T) is well recognized as a protective approach to patients with acute respiratory distress syndrome (ARDS), but the optimal level of positive end-expiratory pressure (PEEP) remains uncertain. This study aims to evaluate two protective ventilatory strategies sequentially applied in patients with early ARDS.Ventilation with low tidal volume  adjusted according to the ARDSnet low-PEEP table (ARDSnet-24 h). During the next 24 h, nine patients with PaO2/FIO2 ratio below 350 mmHg were ventilated with PEEP titrated according to the Open Lung Concept protocol (ARDSnet + OLC). In the other six patients, regardless of their PaO2/FIO2 ratio, the ARDSnet remained for a further 24 h (ARDSnet-48 h). Ventilatory variables, arterial blood-gas and cytokine were obtained at baseline, 24 and 48 h. Additionally, whole-lung-computed tomography was acquired at 24 and 48 h.P = 0.008) with a decrease in collapsed regions (P = 0.008) was observed in the ARDSnet + OLC group compared with the ARDSnet-24 h group. A reduction in IL-6 in plasma (P < 0.02) was observed throughout the protocol in the ARDSnet + OLC group. Compared with the ARDSnet-48 h group, the ARDSnet + OLC presented smaller amounts of collapsed areas (P = 0.018) without significant differences in hyperinflated regions and in driving and plateau pressures.A sustained improvement in PaO2/FIO2 ratio . RBR-5zm9pr. 04th November 2015 T) have been shown to induce lung injury and are associated with increased mortality in patients with Acute Respiratory Distress Syndrome (ARDS) [T is well recognized as a protective approach [Ventilatory strategies employing high tidal volumes (Ve (ARDS) , 2. Althapproach , 4, the approach –7.T failed to show differences in mortality [Large trials comparing high and low levels of PEEP with low Vortality –10, althortality , 10. Thiortality , 7 and mortality , 11.Although it has already been shown that recruitment maneuvers associated with PEEP titration determine improvement in lung compliance and oxygenation, and reduction in cytokines levels, these analyses were mainly done in a transversal way. In the research that made a prolonged analysis (until 40 h), there was no tomographic evaluation. A prolonged longitudinal conjoint analysis of lung aeration by computed tomography (CT) scan and cytokines is lacking , 13.In the present study, we evaluated the effects on pulmonary function, aeration and inflammatory response of two protective ventilatory strategies with low and high levels of PEEP individually titrated and sequentially applied in patients with early-established ARDS. Our analysis focused on the effects of each ventilatory strategy regarding oxygenation, lung mechanics, pulmonary aeration and inflammation after 24 h of mechanical ventilation. Our hypothesis is that individually titrated PEEP levels add benefits to protective ventilatory strategies.2/FIO2 ratios lower than 300 mmHg after 30 min of mechanical ventilation with a PEEP of 5 cmH2O, an FIO2 of 1.0 and a VT ranging from 8 to 10 mL/kg of ideal body weight (IBW), along with hemodynamically stable parameters  over the preceding 6 h [The present study was conducted at the Hospital Copa D’Or, a tertiary care hospital located in Rio de Janeiro, Brazil. The Hospital Institutional Review Board (IRB) approved the study protocol (number: HCB027/05) and written informed consent (including the permission to publish indirect identifiers) was obtained from all patients or next-of-kin relatives. Fifteen patients with clinical ARDS diagnosis  with PaOding 6 h , were enPatients were excluded if more than 48 h had elapsed since their diagnosis of ARDS, or if any of the following clinical conditions were identified: pneumothorax, pneumomediastinum, bronchopleural fistula, subpleural blebs, increased intracranial pressure, a body weight greater than 140 kg, pregnancy, or a coexistent disease with an expected 6-month mortality risk exceeding 50 %.T of 6 mL/kg (ranging from 4 to 8 mL/kg), and plateau pressure maintained below 30 cmH2O over the next 24 h. After this period, respiratory variables and arterial blood samples were collected, and patients were transported to the Radiology Department for CT-scan imaging, in SERVOi, without ventilator disconnection (ARDSnet-24 h). After 24 h of ventilation according to ARDSnet, the first nine patients with the PaO2/FIO2 ratio below 350 mmHg were ventilated according to the Open Lung Concept (OLC) for the next 24 h (ARDSnet + OLC). The next six patients, regardless of their PaO2/FIO2 ratios, served as controls and remained on the ARDSnet-low PEEP table protocol for an additional 24 h (ARDSnet-48 h). At the end of this period, arterial blood samples, respiratory variables and a new whole-lung CT-scan were acquired.Figure 2O; inspiratory time of 3 s; inspiratory to expiratory ratio (I:E) of 1:1; FIO2 of 1.0 and PEEP sequentially increased to 25 and 30 cmH2O; two minutes per step. Thereafter, driving pressure was adjusted to keep a VT of 6 mL/kg (IBW) and respiratory rate (RR) was increased to 15 bpm with I:E ratio of 1:2–1:3 [In the OLC protocol, an RM was performed in Pressure Controlled Ventilation (PCV): driving pressure of 20 cmH 1:2–1:3 .2O while keeping all other parameters constant for at least 20 min [2/FIO2 ratio was lower than 350 mmHg [2O and PEEP of 30 cmH2O) was repeated. Thereafter the driving pressure was adjusted to provide a VT of 6 mL/kg and the PEEP was adjusted to 19 cmH2O. Twenty minutes afterwards, a new blood sample was collected and if the PaO2/FIO2 ratio remained below 350 mmHg, the last step of the RM was repeated and after driving pressure adjustment PEEP was set at 21 cmH2O. Twenty minutes later, if the PaO2/FIO2 ratio was still lower than 350 mmHg, the PEEP associated with the highest PaO2/FIO2 ratio was selected.Immediately after the RM, PEEP was adjusted to 17 cmHt 20 min . After t350 mmHg , the las2O and the pH higher than 7.2, with the respiratory rate ranging from 15 to 20/min. No further RMs were performed throughout the OLC protocol.During the OLC protocol, the driving pressure was continuously adjusted to keep Pplat below 30 cmH2 of 1.0 according to the respective ventilatory strategy.Whole-lung helical CT-scan images were acquired during an expiratory breath-hold maneuver (6 s) at 24 and 48 h of the protocol. During CT acquisitions, patients were sedated, paralyzed and ventilated with an FIOCT images were acquired on one of three scanners: a Light Speed QX/i, a Light Speed Pro 16, or a Light Speed VCT . CT scans were obtained sequentially using the following parameters: 0.8 s (Light Speed QX/i) or 0.5 s (Light Speed Pro 16 and Light Speed VCT) axial time rotations, 1.25-mm section reconstructions, 5-mm intervals, 120 kVp, 150–250 mA (Light Speed QX/i) or mA adjustment (Light Speed Pro 16 and Light Speed VCT), and a 512 × 512 pixel matrix.Image analyses were performed with a purpose-built routine written in MatLab (Mathworks) by