sites .As noted above, heart rate was determined at 4 time points throughout each measurement procedure . Mean heart rate differed significantly over time  and was censored from the analyses of BP 2–6 results because collection of coccygeal measurements would not have been performed in this case given prior knowledge of its orthopedic disease. Even after censoring results for the previously described dog, radial and coccygeal artery blood pressure measurements were poorly correlated . Thus, the final crossover model included measurement period, site, and mean heart rate. Of these, there was no significant effect of measurement period (P > 0.2) on BP 2–6 results, thereby indicating that the washout period between treatments was sufficient. Radial artery BP 2–6 results significantly differed from coccygeal results . Mean radial BP 2–6 was higher than coccygeal BP 2–6 , but discordance occurred in both directions. A significant positive association was also found between BP 2–6 and mean heart rate .Discordance in radial and coccygeal artery SAP measurements occurred in both directions across all BCS  and MCS.vs. 2 (3.2%) dogs based on coccygeal SAP measurements.Mean radial and coccygeal BP 2–6 were 129 ± 18.0 mmHg and 120 ± 18.8 mmHg, respectively. Of the 62 dogs, 8 (12.9%) were categorized as hypertensive based on radial SAP measurements, vs 6 (9.7%) dogs based on coccygeal SAP measurements. Two dogs with histories of refractory hypertension (>190 mmHg) that were enrolled in the study were normotensive (mean 140 mmHg). No dogs were categorized as hypotensive based on radial SAP measurements Radial and coccygeal artery blood pressure measurements were poorly correlated in this study. Although discordance between measurements taken at these two sites occurred in both directions, mean radial BP2–6 measurements were significantly higher than those obtained at the coccygeal artery. Consistent with previous reports , no signSeveral previous studies have also identified discordance between indirect and direct blood pressure measurements taken at different sites . Bodey &vs. the mean of the following five in spite of continuing changes in heart rate. This suggests that the positive association between average heart rate and mean SAP at each measurement site is more likely due to underlying physiologic processes vs. persistent white-coat effects.White-coat hypertension refers to an increase in blood pressure secondary to the stress and anxiety associated with the measurement process . It is pGiven caseload and personnel constraints in many practices, it can be challenging to consistently make time for adequate acclimation, as well as collection of a full series of SAP measurements. The importance of measuring SAP prior to other interventions and allowing patients to acclimate to their surroundings—including veterinary personnel—prior to blood pressure measurement cannot be overstated, however. In one study comparing blood pressure measurement results for healthy cats and cats with experimentally-induced chronic kidney disease , white-cCurrent guidelines for indirect measurement of blood pressure in dogs recommend selecting a cuff size that is approximately 40% of the appendage circumference . UndersiOne limitation of this study was the lack of direct arterial measurements to compare to indirect SAP measurement results. However, as discussed above, direct SAP measurement is invasive and can be painful, limiting its utility in evaluation of blood pressure in conscious animals on an outpatient basis. Additionally, direct SAP results vary depending on the vessel used and position of the animal, as demonstrated by Instead of using a crossover design, simultaneous measurement at both sites could have been considered to decrease any discordance due to moment by moment variation in blood pressure. This would have required either collection of all measurements with the foot elevated and the dog in a standing position, which is not a commonly used or recommended position for radial SAP measurement, or in lateral recumbency. Because the authors have found the coccygeal site to be particularly useful for accurate SAP measurement in dogs resistant to sitting or lying down, collection of coccygeal measurements in lateral recumbency was considered to limit the clinical applicability of the results. Finally, simultaneous cuff inflation at two sites is not consistent with standard measurement technique in clinical practice and it is unknown how that would have affected measurement-associated white-coat effect. The decision to maximize clinical relevance of the results by using a crossover design instead of collecting pressures simultaneously is unlikely to have substantively influenced the results given the lack of significant differences  among measurement results series (first measurement vs 2–6 vs 1–6) for either site and lack of period effects (which would have suggested a change in pressure in the time intervening between the two measurement series).There were a number of additional limitations in the present study. In accordance with ACVIM guidelines, headphones were used for collection of SAP measurements in this study. The results, therefore, cannot be directly translated to other techniques including Doppler measurements taken without the use of headphones. A limited number of under-conditioned and sarcopenic dogs were available for enrollment in the study, with only 8 dogs in the BCS 1–2 group and only 6 dogs in the MCS 0–1 group. These demographics reflect the local population, which primarily includes pets of ideal or over-conditioned BCS. Although patients were recruited from both a healthy and an unhealthy population, most animals with higher BCS and MCS were not clinically ill. It is possible that diseases associated with hypertension, muscle wasting, and underconditioning–like chronic kidney disease–might affect accurate blood pressure measurement differently at one or both of the measurement sites. Six dogs in the study had hyperadrenocorticism see , but theIndirect Doppler flow SAP measurements obtained at the radial and coccygeal artery sites were only moderately correlated. Mean radial measurements were 9 mmHg higher than coccygeal measurements, but discordance occurred in both directions. No association was found between measurements obtained at either site and age, weight, BCS, MCS, and anxiety score. Interestingly, no association was found between cuff size and blood pressure measurement at either site, suggesting that use of a cuff outside the recommended range might have little impact on the accuracy of results in a clinical setting.Heart rate decreased throughout each data collection series, with results at the conclusion of SAP measurement significantly lower than those obtained at the beginning of SAP determination. However, there was no significant difference between the first SAP measurement, the mean of the additional five readings (BP 2–6), and the mean of all six readings (BP 1–6). In clinical situations where time is limited, the authors recommend that fewer blood pressure measurements be obtained instead of decreasing time devoted to patient acclimation to the environment and personnel.10.7717/peerj.3101/supp-1Table S1Click here for additional data file.10.7717/peerj.3101/supp-2Data S1Click here for additional data file.


Blood pressure (BP) is one of the most important variables evaluated during almost every medical examination. Most national anesthesiology societies recommend BP monitoring at least once every 5 min in anesthetized subjects undergoing surgical procedures. In most cases, BP is monitored non-invasively using oscillometric cuffs. Although the risk of arterial cannulation is not very high, the invasive BP monitoring is usually indicated only in the case of high-risk patients or in complex surgical procedures. However, recent evidence points out that when using intermittent BP monitoring short periods of hypotension may be overlooked. In addition, large datasets have demonstrated that even short periods of low BP (or their cumulative duration) may have a detrimental impact on the development of postoperative outcome including increased risk of acute kidney or myocardial injury development. Recently marketed continuous non-invasive blood pressure monitoring tools may help us to recognize the BP fluctuation without the associated burden of arterial cannulation filling the gap between intermittent non-invasive cuff and continuous invasive arterial pressure. Among others, several novel devices based either on volume clamp/vascular unloading method or on applanation tonometry are nowadays available. Moreover, several near-future smart technologies may lead to better hypotension recognition or even prediction potentially improving our ability to maintain BP stability throughout the anesthesia or surgical procedure. In this review, novel or emerging technologies of non-invasive continuous blood pressure assessment and their potential to improve postoperative outcome are discussed. Since the end of nineteenth century, when non-invasive monitoring using Riva-Rocci sphygmomanometer was improved and implemented into wide clinical praxis by Harvey Cushing, blood pressure (BP) became one of the three most important vital signs evaluated in the perioperative care. It is quite difficult to ascertain the contribution of BP monitoring to the improvement of postoperative outcome at that time, however, performing nowadays any anesthesia procedure without knowing patient’s BP is literally inconceivable. The American Society of Anesthesiologists (ASA) recommends in the Standards for basic anesthetic monitoring, that BP should be monitored in all anesthetized persons at least at 5-min intervals . The samUsing the intermittent cuff, NIBP monitoring may leave BP fluctuations undetected or may lead to late recognition and delayed correction , 7. SeveIn this literature, we may find numerous definitions of IOH. Bijker et al. have identified 140 different definitions in 130 studies  ranging Salmasi et al.  have demThe association between low intraoperative pressures