Non-enzymatic glycation increases hemoglobin-oxygen affinity and reduces oxygen delivery to tissues by altering the structure and function of hemoglobin.2) in type 2 diabetic patients during mechanical ventilation or oxygen therapy.We investigated whether an elevated blood concentration of glycosylated hemoglobin (HbA1c) could induce falsely high pulse oximeter oxygen saturation (SpO2) and partial pressure of oxygen (PO2) were determined with simultaneous monitoring of SpO2 in 261 type 2 diabetic patients during ventilation or oxygen inhalation.Arterial oxygen saturation  and SpO2  were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% , but PO2 did not significantly differ between the two groups. Bland-Altman analysis demonstrated a significant bias between SpO2 and SaO2  and limits of agreement (0.76% and 2.92%) in patients with HbA1c >7%. The differences between SpO2 and SaO2 correlated closely with blood HbA1c levels .Blood concentration of HbA1c was >7% in 114 patients and ≤ 7% in 147 patients. Both SaO2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.Elevated blood HbA1c levels lead to an overestimation of SaO PatientPeripheral venous blood was collected after an overnight fasting in all patients, and serum levels of glucose, blood urea nitrogen, creatinine, total cholesterol, low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides were measured with standard laboratory techniques on a Hitachi 912 Analyzer . Hemoglobin concentrations were determined with a model T-890 Coulter . In order to exclude individuals with abnormal hemoglobin, electrophoresis was carried out according to the method of Marengo-Rowe. Blood H2 monitoring with pulse oximetry. Blood was drawn anaerobically into a preheparinized 1-mL syringe, and mixed well before measurement. After removal of all air bubbles from the syringe, in vivo pH, partial pressure of carbon dioxide (PCO2), SaO2, partial pressure of oxygen (PO2) and carboxyhemoglobin were directly measured using a Cobas b 221 blood gas analyzer . All measurements were completed within 5 min of blood sampling. Arterial blood gas analysis and SpO2 values were one measurement per patient.Arterial blood gases were determined during simultaneous SpO2 was monitored continuously with a pulse oximetry , which detects oxygen saturation by measuring transdermal light absorption in the blood flow through a fingertip (DS 100A finger probe). SpO2 values were recorded only after a consistent reading, with a strong arterial waveform signal and a pulse reading identical to the patient’s heart rate.SpO2 -SaO2) and HbA1c was analyzed using Pearson correlation coefficients. Accuracy (SpO2 - SaO2) of SpO2 was examined by the method of Bland and Altman analysis[2 and SaO2, precision was determined by the standard deviation of the mean difference, and limits of agreement (mean difference ±1.96SD) was defined as a proportional function of distribution for differences between the 2 measurements. Data were analyzed using the Statistical Packages for Social Sciences . A 2-tailed p value < 0.05 was considered statistically significant. Only one measurement per patient for arterial blood gas and SpO2 was made.Baseline characteristics are expressed as mean and standard deviation (SD) for continuous variables, and percentages for categorical ones. Chi-square test was used to analyze dichotomous variables. Comparisons of continuous variables between groups were made by the appropriate Student’s t tests. Correlation between difference  and SpO2  were significantly higher in patients with HbA1c >7% than in those with HbA1c ≤ 7% , but PO2 did not significantly differ between the two groups.Both SaO2 were slightly elevated in patients with HbA1c >7%, but did not reach statistical significance levels (p >0.05). Body temperature, pH, and carboxyhemoglobin were similar in the two groups   between the two methods was 1.83 ±0.55% (95% CI1.73% -1.94%) and limits of agreement were 0.76% and 2.92% in patients with HbA1c >7%  and bias (1.83 ±0.55%) compared with those with HbA1c ≤ 7%, suggesting that elevated blood HbAlc levels led to an overestimation of SaO2 by pulse oximetry.The present study is the first to demonstrate that despite similar levels of red blood cell 2, 3-DPG, PO2 with SpO2 has become the standard care for patients with critical conditions[2, SaO2 was higher in type 2 diabetic patients with HbA1c > 7%, which is likely due to an increased hemoglobin-oxygen affinity. Our results are in line with previous findings that higher blood concentrations of HbA1c significantly reduce oxygen dissociation velocity[Hypoxemia denotes a condition that is characterized by low oxygen content or percent saturation of hemoglobin with oxygen. Arterianditions,21, to dnditions-25 and tnditions,11,26. Ivelocity. Althougvelocity,29.2 by a mean of 2.7% when compared with those with HbA1c ≤ 7%. Previous studies showed that older women have higher HbA1c than men, even after controlling for body mass index[2 and SaO2 may be mainly related to HbA1c levels as higher HbA1c levels were associated with great differences .The major finding of this study is that in type 2 diabetic patients with poor glycemic control, pulse oximetry overestimated arterial blood gases-determined SaOss index, and accss index. However2 could cause under-diagnosis of hypoxemia in type 2 diabetic patients. Second, because a greater SpO2 was required to achieve the same arterial blood gases-determined PO2 for diabetic patients with HbA1c >7% compared with those with HbA1c ≤ 7%, care should be taken in adjusting oxygen supply during mechanical ventilation or oxygen therapy. The reason for a higher SpO2 than SaO2 may be partly explained by an extensive accumulation of AGE in the skin collagen in patients with poor glycemic control[2 needs to be determined with a high degree of accuracy, arterial blood gases are recommended in type 2 diabetic patients with poor glycemic control.Our findings may be of important clinical relevance. First, falsely high SpO control, interfe control,32. Thes control,34, and 2 because of a specially selected study population as all patients were receiving mechanical ventilation and/or oxygen therapy. The oxyhemoglobin dissociation curves could actually be fitted with non-linear regression, and a partial pressure of oxygen in blood associated to a hemoglobin oxygen saturation of 50% (P50) could also be calculated[2, and control for other effects. By creating a gas pocket with CO2 and O2/N2 mixtures, one can create a much more detailed oxyhemoglobin dissociation curve. The US FDA requires testing balanced by gender and ethnicity. Repeated measures statistics would then be necessary, and P50 is not determined quite as precisely unless the sample is near a SaO2 of 50%. Certainly, it remains unclear whether the issue with diabetic patients would be safe given the possibility of cardiovascular disease, although younger subjects could be reasonable.Due to relatively small sample size, potential for selection bias may raise some concerns on the statistical precision of the estimates. A large-scale study is warranted to confirm our findings. The other major limitation is that most of the data are at high SaOlculated. Most ox2 by SpO2, suggesting that arterial blood gas analysis may be needed for type 2 diabetic patients with poor glycemic control during the treatment of hypoxemia.Elevated blood HbA1c concentrations lead to an overestimation of SaO2: Partial pressure of carbon dioxide; PO2: Partial pressure of oxygen; SaO2: Arterial oxygen saturation; SD: Standard deviation; SpO2: Pulse oximeter oxygen saturation.AGE: Advanced glycation end products; 2, 3-DPG: 2, 3-diphosphoglycerate; CI: Confidence interval; HbAlc: Glycosylated hemoglobin A1c; HDL: High-density lipoprotein; LDL: Lower-density lipoprotein; PCOThe authors declare that they have no competing interests.LJP designed the study and drafted the manuscript; YS collected the samples and performed the experiments; LL participated in the whole process of experiments; RYZ and QZ contributed to data analysis; WFS was responsible for the whole research project and prepared the manuscript. All authors have read and approved the final manuscript.


