In regression analysis, older age, higher BMI, smoking, and lower serum selenium concentrations were independently correlated with the greater cIMT. Higher BMI and smoking were independent risk factors for the lower TAS, and the use of ACE inhibitors, β-blockers, and higher Se-S were independent factors of protection against the lower TAS. In patients with arterial hypertension, the lower total antioxidant status due to lower serum selenium concentrations may be correlated with an increase of the carotid intima media thickness measured using ultrasound.The objective of the study was to establish the correlation between serum selenium concentrations, total antioxidant status, and the carotid intima media thickness in ultrasound assessment in patients with arterial hypertension. A group of 76 people suffering from arterial hypertension was qualified to participate in the study. The mean age of the respondents was 53.48 ± 12.78. Serum selenium concentrations (Se-S) and total antioxidant status (TAS) were determined in all respondents. Se-S were determined by hydride generation atomic absorption spectroscopy (HGAAS). The antioxidant status was assessed by the enzyme-linked immunosorbent assay (ELISA). In addition, an ultrasound exam of the carotid arteries was performed, and the intima media thickness (cIMT) was measured. In the study group, Se-S and TAS were 89.73 ± 18.99 µg/L and 1.18 ± 0.35 mM. However, the cIMT measured using ultrasound was 0.68 ± 0.15 mm. cIMT was significantly greater in patients with arterial hypertension with Se-S < median in comparison to patients with arterial hypertension with Se-S ≥ median (0.73 ± 0.19 mm vs. 0.65 ± 0.10 mm,  Selenium is an essential micronutrient that has a huge impact on human health. It is a component of many enzymes and it plays a key role in the optimization of metabolic reactions and protection against oxidative damage ,2,3. In One of the aspects of scientific research on the importance of selenium is research determining its impact on the cardiovascular system, including the development and course of arterial hypertension . The corArterial hypertension is one of the major risk factors for cardiovascular disease. Arterial hypertension can occur on its own, but most often it is accompanied by other abnormalities, such as dyslipidemia and glucose intolerance, which increase its impact on the risk of cardiovascular diseases . ConsideAccording to the recommendations of scientific societies, increased cIMT, like the presence of atherosclerotic plaques in the carotid arteries, is a recognized organ complication of arterial hypertension. cIMT thickening is an early marker of atherosclerosis, which is observed before the formation of atherosclerotic plaque. The normative range of cIMT is estimated to be within 0.4–0.9 mm, with an increment of about 0.1 mm for each decade of life . MoreoveIn connection with the above-mentioned importance of selenium in the body , the postulated role of selenium in the development of hypertension, the importance of cardiovascular consequences of arterial hypertension as predictors of cardiovascular risks, and the diagnostic usefulness of ultrasound assessment of the carotid intima media thickness, it seems justified to verify the correlation between serum selenium concentrations, the total antioxidant status, and the carotid intima media thickness in ultrasound assessment in patients with arterial hypertension without other clinically evident cardiovascular diseases.The objective of the study was to establish the correlation between serum selenium concentrations, the total antioxidant status, and the carotid intima media thickness in ultrasound assessment in patients with arterial hypertension.The studies were carried out as part of the research project entitled “Selenium and zinc deficiency as predictors of subclinical cardiovascular complications in hypertension” (Simple STM.A100.17.050), which was approved by the local ethics committee.The studies were conducted between 2017–2019 in the hypertensiology clinic of the university hospital. The study group of patients was recruited from among those hospitalized in the clinic to evaluate the effectiveness and possible optimization of the treatment of arterial hypertension and to assess the cardiovascular consequences of the underlying disease. The inclusion criteria for the study were: age over 18 years, diagnosed and pharmacologically treated arterial hypertension, and no modification of the therapy of arterial hypertension in the last 12 months. Based on the adopted inclusion criteria, 141 patients were qualified to participate in the study. The size of the originally recruited group of respondents was reduced by excluding persons meeting the adopted exclusion criteria. Exclusion criteria were type 2 diabetes, ischemic heart disease, stroke, peripheral arterial disease, renal failure, and hyperthyroidism or hypothyroidism. Based on the accepted exclusion criteria, a total of 65 patients were excluded from the study: 44 people due to type 2 diabetes, 22—ischemic heart disease, 19—stroke, 15—peripheral arterial disease, 2—renal failure, and 2—hyperthyroidism or hypothyroidism. Most of the patients excluded from the study had more than one exclusion criterion. Ultimately, the study group consisted of 76 people. The clinical characteristics of the study group of patients are presented in The project methodology included a questionnaire, laboratory analysis, and an ultrasound exam of the carotid arteries.The questionnaire included questions about the patient’s health , the presence of comorbidities, and the basic risk factors for cardiovascular diseases. The performed laboratory analyses included the determination of the basic parameters of lipid and carbohydrate metabolism in the blood, determination of serum selenium concentrations (Se-S), and determination of serum antioxidant status (TAS).Total cholesterol, LDL and HDL, triglycerides, and blood glucose were determined using commercially available standard tests.Serum selenium concentrations were determined using hydride generation atomic absorption spectroscopy (HGAAS). The antioxidant status (TAS) was assessed using the enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s instructions . The Se-S and TAS determination methodology used was analogous to that described previously, for example, by Gać et al. 2020) [20 [20].Carotid ultrasound exams were performed using the ALOKA ProSound 6 device . The exams were performed for the presence of (significant/ insignificant) carotid stenosis and/or occlusion. In addition, the intima media thickness (cIMT) was assessed. The exams were performed in the supine position with the patient’s head tilted about 30–45° from the examined artery. A linear probe with a frequency of 7–10 MHz was used for the measurements. The exams were begun with B-mode imaging, identifying the common carotid artery (CCA) in the transverse plane. In the longitudinal plane, the vessel was visualized using the optimal depth and setting the focus (single) to the depth of the artery being assessed. The IMT measurements were taken 1–2 cm below the division for the internal carotid (ICA) and external carotid (ECA) artery, on the posterior wall, in an area without plaque, with a clearly identified double line pattern. When atherosclerotic plaque was observed (thickness over 1.5 mm), its morphology was assessed with B-mode imaging, and in the next stage, the surface of each plaque was assessed—the blood flow spectrum was analyzed at the level of atherosclerotic plaques using the spectral recording option. In color imaging, the presence of acceleration typical of significant vasoconstriction was either excluded or confirmed. The carotid arteries on the opposite side were examined in an analogous manner. The mean value of the measurements for the right and left sides was taken as the final intima media thickness.For comparative analysis, the study group of patients was divided using serum selenium concentrations and serum antioxidant status as median cut-off points. Based on the Se-S median of 88.48 μg/L, the subgroups of low-Se (Se-S < median) and high-Se (Se-S ≥ median) patients were distinguished. Based on the TAS median of 1.18 mM, the subgroups of low-TAS (TAS < median) and high-TAS (TAS ≥ median) patients were distinguished. For a similar purpose, the group of respondents was divided according to the cIMT median of 0.70 mm. On this basis, the low-cIMT (cIMT < median) and high-cIMT (cIMT ≥ median) patient subgroups were distinguished. Each group consisted of 38 patients.t-test was used to test the significance of the hypotheses. In the case of variables with a distribution other than normal, the Mann–Whitney U-test was used for independent quantitative variables. Results for qualitative variables were expressed as percentages. The chi-square test was used to test the significance of the hypotheses for independent qualitative variables. To determine the correlations between the studied variables, correlation, and regression analysis was performed. The parameters of the model obtained in the regression analysis were estimated using the least squares method. The level of statistical significance was set at p < 0.05.The obtained results were statistically analyzed with the use of the “Dell Statistica 13” statistical package . Results for quantitative variables were expressed as mean values ± standard deviations. The distribution of quantitative variables was checked using the Shapiro–Wilk test. For independent quantitative variables with a normal distribution, the Se-S and TAS in the entire group of patients suffering from arterial hypertension were 89.73 ± 18.99 µg/L and 1.18 ± 0.35 mM. Ultrasound exam of the arteries revealed the presence of atherosclerotic plaques in 59.2% of