Patients with inflammatory joint diseases (IJD) have a high prevalence of hypertension and increased arterial stiffness. The aim of the present study was to evaluate the effect of long-term rosuvastatin treatment on arterial stiffness, measured by augmentation index (AIx) and aortic pulse wave velocity (aPWV), and blood pressure (BP) in IJD patients with established atherosclerosis.Eighty-nine statin naïve IJD patients with carotid atherosclerotic plaque(s)  received rosuvastatin for 18 months to achieve low-density lipoprotein cholesterol goal ≤1.8 mmol/L. Change in AIx (ΔAIx), aPWV (ΔaPWV), systolic BP (ΔsBP) and diastolic BP (ΔdBP) from baseline to study end was assessed by paired samples t-tests. Linear regression was applied to evaluate associations between cardiovascular disease (CVD) risk factors, rheumatic disease specific variables and medication, and ΔAIx, ΔaPWV, ΔsBP and ΔdBP.2 (p = 0.03), ΔsBP: -5.27 mmHg (p = 0.004) and ΔdBP -2.93 mmHg (p = 0.01). In linear regression models, ∆aPWV was significantly correlated with ΔsBP and ΔdBP .AIx, aPWV, sBP and dBP were significantly reduced from baseline to study end. The mean (95%CI) changes were: ΔAIx: -0.34 % (p = 0.03), ΔaPWV: -1.69 m/sThere is an unmet need of studies evaluating CVD prevention in IJD patients. We have shown for the first time that long-term intensive lipid lowering with rosuvastatin improved arterial stiffness and induced a clinically significant BP reduction in patients with IJD. These improvements were linearly correlated and may represent novel insight into the pleiotropic effects by statins.NCT01389388ClinicalTrials.gov  Patients with inflammatory joint diseases (IJD), including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA), have an increased risk of atherosclerotic cardiovascular disease (CVD) .Hypertension (HT) is common in patients with IJD and is one of the most important predictors of CVD in the general population ,3. ConsiArterial stiffness reflects the cumulative effect of traditional and novel CVD risk factors on the large arteries , and is ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases, the RORA-AS study, that rosuvastatin treatment over 18 months induced carotid plaque regression in IJD patients . Patients suffering from atrial fibrillations were excluded from this analysis.The Sphygmocor apparatus  is the most commonly used device for estimating arterial stiffness , and waset al. , rheumatic disease activity  or LDL-c, and 2) evaluate correlations of ΔAIx, ΔaPWV, ΔsBP and ΔdBP with area under the curve (AUC) inflammation  and change in c-IMT, CP height, inflammation , rheumatic disease activity , LDL-c, body mass index (BMI) and lifestyle parameters , during the study period.Model assumptions and validity were assessed using residuals. Two-sided p-values < 0.05 were considered significant. Statistical analyses were performed using SPSS version 21 .A flow chart of the RORA-AS study is shown in 2, respectively. Brachial BP was also significantly improved as the mean (SD) sBP was reduced by -5.27  mmHg and dBP was reduced by -2.93  mmHg  mmHg . The tre00) mmHg .The adjusted linear regression analyses with ∆AIx and ∆aPWV as dependent variables  indicateFor ∆sBP and ∆dBP, the adjusted multiple linear regression analyses  showed aEstimates from the unadjusted linear regression analyses with ∆AIx, ∆aPWV, ∆sBP and ∆dBP as dependent variables  did not Additional unadjusted linear regression analyses revealed that age was the only significant baseline predictor for change in arterial stiffness or BP levels, as increasing age could predict ∆aPWV (p = 0.01) and ∆dBP (p = 0.03) . In unadThe main findings in the present study were that BP and arterial stiffness were significantly improved in IJD patients with established atherosclerosis who received intensive lipid lowering with rosuvastatin over 18 months. Further, we found a significant correlation between the observed reduction in aPWV and BP levels, irrespective of change in antihypertensive medication. Our results also showed that the reduction in BP seen in IJD patients treated with rosuvastatin was larger in patients with higher baseline BP.Previous studies have reported a significant reduction in AIx and aPWV in RA patients following short-term (12 weeks), low- and moderate-dose primary CVD preventive treatment regimens with simvastatin and atorvastatin ,18. HoweFurthermore, our study is the first to indicate a potentially clinically significant antihypertensive effect by statins in patients with IJD.Two previous meta-analyses have reported a modest, but clinically important antihypertensive effect by statins in other high CVD risk populations ,21. Our We did not detect a correlation between BP lowering and inflammatory variables in our patients. Furthermore, we did not detect a correlation between the improvement in arterial stiffness or BP with LDL-c reduction in our study, which is in line with previous reports ,19,21.It has been hypothesized that the antihypertensive effects by statins is related to their ability to reduce arterial stiffness ,29. Our The change in AIx during the study was not correlated with or predicted by traditional CVD risk factors, rheumatic disease variables or medication use. Although AIx and aPWV are both indices of arterial stiffness, they cannot be regarded as interchangeable measures . While aThe relatively low number of patients in the study was a consequence of that the statistical strength of the RORA-AS study was calculated on the basis of its primary end-point, namely CP height reduction. Nevertheless, the current study is to our knowledge the largest study to evaluate the effect of statins on arterial stiffness in patients with RA and the first to evaluate this matter in patients with AS or PsA. Results from a control group in a randomized designed trial would also have been advantageous. However, the ethical implications of giving a placebo to patients with established atherosclerosis over the course of 18 months precluded this. On the other hand, as arteries become stiffer with increasing age , it is nIn conclusion, IJD patients with established atherosclerosis experienced a reduction of arterial stiffness and a clinically important BP reduction after intensive lipid lowering with rosuvastatin for 18 months. In addition, we have shown that the improvement of aPWV and reduction in BP levels were correlated; this may provide novel insight into the mechanisms responsible for the pleiotropic effects by statins.S1 File(PDF)Click here for additional data file.S2 File(PDF)Click here for additional data file.S3 File(PDF)Click here for additional data file.S1 TableRA: Rheumatoid arthritis, AS: Ankylosing spondylitis, PsA: Psoriatic arthritis, Paired samples t-test by diagnose.(DOCX)Click here for additional data file.S2 TableΔ: Change from baseline to study end, aPWV: aortic pulse wave velocity, AIx: Augmentation index, sBP: Systolic blood pressure, dBP: Diastolic blood pressure, bMARDs: Biological disease-modifying anti-rheumatic drugs, sDMARDs: synthetic disease-modifying anti-rheumatic drugs, NSAIDs: Nonsteroidal anti-inflammatory drugs, CRP: C-reactive protein, ESR: Erytrocyte sedimentation rate, DAS28: Disease activity score 28 joints, ASDAS: Ankylosing spondylitis disease activity score, LDL-c: Low-density lipoprotein cholesterol, Unadjusted linear regression analyses.(DOCX)Click here for additional data file.S3 TableΔ: Change from baseline to study end, AIx: Augmentation index, aPWV: aortic pulse wave velocity, sBP: systolic blood pressure, dBP: diastolic BP, BMI: Body mass index, Anti-HT: Antihypertensive medication , AntiHT change: New antihypertensive medication, drug switch or dose adjustment, Physical activity: ≥ 1 per week, reported on patient questionnaire, CRP: C-reactive protein, AUC: Area under the curve, ESR: Erytrocyte sedimentation rate, DAS28: Disease activity score 28 joints, ASDAS: Ankylosing spondylitis disease activity score, LDL-c: Low-density lipoprotein cholesterol, c-IMT: Carotid intima-media thickness, CP: Carotid plaque. Unadjusted linear regression analyses.(DOCX)Click here for additional data file.