A number of studies have focused on the association between sphingomyelin (SM) levels and atherosclerosis, however, there are few data concerning the correlation of SM with nondipper hypertension. The present study aimed to investigate the correlation between plasma SM levels and nondipper status in patients with hypertension. A total of 200 hypertensive patients were enrolled and divided into two groups according to their ambulatory blood pressure monitoring (AMBP) results: Dipper group (84 patients) and nondipper group (116 patients). All patients were subjected to transthoracic echocardiography examination and laboratory tests. No statistically significant difference was observed between the two groups in terms of basic clinical characteristics. However, the plasma SM levels in the dipper group were significantly lower than those of the nondipper group . The left ventricular mass index (LVMI) was higher in the nondipper patients than in the dipper patients and the diastolic function parameters in the nondipper patients were less favorable. Correlation analysis showed that the SM level was negatively correlated with the magnitude of systolic blood pressure (SBP) fall at night  and diastolic blood pressure (DBP) fall at night . The nondipper status had contributory effects on hypertensive concentric hypertrophy and diastolic function impairment. In addition, the plasma SM level was associated with a nondipper pattern of hypertension. Essential hypertension is a complex disease associated with an increased risk of cardiovascular disorders. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) is easily able to detect the circadian blood pressure (BP) pattern of an individual: systolic blood pressure (SBP) and diastolic blood pressure (DBP) show a nocturnal reduction of ≥10% in healthy subjects. Patients whose BP does not decrease during sleep compared with daytime levels are defined as nondippers. Nondipper hypertensive patients have been reported to be at high risk for target organ damage, including stroke, left ventricular hypertrophy, carotid artery disease, microalbuminuria, nephropathy and myocardial infarction , serum cSphingomyelin (SM) is a ubiquitous substance present in cell membranes where cellular processes including signal transduction, membrane trafficking and protein sorting occur . Cross-sThe study was conducted on patients who attended the outpatient department of Tongji Hospital Affiliated to Tongji University . The study participants consisted of 200 consecutive hypertensive patients. BP was measured from the right arm using a standard mercury sphygmomanometer after 10 min of rest with the patient in the sitting position. SBP was measured at Korotkoff phase I and DBP at Korotkoff phase V, following recommendations of the American Heart Association . BP was A venous blood sample was collected from each participant under fasting conditions. Fasting blood glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, urea nitrogen, creatinine and uric acid were measured by standard laboratory methods.Plasma SM levels were measured with an enzymatic method using a four-step procedure according to a previous study . In the Ambulatory 24-h BP monitoring was performed using a SunTech Oscar2 ABPM recorder . Automatic BP recordings were obtained every 30 min during the 24-h period. The cuff was placed around the non-dominant arm of the subjects. Daytime was defined as 7:00 a.m. to 11:00 p.m. and nighttime was defined as 11:00 p.m. to 7:00 a.m. The percentage of nocturnal BP dipping was calculated using the following formula: 100 × [1-(nighttime SBP/daytime SBP)]. A nocturnal BP dip was defined as a >10% reduction in both nocturnal SBP and DBP compared with the average day-time BP. Detection of a <10% reduction in either SBP or DBP was regarded as nondipper hypertension.All participants underwent complete transthoracic echocardiographic studies , including two-dimensional, color flow and spectral Doppler imaging, using a 2.5–4.0 MHz transducer. An electrocardiograph was recorded simultaneously for every subject. Echocardiographic measurements were obtained with participants in the left lateral decubitus position. Three consecutive cycles were averaged for each parameter. The examinations were performed by an experienced cardiologist who had no knowledge of the participant's clinical information.3 − (LVDd)3]− 13.6 and BSA (kg/m2) = 0.06 × height + 0.0128 × weight − 0.1529. M-mode tracing of LV was obtained in the parasternal long-axis view with the cursor placed at the tip of the mitral valve leaflets. Left ventricular ejection fraction (LVEF) was estimated using a modified Simpson's biplane method , left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter (LVSd), interventricular septum thickness in diastole (IVST), posterior ventricular septum thickness in diastole (PVST) and left ventricular mass index  were collected. The left ventricular mass (LVM) and body surface area (BSA) were calculated using the formula : LVM (g)e method .Pulsed Doppler recordings of mitral flow velocities were obtained from the apical 4-chamber view by placing the sample volume between the tips of the mitral leaflets and LV outflow velocities were obtained by placing the sample volume in the outflow tract below the aortic valve leaflets. Peak early (E) and late diastolic (A) transmitral filling flow velocities, the E/A ratio and the deceleration time (DT) of the E wave were measured. Isovolumic relaxation time (IRT), defined as the time from aortic valve closure to mitral valve opening, was assessed by simultaneously measuring the flow into the LV outflow tract and mitral inflow by Doppler echocardiography.2 test. Pearson correlation was used to evaluate the association between SM levels and demographics or laboratory parameters. P<0.05 was considered to indicate a statistically significant result.Statistical analyses were made using SPSS  software. Numerical variables are presented as mean ± standard deviation and categorical variables are presented as percentage values. The Student's t-test was used for group comparisons. The Mann-Whitney U test was used for comparison of abnormally distributed data. Categorical data were compared with the χAccording to 24-h ABPM monitoring, dipper and nondipper hypertension was noted in 84 patients (42%) and 116 patients (56%), respectively. Comparisons of clinical and biochemical variables in the dipper and nondipper groups are shown in The ABPM parameters of the patients are summarized in 2, P=0.02; 122.8±12.1 vs. 108.9±14.6 g/m2, P=0.007; 234.9±19.5 vs. 211.3±25.4 msec, P=0.03; and 100.1±7.3 vs. 85.7±8.2 msec, P=0.02, respectively), while the E/A ratio was lower in the nondipper group than in the dipper group .The results of the echocardiographic examinations are shown in In correlation analyses, the plasma SM level was identified to be negatively correlated with the magnitude of SBP fall at night (r=−0.42, P<0.01; In this study, it was demonstrated that the LVMI and left ventricular diastolic parameters were less favorable in the nondipper hypertensive group compared with the dipper group. In addition, plasma SM levels were significantly increased in nondipper hypertensive patients compared with those in dipper hypertensive patients. Furthermore, plasma SM levels were negatively correlated with the fall in SBP and DBP at night. To the best of our knowledge, this is the first study to investigate the association between plasma SM levels and the BP nondipper pattern.A 24-h ABPM is an effective, reliable, noninvasive and inexpensive method for BP ambulatory measurement and circadian rhythm determination. Based on the ABPM results, hypertension may be easily classified as dipper or nondipper pattern. The nondipper pattern has been demonstrated to be associated with an increased risk of cardiovascular, cerebrovascular and renal complications ,12,13. Iet al observed that the plasma SM level was positively and independently correlated with age, BMI and SBP (et al then investigated whether plasma SM was an early atherogenic risk factor and examined the associations between plasma SM level and carotid intimal-medial wall thickness, ankle-arm BP index and the Agatston coronary artery calcium score in asymptomatic adults. Nelson et al concluded that plasma SM was associated with subclinical atherosclerotic disease (Although the detrimental impacts of the nondipper BP pattern have been studied extensively among hypertensive patients, its exact mechanisms of action have not yet been elucidated. It has been suggested that nondippers display impaired autonomic dysfunction , higher  and SBP . Nelson  disease . In the  disease , we suggIn conclusion, the present study indicated that the nondipper pattern had contributory effects on hypertensive concentric hypertrophy and diastolic functional impairment. In addition, the plasma SM level was associated with the nondipper pattern in hypertensive patients. The measurement of SM may be used to indicate an increased risk of nondipper hypertension-associated adverse cardiovascular events. The major limitation of this study is its relatively small sample size and lack of a control group. Further large-scale studies are required to assess the effects of SM on the development of nondipper hypertension.


Interventional diagnostic procedures are established for several diseases in medicine. Despite the KDOQI guideline recommendation for histological diagnosis of kidney disease to enable risk stratification, its optimal time point has not been evaluated. We have therefore analyzed whether histological diagnosis of glomerulonephritis (GN) at an early stage of chronic kidney disease (CKD) is associated with different outcome compared to diagnosis at a more advanced stage.A cohort of 424 consecutive patients with histological diagnosis of GN were included in a retrospective data analysis. Kidney function was assessed by glomerular filtration rate (GFR) estimation at the time point of kidney biopsy and after consecutive immunosuppressive therapy. Censored events were death, initiation of dialysis or kidney transplantation, or progression of disease, defined as deterioration of CKD stage ≥1 from kidney biopsy to last available kidney function measurement.p < 0.001 for all). Patients with CKD stage 1 and 2 at kidney biopsy had fewer endpoints compared to patients with a GFR of <60 ml/min (p < 0.001).Occurrence of death, dialysis/transplantation or progression of disease were associated with GFR and CKD stage at the time of kidney biopsy (Kidney function at the time point of histological GN diagnosis is associated with clinical outcome, likely due to early initiation of specific drug treatment. This suggests that selection of therapy yields greatest benefit before renal function is impaired in GN. The time points when interventions should be recommended have been investigated and established in multiple fields of medicine. For patients with renal disease kidney biopsy can be necessary for diagnosis and treatment selection. Technical advances  improved the general implementation of this procedure . Major cThe incidence of chronic kidney disease (CKD) is increasing in the western communities and outcomes are poor. The number of patients with CKD undergoing maintenance hemodialysis is expected to rise further . ComplicThere is insufficient evidence to conclude best timing of invasive diagnostic procedures in patients with several kidney diseases. An early kidney biopsy may be of particular interest for those patients where disease classification is based on histological diagnosis and where the disease progression can be mitigated by treatment. While current guidelines have established the medical management of glomerulonephritis (GN) including the necessity of histological analysis and administration of immunosuppressive therapies, it is yet unclear if early diagnosis may result in prevention of CKD development in this heterogeneous group of patients.We therefore performed a retrospective analysis to address the question if diagnosis of GN from an early kidney biopsy before kidney function impairment, as classified by glomerular filtration rate (GFR) and CKD stage, is associated with different outcome compared to diagnosis of GN at a later CKD stage.Retrospective data from 917 consecutive patients who underwent kidney biopsy between 1992 and 2009 were identified. Among those 171 patients had diabetic nephropathy or secondary focal segmental glomerulosclerosis (FSGS) and were excluded. From 322 patients no follow up was available. Thus, 424 patients with a histological diagnosis of GN who received immunosuppressive therapy were included into the analysis  estimation was calculated via the MDRD formula . PrimaryIndications for kidney biopsy were proteinuria, microhematuria or increments in serum creatinine alone or in combination. The histological classification of GN was derived from laboratory reports of the Department of Pathology at the Vienna General Hospital, which has also been used for clinical decision making in these patients. Baseline characteristics and co-morbidities are shown in Table U test or the chi-squared test were used as appropriate. The Kaplan-Meier method was used to determine event-free survival and the log rank test was used to compare survival between subgroups. Univariate and multivariate regression analysis were performed using the Cox proportional hazard regression model to determine the effect of various variables on survival. Potential predictors were defined a priori or based on associations in the univariate analysis at a conservative threshold (p < 0.10). The Hosmer-Lemeshow test was used to assess goodness of model fit. We used SPSS Statistics for data management and calculations. A two sided p-value less than 0.05 was considered statistically significant. The authors performing the data analysis (D.G.H. and V.F.) were masked and were not involved in the data acquisition.For data description results are presented as median and 25–75% interquartile range or mean and standard deviation as appropriate. For univariate analysis the Mann Whitney P < 0.05 vs baseline). In subgroup analysis significant improvements in GFR were seen after one month for patients with vasculitis, IgA-Nephropathy and Systemic Lupus Erythematosus (SLE) , and at study end for patients with membranous GN, IgA-Nephropathy and vasculitis .The median observation time was 4.0 years . Overall, 106 (25%) patients had CKD stage 1, 65 (15%) patients had CKD stage 2, 109 (26%) patients had CKD stage 3, 70 (17%) patients had CKD stage 4, and 74 (17%) patients had CKD stage 5 before kidney biopsy. Estimated GFR slightly improved in pooled analysis during the observation period from 45 ml/min (IQR: 23–80) to 51 ml/min (IQR: 25–83) after 1 month and to 52 ml/min (IQR: 29–76) at the end of the observation period (Kidney function remained stable or improved in 216 (51%) patients. 