the patients. In the studied group of patients, the presence of insignificant carotid stenosis was observed in 14.5% of the patients. Significant carotid stenosis or carotid occlusion were not demonstrated. The cIMT measured by ultrasound was 0.68 ± 0.15 mm.In comparative analyses, cIMT was significantly greater in patients with arterial hypertension with Se-S < median in comparison to patients with arterial hypertension with Se-S ≥ median, as well as in patients with arterial hypertension with the TAS < median than in patients with arterial hypertension with the TAS ≥ median. Se-S was statistically significantly lower in patients with arterial hypertension with the cIMT ≥ median compared to patients with arterial hypertension with the cIMT < median. The subgroups that differed in Se-S and TAS did not differ in the incidence of atherosclerotic plaques and carotid vasoconstriction. The full results of serum selenium concentrations (Se-S), total antioxidant status (TAS), and parameters of carotid ultrasound exam in the studied subgroups of patients are presented in p < 0.05) and between TAS and cIMT  were documented in the study group of patients. Statistically significant correlations are presented in By means of correlation analysis, negative linear correlations between Se-S and cIMT , smoking, taking antihypertensive drugs , parameters of lipid metabolism , the parameter of carbohydrate metabolism (blood glucose concentration), serum selenium concentrations, and total antioxidant status. Then, recognizing statistically significant correlations from univariate regression models as a method indicating potentially independent variables, using multivariate regression analysis, a regression model was obtained, defining the factors independently related to the cIMT in the study group of patients:The obtained regression model indicates that in the study group of patients, older age, higher BMI, smoking, and lower serum selenium concentrations are independent risk factors for the greater cIMT. The results of the estimation of variables related to the cIMT measured by ultrasound are presented in Since the correlation between Se-S and cIMT and TAS and cIMT was statistically significant in univariate regression analysis, and the correlation between Se-S and cIMT was statistically significant in multivariate regression analysis, with no statistical significance of the correlation between TAS and cIMT, the next step involved regression analysis concerning the determination of variables potentially related to TAS. Following the methodological procedure analogous to the estimation of cIMT-related variables, the following final regression model was obtained for TAS:The obtained model shows that among the patients, higher BMI and smoking are independent risk factors for the lower TAS, and the use of ACE inhibitors, β-blockers, and higher Se-S are independent factors of protection against the lower TAS. The results of the estimation of variables related to the total antioxidant status are presented in The obtained results indicate that patients with arterial hypertension with lower serum selenium concentrations and lower serum total antioxidant status are characterized by a greater carotid intima media thickness assessed by ultrasound. In comparative analyses, it was documented that cIMT was significantly greater in patients with hypertension with Se-S < median in comparison to patients with arterial hypertension with Se-S ≥ median, as well as in patients with arterial hypertension with TAS < median than in patients with arterial hypertension with the TAS ≥ median. Moreover, Se-S were statistically significantly lower in patients with arterial hypertension with the cIMT ≥ median compared to patients with arterial hypertension with the cIMT < median. In addition, the existence of a correlation between serum selenium concentrations and cIMT, as well as between serum selenium concentrations and serum total antioxidant status, was demonstrated by correlation analysis and univariate regression analysis.Based on multivariate regression analysis, it was documented that while lower serum selenium concentrations are a statistically independent risk factor for increased ultrasound-assessed cIMT, the correlation of lower total antioxidant status and higher cIMT should be considered secondary to the relationship between Se-S and TAS. A significant correlation between Se-S and cIMT in the multivariate estimation was documented in the regression analysis, with no significance of the correlation between TAS and cIMT and the significance of the correlation between Se-S and TAS in an analogous type of estimation.The obtained results are in line with the long-standing trend of investigating the relationship between the blood selenium concentration and the severity of early atherosclerotic lesions in the carotid arteries. The data that we have at our disposal based on previous research on this topic is inconclusive, moreover, it concerns various population groups. In the 1990s, Salonen et al. (1991 and 1993) indicated the existence of inversely proportional correlation between serum selenium concentrations and cIMT. In the first study conducted by this team, a group of 126 randomly selected Finns was examined and it was shown that the mean increase in maximum cIMT after two years was significantly greater in men with lower serum selenium concentrations compared to men with higher serum selenium concentrations . At the same time, it was indicated that the above correlation was independent of age and tobacco smoking; moreover, attention was drawn to the synergy of higher serum copper levels, lower serum selenium concentrations, and higher LDL cholesterol in the process of atherogenesis . AnotherSome of the studies published so far on the importance of selenium for the development of early atherosclerotic lesions in the arteries differ significantly in terms of methodology. The authors of these studies use the supply of selenium in the diet as an indicator of selenium availability for the organism instead of selenium concentrations in biological material. For example, in the study conducted by Ferreira et al., the influence of antioxidant consumption on the occurrence of subclinical cardiovascular disease (CVD) was analyzed in a group of 96 postmenopausal women. Food consumption was assessed using a validated food frequency questionnaire. Subclinical CVD was defined as cIMT > 0.9 mm and/or the presence of at least one plaque in any of the segments of the cervical arteries examined. It has been shown, among others, that study participants with subclinical CVD significantly more often consumed lower doses of selenium in their diet . The Karp > 0.05) [The correlation between Se-S and cIMT has prompted some researchers to consider selenium supplementation as a potential non-pharmacological method of reducing cardiovascular risk. The SU.VI.MAX study contradicts the effectiveness of such supplementation. Zureik et al. showed that people receiving a combination of antioxidants in low doses  daily compared to those receiving placebo, after a follow-up period of about seven years did not differ in cIMT assessed via ultrasound  . Interesp < 0.05). It was concluded that occupational exposure to mercury accelerates the occurrence of early carotid atherosclerotic lesions, and the disturbance of the antioxidant status of the body may be responsible for their development [n = 42) and a control group of healthy participants (n = 20). It showed that cIMT was significantly greater, while the TAS was significantly lower in patients with hypertension compared to the control group. At the same time, however, multivariate regression analysis, like in our studies, did not show that the TAS was an independent predictor of an increase in cIMT [The results of our studies indicate a lower total antioxidant status as an indirect indicator of early atherosclerotic lesions in the carotid arteries, conditioned by low blood selenium concentrations. Thus, they constitute an important voice in the discussion on the correlation between the total antioxidant status and cIMT, in which, in recent studies, there are reports both confirming the existence of one and excluding it. Similar results to those currently discussed were obtained by Skoczynska et al. and Bogdanski et al. ,32. The elopment . The sec in cIMT ,34. It s in cIMT . In a st in cIMT ,36. Amon in cIMT . Cakir e in cIMT . HoweverA potential pathogenic mechanism of atherosclerosis acceleration because of selenium deficiency is the shift of the redox balance of the organism, because of the reduction of the antioxidant potential, towards increased oxidative activity. Selenium deficiency, due to selenoprotein deficiency, reduces the effectiveness of removing lipid oxidation products, mainly lipid hydroperoxides. Together with other oxidative mechanisms, it contributes to damaged endothelium, causes inflammation, increased blood prothrombotic activity, spasms, and permanent/irreversible proliferation of vascular walls.The discussed studies have several major limitations. In terms of the study group, a significant limitation is its limited number, overrepresentation of overweight or obese patients, and small number of patients with selenium deficiency. In terms of methodology, the main limitation of the study is the lack of determination of selenoproteins and markers of inflammation. In light of current research, it is believed that the selenoprotein P concentration in plasma is the most conclusive marker for determining the optimum supply of selenium . In addiIn patients with arterial hypertension, the lower total antioxidant status conditioned by lower serum selenium concentrations may be correlated with an increase in the carotid intima media thickness assessed by ultrasound.