one of the authors (ARC). The region of interest (ROI) was manually selected in each slice by taking the inner contour of the thorax but excluding the chest wall, mediastinum, pleural effusions and regions presenting partial volume effects. For each ROI, the total volume of hyperaerated , normally (−900 to −500 HU), poorly (−500 to −100 HU) and non-aerated (−100 to +100 HU) regions were computed and color mapped . AdditioArterial blood samples, collected at Baseline, 24 and 48 h during the protocol, were centrifuged and the plasma stored at −70 °C for subsequent cytokine analysis.Interleukins 6 and 8 (IL-6 and −8) were measured using commercially available ELISA kits in accordance with the manufacturer’s instructions .P < 0.05. The temporal effects related to changes in aeration, ventilatory variables, and cytokine analyses in each group were compared with the Wilcoxon sign rank test for paired samples. Comparisons between groups (ARDSnet-48 h and ARDSnet + OLC) were performed with the Mann–Whitney test using the SPSS statistical package .Data are presented as median, first and third quartiles. Differences were considered significant if 2/FIO2 ratio (Table Baseline parameters are presented in Table io Table . Accordi2 (P = 0.002) and a reduction in pH (P = 0.017) were observed after the first 24 h of ARDSnet strategy compared with Baseline. The institution of the OLC led to a significant and sustained improvement in the PaO2/FIO2 ratio (P = 0.008) with increased respiratory system compliance (P = 0.04) compared with Baseline. No significant difference was observed in PaCO2 (P = 0.26), driving or plateau pressures . No significant improvement in oxygenation was observed in the ARDSnet-48 h group. The use of vasopressors and MAP levels were comparable among groups, although a lower fluid balance was observed in the OLC group (P = 0.04).Respiratory variables are presented in Table 2/FIO2 ratio higher than 350 mmHg, even at the highest PEEP level employed (21 cmH2O). The PEEP was then adjusted according to the maximal oxygenation level reached at 19 cmH2O in 2 cases and 17 cmH2O in the other case.No hemodynamic instability was observed during recruitment. During PEEP titration, three patients did not reach a PaOP = 0.008) was observed after 24 h with OLC compared with the first 24 h with the ARDSnet protocol. No significant changes in aeration were observed in the ARDSnet-48 h group when compared with the first 24 h with ARDSnet. Comparing the OLC group with the ARDSnet-48 h group, a higher fraction of normally aerated (P = 0.015), with a lower fraction of collapsed regions (P = 0.018), was observed. No significant difference in hyperinflated regions was observed (P = 0.179) among groups.Morphological CT-scan data are shown in Table The distribution of voxels per HU in each protocol is presented in Fig. Representative 3D reconstructions with the respective histograms of voxels distribution of two patients are shown in Figs. P = 0.02) and ARDSnet 24 h  a sustained improvement in oxygenation with a reduction in non and poorly aerated areas was observed after 24 h of mechanical ventilation with the OLC; 2) no significant increase in driving or plateau pressures, hyperinflated areas or cytokine levels occurred with OLC.The hazardous effects of ventilation with high volumes are well known , 19. SinRegarding oxygenation and respiratory system mechanical properties, there was a sustained improvement in oxygenation after 24 h of ventilation with the OLC, as well as an increase in respiratory system compliance in agreement with previous results . The ben2O were applied during the RMs, which appears to be necessary to open the more dependent areas of the lung [2/FIO2 ratio higher than 350 mmH2O seems to result in less than five percent of the collapsed areas [In the current study, maximal pressure levels higher than 40 cmHthe lung . The useed areas .In our study, RMs with high pressures were not associated with deleterious hemodynamic effects. This was associated with the inclusion of patients with early ALI/ARDS who have less stiff chest walls and higher recruitment potentials , 19.As previously reported , RM withThe sequential approach adopted in the OLC group suggests the possibility that the progressive fall in plasma IL-6 levels may have resulted as a consequence of an improvement in clinical status. To evaluate this possibility, we analyzed a second group, which was ventilated for 48 h in the ARDSnet protocol (ARDSnet-48 h), but we did not find significant changes in cytokine levels Fig. .2/FIO2 ratios were allocated in the ARDSnet + OLC group, maybe supporting the differences in the results favoring this group.The study has limitations. First, it had a small sample size as it was designed to evaluate physiological variables. Second, it was done during 48 h, so inferences regarding clinical outcomes and security cannot be made after this period. Also, as it was a 48 h study, we could not assure that spontaneous breaths were not present all the time, and if so, probably it would be present more often during ventilation with higher PEEP levels and could interfere with the results in the OLC group. It is also important to emphasize that comparisons between the final results of the two groups (ARDSnet + OLC and ARDSnet-48 h) should be done with caution as patients with worse PaOIn summary, our data suggest that the OLC provides an effective approach to reduce the fraction of collapsed tissue without significantly increasing the fraction of hyperinflated tissue and without increasing plasma cytokine levels. We believe that this strategy could provide a viable alternative treatment option for patients with ALI/ARDS. Further studies are warranted to confirm our results and to identify subgroups of patients that will benefit the most from this strategy.Mechanical ventilation based on an OLC, applying an individually tailored PEEP, can induce sustained improvement in pulmonary function, with better pulmonary aeration and less hyperinflated areas, without increment in cytokines.2, arterial pressure of carbon dioxide; PaO2/FIO2, arterial pressure of oxygen/inspiratory fraction of oxygen ratio; PCV, pressure controlled ventilation; PEEP, positive end-expiratory pressure; RM, Recruitment maneuver; ROI, region of interest; RR, respiratory rate; SOFA, sequential organ failure assessment; VT, tidal volumeApache, acute physiology and chronic health evaluation II score; ARDS, early acute respiratory distress syndrome; ARDSnet, ARDS network; CT, computed tomography; HU, hounsfield units; I:E, inspiratory to expiratory ratio; IBW, ideal body weight; IL, interleukins; IRB, The hospital Institutional review board; MAP, mean arterial pressure ; OLC, open lung concept protocol; PaCO