and increased risk of vascular brain injury (namely stroke) and increased mortality was stressed by the results of the POISE trial . The extIntraoperative hypotension and higher occurrence of organ complications may be also linked to increased postoperative mortality in non-cardiac surgery patients as demonstrated by Mascha et al. . NaturalBased on all these large population samples, the risks of IOH are undeniable, especially in non-cardiac surgery patients. Moreover, the inconsistency of IOH thresholds leading to different complications may be attributed to different organ needs and population under study. The threshold of AKI and MI increased risk of MAP below 60–65 mmHg corresponds with the lower inflection point of renal and myocardial autoregulation curves. Because the brain autoregulation’s plateau starts at lower MAPs, the threshold observed is lower (drop of more than 30% of chronic MAP). Finally, the burden of global hypoperfusion has to be much higher to induce life-threatening situation—i.e., TWA MAP 50 mmHg corresponds with profound hypotension throughout the procedure as well as SAP lower than 70 mmHg or MAP drop of 50%. Therefore, nowadays, the question should not state: “Is IOH dangerous?” but “How the IOH could be prevented…” Several hints may be already found in the literature. First the “Triple low study”  and its Since the second half of twentieth century, several technologies of continuous NIBP assessment have been available. Unlike the occlusive technique used in standard pressure cuffs (both Riva-Rocci–Korotkoff and oscillometric methods), these techniques are non-occlusive based on pressure transduction over the vessel wall under dedicated conditions. Important base for this research was Etienne-Jules Marey’s development of former Vierordt’s sphygmograph into portable form in 1860. In his later works, Marey described the relationship between the amplitude of pulse and pressure imposed on the vessel wall from the outside: i.e., the largest oscillations are observed in the moment of zero transmural pressures. Besides, the contemporary technologies of continuous NIBP monitoring Figure . On the The Czech physiologist Jan Peňáz first described the volume clamp method in 1973. In this semiocclusive technique, the volume of finger arteries is assessed using infrared photo-plethysmography. Next, using fast reacting inflatable pressure cuff, the volume of blood is held constant. The pressure which is needed to maintain a constant blood volume is proportional to the BP. To obtain real BP values , the zero transmural pressure needs to be obtained. Under zero transmural pressures , the pressure outside  and inside the vessel are equal hence enabling the reconstruction of BP curve and assessment of numerical values. Based on the Marey’s experiments, the zero transmural pressure is accompanied by the maximal amplitude of pulse oscillations. However, the vascular tone may change in time making the vascular unloading far from being constant. In the 1995, Karel Wesseling developed the Physiocal™ algorithm for automatic vascular unloading set point assessment that leads to gross improvement in the device accuracy. The device enabling non-invasive finger cuff was later marketed under the name Finapress/Portapress. Nowadays, different methods of vascular unloading are used by divergent devices. Because the pressure tracing monitored using this technique corresponds with the pressure inside finger arteries, a further mathematical processing is needed to reconstruct either radial or better brachial pressure curve or values.A higher than venous pressure inside the finger cuff leads to venous congestion distally to the probe. This so-called blue finger syndrome is mostly regarded as unpleasant or disturbing. In any case, it may limit the length of the monitoring in conscious subjects. Under several non-frequent conditions—as for instance Raynaud’s syndrome—this method of pressure monitoring is better to be avoided. The accuracy of the monitoring may be significantly affected in patients with finger edema or low perfusion due to blood redistribution (low cardiac output), chronic vascular disease, or peripheral vasoconstriction .ClearSight technology marketed by Edwards Lifesciences Inc.  is a direct successor of former Finapress and Nexfin  devices encompassing the Physiocal™ vascular unloading algorithm. A disposable single-use cuff is placed around the second phalanx of finger  connected to a band held pressure controller. The pressure inside the finger cuff is determined by the photo-plethysmographic sensors inside the cuff at a rate of 1,000 Hz. Within a time span of 5–70 beats the set point is reassessed using Physiocal™ algorithm. Mathematical inversed transfer function reconstructs the brachial BP curve out of the finger tracing and heart reference system is available to eliminate inaccuracies induced by hand vertical movements. Using the pulse contour analysis (adapted Modelflow method), advanced hemodynamic variables are calculated from the reconstructed pressure curve. The results of validation studies concerning BP and cardiac output accuracy performed using Nexfin device are also applied to the ClearSight, because this technology is a direct successor of the former one.The CNAP device  is second currently available device based on the Peňáz’s principle. In contrast to the ClearSight, the finger probes of CNAP are more robust and durable. Two neighbor fingers (either index and middle or middle and ring finger) are inserted into a double lumen plastic tunnel encompassing the inflatable finger cuffs. This setting enables periodical finger switch and to avoid the prolonged venous congestion of the acral part. A system of interlocking control loops  is used for optimal vascular unloading. Upper arm oscillometric cuff calibration  is necessary for brachial pressure reconstruction. According to the manufacturer, such calibration should be performed in 15- to 30-min window; however, frequent recalibrations (each 5 min) are probably more appropriate to maintain adequate accuracy . HoweverThe T-line  is the last commercially  available option of continuous NIBP monitor. Unlike previous ones, T-line is based on radial arterial wall applanation based on the Pressman and Newgard device described in the 1963 . A pressBasically, the described CNBP monitoring tools may help to improve perioperative care in two ways. First to replace contemporary invasive means and second to improve monitoring in patients who were deemed too good to have such invasive BP assessment. In 2012, Kirov et al.  have proThe first option, decreasing monitoring associated burden in patients currently monitored using invasive arterial pressure, seems to be far less important in the clinical routine. First, the risks associated with arterial cannulation, especially radial, are not negligible , but ratFrom this perspective, the second option (increasing the spectrum of monitoring in “good patients”) might be far more clinically relevant. Because of the intermittent nature of NIBP, BP fluctuations may be missed. In 2012, Chen et al.  have demHowever, decreasing the risks of IOH is not the only possibility how CNBP devices may impact on rate of postoperative complications. Given the reconstruction of arterial curve, a beat-to-beat analysis of hemodynamic variables and/or their induced fluctuations are inevitably part of the displayed information. Variation in pulse pressure (PPV) induce by mechanical ventilation has been shown to be an excellent predictor of fluid responsiveness . The useAt any case, use of CNBP devices for intraoperative hemodynamic care seems to offer a large field of small improvements in patients’ care and may be deemed as a natural part of current and future Enhanced Recovery programs. However, it should be noted that at current state large outcome data  as well as cost-effectiveness studies are missing. This coupled with price of the equipment and/or disposables create a not negligible impediment in routine use. At the end of the day, BP and flow are only global hemodynamic indicators and possess only limited information about end-organs perfusion and tissue metabolic well-being. Future clinical research should therefore try to couple these macrohemodynamic indices with monitoring of organ perfusion and assess impact of both these factors on patients’ postoperative outcome.Because the ability to assess the patients’ hemodynamic status is so appealing for the domain of anesthesiology, perioperative and intensive care multiple further technologies are in the pipeline of development. Practical applications based on pulse transit time , 42 and Such Smart software development may significantly alter the way patients will be monitored in the future. Over the past decade, we have significantly improved the way how we analyze the arterial pressure curve, but still the modality is not fully exploited. Assessing dynamic arterial elastance to predict pressure response on fluid administration is still in its basics , but mayBlood pressure monitoring is a vital part of perioperative care. Current technologies  enable much wider application of continuous monitoring hopefully leading to decrease in undesired BP fluctuations and hypotensive periods. Sophisticated analyses of arterial pressure curve make possible to monitor not only BP but also blood flow (and its variations). These new monitoring tools available today may significantly influence perioperative care especially in intermediate risk patients. However, to which extent the macrohemodynamic parameters improvement impact postoperative outcome in this patient population has to be determined in forthcoming studies. Future developments in this field coupled with smart technologies and in conjunction with other possibilities to assess end-organ perfusion may further improve patient care.AS and JB both wrote the manuscript, performed the literature search needed, and approved the final form of the text.JB is in a long-term relationship with Edwards Lifesciences Inc. and CNSystems Medizintechnik AG . AS has no conflicts to declare.