Blood pressure (BP) management is a crucial part of critical care that directly affects morbidity and mortality. While BP has become a mainstay in patient care, the accuracy and precision of BP measures across commonly used sites  and methods have not been established. This study begins to fill this gap in literature by testing the null hypothesis that BP measurement does not vary according to site. This is a prospective, non-randomized, cross-sectional study of 80 neurocritical care unit patients. Near simultaneous non-invasive blood pressure (NIBP) readings from 4 different locations  and, when available, intra-arterial blood pressure readings (IABP) were included. Pearson correlation coefficients and one-way repeated measures ANOVA were used to observe the systolic, diastolic, and mean arterial pressure (MAP) correlations. The BP measured at the four most common sites  had adequate correlation coefficients but were statistically significantly different and highly unpredictable. The median inter-site systolic variability was 10 mmHg (IQR 2 to 10 mmHg). The median inter-site MAP variability was 6mmHg with an interquartile range (IQR) of 3 to 9 mmHg. As expected, the values correlated to show that patients with high BP in one site tended to have high BP in another site. However, the unpredictable inter-site variability is concerning within the clinical setting where oftentimes BP measurement site is not standardized but resulting values are nevertheless used for treatment. There is prominent inter-site variability of BP measured across the 4 most common measurement sites. The variability persists across non-invasive (NIBP) and invasive (IABP) methods of assessment. Moreover, BP measurement is influenced by other physiological factors, such as position changes  and external factors, such as the measurement site used for the non-invasive blood pressure (NIBP) machine2. This variability lends ambiguity to BP measurements in the critical care setting, where accuracy is paramount as a basis for medical interventions. It is particularly crucial in the NSICU setting, where minute fluctuations in Intracranial Pressure (ICP) and Cerebral Perfusion Pressure (CPP) can lead to acute deterioration of the patient’s neurological status3.Blood pressure (BP) monitoring is essential to neuroscience intensive care unit (NSICU) patient management. Adequate cerebral perfusion is dependent upon central BP control, maintained through the modulation of various factors such as cardiac output, vascular tone, systemic vascular resistance, and intravascular volume. Although BP can be measured at multiple sites , there is no gold standard for site selection. Inconsistencies in BP readings may occur due to inter-observer variability, technical issues, or methods and locations for measurement. The true value of a patient’s BP cannot be measured with total precision, owing to its natural variability over time, as well as the limitations of the methods used to measure BP3. Evidence has shown that cerebral autoregulation becomes dysfunctional after injuries such as an acute stroke, and cerebral blood flow becomes more susceptible to fluctuations in MAP, potentially exposing brain tissue to hypoperfusion and subsequent ischemia or hypertensive damage and possible hemorrhage3. Overall, BP is also transiently elevated in the setting of acute stroke due to neuroendocrine factors, physical stress, infarct topography, and central mechanisms of BP control4.To better understand BP management in the setting of neurological diseases such as tumors and stroke, it is important to have a firm grasp of cerebrovascular physiology and its compensatory mechanisms at the onset of acute injury. Under normal conditions, the brain adjusts the downstream cerebrovascular resistance by reflex vasoconstriction or vasodilation of cerebral arterioles, a function known as autoregulation. This ensures that cerebral blood flow remains relatively constant across a wide range of mean arterial pressure (MAP)5 as it is able to measure the beat-to-beat value of BP in the absence of technical errors, reflecting the constant fluctuations of BP in real time. There are, however, various technical limitations associated with the method, such as: errors due to over- or under-dampening, calibration errors, motion artifacts, in-line clotting, or the presence of pre-existing systemic vascular disorders affecting the integrity of the patient’s arteries. The IABP measurement, maintenance, and troubleshooting requires more clinical expertise for safe management. Additionally, it is an invasive device that carries its own host of risks. It is therefore common practice to use NIBP machines for majority of patients within and beyond critical care, as well as during the hyperacute phase of managing critical emergencies when an arterial access has not yet been established6. The substitution of NIBP for IABP measurement is done despite the limited amount of data available concerning their correlation; furthermore, the impact of age, sex, and body mass index (BMI) on NIBP-IABP correlation has not been studied7. This study aims to address the gap by observing the correlations between two different methods of BP measurement (NIBP and IABP) used in the NSICU and across four different measurement sites .Invasive arterial blood pressure (IABP) measurement is considered to be the gold standard of BP measurement in the critical care settingThis is a prospective, non-randomized, observational study to correlate blood pressure readings in acutely ill patients admitted with a neurological diagnosis to a 20-bed NSICU in a comprehensive stroke certified academic center. The team collected data from a total of 82 patients over a period of four months (April-July 2019). All study procedures were approved by the University of Texas Southwestern Medical Center Institutional Review Board prior to the initiation of the study. Likewise, the study team weighed the risks and benefits to the patients before initiation and ensured that all study procedures followed Helsinki guidelines. Patients were screened daily using the electronic medical record (EMR). Patients were eligible for the study if they were: over 18, were English speaking, and were admitted to the NSICU with a neurological diagnosis. Patients were excluded if they had any of the following: contra-indication to bilateral upper arm or wrist NIBP measurements, missing an upper limb or upper limb fracture, or a diagnosis of Raynaud’s disease. Once deemed eligible, the patient or their legally authorized representative were consented for the study through a written informed consent.After consent was obtained, we consulted with the patient’s primary nurse to ensure that the patient was in an appropriate condition to perform measurements. A stopping rule was that if the patient was clinically unstable, unable to tolerate multiple NIBP measurements for any reason , unable to tolerate having the head of bed at 30 degrees, or otherwise indisposed, we would terminate the attempt and return at another time. No patients met this stopping rule and all measurements were completed during the first encounter.Each enrolled patient underwent a one-time BP reading from four different measurement sites at near-simultaneous times. We identified and placed appropriately-sized BP cuffs on the left upper arm (LA), right upper arm (RA), right wrist (RW), and/or left wrist (LW) Fig.  for NIBPAll blood pressure values were obtained using the IntelliVue MP40  monitoring system. To obtain near-simultaneous readings, researchers used two separate IntelliVue monitors that provided oscillometric NIBP readings. If an arterial line was present, the transducer was calibrated and leveled by the primary nurse prior to the reading, ensuring a normal flush test, adequate dampening, and brisk aspiration. The IABP value was noted simultaneous to the first NIBP reading. The research team member noted the location of the arterial line  as well as the patient’s heart rate and cardiac rhythm at the time of the first NIBP reading. The first measures were taken in the upper arms, with the study member pushing the “Start” button on the two monitors simultaneously. Immediately after the BP values appeared on the IntelliVue monitors, a reading was taken from the arterial line (if present). Then the two monitors were connected to the wrist cuffs and BP measurements were taken in the lower arms. The BP measurements were first recorded with paper and pen. After sampling, all demographic data and BP measurements were abstracted to an electronic spreadsheet before being converted to SAS v 9.4 (SAS Institute) for analysis.et al.8 From 136 patients with paired samples, there was a statistically significant difference of 9 mm Hg in SBP using head of the bed (HOB) location (141.63 [25.229] versus 129.40 [28.704]). From these data, it was estimated that 78 patients were adequate to reject the null hypothesis 9. This number was rounded upwards to remain conservative, and a sample of 80 was selected.Sample size was estimated using data from McNett Descriptive data were derived for BP from each site . After the initial assumption of approximately normal distribution was rejected for 3 BP measures (Shapiro-Wilk p < 0.05), all BP measures were log transformed (Shapiro-Wilk range p = 0.17 – p = 0.88). Histograms were constructed to test the assumption that blood pressure values are approximately normally distributed. An ANOVA test was used to identify differences in means of blood pressure by site. Simple regression models were used to examine association of blood pressure with the reference site (LA) and other sites. Multivariate regression was used to explore any potential moderator effect.Of 82 patients enrolled, 2 were excluded as being previously enrolled 1) on a prior admission and 1 withdrew prior to BP sampling. Of 80 patients in this analysis, 41(51.3%) were male, mean age = 52.84 +/− 17.94) years old, and mean BMI = 30.18 +/− 7.74). Demographics were representative of the local population, majority Caucasian and non-Hispanic as detailed in Table  on a priBoth left and right mean upper arm NIBP [systolic/diastolic (MAP)] were lower than left and right mean wrist NIBP . Of the 29 patients with arterial access, 16 had left radial arterial lines [mean IABP = 127/61 (80)], 7 had right radial arterial lines [mean IABP = 139/63 (88)], 4 had left brachial arterial lines [mean IABP = 138/73 (91)], and 2 had right brachial arterial lines [mean IABP = 122/68 (85)].Systolic readings were isolated and comparative analysis of two different measurement sites showed significant differences in blood pressures Fig. . The LA Pearson Correlation Coefficient (PCC) matrix was used to examine NIBP in LA, RA, LW, RW, and IABP for systolic, for diastolic, and for MAP Table ; Fig. 1.et al.10 who found a lack of concordance in left and right upper arm BP measurements. In simplest terms, when a clinician measures the blood pressure on the left arm, the clinician only has the value for the left arm. It is worth noting that some inter-site mean differences were above 10 mmHg  and all inter-site mean difference comparisons were at least 7 mmHg for SBP, which is often the treatment parameter used for patients in the NSICU  guidelines where cerebral perfusion is at risk even though CPP, which calculates from the MAP, appears to be a more appropriate target. There are currently no established guidelines for MAP or CPP measurement in neurocritical care7. Given the wider mean differences between SBP readings from two sites that also reflect strong correlation coefficients, MAP appears to be the more consistent metric by which to decide treatment in the clinical