A critical issue in the management of chronic kidney disease (CKD) is to prevent patients from the progression to end-stage kidney disease (ESKD), however, there is only limited number of biomarkers for the discrimination of the high-risk CKD patients. We aimed to identify the metabolites which possess the ability to predict the earlier kidney deterioration. We performed capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling in a prospective cohort, which consisted of referred 112 CKD patients with median follow-up period of 4.4 years. The association between the levels of candidate metabolites and the outcomes  were assessed by multivariate Cox proportional hazard models after adjusting for the baseline covariates. A total of 218 metabolites were detected in the plasma of CKD patients. We identified 16 metabolites which have predictive values for the composite outcome: The risk for composite outcome was elevated from 2.0- to 8.0-fold in those with higher levels of 16 plasma metabolites. Our results suggest that the measurement of these metabolites may facilitate CKD management by predicting the risk of progression to ESKD. Chronic kidney disease (CKD) is a global health problem345Taking the fact that kidney is one of metabolically-active organs791011121517We conducted capillary electrophoresis and liquid chromatography mass spectrometry (CE-MS)-based metabolic profiling21We performed a metabolic profiling from a prospective cohort, which consisted of referred CKD patients. Data were generated from 112 participants with median follow-up period of 4.4 years . The baseline characteristic is shown in Metabolomic analyses were performed using the plasma samples of this cohort. Out of 579 metabolites in the library, a total of 218 metabolites were detected in the plasma of CKD patients. Among them, 129 metabolites, including creatinine and urea nitrogen, were above the detection limits in at least 40% of study subjects and were subjected to the rest of the analyses. The levels of 73 out of 129 metabolites were significantly correlated with eGFR : the increased levels of urea and creatinine, which represent kidney function, showed the strongest correlation with the decreased level of eGFR, whereas the levels of the rest of metabolites variably, but less strongly, correlated.The levels of metabolites were divided into three tertiles and were subjected to the Cox regression analyses. The Holm-corrected multiple testing revealed that the levels of 26 out of 127 metabolites (creatinine and urea were excluded) had predictive values on the composite outcome  in diabetic patientset al. demonstrated that the levels of 12 metabolites were associated with the presence of diabetes in CKDet al. demonstrated that the levels of some plasma metabolites had significant odds ratios for the incidence of ESKD during the observational period in diabetes patients et al. and Yu et al. demonstrated that a subset of blood metabolites in study participants (eGFR ≥60 mL/min/1.73 m2) were associated with the onset of incident CKD (defined by eGFR of <60)15et al. demonstated that the levels or the combined ratios of some serum metabolites were associated with the decreased ratio of eGFR17The number of studies using metabolomics in CKD studies as a tool is increasing, which strongly suggests the growing interests of this field91011121415161718The 16 metabolites identified in the present cohort are located on widely variable metabolic pathways. These pathways include nucleotides (cytidine and uridine), glycolysis , amino acids (guanidinosuccinate [guanidinosuccinic acid] and 3-methylhistidine), amino sugar (N-acetylneuramine [N-acetylneuraminic acid] and glucoronate [glucuronic acid]), biotin (pimelate [heptanedioic acid]), glutathione (5-oxoproline [pyroglutamic acid]), and taurine (isethionate [2-hydroxyethanesulfonate]). In addition, the origins or pathways of some metabolites are unidentified . These metabolites might be originated from extracorporeal metabolisms such as gut flora, dietary, and environmental chemicals, whose importance in CKD patients are rediscovered recentlyet al. reported that lower levels 5-oxoproline was associated with incidence of CKDThe association with kidney function have been demonstrated in some of metabolites identified in this study. Guanidinosuccinate, trimethylamine N-oxide, 3-methylhistidine289This study has some limitations that need to be addressed in further studies. Although the present study was strengthened by the longitudinal observation, the limitations exist on relatively small number of the cohort and the dependence only on the baseline characteristics. We performed power analyses using a type I error of 5% and 80% power. These analyses revealed that 19 or 65 patients would be needed for the median (3.62 for uridine) or lowest hazard ratios  of the selected metabolites in the prediction set, respectively. Therefore, we had enough sample size to determine the association between composite outcomes and these metabolites, though the effects of unselected metabolites might be underestimated. This is especially the case in the presence of statistical processes of multiple comparison or adjustments. The correlations between the metabolites identified in this study and eGFR also complicated the results. Although our results were achieved by adjusting for eGFR, we could not completely rule out residual confounding due to kidney function. We considered that the levels of these metabolites in CKD patients may not be simple reflections of the decreased level of eGFR based on the following observations34In summary, 16 metabolites were related to higher risk of the deterioration of kidney function in advanced CKD patients. Our studied population is based on referred CKD patients, who need immediate and impeding improvement of medical care. Measurement of the metabolites identified herein may facilitate our management of advanced CKD patients through the additional information on the clinical parameters, such as eGFR and urinary protein level. We propose that the metabolomic profiling of CKD patients will potentiate us to perform tailored management of CKD.We prospectively enrolled 118 consecutive patients with CKD stages 3, 4 and 5, who were not on dialysis, from a single nephrology department at Rinku General Medical Centre between August 2005 and January 2009. Baseline blood samples from patients after an overnight fast were collected. Patients with insufficient blood samples were excluded beforehand. This study was approved by the institutional ethics committees of Rinku General Medical Centre and Osaka General Medical Centre, and was adherent to the Declaration of Helsinki. All patients provided written informed consent to participate in the study.Baseline inclusion criteria included age less than 90 years, no complication of malignancy, and no active infection. Patients with incomplete baseline data (n = 2) and started kidney replacement therapy within 1 month after the enrollment (n = 4) were excluded. Final analysis covered the remaining 112 patients.−1.094 × age−0.287, where age is in years, SCr is in mg/dL and the glomerular filtration rate (GFR) is in mL/min/1.73 m2 body surface area. The product of this equation for women was multiplied by a correction factor of 0.739. Serum creatinine was measured by enzymatic methods in the same laboratory. Random urine samples (10 mL) were also collected at baseline to measure the ratio of urinary protein to creatinine. Other baseline variables included age, sex, diabetes defined according to the International Classification of Diseases, Tenth Revision (ICD-10) codes E10-E14, systolic blood pressure, diastolic blood pressure, hemoglobin, albumin, calcium, phosphate, and use of renin-angiotensin system inhibitor, beta-blocker, and calcium blocker. Cardiovascular disease included ischemic heart disease (ICD-10 codes I20-I25), heart failure (ICD-10 code I50), and stroke (ICD-10 codes I60-I67).Kidney function was evaluated from baseline data at the first visit to our outpatient clinic using the estimated glomerular filtration rate (eGFR) based on the equation for Japanese populationThe primary end points were end-stage kidney disease (ESKD) requiring kidney replacement therapy and a composite of ESKD and all-cause of death.Patients received regular follow-up care in the outpatient ward. Data were collected from source documentation at the end of 2011. The baseline and follow-up data were collected from hospital medical records and discharge abstracts, outpatient visit records, contact with primary and dialysis care physicians and death certificates. End points were validated by at least two physicians. The follow-up of patients is available with accuracy because i) this facility is the central hospital of the southern area of Osaka prefecture, and there is no other central hospital in this region, and ii) regional partnership with the primary and dialysis care physicians has been well-established.Metabolites were measured as previously reported with modification21m/z range. A mixed solution of the standards were prepared immediately before CE-TOFMS analysis as previously described38Measurement of metabolites was performed using CE-TOMFS21Raw data were processed using software (MasterHands) developed in-house as previously describedP < 0.05. Statistical analyses were performed using R environment for statistical computing, version 2.15.2We constructed multivariate Cox proportional hazard models to assess an association between each candidate metabolite and the outcome after adjusting for the baseline covariates. Multiple comparison of the hazard models were performed with the Holm method. Log-rank test was used to assess the equality of survival distribution stratified by the median values. Statistical significance was defined as How to cite this article: Kimura, T. et al. Identification of biomarkers for development of end-stage kidney disease in chronic kidney disease by metabolomic profiling. Sci. Rep.6, 26138; doi: 10.1038/srep26138 (2016).


Cadaveric kidney transplantation is performed according to a patient list formed by matching and point score in our country. Demand for renal transplantation can not be met by the number of cadavers introduced to the system because of the increase in number of patients with chronic renal failure who require renal transplantation.We reviewed the results of the patients who had cadaveric kidney transplantation to assess the kidney transplantations in the Turkish Organ and Tissue Information System.The results of the patients who had cadaveric kidney transplantation between years 2011-2014 were reviewed. Patients' age, gender and tissue antigen integration were determined. The chronic rejection and primary graft failure rates were recorded. Survival rates of the grafts and patients during 3, 6, 9, 12, 24, 36 ve 48 months were determined. Kaplan-Meier method was used to calculate the survival rates.The number of kidney transplantations was 11755 between years 2011-2014 in Turkey. The source of organ in 19.2 % of the transplantations was cadaveric. The mean age of the patients who had cadaveric kidney transplantation was 42.3 ± 14.4 (mean ± SD), and 57.6% (1301) of the patients were male and 42.4% (957) were female. Chronic rejection and primary graft failure were determined in 4.9% (110) of the patients. Patient and graft follow-up periods were 23.4 ± 14.9 (mean ± SD) months and 22.7 ± 14.4 (mean ± SD) months, respectively. Mean survival time of the patients was 46.81 ± 0.288 months, and survival times for 3, 6, 9, 12, 24, 36 and 48 months were % 95.3 ± 0.004; % 93.4 ± 0.005; % 92.4 ± 0.006; %91.8 ± 0.006; % 91.4 ± 0.006; %91.3 ± 0.006 and % 91.1 ± 0.006, respectively. Mean survival time of the graft was 46.56 ± 0.23 months in these patients and survival times of the graft for 3, 6, 9, 12, 24, 36 and 48 months were % 98.1 ± 0.003; %97.2 ± 0.004; %96.3 ± 0.004; %96.4 ± 0.004; %95 ± 0.005; %94.1 ± 0.006 and %91.7 ± 0.013, respectively.Although there are attempts to increase cadaveric donation in the whole world, it is still poor because of the reluctance and irrelevance of the donor families. Even though, the patient and graft survival rates were higher in live kidney transplantations than cadaveric kidney transplantations. In recent decade, cadaver-kidney transplantations also had high success rates. In our opinion, cadaver-kidney transplantations should be increased in respect of the results of the cadaver-kidney transplantations in our country.


