Offspring born following maternal gestational diabetes are at risk of excessive childhood weight gain and Type 2 diabetes in childhood, which in turn is associated with an increased rate of hypertension.We aimed to determine the systolic and diastolic blood pressure at two years of age in a cohort of children exposed to gestational diabetes mellitus using data from the MiG trial of metformin use in gestational diabetes. The secondary aim was to analyze these data by randomization of treatment to insulin or metformin.The offspring of women who had gestational diabetes and had been assigned to either open treatment with metformin  or insulin in the MiG trial were followed up at 2 years of age. Oscillometric measurement of BP in the right arm was performed by a researcher using an appropriately sized cuff.A total of 489 measurement blood pressure measurements were obtained in 170 of the 222 children who were seen at a median (range) age of 29 (22–38) months corrected gestational age. At the time of assessment the mean (SD) weight and height was 13.8(2) kg and 90 (4.2) cm respectively. For the whole group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic pressure was 55.7 (8.1) mmHg. No difference was found between the metformin and insulin treatment arms. In a regression model, height and weight were only two factors associated with the levels of systolic blood pressure. For each additional kg the systolic blood pressure increased by 1.0 mmHg. For each additional cm of height the systolic blood pressure increased by 0.42 mmHg.Blood pressure data was obtained at approximately two years of age in a substantial cohort of children whose mothers received treatment for GDM. These novel data compare favorably with published norms.ACTRN12605000311651).This study was registered under the Australian New Zealand Clinical Trials Registry ( Fetal exposure to high circulating blood glucose associated with maternal diabetes can result in major childhood effects for the offspring, particularly increased rates of obesity and Type 2 diabetes. Although these effects have been known for some time, there has been more of a focus on the topic over the last decade. Indeed, a recent review on infants born to mothers with gestational diabetes mellitus (GDM) highlighted both the increased incidence of GDM, associated with the obesity pandemic, and the potential threat to global health from long term and transgenerational effects .In a landmark study of pregnancy outcome in Pima Indians, children born to mothers with Type 2 diabetes or gestational diabetes mellitus (GDM) were larger for gestational age at birth and heavier at five years of age compared with those born to non-diabetic women -5 and anChildren who develop childhood Type 2 diabetes also have an increased rate of hypertension. In one surveillance report there was a six fold increase in risk, and nearly a quarter of children with Type 2 DM were found to have hypertension . A combiAlthough very low birth weight and premature infants are reported to demonstrate elevated blood pressure (BP) measurements in the preschool time period ,8 there The original MiG trial methods have been previously reported ,11. WomeWomen who had consented to further follow-up of their child were telephoned around the child’s second birthday to invite ongoing participation and assessment. In Auckland, a home visit was arranged and simple anthropometry measurements of the mother and child were made. A follow-up appointment was made within 1 to 2 weeks of the home visit to attend the Liggins Institute, University of Auckland, for the child to have a physical examination, including formal blood pressure measurement. In Adelaide, all but two of the follow-up assessments were performed in hospital at an outpatient research clinic, when formal blood pressure and anthropometric measurements were made. Blood samples were drawn as possible, and Bayley assessment and body composition studies were also performed, either at the same or a separate occasion.ACTRN12605000311651).This follow-up study had ethical approval from the Northern A Health and Disability Ethics Committee in Auckland and the Women's and Children's Hospital Network Human Research Ethics Committee in Adelaide. Written informed consent was again obtained for each participant. It ran from November 2004 to February 2008. The study was registered under the Australian New Zealand Clinical Trials Registry . Measurements were made from the right arm using an appropriately sized cuff.Data are presented as mean (SD) unless not normally distributed, when median (range) is used. Continuous data were analysed using stepwise linear regression. An initial model was obtained by fitting outcome to all covariates: gestation age, ethnicity, height, weight, waist, hip, chest and arm measurements. Factors were then removed stepwise in descending order of P-values whenever they were found to be non-significant (P < 0.05), yielding the final model. Categorical data were analysed using Chi square and Fischer’s exact test as appropriate. Box and whisker plots have been used to illustrate the data distribution.Blood pressure measurements were obtained in 170 (53%) of the total children  weight and height was 13.8 (2.0) kg and 90.0 (4.2) cm for the whole study group. There were no differences in weight at 13.7 (1.9) kg versus 14.0 (2.0) kg and height at 90.5 (4.7) versus 90.4 (5.1) cm for insulin and metformin groups respectively. Sex was also equally distributed between the treatment groups with 41 males (47.1%) in insulin group and 40 males (48.2%) in the metformin group.A total of 489 measurements were recorded from 170 children (mean 2.9 per child). For the whole group the mean (SD) systolic pressure was 90.9 (9.9) mmHg and mean (SD) diastolic pressure was 55.7 (8.1) mmHg. Distribution of systolic and diastolic pressures divided by treatment group and gender are shown in the figure . For each additional cm of height the systolic blood pressure increased by 0.42 mmHg . No difference was found between the metformin and the insulin arms.th centile for systolic/diastolic blood pressure was 99/51 with 5th centile 87/39 and 95th 114/64 mmHg at 3 years.In this study we report data on blood pressure obtained at approximately two years of age in a substantial cohort of children whose mothers had received treatment during their pregnancy for GDM. These novel data are reassuring for the group as a whole with a mean systolic pressure of 90.9 mmHg and mean diastolic pressure of 55.7 mmHg, which compares favorably with published norms for children not exposed to GDM ,12. Van th centile [In a study of infants from the USA who were exposed to GDM, the mean systolic BP at 3 years of age was reported to be 3.2 mmHg higher than that in controls born to normoglycaemic mothers after adjustment for sex age and measurement condition. In this study population, of whom 73% were born to mothers described as white American, the mean systolic BP was 92 mmHg, which is similar to the US 50 centile  has repo centile . The autThe methodology for the study is robust in that the BP data were prospectively collected by dedicated researchers, all highly motivated and who had time to settle the child and achieve a co-operative state prior to performing the measurements. Attempts were made to collect more than one recording. In addition, treatment allocation was subject to the usual care involved in a randomized controlled trial.The two study limitations of note were first that, as mentioned above, two years of age is early in childhood to detect significant differences in cardiovascular health, and second, that BP measurement was only obtained from the subgroup of the offspring (53%) who returned to the follow up appointment. The rate of successfully measuring blood pressure in our cohort is comparable with that published by Van Houten et al. , who repIt is recognized that adverse perinatal events, including prematurity, may be associated with elevated blood pressure in childhood . An incr


The bladder outlet obstruction index (BOOI), also known as the Abrams-Griffiths (AG) number, is the most widely used index for predicting BOO. However, the obstructed prostatic urethra determined by the BOOI is often inconsistent with endoscopically-proven obstruction. We assessed abdominal straining pattern as a novel parameter for improving the prediction of BOO.detQmax+ΔPabd)-2Qmax.We retrospectively reviewed the pressure-flow studies (PFS) and cystourethroscopy in 176 BPH/LUTS patients who were unresponsive to medical therapy. During PFS, some groups of patients tried to urinate with abdominal straining, which can increases intravesical pressure and underestimate BOOI theoretically. Accordingly, the modified BOOI was defined as  was 11.81±13.04 cmH2O, and it was 0–9 cmH2O in 75 (57.7%), 10–19 cmH2O in 23 (17.7%) and ≥20 cmH2O in 32 (24.6%) patients. An endoscopically obstructed prostatic urethra in 92 patients was correctly determined in 47 patients (51.1%) by the original BOOI versus 72 patients (78.3%) based on the modified BOOI. Meanwhile, an “unobstructed” urethra according to the original BOOI was present in 11 patients (12.0%), whereas according to the modified BOOI, only 2 (2.1%) would be labeled as “unobstructed”. In receiver operating characteristic curves, the area under the curve was 0.906 using the modified BOOI number versus 0.849 in the original BOOI (p<0.05).Ultimately, 130 patients were eligible for the analysis. In PFS, ΔPThe change in abdominal pressure was correlated with endoscopically-proven obstruction. Our simple modification of the BOOI on the basis of this finding better predicted bladder outlet obstruction and, therefore, should be considered when evaluating BOO in patients with LUTS/BPH. Benign prostatic hyperplasia (BPH), which includes benign prostatic enlargement (BPE) and benign prostatic obstruction (BPO), has conventionally been considered a major factor in causing male lower urinary tract symptoms (LUTS) . RecentlUrodynamic studies, especially pressure-flow studies (PFS), are known to be the gold standard tool for diagnosing the existence of BOO. Since 1972, studies have been attempting to simplify the diagnosis of BOO in men and to create a standardized method for diagnosis using PFS. The best-known methods for the diagnosis of BOO are the Abrams-Griffiths (AG) nomogram and number, the Schafer nomogram, the group-specific urethral resistance factor (URA), the detrusor-adjusted