Introduction: Fibroblast growth factor-23 (FGF23) is found as a bone derived hormone which can influence the serum levels of parathormone, phosphorous and 1, 25-dihydroxyvitamin D. FGF23 may be a cardiovascular biomarker in patients with chronic kidney disease (CKD). While, FGF23 is inversely correlated with serum adiponectin level, thus it is possible that FGF23 is correlated to fat mass and related to dyslipidemia in CKD.Objectives: In this investigation, we studied the association of serum levels of FGF23 with serum lipid profile, body mass index (BMI), and various cardiovascular risk factors in patients with CKD.Patients and Methods: This is a cross-sectional study, which was conducted on 80 non-dialysis patients (glomerular filtration rate [GFR] <60 cc/min) with CKD. Laboratory results and demographic information recorded in pre-defined data sheets and their relationship with FGF23 were analyzed.Results: Eighty patients were studied. Mean ± standard deviation (SD) of serum creatinine and FGF23 were 2.18 ± 0.73 mg/dl and 15.028 ± 20.20 RU/ml respectively. The correlation between FGF23, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), ApoA, ApoB, intact parathyroid hormone (iPTH), calcium, phosphorous, alkaline phosphatase, 25-hydroxyvitamin D, BMI, waist girth, serum triglyceride and cholesterol was not significant (P > 0.05). In this study, the correlations of FGF23, with serum albumin (P = 0.036) and systolic blood pressure (P = 0.001) were significant.Conclusion: Our study showed that there are not any significant correlations among FGF23, BMI and lipid profile. There are not any significant correlations between FGF23 and age, sex, and level of calcium, phosphorous, vitamin D. However, the relationships between FGF23 and serum albumin was negatively significant. Additionally we detected a positive significant correlation of FGF23 with level of systolic blood presure. In a study on 80 chronic renal failure patients not yet on dialysis with mean age of 59.82 ± 14.49 years, and serum level of fibroblast growth factor-23 (FGF23) of 15.028 ± 20.20 RU/ml, we found relationships of FGF23 with serum albumin (negative significant correlation) and systolic blood pressure (positive and significant).The mortality rates in patients with chronic renal failure are higher than the others. Around 50% of these patients die as a result of cardiovascular disease conditions such as pulmonary edema, chronic heart failure, fatal arrhythmias, pericarditis, valvular disease and cardiogenic shock are some of cardiovascular disorders (CVD), as the leading cause of death in these patients. This can be probably due to a higher prevalence of important risk factors such as hypertension, anemia, uremia, disturbances in calcium, phosphorous and sodium, balance, dyslipidemia, atherosclerosis, diabetes mellitus and smoking. Chronic kidney disease (CKD) has been known as a serious condition which has significant complication. CKD is known as a risk factor of disorders such as cardiovascular diseases, electrolyte disturbances, bone disease, cognitive and psychological disorders and many other disease. The nature of this disease is progressive which causes new complications too. On the other hand, there are various parameters which can significantly affect the progress and complications of CKD -4.Terminal stage of chronic renal failure named end-stage renal disease (ESRD). At this stage, patients will need renal replacement therapy. In ESRD patients have lower life expectancy and life quality than general population. Overall mortality rates in these patients are significantly higher than general population. Dialysis and kidney transplantation are two common methods of renal replacement therapy. Availability of the two methods, dialysis quality and support quality for kidney transplantation patients are factors which are strongly related to socio-economic conditions, health care facilities and health care constitutions of the society .In this investigation, we studied the correlation of serum levels of FGF23 with serum lipid profile, BMI and some of the other cardiovascular risk factors in a group of patients with CKD not yet on dialysis.This is a cross-sectional study which was conducted on 80 non-dialysis patients (glomerular filtration rate [GFR] <60 cc/min) with CKD.Patients’ demographic information and medical history of the study population including age, sex, height, weight, history of smoking, heart disease, hypertension, diabetes, hyperlipidemia and drug history were obtained and recorded in pre-defined data sheets. Blood pressure of the patients were recorded. Laboratory measurements including serum levels of creatinine, triglyceride, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Apo A, Apo B, fasting blood sugar (FBS), serum levels of calcium, phosphorous, magnesium, alkaline phosphatase, intact parathyroid hormone (iPTH), 25-hydroxyvitamin D level, uric acid and albumin were measured after 12 hours fasting before obtaining their blood specimens, using standard kits. Serum FGF23 was assessed by ELISA method . Waist girth measured and body mass index (BMI) was also calculated by standard method (NIH).The exclusion criteria were using steroids, nonsteroidal anti-inflammatory drugs (NSAIDs) or estrogens. Also presence of active or chronic infection and malignancies were the other exclusion criteria.The research followed the tenets of the Declaration of Helsinki. Informed consent was obtained and the research was approved by the Ethics Committee of Tehran University of Medical Science .T test and Mann-Whitney U test was used for analyzing the serum levels of qualitative variables and chi-square and Fisher’s exact test for quantitative variables. P value lower than 0.05 was considered statistically significant. The distribution of quantitative data were assessed by one sample Kolmogorov–Smirnov test. Since FGF23 had not a normal distribution, Spearman’s correlation was used for the relation to quantitative variables. Statistical analysis was conducted by SPSS version 18.Quantitative variables were calculated as mean ± standard deviation (SD). This study included 44 men (55%) and 36 women. The mean age of patients was 59.82±14.49 years.P=0.55), serum creatinine (P=0.19), LDL-C (P=0.063), HDL-C (P=0.168) and serum triglyceride levels (P=0.99) was not significant. Likewise, the association of FGF23 serum with serum cholesterol (P=0.63), Apo A (P=0.21), and Apo B (P=0.74) was not significant. Accordingly, the correlation of FGF23 with intact PTH was not significant (P=0.28) (P=0.11). We categorized GFR into three groups in patients with following prevalence. Group 1 with GFR of 45-59 = 24 cc/min (29.6%), group two with GFR of 30-44 = 34(42%) and group 3 with GFR of 15-29 cc/min = 22 (27.2%). None of the groups had correlation with FGF , diabetes mellitus 18 21.7%), glomerulonephritis 10 (12%), renal stones 4 (4.8%), cysts 2 (2.4%) and unknown 15 (18%) . The mea1.7%, glo(P=0.28) . The cor P>0.05; .P=0.001, P=0.036) was negatively significant.In this study, the association of FGF23 with