setting. However, it is still important to consider that the MAP will not be exactly the same at any given time from site to site.Mean differences between inter-site MAP comparisons followed the same trend, but the values were smaller than those for SBP. Interquartile range distribution showed that the range of mean differences between MAP readings were all 6 to 7 mmHg apart. Although mean pressure is the true driving pressure for peripheral blood flow and MAP is the parameter physically measured by oscillometric devices, current guidelines for clinical practice have been slow to incorporate NIBP MAP for vital signs monitoring and decision-making in the NSICUUpper arm measurements were consistently lower than wrist measurements, which could be attributed to the anatomical differences between the upper arm and the wrist, insofar that the wrist arteries are surrounded by tendons and bones and therefore less reactive to the external pressure applied by the NIBP cuff. The wrist sites are also more distal to the heart, and a more proximal site such as the upper arm would reflect central pressures more accurately. This consistent mismatch is worth considering in the clinical setting and in practice, we suggest avoiding wrist NIBPs if at all possible and other alternatives are available.12, unruptured intracranial aneurysm13, and acute ischemic stroke14 do recommend strict BP control but they do not specify a measurement site. The AHA guidelines for the measurement of BP in humans recommends that NIBP should be measured in the upper arm but it does not specify which arm; it does recommend using the higher BP reading for treatment purposes in the case of clinically significant inter-arm differences (defined as SBP or DBP difference ≥10 mmHg)15. However, this recommendation is for the management of hypertension in the general population and does not account for the special needs of neurocritical care patients, especially as some NSICU cases require permissive hypertension for cerebral perfusion (such as in acute ischemic stroke or high-grade vessel stenosis). A small correlational study4 conducted in 2007 observed that: (1) systolic NIBP readings consistently underestimate the systolic IABP readings by a significant margin, and (2) the higher the patient’s SBP, the greater the discrepancy between systolic IABP and NIBP. This makes the AHA recommendations even more problematic, as there is no existing guideline for when a clinician must decide between correct but significantly different NIBP and IABP measurements for treatment.The AHA guidelines for the management of intracerebral hemorrhage17.Although there was a smaller number of enrolled patients with arterial lines, it shows that IABP readings demonstrate greater range, variance, and weaker inter-site correlation than the NIBP readings. This is an important point of consideration in the NSICU setting, where IABP is preferred over NIBP when deciding on treatment. This correlational unreliability effectively challenges the widely accepted concept that IABP is the “gold standard” for BP measurement. Notably, applying a Bonferroni correction to the Pearson Correlation Coefficients resets the rejection for the null to p < 0.0017 and two of the correlations in Table 18. It should also be noted that we used the first and only NIBP measure for each site, whereas guidelines recommend taking multiple measurements. However, our design reflects the practice used in most intensive care units wherein the NIBP is checked once unless the value is considered the product of an obvious measurement error. Some measurements were performed on stroke patients’ paretic arm, which can alter the NIBP readings due to differences in muscle tone19.Limitations for this study include its relatively small sample size enrolled from a single center. The study was designed for pragmatic  sampling because the nurse investigators could not work 7-days a week; however, this sampling strategy has been successfully used in clinical nursing researchThe use of nearly-simultaneous measurements was pragmatic and it is possible that hemodynamic changes are responsible for all of the BP differences; this could be examined in a future study. Due to the limitations of current NIBP technology, we are unable to ensure (even if the measurements were initiated at the exact same time on both arms) that the machine will give a result at the same time, hence the study was limited to near-simultaneous results. Additionally, it is not possible to retrieve wrist and upper arm results from the same arm at the same time due to the mechanics of NIBP measurement restricting blood flow to the distal extremity.Furthermore, this study is not designed to be able to determine which measurement site or method is best used as a standard of practice. It is worth note that in patients who suffer rapid BP fluctuations , NIBP machines are limited in their capacity to track real-time BP changes. Although it was not an exclusion criterion, none of the enrolled patients in this study had atrial fibrillation or atrioventricular blocks.Finally, this study was not structured to test the hypothesis on healthy participants, which could serve to highlight the hemodynamic changes brought about by neurovascular diseases and also verify whether or not the inter-site variabilities we found in neurologically ill patients remain consistent even in a healthy cohort. Future research using different methodological approaches to explore this old issue may yield different results.does matter when measuring BP; however, this study cannot conclusively recommend which site to use above others. Further investigation through larger trials is warranted to better understand the correlation between different measurement sites and methods, as well as to identify the most accurate method of measuring BP in the clinical setting. In light of these findings, clinicians should consider standardizing the BP measurement site and method upon admission for consistent readings and better clinical decision-making.The study highlights the inter-site variability of BP using both NIBP and IABP measurements. Comparative analysis showed positive correlation between different measurement sites, but the difference in BP values was neither fixed nor predictable in any two particular sites. Each measurement site yielded distinctly different results from the others. Therefore, location


Text CorrectionThere was an error in the original article . ", Wbaseline is the weight at baseline, Fdose is the dose of furosemide on days 1–3 (40 mg) .All consecutive HF subjects discharged alive after an acute episode of cardiac decompensation with fluid overload  were enrolled in an out-patient clinic follow-up (from January 2017 to December 2019). Patients were classified as having CHF according to the criteria commonly accepted in literature [18], such as the presence of 2 major criteria or 1 major criterion +2 minor criteria according to the Framingham score and a NYHA functional class II, III or IV, due to an exacerbation of symptoms with at least 1 class deterioration. Patients with symptoms of CHF, plasma NT-proBNP > 125 pg/mL and left ventricular ejection fraction (LVEF) < 50% were defined as both in heart failure with reduced ejection fraction (HFrEF). Patients with symptoms of CHF, plasma NT-proBNP > 125 pg/mL, LVEF > 50% and diastolic dysfunction were defined as HF preserved ejection fraction (HFpEF). The presence of inadequate echo images or no adherence to the therapy (medication adherence was assessed using a self-reported measure) and disagreement with the periodical follow-up were considered exclusion criteria. Eligible patients underwent a clinical examination, a 12-lead electrocardiogram, BNP plasma level determination, body weight measurement at admission and on Day 4 of hospitalization, water composition (on admission and at discharge), 6-min walk test (6MWT), noninvasive cardiac output and a transthoracic echocardiogram within 48 h of hospital discharge. Serum creatinine was checked on clinical stability and glomerular filtration rate (GFR) calculated with the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation. The measurement to “diuretic response”, as described by Valente et al. [16], was calculated as follows:The authors apologize for any inconvenience caused and state that the scientific conclusions are unaffected. The original article has been updated.Editorial NoteFollowing a request by the license holders of the scale measuring therapeutic adherence referred to in the article, the authors and journal published this correction. The issues have been previously described .The Committee on Publication Ethics (COPE) has noted this type of behavior that is stated to hold “authors to ransom”, and recommends to emphasize that “this is not good for the advancement of scientific knowledge or in the public interest” .


Type A acute aortic dissection is a life-threatening disease associated with adverse clinical outcomes. Acute kidney injury (AKI) is common after surgery. However, the relationship between intraoperative blood transfusion and postoperative AKI remains unclear.The records of 130 patients who underwent type A acute aortic dissection surgery from January 2015 to December 2018 were retrospectively analyzed. According to the Kidney Disease Improving Global Outcomes criteria, postoperative AKI was defined based on serum creatinine concentration. Multivariable logistic regression analysis was applied to estimate the independent association between intraoperative blood transfusion volume and the risk of postoperative AKI.n = 21). Multivariate logistic regression showed that the amount of intraoperative blood transfusion was independently associated with the risk of postoperative AKI in a dose-dependent manner. Every 200 ml increment of blood transfusion volume was associated with a 31% increase in AKI risk .Postoperative AKI was observed in 82 patients (63.08%). The in-hospital mortality was 16.15% (Intraoperative transfusion volume may increase the incidence of postoperative AKI. The mechanism and influence of transfusion thresholds on AKI need to be explored in the future. Acute aortic dissection remains a clinical emergency characterized by anterior chest or back pain and has high morbidity and mortality, especially for type A acute aortic dissection. Unlike other elective cardiac surgery, in emergency aortic repair for type A acute aortic dissection, patients often suffer from unstable hemodynamics, coagulopathy, and organ malperfusion. Acute kidney injury (AKI) is a common complication and has been reported as an important risk factor for mortality in patients undergoing cardiac surgery , 2. MoreThe study was a retrospective cohort design, including patients who underwent type A acute aortic dissection surgery in the Center Hospital of Wuhan from January 2015 to December 2018. The diagnosis of type A acute aortic dissection was in accordance with contrast-enhanced computed tomography. This study was approved by the ethics committees of this hospital . Data were anonymous, and the requirement for informed consent was waived. The following patients were not eligible for participation: death within 24 h after surgery; renal artery dissection or occlusion; preoperative shock (a systolic blood pressure < 90 mmHg); dialysis-dependent before surgery; no serum creatinine measures after surgery; missing blood transfusion volume. Finally, a total of 130 patients among 158 participants were eligible for the study  and EmpowerStats  with a two-sided significance threshold of P < 0.05.The parameters were summarized as mean ± standard deviation (SD) for normally distributed continuous variables, median with