The aim of the study was to explore the prevalence and risk factors for technical-induced hemolysis in adults supported with veno-venous extracorporeal membrane oxygenation (vvECMO) and to analyze the effect of hemolytic episodes on outcome. This was a retrospective, single-center study that included 318 adult patients  with acute respiratory failure treated with different modern miniaturized ECMO systems. Free plasma hemoglobin (fHb) was used as indicator for hemolysis. Throughout a cumulative support duration of 4,142 days on ECMO only 1.7% of the fHb levels were above a critical value of 500 mg/l. A grave rise in fHb indicated pumphead thrombosis (n = 8), while acute oxygenator thrombosis (n = 15) did not affect fHb. Replacement of the pumphead normalized fHb within two days. Neither pump or cannula type nor duration on the first system was associated with hemolysis. Multiple trauma, need for kidney replacement therapy, increased daily red blood cell transfusion requirements, and high blood flow (3.0–4.5 L/min) through small-sized cannulas significantly resulted in augmented blood cell trauma. Survivors were characterized by lower peak levels of fHb [90  mg/l] in comparison to non-survivors . In conclusion, marked hemolysis is not common in vvECMO with modern devices. Clinically obvious hemolysis often is caused by pumphead thrombosis. High flow velocity through small cannulas may also cause technical-induced hemolysis. In patients who developed lung failure due to trauma, fHb was elevated independantly of ECMO. In our cohort, the occurance of hemolysis was associated with increased mortality. The application of extracorporeal membrane oxygenation [ECMO] for patients with refractory respiratory failure failing conventional therapy has increased considerably  with impMajor contributors of technical-induced hemolysis may consist of sublethal damage to erythrocytes by shear stress –11, highThe aim of the current study was to analyze (i) the incidence of technical-induced hemolysis using different modern ECMO-systems, (ii) the specific reasons for episodes of moderate/severe hemolysis, (iii) possible technical causes for hemolysis, and (iv) the influence of high fHb on survival.This is a retrospective analysis on prospectively collected data (Regensburg ECMO database) from 318 consecutive patients on vvECMO (2009–2014) . Patient2 > 70 mmHg, pH normal) aiming for a fraction of inspired oxygen (FiO2) < 60%, a peak inspiratory pressure < 28 cmH2O, and a tidal volume (TV) < 4 mL/kg predicted bodyweight. The positive end-expiratory pressure (PEEP) initially was kept high to avoid lung de-recruitment ECMO blood flow (maximum 4.5 L/min), FiO2 and PEEP were adjusted to maintain an arterial oxygen saturation of > 90%. Sweep gas flow, TV and respiratory rate (RR) were adjusted according to the arterial partial pressure of carbon dioxide (PaCO2) aiming at a normal pH. Hemoglobin was kept > 8 g/dL. The anticoagulation protocol was based on a continuous intravenous heparin application. In patients without elevated bleeding risk an activated partial thromboplastin time (APTT) of 50–60 seconds was persued.Indications for vvECMO treatment have been defined previously ,24 in acStudy patients required one (n = 211) or more oxygenators (n = 107) during the support interval. Different ECMO-systems from three companies  were applied as the initial ECMO-system. Variable types of back-flow cannulae ; Maquet), drainage cannulae , and single dual-lumen cannulae  were inserted.CVVHD is a short-term treatment utilized in intensive care unit (ICU) patients with acute or chronic renal failure. Dialysis was undertaken with the aid of the Genius® single-pass batch-dialysis system with a high-flux polysulfone dialyser FX 60 . Blood flow and countercurrent dialysate flow ranged between 120 and 250 mL/min. Patients with acute kidney failure requiring ECMO therapy were supported with CVVHD both before initiation or during ECMO treatment.3/s) per cross section area of the cannula (m2).Routine laboratory parameters included measurement of LDH and fHb. Blood samples were collected via arterial catheters using lithium-heparin tubes. According to the ELSO Registry, the present study defined hemolysis complicating ECMO support as fHb > 500 mg/L , 26, 27.Data from all patients were evaluated to give an overview of fHb levels. Then, a detailed case-by-case analysis of outlier peak values of fHb was done to explore individual causes with significant hemolysis. After identifying these episodes, respective data were cleared from further analysis. Finally, all data originating from the first ECMO-run were collected to analyze the effect of different pump and cannula types, duration of the ECMO-run, diagnosis leading to lung failure and ECMO therapy, blood flow, and amount of RBC transfusions per day on the development of hemolysis.Continous data are expressed as median values and interquartile ranges (IQR: q3-q1); categorical variables are presented as absolute numbers and proportions. Due to the right-skewed distribution of the fHb and LDH values, nonparametric statistical methods were used for all analyses. To analyze the impact of all possible predictors  can indicate pumphead thrombosis (PHT) . In 8 paIn contrast, acute clot formation within the oxygenator  resulted in a marked increase in pressure-drop across the oxygenator, but fHb remained stable  mg/L; day of replacement, 86  mg/L).Data from the first ECMO run were analysed to evaluate the effect of ECMO duration, pump and cannula type, blood flow, flow velocity, diagnosis resulting in ECMO treatment, concurrent use of CVVHD, and the impact of RBC transfusions on fHb. The association of potentially relevant technical and clinical factors with hemolysis during vvECMO therapy is summarized in Regarding the time course on the first MO , no signThe blood pumps of the different ECMO-systems were operated at distinct device-settings . Due to Blood flow was classified into 3 groups . The linear mixed models demonstrated a significant impact of blood flow on fHb (p = 0.002), but not on LDH (p = 0.134). Low and medium blood flows were associated with a lower fHb level, while higher blood flow resulted in a moderate increase in fHb  L/min, p = 0.02; single 23 Fr, 2.7  L/min, p = 0.005; vs Avalon 27 Fr, 2.4  L/min) and generated less negative pressure  mmHg, p≤0.001; single 23 Fr, -7.0  mmHg, p = 0.005; vs Avalon 27 Fr, -29.0  mmHg). Within the used blood flows, there was no difference in fHb levels  mg/L; single 23 Fr, 59  mg/l; vs Avalon 27 Fr, 57  mg/L); non-significant) or LDH (not shown).To analyze the influence of different causes resulting in lung failure and ECMO therapy on fHb and LDH, patients were categorized into 4 diagnostic groups , Fig 5: Renal failure and the need for CVVHD resulted in an increase of fHb (p = 0.036) and LDH (p≤0.001) compared to patients without renal failure. ECMO therapy without CVVHD was associated with lower levels of fHb and LDH compared to patients with CVVHD-requirement before and/or during ECMO therapy .An increased demand of RBCs per day was associated with a rise in fHb (p = 0.001) . The larTo determine the independent effect of each factor, the variables diagnostic group, number of RBCs per day, flow velocity, blood pump type and CVVHD were included into the analysis. The multivariable model showed, that higher levels of fHb were significantly associated with patients who required ECMO therapy due to acute respiratory failure triggered by multiple trauma (p = 0.003), high numbers of RBCs per day (p = 0.017) and high flow velocity (p = 0.013). Blood pump type and need of CVVHD had no independent effect on fHb values .Peak levels of fHb and LDH were obtained from each patient to describe their impact on survival. Mortality on ECMO was both linked to higher peak levels of fHb and LDH . LogistiBesides thromb-embolic complications and bleeding, hemolysis was a serious problem with early extracorporeal lung support. In recent years several new, technically optimized ECMO-systems have been developed. Improved pump design, low resistance oxygenators, plasma-tight gas exchange membranes made of poly-methyl-pentene and surface-coating of all compartments resulted in less need of systemic anticoagulation and better biocompatibility also in mid- and long-term application. To our knowledge, there has been no comprehensive analysis on the incidence and the causes of hemolysis in the adult population with this new devices.Recently, it was shown that only one third of pediatric patients on ECMO were free of hemolysis, but almost 7% displayed severe hemolysis with fHb values larger than 1000 mg/L . HemolysIn contrast, AOT or clotting within the oxygenator did increase D-dimers, but not fHb, probably because no disruption of erythrocytes occurred ,31.Of a total of 4,142 measurements of fHb, only 1.7% were above 500 mg/l. This striking difference to the pediatric population may be explained by the fact, that we solely analysed vvECMO runs, whereas Lou et al.  mainly iDue to the risk of hemolysis on ECMO support , daily rTechnical-induced hemolysis can result from several factors  includinIn previous bench studies, a correlation between hemolysis and the pressure drop across the oxygenator during ECMO was proven for polypropylen oxygenators that were available for pediatric cardiopulmonary bypass . The use2-removal on blood flows up to 2 l/min and can cause hemolysis if run on higher flows. Therefore, both the choice of cannula and adaptation of the blood flow can prevent technical-induced hemolysis [Higher levels of fHb may be due to higher blood flows, but could also be explained by a higher severity of disease with sepsis. Therefore, we analysed whether an increase of flow velocity causes more hemolysis. We could demonstrate a correlation between the two factors especially with higher flow velocities . Within emolysis .It is well known that high negative pressures, e.g. generated by kinking of lines or obstruction of in-flow can cause cavitation and hemolysis . The negPatients, who required CVVHD prior to ECMO initiation displayed a significantly higher level of fHb. Comparable results were demonstrated in pediatric patients requiring ECMO support following congenital surgical repair . It was Patients who developed lung failure after multiple trauma showed significantly higher fHb values compared to patients with lung failure of other diagnostic groups. These patients often required ECMO support after severe hemorrhage, high velocity accidents or blast injury, extensive surgery and necessity for multiple transfusions . Both inMultivariable statistical analysis revealed that higher levels of fHb are associated with multiple trauma, increased RBC transfusion and high flow velocity. Increased levels of fHb and LDH were associated with a higher mortality in our study, which is in accordance with previous data on patients with sepsis . Due to Our study has several limitations. It is a retrospective monocentric analysis which intended to find possible causes for hemolysis in adult patients on vvECMO. We have tried to study outliers individually to identify rare causes of hemolysis, as statistical methods are inclined not to detect the extremes. Almost all patients who were in need of ECMO had severe sepsis, which itself can cause hemolysis, thus, the observed levels of fHb most likely were not solely due to ECMO, but may have been related to other causes. Our investigations relate to the blood flows and cannulae used in this study and can not be generalized to other centers which may use larger blood flows or smaller cannulae. Finally, intravascular hemolysis and increased levels of fHb are a late marker of blood trauma. Activation and destruction of platelets may be a more suitable parameter to detect subtle injury.This is the first study with a large cohort of adult patients treated with vvECMO which investigated the incidence and possible causes of hemolysis. It proves that modern miniaturized ECMO devices are safe and generally do not cause significant hemolysis during long-term use. LDH commonly is elevated in patients with severe sepsis and thus is an unreliable parameter for hemolysis on ECMO. Marked hemolysis is seen in about 3% of patients and often due to a clot within the pump head, which should trigger prompt exchange. Expectedly, high flow velocity can cause more blood damage. In consequence, the size of cannulae has to be guided by expected need of blood flow. It is advisable that fHb is routinely measured in all patients on ECMO on a daily basis to detect problems at an early stage.