Although the utility and benefits of anesthesia and analgesia are irrefutable, their practice is not void of risks. Almost all drugs that produce anesthesia endanger cardiovascular stability by producing dose-dependent impairment of cardiac function, vascular reactivity, and compensatory autoregulatory responses. Whereas anesthesia-related depression of cardiac performance and arterial vasodilation are well recognized adverse effects contributing to anesthetic risk, far less emphasis has been placed on effects impacting venous physiology and venous return. The venous circulation, containing about 65–70% of the total blood volume, is a pivotal contributor to stroke volume and cardiac output. Vasodilation, particularly venodilation, is the primary cause of relative hypovolemia produced by anesthetic drugs and is often associated with increased venous compliance, decreased venous return, and reduced response to vasoactive substances. Depending on factors such as patient status and monitoring, a state of relative hypovolemia may remain clinically undetected, with impending consequences owing to impaired oxygen delivery and tissue perfusion. Concurrent processes related to comorbidities, hypothermia, inflammation, trauma, sepsis, or other causes of hemodynamic or metabolic compromise, may further exacerbate the condition. Despite scientific and technological advances, clinical monitoring and treatment of relative hypovolemia still pose relevant challenges to the anesthesiologist. This short perspective seeks to define relative hypovolemia, describe the venous system’s role in supporting normal cardiovascular function, characterize effects of anesthetic drugs on venous physiology, and address current considerations and challenges for monitoring and treatment of relative hypovolemia, with focus on insights for future therapies. To survive anesthesia is to survive a potentially life-threatening event. What other form of medical practice is designed to intentionally depress or inhibit a spectrum of neurophysiologic processes so as to be able to painlessly inflict varying degrees of medical or surgical psychological or physical trauma. Although the potential benefits and utility of anesthesia and analgesia are obvious, the practice of anesthesia is not without risk, particularly in animals. Indeed, the adverse events associated with anesthetizing animals, although similar to those reported in humans, are far more common than reported for humans –4. A recMaintenance of adequate CO and arterial blood pressure are dependent upon a normal blood volume, vascular tone , venous return (more appropriately “venous excess”), heart rate (HR), ventricular function, and multiple autoregulatory (compensatory) mechanisms, and are vital for preserving tissue perfusion and oxygen delivery DO2) , 20, 21. , 20, 21The driving pressure for blood flow returning to the heart from peripheral veins is theorized to be determined by the pressure gradient between a proposed “pivoting pressure,” termed the mean circulatory filling pressure (MCFP), and the right atrium (CVP) , 33–35. Hypovolemia is categorized as either absolute or relative. Absolute hypovolemia  is either controlled (hemorrhage that has been stopped) or uncontrolled (hemorrhage that has not stopped) and implies the loss of blood, plasma or water from the vascular compartment. Absolute hypovolemia can be conceptualized as a decrease in blood volume relative to a normally sized vascular compartment Figure . AlternaATP channels), excess production of the inducible form of nitric oxide , and deficiency of the hormone vasopressin . The combined effects of ischemia-induced acidosis and production of vasodilatory prostaglandins , activation of KATP channels, and the production of iNOS in animals that are septic or have chronic heart failure, in conjunction with the confounding effects of acidosis and hypothermia, create an ideal environment for vasodilatation, relative hypovolemia and vascular hyporesponsiveness or refractoriness to fluid administration and the administration vasoactive compounds  drug toxicity , (2) impairment or loss of compensatory mechanisms, (3) coexisting or induced metabolic (pH < 7.15) or respiratory (PaCO2 > 80 mm Hg) acidosis; or concurrent, (4) traumatic or surgically induced inflammation, (5) sepsis, (6) cardiogenic shock, and (7) hypothermia. Multiple cellular mechanisms have been implicated in the development of vasodilation and vasodilatory shock that include: a decrease in L-type calcium channel ion transport or myofilament sensitivity to calcium, activation of vascular smooth muscle ATP-sensitive potassium channels . Mo. Mo17). Identifying and treating relative hypovolemia and tissue hypoperfusion may pose a challenge to the anesthesiologist. During anesthesia, maintenance or prompt reestablishment of appropriate DO2 to all tissues is a main concern . EffectiPresently, perioperative monitoring is largely based on macrocirculatory variables, which may fail to detect relative hypovolemia –85. IndeSelection of monitoring procedures depends on a number of factors involving available technology and resources, the anesthesiologist’s familiarity with each technique, patient status, and the surgical or medical procedure being performed. In this regard, continuous clinical reassessment of patient status and anesthetic depth remain important tools that should be applied to all . Adding dynamic variables , it may add valuable information about a patient’s condition, particularly when values are outside the normal range, or when extreme, unpredicted, or seemingly paradoxical changes occur, related or not with therapeutic interventions  , followeIn the context of decreased effective circulating blood volume related to anesthesia and surgical trauma, fluids are generally proposed as a first line therapy, aiming to increase plasma volume, MCFP and the pressure gradient for venous return . Howeverdynamic indices such as systolic pressure variation (SPV), pulse pressure variation (PPV), stroke volume variation (SVV), plethysmographic variability index, aortic flow peak velocity variation (ΔVpeak), and caudal vena cava distensibility index (CVCDI), have demonstrated promise in predicting preload responsiveness and help guide fluid therapy .g., PPV .Fluid therapy for the treatment of anesthetic-associated relative hypovolemia and hypotension remains largely ineffective and predisposes to fluid overload , 203. NoIn summary, anesthesia-induced relative hypovolemia remains an underappreciated and often occult cause of poor tissue perfusion. The venous side of the circulation contains the majority of the blood volume and is a pivotal contributor to SV and CO. Vasodilation, particularly venodilation, is a primary cause of relative hypovolemia induced by anesthetic drugs. As with any hypovolemic state, relative hypovolemia may reduce venous return, CO, tissue oxygen delivery, and eventually arterial blood pressure, when compensatory mechanisms are inadequate or impaired. Tissue oxygen debt can lead to significant morbidity and mortality. Conventional, clinical monitoring, and diagnosis of relative hypovolemia during anesthesia relies on subjective clinical and objective macrohemodynamic measurements , and global perfusion assessments . Beyond correction of anesthetic plane, drug choice, and ventilation, therapeutic intervention typically consists of fluid administration, vasoactive and/or inotropic agents, seeking to optimize preload, afterload and cardiac function, with the ultimate goal of maintaining or restoring the effective circulatory volume (Vs), and microcirculatory flow. While many current fluid therapy strategies and fluid monitoring techniques remain under active research and debate, intravenous fluid therapy remains a first line therapy. Intravenous fluid therapy should be personalized and tailored to each patient’s requirements based upon a clear indication, consideration of potential benefits vs. harms, and objective measures for determining its effects. Variability in current practices related to crystalloid or colloid “fluid bolus,” “fluid challenge,” or assessment of “preload responsiveness” including methods for the assessment of “hemodynamic improvement,” in addition to longer term outcomes, preclude comparisons for substantive conclusions , 212–216WM originated the concept for the article. JN-M and WM contributed to drafting and reviewing the manuscript.The authors declare that the manuscript was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


CIN); however, they only contain patients receiving intra‐arterial contrast media for coronary angiographic procedures, which represent a small proportion of all contrast procedures. In addition, most of them evaluate radiological interventional procedure‐related variables. So it is necessary for us to develop a model for prediction of CIN before radiological procedures among patients administered contrast media.Several models have been developed for prediction of contrast‐induced nephropathy  curve (AUC) of 0.907 and gave prediction accuracy of 80.8%, sensitivity of 82.7%, specificity of 78.8%, and Matthews correlation coefficient of 61.5%. For the first time, 3 new factors are included in the model: the decreased sodium concentration, the INR value, and the preprocedural glucose level.A total of 8800 patients undergoing contrast administration were randomly assigned in a 4:1 ratio to development and validation data sets. CIN development and thereby provides preventative measures for CIN.The newly established model shows excellent predictive ability of  Contrast‐induced nephropathy (CIN) is an important cause of acute kidney injury (AKI) in both ambulatory and hospitalized patients. With the wide use of contrast media (CM), CIN has become the third prevalent cause of all hospital‐acquired renal failure, accounting for 10%.Unfortunately, few strategies have been shown to prevent and cure CIN effectively. Therefore, it is important to comprehensively assess the risks of CIN before CM administration and to take preventative measures. Preexisting chronic kidney disease and diabetes mellitus are the most important risk factors for CIN. Age over 70, preprocedural dehydration, congestive heart failure, anemia, volume and type of CM administered, and concurrent administration of nephrotoxic drugs were found to be potential risk factors.The purpose of this study was to determine the incidence and to assess predictive factors of CIN in Chinese patients and to develop a predictive model that could provide a good prediction for CIN before patients were exposed to CM.The study protocol was approved by the Medical Ethical Committee in the Third Xiangya Hospital of Central South University (No. 2016‐S160). All subjects were anonymized so informed consent was not required. This study conformed to the ethical guidelines of the 1975 Declaration of Helsinki and Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.2) (n=422), age ≤15 (n=635), missing variables more than 30%, which means that the number of missing variables is greater than 25 in the 83 variables (n=4914), and without serum creatinine value within 14 days before CM procedures or within 72 hours after procedures (n=55 478).We performed a retrospective single‐center case control study in hospitalized adults from September 2007 to January 2015. According to our institute protocol, patients were included if they were treated with CM for coronary angiography or percutaneous coronary intervention