interquartile range for continuous variables with skewed distribution, and frequency (percentage) for categorical variables. Multivariable logistic regression was applied to estimate the risk of postoperative AKI. The variables used in multivariable analysis included clinical factors that are known to increase postoperative AKI to control confounding bias. Nonlinear relationship was explored between intraoperative blood transfusion volume and AKI risk following emergent thoracic aortic surgery via the smoothing plot generated by generalized additive model with an adjustment for potential confounders. All of the analyses were performed using R (A total of 130 patients with type A acute aortic dissection were included in this study (Table Demographic and perioperative characteristics stratified according to Improving Global Outcomes criteria  were shoWorse in-hospital outcomes were observed in patients with AKI, which contributed to approximately 14.62% of in-hospital death. Patients with AKI had long intubation time and ICU stay, and patients with stage 3 AKI were susceptible to renal replacement therapy. The major adverse events, including perioperative ARDS, perioperative myocardial infarction, stroke, and redo surgery, were more frequent in patients with AKI than those without.No difference was observed in the pre-transfusion Hgb level between patients with and without AKI. Patients with AKI received much more amount of blood transfusion than those without AKI. A nonlinear relationship between intraoperative blood transfusion volume and AKI was explored. We observed the risk of postoperative AKI increased with an increment of blood transfusion volume, and the curve tends to go down when the amount of blood transfusion is above 4000 ml Fig. . In dose. reported that perioperative red blood cell transfusion was the independent predictor of postoperative AKI in patients undergoing isolated coronary artery bypass grafting [Type A acute aortic dissection is a severe disease related to increased morbidity and mortality. Patients undergoing cardiac surgery suffer from a series of complications, including bleeding, ARDS, acute myocardial infarction, stroke, AKI, and infection. Postoperative AKI is a common complication of cardiac surgery with CBP. Volume depletion, hypotension, anemia, and blood transfusion increase the incidence of AKI , 4. In tgrafting . Meanwhigrafting . Howevergrafting , 15.. found a linear relationship between blood transfusion volume and risk of AKI in a randomized goal-directed fluid resuscitation study [To the best of our knowledge, the current study is the first to investigate the association of intraoperative blood transfusion volume with postoperative AKI in patients undergoing type A acute aortic dissection surgery. We observed a nonlinear relationship between intraoperative blood transfusion volume and postoperative AKI. A 31% increment of the postoperative AKI risk was observed for every 200 ml of blood transfusion received when the total volume was lower than 4000 ml. However, no difference was observed when the blood transfusion volume was higher than 4000 ml. Different from the nonlinear association reported in our study, Karkouti et alon study . In theiAKI is a common adverse event for type A acute aortic dissection. Our study also evaluated the relationship between postoperative AKI and in-hospital major adverse events. An association was found between the incidence of AKI and major adverse events. Patients with AKI were associated with long ventilation time and prolonged ICU stay. Moreover, the severity of AKI was correlated with worse in-hospital outcomes. These associations were confirmed in prior studies , 17.The mechanisms through which blood transfusion volume increased the risk of postoperative AKI are not illuminated, but several potential explanations are considered. The pathogenesis of AKI is mostly related to inflammation, renal hypoxia, impairment of tissue oxygen delivery, and oxidative stress. Patients who undergo cardiac surgery with CPB are subjected to the initiation phase of ischemia–reperfusion kidney injury and the extension phase of kidney injury. The initiation phase is characterized by renal artery vasoconstriction and increased oxygen consumption. Patients in the initiation phase have an increased risk of aggravation to the extension phase, which may lead to AKI development if they cannot recover or if they suffer from other external risk factors, such as blood transfusion, ischemia, and anemia , 18, 19.This study is subjected to several limitations. Firstly, the causality could not be established because of the nature of the observational study. Thus, further prospective intervention study is needed. Secondly, type A acute aortic dissection surgery is a complicated procedure. We are often forced into the situation where multiple transfusions are required.The appropriate timing of blood transfusion could not be determined, which is an interesting topic to study in the future. Thirdly, because the sample size for this study is relative small, perhaps the influence of blood transfusion volume becomes less important. Fourthly, multiple factors may cause postoperative AKI after aortic surgery, including preoperative shock or hypotension, renal artery dissection or occlusion, anemia, surgical trauma, prolonged use of CPB, hypothermia, and extensive blood product, during the study period, it is very difficult to take all factors into consideration. Fortunately, most important variables are included in our study to discuss the incidence of AKI. Fifthly, the residual confounding and bias could not be totally addressed in the observational study.Our study showed that the amount of intraoperative blood transfusion was an independent risk factor for postoperative AKI in patients with type A acute aortic dissection. Intraoperative transfusion volume might increase the incidence of postoperative AKI, and the mechanism underlying transfusion thresholds on AKI should be further investigated.


Partial or total non-adherence has been recognized as major issues in the long-term management of hypertension. This study aims to investigate the prevalence and associated factors of compliance behaviors among Chinese middle-aged and older hypertensive patients. A sample of 6308 hypertensive patients aged ≥45 years was obtained from the 2015 China Health and Retirement Longitudinal Study (CHARLS) data. Two compliance behaviors were involved including medication and blood pressure monitoring. Stratified binary logistic regression analysis was employed to examine the associated factors. 77.2% of the participants reported medication compliance, and 40.7% complied with blood pressure monitoring. Better medication compliance associated with older age, overweight or obesity, one or ≥3 complications, no drinking, living in urban areas, and health education. Better blood pressure monitoring compliance associated with older age, overweight or obesity, ≥3 complications, normal activities of daily living (ADL), no smoking, sleep duration of 6–8 h, better cognitive function, living in urban areas, education level of middle school or above, and health education. Chinese middle-aged and older hypertensive patients experienced unoptimistic compliance behaviors, especially for blood pressure monitoring. Special attention and targeted interventions are urgent for the high-risk population of poor compliance behaviors, such as rural individuals, low educational population, and younger hypertensive patients. Population ageing has become an irreversible phenomenon worldwide. China is one of the most ageing countries with the number of people aged 65 and above ranking first in the world . By the Patient compliance generally refers to the degree to which the patient’s behavior  conforms to the clinical doctor’s prescription or advice . PreviouPrevious studies conducted in different regions , differeIndividuals’ compliance behaviors are usually influenced by multiple factors. Previous studies have reported the correlations between compliance behaviors and gender , health In July 2019, the Chinese government implemented “Healthy China Action (2019–2030)” , in whicThis study is designed as a cross-sectional study. We used data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort survey conducted by National School of Development, Peking University. In this survey, Chinese adults aged 45 years and older were investigated adopting a multi-stage stratified cluster sampling method . CHARLS n = 21,097). Middle-aged and older individuals diagnosed with hypertension were included as study subjects (n = 6424). Participants aged ≥45 years were selected based on the WHO age criteria for middle-aged and older people. Hypertension was identified based on participants’ self-report, i.e., respondents answered “yes” in the following two questions were recognized as hypertensive patients: “Have you been diagnosed with hypertension by a doctor?” and “Do you know if you have hypertension?” We excluded subjects with missing information on compliance behaviors and predictor variables listed below (n = 116). Finally, 6308 individuals with hypertension were included in the analyses.This study used the 2015 CHARLS data , how many times have you had blood pressure examination?” According to the health management guideline for hypertension , hyperteThis study applied Health Ecology Model to interpret the associated factors of compliance behaviors, which was widely applied in health management of chronic diseases . The modDownstream factors included age, sex, body mass index (BMI), number of complications (hypertension was excluded), and activities of daily living (ADL). Individuals’ ADL ability were measured through six basic activities of daily living (BADL) and six instrumental activities of daily living (IADL), including toileting, eating, dressing, controlling urination and defecation, getting out of bed, bathing, doing household chores, preparing hot meals, shopping, making phone calls, taking medications, and managing assets. In this study, participants who reported impaired function in any one of the 12 activates were considered as ADL decline.Midstream factors consisted of smoking, drinking, regular exercise, sleep duration, depression, and cognitive function. Depression was assessed by the modified 10-Item Center for Epidemiologic Studies Depression Scale (CESD-10) . The scaUpstream factors included marital status, place of residence, educational level, personal income, medical insurance, and health education. The detailed information of all the above variables, including the source of items in the CHARLS 2015 Questionnaire, re-coding, classification, or definition, are summarized in p-value <0.05 in chi-square tests were selected as independent variables for regression models. Compliance behaviors, i.e., compliance with medication and compliance with blood pressure monitoring, were set as dependent variables, respectively. For each dependent variable, 4 models were established using stratified unconditional binary logistic regression analysis. Firstly, downstream factors with significant difference in chi-square tests were included as reference model (model 1). Secondly, the midstream and upstream factors with significance in chi-square tests were included in model 2 and model 3, respectively, in which downstream factors were controlled to compare the effect of different factors on compliance behaviors. Finally, all the independent variables with significant differences in chi-square tests were included in the same model (model 4). Hosmer–Lemeshow test was applied to evaluate the goodness of fit of each model.Data analyses were performed by using