Background: In many Western populations, blood pressure varies moderately with season and outdoor temperature. Relatively little is known about effects of seasonal changes in blood pressure on the detection and control of hypertension in general populations, especially in low- and middle-income countries.Methods: We analysed cross-sectional data of 57 375 (42% men) participants aged 30–79 (mean 52.3) years who were enrolled during 2004–08, as part of the China Kadoorie Biobank, from a rural county in the south-east costal Zhejiang Province. Analyses related daily mean outdoor temperature, obtained from local Meteorological Bureau, to mean systolic (SBP) and diastolic blood pressure (DBP), rate of newly detected hypertension and, among those with self-reported physician-diagnosed hypertension, rate of adequate blood pressure control, using multiple linear and logistic regression models.Results: The overall mean blood pressure was 135.9 mmHg for SBP and 80.5 mmHg for DBP. Daily outdoor temperature ranged between −2.9 and 33.7°C, with July being the hottest month (mean 29.4°C) and January the coldest (mean 4.0°C). Comparing January (the coldest month) with July (the warmest), the differences in the adjusted SBP/DBP were 19.2/7.7 mmHg. Each 10°C lower ambient temperature was associated with 6.9/2.9 mmHg higher SBP/DBP,14.1% higher prevalence of newly detected hypertension and, among those with pre-diagnosed hypertension, 13.0% lower hypertension control rate.Conclusion: In rural China, lower outdoor temperature is strongly associated with higher mean blood pressure and hypertension prevalence as well as poorer hypertension control, and should be considered when conducting population-based hypertension surveys and providing treatment for hypertensive patients. The significant seasonal variations in blood pressure were primarily driven by changes in outdoor temperature.When outdoor temperature dropped, blood pressure increase dramatically and a higher prevalence of hypertension could be detected. This should be taken into account when conducting and evaluating population-based hypertension survey.Lower outdoor temperature could attenuate the blood pressure control rate in people with known hypertension. This should be considered by hypertensive patients and their care/treatment providers.Hypertension, or raised blood pressure, is a common, dangerous and treatable condition, but its detection and control remain a major health challenge in many parts of the world, particularly in low- and middle-income countries such as China. Several environmental and lifestyle factors are known to be associated with raised blood pressure, including cold temperature, alcohol drinking, adiposity and salt intake. In Western populations where most people have good access to adequate housing and health care, mean blood pressure in adults tends to vary only moderately with outdoor temperature.To fill in this knowledge gap, we report a detailed analysis of cross-sectional data of over 50 000 adults from a rural coastal area in the south of Yangzi River, from the China Kadoorie Biobank (CKB) study.Detailed information about the CKB study design and recruitment strategy has been reported previously.The study was approved centrally by the ethics committees of the University of Oxford and the Chinese Center for Disease Control and Prevention (CDC). In addition, ethics approval was also obtained from the institutional research board at the Zhejiang Provincial CDC and Tongxiang CDC. All participants provided written informed consent.Information about socio-demographic, lifestyle and medical history was collected using an interviewer-administered laptop-based electronic questionnaire.In the present analysis, hypertension detection rate was defined as proportion of people who had mean SBP ≥140 mmHg or mean diastolic blood pressure (DBP) ≥90 mmHg among those without self-reported physician diagnosed hypertension. Hypertension control rate was defined as proportion of people with prior hypertension whose measured SBP <140 mmHg and DBP <90 mmHg.Local daily outdoor temperature data collected at four time points  during the day for whole of the study period was provided by Tongxiang Meteorological Bureau. Mean monthly, spring , summer , autumn , and winter  outdoor temperature was calculated as the average of outdoor temperatures during the days when participants were surveyed in that month or season.Sedentary leisure time was defined as time spent in sitting-down activities outside work, such as watching TV, reading a newspaper and using a computer. Height and weight were measured following standard protocols and BMI was calculated as weight (in kg) divided by the square of standing height (in m).Least squared means of SBP and DBP were calculated for each season (regardless of the year) and calendar month during the 3.5 years’ study period, with adjustment for age, sex and education level. In additional analyses, outdoor temperature was also adjusted for.The least square means of SBP in each calendar month were also analysed separately in certain subgroups, including by age , BMI categories, smoking status , alcohol drinking status , hypertensive status and fruit intake. Analyses were adjusted for mean age, sex and education level, where appropriate.Multiple linear regression models were used to estimate changes in blood pressure per 10°C lower outdoor temperature, adjusting for age, sex and education level. In additional analyses, season, physical activity (daily hours spent on sedentary leisure activities), dietary factors (i.e. fruit and pickled vegetable intake) and BMI were adjusted for, first individually and then jointly.Using logistic regression models, age-, sex- and education-adjusted hypertension detection and control rates were calculated for each calendar month and season (regardless of the year). To estimate changes in detection and control rates per 10°C temperature, parameters of linear regression lines were obtained from plots of age-, sex- and education- adjusted rates in each month against monthly outdoor temperature. All analyses were performed using SAS 9.3 .2 and 6.4%had BMI ≥28 kg/m2 (cut-off points often used to define overweight and obesity in Chinan = 8216) reported having physician-diagnosed hypertension, and of these 90.7% reported taking antihypertensive drugs. A further 26.9% (29.5% in men and 25% in women) had measured SBP ≥140 and/or DBP ≥90 mmHg (i.e. newly detected hypertension) at the baseline survey. The overall mean (SD) SBP and DBP were 135.9 (21.4) and 80.5 (10.7) mmHg, respectively, with SBP and DBP both being about 2 mmHg higher in men than in women ] age was 52.3 (9.9) years, 41.6% were men and 55.9% had formal education, which was higher in men than in women (73% vs 43.7%) . Among min women .Table 1eTable 1, available as Supplementary data at IJE online).Participants recruited in different seasons were very similar in terms of age and BMI. For both men and women, those recruited in spring had the highest prevalence of physician-diagnosed hypertension and antihypertensive treatment, and those in autumn had the lowest . In general, SBP reached a peak (146.1 mmHg) in January and dropped to the lowest level (126.9 mmHg) in July. This variation was slightly larger in men than in women (20.3 vs 18.1 mmHg), increased with age (from 16.1 mmHg in those aged 30–39 years to 22.9 mmHg in those aged 70–79 years), and was more extreme among those with BMI <18.5 kg/m2 (24.5 vs 18.5–19.8 mmHg in the other three groups), but not much affected by other factors (Average daily outdoor temperature during the study period ranged from −2.9 (°C) to 33.7°C (data not shown), with the highest mean monthly temperature observed in July (29.4°C) and the lowest in January (4.0°C) . When ou factors . The seaeTable 1, available as Supplementary data at IJE online).eFigure 2, available as Supplementary data at IJE online). Using individual data in the model, each 10°C lower temperature was associated with 6.9/2.9 mmHg higher SBP/DBP. These associations hardly changed after additional adjustment for season, physical activity, fruit intake, pickled vegetable intake and BMI (data not shown).There was an almost perfect linear inverse association between mean monthly outdoor temperature and mean monthly BP, regardless of study year (The highest hypertension detection rate was seen in January (56.0%) and the lowest in July (16.7%) . By contIn this large study of rural farmers from the south-east coastal region of China, we observed large seasonal variations in blood pressure, driven primarily by changes in outdoor temperature. Each 10°C lower outdoor temperature was associated with 6.9/2.9 mmHg higher SBP/DBP, a 14.1% absolute increase in hypertension detection rate and, among those with self-reported physician-diagnosed hypertension, a 13.0% absolute decrease in hypertension control rate. Comparing with the hottest month (July), participants recruited in the coldest month (January) were three times more likely to be diagnosed with hypertension (56.0% vs 16.7%), and six times less likely to have appropriate control of blood pressure if they had had hypertension (7.9% vs 45.5%).,Several studies have previously reported on the seasonal variation of blood pressure, using either spot clinic blood pressure,,A few mostly hospital-based studies have also reported on the association of season or ambient temperature with detection and control of hypertension. In a small study of 275 women aged 18–40 years in Delhi, India, where the mean outdoor temperature differed by about 19°C between winter and summer, mean SBP increased by 11 mmHg from summer (114 mmHg) to winter (125 mmHg) and at the same time the detection rate of hypertension almost doubled, from 16% to 31%.,Seasonal variation in blood pressure is not a new phenomenon and is probably mediated mainly by ambient temperature.In this study, we used the average of two blood pressure measurements made at the study clinics during daytime, which may not provide a good estimate of an individual’s usual level of blood pressure in a given condition, including season. Moreover, we used daily temperatures measured at the nearest meteorological offices from survey sites, which may not be a perfect measure of the ambient temperature to which the study participants had recently been exposed. Furthermore, no information was available on indoor temperature at home, workplace or survey clinics, nor about the time each participant spent indoors, so their effects could not be assessed directly. If, however, the measured outdoor temperatures were only partially correlated with the usual temperature to which participants were exposed during the day, our study findings may greatly underestimate the real association between ambient temperature and blood pressure.,Our study findings have implications for assessing the population burden and evaluating the clinical management of hypertension, even though the study population is not intended to be representative of the general population in China or in Zhejiang Province.Supplementary data are available at IJE online.Kadoorie Charitable Foundation; Wellcome Trust; UK Medical Research Council; British Heart Foundation and Cancer Research UK. The baseline survey and first re-survey in China were supported by a research grant from the Kadoorie Charitable Foundation in Hong Kong. Follow-up of the project during 2009–14 is being supported by the Wellcome Trust in the UK (grant 088158/Z/09/Z). The project is also supported by core funding to the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) at Oxford University from the UK Medical Research Council; the British Heart Foundation and Cancer Research UK.The China Kadoorie Biobank was supported by the:


Chronic monitoring of heart rate, blood pressure, and flow in conscious free-roaming large animals can offer considerable opportunity to understand the progression of cardiovascular diseases and can test new diagnostics and therapeutics. The objective of this study was to demonstrate the feasibility of chronic, simultaneous measurement of several hemodynamic parameters  using a totally implantable multichannel telemetry system in swine heart failure models. Two solid-state blood pressure sensors were inserted in the left ventricle and the descending aorta for pressure measurements. Two Doppler probes were placed around the left anterior descending (LAD) and the brachiocephalic arteries for blood flow velocity measurements. Electrocardiographic (ECG) electrodes were attached to the surface of the left ventricle to monitor heart rate. The telemeter body was implanted in the right side of the abdomen under the skin for approximately 4 to 6 weeks. The animals were subjected to various heart failure models, including volume overload , pressure overload  and dilated cardiomyopathy . Longitudinal changes in hemodynamics were monitored during the progression of the disease. In the pacing-induced tachycardia animals, the systemic blood pressure progressively decreased within the first 2 weeks and returned to baseline levels thereafter. In the aortic banding animals, the pressure progressively increased during the development of the disease. The pressure in the A-V fistula animals only showed a small increase during the first week and remained stable thereafter. The results demonstrated the ability of this telemetry system of long-term, simultaneous monitoring of blood flow, pressure and heart rate in heart failure models, which may offer significant utility for understanding cardiovascular disease progression and treatment. Blood pressure, blood flow and heart rate are often altered under different cardiovascular conditions, such as heart failure. The monitoring of these parameters is therefore seminal in the study of cardiovascular physiology, pathogenesis, pharmacology and treatment modalities. Although many methods have been used to perform these measurements, the animals are typically under anesthesia where the normal physiological regulation may be affected Radio-telemetry is an alternative method that addresses some of these shortcomings. It provides continuous recordings without stress from any exogenous factors. This technology has been developed and tested in both small and large animals We previously developed an implantable radio-telemetry system with multichannel and long life battery that was tested in normal animals The telemetry unit, the receiver, and the signal processing stations  were proThe implant was powered by a lithium battery , which lA remotely positioned radio frequency transceiver link was attached to the base station decoder/controller unit through a cable. This allowed the base station decoder/controller unit to be placed in a remote location away from the animals' housing, which minimized the effects of human presence. The transceiver was placed near the animals' cage, which allowed the swine free movement within the pen. The signals were automatically registered and saved in a computer using a data acquisition system . An illustration of the telemetry implant in an animal and the data acquisition system are shown in 2. Electrocardiographic (ECG) leads were attached to the swine limbs. Body temperature was maintained at 37.5±0.5°C and pH at 7.4±0.1. Heart rate, respiratory rate, SpO2 and ETCO2 were monitored during the duration of the procedure. All animal experiments were performed in accordance with national and local ethical guidelines, including the Principles of Laboratory Animal Care, the Guide for the Care and Use of Laboratory Animals and the National Association for Biomedical Research Eight Yorkshire swine (40–55 Kg body weight) of either sex were used in this study. The animals were divided into 3 groups according to the heart failure model: volume overload , pressure overload , and dilated cardiomyopathy . The animals were fasted overnight and surgical anesthesia was induced with TKX  and maintained with 1–2% Isoflurane-balance OThe chest was opened through a median sternotomy under sterile conditions. A subcutaneous pouch was created on the right lumbar area of the abdomen to hold the implant unit and the battery. The flow probes, pressure sensors and ECG leads were tunneled subcutaneously towards the chest and into the chest cavity. The left anterior descending (LAD) artery was dissected free from the surrounding tissue and a 2.5 mm diameter Doppler flow transducer was secured around the artery. The proximal portion of the brachiocephalic artery close to the aortic arch was also dissected free from the surrounding tissue and a 4.5 mm diameter Doppler flow transducer was placed around the artery. The angle of the ultrasonic crystal (0.5 mm in diameter) embedded in the transducer was pre-fixed relative to the blood vessel wall and the space between the crystal and the vessel was filled with ultrasound gel. A Millar pressure sensor was inserted into the left ventricle (LV) through an 18 gauge needle puncture in the free wall close to the apex. Similarly, another pressure sensor was inserted into the aortic arch and advanced towards the descending aorta to measure systemic pressure. The two ECG leads were sutured to the surface of the heart, one close to the base and the other close to the apex. The pressure sensors and ECG electrodes were secured with silk suture on the heart's surface and the connecting cables were secured to the chest wall. All signals were monitored for approximately 15 minutes to attain stability before the chest was closed.After adequate anesthesia, a mid-incision was made on the abdomen. The intestines and bladder were gently moved to one side inside the abdomen to expose the distal aorta and inferior vena cava. Heparin (∼100 IU/kg) was administered to achieve an activated clotting time of >200 seconds prior to creation of the fistula. Both aorta and cava were carefully dissected and partially occluded with an atraumatic tissue clamp. A lateral incision (approximately 0.6 mm) was made on both the aorta and the cava and the free edges were sutured together to create the fistula. The clamp was released and the patency of the fistula confirmed.The chest was opened through a mid sternotomy and the heart was cradled using the pericardial sac. The ascending aorta  was carefully dissected and a sterile constrictor (made of a cable tie recovered with tygon tubing) was placed around it. A Mikro-tip pressure sensor (Millar Instruments) was inserted into the aorta by needle puncture, and the constrictor was cinched until the aortic pressure doubled the baseline. The pressure was recorded for approximately 15 minutes to ensure stability.After opening the chest, two pacemaker leads were secured on the surface of the LV with non-absorbable sutures. The main lead was tunneled through the right fifth intercostal space from the chest cavity to the exterior. The lead was secured to the body of the pacemaker, and the pacemaker was then placed under the skin. The pace pulse was set at 190–230 bpm using a programmer.All three heart failure models were established one week after the telemetry implant. The animals were followed for 4 to 6 weeks during the progression of the disease.All data were expressed as mean ± SD. Comparisons of results between two groups were performed by a paired t-test. Multiple group comparisons were performed with analysis of variance (ANOVA). P<0.05 was considered statistically significant.After the telemetry device was implanted, the measurements were recorded continuously during the first 24 hrs. to verify the stability of the device. The data were sampled at 100 Hz from the base station decoder/controller analog output using Acqknowledge software version 4 . Flow, pressure, and ECG signals were recorded at baseline (before any heart failure model was initiated), as shown in p<0.001) and second (200.3±15.4 mmHg) weeks. Interestingly, during the third week of aortic banding, the LVESP decreased (164.2±7.2 mmHg) significantly (p<0.001), and then progressively increased (180.3±26.5 mmHg) again until the end of the study duration (p = 0.33) during the first week post-stenosis but showed a significant increase  during the second week. Thereafter, the LVEDP progressively decreased (8.4±6.6 mmHg) to approximately the baseline values (7.1±12.9 mmHg) by the end of the study (p<0.05) and second (180±21.9 mmHg) weeks. Similar to the pattern observed for the LVESP, the mean aortic pressure significantly decreased  during the third week, and then progressively increased (187.9±38.9 mmHg) again until the end of the study  by the end of the study (p<0.001) by the end of the study (p<0.05) during the development of heart failure  fluctuated during the development of heart failure , increasing significantly  until the end of the study  immediately dropped (70±14.2 mmHg) after initiation of pacing, and monotonically decreased thereafter until the end of the study (49±4.5 mmHg), although the values between baseline and end-stage heart failure were not significantly different (he study .p<0.05) throughout the remainder of the study duration (p<0.05) with the development of heart failure (p<0.05) during the development of the disease (p<0.05). Interestingly, the difference between max and min flow velocity (pulse velocity) decreased with the progression of the disease  during the development of the disease  between the telemetry system presented here  and the The heart failure models used in this study are well established in both small and large animals, and the telemetry system implanted in the swine reliably detected hemodynamic changes during progression of the disease. The data collected was used to analyze LVESP and LVEDP as markers of heart failure, blood pressure as a marker of systemic circulation, and coronary flow for myocardial perfusion. The aortic banding animals showed a progressive increase of the systemic blood pressure , which iIn the A-V fistula animals, the LV pressure also showed a non-monotonic pattern, with a drastic increase (more than double) at the end of the study . FurtherIn pacing-induced tachycardia animals, there was a transient decrease of the aortic pressure during the first 2 weeks of rapid pacing, which then progressively increased for the remainder of the study . The conFirst, careful placement of the flow probe around the vessel is necessary to ensure that blood flow does not become restricted when the vessel remodels (enlarges) as the disease progresses. This can be avoided by placing the probe loosely around the vessel wall. Eventually, the connective tissue will cover the flow probe and help secure the position around the vessel.Second, the time acquisition mode is a concern. During the approximately 4 weeks of telemetric measurements, we used a combination of continuous data recording and automated timed-acquisition mode data recording (20 min of data recording followed by 100 min power-down period). The timed-acquisition mode prolongs the battery life and reduces the amount of data collected, but this poses a risk of missing some meaningful and interesting data. Future improvements can be made by introducing internal trigger sensors.In summary, this novel implantable telemetry system is capable of collecting high quality data over extended periods of time. To our knowledge, this is the first telemetry system implanted in a large animal model of heart failure. The system can monitor blood pressure, blood flow and ECG signals simultaneously in free-ranging animals. The compact size and high reliability of the implant provide significant utility for the long-term measurement of cardiovascular vitals in health and disease.


Soluble guanylate cyclase (sGC) is an endogenous receptor for nitric oxide (NO). Binding of NO to sGC activates the enzymatic activity, catalyzing the conversion of GTP into cGMP. cGMP acting as a second messenger, evokes a number of physiological responses including the regulation of blood pressure by relaxing vascular smooth muscle cells. Elevated reactive oxygen species can reduce the bioavailability of NO leading to dysregulation of the NO-cGMP signaling pathway and this has been associated with multiple diseases including diabetes, hypertension, and heart failure. Stimulators of sGC synergize with NO to enhance NO signaling and thus represent a new therapeutic mechanism. The sGC stimulator riociguat (Bayer) was recently approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension. We have discovered a novel pyrazole-pyrimidine class of sGC stimulators with drug-like properties. These compounds synergize with NO to stimulate sGC in isolated enzyme and whole cell assays, relax pre-constricted aortic smooth muscle preparations ex vivo, and potently reduce blood pressure in normotensive and spontaneously hypertensive rats (SHR). Additionally, sustained and dose-dependent blood pressure lowering effects were observed in the Dahl salt-sensitive rat model of hypertension and heart failure. Furthermore, sGC stimulator treatment resulted in protection from end organ damage and reduction in biomarkers of fibrosis and inflammation in rats. The blood pressure lowering effects observed in the rat with a sGC stimulator can be combined with existing antihypertensive mechanisms underscoring the potential utility of this mechanism for the treatment of resistant hypertension. We observed differences between various sGC stimulators in their pharmacological and pharmacodynamic effects, which may enable the therapeutic use of these molecules in a variety of different indications.