208 patients had a progression of disease (49%). Of these, 144 patients underwent dialysis (34%) and 98 patients had subsequent kidney transplantation (23%). 47 patients (11%) died during the observation period. Distribution of mortality, dialysis/transplantation and progression of disease according to histological diagnosis is shown in Figure p < 0.01). Multivariate regression analysis detected membranous GN as an independent predictor for progression/persistence of proteinuria (p < 0.01).Data of quantitative proteinuria one month after initiation of immunosuppressive therapy was accessible in 174 patients. Of these 42 patients (24%) had proteinuria of >3.5 g/d. Univariate regression analysis including underlying diseases, age, sex and GFR identified membranous GN and vasculitis as predictors for progression/persistence of proteinuria (for both n = 171) were compared with the group of subjects with impaired renal function at CKD stages 3, 4 and 5 (n = 253). Patients undergoing kidney biopsy at CKD stage 1 and 2 had a markedly better overall event-free survival than the group of patients with higher CKD stages . Disease progression was associated with increased mortality during follow-up , dialysis/transplantation (AUC: 0.71 and 0.73), and progression of disease (AUC: 0.58 and 0.6) (Figure  for bothMultivariate regression analysis revealed that mortality was associated with CKD stages, but not with dialysis/transplantation and progression of disease Table . IndepenIn this large sample of patients with different etiology of GN an early time point of kidney biopsy was associated with smaller declines in kidney function, a less frequent incidence of dialysis/transplantation, and death. Preserved kidney function at the time point of biopsy was a strong predictor of salutary outcome in patients with CKD.Overall, immunotherapy prevented deterioration of kidney function in approximately half of the cohort of patients with GN. This treatment response is comparable with that shown across the groups of subjects with different histological diagnoses of GN in other studies -17. WhenThe association of CKD stages with mortality is comparable with data obtained in the general population ,19. Our Our analysis revealed strong associations of mortality with age. This is in accordance with other data regarding the progression of disease . Kidney A limitation of the analysis of efficiency of drug treatment is the fact that response rates have improved over time by the availability of refined dosing schemes and new drugs. However, this does not limit the principal finding of this observational study, because no therapy was withheld and all patients had access to optimized medical treatment provided by the national sickness fund during the observation period. This study has not compared individual treatments within groups of patients with different GN entities and numbers within subgroups are too small for such analysis. While this is a large study, the median follow-up is 4 years, which may not be long enough to observe clinically relevant outcome or progression in diseases such as IgA nephropathy or membranous nephropathy. A further limitation of our study is that only a controlled interventional trial may demonstrate if baseline differences may be accounted for the results seen. However, ethical concerns prevent conduct of such a trial.In summary, kidney biopsy at CKD stages 1 or 2 and consecutive therapy preserves kidney function and prevents disease progression through early initiation of therapy. The present observational data clearly supports the concept of early kidney biopsy in patients with suspected GN.The authors declare that they have no competing interests.AF, SP, HF, GFW and JP carried out the data acquisition. DGH and AS did the data administration. DGH and VF performed the statistical analysis. DGH, VF, WHH and MW wrote the manuscript. All authors read and approved the final manuscript. Authors state that they have no conflict of interest.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/13/34/prepub


Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil.NCT00971165ClinicalTrials.gov:  Cardiovascular disease (CVD) is the leading cause of death in Brazil, and high blood pressure is its major risk. factor. The prevalence of hypertension in Brazil is within 22.3 to 44% of adults . The benData from some trials have shed some concern about the safety of ARB agents , but theA complex clinical trial investigated the efficacy of an ARB agent and of an ACE inhibitor to prevent renal damage in patients with type I diabetes . Change There is no head-to-head comparison between diuretics and ARB agents in the prevention of hard cardiovascular outcomes, and even the comparison of their blood pressure-lowering effects was scarcely reported. Despite this, ARB agents are the leading brands in terms of profits in various countries in the world, including Brazil. This leadership seems to be based on a strong commercial strategy, which may have introduced bias in the evidences of clinical trials in favor of these drugs ,12. The Diuretics are at least as efficacious as other blood pressure-lowering drugs, are well tolerated, have longer duration of action and the advantage of very low cost to be used in a population intervention . ChlorthA study comparing diuretic with an ARB agent is therefore scientifically required. It would be also important in Brazil, in order to support the decisions of the Public Health System in regard to blood pressure drugs supply for the Brazilian population. Such a study was demanded and funded by the Health and Technology Ministries in Brazil.ARB agents have good tolerability and putative pleiotropic effects, particularly renal protection, which support their preference by physicians as an antihypertensive agent. Independent assessments of the evidence have questioned these advantages, and a concern with the safety of these agents, such as the loss of nephroprotection in patients with diabetes, has emerged. Diuretics, particularly chlorthalidone, are as efficacious as newer agents in managing hypertension. Its main adverse effect, hypokalemia, which is associated with arrhythmias and hyperglycemia, can be circumvented by the association of potassium-sparing diuretic, such as amiloride. Blood pressure has been a valid surrogate of the beneficial effects of blood pressure-lowering drugs. In this scenario, the PREVER treatment trial will compare the antihypertensive efficacy of the association of chlorthalidone plus amiloride with losartan, for the initial management of hypertension . Other intermediate outcomes, such as microalbuminuria and left ventricular hypertrophy, and major cardiovascular outcomes, are going to be investigated. Even if the null hypothesis is not rejected , the information will be useful for health care policy to treat hypertension in Brazil.1. Is losartan more efficacious and safe than the association of chlorthalidone with amiloride as the first option to control blood pressure in patients with stage I hypertension?2. Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the development of target-organ damage in patients with stage I hypertension?3. Is losartan more efficacious than the association of chlorthalidone with amiloride as the first option to prevent the occurrence of major cardiovascular events in patients with stage I hypertension?randomized, double-blind, clinical trial, controlled by an active treatment.patients older than 40 years of age with Stage I hypertension.low life expectancy, other indications for the use of diuretics, such as cardiovascular disease, intolerance to the study drugs, pregnancy.by a computer generated list, using a validated software , with variable block sizes and stratified by center.Chlorthalidone plus amiloride up to 25 and 5 mg daily, versus losartan up to 100 mg daily. Amlodipine up to 10 mg daily and propranolol up to 160 mg/day, in an open fashion, will be added if blood pressure is not controlled. Figure 1. Blood pressure variation and proportion of use of add-on drugs.2. Adverse events.3. Development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG.fatal or major cardiovascular events.th, 12th. and 18th. months. Figure for evaluation and enrollment and thereafter consultations at the 3th., 6th., 9Blood pressure will be measured at the follow-up visits by average blood pressure .adverse events will be investigated by open questions and by a semi-structured questionnaire including general symptoms and the presumed adverse effects of the drugs used in the trial. Laboratory adverse events, such as hypokalemia, hyperuricemia and diabetes (glycated hemoglobin and fasting glucose) will be investigated at the final visit of the participantsMicroalbuminuria will be determined by nephelometry. Left ventricular hypertrophy will be investigated by electrocardiogram, using the Sokolow-Lyon voltage and the Cornell voltage-duration product.from a statistical point of view they will be secondary events, in face of the power of the sample calculated for the trial. Figure for non-inferiority, with a P alpha of 0.01, power of 99%, and SD of 12 mmHg, and maximum acceptable absolute difference of 4 mmHg (diastolic), it will be necessary to study 433 patients per group, rounded to 500 patients to compensate losses. The difference of 5 mmHg (diastolic) has been achieved, on average, in clinical trials that have demonstrated the advantage of a drug over placebo or other drug in the prevention of major cardiovascular outcomes. In face of the other primary hypotheses of the trial, and other subprojects that will be undertaken in some centers, it was decided to study 1200 patients per group.the cumulative incidence of target-organ damage and adverse events will be analyzed by Chi-square test. Blood pressure will be compared by ANOVA for multiple measurements and factors, testing for the time-group interaction. The primary analysis will be by intention-to-treat. An attempt to measure blood pressure at the end of trial even for participants that abandoned the treatment will be undertaken. The rates of controlled blood pressure by treatment will be evaluated by survival curves and tested by Cox models, censoring the cases lost in the follow-up. In case of uneven losses by group, sensitivity analysis will be undertaken.This is a nation-based trial, with 24 clinical centers distributed in 9 States. A Coordinating Committee is responsible for the elaboration of this proposal and for the main decisions of the trial. The study organizational chart will include an executive Committee, a safety committee, outcome committee, lab and EKG centers, and the research units.The project and the informed consent form were approved by the Ethics committee of the Hospital de Clínicas de Porto Alegre, which is accredited by the Office of Human Research Protections as an Institutional Review Board, and by the Ethic Committees of the participating centers. All participants will be asked to sign the informed consent to participate in the studyACE: angiotensin converting enzyme; ALLHAT: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; ARB: Angiotensin-receptor blockers; CHD: coronary heart disease; CVD: Cardiovascular disease; EKG: electrocardiogram; ONTARGET: The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial; PREVER: Prevention of cardiovascular events in patients with hypertension and pre-hypertension study; VALUE: Valsartan Antihypertensive Long-term Use EvaluationThe authors declare that they have no competing interests.FDF conceived the study; all authors participated in the trial design and methodological considerations, contributed to the draft of this manuscript for intellectual content and approved its final version. They are the coordinators of the clinical centers that will enroll the trial participants.