systolic blood pressure was positively significant 2 D3] synthesis, leading to reabsorption of calcium and reducing urinary excretion of calcium by kidneys. On the other hand, PTH also increase calcium uptake from bones.2 D3 through increasing CYP27b1, increasing reuptake of calcium in proximal tubules and in distal tubules by regulation of TRPV5. Furthermore, PTH increases the uptake of calcium and phosphate in bones through inducing RANKL by osteoblasts (which in turn stimulate osteoclasts that increase uptake from bones). Additionally, increase of 1,25 (OH)2 D3 production by kidneys, causes an increase in phosphate and calcium reabsorption by small intestine. Overall, uptake of calcium from bones, decreases in urinary excretion of calcium and increases in its absorption by intestine results to normalizing serum calcium levels. Increasing the uptake of phosphate from bones and by intestines is regulated by PTH and reduces the reuptake of phosphate in renal tubules to balance the levels of phosphate. In fact, FGF23 and bone-kidney axis act as a biological route which have recently been discovered as the main players in CKD-mineral and bone disorder (CKD-MBD). Recent findings showed that osteoblasts and osteocytes are important sites for FGF23 production. FGF23 is excreted by bone, targets kidneys, and regulates phosphate and also vitamin D metabolism. It may also have other functions in regulating parathyroid and phosphate which needs to be studied further   further -8. In th further . The stu further .Holeck et al showed a correlation between FGF23 and metabolic syndrome in another study. They detected serum value of FGF23 was high in obese and premenopausal women. They concluded that, FGF23 is probably related to the reduction of serum phosphorous in obese patients . In animIn our study, only level of blood pressure and serum albumin levels were significantly correlated with FGF23. These require further investigation to better understand of this aspect of CKD patients.Small proportion of the patients was a limitation of our investigation. Our study was cross-sectional and we could not compare our findings with a control group. Hence, it is suggested to conduct case-control studies with larger sample sizes to better assess the role of FGF23 in renal disease more precisely.Authors are grateful to research Deputy of Department of Nephrology, Tehran University Medical Sciences, for their financial support of this project.The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.All authors contributed to design of the research. PY, FD and SS conducted the research. SS and AP analyzed the data. PS and AP prepared the manuscript. All authors read, revised, and approved the final manuscript.Ethical issues  have been completely observed by the authors.This paper is extracted from thesis of Dr. Fatemeh Yaghoobi and financial support was provided by the Chronic Renal Failure Research Center of Tehran University of Medical Sciences.


Adolescents with type 1 diabetes and obesity present higher cardiovascular risk and ambulatory blood pressure measurements (ABPM) has been shown to predict vascular events, especially by identifying the nondipper status. The aim of our observational cross-sectional study conducted in adolescents with type 1 diabetes, overweight subjects and healthy controls was to assess mean blood pressure parameters to identify subclinical cardiovascular risk.The study included adolescents patients with type 1 diabetes followed in our Pediatric Department in University of Catania between January 2011 and 2013. A total of 60 patients were enrolled, and 48  completed the study. For each subject we performed systolic and diastolic Ambulatory Blood Pressure Measurements (ABPM) during wakefulness and sleep recording blood pressure every 30 min for 24 h with the Tonoport V/2 GE CardioSoft V6.51 device. We compared the data of patients with those of overweight subjects and healthy controls.ABPM revealed no significant difference between type 1 diabetic patients and overweight subjects in 24 h Systolic, 24 h Diastolic, Day-time Systolic, Night-time systolic and Day-time Diastolic blood pressure values but significantly different values in Night-time Diastolic blood pressure values (p < 0.001). We found significant differences between type 1 diabetic patients and healthy controls in all 24 h Systolic (p < 0.001), 24 h Diastolic (p < 0.01), Day-time Systolic (p < 0.01), Night-time Systolic (p < 0.001), Day-time Diastolic (p < 0.05) and Night-time Diastolic (p < 0.001) blood pressure values. We detected hypertension in 12/48 (25 %) type 1 diabetic patients and in 10/48 overweight subjects , whereas no-one of healthy controls presented hypertension (p < 0.001). We observed nondipper pattern in 40/48 (83.3 %) type 1 diabetic patients, in 33/48 (68.8 %) overweight subjects , and in 16/48 (33.3 %) of healthy controls .ABPM studies might help to define a subset of patients at increased risk for the development of hypertension. In evaluating blood pressure in type 1 diabetes and overweight subjects, ABPM should be used since a reduced dipping can indicate incipient hypertension. According to the World Health Organization (WHO) cardiovascular disease is the number one cause of death globally: more people die annually from cardiovascular disorders than from any other cause .In recent years hypertension has shown an increase in the prevalence among adolescents and type 1 diabetes and obesity are two conditions with higher risk .Type 1 diabetes is associated with a higher cardiovascular morbidity and mortality rate and hypertension is one of the risk factors leading to increased incidence of vascular events diabetic subjects .Obesity is another independent risk factor for hypertension and more than 60 % of hypertensive patients are overweight .Ambulatory blood pressure measurements (ABPM) have been shown to predict vascular events more accurately than office blood pressure (BP) or random blood pressure measurements and can identify the nondipper status, characterized by a decrease in physiological night-time drop of BP, constituting the first sign of the increase of pressure load on blood vessels , 6.The aim of our observational cross-sectional study, performed in adolescents patients with type 1 diabetes since at least 3 years, overweight subjects and healthy controls aged between 13 and 21 years, was to assess mean blood pressure parameters, to identify subclinic cardiovascular risk of these patients.The mean age of the patients was 15.4 ± 2.3 (13–21) years and duration of diabetes was 8 ± 3.2 (3–17) years.The study included adolescent patients with type 1 diabetes followed in our Cardiology and Endocrinology Clinic of Pediatric Department in University of Catania in Italy between January 2011 and 2013. A total of 60 patients were enrolled, and 48  completed the study.Every patient if of age, or at least one parent or legal