mean passive urethral resistance relation (PURR), and the obstruction coefficient (OCO) 1/2-1)/(7.6*10-4*Qmax2) [detQmax/(40+2Qmax) [Four methods were used to assess bladder outlet obstruction: (1) BOOI = Pax-2Qmax , (2) mod*Qmax2) ,12, and 0+2Qmax) . BOOI wa0+2Qmax) . The con0+2Qmax) . The cut2O. An endoscopically obstructed prostatic urethra was defined when both lobes of the prostate were completely kissing, and regarded as the reference standard, concordant with “severe obstruction” suggested by el Din et al [Cystourethroscopy was performed by a single urologist (K.S.C.), and a 20 Fr rigid cystoscopic sheath was used. The prostatic urethra was inspected at the veru montanum while saline was continuously infused at the pressure of 40 cmHin et al . Two invabd and the two conventional parameters PdetQmax and Qmax, which were used in all four methods. Receiver operating characteristic (ROC) curves were calculated to evaluate the positive impact of the abdominal pressure parameter.Variables in the two groups were compared using Student’s t-test, the Mann-Whitney U test, and the chi-square test. In multivariable models, a backward stepwise elimination process was carried out to identify the most relevant measurements of urodynamic parameters for predicting BOO. This process started with a full model containing all candidate measurements. By stepwise deletion of non-significant variables according to the likelihood-ratio criteria, the final multivariable model contained only significant variables. Based on the result above, multivariate logistic regression analysis was performed with three parameters: ΔPFour method’s grouping results were compared to the endoscopic finding, and the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the diagnostic accuracy of each method were calculated. Consequently, the diagnostic accuracy and the optimal cutoff value point of each method were analyzed by a receiver operating characteristic (ROC) curve. The area under the curve (AUC) for each methods were calculated, and compared using an algorithm suggested by DeLong et al . The cuthttp://www.r-project.org). A P-value <0.05 was considered statistically significant, and all statistical tests were two-sided.All statistical analyses were performed using the R statistical software  were diagnosed as “endoscopically obstructed”, and 38 patients (29.2%) as “endoscopically unobstructed”. As for the urinary symptom questionnaires, the obstructed group had more severe symptom scores in IPSS-total, IPSS-storage, and OABSS. However, there was no difference in IPSS-voiding and IPSS-post-micturition. The transrectal ultrasonographic examination revealed that the prostate volume, transitional zone volume, and transitional zone index in the obstructed group was significantly higher. On the free-flow study, Qo groups .max between the two groups, but PdetQmax was 32.66 ± 15.22 cmH20 in the unobstructed group versus 61.22 ± 27.13 cmH20 in the obstructed group (P < 0.001). Notably, ΔPabd was significantly higher in the obstructed group than in the unobstructed group . Subjects with a ΔPabd ≥10 cmH2O composed 48.9% of the obstructed group but only 26.3% of the unobstructed group . We compared the two ROC curves using the probability variables extracted from the two independent multivariate logistic regression models: (A) PdetQmax and Qmax and (B) PdetQmax, Qmax, and ΔPabd. The latter model was highly predictive of endoscopically proven obstruction . The former model with the two conventional variables had an ROC curve with an AUC of 0.864 (p < 0.001) Comparison of the two methods was performed, and the former model was superior, with a p-value of 0.0058  were determined as “obstructed” according to the original BOOI, but 72 patients (78.3%) were classified as “obstructed” based on the modified BOOI. Additionally, an “unobstructed” urethra according to the original BOOI was present in 11 patients (12.0%), whereas according to the modified BOOI, only 2 (2.1%) would be labeled as “unobstructed”. Diagnostic test validation was performed, and for the 2×2 table validation, the “equivocal group” was classified as the unobstructed group. Validation of each of the methods was based on the accepted cutoff values: OCO (>1), URA (>29), BOOI (>40), and modified BOOI (>40). Of the four methods compared, including BOOI, modified BOOI, URA, and OCO, the modified BOOI showed the highest values in all parameters for test validity . Indeed, 25–30% of men with decreased flow were not obstructed in the Abrams’ study [Uroflowmetry and PVR are simple tests that are performed when BOO is suspected. However, a decreased maximum flow rate can result from either an impaired detrusor contractility or BOO ,18; thers’ study .Due to the weakness of uroflowmetry, the PFS has been used for better definition and grading of the degree of BOO. Several nomograms using a PFS have been introduced to evaluate BOO, and researchers have compared the diagnostic accuracy of the nomograms in various ways. Jimao et al. compared the degree of the agreement between the AG nomogram, URA, and detrusor-adjusted mean passive urethral resistance relation factor (DAMPF); the authors showed the cutoff value in the ROC curve of each method . Cravalhabd was the second most powerful factor, followed by PdetQmax, as revealed in multivariate logistic regression. Based on intuition and our experience in clinical practice, we hypothesized that ΔPabd could be an important clinical factor and may play a role as an independent factor in raising diagnostic accuracy. We attempted to design a new method that would be simple and easily applicable in the clinical practice, while maintaining the basic frame of the conventional methods, which used PdetQmax and Qmax. Considering the availability of parameters and ease of measurability in the clinical setting, we created the new method simply adding the abdominal pressure parameter to the conventional BOOI method. The purpose of this process was not to design the best predictive model by using three parameters, but merely to investigate the feasibility of applying this method to clinical practice in order to obtain better predictive power.Three methods referred to in the current study  all used PdetQmax and Qmax as urodynamic parameters to predict BOO. In our study, we compared all urodynamic parameters between the obstructed and unobstructed groups. Of all the parameters, ΔP2O endoscopically. Because we know the real obstruction grade, we could compare the nomograms more precisely and measure the diagnostic accuracy of each method. After the ROC curve was drawn, the AUC of the modified BOOI had the largest AUC (0.906), indicating high accuracy, while the other methods were between 0.8–0.9 (moderate accuracy). With regards to hydromechanics, theoretically, our modified BOOI can supplement the original BOOI to identify the group with low contractility and low flow rate, which voids using the abdominal pressure. The basis of our theory is similar to the penile cuff test, a well-known noninvasive method for predicting BOO. In the penile cuff test, the degree of obstruction is evaluated by measuring the urine flow rate and the pressure of the urethra, which indicates isovolumetric bladder pressure [In the previous studies, there was an absence of clear criteria for endoscopic bladder outlet obstruction. We referred to the diagram shown by el Din et al. for defining and grading BOO . The autpressure . That tepressure .Predicting who would benefit from invasive treatment modalities is crucial in clinical practice, however, BOOI has several limitations in that respect. Men with a relatively low detrusor pressure at maximum flow and relatively low maximum flow have a high prevalence of discrepancy with URA and Schafer’s grade classifications . In someabd significantly contributes to voiding, acting as a compensatory mechanism for patients with a hypo- or acontractile neurogenic bladder. Although the valid method of analyzing voiding with abdominal straining on the PFS remains undecided, Sekido insists that clinicians should carefully observe the raw pressure-flow traces, in addition to using the nomograms [According to Sekido, Pomograms . In clinmuo) [2O per milliliter per second or the pmuo is >40 cmH2O, then the PFS is obstructed. On the other hand, if the slope is <2 cmH2O per milliliter per second or the pmuo is <40 cmH2O, then the PFS is unobstructed. In our study, among the 92 patients who were endoscopically obstructed, 18 (19.6%) patients were classified as equivocal in the modified BOOI. Among those 18 patients, 5 patients were additionally grouped as “obstructed”, considering pmuo and the pressure-flow slope, and elevating its diagnostic accuracy.Meanwhile, applying the alternative methods to our modified BOOI can further improve its diagnostic accuracy. Lim et al. demonstrated that equivocal cases grouped by BOOI can be classified into obstructed and unobstructed groups using the pressure-flow slope and minimal voiding detrusor pressure (pmuo) . If the Our study had several limitations. We considered the endoscopic prostatic complete kissing as the definition for bladder outlet obstruction. However, in clinical practice, prostatic flow is the result of a variety of influential factors. Flow is not in simple correlation with an endoscopically-proven mechanical obstruction. There are also inherent limitations from the nature of a retrospective study and cross-sectional analysis. Accordingly, a larger prospective cohort study is needed to compare the difference between the preoperative and postoperative PFSs in each patient, in order to confirm the diagnostic usefulness of our modified BOOI. Despite the shortage of the study, this study was maximally controlled in the process of evaluation, and fully demonstrated the possibility of a potentially competitive nomogram. In view of the current data, future studies, which consider the differences in abdominal pressure as a significant clinical factor in predicting BOO, should be performed.We confirmed the impact of abdominal pressure change in predicting endoscopically proven BOO. Our simple modification of BOOI is better correlated with endoscopically-proven obstruction than the original method. Theoretically, it is reasonable to consider the individual difference in abdominal pressure during a PFS, when determining the presence or absence of BOO. However, large prospective studies are needed to validate our suggestions.