Dysregulation of the expression/shuttling of the aquaporin-2 water channel (AQP2) and the epithelial sodium channel (ENaC) in renal collecting duct principal cells has been found in animal models of hypertension. We tested whether a similar dysregulation exists in essential hypertension.CR, u-ENaCβ-CR), prostaglandin E2 (u-PGE2) and cyclic AMP (u-cAMP), fractional sodium excretion (FENa), free water clearance (CH2O), as well as plasma concentrations of vasopressin (AVP), renin (PRC), angiotensin II (Ang II), aldosterone (Aldo), and atrial and brain natriuretic peptide  in 21 patients with essential hypertension and 20 normotensive controls during 24-h urine collection (baseline), and after hypertonic saline infusion on a 4-day high sodium (HS) diet (300 mmol sodium/day) and a 4-day low sodium (LS) diet (30 mmol sodium/day).We measured urinary excretion of AQP2 and ENaC β-subunit corrected for creatinine (u-AQP2CR or u-ENaCβ-CR were measured between patients and controls. U-AQP2CR increased significantly more after saline in patients than controls, whereas u-ENaCβ-CR increased similarly. The saline caused exaggerated natriuretic increases in patients during HS intake. Neither baseline levels of u-PGE2, u-cAMP, AVP, PRC, Ang II, Aldo, ANP, and BNP nor changes after saline could explain the abnormal u-AQP2CR response.At baseline, no differences in u-AQP2CR and u-ENaCβ-CR between patients and controls at baseline. However, in response to saline, u-AQP2CR was abnormally increased in patients, whereas the u-ENaCβ-CR response was normal. The mechanism behind the abnormal AQP2 regulation is not clarified, but it does not seem to be AVP-dependent.No differences were found in u-AQP2NCT00345124. Dysregulation of the expression/shuttling of the renal epithelial sodium channel (ENaC) and the aquaporin-2 water channel (AQP2) has been suggested to play a role in the pathogenesis of essential hypertension.β) and changes in urinary sodium excretion [β has been suggested as a marker of the transport of sodium via ENaC.ENaC is responsible for the reabsorption of sodium through the apical membrane of the connecting tubule and the collecting duct and plays a key role in controlling sodium balance, extracellular fluid volume, and blood pressure. ENaC is a heteromultimeric protein composed of three homologous subunits  ,2. Aldosxcretion . Thus, uAQP2 is the apical water channel of collecting duct principal cells. AVP is the main hormonal regulator of AQP2 ,9. BindiAn increased expression of ENaC subunits and an increased expression and apical targeting of AQP2 has been reported in spontaneous hypertensive rats, an experimental model of hypertension -18. ThesIn the present study, we wanted to test the hypothesis that u-AQP2 and u-ENaC were abnormal in essential hypertension during dietary high sodium (HS) intake and/or during dietary low sodium (LS) intake, and that these variables responded abnormally to a hypertonic saline infusion.β corrected for creatinine (u-AQP2CR and u-ENaCβ-CR), fractional sodium excretion (FENa), free water clearance (CH2O), urinary excretion of prostaglandin E2 (u-PGE2), urinary excretion of cyclic-AMP (u-cAMP), and plasma concentrations of AVP, renin (PRC), angiotensin II (Ang II), Aldo, atrial natriuretic peptide (ANP), and brain natriuretic peptide (BNP) in patients with essential hypertension and normotensive controls during both HS and LS intake. Furthermore, we compared the relative changes in the above mentioned effect variables after a hypertonic saline infusion during both diets.In order to analyse the regulation of the expression/shuttling of AQP2 and ENaC in essential hypertension, we performed a randomised, cross-over trial with patients with essential hypertension and normotensive control subjects. We compared the absolute values of u-AQP2 and u-ENaCThe inclusion criteria for patients with essential hypertension were: 1) white men and women, 2) age between 18 and 65 years, 3) arterial hypertension, defined by 24-h ambulatory blood pressure above 125 mmHg systolic or 80 mmHg diastolic, and 4) body mass index (BMI) ≤ 30 kg m-2. The exclusion criteria were: 1) abnormal renography, 2) a medical history or clinical signs of heart, lung, liver, kidney, brain, endocrine organ, cardiovascular or neoplastic disease, 3) severe hypertension, 4) abnormal biochemical screening of the blood regarding haemoglobin, white blood cell count, platelets, sodium, potassium, creatinine (> 200 μmol l-1), albumin, bilirubin, alanine aminotransferase, alkaline phosphatase, cholesterol, and glucose, 5) abnormal urine screening for blood, albumin, and glucose, 6) abnormal electrocardiogram, 7) drug or alcohol abuse, 8) smoking, 9) pregnancy or breast feeding, 10) blood donation less than one month before the examination, and 11) unwillingness to use contraceptives if fertile woman . The withdrawal criteria were: 1) lack of compliance, 2) withdrawal of consent, and 3) development of one of the exclusion criteria during the study. Antihypertensive agents were discontinued two weeks before each study day. The blood pressure of the subjects was controlled once a week in the two week period. If blood pressures rose to levels above 170 mmHg systolic or 105 mmHg diastolic, substitution treatment with metoprolol was initiated (this did not happen in any of the patients).The inclusion criteria for the normotensive controls were: 1) white men and women, 2) age between 18 and 65 years, 3) 24-h ambulatory blood pressure below 125 mmHg systolic and 80 mmHg diastolic. The exclusion- and withdrawal criteria were the same as for the patients. None of the normotensive controls received any medication, except oral contraceptives.The patients with essential hypertension were recruited from the Nephrological out-patient clinic of the Department of Medicine, Holstebro Hospital. The control subjects were recruited by advertising in public institutions and private companies.http://www.clinicaltrials.gov (NCT00345124).The study was approved by the local Medical Ethics Committee (JRN RRS-2006-1014-(2733-06)). The study was conducted in conformity with the principles of the Declaration of Helsinki, and written informed consents were obtained from all the subjects. The study was registered at the registration site: We performed two randomized, cross-over studies, one with patients with essential hypertension and one with normotensive controls. Each subject was studied on two separate days at least three weeks apart. During four days before the study day, the subjects consumed either a HS or LS diet in randomized order. The results of the patients are compared to the results of the normotensive controls. Furthermore, in both patients and controls the results obtained during HS and LS intake are compared.CR, and the secondary effect variables were urinary sodium excretion rate (UNa), FENa, u-ENaCβ-CR, urine volume (V), CH20, serum osmolality (s-osm), urine osmolality (u-osm), u-cAMP and u-PGE2, plasma concentrations of AVP, PRC, Ang II, Aldo, ANP, BNP, sodium (p-Na), and albumin , systolic and diastolic blood pressure, heart rate, body weight, and glomerular filtration rate (GFR).The primary effect variable was u-AQP2-1 was considered the minimal relevant difference based on interventions in previous pilot experiments. A sample size of 20-21 subjects who could be evaluated had 90% power to detect this difference assuming a level of significance of 5% and a standard deviation of 0.24 ng min-1. Because a few subjects were expected to drop out, 25 subjects were included in each group.A difference in u-AQP2 of 0.25 ng min-1/17.5 g salt day-1) or LS , 4-day diet from the hospital kitchen. Depending on the individually estimated energy requirement, the participants were given either a diet of 8,000 or 11,000 kJ day-1. The energy distribution was: 55% carbohydrates, 15% proteins, and 30% lipids. The 4-day diet was started the following morning.Five days before the study day, the subjects collected a standardized, HS , the last three of 60 minutes duration (P3-P5). The first two clearance periods were baseline periods.-1 of 3% saline were given over 30 minutes.At 10:30 AM, 7 ml kgBlood pressure and heart rate were measured every 30 minutes from 9:30 AM to 1:30 PM.β, u-cAMP, u-PGE2, and 51Cr-EDTA.Urine was collected in each clearance period and analyzed for sodium, osmolality, u-AQP2, u-ENaCBlood samples were drawn every 30 minutes from 9:30 AM to 10:30 AM and every hour from 11:30 AM to 1:30 PM, and were analyzed for sodium, osmolality, and 51Cr-EDTA. In addition, analysis of AVP, PRC, Ang II, Aldo, ANP and BNP were performed from blood samples drawn at 10:30 AM, 11:30 AM, 12:30 PM, and 1:30 PM.ANP in plasma was determined by radioimmunoassay (RIA), as previously described [-1. The coefficients of variation were 12% (inter-assay) and 10% (intra-assay). BNP in plasma was determined by RIA as previously described [-1. The coefficients of variation were 11% (inter-assay) and 6% (intra-assay). AVP in plasma was measured by RIA using a modification of the method described previously [-1. The coefficients of variation were 13% (inter-assay) and 9% (intra-assay). Ang II in plasma was determined by RIA using a modification [-1. The coefficients of variation were 12% (inter-assay) and 8% (intra-assay). Aldo was determined by RIA using a commercial kit . The minimal detection concentration was 22 pmol l-1. The coefficients of variation were 8.2% (inter-assay) and 3.9% (intra-assay). PRC was also determined by a commercial RIA . The minimal detection concentration was 0.5 pg ml-1. The coefficients of variation were 14.5% (inter-assay) and 4.5% (intra-assay).All blood samples were centrifuged for 15 minutes at 3,000 rpm at 4°C. Plasma was separated from blood cells and kept frozen at -20°C until assayed. escribed . ANP wasescribed . Immunoreviously . AVP wasfication  of the mfication . Ang II U-AQP2 was measured by a RIA as previously described [-1. The coefficients of variation were 11.7% (inter-assay) and 5.9% (intra-assay). β U-ENaCwas measured by a newly developed RIA [β was synthesized and purchased by Lofstrand Labs Limited . The β-ENaC antibody was raised against a synthetic peptide in rabbits. The lower detectable limit of the assay was 34 pg tube-1. The inter-assay variation was 12% at a mean level of 78 pg tube-1, and 10% at a mean level of 155 pg tube-1. The intra-assay variation was 6.4% and 9.0% at a mean level of 180 pg tube-1 and 406 pg tube-1, respectively. U-cAMP was measured by RIA using a commercial kit . The minimal detection concentration was 0.05 pmol l-1. The coefficients of variation were 8% (inter-assay) and 3% (intra-assay). 