the Statistical Package for the Social Sciences (SPSS) version 21.0 , with a significance level of 0.05. Descriptive statistics were employed to describe the characteristics of the participants and the condition of compliance behaviors. Chi-square test was used to compare the differences of medication and blood pressure monitoring among participants with different downstream, midstream, and upstream factors. Variables with http://charls.pku.edu.cn/zh-CN/page/data/2015-charls-wave4). Protocols, instruments, and the process used to obtain informed consent in CHARLS were approved by the Biomedical Ethics Review Committee of Peking University (IRB00001052-11015) [This study used de-identified and publicly available data from the CHARLS website (2-11015) . All parn = 3350) were female, 41.8% (n = 2634) aged 65 years and older, 82.8% (n = 5220) were married, 75.8% (n = 4781) received less than 6 years of education, 70.5% (n = 4447) lived in rural areas, and 77.9% (n = 4917) had one or more complications. Details on the demographics characteristics of the participants are listed in A total of 6308 middle-aged and older individuals with hypertension were involved in this study, with an average age of 63.3 years (SD = 9.8). Among the participants, 53.1% (n = 4870) of the participants reported compliance with medication, and 40.7% (n = 2567) reported compliance with blood pressure monitoring. Besides, the median frequency of blood pressure monitoring was 7 times/year in the present sample (n = 145). The most frequency of blood pressure monitoring was 3 times/year (n = 625), accounting for 9.9% of the total participants.With regards to compliance behaviors, 77.2% . The behavior of compliance with blood pressure monitoring significantly differed in participants with different sex, BMI, number of complications, ADL, smoking, drinking, depression, cognitive function, place of residence, educational level, personal income, and health education .The results of chi-square tests are presented in OR = 1.57, 95% CI = 1.34–1.84), 65–74 , and ≥75  reported better compliance with medication. Compared with normal BMI, overweight  and obese  participants reported higher proportion of medication compliance. Compared with participants with no complication, those with one  and ≥3  had better compliance with medication. Individuals who received health education  were more likely to report medication compliance. Participants who drank  or lived in rural areas  reported a lower proportion of compliance with medication. Hosmer–Lemeshow test indicated good fitness of the model .OR = 1.16, 95% CI = 1.00–1.34), 65–74 , and ≥75  were more likely to comply with blood pressure monitoring. Compared with normal weight, overweight  and obese  participants showed higher proportion of compliance with blood pressure monitoring. Participants with ≥3 complications reported better blood pressure monitoring compliance behavior than those with no complication . Participants with cognitive function score ≥10  and who received health education  displayed a higher proportion of compliance with blood pressure monitoring. Compared with no formal education or illiterate, participants who received education level of middle school  and high school or above  had a better compliance behavior. However, the odds ratios of people who declined in ADL, smoked, slept less than 6 h and lived in rural areas were 0.845 (95% CI = 0.75–0.95), 0.758 (95% CI = 0.66–0.87), 0.874 (95% CI = 0.78–0.99), and 0.610 (95% CI = 0.54–0.69), respectively. Hosmer–Lemeshow test showed the models fitted well .Compliance behavior is a core connotation and an important premise of the self-management of hypertension. In this study, 77.2% of the participants reported compliance with medication, which is much higher than previous findings in China and slightly lower than Al-Daken and Eshah’s  study inThis study found that 40.7% of the participants reported compliance with blood pressure monitoring, i.e., measuring blood pressure ≥12 times/year. The highest frequency of blood pressure monitoring was 3 times/year (9.9%), with the median frequency of 7 times/year for blood pressure monitoring. The results indicated that the frequency of blood pressure monitoring in Chinese middle-aged and older patients did not meet the recommendations of hypertension prevention and treatment guidelines. Insufficient blood pressure monitoring has become an important loophole in hypertension health management . MoreoveThe results of multivariate analysis indicated that, among the downstream factors, age, BMI, number of complications, and ADL were associated with individuals’ compliance behaviors. Compared with the 45–54 age group, individuals aged 55 years and older reported better compliance behavior in this study, which is consistent with Su et al.  and XiaoThis study found that, in the midstream level, smoking, drinking, sleep duration, and cognitive function were significantly associated with compliance behaviors. Compliance behavior has been identified to be correlated with individuals’ health-related behaviors . As commWe also found that, in the upstream level, place of residence, education level, and health education were related to compliance behaviors of hypertensive patients. In this study, participants who lived in rural areas were less likely to comply with medication than those who lived in urban areas, which is consistent with a population-based study in Taiwan . GeneralTo promote health management of chronic diseases, Chinese government implemented “Healthy China Action (2019–2030)” in July 2019, in which “Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases” was involved as one of the fifteen major actions. Improving compliance behaviors is an important and effective approach to promote the self-management of hypertension patients. On the individual level, targeted health education should be implemented in middle-aged and older hypertensive patients, such as weight control, exercise and diet guidance, and quitting smoking, so as to improve knowledge, enhance awareness, and then promote the change of behaviors and lifestyle. Special attention should be paid to the population who were more likely to have poor compliance behaviors, such as hypertensive patients who were middle-aged, had complications, or drank. At the community level, training on blood pressure monitoring should be provided regularly for hypertensive patients, especially for low socioeconomic status population. Family blood pressure monitoring should be promoted to encourage regular monitoring of blood pressure. It is recommended to further promote the implementation of a Family-Doctor System in China, so as to improve the accessibility of blood pressure monitoring. Besides, it would be helpful if government provided financial assistance for the purchase of blood pressure monitors.Several limitations should be mentioned regarding the present study. Firstly, all indicators applied in this study were obtained through participants’ self-report; thus, they are likely to bring biases. Secondly, there might be a certain degree of inadequacy regarding the definition of compliance behaviors in this study. For example, we only included medication and blood pressure monitoring as two indicators to evaluate patients’ compliance behaviors. Medication compliance behavior was assessed by simply asking if the participants were taking any medicine to treat or control hypertension, which may lead to overestimation of the results. And we did not take into account the amount of medicine or the severity of the diseases. The number of blood pressure monitoring only depended on recall, and the monitor place  was not clear. Thirdly, the cross-sectional nature of this study may be considered as a limitation, since no causal inferences can be drawn from the results. Despite these limitations, this study used nationally representative data to systematically examine the condition and associated factors of compliance behaviors among Chinese hypertensive patients. The results might be a valuable reference for the health management practices of hypertension. What is more, this study contributed to use the Health Ecological Model to explore the effect of multilevel factors on compliance behaviors, providing references for targeted prevention. However, considering the limitations in the present study, future studies should put emphasis on study design and comprehensively focus on hypertensive patients’ compliance behaviors (including lifestyle).In this study, 77.2% of the middle-aged and older hypertensive patients reported medication compliance, and 40.7% reported compliance with blood pressure monitoring, i.e., measuring blood pressure ≥12 times/year. Medication compliance behavior was better among patients who were aged, were overweight or obese, had one or ≥3 complications, received health education, did not drink, and lived in urban areas. Better blood pressure monitoring compliance behavior was associated with older age, overweight or obesity, having ≥3 complications, normal ADL ability, no smoking, appropriate sleep duration, better cognitive function, living in urban areas, higher education lever, and receiving health education. It is necessary to develop targeted interventions towards complication behaviors of hypertensive patients in China, especially for blood pressure monitoring. Special attention should be paid to the high-risk population of poor compliance behaviors, such as rural individuals, low educational population, and younger hypertensive patients. Moreover, supporting policies regarding hypertension management, including popularizing health knowledge, reducing health risk behaviors, and strengthening family blood pressure monitoring, etc., might make great sense.


Background: The epidemic of obesity, along with hypertension (HT) and cardiovascular disease, is a growing contributor to global disease burden. It is postulated that obese children are predisposed to hypertension and subsequent cardiovascular disease in adulthood. Early detection and management of hypertension in these children can significantly modify the course of the disease. However, there is a paucity of studies for the characterization of blood pressure in obese children through ambulatory blood pressure monitoring (ABPM), especially in the developing world. This study aims to characterize ambulatory blood pressure in obese children and to explore feasibility of using office BP that will predict ambulatory hypertension.Methods:In the present study, 55 children with a body mass index (BMI) in the ≥95th percentile for age and sex were enrolled in a tertiary care hospital and underwent 24 h of ABPM and detailed biochemical investigations.Results:Ambulatory hypertension was recorded in 14/55  and masked hypertension in 2/26 (7.69%). For office SBP percentile the area under curve (AUC) was 0.773  and for office DBP percentile the AUC was 0.802 . The estimated cut offs (Youden's index) for office blood pressure which predicts ambulatory hypertension in obese children were the 93rd percentile for systolic BP (sensitivity-67% and specificity−78%) and the 88th percentile for diastolic BP (sensitivity-83% and specificity-62%).Conclusion:Ambulatory blood pressure abnormalities are highly prevalent among children with obesity. Office blood pressure did not accurately predict ambulatory hypertension. More than half of the children labeled as “hypertension” on office blood pressure measurement in the study were diagnosed to have white coat hypertension (WCH), thus emphasizing the role of ABPM for evaluation of WCH before the child is subjected to detailed investigations or started on pharmacotherapy. The epidemic of