Thalassemia is the most common inherited disease in southern China. However, this disorder is usually ignored by Jiangxi provincial health system and government due to lack of epidemiological data.A total of 9489 samples from Hakka Han and Gan-speaking Han in three geographical areas of Jiangxi Province were analyzed for both complete blood cell (CBC) count and reverse dot blot (RDB) gene chip for thalassemia.1182 cases of suspected thalassemia carriers with microcytosis (MCV<82 fL) were found by CBC count, and were tested by RDB gene chip to reveal a total of 594 mutant chromosomes, including 433 α-thalassemia mutant chromosomes and 172 β-thalassemia mutant chromosomes. Our results indicated a higher prevalence of thalassemia with the heterozygote frequency of 9.49% in southern Jiangxi province, whereas the low frequency was found in middle (3.90%) and northern Jiangxi (2.63%).Based on the epidemiological data, the estimated numbers of pregnancies in Jiangxi province in which the fetus is at risk for β-thalassemia major or intermedia, Bart's hydrops fetalis and Hb H disease are 34 , 79  and 39  per year, respectively. We suggested that prevention network of thalassemia should be established, especially in high prevalent southern Jiangxi (Hakka Han), including establishment of thalassemia database collection, hematological analysis laboratories, genetic counselling clinics, prenatal diagnosis centers and neonatal screening centers. Thalassemia is inherited as an autosomal recessive disorder characterized by microcytic hypochromic anemia, and a clinical phenotype varying from almost asymptomatic to a lethal hemolytic anemia. It is probably the most common monogenic gene disorder in the world and is especially frequent in tropical and sub-tropical areas such as Mediterranean countries, the Middle East, the Indian subcontinent, southern Far East Africa and Southeast Asia http://www.gztj.gov.cn), Jiangxi province lies on the southern bank of the Yangtze River. It shares a border with Anhui to the north, Zhejiang to the northeast, Fujian to the east, Guangdong to the south, Hunan to the west, and Hubei to the northwest. 99.73% of inhabitants of Jiangxi province are Chinese Han, predominantly Gan-speaking Han and Hakka Han. Two decade have elapsed since a relative low incidence of thalassemia  was reported by a large scale survey of hemoglobin variants and thalassemia in Jiangxi province (1987), this disorders was usually ignored by health system and government Previous studies have indicated that there was a high population frequency of thalassemia in southern China, mainly in southern regions of the Yangtze River, particularly in the three most southerly provinces of China-Guangdong, Guangxi and Hainan Here, we perform a large-scale survey of thalassemia in 9489 healthy subjects, which firstly allows a sight into the prevalence and molecular characterization of thalassemia in Jiangxi province. It is a prerequisite for defining a specific policy for carrier screening, genetic counseling and prenatal diagnosis.The study population included 9489 unrelated subjects between August 2011 and November 2011. These subjects visited medical units for routine healthy examination including blood tests, and the discarded blood samples were used for further study. The ages of these subjects ranged from 18 to 70-year-old and about 99% were Jiangxi natives, i.e. Information sheets with nationality, sex, age, dialect, natives or not and written consent forms were available in Chinese to ensure comprehensive understanding of the study objectives, and informed consent was signed or thumb printed by the participants. All studies were approved by the Ethics Committee of First Affiliated Hospital of Gannan Medical University and Ethics Committee of Chaozhou Central Hospital Affiliated to Southern Medical University. 2, was obtained from each participant. RBC indices were determined according to standard laboratory procedures by Beckman Coulter-LH750 blood analyzer . Quality control of complete blood count (CBC) was monitored through participation in the National External Quality Assurance Scheme of China and Randox International Quality Assessment Scheme (RIQAS). Subjects with low red blood cell mean corpuscular volume (MCV) values (<82 fL) were considered possible thalassemia carriers.These subjects received hematological screening for the presence of thalassemia in Medical Laboratory of the First Affiliated Hospital of Gannan Medical University, Central Hospital of Iron Industry Limited Corporation of Xinyu and Jiangxi Provincial People's Hospital. 2 mL peripheral blood, which was anti-coagulated with 4.0 mg EDTA-K3.7, −α4.2, two α-thalassemia mutations [Hb Constant Spring (HBA2: c.427T>C) and Hb Quong Sze (HBA2: c.377T>C)], and 16 known β-thalassemia mutations most commonly seen in the Chinese population  were analyzed by a commercial thalassemia RDB gene chip . The kit of the gene chip was approved by Chinese SFDA (REG.NO: SFDA (P) 20123400399) Genomic DNA of subjects with MCV<82.0 fL were extracted from peripheral blood leukocytes by DNA blood mini kit . The DNA concentration was determined by UV spectrophotometer  at the wavelength of 260 nm. The three known α-thalassemia deletions –SEA, −α2 test. P<0.05 was considered statistically different.Statistical analysis was conducted with SPSS 16.0 statistical software. The prevalence of different thalassemia alleles was calculated from the standard Hardy-Weinberg formula. Data from the three regions in Jiangxi province and previous studies were analyzed by Pearson χA total of 9489 blood samples were obtained and analyzed from three regions of Jiangxi province. 1182 cases of microcytosis (MCV<82 fL) were found. The percentage of microcytosis in Ganzhou region, Xinyu region and Nanchang region was 20.15% (1006/4992), 4.69% (47/1002) and 3.69% (129/3495), respectively.3.7, −α4.2), two α-thalassemia mutations (Hb Constant Spring and Hb Quong Sze) and 16 known common Chinese β-thalassemia mutations. The results of the survey of population among 9489 blood samples were shown in P>0.05).All 1182 microcytosis samples were analyzed by a RDB gene chip for the three known α-thalassemia deletions , was also similar to average level of Guangdong province  P = 0.000) High prevalence of α/β-thalassemia in the Hakka population of southern Jiangxi province (9.49%) was similar to the situation in Hakka population of Meizhou region in Guangdong province . Children with β-thalassemia major need regular blood transfusions, iron chelation therapy with deferoxamine and even hematopoietic stem cell transplantation. The annual cost of blood transfusions and deferoxamine treatments for one patient with β-thalassemia major is estimated to be about ¥100,000/$15,690 in China Based on our epidemiological results, thalassemia is a large public health problem in Jiangxi province, especially in Ganzhou region. Ganzhou is a relative poverty-stricken mountainous region in Jiangxi province. The annual per capita disposable income of the urban residents and the annual per capita net income of rural residents are only ¥18,704.7/$3,069.4 and ¥5,301/$869.9 (2012), respectively (Data from the Webpage of the Ganzhou government (


Active engagement in the management of hypertension is important in improving self-management behaviors and clinical outcomes. Mobile phone technology using wireless monitoring tools are now widely available to help individuals monitor their blood pressure, but little is known about the conditions under which such technology can effect positive behavior changes or clinical outcomes.To study the influence of wireless self-monitoring program and patient activation measures on health behaviors, medication adherence, and blood pressure levels as well as control of blood pressure in hypertensive patients.We examined a subset of 95 hypertensive participants from a 6-month randomized controlled trial designed to determine the utility of a wireless self-monitoring program , which consisted of a blood pressure monitoring device connected with a mobile phone, reminders for self-monitoring, a Web-based disease management program, and a mobile app for monitoring and education, compared with the control group receiving a standard disease management program. Study participants provided measures of patient activation, health behaviors including smoking, drinking, and exercise, medication adherence, and blood pressure levels. We assessed the influence of wireless self-monitoring as a moderator of the relationship between patient activation and health behaviors, medication adherence, and control of blood pressure.Improvements in patient activation were associated with improvements in cigarette smoking  and blood pressure control . This relationship was further strengthened in reducing cigarettes , alcohol drinking , and systolic  and diastolic blood pressure  at 6 months among individuals participating in the wireless self-monitoring program. No differences were observed with respect to medication adherence.Participation in a wireless self-monitoring program provides individuals motivated to improve their health management with an added benefit above and beyond that of motivation alone. Hypertensive individuals eager to change health behaviors are excellent candidates for mobile health self-monitoring..ClinicalTrials.gov NCT01975428, https://clinicaltrials.gov/ct2/show/NCT01975428 (Archived by WebCite at http://www.webcitation.org/6iSO5OgOG) Hypertension is the single greatest attributable risk factor for death and disease burden worldwide from noncommunicable disease . ManagemThe success of long-term effective control of blood pressure largely depends on patient self-management, where the individual plays a central role in their decisions and behaviors regarding management of this chronic condition. Self-management skills in chronic conditions include medication adherence, dietary compliance, self-monitoring of key parameters such as blood pressure, and coping skills to better manage anger or frustration that comes from living with disease ,6. A varThe Patient Activation Measure (PAM) is one of the tools for measuring an individual’s skills, confidence, and knowledge in managing his or her own health ,9. PAM s1clevels in diabetic patients [Higher PAM scores have shown strong relationships with better performance of self-management behaviors, higher medication adherence, and higher quality-of-life score in patients with chronic condition ; clinicapatients ; and lowpatients . PAM scopatients .With the development of mobile medical technologies, tools to enhance self-management that combine home monitoring with near real-time bidirectional communication and feedback are becoming more widely available through mobile phones and wireless hubs . The greHowever, the mechanism of improved blood pressure control in individuals utilizing blood pressure self-monitoring is still not well understood. According to a meta-analysis of blood pressure self-monitoring on medication adherence and lifestyle factors from 28 trials with 7021 participants, monitoring was shown to have a small but significant effect on medication adherence but an inconclusive result related to diet and physical activities . One othWe originally performed the prospective, randomized controlled trial of the effect of wireless self-monitoring program on health care utilization in a heterogeneous group of patients with hypertension, type 1 or type 2 diabetes mellitus, or cardiac arrhythmia . This stHowever, to date there have been limited studies of PAM, its modifiability through mHealth blood pressure self-monitoring, and their effects on behavioral factors, medication adherence, and blood pressure levels in a hypertensive population. Our study aimed to evaluate the interaction between wireless self-monitoring program and PAM in positive behavior changes, medication adherence, and control of blood pressure among hypertensive patients.This study was a secondary analysis of a prospective, randomized controlled, 2-group, pre-post intervention trial on the 6-month effectiveness of mobile phone–based self-monitoring program of chronic conditions on health care utilization . The triCurrent Procedural Terminology (CPT) code related to one or more of the following diagnoses: hypertension, diabetes, or cardiac arrhythmia according to a medical claims database. The 3998 eligible individuals were identified according to inclusion criteria of being able to attend visits at a Scripps facility, being able to access the Internet, participating in HealthComp disease management program, and being willing to use wireless devices, iPhone, and the HealthyCircles Platform. They were also identified as the highest 25% in terms of their 2012 medical billing data to account for the highest health care spending and resource utilization. Individuals were recruited through an emailed invitation letter, followed up with a telephone call. If individuals expressed interest in the study, they were provided with a link to a Web-based informed consent form through email. After consenting to the study, study participants completed a Web-based survey that included demographic, health, and technology-related questions. Afterward, participants were randomized to control or intervention and brought in for an enrollment visit with an unblinded research coordinator, which they repeated at the conclusion of their 6-month study enrollment at a Scripps facility. Participants were blind to their assigned group before enrollment. All participants were randomized (ratio 1:1) to either intervention group, receiving wireless monitoring program plus disease management, or control group, receiving standard disease management program.In brief, this study was a collaboration between Scripps Translational Science Institute, Scripps Health, HealthyCircles by Qualcomm Life, and HealthComp, the third-party administrator for Scripps Health responsible for processing all health care insurance claims for employees and dependents. Study participants in the primary trial were drawn from a pool of eligible employees and dependents insured by Scripps Health in 2012 and identified to have a Our study focused only on those enrolled