guardian if underage, gave their written informed consent before the patient’s inclusion in the study. The study was conducted in accordance with the Helsinki Declaration, and the study protocol was approved by the  Ethics Committee of the Medical University of Catania.The diagnosis of diabetes was made according to the current criteria of the GUIDELINES ISPAD American Diabetes Association: symptoms of diabetes; random plasma glucose or 2-hour plasma glucose during oral glucose tolerance testing of 200 mg/dL or greater, or fasting plasma glucose of 126 mg/dL or greater; detection of diabetes-specific autoantibodies; increased glycosylated hemoglobin A1c (HbA1c) levels .Inclusion criteria comprised a diagnosis of type 1 diabetes for >3 years, a mean HbA1c value between 6.5 and 10.7 % for the past 12 months, Tanner stage 3 or above.Exclusion criteria were other coexisting metabolic, endocrine, or genetic disease; taking any medications affecting substrate metabolism (excluding insulin), psychotropic medications, weight loss medications, and oral contraceptives, a cut-off HbA1c level of 10.7 % , prepubertal or early pubertal children (Tanner stage 1 and 2) (to control for the well-described changes in the rates of diabetic complications after puberty). Seven children with Celiac disease, four with thyroiditis and another one with vitiligo dropped out the study.The mean age of the patients was 15.4 ± 2.3 (13–21) years and duration of diabetes was 8 ± 3.2 (3–17) years.1c in the last year, lipid profile and microalbuminuria.Scheduled examination contemplates anamnestic assessment including age, adherence to drug treatment, smoking habits, alcohol consumption, duration of diabetes, other illness associated, family history of cardiovascular diseases; clinical examination with noting the presence and degree of acanthosis nigricans if present, measurement of height and weight with calculation of body mass index (BMI), systolic and diastolic BP, ABPM; blood testing including mean value of HbA2), with percentiles calculated from the year 2000 CDC growth charts and reference datasets [Height was measured by stadiometer and weight was measured on a calibrated scale as part of routine clinical care. BMI was calculated as weight in kilograms divided by height for meters-squared , percent of hypertensive measures, and percentage of nocturnal drop of systolic and diastolic BP. We defined hypertension as 24-h systolic/diastolic/mean arterial blood pressure values over the 95th percentile based on sex and height  accordinWe compared the data of patients with those of overweight subjects and healthy controls. We identified overweight subjects as people with BMI over 85th for age percentile without other diseases and healthy controls as subjects with normal axiological parameters and without cardiovascular, metabolic, respiratory, neurological, gastrointestinal, blooding diseases.t test. We calculated statistically significant differences for diabetic patients and overweight subjects or healthy patients using the χ2 test. Statistical significance was set at levels of p < 0.05, p < 0.01, and p < 0.001.For nominal characteristics, the number of patients and percentages are given. Descriptive statistics were calculated for all demographic and clinical variables. For each data we calculated mean ± SD (Standard Deviation). For the evaluation of statistically significant parameter differences within the whole sample and specific subgroups, we used the independent two-sample Student’s The correlation between numerical variables was calculated through Spearman’s correlation coefficient. For the categorical variables we analyzed the odds ratio (OR) with the 95 % confidence interval.The demographic and clinical characteristics of the subjects are listed in Table The blood pressure profiles and the results from analysis of OR with the 95 % confidence interval and t student test of all subjects are summarized in Tables We detected hypertension in 12/48 (25 %) type 1 diabetic patients and in 10/48 overweight subjects , whereas no-one of healthy controls presented hypertension (p < 0.001). We observed nondipper pattern in 40/48 (83.3 %) type 1 diabetic patients, in 33/48 (68.8 %) overweight subjects , and in 16/48 (33.3 %) of healthy controls . Finally we noticed hypertension and nondipper pattern at the same time in 4/48 (8.3 %) type 1 diabetic patients and in 3/48 (6.2 %) overweight subjects , whereas no-one of healthy controls showed these anomalies in blood pressure values (p < 0.001). We found 8/13 (61.5 %) dipper status among patients with albuminuria and 32/35 (91.4 %) dipper status among patients without albuminuria.We did not find correlation between alteration of blood pressure circadian rhythm and HbA1c, duration of diabetes, total cholesterol, BMI or microalbuminuria (p = ns).Our study shows the relevance of borderline systemic arterial pressure alterations identifiable by using of Ambulatory blood pressure Monitoring in type 1 diabetic patients and overweight subjects in adolescence.In our series we detected significant difference in number of hypertensive subjects between type 1 diabetic patients and healthy controls (p < 0.001), demonstrating that type 1 diabetes and obesity may be a considerable risk factor for hypertension, but not between type 1 diabetic patients and overweight subjects (p = ns) because also obesity, likewise diabetes, is associated with increase of cardiovascular diseases.We found significant difference between type 1 diabetic patients and healthy controls in all values of 24 h Systolic (p < 0.001), 24 h Diastolic (p < 0.01), Day-time Systolic (p < 0.01), Night-time Systolic (p < 0.001), Day-time Diastolic (p < 0.05) and Night-time Diastolic (p < 0.001) blood pressure but only in night-time diastolic blood pressure values between diabetic patients and overweight subjects (p < 0.001).Both type 1 diabetes and overweight are conditions with increased cardiovascular risk. Type 1 diabetes patients present in the long-term outcome microangiopathy and macro angiopathy such as nephropathy, retinopathy, and cardiovascular disease, that lead to increased morbidity and premature mortality  and elevThe pathogenesis of vascular complications still remains incompletely understood; however, endothelial dysfunction (ED) is thought to play a central role  and the There is some evidence that endothelial-dependent responses of the microvasculature and macro vasculature are impaired in children with type 1 diabetes when vascular complications are still subclinical , 18. TheIn this prospective, the β2 adrenergic receptor seem play a role in both endothelial dysfunction and insulin release. Vascular β2 adrenergic receptors (β2ARs) mediate adrenergic vasorelaxation through direct activation of vascular smooth muscle cells, since the β2 ARs are expressed on endothelial cells (EC) and their stimulation causes endothelial nitric oxide synthase (eNOS) activation. This response is available to low concentration of agonist in several vascular districts .The noradrenergic system provides fine-tuning to the endocrine pancreas activity through the function of a- and b-adrenergic receptors (ARs). The reciprocal regulation exerted by insulin and the adrenergic system has been well documented through a large number of studies. More recent evidence shows that mice with simultaneous deletion of the three known genes encoding the bARs  present a phenotype characterized by impaired glucose tolerance. Studies with b2AR agonists further suggest that the b2AR may play an important role in regulating insulin secretion. In addition, different human polymorphisms in the b2AR gene have been associated with higher fasting insulin levels. Nevertheless, the impact of the b2AR subtype on glucose tolerance and insulin secretion is still unclear .Overweight and hypertension appear also to be inextricably linked . The patAmong these, likewise to diabetes, there are also oxidative stress and inflammation that leads to endothelial dysfunction interacting with the microvascular endothelium in the mechanisms of obesity-associated hypertension . On one In our study we also observed a higher number of subjects with altered circadian blood pressure rhythm in type 1 diabetic patients and in overweight subjects than in healthy controls.Lack of nocturnal fall in BP and higher nocturnal BP values suggest target organ damage in primary hypertension . Obese aSome cohort studies showed that blood pressure increases with increasing weight in both obese and normal weight individuals , 33. In There is some evidence that birth order influences growth and metabolism, from infancy to early adulthood. Importantly, first-born children have reduced insulin sensitivity and higher daytime blood pressure . AlthougSome genes have been identified in the background of hypertension. CaMKIV plays a relevant role in the regulation of the vascular tone by a mechanism that involves eNOS activation through phosphorylative events. Impairment of CaMK-mediated activation of eNOS, as in CaMK4 gene deletion, induces hypertension, as demonstrated by the fact that CAMK4_/_ mice display a hypertensive phenotype that leads to typical organ damage .The G-protein coupled receptor kinases (GRKs) are important regulators of beta-adrenergic signaling and play a role in regulation of peripheral vascular tone. Indeed, GRK2 levels and activity have been found increased in lymphocytes from hypertensive patients. Since a generalized impairment of b-adrenergic mediated vasodilation has been shown both in animal models of hypertension and in human hypertensive subjects, this alteration has been related to the increased GRK2 abundance and activity .ADRBK1) and GRK5 (GRK5) might be important pharmacogenetic targets [Down regulation of β-adrenergic signaling is mediated via GRK2 and GRK5 that phosphorylate cardiac β-adrenergic receptors leading to β-arrest in recruitment and G protein uncoupling. Given the important role of GRK2 and GRK5 in β-adrenergic signaling, functional genetic polymorphisms in the genes coding for GRK2  compared with healthy, normotensive obese and metabolic dysregulation (including hyperinsulinemia that induces the activation of the SNS and also has a direct action on the kidney to stimulate sodium retention, adipokine imbalance, and increased inflammatory cytokines .Angiotensin II promotes the growth and differentiation of adipocytes , the decAttenuation of the nighttime fall in blood pressure has been shown to be associated with an increased risk of left ventricular hypertrophy, increased intima media thickness  and incrAmbulatory blood pressure measurements in type 1 diabetic patients and overweight subjects should be considered during the follow-up of these patients because they can reveal an altered circadian blood pressure rhythm that has been shown to led to higher mortality and morbidity for vascular events as compared with patients with normal rhythms , 61.Blood pressure exerts a dose-dependent effect on cardiovascular risk and it is involved in the developing of coronary artery disease .The impact of sub clinical hypertension occurring at young ages is demonstrated by the correlations found between adolescent and adult BP readings. This relationship is illustrated by the ‘tracking’ phenomenon: subjects presenting BP values in a higher percentile during childhood and adolescence, likely will have their BP values in the same range during maturation, therefore it is possible to give a enough close prediction of who will have got a higher risk in adulthood . Since aOur study has several limitations. This is a cross-sectional analysis, and therefore no data on the progression of complications or survival are available. The sample is relatively small, and thus additional studies in larger cohorts including longitudinal data are recommended to further study the prevalence of altered circadian blood pressure rhythm in type 1 diabetic patients.Another limitation of our study is heterogeneity of age of the cohort, but this was necessary to assess a large-enough sample in this single-institution study.We included only patients with type 1 diabetes who had relatively good control of their diabetes and thus these data cannot be generalized to those with poor control. However, the effect of poor control of diabetes on microvascular and macro vascular complications is already well known and has been studied in large multicenter trials. We did not subdivide or stratify by gender, so we could not study the difference between the sexes.Future research in this area of inquiry should include the analysis of genetic profiles of diabetic, overweight and healthy controls, include larger samples drawn from diverse populations, stratify analysis by gender, to identify an eventual correlation between genetic features and clinical severity.Subclinical hypertension and reduced dipping can indicate incipient hypertension and ABPM studies might help to define a subset of patients at increased risk for the development of hypertension, who might benefit from the early introduction of anti-hypertensive strategies. We suggest to include ABPM in follow-up of type 1 diabetes and overweight subjects because it correlates much better with the prevalence of cardiovascular events than that provided by casual measurements. ABPM also offers numerous advantages over casual measurements in adolescents, as the measurements take place during everyday activities on the one hand and nighttime sleep on the other, thus providing continuous data about BP and it is better correlated with target organ damage than are office measurements. Considering the ‘tracking’ phenomenon in which adolescent hypertension translates into adult hypertension, it is of great importance that patients with the highest risks should be screened out based on reliable data.