High prevalence of masked hypertension as well as persistent hypertension was observed in the Chronic Kidney Disease Japan Cohort (CKD-JAC) study. We proposed a novel indicator of blood pressure (BP) load, hyperbaric area index (HBI), calculated from ambulatory blood pressure monitoring (ABPM) data. The characteristic of this index and its relationship with kidney function were also evaluated.The CKD-JAC study, enrolled 2,977 patients, is a prospective observational study started in September 2007. ABPM was conducted in a sub-group from September 2007 to April 2010 and baseline ABPM data of 1,075 subjects  were analyzed.2 in eGFR]. The HBI was a significant factor to associate with reduced kidney function, after adjusting with nocturnal BP change (NBPC), sex, and other variables .Mean systolic HBI of male and female patients were 242.3 and 176.5 mmHg×h, respectively. HBI sensitively reflected sex , seasonal effects (51.6 mmHg×h higher in winter than in summer), and advancing CKD stage [(16.5 mmHg×h higher) per −10 mL/min/1.73 mOur findings suggested that HBI might be a novel sensitive indicator for the reduction of kidney function, independent of patterns of NBPC. Blood pressure (BP) is one of the most important risk factors for cardiovascular diseases (CVDs). The prevalence of chronic kidney disease (CKD) in Japanese adults has been estimated to be 13 % , 3.Ambulatory blood pressure monitoring (ABPM) has come to be used as a powerful medical examination device since late 80s, and various indicators calculated from ABPM data have been reported as novel predictive factors for several organ injuries –7. The fWe recently reported the high prevalence of masked hypertension in CKD population and the association between NBPC and the reduction of kidney function using the ABPM data in the CKD Japan Cohort (CKD-JAC) study . In thisThe CKD-JAC study was started in September 2007 to investigate CKD patients in Japan. 2,977 subjects were enrolled and followed until December 2012. A detailed description of this study has been published . In brieABPM was conducted within a half year after starting observation. BP was measured every 30 min for 24-h period with the TM-2421 device . ABPM data were collected on 1,117 cases. Every case was visually inspected and 34 cases were determined to be invalid as examinations. Duplication was seen in 2 cases, and 6 subjects withdrew consent. Therefore, 1,075 cases were available for analyses  and morning BP change. The degree of NBPC was calculated by the following equation:Details including cutoff points of NBPC patterns and NBPC definition were described in our previous paper .Hyperbaric area (HB) was defined as the area encircled by polygonal line of ambulatory BP and two boundary lines of hypertension: 135/85 mmHg (during awakening) and 120/70 mmHg (during sleeping), based on Japanese Hypertension guidelines . The areSerum creatinine (Cre) from single blood sampling at the baseline was measured at a central laboratory and eGFR was calculated by the following Japanese equations :\documenCKD stage was defined using eGFR; 60 > eGFR ≥ 30 for stage 3, 30 > eGFR ≥ 15 for stage 4 and 15 > eGFR ≥ 10 for stage 5.t test, and ANOVA was used for comparisons among more than 3 groups. For categorical variables, Chi-squared test (2 × 2 contingency table), or Cochran–Mantel–Haenszel test (m × n table) was performed. Simple linear regression analysis or Chi-squared test was used for univariate evaluations to investigate the relationship between ABPM parameters and background factors including patient questionnaires. Multiple regression analysis was used for multivariate evaluations including variables with p values <0.1 explored above. Two-way ANOVA was performed to investigate the relationship between kidney function and two indicators from ABPM (NBPC and HBI). The performance of SBP indicators as a discriminator for reduced kidney function was examined using receiver-operating characteristic curve (ROC) analysis.All variables were reported as mean ± SD unless otherwise indicated. Continuous variables from two groups were compared with All statistical analyses were performed using the SAS software program for Windows .2 in female and 23.6 kg/m2 in male, and the mean office BP was 129.8/76.3 mmHg in female and 132.1/77.6 mmHg in male. The proportion of subjects according to CKD stage  was as follows: stage 3, 43.0 %/44.3 %; stage 4, 42.0 %/41.6 %; and stage 5, 15.0 %/14.1 %. Proteinuria was observed in 89.6 % of the female and 88.0 % of the male, and diabetes in 32.6 % of female and 37.1 % of male. Approximately 10 % of the subjects had not been prescribed even one antihypertensive drug.Table In patient questionnaires, 12.8 % of females and 22.8 % of males had nocturia. In addition, ~20 % of subjects reported that it was extremely hard to sleep due to the ABPM.The breakdown of the NBPC patterns  was as follows: extreme dipper 10.2 %/9.5 %, dipper 35.9 %/37.2 %, non-dipper 37.7 %/38.1 %, and riser 16.3 %/15.1 %. Approximately 27 % of subjects had their measurements taken during summer  and males (p < 0.001). HBI increased by 26.0 mmHg×h in females and 39.7 mmHg×h in males for every 10 mL/min/1.73 m2 decreasing in eGFR. HBI was high in cases when office SBP/DBP were high (p < 0.001), and it was significantly higher in winter than in summer . On the other hand, there were no significant differences between with and without much difficulty in sleep in both sexes.We evaluated the relationship between HBI and background factors stratified by sex Table . HBI incp value ≤0.1, including eGFR, proteinuria, and season, were taken into multiple regression model as independent variables so that we could assess their effects on HBI (Table p = 0.003) and was 54.7 mmHg×h higher in males than in females. Subjects with proteinuria had higher mean HBI than subjects without proteinuria by 43.5 mmHg×h (p = 0.05), and subjects whose measurements were taken in the winter had higher mean HBI than subjects whose measurements were taken in summer by 51.6 mmHg×h (p < 0.001). ABPM examination itself interfered with the sleep of some subjects, but the relationship between sleep and HBI values was not significant (p = 0.71).Sex and other ten variables with BI Table . It shoup value between office SBP and 24-h mean SBP was 0.16, and that between office SBP and HBI was 0.23.We evaluated the performance characteristics of three BP indicators on kidney function: office BP, 24-h mean BP, and HBI using ROC curve Fig. . ReducinFinally, we examined the relationship between two ABPM indicators (HBI and NBPC) and eGFR at the same time point. First, patients were divided into two groups by NBPC: one is sufficient NBPC group with dipper or extreme-dipper, and the other is insufficient NBPC group with non-dipper or riser. And then each group is divided into two groups by with/without BP load Fig. . eGFR wap = 0.13, males: p = 0.37), whereas BP load was significantly associated with eGFR . The interaction term between NBPC and BP load was not significant .We then examined the relationship between NBPC or BP load and eGFR by two-way analysis of variance upon due consideration of the interaction between NBPC and BP load Table . NBPC wa2 decrease in eGFR (p = 0.08), while 100 mmHg×h increase in HBI corresponded to 0.72 mL/min/1.73 m2 decrease in eGFR (p ≤ 0.001). Another analysis using a model that included the season and the quality of sleep, both of which influenced the degree of NBPC, produced similar results  as well as sex and age as independent variables, and eGFR as a dependent variable Table , left. 1ts Table , right.TRecently, several studies showed that ABPM correlated more strongly with hypertensive target organ damage than office BP readings –22. YamaIn our previous paper, we reported that the prevalence of non-dipper or riser was lower among subjects with CKD stage 3 than in CKD stage 4 or 5. We also reported that when determining NBPC patterns, information regarding the season, the patient’s sleep quality, and nocturia should be taken into account . After aThere was still insufficient solid evidence that HBI reflected the BP load on organs , 25. OurSubjects with non-dipper pattern of night-time blood pressure were reported to be associated with cardiovascular and cerebrovascular diseases , 26. Howp = 0.64/males: p = 0.58). Hence, these two factors could be understood as having effects of BP on kidney function from different perspectives.In two-way analysis of variance Table , the intp < 0.001) and it was suggested that the effect of 100 mmHg×h HBI increase on eGFR was the equivalent of the effect of three-year increase in age on eGFR. 100 mmHg×h HBI increase was equivalent to mean BP increase of only 4.2 mmHg throughout 24 h. It could be realized that how effects of BP load on kidney function were great.We also evaluated the relationship between these two factors and eGFR with multiple regression model adjusted with several background factors. As shown in Table HBI has basically same meaning as office BP and 24-h mean BP. All of them are BP load to organs. We provided comparative performance measurements among them using ROC curves. ROC showed superiority of 24-h mean BP and HBI against office BP. Unfortunately, there were no significant differences between 24-h mean BP and HBI. However, these results indicated that it was insufficient to understand CKD patients’ BP control using solely office BP and that ABPMs were needed.These results represented a first possible step towards evaluating BP load by HBI, because HBI strongly reflected background factors that may have association with kidney function. As next step, we will evaluate BP load by HBI accurately as a prognostic predictor for kidney function deterioration and CVDs by using prospectively collected data in the CKD-JAC study.This paper was limited in that data analyzed were cross-sectional data at the enrollment. The last patient was out of this study in December 2012 and now we are carring out data cleaning.This study has clarified that HBI is able to separate the BP loads from background factors quantitatively. NBPC is one of the most useful indicators of the BP loads on clinical settings, and HBI may provide another index for this purpose. Because HBI was a sensitive indicator of kidney function, it also might be a predictor of future kidney function reduction, independent from patterns of NBPC. When the data cleaning has been completed, we will evaluate HBI as a prognostic indicator for kidney function and CVDs.