2 U-PGEwas measured by RIA using a commercial kit . The minimal detection concentration was 8.26 pg ml-1. The coefficients of variation were 10.9% (inter-assay) and 6.3% (intra-assay).Urine samples were centrifuged for 5 minutes at 3,000 rpm, and 125-1000 μl of the supernatant was freeze dried and kept frozen at -20°C for two to eight months until assayed. We have done pilot experiments to ensure that the concentration of the effect variables in the urine does not decrease over time. The experiments showed that the effect variables are stable at -20°C for two years. escribed . The antoped RIA . ENaCβ wS-osm and u-osm were measured by freezing-point depression (Advanced Model 3900 multisampling osmometer). H2O Cwas determined according to the formula: CH2O = V - Cosm, where V is the urine output, and Cosm is the osmolality clearance.sodium and creatinine were determined at the Department of Clinical Biochemistry, Holstebro Hospital, Denmark using conventional methods. All clearances were standardized to a body surface area of 1.73 m2. GFR was measured using the constant infusion clearance technique with 51Cr-EDTA as reference.Urine was screened for blood, albumin, and glucose with standard urine test strips. Plasma and urinary concentrations of 24-h ambulatory blood pressure was measured with BOSO TM-2450 .Clinic blood pressure was measured with UA-743 digital blood pressure meter .Statistical analyses were performed using SPSS version 15 . Single baseline values were obtained by taking the weighted average of the measurements from the two baseline periods. The baseline values of the two groups were compared by Student's t-test. The baseline values during HS and LS intake were compared by paired samples t-tests. We used the "General Linear Model Repeated Measures" procedure in SPSS with time as within-subject factor and blood pressure as between-subject factor to compare the effect of blood pressure. The changes in response to the hypertonic saline infusion in each group were analyzed with the "General Linear Model Repeated Measures" procedure with time as within-subject factor and paired samples t-tests with Bonferroni correction as post hoc tests. P values < 0.05 were considered significant. Variables are normally distributed and presented as means with standard deviations (SD) or 95% confidence intervals, if not otherwise stated.Twenty five patients with essential hypertension and 25 normotensive controls were enrolled in the study. Four patients were withdrawn from the study because they withdrew their consent to participation. Five normotensive controls were withdrawn from the study, two because of failure to obtain intravenous access, and three because of withdrawal of consent to participation. Table CR and u-ENaCβ-CR were the same in patients and controls in the 24-h urine. U-AQP2CR was significantly lower during LS intake than HS intake in both patients and controls, whereas u-ENaCβ-CR was the same during LS and HS. The only significant difference between patients and controls was a significantly lower u-osm in the patients during LS intake. UNa was significantly lower in both patients and controls during LS intake compared to during HS intake, indicating that both groups had kept the supplied diets.Table Na, FENa and u-ENaCβ-CR), Table H2O, u-AQP2CR, u-osm, u-c-AMP, u-PGE2, and s-osm), Table The effect variables are shown in Table Na and FENa ), while it increased from 79.3 kg (SD 12.3) to 79.9 kg (SD 12.3) during LS intake. The increase was statistically significant (0.6 kg (SD 0.5), P < 0.001). The body weight of the control subjects increased significantly during both diets (HS: from 75.2 kg (SD 14.3) to 75.5 kg (SD 14.3), P = 0.007; LS: from 74.4 kg (SD 14.1) to 75.1 kg (SD 14.2), P < 0.001). The relative increase was higher during LS intake than during HS intake (1.1% (SD 0.5) vs. 0.4% (SD 0.6), P < 0.001).P-Na increased in response to the hypertonic saline infusion in both groups during both diets with maximum after 60 minutes. During LS intake the relative increase in p-Na was slightly but significantly higher in the patients compared to the controls (3.6% (SD 0.9) vs. 3.0% (SD 0.9), P = 0.039). The relative increases were not significantly different between HS and LS intake in any of the two groups.P-albumin fell significantly in response to the hypertonic saline infusion in both groups during both diets to comparable levels at the end of the study day (data not shown). The decrease was significantly higher during LS intake.During LS intake, the hypertonic saline infusion caused a significant decrease in GFR in the patient group 60 minutes after infusion start (Table CR and u-ENaCβ-CR in patients with essential hypertension and normotensive control subjects during HS and LS intake. Furthermore, we compared the relative change in u-AQP2CR and u-ENaCβ-CR in response to a hypertonic saline infusion in patients and controls. U-AQP2CR and u-ENaCβ-CR were normal in essential hypertension at baseline. However, in response to the hypertonic saline infusion, u-AQP2CR was abnormally increased in essential hypertension, whereas the response in u-ENaCβ-CR was normal.In the present study, we compared u-AQP2Both the systolic and the diastolic blood pressures were significantly higher in the patients than in the normotensive controls during both diets as expected. The subjects were studied in the supine position, which explains the rather low blood pressure levels in both groups throughout the study days.β-CR and u-AQP2CR were not abnormal in patients with essential hypertension. U-osm, V, UNa, and FENa were similar in patients with essential hypertension and normotensive controls during both HS and LS intake.Surprisingly, and in contrast with results from experimental models of hypertension -18,33,34Thus, altogether these results indicate that the expression of AQP2 and the expression of ENaC are not increased in essential hypertension.AVP and u-cAMP were not increased in the patients with essential hypertension compared to the normotensive controls during any of the diets. The activity of the renin-angiotensin-aldosterone system has previously been reported to be suppressed in hypertensive patients compared with normotensive controls during low and normal sodium intakes . In the CR during LS intake than during HS intake in both groups and a concomitant significantly lower V during LS intake. Recently, our group reported lower AQP2 during LS intake compared to during HS intake in young healthy subject, in agreement with the present study [We found a significantly lower u-AQP2nt study . In the nt study . In suppnt study .One should remember that both patients and control subjects were water loaded in order to make urine collection possible. We believe that this is the reason for the low osmolalities during the first hours of the study days.β-CR during LS intake compared to during HS intake in the patients with essential hypertension at baseline, but not in the normotensive controls. LS intake is known to increase open probability of ENaC and the number of active ENaCs in normotensive mice [β-CR between HS and LS intake was present in the patients with essential hypertension during the 24-h urine collection. Therefore we speculate that the difference in u-ENaCβ-CR between HS and LS intake at baseline in the patients with essential hypertension could be by chance.We found a significantly lower u-ENaCive mice . No diffCR increased significantly more in response to the hypertonic saline infusion in patients with essential hypertension than in normotensive controls, which suggests that the patients reabsorb a larger proportion of the infused water. Thus, somehow the antidiuretic effect of the hypertonic saline is increased in essential hypertension. The underlying regulatory mechanism is unknown. Abnormalities in AVP, PRC, Ang II, Aldo, ANP, BNP, u-PGE2, u-cAMP, GFR, blood pressure and heart rate were not responsible for the difference, since these effect variables changed in similar manner in patients and controls.U-AQP2Jackson et al. have previously shown that Ang II has an enhanced ability to reduce urinary cAMP excretion in spontaneously hypertensive rats . We specCR in response to a hypertonic saline infusion has been measured in patients with essential hypertension. U-AQP2CR increased considerably, but the regulatory mechanism is unknown.To our knowledge this is the first time that the change in u-AQP2β-CR in response to the hypertonic saline infusion, since Aldo decreased and UNa and FENa increased in both patients and controls. Instead we found a small but significant increase in u-ENaCβ-CR in response to the hypertonic saline. The explanation of this phenomenon is not clear for the time being. A considerable decrease in the renal sodium absorption more proximal in the nephron might be compensated for by an increase in absorption in the distal part of the nephron, but additional studies are required to determine the precise use of u-ENaCβ-CR as biomarker for ENaC activity. Whether membrane shedding plays a role in the increase in u-ENaC awaits further studies. A significantly higher natriuretic response was observed in the patients two hours after the hypertonic saline infusion during HS intake (Table β-CR to hypertonic saline infusion was the same in patients with essential hypertension and normotensive controls. Thus, an abnormal regulation of ENaC could not explain the phenomenon of exaggerated natriuresis in essential hypertension.One would have expected a decrease in u-ENaCke Table . The simThe strengths of this study lie in the design. The study is a controlled clinical study with an age- and sex-matched control group. The salt intake and fluid intake are standardised and controlled. Furthermore the patients with essential hypertension pause their antihypertensive medication during the study. Thus, the results are not confounded by different salt or water balance or antihypertensive drugs.A limitation of the study is that the threshold for hypertension is quite modest, which may explain why few differences are seen. We cannot exclude that we would have found a more pronounced difference in the AQP2 response to the hypertonic saline between patients and controls, if we had included patients with more severe hypertension.CR and u-ENaCβ-CR between patients and controls at baseline. However, in response to the hypertonic saline infusion, u-AQP2CR was abnormally increased in essential hypertension, whereas the response in u-ENaCβ-CR was normal. The underlying mechanism for the abnormal regulation of AQP2 expression is not clarified, but it is not AVP-dependent.In conclusion, no difference was found in u-AQP2The authors declare that they have no competing interests.CCG conceived of the study, participated in the design, coordination of the study, and recruitment of subjects, carried out the experiments, analyzed the data, performed the statistical analysis, and drafted the manuscript. JNB helped to draft the manuscript. TGL assisted in the experimental part of the study. HV assisted in the experimental part of the study. EBP conceived of the study, participated in the design of the study and the recruitment of subjects, was responsible for the laboratory analyses, and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2369/13/15/prepub