or received intravenous CM such as for CT or endovascular procedures (n=69 827), identified by the electronic medical record system at the Third Xiangya Hospital of Central South University, Changsha, China. The exclusion criteria were preprocedure estimated glomerular filtration rate (eGFR) under 15 mL/ concentration at the earliest within 14 days before a procedure was defined as the baseline, and the highest Scr within 72 hours after the procedure was used as the follow‐up Scr to evaluate the incidence of CIN.2) as estimated with the modified MDRD formula.In this study, CIN was defined as an increase of Scr of 0.5 mg/dl (44.2 μmol/L) or 25% relative increase in serum creatinine from the baseline value to 72 hours after exposure to CM in the absence of alternative causes for acute kidney injury according to the Contrast Media Safety Committee (CMSC). Creatinine clearance was calculated using the modification of diet in renal disease (MDRD) equation, and chronic kidney disease was defined as eGFR<60 mL/.Continuous variables of each group are presented as mean±standard deviation, and the categorical variables are expressed as absolute values and percentages. A t test was used to compare the normally distributed continuous variables; otherwise, the Mann‐Whiney U test was used. Categorical variables were performed by chi‐squared test. A 2‐tailed value of We developed the prediction model based on machine learning. Randomization and data analysis were performed using random forests (RF), an ensemble of decision trees.The selected 8800 patients were randomly divided into 2 separate data sets: 80% of the patients  in our database were selected to the training data set , and the remaining 20%  were reserved as the external validation sets  to obtain unbiased estimates of correct classification rates and variable importance.In this model RF is also used to assess the importance of variables in model quality when each variable is replaced in turn by random noise in each tree. The variable importance is measured by the resulting deterioration in model quality. The deterioration in model quality can be assessed by the change in misclassification rates for the out‐of‐bag validation. The heuristics was based on the Gini criterion. Specifically, we recorded the decrease in the Gini node impurity for the variable Xj, which was used to form the split at each split. In the forest where Xj formed the split, the average of all decreases in the Gini impurity decided the Gini variable's importance. In addition, the AUC was also used to assess the importance of selected variables: when a variable is excluded in the model, the larger the change in value of AUC is, the more important the variable is.Five‐fold cross‐validation was primarily used as an internal validation to evaluate the prediction accuracies of the model. Briefly, we split the data set into 5 roughly equal‐sized parts, and then 4 of them were fit into the model while the other part was used to calculate the error rate. The process was repeated 5 times so that every part could be predicted as a validation set.The prediction performance was assessed by several criteria including the overall prediction accuracy (R), sensitivity (SE), specificity (SP), and Matthews correlation coefficient (MCC). The equations are as follows:SE and SP allow computation of the percentage of correctly predicted CIN and non‐CIN, respectively, while prediction accuracy means percentage of correctly predicted CIN and non‐CIN. MCC is the statistical parameter to assess the quality of prediction and to take care of the data unbalancing. The Matthews correlation coefficient ranges from −1 to 1. MCC=1 indicates the best possible prediction, and MCC=−1 points out the worst possible prediction.Of a total of 69 827 patients administrated CM, 8800 patients  were included in this study. Of them, 1173 (13.3%) developed CIN. Table 2) (SD 53 mL/[min·1.73 m2]). Chronic kidney disease was present in 962 patients (13.7%).Eighty‐three variables including demographic information, comorbidities, medications, and laboratory values were collected for each patient. Among the 8800 patients, there were 1656 patients undergoing percutaneous coronary intervention, and of them, 195 (11.8%) suffered from CIN. The incidence in the other CM procedures can be seen in Table In general, as more variables are chosen, the error of the model will be smaller. However, increasing the number of variables does not benefit clinical practice. To identify the prominent features, we carried out variable selection using different feature subsets by the RF method. Figure +), plateletocrit (PCT), international normalized ratio (INR), and blood glucose (BG). The importance of the 13 variables is demonstrated in Figure Thus, our final model included 13 indispensable features for CIN prediction: baseline eGFR, red cell distribution width (RDW), triglycerides, the most recent serum creatinine before the procedure, high‐density lipoprotein cholesterol (HDL), total cholesterol, low‐density lipoprotein cholesterol (LDL), blood urea (BU), platelet larger cell ratio (P‐LCR), serum sodium  was developed on basis of the sensitivity and specificity of the above values. The area under the ROC curve (AUC) is often used as an additional performance index. The closer AUC was to 1, the greater was the predictive ability of the model. A model with no predictive ability would yield the diagonal line. Figure The prediction accuracies of the model were internally evaluated by 5‐fold cross‐validation. On the average, the prediction model gave a prediction accuracy of 82.2%, sensitivity of 84.4%, specificity of 79.9%, and Matthews correlation coefficient of 64.4%.In order to examine the performance of the newly developed model, we tested our training models based on a data set containing 231 patients with CIN and 1529 patients without CIN for an external validation. The basic information comparing the training and validation sets is showed in Table With the increasing use of CM, CIN has become the third leading cause of hospital‐acquired acute renal failure, contributing to growing in‐hospital morbidity and mortality, hospitalization prolongation, and increase in costs.Several models have been developed for the prediction of CIN; however, they just focus on patients receiving intra‐arterial CM for coronary angiographic procedures, which represent only a small proportion of all contrast procedures.Here, we developed a prediction model of CIN with preprocedure variables by RF, which was composed of Chinese patients administered CM. The new system was first established to provide a prediction model of contrast‐induced AKI using preprocedural variables in an unselected population. The AUC of this newly developed model was 0.907, demonstrating good discriminative power. Although the present model did not include procedure‐related variables, its predictive value was better than that of the Mehran risk score, whose AUC was 0.67. The prediction accuracies were internally evaluated by 5‐fold cross‐validation and tested by the test data set for an external validation. Thirteen of 83 variables were chosen in our risk prediction model for CIN. A strong relationship is found between decreased sodium and increased risk of CIN in patients who underwent CM administration. Additionally, INR is also observed to be a powerful factor affecting CIN prediction. In addition, we used the preprocedural glucose level in a CIN risk prediction model for the first time in the present study.Our study is the first to show a relationship between decreased serum sodium and increased risk of CIN among patients who underwent CM administration. For 1 thing, hospital‐acquired lower serum sodium is found to coincide with various inflammatory conditions.Our research indicates that baseline eGFR is an important risk factor, as has been found in previous studies.Blood urea, a parameter for evaluation renal function, is also in our model, although the renal function is mainly evaluated by eGFR. Furthermore, blood urea plays a fundamental and direct role in fluid and sodium homeostasis regulated by neurohormonal systems.The RDW, reported routinely as part of an automated full blood count and used to evaluate the size of circulating red blood cells and the possible causes of anemia, is a main risk factor in the development of CIN. It has been found that RDW correlates with kidney function. Moreover, recent studies have reported an independent association between increased RDW and CIN in patients who underwent PCI.Although several studies have indicated that elevated glucose level is a risk factor of CIN,By examining the relationships among HDL cholesterol, LDL cholesterol, triglycerides, serum total cholesterol, and CIN, our study found that hypercholesterolemia, hypertriglyceridemia, or low HDL would raise the risk for CIN. Such blood lipid factors result in reducing the production of nitric oxide and increasing oxidative stress and inflammation in the kidney.For the first time, the elevated INR has been reported in a CIN prediction model. INR monitoring is essential during oral anticoagulation therapy to minimize bleeding complications and thrombotic events. INR elevation indicates that the glomerulus may hemorrhage, and red blood cell casts obstruct renal tubules.We also find that platelet activity biomarkers may correlate with the development of CIN. Those reflecting the platelet reactivity, including platelet count (PC), platelet–larger cell ratio (P‐LCR), mean platelet volume (MPV), and platelet distribution width (PDW), were evaluated in this study. PC and P‐LCR, the index of the platelet reactivity, are significant variables in this model. Thrombocytopenia has often been cited as an indicator of critical illness severity,A risk prediction model with excellent predictive ability for CIN in Chinese patients has been successfully established. This model can be applied to patients administered CM for coronary procedures and other contrast procedures such as intravenous contrast‐enhanced CT, CT angiography, and noncoronary angiography. For the first time, there are 3 new factors included in the model: the decreased sodium concentration, the INR value, and the preprocedural glucose level.The potential limitations of our study should be mentioned. First, this study is limited by its retrospective design, whose inherent weakness cannot be avoided. Second, our prediction model is derived and validated by a single center. For the wide application of the prediction model, it still needs to be validated in a multicenter trial. Third, any variable that was missing for more than 30% of the population was not assessed in the present study. Finally, we ignored unstructured clinical notes. Future studies addressing these limitations are necessary.Yin and Zuo conceived and designed the study. Yin, Zuo, and Yi performed data acquisition and statistical analyses. Yin and Guan managed the patient database. All authors were involved in the data interpretation and discussion of the results. Yin, Wang, and Li prepared the figures. Yin and Zuo drafted the manuscript. All authors approved the final version of the manuscript.This study was supported by the Program for New Century Excellent Talents in University (NCET‐13‐0605), the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University (No. 20150218), National Natural Science Foundation of China (81102512), and the National Clinical Pharmacy Key Specialty Construction Project.None.