obesity, along with hypertension (HT) and cardiovascular disease, is a growing contributor to global disease burden . StudiesObese children with ABPM have shown a prevalence for ambulatory hypertension ranging from 25% to as high as 48.6% in previous studies . HoweverThis is an observational study and was carried out in a tertiary care teaching hospital in central India. As per departmental protocol, all outpatient-registered children undergo anthropometry with a trained staff. For the present study, children aged 5–18 years with a body mass index (BMI) in the ≥95th percentile for age and sex were enrolled after obtaining written informed consent. Children with congenital malformations, chronic kidney disease, congenital heart disease, malignancy or bone marrow transplant, evidence of raised intracranial pressure, taking medications which are known to increase blood pressure, and other systemic illnesses associated with hypertension were excluded from the study. The study was carried out from December 2015 to December 2017.After obtaining written informed consent, variables such as weight, height, waist circumference, neck thickness, serum uric acid, fasting blood sugar, triglycerides, urinary sodium, and urinary creatinine were collected in a case record form.Three resting blood pressure measurements were obtained from the right upper arm using an aneroid sphygmomanometer and appropriate size cuff, on two separate occasions. The office blood pressure was obtained by averaging the systolic and diastolic blood pressure.For ambulatory blood pressure monitoring (ABPM), a Meditech ABPM-05 device was use . The patTwenty-four hours urinary creatinine and urinary sodium was obtained within 48 h of undergoing ABPM. Serum uric acid, fasting blood sugar, and triglycerides levels were also collected. Salt intake was calculated by using the formula: salt intake = 24 h urinary sodium excretion X (0.0588).t-test or Mann-Whitney test for numerical variables. We used Receiver Operating Characteristic (ROC) curve analysis to determine appropriate cut-offs of SBP and DBP office based percentiles against a reference of hypertension diagnosed by ABPM. Optimal cut-off was determined by Youden's index. For ROC analysis we used easy ROC web tool (Epi Info 7 (CDC Atlanta) software was used for data entry and analysis. Categorical variables were summarized by frequency and percentage while numerical variables were summarized by mean and standard deviation. Systolic and diastolic blood pressure was measured through ABPM and at office were also converted into categorical variables such as ambulatory hypertension, white coat hypertension, masked hypertension, pre-hypertension, and hypertension by using appropriate cut-offs suggested by AAP. Differences in various clinical and demographic characteristics of those with ambulatory hypertension and those without it were compared by using Chi-square test for categorical variables and web tool .This study protocol was approved by the Institutional Human Ethics Committee (IHEC) of the institute (IHEC-LOP/2015/IM0080). All children diagnosed as having hypertension were managed as per standard treatment protocols. Nutrition, physical activity, and other lifestyle modifications for obese children were also provided as per standard protocol.A total of 55 obese children underwent detailed procedure and investigations. The mean age (SD) of our study population was 11 years (±2.39) with a male to female ratio of 1.8. Family history of hypertension was present in 69% of children. Mean (SD)salt intake in male and female obese children was found to be 8.32 (±3.5) gm and 5.01 (±2.6) gm, respectively .As per the new AAP standards, elevated blood pressure (office) was present in 9% and office hypertension in 52.7% of the obese children. Ambulatory hypertension was recorded in 14/55(25.45%), white coat hypertension (WCH) in 17/29 (58.62%), and masked hypertension (MH) in 2/26 (7.69%). Impaired dipping for systolic blood pressure was recorded in 63.6%, while diastolic impaired dipping was recorded in 50.9% of the obese children .The prevalence of ambulatory hypertension increased with increasing BMI  and the p = 0.005) and for office DBP percentile, the AUC was 0.802   was 0.773  . The optThe present study shows a high prevalence of ambulatory hypertension in obese Indian children (25.45%) with a high percentage of children having impaired dipping status. In the present study, the presence of masked hypertension and white coat hypertension is found to be 7.69 and 58.62% respectively, using the newer AAP nomograms for office blood pressure monitoring. Our estimated cut-offs to predict ambulatory hypertension are lower than the existing definition of hypertension based on office reading and do not have optimal diagnostic test properties, thus emphasizing the role of ABPM for diagnosis of hypertension in obese children. A recent study assessing the impact of 2017 blood pressure guidelines by AAP in overweight/obese youth found a 13% increase in the prevalence of high blood pressure as compared to European Society of Hypertension Guidelines 2016 , 13. AnoThe American Academy of Pediatrics 2017 guidelines emphasized on evaluation for white coat hypertension before diagnosing hypertension, as the observed frequency of WCH is high in pediatric studies , 15. ThePrevious studies utilizing ABPM in obese children have shown the prevalence of ambulatory hypertension ranging from 20% to as high as 60% , 6, 17. After publications of newer AAP nomograms, only a few studies were conducted to predict ambulatory hypertension based on office blood pressure in adolescents. Hamdani et al. evaluated ambulatory blood pressure monitoring in 247 adolescents and found that clinic systolic in the 85th percentile may be the optimal threshold at which ambulatory BP monitoring should be performed . The autThe major strengths of the present study are: (1) This study demonstrates feasibility and significance of performing ABPM among obese children. (2) This study also suggests that by using AAP 2017 clinical practice guidelines, a higher number of obese patients are diagnosed with hypertension.The study is not without limitations, with some major limitations being: (1) The clinical BP was measured by an auscultatory method and ambulatory blood pressure was measured by an oscillatory method, which are not correlated and have restricted reproducibility , 22; (2)Ambulatory blood pressure abnormalities are highly prevalent among children with obesity. Office blood pressure did not accurately predict ambulatory hypertension. More than half of the children labeled as “hypertension” on office blood pressure measurement in the study were diagnosed as having white coat hypertension (WCH), thus emphasizing the role of ABPM for the evaluation of WCH before the child is subjected to detailed investigations or started on pharmacotherapy.drgcbhatt@gmail.com.Due to ethical restrictions imposed by the author's Ethics committee, it is not possible to deposit data to a public repository. Interested researchers are kindly asked to send appropriate requests to the corresponding author Girish C. Bhatt, The studies involving human participants were reviewed and approved by All India Institute of Medical Sciences, Bhopal. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.GB conceptualized and wrote the manuscript. PG, SJ, SG, NG, and RM helped in carrying out the research work and reviewed the manuscript for critical inputs. AP and GB developed the protocol and carried out statistical analysis. All authors read and approved the final version of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Fabry disease (FD) is a rare cause of end-stage renal disease requiring kidney transplantation. Data on the incidence of unrecognized FD in kidney transplant recipients are scarce and probably underestimated. This study evaluated the incidence of FD in a population of kidney recipients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach. Two hundred sixty-five kidney transplant recipients were screened with a genetic analysis for α-galactosidase A (GLA) mutation, with measurement of α-Gal A enzyme activity and Lyso Gb3 levels. Screening was also extended to relatives of affected patients. Seven patients (2.6%) had a GLA mutation. Two patients had a classic form of FD with Fabry nephropathy. Among the relatives, 15 subjects had a GLA mutation, and two had a Fabry nephropathy. The clinical and diagnostic assessment was completed after a median of 3.2 months, and mean time from diagnosis to treatment was 4.6 months. This study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients. Evaluation and management by a multidisciplinary team allowed for an early diagnosis and treatment, and this would result in a delay in the progression of the disease and, finally, in better long-term outcomes. Fabry disease (FD) is a rare X-linked lysosomal storage disorder, caused by deficiency of the enzyme α-galactosidase A (GLA), resulting in an accumulation of globotriaosylceramide in tissues, mainly heart, brain and kidney, leading to progressive organ dysfunction . The estProgressive renal impairment is a pervasive clinical manifestation of Fabry disease. Studies on FD screening in a hemodialysis population found a prevalence of FD ranging between 0.02% to 1.2% ,12,13,14Kidney transplantation represents the best replacement therapy for patients with end-stage renal disease  and is aThe incidence of FD among kidney transplant recipients is not well known. A recent review of screening studies performed in the period 1995–2017  found a In this study, we investigated the incidence of unrecognized Fabry disease in a population of kidney transplant recipients performed at a single institution, with the extension of screening to the relatives of the affected patients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach.Kidney transplant recipients, aged >18 years, who received a graft between 2000 and 2017, with a functioning graft followed at the Organ Transplant Unit of the University Hospital of Catania, Italy, were included in this study. All patients underwent single kidney transplantation with standard procedure and were on a triple immunosuppressive regimen, as previously described . PatientAll patients included in the study underwent a genetic analysis for GLA mutation to confirm the diagnosis of Fabry disease. We also measured α-Gal A enzyme activity and Lyso Gb3 levels in all patients. Determination of α-Gal A enzyme activity was performed by using the dried blood spot technique, as previously described by Chamoles et al. . Blood wPathogenic variants: a well-established disease-causing DNA change, with a strong genotype–phenotype correlation;Likely pathogenic variants: probable cause of the patient’s phenotype;Variants of uncertain significance (VUS): genetic variant with unknown or questionable impact on a particular clinical phenotype;Likely benign: a variant not likely be the cause of the disease/phenotype;Benign: a variant that is not considered to be the cause of the disease/ phenotype.GLA mutations were classified following the indication of ACMG recommendations :PathogenPatients with GLA mutation were followed by the Fabry multidisciplinary team of the University Hospital of Catania, Italy, which was responsible for the clinical and therapeutic assessment of patients. The Fabry multidisciplinary team of the University Hospital of Catania included more than 30 specialists with specific expertise on Fabry disease, which are actively involved in the diagnosis and management of potential FD patients, with the aim to significantly reduce the time to diagnosis and treatment.Cardiovascular evaluation, including