To examine characteristics of ocular hypertensive subjects and potential associations with estimated cerebrospinal fluid pressure (estCSFP).2]+0.16×Diastolic Blood Pressure [mmHg]−0.18×Age [Years]−1.91. Estimated trans-lamina cribrosa pressure difference (estTLCPD) was IOP–estCSFP.The population-based Beijing Eye Study 2011 included 3468 individuals with a mean age of 64.6±9.8 years. Ocular hypertension was defined as intraocular pressure (IOP) >21 mmHg, normal optic nerve head appearance and normal retinal nerve fiber layer thickness. IOP was corrected for its dependence on central corneal thickness (CCT) and corneal curvature radius. Estimated CSFP was calculated as CSFP [mmHg] = 0.44×Body Mass Index [kg/mP<0.001) were higher in the ocular hypertensive group than in the normotensive group. In binary regression analysis, ocular hypertension was associated with increased estCSFP : 1.08; 95% confidence interval (CI): 1.01, 1.17) after adjusting for prevalence of arterial hypertension , retinal nerve fiber layer thickness  and blood glucose concentration .EstCSFP  and estTLCPD  as compared to ocular normotensive subjects had a significantly higher estCSFP in univariate analysis and in multivariate analysis. Despite of a higher estCSFP, estTLCPD was still markedly higher in ocular hypertensive eyes than in ocular normotensive eyes. Ocular hypertension has been defined by an intraocular pressure (IOP) higher than 21 mm Hg, a normal optic nerve and normal visual field The Medical Ethics Committee of the Beijing Tongren Hospital approved the study protocol and all participants gave informed written consent, according to the Declaration of Helsinki.The Beijing Eye Study 2011 is a population-based cross-sectional study in Northern China on subjects aged 50+ years P<0.001) and shorter corneal curvature radius (P<0.001) after adjusting for parameters such shallower anterior chamber depth, longer axial length, younger age, higher pulse rate, higher prevalence of arterial hypertension, and higher blood concentration of triglycerides and cholesterol. The regression coefficients of the associations between IOP and CCT or corneal curvature were used for the formula of the corrected IOP: “IOPcorrected = IOPmeasured−((CCT [µm]−532)×0.038)+×1.11)”. Mean CCT was 532 µm, and mean corneal curvature radius was 7.62 mm. Using this formula to arrive at the corrected IOP, the measured IOP was decreased by 3.8 points for each 100 µm which the cornea was thicker than the average mean of 538 µm, and the measured IOP was increased by 1.11 points for each mm, the corneal curvature radius was larger than the average mean of 7.62 mm. This formula was partially similar to the one developed by Kohlhaas and colleagues, in which an approximately 1-mm Hg correction for every 25-µm deviation from a CCT of 550 µm was suggested The measured IOP was corrected for its dependence on central corneal thickness (CCT) and anterior corneal curvature radius Ocular hypertension was defined by a corrected IOP higher than 21 mm Hg, a normal retinal nerve fiber layer as measured by spectral-domain OCT, and a normal appearance of the optic nerve head. The latter was defined by a normal shape of the neuroretinal rim following the ISNT  rule P>0.10). Performing a multivariate analysis in the training group with the lumbar CSFP measurements as dependent variable and age, body mass index and blood pressure as independent variables revealed, that estimated CSFP was best described by the formula of Estimated CSFP [mmHg] = 0.44×Body Mass Index [kg/m2]+0.16×Diastolic Blood Pressure [mmHg]−0.18×Age [Years]−1.91 P = 0.29) from the calculated CSFP (13.3±3.2 mm Hg). The coefficient for the correlation between the calculated CSFP value and the measured lumbar CSFP was r: 0.59. The Durbin-Watson value was 2.08. Durbin-Watson values falling into the acceptable range of 1.5 to 2.5 indicate a non-significant autocorrelation for the residuals in the multiple regression models. The intra-class correlation coefficient was 0.71. The Bland-Altman analysis revealed that 40 out of 42 measurements were within the 95% limits of agreement . First, we examined the mean values (presented as mean ± standard deviation). Second, we corrected the IOP measurements for the dependence on CCT and corneal curvature as described above. Third we identified the ocular hypertensive group and looked for differences between the later and the ocular normotensive group in univariate analysis. Fourth, we performed a multivariate binary regression analysis with the presence of ocular hypertension as dependent variable and all parameters as independent variables which were significantly associated with ocular hypertension in the univariate analysis. We then dropped those parameters which were no longer significantly associated with ocular hypertension. Fifth, we searched for associations between the estimated CSFP and other parameters including IOP. Only one randomly selected eye per individual was included into the statistical analysis. Odds ratios (OR) 95% confidence intervals (CI) were presented. All Measurements of IOP, central corneal thickness, corneal curvature radius, blood pressure, and body height and weight and assessable optic disc photographs and OCT images were available for 6064 (87.4%) eyes. Out of these, 5280 eyes of 2819 subjects (1607 (57.0%) women) fulfilled the inclusion criteria of a normal retinal nerve fiber layer and a normal appearance of the optic nerve head. Mean age was 63.7±9.4 years  and mean refractive error was −0.03±1.70 diopters .P = 0.003) and estimated TLCPD  were significantly higher  and mean corrected IOP was 14.7±2.5 mm Hg . The definition of ocular hypertension was fulfilled by 70 (1.3%) eyes of 62 (2.2%) subjects (32 (52%) women). For 51 of the 70 ocular hypertensive eyes, results of frequency doubling perimetry performed at the baseline survey in 2001 were available. All test points were tested normal in 48 (94%) eyes, while one (2%) eye had one test point positive. Two additional eyes (4%) showed an unreliable visual field test result. Mean age of the ocular hypertensive subjects was 63.6±8.9 years (range: 50–84 years) and mean refractive error was 0.16±1.66 diopters (range: −5.50 to +6.38 diopters). In the ocular hypertensive group as compared with the ocular normotensive group, estimated CSFP , higher prevalence of the rural region as site of habitation (P = 0.003), higher values for the blood concentration of glucose (P = 0.04), higher estimated CSFP (P = 0.003) and higher estimated TLCPD (P<0.001), and thicker retinal nerve fiber layer (P = 0.02)  . Due to P = 0.02), thinner retinal nerve fiber layer (P = 0.03), higher blood concentration of glucose (P = 0.006), and marginally significantly with higher prevalence of arterial hypertension (P = 0.07)  correlated with ocular hypertension. If due to its statically marginal association with ocular hypertension arterial hypertension was dropped from the model, the association between ocular hypertension and estimated CSFP became stronger .In the binary regression analysis, ocular hypertension remained significantly associated with increased estimated CSFP ( = 0.07) . If treaIn our population-based study with correction of the IOP measurements for their dependence on CCT and corneal curvature radius, ocular hypertensive subjects had a significantly higher estimated CSFP after adjusting for arterial hypertension, blood glucose concentration and retinal nerve fiber layer thickness. Despite of the higher estimated CSFP, however, the estimated TLCPD was still markedly higher in ocular hypertensive eyes than in ocular normotensive eyes.These results confirm a previous hospital-based study by Ren and colleagues In the population-based Central India Eye and Medical Study and in the Beijing Eye Study, a smaller neuroretinal rim which can be considered as surrogate for glaucomatous optic nerve damage, was associated with a lower body mass index P<0.001)  . One mayP<0.001) higher systolic and diastolic blood pressure . Differences between glaucomatous subjects and non-glaucomatous subjects in estimated CSFP were more pronounced for open-angle glaucoma than for angle-closure glaucoma (3.0 mmHg versus 1.8 mmHg), while differences between glaucomatous subjects and non-glaucomatous subjects in IOP were higher for angle-closure glaucoma than for open-angle glaucoma (8.5 mmHg versus 3.0 mmHg). Presence of open-angle glaucoma was significantly associated with estimated TLCPD  but not with IOP . Prevalence of angle-closure glaucoma was significantly associated with IOP  but not with estimated TLCPD (P = 0.92). It was concluded that in open-angle glaucoma, but not in angle-closure glaucoma, estimated TLCPD versus IOP showed a better association with glaucoma presence and amount of glaucomatous optic neuropathy. Similar results were obtained in the Beijing Eye Study, in which IOP was higher (P = 0.008), estimated CSFP was lower (P<0.001) and estimated TLCPD was (P<0.001) higher in the glaucoma group than in the non-glaucomatous group P<0.001) but not with IOP (P = 0.22), while angle-closure glaucoma was associated with higher IOP (P = 0.03) but not with estimated TLCPD (P = 0.98) in multivariate analysis. In the Central India Eye and Medical Study as well as in the Beijing Eye Study, higher estimated CSFP was correlated with higher IOP in univariate analysis and in multivariate analysis The findings obtained in our present study fit with observations made in another recent study. In the Central India Eye and Medical Study, the mean estimated TLCPD was 3.6±4.3 mm Hg in the non-glaucomatous population and 9.67±8.2 mm Hg in the glaucomatous group Interestingly, recent studies revealed that the estimated CSFP was correlated with other ocular parameters and diseases, in addition to ocular hypertension and open-angle glaucoma. A higher estimated CSFP was associated with a thicker subfoveal choroidal thickness, wider retinal veins, in particular in arterial hypertensive patients, a higher intraocular pressure (own data) and a higher prevalence of diabetic retinopathy P-value of <0.05, the low coefficients showed that only a fraction of the variability in the prevalence of ocular hypertension could be explained by that relationship. Fifth, as for any population-based study, the rate of non-participation or non-availability of examination results can matter. In our study, the participation rate was 78.8% what may be acceptable.Potential limitations of our study should be mentioned. First, the whole statistical analysis depended on the formula to calculate the CSFP. The study, in which the basis parameter for that formula were assessed included a relatively small number of subjects, and these subjects had a clinic al reason to undergo lumbar puncture In conclusion, ocular hypertensive subjects as compared to ocular normotensive subjects had a significantly higher estimated CSFP after adjusting for arterial hypertension, pulse rate, blood glucose concentration and retinal nerve fiber layer thickness. Correspondingly, higher CSFP was associated with higher IOP. Despite of the higher estimated CSFP, the estimated TLCPD was markedly higher in ocular hypertensive eyes than in ocular normotensive eyes. Besides an elevated CSFP, other additional parameters may be at play in eyes which did not develop glaucomatous optic neuropathy despite elevated IOP.