Hypertension has proven to be a strong liability with 13.5% of all mortality worldwide being attributed to elevated blood pressures in 2001. An accurate blood pressure measurement lies at the crux of an appropriate diagnosis. Despite the mercury sphygmomanometer being the gold standard, the ongoing deliberation as to whether mercury sphygmomanometers should be replaced with the automated oscillometric devices stems from the risk mercury poses to the environment.This study was performed to check the validity of automated oscillometric blood pressure measurements as compared to the manual blood pressure measurements in Karachi, Pakistan.Blood pressure was recorded in 200 individuals aged 15 and above using both, an automated oscillometric blood pressure device (Dinamap Procare 100) and a manual mercury sphygmomanometer concomitantly. Two nurses were assigned to each patient and the device, arm for taking the reading and nurses were randomly determined. SPSS version 20 was used for analysis. Mean and standard deviation of the systolic and diastolic measurements from each modality were compared to each other and P values of 0.05 or less were considered to be significant. Validation criteria of British Hypertension Society (BHS) and the US Association for the Advancement of Medical Instrumentation (AAMI) were used.Two hundred patients were included. The mean of the difference of systolic was 8.54 ± 9.38 while the mean of the difference of diastolic was 4.21 ± 7.88. Patients were further divided into three groups of different systolic blood pressure <= 120, > 120 to = 150 and > 150, their means were 6.27 ± 8.39 , 8.91 ± 8.96  and 10.98 ± 10.49  respectively. In our study 89 patients were previously diagnosed with hypertension; their difference of mean systolic was 9.43 ± 9.89  and difference of mean diastolic was 4.26 ± 7.35 .Systolic readings from a previously validated device are not reliable when used in the ER and they show a higher degree of incongruency and inaccuracy when they are used outside validation settings. Also, readings from the right arm tend to be more precise. One of the most common medical tests done on thousands of patients every day is a blood pressure measurement. An accurate measurement is vital in providing appropriate treatment. It aids in the diagnosis of various conditions; ranging from dehydration in diarrhoea patients with low readings to vascular disease patients with elevated readings. A BP reading can be the defining point of treatment in patients with chest pain or altered mental status.Hypertension is one of the leading causes of developing atherosclerosis, cerebrovascular disease, stroke, ischemic cardiac disease, congestive heart failure and myocardial infarction . ElevatePhysicians are thus advised to routinely check for BP elevation in all of their patients. Overestimation of BP can expose the patient to the potential adverse effects of drug treatments as well as unnecessary medical costs and dietary restrictions. While with an underestimated reading, the patient is at a risk of HTN related diseases, which can significantly reduce life expectancy. Therefore an accurate reading is essential .There are three non-invasive modalities commonly used to check blood pressure throughout the world, namely the manual mercury sphygmomanometer, aneroid meter and the automated oscillometric device. The manual mercury sphygmomanometer is considered to be the gold standard  that is,A myriad of factors can affect manual blood pressure measurements such as the site of placement of the cuff, the size of the cuff, type of stethoscope, following the proper protocol, patient’s age group, pregnancy, exercise, arrhythmias and the white coat response . ReadingApart from the above-mentioned causes that are mostly associated with the manual mercury sphygmomanometer, there are causes that might influence the readings of both AO BP devices and the manual BP like respiration, emotions, tobacco, alcohol, temperature, bladder distension, pain and exercise. Most of these are controllable, while some are non-modifiable like age, race and diurnal variation -15. AutoMultiple studies suggest that the AO devices should replace the conventional manual mercury sphygmomanometer, as the latter is destined to become obsolete , 18. HowThis study was conducted at a tertiary care hospital in Karachi, Pakistan, using the resources at hand, with the available AO BP instruments and the mercury sphygmomanometer. The study was performed to check the validity of AOBP measurements as compared to the manual BP measurements in Karachi, Pakistan.The study was conducted at a tertiary care hospital in Karachi, Pakistan. This hospital is equipped with AOBP monitors, Dinamap Procare 100 and manual mercury sphygmomanometers with a Littman classic II stethoscope. This was a double-blind randomised clinical crossover trial. Every patient was assigned two staff nurses who used an automated oscillometric blood pressure device and a manual mercury sphygmomanometer on the patient concurrently. The device, arm for taking the reading and nurses were randomly determined. Both the nurses remained blind of the readings they recorded.All patients were in a supine position when their BP was checked. Patients aged 15 and above were included, whereas patients with complaints of chest pain, altered mental status, GCS < 12/15 and patients who had smoked within the last 30 minutes were all excluded.Randomization was done by giving the staff nurses printed forms that they filled and then sealed in the same envelope for a given patient. The crossover was achieved by taking manual than auto or auto and then manual measurements. The form consisted of fields that required the name of the device, arm from which the reading was taken, presenting complaint, history of HTN, DM, IHD, renal diseases, neurological disorders, and chronic respiratory tract diseases.p-values of 0.05 or lower were considered to be significant. Bland- Altman plots were employed to graphically represent the data. This study was done from February 2015 to May 2015. The sample size was 200.The analysis was done using SPSS version 20. Test of significance was T test and The Emergency Department is one of the most vital departments in the hospital. Decisions made in the ED shape the rest of the therapy for the patient. EDs all over the world receive a diverse array of patients from all age groups with a variety of clinical conditions. Accurate blood pressure measurements are pivotal for treatment, especially for patients with deteriorating conditions. In 2011, a study suggested that substituting automated oscillometric devices for auscultatory devices could cause grave repercussions for patients in specific circumstances; and in cases of trauma or deteriorating patient condition, manual BP should be given preference . DespiteEven at very low levels, environmental mercury can act as a potent neurotoxin and cause serious harm. Health care facilities are one of the main sources of mercury pollution via emissions from incineration of medical waste. Mercury sphygmomanometers, collectively, are the largest reservoir of mercury in the health care setting, often containing 80-100 g/unit. The WHO considers them a major occupational hazard, as inadequate care may result in dangerous exposures to patients and health care staff . WHO andAutomated oscillometric devices, on the other hand, are not only considered environmentally safe but they also have a significant advantage over their manual counterparts (mercury or aneroid): they don’t require a trained professional to take a reading. This makes them perfect for ambulatory readings for patients and to monitor BP at home. Primarily for this reason, oscillometric devices are gaining fame. A bias commonly faced by physicians is white coat hypertension, and it has been proven that automated oscillometric devices substantially remove this effect leading to more accurate readings , 24.Many oscillometric devices are available in the market. Most of these devices are not put through any validation and yet they are still being sold and used by the population. Thus there is a growing concern regarding many of these devices , 26. TheOscillometric devices can have unreliable readings when used on diabetic patients, pregnant women, elderly patients and patients with arrhythmias , 29. TheIn our study, the mean of difference in manual systolic and automated systolic blood pressure was 8.54 with a standard deviation of ± 9.38, while the mean of difference in manual diastolic and automated diastolic was noted to be 4.21 with a standard deviation of ± 7.88. The range of difference between manual systolic and automated systolic blood pressure was calculated to be -20 to +38, while the difference between the manual diastolic and automated diastolic blood pressure was -17 to +29. The 95% CI for systolic blood pressure lies in the range of -9.84 to +26.92.This range of 36.76 demonstrates that automated blood pressure monitors lack precision for use at the emergency department. The 95% CI for diastolic blood pressure lies in between +19.66 to -11.24, this range of 30.9 is yet again not precise enough to yield a reliable diastolic blood pressure reading in the ED. The plots in Exploring this further, we divided the patients into three groups based on their BP readings: patients who had a manual systolic reading of below 120 mmHg, those who had readings between 120 mmHg and 150 mmHg and those who had readings above 150 mmHg. The differences between manual and electronic readings for the three groups are given as follows.A one-tailed t-test was done to see whether the observed error of electronic equipment was statistically different from the recommended AAMI criteria: mean < 5 mmHg and a standard deviation < 8 mmHg. Based on the p-values, patients who had systolic blood pressure less than 120 mmHg fell within acceptable range.We also observed differences in measurements between the left arm and the right arm, particularly for Systolic readings. SBP measured on the right arm had less error and less standard deviation as compared to measurements on the left arm.Analysing this further, we checked whether the error component of the electronic device was varying based on the arm of measurement and the actual  blood pressure readings. One-tailed t-tests were done to check if each group was statistically different from the recommended AAMI criteria (mean of < 5 mmHg and standard deviation of < 8 mmHg).The null hypothesis was that the observed error is not different from the AAMI criteria. Where the null hypothesis was rejected, the p-values have been marked in red, which indicate that there is a difference between the observed error and the AAMI criteria.From this table  it can bp-value 0.000), while the mean of difference of diastolic blood pressure was 4.26 with a standard deviation of ± 7.35 , this shows that there is greater variability of the measurements when automated devices are used on hypertensive patients. Van Popele et al reported that increased arterial stiffness causes higher SBP and DBP readings on oscillometric devices although the underlying mechanism of why it occurs is not clear [While some studies clearly favour oscillometric devices , others ot clear . In our ot clear .et al showed that most of the devices approved by the BHS and AAMI are able to reproduce the results during protocol testing  with 60-86% of the measurements collected within the reference range of 5 mmHg. However, in devices tested in community/clinic-based studies only 35-46% values were within 5 mmHg of the observed value [et al stated that the poor performance in community settings is because the devices do not perform up to par when they are tested outside the validation setting . This is an evident finding in our study, where only 33% of systolic measurements and 44.5% of diastolic measurements were within the range. Skirton et al suggested that hypertensive patients, patients with arrhythmias and trauma should be monitored with manual meters as opposed to automated. In our study, in 89 patients with diagnosed HTN, 24.7% of systolic measurements and 39.3% of diastolic measurements were within reference range [et al [An automated device is only recommended if AAMI criteria are fulfilled; that is both systolic and diastolic measurements should not have a mean difference > 5 mmHg or a standard deviation > 8 mmHg. The British Hypertensive Society denotes a grade of A or B if a device is approved , 35. Theed value . Wan et ce range . The dece [et al .Health care is a rising burden on governments across the world. This is further magnified when developing nations are taken into consideration. There are 28 recommended devices that are considered to be reliable by the British Hypertension Society, which roughly range from 136 GBP to 2000 GBP . In PakiIn conclusion, mercury is an environmental hazard and will probably face a worldwide ban as more awareness spreads, thus urgent research for developing new and accurate devices is warranted. Furthermore, separate protocols and criteria have to be established for the use of automated devices in different departments, as the ideal conditions in which these devices are tested won’t be available when these devices are put to test on the field. Our study shows that systolic readings from a previously validated device are not reliable when used in the ED. Secondly, if the blood pressure is measured for the right arm then there is a higher chance of an accurate reading. Lastly, even validated devices show great variability and low precision when they are used outside validation setting. Thus the role of automated blood pressure monitors should be evaluated for their use in the emergency departments.Awareness needs to be spread amongst physicians that there is a higher level of discrepancy when using these devices on hypertensive patients. Researchers are required to test aneroid blood pressure monitors and there is an urgent need for developing low cost but reliable automated blood pressure devices so that the transition of banning mercury sphygmomanometers is smooth.