echocardiography, nailfold videocapillaroscopy with post-occlusive reactive hyperemia, color doppler ultrasound of carotid arteries and magnetic resonance imaging (T1 mapping) of heart;Nephrological evaluation, including doppler ultrasound of kidney and evaluation of the estimated glomerular filtration rate by using the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, microalbuminuria and proteinuria ;Neurologic investigation, including trans-cranial Doppler ultrasound and magnetic resonance imaging of the brain (T2 mapping) ,24;Ophthalmologic investigation, including confocal microscopy ;Dermatologic examination, including dermatoscopy;Gastroenterological and endocrinological examinations;Pneumological examination;Psychological and psychiatric examinations.All patients with a GLA mutation underwent a complete genetic screening extended to relatives, an evaluation of kidney functionality and the following investigations:Asymptomatic patients with no relevant signs and symptoms of FD or alterations at imaging were followed on a yearly basis.Patients with signs and/or symptoms of Fabry disease  were included in an institutional database and were evaluated for enzyme replacement therapy according to the consensus guidelines ,26,27, wA total of 265 kidney transplant recipients were screened for FD .There were 175 males (66%) and 90 females (34%), with a mean age of 53.6 ± 12.1 years and a mean time from transplant of 6.1 ± 2.3 years. Glomerulonephritis was the most common cause of ESRD (30.9%), followed by autosomal dominant polycystic disease (21.9%), but 106 patients (40%) had an unknown cause of ESRD. The mean α-Gal A enzyme activity was 6.40 ± 9.89 μmol/l/h, while mean Lyso Gb3 was 1.19 ± 0.8 ng/mL.The screening identified seven (2.6%) kidney transplant recipients with a GLA mutation .Two kidney transplant recipients had a classic form phenotype with Fabry nephropathy: a 52-year-old man underwent kidney transplantation for ESRD of unknown origin. At the time of transplant, the patient presented with a severe left ventricular hypertrophy (LVH). The screening was made two years after transplantation and identified a hemizygous pathogenic mutation (c493G > C [p.Asp165His]). The patient presented also recurrent abdominal pain, and diffuse angiokeratomas. Two months later, the patient began the enzyme replacement therapy with algasidase α. The patient, however, experienced a progressive worsening of the graft function and recurrence of abdominal pain and is now considered for switch to algasidase β. His 20-year-old daughter with the same GLA mutation presented with a significant proteinuria (>0.6 g/24 h) and was initially treated with algasidase α and then with migalastat. The second patient was a 58-year-old woman who received a kidney transplant for an ESRD of unknown origin. Early post-transplant follow-up identified a left ventricular hypertrophy so that the patient underwent the screening for Fabry Disease, which identified a heterozygous pathogenic GLA mutation (c.658 C > T [p.R220X]). The patient immediately started enzyme replacement therapy with algasidase β and, at 8-year follow-up, she had a stable renal function and a slight reduction of LVH. One brother and one sister presented the same mutation, but their clinical symptoms were mainly recurrent cerebral events and a mild renal insufficiency. They were both initially treated with algasidase β and then, as a consequence of the enzyme shortage, with algasidase α. They are both in good clinical conditions, with no progression of renal disease at 8-year follow-up. Five more kidney transplant female recipients had a GLA mutation: four were considered pathogenic, but the diagnostic assessment did not identify organ damage other than kidney disease, while in one patient the variant was considered benign; finally, no further patients required the enzyme replacement therapy. Interestingly, a female patient with the heterozygous variant c.937G > T (p.Asp313Tyr) received her living transplant from the father who carried the same mutation. No further clinical manifestations of FD were encountered in both the donor and recipient. The recipient had a progressive worsening of renal function, but renal biopsy performed 7 years after transplantation showed only a mild interstitial fibrosis and tubular atrophy, suggesting a chronic allograft nephropathy, with no evidence of FD progression on electron microscopy. The donor is in good clinical conditions with a normal renal function 8 years after the donation.The study was extended to the probands’ families. This screening identified 15 subjects with a GLA mutation. All subjects underwent a complete evaluation for the FD phenotype, and two more patients with a significant proteinuria (>600 mg/dL), a normal renal function and recurrent cerebral events (one patient), were treated with algasidase α and migalastat, respectively. The clinical and diagnostic assessment was completed after a median of 3.2 months, and the mean time from diagnosis to treatment was 4.6 months, suggesting that an in-house multidisciplinary approach may increase the rate of diagnosis of FD and significantly reduce the delay in the diagnosis and treatment.Kidney involvement is a common complication of Fabry disease. Microalbuminuria and proteinuria are present in a high proportion of patients with FD  and afteOlder studies from large international registries reported an incidence of FD among patients on dialysis ranging between 0.016%  and 0.01Kidney transplantation may be a relevant option for the management of Fabry end-stage nephropathy, although few cases of kidney transplantation for Fabry disease have been reported in literature. The collaborative transplant study, which includes most of the transplant centers worldwide, identified a total of 143 kidney transplantations performed for Fabry disease in the period 1990–2016, and this accounts for only the 0.01% of kidney transplants for rare causes of ESRD . This inHowever, very few studies investigated the incidence of unrecognized FD in kidney transplant recipients ,33,34,35This study evaluated the incidence of unrecognized FD in a population of kidney transplant recipients performed at a single institution. Moreover, the study was extended also to family members of the affected patients. The screening identified an unexpectedly high incidence of previously unrecognized GLA mutations in kidney transplant recipients. Seven kidney transplant recipients (2.6%) reported a GLA mutation: two patients had a classic phenotype with Fabry nephropathy and started the enzyme replacement therapy, while in four patients we found a pathogenic mutation with no clear evidences of FD-related clinical manifestations. Notably, this was the first study identifying pathogenic mutations of GLA gene in female kidney transplant recipients.Interestingly, one female patient received the graft from his father who had the GLA mutation p.D313Y. This mutation was also encountered in the other four patients, who were asymptomatic with normal LysoGb3 values. This variant is considered of uncertain significance, following the American College of Medical Genetics and Genomics (ACMG) recommendations, and is widely reported in literature to have a low clinical significance ,37, althA recent systematic review  evaluatiThere are eight reports in literature of kidney transplantation from a living donor with GLA mutation ,41,42,43The incidence of unrecognized FD in our population was considerably higher than previously reported. This was probably related to the homogeneity of the study group and to the presence of many clusters of FD in our region. Moreover, the study was extended also to patients with a known causal diagnosis of end-stage renal disease, and this probably increased the likelihood of finding a GLA mutation.This study, for the first time, extended the screening also to the probands’ families and we were able to find 15 relatives of transplant patients with GLA mutations. This allowed for a prompt diagnosis and treatment was started before irreversible organ damage: three relatives started the enzyme replacement therapy due to Fabry nephropathy with proteinuria, and they have a stable renal function at last follow up. Two more patients with cerebral complications are on enzyme replacement therapy in good clinical conditions eight years after diagnosis. We found eight patients with the p.F113L variant, which has been associated in literature with the late-onset form of FD, with severe cardiac involvement particularly in homozygosis ,36. The In our study, two patients  with the p.F113L variant presented with proteinuria, initial kidney impairment, and cerebral disorder, and they immediately started the ERT. In six female patients, with normal Lyso-Gb3 levels, the complete clinical evaluation was negative for FD-related symptoms.Clinical diagnosis of Fabry disease may be challenging, because most of the symptoms may overlap with those of other diseases. This is particularly true in patients with ESRD undergoing kidney transplantation, where many transplant-related complications  are very similar to FD symptoms, meaning that the diagnosis may be not suspected and largely delayed. Data from large registries demonstrated that the median delay in the diagnosis of FD was 14 years in adults and 5 years in children, after a consultation of about 10 specialists with various degrees of experience in this field ,46, and Since 2008, the University Hospital of Catania is a referral center for Fabry Disease, with a multidisciplinary team with specific expertise in Fabry disease, with the aim of increasing the rate of early diagnosis of FD, and to reduce the delay in treatment. Notably, all the specialists involved in the multidisciplinary team work at the same hospital, avoiding the need for multiple time-consuming and costly visits to different hospitals. The multidisciplinary team evaluated all patients with a GLA mutation found at screening in kidney transplant recipients and in probands’ families, and this allowed for a significant reduction in time for the clinical assessment, which was completed after a median of 3.2 months, with a mean time from diagnosis to treatment of 4.6 months. A timely diagnosis allowed for a prompt treatment, before irreversible organ damage developed and this, in principle, could be associated with better long-term outcomes. Graft and patient survival in Fabry patients are comparable with that of non-Fabry patients undergoing a kidney transplantation ,48,49,50Although the study reported some new and important findings, we are conscious of its limitations: the study sample is relatively small, but the population presented is homogeneous and this reduced the potential bias deriving from different races, populations, type of transplants, and immunosuppressive protocols; moreover, the study did not include all patients undergoing a kidney transplantation at our institution. In conclusion, this study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients. Although most variants were potentially pathogenic, most patients did not have clinical symptoms attributable to FD. The screening allowed for identifying many patients with GLA mutations among relatives of kidney recipients, who received their treatment at a very early stage. This would encourage the screening in all kidney transplant populations, particularly in those patients with an unknown cause of ESRD. Evaluation and management by a multidisciplinary team allowed from an early diagnosis and treatment, before the development of irreversible organ damage, and this would result in a delay in the progression of the disease and, finally, in better long-term outcomes.