Several studies on diagnostic accuracy of pleural N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) for effusions from congestive heart failure (CHF) conclude that pleural NT-pro-BNP is a useful biomarker with high diagnostic accuracy for distinguishing CHF effusions. However, its applicability in critical care settings remains uncertain and requires further investigations.NT-proBNP was measured in pleural fluid samples of a prospective cohort of intensive care unit patients with pleural effusions. Receiver operating characteristic curve analysis was performed to determine diagnostic accuracy of pleural NT-proBNP for prediction of CHF effusions.One hundred forty-seven critically ill patients were evaluated, 38 (26%) with CHF effusions and 109 (74%) with non-CHF effusions of various causes. Pleural NT-proBNP levels were significantly elevated in patients with CHF effusions. Pleural NT-pro-BNP demonstrated the area under the curve of 0.87 for diagnosing effusions due to CHF. With a cutoff of 2200 pg/mL, pleural NT-proBNP displayed high sensitivity (89%) but moderate specificity (73%). Notably, 29 (27%) of 109 patients with non-CHF effusions had pleural NT-proBNP levels >2200 pg/mL and these patients were more likely to experience septic shock  or acute kidney injury .Among critically ill patients, pleural NT-proBNP measurements remain a useful diagnostic aid in evaluation of pleural effusions. However, patients with non-CHF effusions may exhibit high pleural NT-proBNP concentrations if they suffer from septic shock or acute kidney injury. Accordingly, it is suggested that clinical context should be taken into account when interpreting pleural NT-proBNP values in critical care settings. Pleural effusions are common manifestations of a variety of diseases and congestive heart failure (CHF) is the leading cause of pleural effusions. Traditionally, the well-established criteria of Light are usually used to determine whether the effusion is a transudate or an exudate in the first step of evaluating patients with pleural effusions N-terminal pro-B-type natriuretic peptide (NT-proBNP) and its C-terminal counterpart, BNP, are derived from the precursor peptide, namely proBNP. The precursor proBNP is synthesized mainly in heart ventricles and is stimulated by increased tension or stretching of the ventricular wall. Serum NT-proBNP measurement is a biomarker of cardiac dysfunction and has been proven to be a useful tool in diagnosis of CHF Accordingly, the present study aimed to investigate the applicability of NT-proBNP in pleural effusions in discriminating between CHF and non-CHF effusions among critically ill patients.The present study was carried out prospectively between September 2012 and July 2014 at National Taiwan University Hospital in Taipei, Taiwan. During this time, pleural effusion samples from consecutive patients who had undergone thoracentesis in the medical intensive care unit (ICU) were studied. When repeated thoracentesis were required, only the first episode was included. In addition, patients with effusions of uncertain etiology or effusions with more than one possible cause were excluded from the analysis. The decision to undertake thoracentesis was made by the intensivists in charge of patients.This study was approved by the Research Ethics Committee of National Taiwan University Hospital, and all patients or the next of kin gave written informed consent.Biochemical analysis , bacterial, fungal and mycobacterial culture, Gram stain, acid-fast bacilli smear, and cytological examinations were performed for all pleural effusion samples shortly after thoracentesis. Meanwhile, concentrations of albumin, total protein and lactate dehydrogenase in the serum were measured by standard methods, and the upper limit of normal for serum lactate dehydrogenase was 271 IU/L at our hospital. In addition, a 5-mL sample of pleural effusion was collected in the ethylenediaminetetraacetic acid tube, which was centrifuged at 4°C. Subsequently, the supernatant was frozen at −70°C until the NT-proBNP assay was performed. The storage stability of pleural NT-proBNP has been demonstrated in this study .Pleural NT-proBNP levels were determined in duplicate using the commercially available enzyme immunoassay kit  following the manufacturer's instructions. The test has intra- and inter-assay coefficients of variation of 4–7% and 9–12%, respectively, and a measuring range of 0–640 fmol/mL. Using the manufacturer-provided conversion factor, the upper limit of this range was converted to 5400 pg/mL (1 fmol/mL  = 8.475 pg/mL). Samples with values above the upper limit of detection were assayed again after dilution. The investigators involved in NT-proBNP measurements were unaware of clinical data.Patient records were evaluated in detail to obtain demographics, comorbidities, and events during the ICU stay. The presence of uni- or bilateral pleural effusions was confirmed by chest ultrasound examination. The causes of effusions were determined based on predefined criteria by two independent investigators blinded to pleural NT-proBNP levels. If there was discordance, it was resolved by consensus. Specifically, diagnosis of CHF was made according to clinical symptoms, medical history, physical examination, chest radiography and response to diuretic therapy, and confirmed by echocardiographical evidence of left ventricular systolic dysfunction, severe valvular disease or severe left ventricular diastolic dysfunction. The cause of pleural effusions was ascribed to hypoalbuminemia if the serum albumin level was ≦1.8 g/dL and there were bilateral effusions with no pulmonary parenchymal disease. Malignant pleural effusions were diagnosed if malignant cells were detected on cytological examination of pleural effusions or biopsy specimens. Parapneumonic effusions were associated with the clinical and radiological diagnosis of bacterial pneumonia. Other causes of pleural effusions were defined by clear clinical pictures or established diagnostic criteria. In the present study, the terms transudate or exudate were used to label effusions based on their etiologies rather than on criteria of Light et al. 2 tests. To determine the discriminative power of various cutoffs of NT-proBNP, the receiver operating characteristic (ROC) curve was drawn and the area under the curve (AUC) was calculated. The best cutoff was determined by the Youden index, and the sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated according to standard formulae. A two-tailed P value of <0.05 was considered statistically significant. All data were analyzed using SPSS for Windows version 15.0 .Quantitative variables were presented as means and standard deviations, and were analyzed by the independent sample t-test. Qualitative variables were presented as numbers and percentages, and were analyzed by the Fisher exact or χDuring the study period, pleural effusion samples were collected from 147 medical ICU patients with a mean age of 71 years. Depending on the causal disease of the effusions, 67 were labeled as transudates and 80 were labeled as exudates . The cliIn distinguishing between patients with CHF effusions (n = 38) and patients with non-CHF effusions (n = 109), the AUC for pleural NT-proBNP was 0.87 . The ROCIn all, 6 (16%) of the 38 patients with CHF effusions would have been misclassified by the Light's criteria . Five ofFor the first time, this study evaluated the effectiveness of pleural NT-proBNP in diagnosis of CHF pleural effusions among ICU patients. We demonstrated that NT-proBNP levels in pleural effusions were significantly higher in patients with CHF effusions as compared to the others. For diagnosing CHF effusions, using the ROC curve analysis, pleural NT-proBNP showed an AUC of 0.87, indicating its good, although not excellent, diagnostic accuracy, and an NT-proBNP level of >2200 pg/mL displayed a sensitivity of 89% and a specificity of 73%. Of note, in patients with non-CHF effusions, more than one fourth (27%) of them had pleural NT-proBNP levels of >2200 pg/mL and these patients were more likely to experience septic shock and acute kidney injury than the others.In the past decade, a number of studies assessing the diagnostic utility of pleural NT-proBNP in CHF effusions have been reported In terms of ROC curve analysis, previous studies have demonstrated excellent diagnostic accuracy of pleural NT-proBNP in diagnosis of CHF effusions. Even more surprisingly, Tomcsanyi, Kolditz, and Liao et al. reported an AUC of 0.98–1 A major difference between previous studies and ours is that we specifically enrolled critically ill patients and found a moderate specificity of pleural NT-proBNP in diagnosing CHF effusions. Twenty-seven percent of patients with non-CHF effusions had pleural NT-proBNP levels of >2200 pg/mL. A significantly higher proportion of these patients suffered from septic shock and acute kidney injury as compared to those having pleural NT-proBNP levels of ≦2200 pg/mL. The role of elevated NT-proBNP levels in cardiovascular diseases is well established Light's criteria remain the reference standard for distinguishing transudates from exudates and are always applied in the first step in the evaluation of pleural effusions One limitation of the present study needs to be addressed. The kit for assaying NT-proBNP in this study differs from the commonly used electrochemiluminescence immunoassay for NT-proBNP offered by Roche Diagnostics; however, the diagnostic cutoff of NT-proBNP we established is well within the range reported in other studies using the Roche assay In conclusion, the diagnostic accuracy of pleural NT-proBNP in differentiating between CHF and non-CHF effusions remains good in critically ill patients, although its diagnostic specificity is moderate. Pleural NT-proBNP levels of ≦2200 pg/mL virtually exclude diagnosis of CHF effusions; however, NT-proBNP levels of >2200 pg/mL in pleural effusions should be interpreted with caution. Patients with non-CHF effusions may have pleural NT-proBNP levels above the best cutoff if they experience septic shock or acute kidney injury. This study suggests that pleural NT-proBNP and Light's criteria should be complementary to each other in the diagnostic approach of pleural effusions and clinical context should be taken into account when interpreting pleural NT-proBNP values in the ICU setting.S1 FigureScatterplot with linear regression showing the storage stability of pleural N-terminal pro-B-type natriuretic peptide (NT-proBNP). Thirty pleural effusion samples were assayed for NT-proBNP both immediately after sample collection and at approximately one month after storage at −70°C.(TIF)Click here for additional data file.


P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF  and positively with LV end-diastolic dimensions , LV end-systolic dimensions , and left atrial diameters . A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF . These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4,  Members of the cathepsin family were original identified as proteases that act the lysosome –3. RecenWe recruited 134 consecutive patients with CHF who were admitted to Yanbian University Hospital  between March 2012 and March 2014 for the in-hospital treatment of decompensation of CHF. All enrolled patients had New York Heart Association (NYHA) functional class II–IV and CHF with a reduced ejection fraction of ischemic , hypertension (diagnosis of primary hypertension), and idiopathic dilated cardiomyopathic etiologies. These CHF patients were taking standard medical therapeutics with diuretics, inotropic agents , statins, a β-blocker, angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin type 1 receptor blockers (ARBs). We divided the CHF patients into two groups by their left ventricular (LV) ejection fraction (LVEF) values: the 44 patients showing LVEF < 40% (the “lowLVEF” group) and the 90 patients showing LVEF values ≥ 40% (the “highLVEF” group).Based on the elevation of cardiac biomarkers (at least one positive biomarker: creatine kinase-MB or troponin T), an electrocardiogram indicative of new ischemia (new ST-T change or new left bundle branch block), and a history of prolonged chest pain, acute myocardial infarction was diagnosed . We defiPatients with prior evidence of end-stage renal disease with maintenance hemodialysis, congenital heart disease, pericarditis, primary valvular disease, hypertrophic cardiomyopathy, acute myocarditis, or secondary cardiac muscle disease caused by any known systemic condition, were excluded. This study protocol was approved by the Ethics Committee of Yanbian University Hospital, and written informed consent was obtained from all patients.Venous blood samples were obtained for chemical analysis after an overnight fast. Serum CatK levels were evaluated by using enzyme-linked immunosorbent assay (ELISA) kits  in duplicate. The levels of N-terminal pro-brain natriuretic peptide (NTproBNP), troponin I, low-density lipoprotein (LDL), high-density lipoprotein (HDL), high-sensitive C-reactive protein (hs-CRP), and hemoglobin A1c were studied at the clinical laboratory of Yanbian University Hospital . We presented circulating CatK values as ng/mL.We performed echocardiography using a Sonos 2500 ultrasound system  equipped with a 2.5- to 3.5-MHz transducer . The LV t-test or a one-way analysis of variance (ANOVA) followed by a Tukey post hoc test. The levels of hs-CRP, NTproBNP, and troponin I were logarithmically transformed because the data showed a skewed distribution. If the homogeneity of variance assumption was violated, the nonparametric Kruskal-Wallis test was used instead. The correlation analysis was performed using a linear regression analysis. The factors that related at the P < 0.1 level were isolated as independent variable candidates for the multiple logistic regression analysis, which was used to evaluate the independent contribution of clinical parameters to CHF. StatFlex  was used for all statistical analyses. P-values < 0.05 were considered significant.Continuous variables are expressed as mean 6 SD or as median and interquartile range for nonparametric variables. Categoric variables were compared with the Pearson chi-square test or the Fisher exact test. Comparison of continuous variables between groups was performed with the unpaired Student’s The patient characteristics are presented in P < 0.01), LVDs , and LAD  values compared to the highLVEF patients.There were no significant differences in IVST or LVPWT between the lowLVEF and highLVEF groups . As antiP < 0.001), whereas there were no significant differences in blood Na+, lipid profile (LDL and HDL), hemoglobin A1c, creatinine clearance rate, hs-CRP, NTproBNP, or triponin I between the groups.As shown in r = −0.4, P < 0.001) and correlated positively with the LVDd  and LVDs  levels . However, there were no correlations between the levels of CatK and the patients’ ages  or BMI .Our linear regression analysis showed that the CatK levels correlated negatively with the LVEF  levels . There wP < 0.05), LAD , LVDd , and the CatK  levels were significantly correlated with CHF . Third, we excluded patients with congenital heart disease, end-stage renal disease with maintenance hemodialysis, primary valvular disease, pericarditis, hypertrophic cardiomyopathy, or secondary cardiac muscle disease. It is unclear how their exclusion or inclusion would influence our current findings.In summary, present findings suggested that the evaluation of peripheral blood CatK may provide a noninvasive way of showing and monitoring both the mechanism and extent of cardiac remodeling and dysfunction in CHF patients. However, further investigations and prospective clinical trials that elucidate the exact role of CatK-related proteolysis in CHF and the importance and value of screening proteolysis and extracellular matrix degradation in clinical settings will be required to conduct near future.S1 Fig(PDF)Click here for additional data file.S1 Table(PDF)Click here for additional data file.S2 Table(PDF)Click here for additional data file.S3 Table(PDF)Click here for additional data file.S4 Table(PDF)Click here for additional data file.