Intra-abdominal pressure (IAP) is most commonly measured via the bladder with the patient in the supine position. In the ICU, patients are nursed with the head of the bed elevated at 30° (HOB30) to reduce the risk of ventilator-associated pneumonia. This study investigated whether gastric pressure at HOB30 can be used as a surrogate measure of IAP via the bladder in the supine position.A prospective observational study was conducted in a single-centre intensive care unit. A total of 20 patients were included. IAP was recorded simultaneously via the bladder catheter  and via nasogastric tube  in the supine and HOB30 position. Each patient had three sets of IAP measurements performed at least 4 h apart.In the supine position, mean IBP was 12.3 ± 4.5 mmHg compared to IGP of 11.8 ± 4.7 mmHg. The bias between the two groups was 0.5 and precision of 3.7 . At 30 degrees, mean IBP was 15.8 ± 4.9 mmHg compared to IGP of 13.1 ± 6.1 mmHg. The bias between both groups was 2.7 with a precision of 5.5 . Comparing IBP in the supine position with IGP at 30° showed a bias of -0.8 and precision of 5.6 .IAP measured via a nasogastric tube was less influenced by changing the body position from supine to HOB30 than was bladder pressure. Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) are associated with increased morbidity and mortality in critically ill patients ,2. As a http://www.wsacs.org) recommends the measurement of IAP via the bladder in the supine position at end-expiration, ensuring that abdominal contractions are absent and with the transducer zeroed at the level of the mid-axillary line [The World Society of Abdominal Compartment Syndrome  to ensure that abdominal muscle contractions were absent. Written informed consent was obtained by the next of kin as determined by the ethics committee.Once the patient was enrolled, IBP was measured according to the WSACS consensus recommendations using the standard bladder technique . The IBPGastric pressures were measured via a standard nasogastric tube. Prior to measurement, the nasogastric tube was aspirated for air or gastric contents, and its position was confirmed by chest X-ray. A three-way stopcock was attached between the nasogastric tube and a standard pressure monitoring line. A Luerlok syringe was attached to one port of the stopcock for the instillation of 100 ml of sterile saline from the closed pressure monitoring system to ensure a continuous column of fluid between the stomach and the pressure transducer. A point level with the xiphisternum on the mid-axillary line was marked, and the transducer was zeroed at that level. This position corresponds to the position of the stomach allowing accurate measurement of gastric pressure in different body positions. After each measurement, the instilled volume of saline was then aspirated out of the nasogastric tube.Each set of measurements included IBP and IGP in the supine position followed by the semi-recumbent position at HOB30. All four measurements were taken over a period of 5 to 10 min or less to reduce the possibility of changes in IAP over time. Three sets of readings were taken at least 4 h apart over a 24-h period.Once patients were enrolled in the study, data on patient demographics including age, sex, weight, height, body mass index, diagnosis at admission, co-morbidities and presence of IAH risk factors were collected. Severity of illness for the 24-h period before the first IAP measurement was documented through calculation of the Acute Physiology and Chronic Health Evaluation score II, Simplified Acute Physiology Score II and Sequential Organ Failure Assessment Scores. For each set of IAP readings, mean arterial pressure, positive end-expiratory pressure and RASS were recorded. All study data were recorded on a case report form on paper and subsequently entered as de-identified patient data on a secure Microsoft Access database.IAH was defined by a sustained or repeated pathological elevation in IAP ≥ 12 mmHg, whilst ACS was defined as a sustained IAP > 20 mmHg that is associated with new organ dysfunction/failure .t tests were used to test for statistical significance between two different measures of pressure on the same patients at the same times. General linear modelling (GLM) for repeated measures was used to test whether differences between the same measures of pressure on the same patients changed significantly over time. A significant level of p < 0.05 was used throughout. For assessing agreement between two methods of measurement of IAP, we used Bland-Altman plots [r2) is +1 in the case of a perfect positive (increasing) linear relationship, and as it approaches zero, there is less correlation.Statistical analysis was performed using Medcalc  and PASW Statistics 18 . Data are presented as proportions  or mean ± standard deviation (SD). Paired Student's an plots . The WSAan plots . PearsonThere were 20 patients enrolled in the study with a total of 240 IAP measurements. Patient demographics and severity of illness are presented in Table p > 0.34; Bonferroni-corrected pairwise comparisons, p ≥ 0.50). Therefore, the results for all 60 sets of measurements were pooled.GLM for repeated measures showed that for all four measures, the IAP did not change significantly over time (Huyn-Feldt test for within-subjects effects p = 0.037), whereas the mean difference in the HOB30 for IGP and IBP was -3.5 ± 3.0 mmHg (p < 0.001) (Figure In the supine position, the mean IBP was 12.3 ± 4.5 mmHg compared to an IGP of 11.8 ± 4.7 mmHg (Figure This study found that IGP changed to a lesser degree than IBP when changing the body position from supine to HOB30. The WSACS recommends using the IBP in the supine position to indirectly measure IAP, but gastric pressures have shown to be a valid alternative in cases where the bladder is contra-indicated. Collee et al.  used a sMost patients in the ICU are nursed with the head of bed elevated at 30° to 45° to reduce the risk of ventilator-associated pneumonia ,8. StudiIdeally, we need to have a method of measuring IAP in HOB30. In this study, IGP HOB30 was compared with the gold standard IAP supine via the bladder. Comparing the two methods, we found an acceptable bias, but the precision and limits of agreement exceeded the pre-defined range . TherefoIt is uncertain if this IBP increase between supine and HOB30 is a true pressure increase throughout the entire abdomen or represents a pressure gradient within the abdomen caused by a hydrostatic fluid column or a compression of abdominal organs with a subsequent compression on the bladder or even a localized pressure difference .There might have been extra-abdominal body components such as the mediastinum or lungs increasing IAP, which might have affected IGP and IBP readings to different extent. If we believe that the abdomen behaves as a hydraulic system , then thThe main limitations of our trial are that it only represented a very small group of patients. Forty percent of the patients had IAH but only one patient had ACS, and we cannot be certain that with higher IAP values the correlation between IBP in the supine position and IGP in the HOB30 might have improved. Although we did pay attention to make sure that the stomach was in a period of quiescent motor activity with no evidence of the phase 2 or 3 of the migrating motor complex, this could not be excluded entirely and may have influenced the IGP readings. Gastric motor activity was recorded by Collard and Romagnoli at a rate of about three cycles per minute . EnteralAs for IBP measurements, increasing volume of fluid installed into the bladder can produce falsely elevated measurements. Therefore, the amount of 100 ml of normal saline might have been too high to adequately measure IGP. Some of these questions may be solved through bypassing the effects associated with fluid-filled systems and measuring IAP with a balloon-tipped catheter.There are no guidelines towards critical IAP levels in patients with the HOB elevated, and it may well be that the higher readings ascertained in this position are accurate. Further research should be directed as to whether early interventions for raised IAP in the semi-recumbent position provide better outcomes in patients with ACS. Based on our results, IGP in the semi-recumbent position cannot be recommended as an estimate for IAP in supine position. Instead, IAP should be taken via an indwelling bladder catheter with the patient in a supine position to standardize values when intermittent readings are required. If readings are taken in different positions or by different routes, accuracy is reduced.Based on our results, IGP at HOB30 position cannot be used as a surrogate measure of IBP in supine position. Although previous studies have implicated that IGP and IBP can be used interchangeably, we found large limits of agreement between the two methods. IAP measured via the nasogastric tube was less influenced by position than was the IAP measured via bladder catheter. Further research is required to assess the implication of increased IAP readings in the semi-recumbent position and whether this is due to the abdomen not being a hydraulic compartment or whether this reflects a true local increase in IAP.ACS: abdominal compartment syndrome; GLM: general linear modelling; HOB: head of bed elevation; HOB30: head of bed elevation at 30°; IAH: intra-abdominal hypertension; IAP: intra-abdominal pressure; IBP: intrabladder pressures; IGP: intragastric pressures; LA: limits of agreement; RASS: Richmond Agitation and Sedation Scale; SD: standard deviation; WSACS: World Society of Abdominal Compartment Syndrome.The authors declare that they have no competing interests.NR, BDK and AR participated in the design of the study. BDK and NR contributed to data collection. BDK, AR and WD performed the statistical analysis. NR and BDK drafted the manuscript. AR, NR and WD revised the manuscript. All authors read and approved the final manuscript.