CEL gene harbours a variable number of tandem repeats (VNTR) region in exon 11. Variation in this VNTR has been linked to monogenic pancreatic disease, while conflicting results were reported for chronic pancreatitis (CP). Here, we aimed to investigate a potential association of CEL VNTR lengths with alcoholic CP.Carboxyl-ester lipase (CEL) contributes to fatty acid ethyl ester metabolism, which is implicated in alcoholic pancreatitis. The Overall, 395 alcoholic CP patients, 218 patients with alcoholic liver cirrhosis (ALC) serving as controls with a comparable amount of alcohol consumed, and 327 healthy controls from Germany and the United Kingdom (UK) were analysed by determination of fragment lengths by capillary electrophoresis. Allele frequencies and genotypes of different VNTR categories were compared between the groups.P = 0.04) compared to controls, whereas twelve repeats were enriched in German ALC compared to alcoholic CP patients (P = 0.03). Frequencies of CEL VNTR lengths of 14 and 15 repeats differed between German ALC patients and healthy controls . However, in the genotype and pooled analysis of VNTR lengths no statistical significant association was depicted. Additionally, the 16–16 genotype as well as 16 repeats were more frequent in UK ALC than in alcoholic CP patients . In all other calculations, including pooled German and UK data, allele frequencies and genotype distributions did not differ significantly between patients and controls or between alcoholic CP and ALC.Twelve repeats were overrepresented in UK ACP patients (CEL VNTR lengths are associated with alcoholic CP. However, our results suggest that CEL VNTR lengths might associate with ALC, a finding that needs to be clarified in larger cohorts.We did not obtain evidence that  PRSS1 (cationic trypsinogen), CFTR (cystic fibrosis transmembrane conductance regulator), SPINK1 , CTRC (chymotrypsinogen C), CPA1 (carboxypeptidase A1) and the CLDN2-MORC4 locus have been identified to increase risk of CP development, a rare variant in PRSS2 (anionic trypsinogen) and a common variant in the PRSS1-PRSS2 locus are protective [Chronic pancreatitis (CP) is a recurring and painful inflammatory disease leading to exocrine and endocrine insufficiency in many patients ,2. In thotective –10.SPINK1, p.R254W in CTRC, and common variants of the PRSS1-PRSS2 and CLDN2-MORC4 locus [In alcoholic CP, genetic associations have been described for the variants p.N34S in C4 locus ,8,11. ThCarboxyl-ester lipase (CEL) is secreted into the pancreatic juice and contributes to the hydrolysis of dietary lipids in the duodenum ,13. PancCEL and the neighbouring CEL pseudogene (CELP) confers disease risk in non-alcoholic and alcoholic CP [CEL exon 11. This VNTR encodes a repetition of 11 amino acids located in the C-terminal part of the protein [CEL-MODY, an autosomal dominantly inherited disease characterized by monogenic diabetes and pancreatic exocrine dysfunction [CEL allele in the general population contains a VNTR of 16 segments, but VNTR lengths can vary between 3 and 23 repeats [A hybrid allele comprising parts of holic CP . A varia protein –21. Varifunction . The mos repeats –23. The CEL VNTR repeats  with alcoholic CP, whereas no association was found in non-alcoholic CP patients and in patients with alcohol abuse and no signs of CP [CEL VNTR lengths in alcoholic and non-alcoholic CP patients was identified [CEL VNTR in alcoholic CP, we have here investigated alcoholic CP patients as well as patients with alcoholic liver cirrhosis (ALC) and healthy controls from Germany and the United Kingdom. We employed an established screening method that accurately identifies the length of the CEL VNTR [A Japanese study described an association of longer ns of CP . Notablyentified . To clarCEL VNTR .http://home.uni-leipzig.de/ethik/index.htm; Approval: 376-11-12122011) and the Multicentre Research Ethics Committees for Liverpool  approved the study protocol and all patients gave written informed consent. Diagnosis of CP was based on two or more of the following findings: presence of a typical history of recurrent pancreatitis or recurrent abdominal pain typical for CP, pancreatic calcifications and/or pancreatic ductal irregularities revealed by endoscopic retrograde pancreatography or by magnetic resonance imaging of the pancreas and/or pathological sonographic findings. Alcoholic CP was defined in patients who had consumed more than 80 g/d alcohol for at least two years in men and more than 60 g/d for women.The medical ethical review committee of the University Leipzig  or due to unequivocal clinical and laboratory findings in men who consumed more than 80 g/d and in women who consumed more than 60 g/d for at least 10 years. Such findings were abnormal aminotransferase level, gamma glutamyl transpeptidase level, coagulation tests, serum albumin concentration and platelet count, and/or complications related to liver cirrhosis including esophageal varices, ascites, hepatic encephalopathy and typical liver morphology in sonography or computed tomography. Other etiologies of liver cirrhosis were excluded by standard laboratory tests.In total, we enrolled 293 German alcoholic CP patients , 127 German ALC patients , and 236 healthy German controls . No samples overlapped with those formerly reported in . From thCEL VNTR lengths, polymerase chain reaction (PCR) followed by DNA fragment analysis was performed as described in [CEL VNTR repeats.Genomic DNA was extracted from peripheral blood leukocytes according to a standard protocol (QIAmp DNA Blood Mini kit (Qiagen Cat No./ID 51106) or MagNA Pure isolation kit (Roche Cat# 03730964001)). For analysis of ribed in . BrieflyP-values calculated using the Simple Interactive Statistical Analysis webpage (www.quantitativeskills.com/sisa/index.htm). P-values <0.05 were considered statistically significant.The significance of the differences between VNTR frequencies was tested in affected individuals and controls by two-tailed Fisher's Exact or Pearson’s Chi-square test and CEL VNTR lengths ranged from 7 to 23 repeats in the overall study population. In each of the three cohorts, the most frequent allele contained 16 repeats . The distribution of VNTR lengths in healthy controls was comparable to that of previous studies [ studies , 25 and CEL, implying that they carry an extra copy of the VNTR region [During fragment analysis, some samples  exhibited three NED-labelled peaks instead of the expected one or two peaks . The reaR region , 23. We P = 0.04; odds ratio (OR) = 7.36; 95% confidence interval (CI) = 0.91–53.39), that was not seen in the German cohorts (Tables CEL duplication variants) contribute to alcoholic CP risk, genotype frequencies were calculated in both groups. Again, there was no significant difference between alcoholic CP patients and healthy controls  versus controls (0.5%) . In contrast, an underrepresentation of 15 repeats was found in German patients (9.7%) compared with controls (17.0%)  . Calculations of pooled VNTR lengths and genotype distribution in cohorts from both countries did not show differences between the groups  vs. controls (11.7%) 33–0.85) . In the % vs. con5 . In thP = 0.03; OR = 0.11; 95% CI = 0.01–0.96)    . Analyse30–0.96) .CEL VNTR lengths are associated with alcoholic CP. This is in contrast to the previous Japanese study, which reported significant underrepresentation of the NN and overrepresentation of the NL genotype in alcoholic CP patients [N-allele, less than 16 repeats to the S-allele, and more than 16 repeats to the L-allele of the Japanese study [Taken together, this study of patients with alcoholic CP or ALC and healthy controls from two countries has identified no evidence that patients . Of notese study . If so, se study .Explanations for this discrepancy might be methodological in that alleles have been characterised differently. In addition, there could be differences in alcohol consumption between Japanese and European populations, since the Japanese VNTR study did not include the quantity of alcohol consumed in the definition of alcoholic CP. Furthermore, a proportion of the Japanese alcoholic controls may have had ALC or alcoholic CP. This is due to the fact, that these individuals had documented attacks of acute pancreatitis, but a normal pancreatogram on endoscopic retrograde cholangiopancreaticography (ERCP), which makes alcoholic CP unlikely, but does not rule this out . MoreoveAlcoholic CP and ALC can be found concomitantly in patients, indicating that common pathways for disease development might be involved. It has been reported that clinical alcoholic CP and ALC occur concurrently in around 16–20% of alcoholic CP/ALC cases, but the prevalence may be higher at a histological level –29. It iCEL VNTR lengths with the disease pathogenesis of ALC, however, the definite repeat lengths cannot be defined in this stage. A possible pathophysiological explanation for how CEL VNTR length contributes to ALC development might be the determination of plasma lipid levels, as CEL VNTR length seems to influence total and low density lipoprotein cholesterol levels [In our comparison of German ALC patients with healthy controls, 14 repeats were enriched in patients while 15 repeats were underrepresented. Further, 12 repeats were enriched in German ALC compared to alcoholic CP patients. Additionally, 16 repeats were overrepresented in ALC patients from the UK in comparison to alcoholic CP patients and with borderline significance in comparison to controls. As well the NN genotype was more frequent in ALC than in alcoholic CP patients. Thus, these results indicate a possible association of l levels . This wol levels . FurtherCEL VNTR (e.g. with 14-16-16 repeats) from those samples that are truly heterozygous with regard to VNTR length (e.g. with 14–16 repeats). Consequently, we might have underestimated the number of carriers with three copies of the VNTR. Nevertheless from our data (Tables In this study we used blood donors as controls, which might bias the results since some controls may suffer from alcoholic CP or ALC. Still, this potential confounder is surmised to be negligible due to the low prevalence of alcoholic CP and ALC in the general population as well as the strict screening protocols that blood donors have to undergo. In addition, allele frequencies and genotype data in our control group are comparable to former reports, and as such indicate that the selected control group is suitable for the conclusions drawn. Another limitation of this study could be that our method cannot distinguish samples carrying an extra copy of the a Tables  and 14 iCEL VNTR lengths in cohorts of patients with alcoholic CP or ALC and healthy controls from Germany and the UK. In line with the former European study [CEL variants may affect the development and progression of ALC.In conclusion, we present a comprehensive analysis of an study , we did