In logistic regression model, it was observed that only resting HR, diabetic neuropathy, and retinopathy were independent associated with CAN. In conclusion, CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications. Indicators of CAN included age, diabetes duration, hypertension, resting HR, diabetic neuropathy and retinopathy, and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for CAN.Cardiovascular disease (CVD) is the leading cause of mortality in patients with type 1 diabetes (T1D). The cardiovascular autonomic neuropathy (CAN), although considered as an independent risk factor for CVD, remains underdiagnosed. The aim of this paper was to determine the prevalence, predictors of CAN in patients with T1D and its association with other chronic complications of diabetes. Patients with T1D underwent a clinical-epidemiological survey, had blood and urinary samples collected, performed ophthalmoscopic and clinical neurological examination and cardiovascular reflex tests. One hundred and fifty one patients with T1D, 53.6% female, 45.7% Caucasian, mean age of 33.4 ± 13 years, diabetes duration of 16.3 ± 9.5 years, and glycated hemoglobin levels of 9.1 ± 2% were evaluated. The prevalence of CAN in the studied population was 30.5%. CAN was associated with age ( Type 1 diabetes (T1D) is the most common endocrine disorder of childhood and adolescence affecting about 10–20 million people worldwide –5.Cardiovascular autonomic neuropathy (CAN) although considered a common diabetic chronic complication  and assoDepending on the methodology and diagnostic criteria, the prevalence of CAN ranges from 2.6 to 90% among patients with diabetes and its prevalence increases with age, diabetes duration, and inappropriate glycemic control , 9 and mCardiovascular autonomic neuropathy has been identified as a strong predictor of CVD in both patients with T1D and type 2 diabetes (T2D). Patients with diabetes and CAN have 5-year mortality rates ranging from 16 to 53%, depending on its severity .Detection of silent myocardial ischemia in asymptomatic diabetic subjects) conducted in patients with T2D, the presence of CAN, determined by abnormal Valsalva ratio, was a strong predictor of silent myocardial ischemia, regardless of the presence of traditional cardiovascular risk factors such as hypertension, age, sex, and smoking (In the DIAD study ( smoking –13.Data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study showed that patients with CAN presented mortality rate approximately 1.55–2.14 times higher than patients without CAN  using the variation of RR intervals of the electrocardiogram are sensitive and specific methods used for the early detection of CAN and seven parameters can be used to assess the presence of CAN: the three spectral analysis frequency bands  and four tests proposed by Ewing  , 18.The consensus of Diabetic Neuropathy Conference held in San Antonio in 1992 , of the The time and frequency-domain HRV parameters seem to be more sensitive and changes in HRV may occur earlier than alterations on cardiovascular reflex tests. Tannus et al.  showed tConsidering the paucity of data in the literature on the prevalence of CAN in the Brazilian population with T1D, this study aimed to determine the prevalence of CAN in Brazilian patients with T1D and to identify clinical and laboratory factors associated with the presence of CAN.This study is a cross-sectional study conducted in patients with T1D attended in the diabetes unit of State University of Rio de Janeiro. Written informed consent for the study was obtained from all of the patients aged 18 years or older or from the parents or guardians of the patients younger than 18 years. The study was approved by each local center’s ethics committee.The inclusion criteria were patients with T1D, defined by a physician based on the criteria of American Diabetes Association (ADA) and Brazilian Diabetes Society (BDS), which include age less than 40 years old at diagnosis, typical clinical presentation , or history of diabetic ketoacidosis or ketonemia and need to use insulin without interruption since the diagnosis; age ≥13 years and diabetes duration ≥5 years. Exclusion criteria were pregnancy, lactation, chronic alcoholism, congestive heart failure, cardiac arrhythmias, acute respiratory failure or severe obstructive lung disease, infections, and acute complications of diabetes.2)], systolic (sBP) and diastolic blood pressure [dBP (mmHg)], HR, ethnicity, age at diagnosis (years), duration of diabetes (years), smoking status, alcohol consumption, daily insulin dose, use of other medications, and associated diseases.The following clinical and demographic data were obtained through an interview during a clinical visit: sex, age (years), weight (kg), height (m), body mass index , creatine phosphokinase (CPK), thyroid stimulating hormone (TSH), free T4, cyanoconalamin, and C-reactive protein (CRP). The low-density lipoprotein (LDL) was calculated using the Friedewald formula , when the values of triglycerides did not exceed 400 mg/dl .Screening for retinopathy by fundoscopy and nephropathy by albuminuria and determination of glomerular filtration rate (GFR) was performed.2  and neuropathic impairment score (NIS) , 34.The evaluation of CAN was performed according to the protocol described elsewhere . BrieflyAutonomic tests were performed in the morning. Subjects were instructed to assume the supine position in a metabolic unit with a controlled temperature (23°C) after an overnight fast or at least 2 h after a light meal  standardized by a dietitian.After 5 min of rest in the supine position with the head elevated 30° and after 5 min of breathing spontaneously, an electrocardiogram (EKG) was recorded for 300 s using a computer. The EKG was analyzed by a mathematical algorithm (fast Fourier transform) and expressed in a diagram of oscillation amplitude (HR variations per second) versus frequency (Hz).The autonomic tests are described below. After each test, a resting period of 1 min was scheduled to prevent influences by the previous tests.The subject was kept in the supine position for at least 1 min and then invited to start the test with a deep inspiration to the maximum total lung capacity for 5 s, which was followed by a forced expiration down to the residual volume for 5 s. The time to alternate the respiratory cycle is signaled directly to the patient by the operator. Such a respiratory cycle was repeated three times. The expiration:inspiration ratio (E:I ratio) was determined by the ratio between the longest and shortest RR intervals obtained during the expiration and inspiration cycles, respectively, and the highest E:I ratio was considered .Without taking a deep breath beforehand, the subject, who was in the supine position, was invited to blow with an open glottis into a mouthpiece connected to a manometer and to maintain a constant expiratory effort equivalent to an intraoral pressure of 40 mmHg for 15 s. This test induces a physiological tachycardia, which persists for a maximum of approximately 14 s. After this period, the expiratory straining is suddenly released, and the subject should breathe regularly and remain silent and motionless until the end of the test. An EKG was continuously recorded for 70 s, when the physiological bradycardia is observed. The Valsalva ratio was determined by the ratio between the longest and shortest RR intervals. The occurrence of facial flushing, plethora, and neck vein engorgement testify to the correctness of the maneuver . The tesAfter lying in the supine position for at least 5 min, the subject was invited to stand up quickly but remain relaxed with their arms at rest alongside the body and without speaking or moving until the end of the test (180 s after standing up). The 30:15 or maximum:minimum (max:min) ratio was determined by the ratio between the longest (maximum bradycardia at approximately the 30th beat) and shortest (maximum tachycardia at approximately the 15th beat) RR intervals.After at least 5 min of supine rest, the blood pressure was measured at baseline and after 3 min of standing. A drop in the systolic blood pressure that was higher than or equal to 20 mmHg was considered abnormal , 24.The diagnosis of incipient and defined CAN was considered in the presence of one and two abnormal cardiovascular reflex tests, respectively , 35.t-test and Mann–Whitney test for variables with normal or skewed distribution, respectively. The chi-square test was used to compare the frequencies of two categorical variables. A Pearson’s correlation coefficient was calculates when applicable. Adjustments were made for potential confounders. A binary logistic regression was performed with diagnosis of CAN (yes/no) as the dependent variable. The following independent variables were included: sex, age, diabetes duration, pulse pressure, resting HR, BMI, hypertension, presence of micro or macroalbuminuria, presence of diabetic neuropathy and retinopathy, HbA1c, urea, creatinine, LDL cholesterol, and hemoglobin. Odds ratios with 95% confidence intervals (CI) were performed when indicated. A two-sided p-value less than 0.05 was considered significant.The statistical analysis was performed using Statistical Package for Social Sciences (SPSS) for Windows (version 13.0). The data are presented as mean ± SD and median (minimum–maximum). Comparison between numeric variables was performed using One hundred and fifty-one patients with T1D were evaluated. Clinical and demographic data for the study population are presented in Table p = 0.074). Data about the prevalence of CAN according to the diagnostic criteria are shown in Table Table p = 0.000), postprandial nausea (p = 0.042), early satiety (p = 0.031), sexual dysfunction (p = 0.049), and gustatory sweating (p = 0.018).The prevalence of autonomic symptoms in the general population, in patients with and without CAN is shown in Table p = 0.01), diabetes duration (p = 0.036), hypertension (p = 0.048), resting HR (p = 0.000), HbA1c (p = 0.048), urea (p = 0.000), creatinine (p = 0.008), GFR (p = 0.000), urinary albumin concentration (p = 0.000), LDL-cholesterol (p = 0.048), free T4 (p = 0.023), and hemoglobin (p = 0.01) (Table p = 0.011).The clinical and laboratory predictors of CAN found in the studied population were age (1) Table . All mic1) Table . Only 1 After logistic regression model using diagnosis of CAN by cardiovascular reflex testes as a dependent variable and sex, age, diabetes duration, pulse pressure , resting HR, BMI, hypertension, albuminuria, presence of diabetic neuropathy and retinopathy, HbA1c, urea, creatinine, LDL, and hemoglobin as independent variables, it was observed that only resting HR, presence of diabetic neuropathy and retinopathy were significantly independent variables associated with the diagnosis of CAN Table .In the present study, the prevalence of incipient, defined, and total CAN in patients with T1D and T1D duration ≥5 years was 19.2, 11.3, and 30.5%, respectively when used only cardiovascular reflex tests; 6.6, 33.8, and 40.4% when using the HRV parameters  and 9.3, 25.8, and 35.1% when used both criteria. The prevalence of CAN assessed by cardiovascular reflex tests was lower than the prevalence reported in the literature (11.3 versus 25%), but quite similar when using cardiovascular reflex tests associated with the HRV parameters  (25.8 versus 25%). As we can see, the prevalence of CAN defined by HRV  was superior to cardiovascular reflex tests, which could corroborate the data from the literature regarding the sensitivity and early detection of cardiovascular autonomic dysfunction by this diagnostic criterion. However, the diagnosis of CAN based only on spectral analysis must be carefully considered since previous study from our group (19) demonstrated that the assessment of HRV by spectral analysis  showed low reproducibility.The agreement of CAN diagnosis for the two diagnostic methods  was moderate. Therefore, analysis of CAN using only frequency-domain HRV analysis should be considered an additional tool for CAN diagnosis according to other studies –18, 36.The incidence of CAN increases with age, diabetes duration and poor glycemic control.  