Long-acting natriuretic peptide (LANP) is one of the peptide hormones in atrial natriuretic peptide (ANP) pro-hormone. Low levels of natriuretic peptide may lead to reduced lipolysis and excessive weight gain in obese patients. The aim of this study was to investigate the relationship between fasting serum LANP level and the metabolic syndrome (MetS) among congestive heart failure (CHF) patients.Fasting blood samples were obtained from 186 patients with normal renal function in cardiac clinic outpatients. CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation.p = 0.002). Forty-six of the CHF patients (46.9%) had MetS. Fasting LANP level negatively correlated with MetS among CHF patients (p < 0.001). Univariate linear regression analysis showed that BUN (p = 0.026) positively correlated with fasting serum LANP levels, while body weight (p = 0.009), BMI (p = 0.004), homeostasis model assessment of insulin resistance  and HOMA-β (p = 0.001) negatively correlated with fasting serum LANP levels among the CHF patients. Multivariate forward stepwise linear regression analysis of the significant variables showed that the HOMA-β  and HOMA-IR  were independent predictors of fasting serum LANP levels in CHF patients.Ninety-eight patients (52.7%) had CHF. There was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased (LANP level is significantly reduced in CHF patients affected by MetS. HOMA-β and HOMA-IR were independent predictors of serum LANP levels in CHF patients. There are four peptide hormones derived from the 126-amino acid atrial natriuretic peptides (ANP) pro-hormone: long-acting natriuretic peptide , vessel dilator , kaliuretic peptide , and ANP (α-ANP) and these peptide hormones have significant diuretic, natriuretic, and blood-pressure-lowering properties in animals and humans [The metabolic syndrome (MetS) is associated with increased cardiovascular events . The preBetween October 2009 and December 2009, 186 consecutive clinic outpatients in a medical center in Hualien, eastern Taiwan  were enrolled into this study. The Protection of the Human Subjects Institutional Review Board of Tzu-Chi University and Hospital approved this study. Patients were excluded if they had any acute infection, acute myocardial infarction, pulmonary edema, liver cirrhosis, thyroid disease, chronic renal failure (serum creatinine ≥1.2 mg/dl) at the time of blood sampling or if they refused to provide informed consent for the study.In the present study, we included patients with stages C/D CHF defined by the American College of Cardiology Foundation and the American Heart Association 2005 Guidelines. Heart failure is a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood . New YorBody weight was measured to the nearest half-kilogram with the patient in light clothing and without shoes. Height was measured to the nearest half centimeter. Waist circumference was measured in a horizontal plane, midway between the inferior margin of the ribs and the superior border of the iliac crest. Body mass index (BMI) was calculated as weight (kilograms) divided by height squared (meters). Bioimpedance measurements of fat mass were performed at the bedside according to the standard, tetrapolar, whole body (hand-foot) technique, using a single-frequency (50-kHz) analyzer . Measurements were carried out by the same operator; fat mass was collected and analyzed by specific formulas provided by the manufacturer -15.g for 10 min. Serum levels of blood urea nitrogen (BUN), creatinine (Cre), fasting glucose, total cholesterol (TCH), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), albumin, globulin, and C-reactive protein (CRP) were measured using an autoanalyzer . Serum LANP  levels were measured using a commercial available enzyme immunoassay kit (EIA). The limit of detection calculated as the concentration of human LANP corresponding to the blank average minus three standard deviations was 0.1 ng/ml. The inter- and intra-assay coefficients of variation for LANP were 6.2% and 5.4%, respectively [Fasting blood samples of approximately 0.5 ml for measuring complete blood count  and other factors were immediately centrifuged at 3000 ectively . Serum iectively . HOMA-β ectively .The prevalence of MetS was defined using the International Diabetes Federation definition . People t test (two-tailed) for the normally distributed data or the Mann–Whitney U test for the parameters that presented with non-normal distribution . The significance of differences of LANP between groups  was analyzed by the Kruskal-Wallis analysis of variance (AVONA) test. Clinical variables that correlated with serum LANP levels in CHF patients were evaluated by univariate linear regression analyses. Variables that were significantly associated with LANP in CHF patients were tested for independency in multivariate forward stepwise regression analysis. Data were analyzed using SPSS for Windows . A p-value < 0.05 was considered statistically significant.Data are expressed as means ± standard deviation (SD) and were tested for normal distribution by Kolmogorov-Smirnov statistics. Categorical variables were analyzed by the Chi-square test. Comparisons between patients were performed using Student’s independent p = 0.037) and higher LANP level (p = 0.035) than patients without CHF. There was no difference of the fasting serum LANP levels (p = 0.090) between HFREF patients  and HFPEF patients . However, there was a tendency toward increased fasting LANP levels as the NYHA CHF functional classes increased in CHF patients . LANP levels did not differ statistically by gender distribution, diabetes, hypertension, hyperlipidemia, ARB, ACEI, CCB, β-blocker, thiazide, statin, fibrate, sulfaurea, metformin, aspirin, or clopidogrel drugs used.The clinical characteristics and fasting serum LANP levels of the CHF patients are presented in Table p = 0.026) positively correlated with fasting serum LANP levels, while body weight , BMI , HOMA-IR  and HOMA-β  negatively correlated with fasting serum LANP levels among the CHF patients.The univariate linear analysis of fasting serum LANP levels in CHF patients is presented in Table 2 change = 0.292, p < 0.001) and HOMA-IR  were the independent predictors of fasting serum LANP levels , 108-amino acid B-type natriuretic peptide (BNP) and 103-amino acid C-type natriuretic peptide (CNP) pro-hormones). The ANP pro-hormone contains four peptide hormones: LANP, vessel dilator, kaliuretic peptide and ANP . High plMetS represents a constellation of hypertension, abdominal obesity, impaired fasting glucose, and dyslipidaemia, and it has been shown to be a risk factor for cardiovascular disease . CHF is Human studies indicated that ANP is removed by the lung, kidney, and liver and degraded by natriuretic peptide receptor-C (NPRC), neprilysin, and insulin-degrading enzyme . The redOur study noted low levels of LANP in CHF patients may lead to decreased lipolysis and this may be linked to the development of MetS and noted a tendency for increasing fasting LANP levels as the NYHA CHF functional classes increased in CHF patients. Our study also found that BMI negatively correlated with fasting serum LANP levels among CHF patients. MetS is associated with increased cardiovascular events . NumerouMany factors may affect serum LANP levels, such as drugs, clearance of LANP, and associated diseases. Type 2 DM is a heterogeneous disorder with a complex aetiology that develops in response to genetic and environment influences. The pathophysiology of type 2 DM is characterized by impaired insulin secretion, peripheral insulin resistance and excessive hepatic glucose production . AlthougOur study has some limitations. Firstly, this study was of cross-sectional design. Therefore, our findings should be investigated in long-term prospective studies before a causal relationship between serum LANP and MetS in CHF patients can be established. Secondly, most studies have focused on ANP effects on lipolysis and adipose tissue. However, lack of LANP effects has been investigated. Thirdly, other N-terminal ANP pro-hormone peptides such as vessel dilator or kaliuretic peptide have the same effects as LANP also needed further investigated. Further studies are needed to show the N-terminal ANP pro-hormone peptides effects on MetS in CHF patients.The present study shows there was a tendency of increased fasting LANP levels as the NYHA CHF functional classes increased and a negative association between circulating fasting LANP and MetS among CHF patients. HOMA-β and HOMA-IR were independent predictors of the serum LANP level among the CHF patients. LANP level was significantly negatively related to the pancreatic beta cell function and insulin resistance in these patients.ANP: atrial natriuretic peptide; BUN: blood urea nitrogen; CHF: congestive heart failure; cGMP: cyclic guanosine monophosphate; Cre: creatinine; CRP: C-reactive protein; HDL-C: high-density lipoprotein-cholesterol; HFPEF: heart failure with preserved ejection fraction; HFREF: and heart failure with reduced ejection fraction; HOMA-IR: homeostasis model assessment of insulin resistance; HOMA-β: homeostasis model assessment of beta cell function; LANP: long-acting natriuretic peptide; LDL-C: low-density lipoprotein-cholesterol; MetS: metabolic syndrome; NPRC: natriuretic peptide receptor-C; TCH: total cholesterol; TG: triglyceride.All authors declare that they have no conflict of interest.Lee CJ researched and analyzed data. Wang JH and Hsu BG designed of the study, interpretation of data and wrote the manuscript. Hsieh JC, Chen YC and Wang JH collected the data. All authors read and approved the final version of the manuscript.