Hypertension is a prevalent cardiovascular disease risk factor among blacks and adolescent hypertension can progress into adulthood.To determine the prevalence of hypertension and prehypertension among secondary school adolescents in Enugu South East Nigeria.A study of 2694 adolescents aged 10-18 years in Enugu metropolis was carried out. Socio-demographic profile anthropometric and blood pressure readings were obtained. Derived measurements such as Prehypertension, hypertension and BMI were obtained.The results showed that the mean systolic blood pressure and diastolic blood pressure for males were 106.66+ 11.80 mmHg and 70.25 + 7.34 mmHg respectively. The mean SBP and DBP for females were 109.83+ 11.66 mmHg and 72.23 + 8.26 mmHg respectively (p < 0.01). Blood pressure was found to increase with age. Prevalence of hypertension and prehypertension was 5.4% and 17.3% respectively with a higher rate in females (6.9%) than males (3.8%). Prevalence of prehypertension among males and females were 14.3% and 20.1% respectively. The prevalence of obesity was 1.9%.Modifiable risk factors exist among adolescents. Early lifestyle modification and a strengthened school health are recommended. Hypertension is the commonest non communicable disease affecting both sexes in all races . It is tMany studies -7 on hypThe risk of developing hypertensive cardiovascular complications is greater in younger than in older individuals . The youThe study was designed to determine the prevalence of arterial hypertension and pre-hypertension among secondary school adolescents in Enugu and also to estimate the proportion of some modifiable risk factors for arterial hypertension; such as obesity, cigarette smoking and alcohol consumption among the adolescents.th percentile of the blood pressure for age, height and sex while pre-hypertension was defined as blood pressure above the 90th percentile but below the 95th percentile or greater than or equal to 120/80 mmHg compared with the Working Group on blood pressure standards recommendations [The study was a cross sectional survey of 2694 secondary school adolescents aged 10-18 years. The study was conducted from October 2009 to June 2010. A multistage sampling method was used to select the subjects from the schools in the three local government areas that make up the metropolis. Schools were stratified into all boys’, all girls’ and co-educational schools. Ethical clearance was obtained from the University of Nigeria Teaching Hospital ethics and Research committee. The participants were apparently healthy secondary school adolescents subjects. Those who were preadolescents were excluded as well as subjects who volunteered history of chronic illness such as bronchial asthma, renal pathologies such as nephrotic syndrome and on chronic medication were also excluded. Data was collected from the participants using a pretested questionnaire. Anthropometric measurements were done using stadiometer. Obesity and overweight were defined as body mass index greater than or equal to age specified international cut off points for child overweight and obesity,  while thndations . Those tndations . AdolescData were analyzed with computerized statistical package for social sciences (SPSS) version 15.0. Data base was created using the soft ware and frequency of variables obtained. Students’ t- test was used to compare mean systolic and diastolic blood pressures and other numeric variables. Chi-squared test was used to compare categorical variables. Correlation coefficient was used to describe strength of association between variables. Significant probability value was P < 0.05.A total of 2694 subjects participated in the study, this comprised 1293 males and 1401 females; male to female ratio of 1:1.08. The mean age of the population was 15.03 ± 1.89 years . The age and sex distribution of the respondents is shown as Table 2 and 21.16 ± 3.29 Kg/M2 respectively. The anthropometric variables were found to increase with age  and 14–16 years (mid adolescent) Table th percentile for both the SBP and DBP were 110 mmHg and 70 mmHg respectively while the 95th percentile value was 125 mmHg for SBP and 84 mmHg for DBP. See Figure Blood pressure was also shown to increase with age. The average yearly increase for DBP was 1 mmHg while the average annual increase of SBP was 2 mmHg. The study group 50Of the 2694 study respondents the 322 (12%) were found to have hypertension, 364 (13.5%) prehypertension and 2008 (74.5%) had normal blood pressure after the first set of measurements.In the last series of measurements, it was found that there were 146 adolescents that had hypertension giving a prevalence of 5.4%. Among these 97 (6.9%) were females and 49 (3.8%) were males. Among the hypertensives 99 subjects (67.8%) were classified as stage I while 47 subjects (32.2%) had stage II hypertension. About 77.3% of the subjects had normal blood pressure values while 467 (17.3%) had pre-hypertension. The prevalence rate of pre-hypertension in males and females were 14.3% and 20.01% respectively p < 0.01.Tables It was found that 219 (8.1%) of the respondents were underweight this comprised 117 (53.4%) females and 102 (46.6%) males p = 0.31, 287 (10.7%) were overweight 186 (64.8%) females and 101 (35.2%) males p < 0.01. The prevalence of hypertension and prehypertension among the overweight subjects were 9.1% and 34.1% respectively.Obesity was found in 52 subjects of the study population giving a prevalence rate of 1.9%. Of the 52 obese subjects there were 33 (63.5%) females and 19 (36.5%) males. Normal blood pressure readings was found in 18 (34.6%) of the obese subjects while prehypertension and hypertension occurred in 17 (32.7%) and 17 subjects (32.7%) respectively.Alcohol consumption was noted among 1035 (38.4%) of the study population. Significant daily intake of alcohol was noted among 2.2% of those that consumed alcohol while 92.3% had non significant intake. Alcohol intake was noted more among the males than the females . However blood pressure profile was independent of alcohol intake. It was also observed that 61 respondents smoked cigarette while 8 respondents smoked marijuana, this comprised 58 males and 11 females giving a prevalence rate of 2.6% blood pressure profile was also independent of the smoking attitude of the adolescents.The prevalence of hypertension in the study population was 5.4% with male and female prevalence rates of 3.8% and 6.9% respectively. This difference in the observed prevalence of hypertension may probably be due to a greater delay in boys in completing pubertal development and attaining final height than in females. In addition greater body mass index and waist circumference noted in females may have contributed to this difference in blood pressure. The observed prevalence rates shows an increase in the prevalence rate of hypertension when compared to a rate of 3.3% obtained in Southwest of Nigeria  though lth percentile for age will assist in the proper evaluation and classification of these individuals, because elevated blood pressure may be an early pointer to some chronic diseases such as nephritic syndrome, chronic kidney disease, adrenal and renal tumors hypercholesterolemia among others [The detection of individuals who have blood pressure greater than or equal to 95g others . It is pThe observed prevalence of pre-hypertension was lower than values obtained by Ejike et al.  in NorthIn the present study the mean SBP and DBP increased with ages in both sexes. There was a more rapid increase between the ages of 13 and 15 years which corresponds to the mid adolescent age group. This age group is usually the period of puberty in adolescents. Similar finding has been documented in the earlier studies ,29. The Blood pressure pattern has been documented to differ between male and females. Both the mean SBP and DBP were significantly higher in females than in males especially during the early and mid adolescent stages. A similar trend has also been noted by Jaddou et al.  and AyooMoreover females were noted to have higher body weight and body mass index than males in the study population. It is possible that these differences may have contributed to the observed differences noted in the blood pressure pattern of both sexes. The anthropometric variables were shown to correlate positively with age, SBP and DBP, and this is consistent with the report of several authors ,22,30. TObesity has been noted to be associated with hypertension, the observed prevalence in the present study is similar to earlier studies in developing countries ,34 but lBlood pressure pattern was independent of risk factors such as smoking and alcohol intake of the participants in this study, this may be due to the quantity consumed and duration of consumption which is usually longer in adult population. It is possible that these young smokers and consumers of alcohol may continue up to adulthood as had been documented by earlier authors ,37. TherThe limitations noted in the study include exclusion of subjects that was based on volunteered information and biochemical analysis that were not done. These could have helped in further identifying subjects with possible secondary hypertension also the lipid profile and presence of insulin resistance were not studied, this leaves room for further studies in these areas. The timing of feeding of the participants were not controlled in the study this could have controlled for transient blood pressure variability immediately after feeding.Our study revealed a relatively high prevalence rate of hypertension and prehypertension among adolescents studied and these were more common among female subjects.It is therefore recommended that periodic screening and monitoring of blood pressure of adolescents should be incorporated into the school health programme, while general public health education on hypertension and its associated risk factors should be strengthened.Written informed consent was obtained from the patients for the publication of this report and any accompanying images.The authors declare no competing interests.FAU was involved in conceptualizing and writing of the manuscript. ANI participated in the sequence alignment and drafting of the manuscript. ARCW contributed in the proof reading and correction of the manuscript while JMC Helped in editing and rewriting the manuscript to journal requirements. All authors contributed to the conception, writing and proof reading of this manuscript.