In this study, clinical and laboratory predictors of CAN were age, T1D duration >10 and 20 years, hypertension, resting HR, HbA1c, LDL-c, urea, creatinine, free T4 and hemoglobin, and the presence of retinopathy, nephropathy and diabetic peripheral neuropathy. Slightly higher levels of free T4, even within the normal range were found in patients with T1D and CAN, possibly suggesting a sympathovagal imbalance .Some studies showed that CAN can reduce the renal release of erythropoietin probably by renal denervation, leading to the development of anemia , 38. In However, it is difficult to differentiate whether the anemia was a result of CAN or diabetic nephropathy since these two diabetic complications are frequently associated.Several studies have suggested a causal relationship between CAN and diabetic nephropathy , 40. ForInflammatory markers such as CRP and IL-6 have been correlated with abnormal HRV . Ridker Autonomic symptoms, although disabling, appears in more advanced stages of CAN, have low sensitivity and specificity and have low association with abnormal cardiovascular reflex tests , 17, 18.This study is one of the first studies that evaluated the prevalence of CAN assessed by the gold standard cardiovascular reflex tests as recommended by the ADA in the Brazilian population, thus allowing the identification of patients with T1D and increased cardiovascular risk. Moreover, this study allowed the identification of some clinical factors that might suggest the diagnosis of CAN.The study had some limitations. Because this was a cross-sectional study we could not establish a causal relationship between the predictors and the diagnosis of CAN. Another limitation is related to data collection on hypoglycemia. Patients self-reported the number and severity of hypoglycemic episodes in the last month. It was not possible to obtain data through the glucometer of all patients, which could underestimate the prevalence of hypoglycemia.In conclusion, CAN is a common chronic complication of T1D affecting about 30% of the studied population and is associated with the presence of other chronic complications of T1D. Indicators of the presence of CAN included age, duration of diabetes, presence of hypertension, resting HR, presence of diabetic neuropathy and retinopathy and symptoms suggestive of autonomic neuropathy. This study confirms the importance of systematic and early screening for this complication.Lucianne Righeti Monteiro Tannus and Marilia Brito Gomes researched data, drafted the manuscript. Karla Rezende Guerra Drummond, Eliete Leão da Silva Clemente, and Maria de Fátima Bevilacqua da Matta contributed to the conception of the work and the acquisition of data for the work. Lucianne Righeti Monteiro Tannus and Marilia Brito Gomes reviewed the manuscript and contributed to the discussion. The writing group takes final responsibility for the paper and is the study guarantor.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.


The aim of the present study was to investigate whether central AT1R blockade attenuates the excess BP elevation in rest-to-active phase in hypertensive rats or not. Stroke-prone spontaneously hypertensive rats (SHRSP) were treated with intracerebroventricular infusion (ICV) of AT1R receptor blocker (ARB), oral administration of hydralazine (HYD), or ICV of vehicle (VEH). Telemetric averaged mean BP (MBP) was measured at early morning (EM), after morning (AM), and night (NT). At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD. At NT, MBP was also significantly lower in ARB than in HYD. These results in MBP were compatible to those in sympathoexcitation and suggest that central AT1R blockade attenuates excess BP elevation in early active phase and continuous BP elevation during rest phase independent of depressor response in hypertensive rats. Abnormal blood pressure (BP) elevation in early morning is known to cause cardiovascular events. Previous studies have suggested that one of the reasons in abnormal dairy BP variability is sympathoexcitation. We have demonstrated that brain angiotensin II type 1 receptor (AT Hypertension is established as a major risk factor for cardiovascular disease, and antihypertensive treatments are necessary to prevent the cardiovascular events . We have1R) in the RVLM decreases blood pressure with sympathoinhibition and improvement of baroreflex sensitivity via reduction of oxidative stress [1R blockade attenuates the excess blood pressure elevation in early active phase (mimicking early morning surge) with sympathoinhibition and improvement of baroreflex in hypertensive rats and if so to determine whether the benefit was independent of depressor response or not.Sympathetic nerve activity is mediated by brain, especially by rostral ventrolateral medulla (RVLM) known as vasomotor center , 11. In e stress , 17, 18.1R receptor blocker , treated with oral administration of hydralazine , and treated with ICV of vehicle  for 2 weeks.The study protocol was reviewed and approved by the Committee on the Ethics of Animal Experiments at the Kyushu University Graduate School of Medical Sciences and conducted according to the Guidelines for Animal Experiments of Kyushu University. Experiments were performed on male stroke-prone spontaneously hypertensive rats (SHRSP) as a hypertensive model with sympathoexcitation . SHRSP were divided into 3 groups, treated with intracerebroventricular infusion (ICV) of AT−1·day−1) in artificial cerebrospinal fluid (aCSF) was infused at 0.5 μL/h for 14 days by using an osmotic minipump  into the right lateral cerebral ventricle of the brain, as described previously [μL/h for 14 days by using an osmotic minipump.In ARB, losartan  and heart rate (HR) were measured using the UA-10 radiotelemetry system  as described previously , 18, 20.We assessed sympathoexcitation by spectral analysis using an adaptive autoregressive model to provide power spectra for systolic blood pressure (SBP). The low-frequency power of SBP (integrating the spectra between 0.04 and 0.15 Hz) was computed by MATLAB , and sympathoexcitation is presented as the normalized unit of the low-frequency component of SBP (LFnuSBP), as previously done in our and other studies , 20–22.We assessed baroreflex sensitivity by spontaneous sequence method, as done in our and other previous experiments , 23, 24.t-test was used to compare the parameters in each group. Differences were considered significant when the P value was less than 0.05.All values are expressed as the mean ± SEM. An unpaired At EM, MBP was significantly lower in ARB to a greater extent than in HYD compared to VEH, though MBP at AM was the same in ARB and HYD . At NT, Throughout a day, HR was significantly lower in ARB than in HYD and VEH .LFnuSBP was shown in Throughout EM, AM, and NT, baroreflex sensitivity was significantly higher in ARB than in HYD and VEH . In HYD,1R blockade would attenuate the excess blood pressure elevation in early active phase and continuous blood pressure elevation during rest phase independent of depressor response in hypertension and that these benefits of central AT1R blockade on dairy blood pressure variability might be due to sympathoinhibition with baroreflex improvement.Our obtained new findings were as follows. (1) At EM and NT, MBP was decreased in ARB to a greater extent than in HYD. (2) At AM, MBP was the same in ARB and HYD. (3) Throughout EM, AM, and NT, LFnuSBP was significantly lower in ARB than in VEH and HYD, and (4) baroreflex sensitivity was improved in ARB, but not in HYD. These results suggest that central AT1R blockade attenuates the excess blood pressure elevation in early active phase. Dairy blood pressure variability and/or morning surge is associated with abnormal regulation of sympathetic nerve activity [1R blockade causes depressor response with sympathoinhibition [1R blockade on MBP at EM was not due to depressor response itself. Interestingly, the benefit at EM was also determined during rest. In the clinical aspects, central AT1R blockade could archive dipper type dairy blood pressure variability in hypertension. We should assess dairy blood pressure variability, especially MBP at EM and NT, not only at active phase.The most impressive results were that central ATactivity , and we hibition , 17, 18.1R blocker improved the impaired baroreflex sensitivity with sympathoinhibition and antioxidant effect in the brain of hypertensive rats [1R-induced oxidative stress in the brain causes sympathoexcitation [1R-induced oxidative stress in the brain should worsen blood pressure variability via sympathoexcitation with baroreflex dysfunction. To determine these aspects, we calculated baroreflex sensitivity by spontaneous sequence method and demonstrated that baroreflex sensitivity was significantly higher in central losartan-treated SHRSP than in hydralazine- or vehicle-treated SHRSP throughout EM, AM, and NT. These results strongly support the conclusion that central AT1R blockade improves blood pressure variability via sympathoinhibition with improvement of baroreflex.In the aspects of mechanisms, we also consider that central infusion of losartan could improve baroreflex sensitivity, resulting in the improvement of blood pressure variability. Previously we demonstrated that central infusion of ATive rats . AT1R-incitation , 18, andcitation , 20. Con1R blocker is beneficial to abnormal blood pressure elevation, as previously shown in our and other works [1R expression in cardiovascular center and do not have the data of angiotensin II content and AT1R expression in RVLM in early morning, after morning, and night. Previous reports indicated that systemic circulatory and tissue renin-angiotensin system are significantly higher at active than at rest phase and that these abnormal circadian rhythms are attenuated by AT1R blocker [1R has circadian rhythm [1R in cardiovascular center strongly at angiotensin II-AT1R activated phase (night-active) and would improve the abnormal circadian rhythm of blood pressure. However, to assess more concrete mechanisms in which intracerebroventricular infusion of losartan improves blood pressure variability, it would be necessary in further examination to determine whether angiotensin II content and AT1R expression in cardiovascular center have circadian rhythm or not.Although we showed that central application (intracerebroventricular infusion) of ATer works , 19, we  blocker –27. Moren rhythm . Conside1R as the suitable target of the treatment with AT1R blockers. Recently, we have suggested that the beneficial effects on central AT1R were different among oral-administered AT1R blockers [1R blockers affecting central AT1R.Our results proposed a novel clinical aspect. We had better focus on the central ATblockers . To arch1R blockade potentially attenuated excess blood pressure elevation in early active phase and continuous blood pressure elevation during rest phase via sympathoinhibition with improvement of baroreflex, independent of depressor response in hypertensive rats.Central AT