in the original study with a diagnosis of hypertension, prescribed at least one or more antihypertensive medications, and completed their 6-month follow-up study visit. The flow of study participants and subset of participants in this study are presented in During the study enrollment visit, all study participants completed the baseline survey if not already completed online and underwent height, weight, and blood pressure measurements, as well as a 12-lead electrocardiogram and fasting blood glucose test in the case of hypertensive individuals with a history of cardiac arrhythmia and diabetes, respectively.Participants randomized to the monitoring group were provided with a study monitoring device according to their condition. Those enrolled with a diagnosis of hypertension received a Withings Blood Pressure Monitor. Participants in the monitoring group also received an iPhone with corresponding apps and were enrolled in the HealthyCircles Platform—an online disease management program featuring educational materials, consumer portals, and a dashboard to link with their families, caregivers, and health care professionals. HealthComp is the third-party administrator for Scripps Health, and HealthComp nursing staff had access to the HealthyCircles care management dashboard that showed the participant’s device monitoring results and trends over time. Readings recorded on the devices were wirelessly uploaded to the HealthyCircles account and were accessible to the patient as well as the HealthComp nurses via an iPhone or computer. Also included in the management platform were reminders for monitoring, information about the disease condition, and general health behavior recommendations. Hypertensive participants in the monitoring group were trained on how to use their mobile phone, the HealthyCircles mobile app, portal, and their device. They were encouraged to use the device 3 times a week, taking 2 measurements per day, with the first in the morning. If their monitoring frequency fell below 3 times per week for 2 consecutive weeks, participants received an email on their HealthyCircles Platform reminding them of the monitoring schedule. If participants were recommended more frequent monitoring by their physician than that asked through the study, they were encouraged to follow the physician’s instructions. All participants, including participants randomized to control group, were enrolled in the HealthComp disease management program, and HealthComp nursing staff could reach out to all participants for the purpose of relaying medical education and wellness information with regard to disease prevention and chronic disease management.past 6 months, how many alcoholic drinks per week do you/did you have? (if you are a current or previous drinker)?” and the answer was coded as one of following categories: never, monthly or less, 2-4 times a month, 2-3 times a week, and 4 or more times a week. Smoking frequency was assessed by one survey item asking, “In the past 6 months, how many cigarettes/cigars per day do you/did you smoke? (if you are a current or previous user of tobacco)” and the answer was coded as one of the following categories: never, 10 or fewer, 11 to 20, 21 to 30, and 31 or more cigarettes. Finally, exercise frequency was assessed using the validated Godin Leisure-Time Exercise Questionnaire (GLTEQ) [Three health behaviors were assessed at both baseline and the 6-month follow-up Web-based survey: frequency of the use of alcohol, smoking, and exercise. Alcohol frequency was assessed by one survey item asking, “In the  (GLTEQ) . The GLT (GLTEQ) . Systoli (GLTEQ) .The primary independent variables of interest were (1) assignment to the wireless self-monitoring or control group and (2) the relative change in the PAM score from baseline to the end of the study. Our primary hypothesis examined the moderator effect of this monitoring group assignment on the relative change in PAM on the outcome measures. That is, we jointly modeled the main effects of wireless self-monitoring and relative change in PAM, and the interaction between these variables. There was a problem regarding the database where a subset of Withings measurements could not be accurately determined, so self-monitoring was simply treated as a dichotomous variable.Meanwhile, PAM was derived from an interval level, unidimensional, Guttman-like measure questionnaire consisting of 13 items. Each item has 4 possible responses ranging from “disagree strongly” (coded as 1) to “agree strongly” (coded as 4). An overall PAM score can be calculated by summing the coded responses. Overall PAM scores are often used to place individuals into 1 of 4 levels based on thresholds. However, as we were interested in changes in patient activation from baseline, we retained the overall scores and calculated the relative change in PAM as the difference in activation score between baseline and follow-up divided by baseline activation score.To account for potential confounding factors, several sociodemographic factors were modeled as potential covariates: age, sex, education level and income level, baseline blood pressure, the number and types of medications , and the frequency with which an individual visited a physician in the 6 months before starting the trial.P<.10) with the outcomes. All data analyses were performed using R software, version 3.2.0 [Because the original trial aimed to evaluate health care resource utilization as measured by health insurance claims and visits to the hospital including office visits, emergency room visits, inpatient stays, and all visits during the study periods, sample size was determined to be powered (a priori) to detect a 1–office visit difference between the control and the monitoring group (assuming a standard deviation of 2 office visits). Univariate analyses were performed on each of the variables assessed. Multivariable regression was performed in a stepwise approach to determine the effects of self-monitoring, relative changes in PAM, and their interaction on behavior changes, medication adherence, blood pressure, and blood pressure control. In total, 3 models were constructed: (1) covariates only, (2) covariates and the main effects of self-monitoring and relative changes in PAM, and (3) covariates, main effects, and their interaction. Covariates were selected based on marginal associations . This includes 52 participants assigned to the monitoring group and 43 participants assigned to the control group.P=.34). Meanwhile, the average number of cigarettes smoked per day across self-identified smokers significantly decreased from 16.7 to 1.9, and the percentage of nonsmokers increased from 72% to 96%. However, the average frequency of alcohol use  and exercise group by GLTEQ categories  did not change over the course of the study. Baseline Morisky Medication Adherence Scale (MAS) scores also did not change over the study period . However, the average systolic and diastolic blood pressure levels decreased across all study participants over the study period . Furthermore, according to JNC 8 guidelines, the frequency of achieved blood pressure control increased from 45% to 59%.Summary statistics of independent and dependent variables of interest are presented in P<.001), alcohol drinking , systolic blood pressure , and diastolic blood pressure  at 6 months. In all these cases, the wireless self-monitoring group had greater decreases in these outcome variables than the control group. This interaction was not a significant predictor of change in exercise per week, Morisky MAS, or achieved blood pressure control—although the main effects of both self-monitoring and changes in PAM were conditionally associated with achieved blood pressure control.Results of the multivariable models examining the relationship with PAM, wireless self-monitoring, and their interaction with the outcome variables of interest are presented in P<.001), frequency of alcohol drinking , systolic blood pressure , and diastolic blood pressure  in the monitoring group. However, no association was observed in the control group: smoking , frequency of alcohol drinking , systolic blood pressure , or diastolic blood pressure .In order to further dissect these interactions, we evaluated the relationship between relative changes in PAM and number of cigarettes smoked per day, frequency of alcohol drinking, and systolic and diastolic blood pressure in the self-monitoring group and control group separately. We observed that increases in PAM scores were significantly associated with a decrease in smoking  whose self-monitoring data were available during the total study period .After 12 weeks, about 70% (23/33) had monitored their blood pressure regularly at a recommended frequency , and at the end of the study period, 55% (18/33) had still participated in the self-monitoring program with a median frequency of 6 per week IQR 5-7; . BaselinOne goal of many chronic disease management programs is to adopt patient activation enhancing strategies in management of chronic disease. Such programs are generally designed to enhance problem solving, decision making, and taking actions . These cWe discovered that changes in PAM were associated decreases in the number of cigarettes smoked, alcohol consumed, and blood pressure in the self-monitoring group alone. This suggests wireless self-monitoring program may reinforce changes of PAM by enhancing the ability to make healthy decisions and to manage blood pressure.To date there have been few studies that have explored the relationship between wireless self-monitoring and changes of PAM in chronic care. One study examining African Americans with uncontrolled hypertension showed that blood pressure self-monitoring did not have any effect on changes of PAM . AnotherWe further discovered that changes in PAM were conditionally associated with changes in health behaviors and blood pressure control. These results support the finding that an increase in PAM score may improve health outcomes and potentially decrease long-term medical costs . ImportaDespite this relationship between changes in PAM and blood pressure control, changes in PAM were not significantly associated with medication adherence. We observed a median Morisky MAS score of 7.0, which indicated relatively medium to high adherence. Our study participants consisted of Scripps Health hospital employees or their families. Thus, participants were likely to have higher health literacy or more availability of health personnel resources than the general population, which could possibly lead to better control of their condition. Furthermore, study participants generally had well-controlled hypertension, because the study participants took on average 2 antihypertensive medications and had a baseline blood pressure of 140.6/89.4 mm Hg, indicating generally mild to moderate hypertension. Finally, one previous study showed that uncontrolled depression was a barrier to antihypertensive medication adherence and was negatively associated with PAM . AlthougThe mechanism by which a wireless self-monitoring program potentiates the effect of changes in PAM on health behaviors and outcomes in hypertensive participants remains unknown. Although many studies have shown that patient activation level is associated with improved health behaviors and clinical outcomes ,13,30,32In this study, the wireless self-monitoring program had integrative multiple components including online portal with social support from their family or friends, reminder for monitoring blood pressure, and education about the disease, as well as recommendation for positive behavior change for better outcomes. A study showed that Internet-based behavior intervention grounded in theory proved to be effective . Among sIn this study, Withings blood pressure monitoring device was used to track patient’s blood pressure. Portable wireless device that enables monitoring of user’s condition in clinical setting or off-site locations has its potential in improving health care with real-time monitoring and convenience. However, there are also potential risks if misused or misinterpreted. In 2015, the US Food and Drug Administration updated the 2013 document titled “Mobile Medical Applications: Guidance for Industry and Food and Drug Administration Staff” . AccordiAlthough more than half the study participants enrolled in this trial were among the top quartile of eligible participants with respect to health care utilization, study participants exhibited relatively high levels of baseline medication adherence and PAM as described previously. The high baseline PAM levels among participants in our study prevented us from investigating the relationship between PAM, wireless self-monitoring, and study outcomes in individuals with low PAM scores.In addition, the study participants were highly educated, were non-Hispanic white, and a female-dominant population compared with a prevalence study in the United States using National Health and Nutrition Examination Survey . BaselinFurthermore, a formal evaluation of the engagement in monitoring activities was not included, although we tried to look at the trends of monitoring frequency and mean systolic and diastolic blood pressure levels in a subset of participants. Over the 24 weeks of the study period, more than half of the participants were actively engaged in the self-monitoring program with recommended frequency, which was different in results of decreased adherence to protocol over time for a weight-monitoring app . This miIdentifying the individual characteristics of mHealth self-monitoring programs that influence behavior will lead to improved systems. Finally, as study participants only participated for 6 months, further studies will be required to evaluate long-term benefit.We discovered that a wireless self-monitoring program in hypertensive patients strengthened the relationship between positive changes in PAM and health behaviors and blood pressure control.Adoption of wireless self-monitoring programs has the potential to enhance strategies for the management of hypertension. Further research should seek to identify individuals who may receive the most benefit from wireless self-monitoring programs.