Background and Objectives. This study aimed to investigate the effect of noise exposure on blood pressure and heart rate of steel industry workers. Materials and Methods. In the present cross-sectional study, 50 workers were selected from a steel company in Fars province, Iran, and exposed to 85, 95, and 105 dB noise levels for 5 minutes. The participants' blood pressure and heart rate were measured using Beurer BC16 pulse meter both before and after the exposure. Results. The study results showed no significant difference in blood pressure and heart rate before and after the exposure. However, the workers' systolic blood pressure had increased compared to before the exposure; of course, the difference was not statistically significant (P > 0.05). Besides, although the subjects' heart rate had reduced in comparison to before the exposure, the difference was not statistically significant (P > 0.05). Conclusion. No significant change was observed in blood pressure and heart rate after acute exposure to 85, 95, and 105 dB noise levels. Noise is one of the physical factors in industries, and, today, more attention is being paid to its harmful effects. After smoking and air pollution, noise pollution is considered as the third cause of heart attack among the residents of Berlin . World HAlmost two thousand years ago, Pliney stated that the individuals living near noisy waterfalls tend to suffer from hearing loss sooner than other people. Also, Ramazzini reported several cases of occupational deafness in 1700 . The resOverall, according to the report by WHO, noise causes 4 million dollars health damage every day , 11, andBased on what was mentioned above and since noise can have both physiological and psychological effects on humans, the present study was conducted in order to investigate the effects of noise exposure on blood pressure and heart rate in steel industry.The present cross-sectional study aimed to investigate the effect of occupational noise exposure on heart rate and systolic as well as diastolic blood pressure. Considering CI = 95% and power of 90%, the sample size of the study was determined as 50 subjects who were selected through simple random sampling. The inclusion criteria of the study were being physically and psychologically healthy, not smoking, not using alcohol, not taking hypnotic drugs, and not working in shifts.The participants' demographic information was gathered through a questionnaire, and their systolic as well as diastolic blood pressure and heart rate were measured using Beurer BC16 pulse meter. In addition to assessing the workplace noise, a sample of the devices' noise was also obtained. In doing so, a microphone was attached to a worker's collar near his ear and the device's noise was recorded for 10 minutes.t-test was used in order to compare the means of the variables before and after noise exposure.Considering the features of steel industry, this study was conducted with exposure to 85, 95, and 105 dB noise levels in controlled experimental conditions for 3 consecutive days. At first, the subjects were placed in a quiet room with the background noise level of 40 dB and their systolic as well as diastolic blood pressure and heart rate was measured. Then, they were exposed to the noise recorded from the workplace at 85, 95, and 105 dB levels for 5 minutes and systolic as well as diastolic blood pressure and heart rate was measured again. In order to eliminate the sequence effect, the experiments were performed with 24 h intervals. Finally, the data were entered into the SPSS statistical software, and paired The demographic characteristics of the study subjects are presented in Overall, devices were there in 38% of the workplace space. Moreover, the results of workplace noise analysis showed that, among the 60 areas under study, 13 (23%) had over 85 dB noise level and 23 (39%) had caution range noise level, that is, 65–85 dB.P > 0.05). On the other hand, diastolic blood pressure increased a little at all the three noise levels. Besides, a decrease was observed in the mean of heart rate at all the noise levels; nevertheless, the changes were not statistically significant (P > 0.05).As the table depicts, the mean of systolic blood pressure has increased at all noise levels except for 85 dB; however, the changes were not statistically significant (Up to now, the mechanism noise that affects blood pressure has not been identified. Nevertheless, several studies have shown high secretion of vasoconstrictors in urine as a result of being exposed to higher than 90 dB noise levels, which might represent the biological effects of noise exposure on blood pressure . In the Overall, since blood pressure and heart rate might be affected by various factors, the results obtained regarding the effects of noise exposure on these parameters must be interpreted with caution.The findings of the present study were in agreement with those of the previous studies conducted on the issue. According to the results, no significant difference was observed in blood pressure and heart rate before and after acute exposure to 85, 95, and 105 dB noise levels.


This study evaluated normotensive diabetic patients’ blood pressure response to graded exercise and their echocardiographic pattern of left ventricular geometry.A descriptive, cross-sectional, hospital-based study was carried out on 30 normotensive type 2 diabetic patients and 34 controls, aged 30 to 60 years. The outcome measures were to determine the exercise-related variable, blood pressure response, and left ventricular geometry by means of echocardiography.p = 0.007). Peak systolic blood pressure was significantly higher in G2 than G1 subjects . Although there was no statistically significant difference in the left ventricular (LV) mass index between the groups, G2 patients had significantly higher relative wall thicknesses than G1 patients .Nineteen (29.7%) and 11 (17.2%) normotensive diabetic subjects had normal left ventricular geometry and concentric left ventricular remodelling, respectively. None of the subjects had concentric or eccentric left ventricular hypertrophy. On this basis, the normotensive diabetic subjects were divided to two groups: G1  and G2 (concentric left ventricular remodelling). The groups had comparable mean age, body mass index (BMI), fasting blood glucose (FBG) and two-hour post-prandial blood glucose values, and heart rate, systolic (SBP) and diastolic blood pressure (DBP) at rest. G2 patients had higher mean duration of diabetes than G1 subjects (69.0 ± 9.48 vs 18.7 ± 8.7 months; Normotensive diabetic subjects with concentric left ventricular remodelling have increased blood pressure reactivity to exercise. It is probable, as suggested in earlier studies, that increased blood pressure reactivity to exercise is an indicator of target-organ damage, particularly in normotensive diabetics. Stress increases blood pressure, and variable individual blood pressure responses have been evaluated with regard to prediction of new-onset hypertension, target-organ damage and incident cardiovascular disease or death.4Arterial stiffness is also related to type 2 diabetes,In light of the above, we set out to investigate the relationship between blood pressure response to graded exercise in normotensive diabetics and their echocardiographic pattern of left ventricular geometry, as evidence of cardiac end-organ damage.Thirty normotensive type 2 diabetic subjects  and 34 normal controls  aged 30 to 60 years were recruited through the medical out-patient department of Obafemi Awolowo University Teaching Hospitals complex (OAUTHC), Ile Ife, Nigeria. Ethical clearance for the study was approved by the Ethics and Research Committee of the Hospital in conformity with ethical guidelines of the 1975 Declaration of Helsinki, and all participants gave written consent to participate.Demographic parameters of the subjects were noted and recorded. All subjects were clinically examined to evaluate their body mass index (BMI) and cardiovascular status at rest. Subjects were considered diabetic if they had fasting plasma glucose (FBG) values ≥ 126 mg/dl (7.0 mmol/l)A resting 12-lead ECG was done to exclude patients with baseline ST-segment abnormalities and bundle branch block. Also excluded were patients with coexisting hypertension or who were on antihypertensive(s), those with established chronic renal failure or serum creatinine levels > 1.5 mg% (132 μmol/l), congestive heart failure, valvular heart disease and other diseases known to influence LV function, such as thyroid disease and severe obesity.All the subjects underwent treadmill-symptom limited maximal exercise using the Bruce protocol.The subjects also had transthoracic two-dimensional (2D) and 2D derived M-mode echocardiography performed, according to standard procedure,2) = 0.80 [1.04 (LVIDD + PWT + IVST)3 – (LVIDD)3] + 0.6 g/BSAEstimated LV mass index . Diabetic subjects had significantly higher FBG values than the controls .The diabetic subjects and controls had comparable ages and BMIs . The patients’ characteristics at rest were not statistically significantly different The normotensive diabetic subjects were then divided into two groups: G1  and G2 (concentric left ventricular remodelling) on this basis. The groups had comparable mean ages, BMIs, FBG and two-hour post-prandial blood glucose values, heart rates, and SBP and DBP at rest p = 0.04). The difference between resting systolic and peak systolic blood pressure (ΔSBP) as well as resting pulse pressure and pulse pressure during exercise (ΔPP) followed a similar trend to that of peak systolic blood pressure. Exercise capacity in G2 subjects was significantly lower than in G1 by 12.94% . Although, there was no statistically significant difference between the LV mass index in the two groups, G2 subjects had significantly higher relative wall thicknesses than those in G1  As shown in The relationship of blood pressure response to exercise and endorgan damage in hypertensive subjects is not clear. Studies on this subject in diabetics are few, especially among blacks, who unfortunately are at higher risk of developing cardiovascular-related complications than their Caucasian counterparts.In this study, gender, age and BMI were comparable among the patients with normal LV geometry and those with LV concentric remodelling. The longer duration of diabetes in patients with concentric LV remodelling supports the earlier assertion that the longer the duration of diabetes, the more the likelihood that the patient will develop cardiovascular complications. This was despite the fact that short-term  glycaemic control was similar in both groups in this study, suggesting that blood pressure response during exercise may not have been much influenced by blood glucose exposure.et al. reported that in the resting state, the presence of hyperglycaemia led to an increase in SBP and DBP independently of endogenous insulin in 20 patients with type 2 diabetes. A reduced availability of nitric oxide was suggested as a possible explanation.16It has been suggested that blood pressure response may be related to blood glucose control.In our study, the peak systolic blood pressure during exercise was significantly higher in patients with LV concentric remodelling than in those with normal LV geometry. This however was not the case with peak diastolic blood pressure. This was reflected in the significant change in pulse pressure (ΔPP) observed during exercise. Pulse pressure provides a crude guide to stiffness of the large conduit arteries.6Exercise capacity was also reduced in patients with LV concentric hypertrophy in our study. This may provide additional explanation for reduced exercise tolerance in normotensive diabetes patients. It has been suggested that the voltage on the ECG of left ventricular hypertrophy may be an early marker of impaired exercise capacity.Normotensive diabetics with concentric left ventricular remodelling have increased systolic blood pressure reactivity to exercise. It is probable, as suggested in earlier studies, that increased blood pressure reactivity to exercise is an indicator of target-organ damage, especially in normotensive diabetics.