P < 0.025). Multivariate-adjusted Cox regression analyses showed that reverse dippers (versus dippers) were associated with a higher risk of total mortality , cardiovascular mortality , renal events  and cardiovascular events  even after adjustment by 24-h systolic BP. These data suggest that a reverse dipping BP pattern, independent of 24-h levels of systolic BP, has prognostic value in CKD patients not undergoing dialysis.The “reverse dipping” blood pressure (BP) pattern has been studied among the general population and in individuals suffering from hypertension. However, the prognosis of this pattern in chronic kidney disease (CKD) patients is not known. We monitored BP throughout the day and followed health outcomes in 588 CKD patients admitted to our hospital. Time to all-cause mortality, cardiovascular mortality, renal events and cardiovascular events was recorded. Multivariate-adjusted Cox regression analyses were carried out to detect the prognostic value of a reverse dipping BP pattern. Prevalence of a “dipper”, “non-dipper” and “reverse dippers” was 34.69%, 43.54% and 18.03%, respectively. Patients with a reverse dipping pattern had a higher prevalence of total mortality, cardiovascular mortality, renal events and cardiovascular events than patients with a dipping pattern ( Chronic kidney disease (CKD) is a public-health issue in China. Prevalence of CKD in China is 10.8%, so the number of patients with CKD in China has been estimated to be ≈119.5 million according to one survey1Ambulatory blood pressure monitoring (ABPM) is a better predictor of target-organ damage and cardiovascular events than clinical monitoring of BP6781011However, data on the prognostic role of a reverse dipping BP pattern on all-cause and cardiac mortality in CKD patients not undergoing dialysis are scarce. One study from Italy suggested that CKD patients not undergoing dialysis with a reverse dipping BP pattern carried a greater risk of renal disease and CVDOf the 588 CKD patients enrolled: 397 patients had chronic glomerulonephritis; 63 cases had diabetic nephropathy; 32 subjects had hypertensive nephropathy; 28 individuals had lupus nephritis; and 68 patients had other causes of renal disease .P < 0.017). Compared with dippers, non-dippers had: higher levels of BUN, intact parathyroid hormone (iPTH) and homocysteine; lower levels of hemoglobin; higher levels of proteinuria; higher 24-h SBP, nighttime SBP and nighttime DBP (P < 0.017). Extreme dippers had lower nighttime SBP and nighttime DBP compared with dippers (P < 0.017) ; higher levels of blood urea nitrogen (BUN) and creatinine; lower levels of hemoglobin and estimated glomerular filtration rate (eGFR); higher levels of proteinuria; higher 24-h SBP, 24-h diastolic blood pressure (DBP), daytime SBP, nighttime SBP and nighttime DBP (< 0.017) .With regard to total mortality, median follow-up was 35 (interquartile range (IQR): 24–49) months, and total follow-up amounted to 1762 patient-years. During follow-up, 44 patients died (event incidence: 24.98 per 1000 patient-years). Causes of death were: fatal heart failure (22 patients); acute myocardial infarction (10); stroke (7); malignant tumor (4); gastrointestinal bleeding (1). Hence, 39 patients among this cohort died of cardiovascular events (event incidence: 22.00 per 1000 patient-years).With regard to renal events, median follow-up was 31 (IQR: 19–45) months, and total follow-up time amounted to 1594 patient-years. During follow-up, 140 renal events were recorded in this cohort (event incidence: 87.83 per 1000 patient-years).With regard to cardiovascular events, median follow-up was 34 (IQR: 24–49) months, and total follow-up time amounted to 1717 patient-years. During follow-up, 74 cardiovascular events were recorded (event incidence: 43.10 per 1000 patient-years): 39 fatal events (as described above) and 35 non-fatal events .P < 0.025)  .P < 0.001). For all endpoints, survival of reverse dippers was lower than that of dippers (P < 0.025)  .versus having a dipping BP pattern) was associated with a higher risk of total mortality , cardiovascular mortality , renal events  and cardiovascular events ; Also, having a non-dipping pattern (versus having a dipping BP pattern) was associated with a higher risk of renal events . When these models were also adjusted for 24-h BP, having a reverse dipping BP pattern (versus having a dipping BP pattern) continued to be associated with a higher risk of total mortality , cardiovascular mortality , renal events  and cardiovascular events ; while non-dippers was no longer associated with prognosis  may have affected the BP pattern, which may have led to different results in different CKD patients.In conclusion, we have provided the first evidence that a reverse dipping BP pattern, independent of 24-h SBP, has prognostic value in Chinese CKD patients not undergoing dialysis. Further, prospective randomized clinical trials are needed to clarify if correction of BP patterns by administration of antihypertensive drugs at night improves the prognosis and attenuates progression of CVD and renal disease in CKD patients.The study protocol was approved by the ethics committee of the Third Affiliated Hospital of Sun Yat-sen University , and was approved by the Institutional Review Board. All methods were carried out in accordance with approved guidelines. Written informed consent was obtained from patients before enrollment. In this prospective cohort study, inpatients were recruited from July 2010 to December 2014. All information was extracted from our entire in-patient ABPM research database which was set up by our research group.Inclusion criteria were patients: age ≥14 but <75 years; with CKD; who promised to return to the Third Affiliated Hospital of Sun Yat-sen University to complete the first follow-up .Exclusion criteria were patients: with acute changes in the eGFR > 30% in the previous 3 months; undergoing dialysis; who had undergone kidney transplantation; with atrial fibrillation; with cardiovascular events in the previous 3 months; who were pregnant; had night-work or shift-work employment; could not tolerate ABPM; had invalid ABPM data.697 CKD patients fulfilled inclusion criteria, 71 patients who fulfilled exclusion criteria were excluded and the detailed reasons could be found in Patients underwent 24-h ABPM using a TM-2430 Monitor  as reported previously23BP was measured for each patient during a visit to the physician. Sphygmomanometer measurements were recorded by the same physician, who was not aware of the results of ABPM recordings, as detailed elsewhere23We collected urine samples from 7 AM to 7 AM the next day to identify the extent of proteinuria and sodium levels over 24 h. These patients were asked to void their bladders before and after urine collection. Proteinuria was measured by immunoturbidimetry. In addition, medical history, including demographic, laboratory data , low-density lipoprotein-cholesterol (LDL-C), homocysteine, uric acid, serum creatinine, BUN), and current therapy were obtained at the initial study visit. All experimental data were measured using a 7180 Biochemistry Auto-analyzer .“ABPM daytime” and “ABPM nighttime” were defined according to patients’ schedules.Participants with a reduction in SBP of ≥10% but <20% at nighttime compared with daytime were considered to have a dipping BP pattern. An extreme dipping BP pattern referred to a reduction at nighttime of >20%. A non-dipping BP pattern referred to a <10% reduction at nighttime. A reversed dipping BP pattern referred to higher SBP at nighttime compared with daytimeCKD was defined according to the KDIGO 2012 clinical practice guidelineStandards of Medical Care in DiabetesDM was defined as the need for anti-DM drugs or meeting the diagnostic criteria based on the Primary endpoints were time to all-cause mortality and time to cardiovascular mortality. Secondary endpoints were time to renal events and time to cardiovascular events.International Classification of Disease. Hospital records were collected to establish the diagnosis based on criteria set by the American College of Cardiology and the European Society of Cardiology29Cardiovascular mortality was defined as death caused by cardiovascular events. Renal events were a composite of doubling of serum creatinine or end-stage renal disease (ESRD), whichever occurred first. The endpoint of ESRD was reached on the day of the first dialysis sessionDescriptive statistics are the mean ± SD for continuous variables and median values/interquartile range for nonparametric variables. Frequency and percentages are used for categorical variables.t-test, or nonparametric tests. Differences among categorical variables were analyzed using the χ2 test or Fisher’s exact test. Comparisons of continuous variables among groups were evaluated by ANOVA, or nonparametric tests. P-values for multiple comparisons were corrected according to the Bonferroni method.Comparisons of continuous variables between groups were evaluated by the Student’s P-value for multiple comparisons was corrected according to the Bonferroni method.We used STATA v14.0 to calculate the prevalence of endpoints. Crude rates and rates standardized by the direct method for sex and age are reported. Comparison of event rates among groups was done by the log-rank test. We used Kaplan–Meier survival curves plotted according to current recommendationsWe used a competing risks model to compute hazard ratios associated with reverse dippers and non-dippers relative to dippers with regard to total mortality, cardiovascular mortality, renal events and cardiovascular events. In partly adjusted models, HRs were adjusted for age, sex, DM, cigarette smoking, alcohol consumption, body mass index, history of CVD, eGFR, hemoglobin level, phosphate level, cholesterol level, proteinuria and blockade of the renin–angiotensin system. In fully adjusted models, HRs were adjusted for these same parameters but also for 24-h BP.P-values were two-sided and the level of the test (α) was set as 0.05. Data were analyzed using SPSS v20.0  and STATA v14.0.All How to cite this article: Wang, C. et al. Prognostic Value of Reverse Dipper Blood Pressure Pattern in Chronic Kidney Disease Patients not Undergoing Dialysis: Prospective Cohort Study. Sci. Rep.6, 34932; doi: 10.1038/srep34932 (2016).