Home (HBPM) and ambulatory (ABPM) blood pressure measurements have their advantages and disadvantages in diagnosing and managing hypertension. We studied HBPMs and ABPMs in volunteers taking part in a survey.(Part 1); 175 also provided data on ABPMs, of which the measurements obtained between 6 am and 10 pm were used in this study (Part 2).Of 366 respondents, 270 provided a total of 5997 triplicate HBPMs Part 1, When all 5997 triplicate HPPMs were considered, 1st readings tended to be significantly higher than those of the 2nd and 3rd for both, systolic and diastolic pressures, but when the consideration was restricted to the very first triplicate of each of the 270 subjects, this was true only for systolic HBPM. Part 2, The ABPMs tended to have a wider range than the corresponding HBPMs, and to be distributed towards higher values. Of the non-parametric indices of (ABPM - corresponding HBPM),  all but the minima had positive values.In triplicate HBPMs, the first measurement is usually but not always the highest. Increasing the number of triplicates provided by each subject increases the chance of discriminating between measurements in the triplicates. ABPMs tended to be higher than the corresponding HBPMs. There is little point nowadays in simply classifying people as “hypertensive” or “non-hypertensive” purely on the basis of one blood pressure measurement - no matter by what means or how confidently it may have been made. For some applications  it is important to be confident about baselines and the changes that may occur with medication. For other applications such as assessing cardiovascular risk, additional factors are at least as important as the blood pressure measurement and choice of the means by which blood pressure is measured may be less critical.Home and ambulatory blood pressure measurements  have their advantages and disadvantages in diagnosing and managing hypertension. Subjects who are taught to use the devices can carry out HBPMs, away from many of the disturbances present in clinical settings, but the time and effort required of the subject place a limit on the number and timing of the measurements that can be made. This is irrespective of recommendations made in various guidelines-4. ABPM We have used data from a blood pressure screening program in order to examine:(i) The discriminating power offered by more numerous HBPMs for distinguishing the first measurement in a triplicate from the second and third;(ii) The difference between ABPM and HBPM in the same subject.http://www.uniklinik-freiburg.de/rechtsmedizin/forschung/phytomedizin.html, details to original articles).The protocol for this single-centre surveillance study was approved by the Committee for Human Ethics of the Kanton Luzern/Switzerland. The study was advertised locally by word of mouth and by flyers distributed in the hospital, inviting would-be participants to contact the Department “Arbeitsmedizinischer Dienst” of the Kantonsspital Luzern. Exclusion criteria included a need for immediate antihypertensive treatment, angina pectoris, atrial arrhythmia, vitium cordis with haemodynaemic impairment, chronic renal or liver diseases and actual or contemplated pregnancy. After written informed consent and assessments of baseline conditions with a standardized questionnaire, blood pressure was measured by the staff using a boso-medicus PC oscillometric device validated according to the AAMI and BHS protocol (grading A/A), Bosch + Sohn GmbH u. Co KG, Jungingen  Participants were then shown how to measure their own blood pressure correctly. Standard size 12 cuffs were used except in patients whose arm circumference exceeded 33 cm, for whom size 15 cuffs were used. They were asked to try to undertake HBPMs three times a day  for the surveillance period. Each measurement was to be made in triplicate, 2 minutes apart, after resting seated for at least 10 minutes, and at least 2 hours after any coffee or smoking. Heart rate was recorded simultaneously. Seven to 10 days later, the HBPM profile was printed out.(ii) Those participants whose HBPM exceeded 125/80 mmHg on average over the surveillance period were invited to participate in a comparison of ABPM and HBPM. The ABPMs were made on the same arm as for the HBPM, using boso TM-2430 PC oscillometric devices. These devices, graded A/A, (best category for systolic and diastolic measures), were validated according to the protocol of the Advancement of Medical Instrumentation and British Hypertension Societies. ABPMs were made every 15 min from 6 am to 10 pm and participants were asked to try to keep the arm still during each measurement. . After the 24 hours of recording, the participant returned to the “Arbeitsmedizinischer Dienst” with a record of his or her activities of the day and the quality of the night’s rest. The data were transferred to the software boso-profilmanager 2 (descriptions of the handling of the devices and data transfer are placed on the above mentioned website).Statistical analysis was carried out using the UNIVARIATE, NPAR1WAY and CORR procedures in SAS 9.2, and the figures were plotted using Microsoft Excel.For a subsidiary investigation into whether there was a gender-related difference in median HBPM in the 347 patients who supplied an adequate number of readings, we used the Multiple Regression procedure in Microsoft Excel to regress participants’ ages, weights, heights and a dummy variable for gender against the median HBPM. We also did it for the 175 participants who were selected by the blood pressure criterion of 125/85 for the comparison between HBPM and ABPM.The characteristics recorded for the 366 consecutively recruited participants are summarised in Table When all participants were considered, maleness was associated with a significantly higher median HBPM than femaleness, even when age, height and weight were allowed for, but this was not so for the 175 patients who were selected for ABPMs. In the sample of 347 participants patients, the ratio of males to females was 1.012:1. In the sample of 175 selected by the blood pressure criterion, the ratio was 1.1875 to 1. Details are given on the webpage.Of the participants whose average HBPM exceeded 125/80, 175 had reasonably complete BPM sets with a mean of 45 systolic HBPM daytime readings (15 triplicates) per participant and 63 systolic ABPM daytime readings  are placed on the above mentioned website.In each sub-plot of Figure This was a purely observational study with no intervention and no prospective hypothesis to test. Any references to “statistical significance” are notional rather than definitive.There is disagreement between guidelines for self-measured BPMs at home: (i) the European Society of Hypertension and the Nonetheless, the differences between triplicates have been sufficient in at least one study for the diagnosis of “hypertension” to be made more frequently with the first than with the mean of the 2nd and 3rd. ConsequSome of the guidelines recommend discarding the higher HBPMs that are often measured initially, but this refinement had no impact in explanatory modelling of cardiovascular risk or organvariability in HBPM had an additional predictive power beyond mean systolic HBPM only in hypertensive patients[Timing of the HBPMs and choice of subject may also be important. For example, in a mixture of normotensives and hypertensive patients seen in the clinic, evening HBPMs predicted stroke more reliably than casual HBPM regardless of the number of measurements. On the patients.Kawabe et al. reportedThe gender differences obtained in our small sample were consistent with those in the review by Reckelhoff.self-measured HBPMs can only be obtained while the patient is awake. The best agreement between ABPM and HBPM appeared to be in the morning between the first HBPM of the day and the mean of the 4 observations taken in the second hour after the patient had wakened[daytime ABPMs and HBPMs.ABPM was developed before HBPM and remains more copiously documented. It can also identify a larger number of features than either clinic or HBPM . It has wakened. We haveA systematic review including six comparisons of HBPM and ABPM found that blood pressures over the criterion of 135/85 mmHg were obtained more frequently overall with HBPMs, the difIt is a plausible conjecture that the behaviour of the measurements at the extremes of their range may be partly due to movement-related measurement artefacts in the ABPMs: the subject may be less inclined to interrupt his or her activity every 15 minutes for the duration of each ABPM whereas he or she might be more likely to stop and be settled for the HBPMs, at least by the time the 2nd and 3rd measurement in each triplicate has been made. The relative symmetry of both distributions in our Figure longer-term monitoring is that because of resource limitations, facilities for ABPMs are usually only available over a shorter time and are more intrusive on activities of daily living.Irrespective of whether it is the ABPM or HBPM that gives a “truer” picture of whether or not a subject should be labelled “hypertensive” at a particular time, we have argued previously on pragmatic grounds that the(1) Numbers of observations do matter. Recommendations for types and numbers of BPM should take into account the stringency required for the purpose to which the BPMs are being put.(2) A more effective harmonization of guidelines is desirable when studying the effects of interventions on blood pressure, not least if those studies are to be included in systematic reviews and meta-analyses(3) Resource limitations, and the time-scale required for the measurements have an important bearing on which measurement technique to use and how many measurements to make.The authors declare that they have no competing interests.All authors have made substantial contributions. Conception: SC-H, PE. Design: SC-H, PE. Acquisition of data: CC (†), BW. Statistical analysis: JS-M. Interpretation of data: SC-H, PE and AB (acknowledged). SC-H wrote the draft which was revised critically for important intellectual content by all authors except CC who died in a tragic accident. All authors except CC have given final approval of the version to be published. Each author should have participated sufficiently in the work to take public responsibility for appropriate portions of the content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2261/14/94/prepub