Background: The underlying cause of high blood pressure in adulthood is rooted in childhood. The evidence points to higher prevalence of hypertension among children in recent years. This study aims to investigate the prevalence of high blood pressure among Ahvaz children, as a sample of Iranian kids, and compare it with relevant reports from other countries.Methods: This cross- sectional study was conducted in various parts of Ahvaz city on school children aged 6-12 from March to June 2013. We measured the height, weight, systolic and diastolic blood pressure, using standardized methods. Systolic and diastolic blood pressure ≥95 percentile for age and sex was identified as hypertension. To analyze the data, statistical tests such as Chi-square, T-test, ANOVA, and Pearson correlation coefficient were used.Results: Overall, 1100 school children (564 boys and 536 girls) participated in the study. The highest level of blood pressure was found among obese children (26.4%) aged 11-12 years. Systolic blood pressure of 9.7% of children was in the pre-hypertension phase and 23.6% of them in the hypertensive phase. Also, with regards to diastolic pressure, 13.5% and 17.1% of the children had pre-hypertension and hypertension, respectively.Conclusion: Considering the high prevalence of hypertension in school children in Ahvaz, we suggest developing a sustainable training program based on intervention for proper nutrition and physical activity in this age group to the Ministry of Health and the Ministry of Education. Approximately 7.6 million deaths  and 92 million disability-adjusted life years worldwide were attributable to high blood pressure in 2001. Hypertension doubles the risk of cardiovascular diseases, including coronary heart disease (CHD), congestive heart failure (CHF), ischemic and hemorrhagic stroke, renal failure, and peripheral arterial disease.2 “In industrialized societies, blood pressure (BP) increases steadily during the first two decades of life. In children and adolescents, BP is associated with growth and maturation”.1 BP changes depending on age and growth, and as the person gets older the heart enlarges and the likelihood of blood pressure increases.3 The evidence shows that a minor increase in blood pressure among children and adolescents is much more common than already thought. High blood pressure in adulthood can be traced back to childhood; also, hypertension in childhood continues to adulthood. In fact, it is said that children with high blood pressure are more likely to be at risk of developing high blood pressure later in life.4 In children and adolescents, hypertension usually is defined as systolic and diastolic blood pressure which is constantly over the 95th percentile for age, sex and height. In addition blood pressure between 90-95 percentiles is considered as pre- hypertension.1,5Elevated blood pressure in childhood is a significant risk factor for cardiovascular disease in adulthood.1Both genetic and environmental factors as well as regional and racial variations are likely to have an impact on the prevalence of hypertension. Obesity and overweight are predominant risk factors for High BP. Adaptation of lifestyles that favorably affect blood pressure has implications for both prevention and treatment of hypertension. Health-promoting lifestyle modifications are recommended for individuals with pre-hypertension and as an adjunct to drug therapy in hypertensive individuals.1 Several studies in Iran have been conducted on high BP in children. For example, a study showed that systolic BP of 11.6% of children aged 6-11 in Birjand were pre-hypertensive and 7.4% were hypertensive.6 In the same line, another study indicated that prevalence of high BP in girls ranged between 4.4 to 9.6 percent and  it was between 3 to 8.2 percent for boys.7Lifestyle changes that effectively lower the blood pressure are weight loss, regular physical activity, reduced salt intake, increased potassium intake and an overall healthy dietary pattern.Thus, as the motto of 1392 goes “take blood pressure seriously” and also due to implications of high blood pressure in adulthood dating back to childhood, the researcher aimed to investigate the prevalence of high blood pressure among school-age children in Ahvaz, 2013.This cross-sectional survey was performed in four educational regions in Ahvaz city on 1100 male and female students. Of them, 536 were girls and the other 564 boys. The sampling was done during March until June 2013.  The sample size was calculated according to previous related articles and using the following formula.2Z pq/d2(N-1)+z2 pqn=NN=the whole population of Ahvaz children in Schools=137993Z=1.96p=the blood pressure ratio in articles=0.5q=1-p=0.5d=0.03th- 6th primary school grades), using random sampling according to the number of students. After determining the number of samples and their choices, written consent was obtained from parents, school officials, and the deputy.The figure 1060 was drawn out of the above formula, but 1100 was chosen presuming some drop outs. The method used in this research is cluster sampling. Thus two schools from each region were selected randomly  for each sample was calculated as the ratio of weight in kg by the square of height in m2. To determine overweight and obesity, percentiles provided by the center for disease control and prevention was used.8 So 85 to 95th percentile for age and sex was defined as overweight and obesity as 95 percentile and higher.The height, weight and blood pressure were measured by the researcher. Data collection procedure was carried out between 8 to 12 am in their respective schools and health rooms where first the height then weight and finally the blood pressure were measured. The student demographic questionnaire was filled out for each participant. The criterion for age calculation was their actual age in years (adjusted with ID); it was then matched with their school year. Height was measured by a tape and in centimeters. Weight was measured in kg using seca scale made in Germany with 0.01 gram readability. In all cases, careful balance of the scale was maintained. Children’s BP was measured after a ten minute break from the right hand in a sedentary state using analog barometer alpk II (made in Japan). Blood pressure measurement was performed by two types of cuffs (depending on the student’s arm size) in sizes 8×18 and 9×20 cm.  Measurement of blood pressure was done on two separate points in time with 20 minute interval.5,9The criterion for high blood pressure was in accordance with the data presented in the tables of National Training Center program for high blood pressure in 2012. These tables represent the systolic and diastolic blood pressure based on age, sex and height. The percentile 90 to 95 was considered as pre-hypertension and the that equal or above 95 as hypertension.Samples were selected from healthy students of each school and children with a history of cardiovascular, renal and endocrine diseases were excluded from the study. Data were collected, using SPSS software, version 20, and for the analysis of the data, K2, T-test, ANOVA, Pearson Correlation Coefficient tests were used.1100 students participated in this study. Most of them were in the age range of 11-12 years (19.2%). 536 (48.7%) students were girls and 564 (51.3%) boys. The systolic blood pressure of 9.7% of the children was in the pre-hypertensive stage and 23.8% of them were hypertensive. Also in regards with the diastolic pressure, 13.5% and 17.1% of the children were pre-hypertensive and hypertensive, respectively .t test, it was revealed that the mean systolic blood pressure in girls was significantly higher than boys. But in terms of mean diastolic pressure there was no statistically significant difference between male and female students and similar BP was observed in both groups  the prevalence of hypertension increased significantly in accordance with increased BMI .6,10 As mentioned before, the prevalence of hypertension in this study is far higher than others studies,6,10 but that of pre-hypertension is much less which indicates that the number of children with hypertension in Ahvaz has increased. It seems that the above results point out to differences in the type and amount of nutrition and perhaps lack of physical activity.In the present study, the prevalence of hypertension in children aged 6-12 in Ahvaz city was 23.6% and that of pre-hypertension was 9.7%. But in other study results the prevalence rates of hypertension and pre-hypertension were 7.4% and 11.5%, respectively;  also other study results have indicated 11.8 and 15.2.11 Also, the results of another study  on 1061 primary school children in Tehran showed that Tehrani kids had lower systolic and diastolic BP than normal blood pressure percentile in American kids.12 Since the above studies were conducted a decade ago, it seems that an increase in the prevalence of hypertension in kids is related to the increasing pace of industrialization of societies and sedentary lifestyle and overweight and obesity epidemic.In the same line, other studies have reported a much lower prevalence of hypertension in school-age children. In a study in Zahedan  conducted on 1500 primary school children, the systolic BP was comparable with international standards.6 But it is in the same line with the results from  another study.12 The reason for this difference could be the impact of the geographic zone, earlier puberty in girls than boys, and as a result the elevated BP in girls due to puberty hormones.In the current study, systolic BP among female students was significantly higher than male students; this is inconsistent with the result of another study.13 It appears that the increase in cardiac mass with aging results in the increase of blood pressure levels in older age groups.This study showed that the mean systolic and diastolic blood pressure increases with age so that the age group of 11-12 had higher systolic and diastolic BP than younger age groups; this is consistent with the findings of another study results.14 A study conducted between 2000 and 2010 in China revealed that the prevalence of hypertension from 2000 through 2010 rose from 19.29% to 26.16% in boys and from 14.69% to 19.77% in girls. Also the prevalence of obesity rose from 22.26% to 32.81% in boys and from 12.22% to 19.49% in girls. These results also corroborate with those of a study in Texas, USA.15 Probably, the epidemic of child obesity and a strong correlation between blood pressure and body weight have increased the prevalence of hypertension in the young population. The roots of obesity as a major cause of hypertension in childhood can lie in the consumption of high-calorie foods such as fast food and carbonated beverages and reduced physical activity due to the replacement of outdoor and active games with watching TV and PC games.In this study, hypertension in overweight and obese students was significantly higher than those with normal weight. The same results were found in another study.According to the findings of this Study, it seems that prevalence of hypertension in Ahvaz school children is high. In this survey, female sex, overweight, obesity and older age were observed as risk factors for high blood pressure among the students. Some essential approaches for primary prevention can be suggested, such as written educational programs for proper nutrition, physical activity and establishing healthy recreations. Furthermore, follow up examinations of blood pressure in six months and one year intervals in children exposed to risk or suffering from high BP is recommended. Hence holding an intervention program by Ministry of Health and Ministry of Education in the interest of prevention and treatment of high blood pressure is suggested.