LVH is highly prevalent in patients with CKD and is independently associated with subsequent cardiovascular events.We hypothesized that adding systolic blood pressure values to LVH might differentiate different subgroups of patients at higher risk of cardiovascular events (CVE) and other adverse outcomes.Retrospective cohort study of 243 patients older than 60 years with stages 1-5 pre-dialysis CKD. LVH was assessed by electrocardiogram or echocardiogram.Cardiovascular events occurred in 7 patients (10.3%) among those with SBP <130 and no LVH, 8 patients (10.5%) among those with SBP ≥130 and no LVH, 7 patients (21.2%) among those with SBP <130 and LVH and 25 patients (37.9%) among those with SBP ≥ 130 and LVH.p = 0.0007; 2.13  p = 0.16 in those with SBP <130 and LVH and 1.20  p = 0.72 in those with SBP ≥130 and no LVH.On multivariate analyses, comparing to SBP < 130 and no LVH, the HR for CVE in those with SBP ≥ 130 and LVH was 4 , No significant differences were noted in changes in renal function and mortality rates among the groups.The combination of higher systolic blood pressure and LVH might identify older patients with CKD at higher risk of cardiovascular outcomes. Cardiovascular disease represents the main cause of morbidity and mortality in patients with chronic kidney disease (CKD).Left ventricular hypertrophy (LVH) is a known manifestation of hypertensive target organ damage.LVH is highly prevalent in patients with CKD and is already present in the early stages of the disease. Its prevalence increases with age, anemia, hypertension and lower renal function , 2.More advanced CKD at baseline may be associated with larger longitudinal increases in left ventricular mass and volume and greater deterioration in diastolic function .On the other hand, more severe LVH is associated with kidney function decline and progression to dialysis , 5.In patients with CKD, LVH and other echocardiographic parameters (including low EF) are independently associated with subsequent cardiovascular events , 7.Because of the above, treating hypertension is of paramount importance in CKD populations. At the same time, the ideal blood pressure target in these patients is a subject of controversy. Retrospective studies in older patients with CKD suggest mortality is increased for systolic blood pressures (SBP) higher and lower than 130-139 mmHg and DBP of 60-79 mmHg .The objective of this study was to assess the prognostic value of combining LVH data with clinical data (SBP) as markers of adverse outcomes in older patients with CKD.Our hypothesis is that adding systolic blood pressure values to LVH might help differentiate different subgroups of patients at higher risk of adverse outcomes.After obtaining approval from the Rice Memorial Hospital Institutional Review Board (Willmar MN), a retrospective cohort study of 243 patients older than 60 years with stages 1-5 pre-dialysis CKD was carried out. These patients were seen in a Nephrology clinic between January of 2013 and November of 2015.Since prior studies in older patients with CKD suggest that mortality is lower for a SBP around 130 mmHg, we decided to use this value as reference .CKD was defined as evidence of structural or functional kidney abnormalities  that persisted for at least 3 months, with or without a decreased glomerular filtration rate (GFR), as defined by a GFR of less than 60 mL/min per 1.73 m2.Patients on renal replacement therapy, history of organ transplant, patients younger than 60 years of age, patients with a clinical diagnosis of congestive heart failure (CHF) at baseline, patients without LVH data.Demographics, comorbidities, LVH assessment by electrocardiogram (ECG) or echocardiogram and laboratory data at baseline and during follow up.Cardiovascular events (CVE) were defined as the composite of new episodes of acute coronary event, decompensated heart failure and cerebrovascular accident  during the follow up period.End stage renal disease requiring dialysis; changes in GFR; all-cause mortality. The cause of death was obtained from the medical records or death certificates.Office systolic blood pressures (SBP) and diastolic blood pressures (DBP) were measured with an automated device, using an adult cuff, with the patient in a seated position. Pulse pressure was determined by subtracting the DBP from the SBP. In the calculation of the mean blood pressure, we used blood pressures collected during regular visits to maintain consistency among all participants. A median of 18  blood pressure readings were obtained for each patient.2  or range if not. For parametric data, differences in the mean were compared by ANOVA. For highly skewed data, the Wilcoxon- Kruskal Wallis Test was used.Differences in proportions were assessed by the Chi square or Fisher’s exact test.Survival curves were generated using the Kaplan-Meier method. Cox proportional hazards models were used to study associations and adjust for confounding factors.P values lower ≤0.05 were considered statistically significant. All the analyses were performed using JMP statistical software version 11.2.0 .The baseline characteristics are depicted in Table Echocardiographic information was present in 160 patients. Electrocardiographic information was present in 84 patients. Whenever the two were present, the echocardiographic data was used for analyses.Primary and secondary outcomes are reported in Table p = 0.0003; 2.18 , p = 0.14 in those with SBP < 130 and LVH and 0.96  p = 0.94 in those with SBP ≥ 130 and no LVH.Comparing to SBP < 130 and no LVH the unadjusted HRs for CVE in those with SBP ≥ 130 and LVH was 4 , On multivariate analyses, after adjusting for confounding factors, the association of LVH and SBP ≥130 with CVE remained significant  might stratify the risk of CVE among older patients with CKD. Furthermore, there appears to be a graded risk, with worse outcomes in those with a SBP ≥130 and LVH vs those with a lower SBP and those without LVH.Higher blood pressure, greater body mass index (BMI), intravascular expansion, advancing age and male gender are associated with an abnormal left ventricular geometry. This cardiac hypertrophy ultimately leads to activation of metabolic pathways that increase extracellular matrix production leading to fibrosis. Fibrosis leads to reduced contractility with myocardial wall stiffening, systolic and diastolic dysfunction, cardiomyopathy, and congestive heart failure. Changes in cardiac remodeling might be fluid, with some patients reversing to normal geometry, especially with optimal blood pressure control –14.Other principles in the treatment of LVH in CKD patients include treatment of the anemia and secondary hyperparathyroidism.Unfortunately we did not have enough data to study LV geometry and other echocardiographic parameters in this study. Other studies have found that CV event-free survival is significantly worse in the presence of concentric LVH and eccentric LVH .There is some evidence that a concentric pattern (vs eccentric) portends a worse cardiovascular prognosis. Others suggest that LVH by itself, regardless of the geometry is associated with worse renal and cardiovascular outcomes , 17.The association of hypertension and adverse outcomes has been well demonstrated. In this study we found no difference in survival among the groups, although the number of events is fairly small and definite conclusions cannot be reached.In the SPRINT trial, aiming for a SBP lower than 120 mm Hg, as compared with less than 140 mm Hg was associated with lower rates of heart failure events, cardiovascular deaths and total deaths .On the other hand, retrospective studies have shown increased mortality with lower blood pressures in the elderly. Kovesdy et al found that patients with a SBP of 130 to 159 mm Hg combined with a DBP of 70 to 89 mm Hg had the lowest adjusted mortality rates, comparing to those with higher or lower BP readings .In 21,000 patients older than 65 years with stage 3-5 CKD not yet on dialysis there was increased mortality with a baseline SBP < 120 mmHg comparing to a SBP between 131-140 mmHg. A SBP higher > 140 mmHg was associated with increased mortality only in the younger patients with CKD [We believe the discrepancy about optimal blood pressure targets in older patients might be related to the presence of CHF, since hypotension in this setting has been associated with reduced survival –24.In this study, we excluded patients with a clinical diagnosis of CHF at baseline, so our findings cannot be applied to those patients with CKD and underlying CHF.In a recent paper we have found that a low SBP (less than 120 mmHg) was associated with worse survival in patients with CKD, nonetheless that patient population had more cardiovascular comorbidities at baseline . Based on our current findings we think studies evaluating the optimal BP target in older patients with CKD might need to differentiate among patients with and without heart failure and LVH .Although this was an observational study, the follow up was extensive, given the unique geographical characteristics of this population. Most patients receive their care in one of two local clinics and are admitted to one or two hospitals which share electronic medical records. This allows for close follow up of outcomes of interest.Among the limitations of this study we cite the retrospective design, small number of patients, lack of significant number of minorities, inability to assess for reversibility of LVH changes, use of ECG and echocardiographic criteria together, although in CKD patients LVH on electrocardiogram is associated with a higher increase in CV mortality than other traditional risk factors .The combination of higher systolic blood pressure and LVH might identify older patients with CKD at higher risk of cardiovascular outcomes. These results should be confirmed with larger studies.