These compounds were evaluated in pharmacokinetic (PK) and blood pressure pharmacodynamics (PD) in vivo rat and dog models and were shown to exhibit sustained compound exposure  after oral dosing, predicting QD dosing in humans. Further, they significantly decreased mean arterial blood pressure (MAP (≥ 10mmHg) after oral dosing. The potential for sGC stimulators to work in combination with reference antihypertensive therapies was assessed in an in vivo PD assay in a spontaneous hypertensive rat (SHR) model. Doses of losartan, atenolol, amlodipine, and our sGC stimulators that induced an effect (< 30mmHg) on MAP were chosen. IWP-121, a representative sGC stimulator, was shown to provide additional MAP lowering effects when combined with losartan, atenolol, or amlodipine, resulting in an increase in overall blood pressure effects between 5-50%. By linking compound concentration to blood pressure change for each compound alone and in combination, we were able to assess the PK/PD relationships for the individual and combined effects.Soluble guanylate cyclase (sGC) stimulators demonstrate smooth muscle relaxation and vasodilation via the nitric oxide (NO)-sGC-cyclic guanosine monophosphate (cGMP) pathway. A novel class of sGC stimulators, the pyrazole-pyrimidines, was synthesized with the objective of creating a potent, once-a-day (QD) oral treatment for cardiovascular diseases. Several compounds from this class were identified as potent stimulators of sGC sGC stimulators from the pyrazole-pyrimidine class demonstrated potent effects in lowering blood pressure in rats and dogs with a PK profile consistent with predicted once a day dosing in humans. Furthermore, sGC stimulator(IWP-121) enhanced the blood pressure lowering effects of standard anti-hypertensive agents in the rat and may provide opportunities for treating patients with resistant hypertension.


Syncope is a common medical problem, with a frequency between 15% and 39%. In the general population, the annual number episodes are 18.1–39.7 per 1000 patients, with similar incidence between genders. The first report of the incidence of syncope is 6.2 per 1000 person-years. However, there is a significant increase in the incidence of syncope after 70 years of age with rate annual 19.5 per thousand individuals after 80 years. It presents a recurrence rate of 35% and 29% of physical injury. Among the causes of syncope, the mediated neural reflex, known as neurocardiogenic or vasovagal syncope, is the most frequent. The others are of cardiac origin, orthostatic hypotension, carotid sinus hypersensitivity, neurological and endocrinological causes and psychiatric disorders. The diagnosis of syncope can be made by clinical method associated with the electrocardiogram in up 50% of patients. Its prognosis is determined by the underlying etiology specifically the presence and severity of cardiac disease. The annual mortality can reach between 18 and 33% if cardiac cause, and between 0 and 12% if the non-cardiac cause. Thus, it is imperative to identify its cause and risk stratification for positive impact in reducing morbidity and mortality. Syncope is the sudden loss of consciousness, associated with inability to maintain postural tone, with immediate and spontaneous recovery without requiring electrical or chemical cardioversion. This framework is secondary to cerebral hypoperfusion, with short duration (average 12 seconds). It has a prevalence of 42%, considering a life time of 70 years and an annual incidence of 6%  preferentially located in the inferolateral wall of the left ventricle, but also in the atria and in the pulmonary artery, and manifests with hypotension and paradoxical bradycardia due to increased activity of inhibitory receptors and consequent parasympathetic hyperactivity  presents as falls, dizziness, or syncope, resulting in functional impairment, with head injury, bone fractures and hospitalization. It is more common in the elderly, with frequency rates of up to 55% in those that residing in institutions, and with prevalence of 12%. Its classic definition is a drop of at least 20 mmHg in systolic and/or 10 mmHg in diastolic blood pressure within 3 min to take an orthostatic position. There are other presentations such as initial OH, when there is a greater than 40 mmHg drop in blood pressure, with less than 30 s in duration, and progressive OH, when the fall of blood pressure levels are gradual, between 3 and 30 min after taking standing position, without bradycardia , within 2 h after meals. The pathophysiology is due to sympathetic dysfunction, with inadequate peripheral vasoconstriction and insufficient heart rate increase. Precipitating factors are vasodilators, high temperature of food or of environment and diets high in carbohydrates  and more frequent in the elderly, especially diabetics with coronary or carotid atherosclerosis. Precipitating factors are sudden movements of the head and neck, cervical compressions and use of tight neck tie  may be presented as syncope.The primary autonomic dysfunction occurs in pure primary dysfunction syndrome (Bradbury–Eglleston), in central nervous system diseases . Secondary dysfunctions occur by changes of aging, due to the involvement of the peripheral nervous system in diabetes mellitus, renal failure, alcoholism, amyloidosis; infections of the nervous system by Chagas disease, human immunodeficiency virus; metabolic diseases such as vitamin B12 deficiency, porphyria; autoimmune diseases such as rheumatoid arthritis and others. And as antihypertensive drugs , anti-depressants may also cause autonomic dysfunction  patients during the mean follow-up of 614 days. Death was considered cardiovascular in 9 patients (26%). And among the patients who died, 82% were older and had cardiac risk factors such as abnormal ECG and/or heart disease. In contrast, among those with no abnormal ECG and/or heart disease, only six (3%) deaths occurred, resulting in a negative predictive value of 97%  and long (1 year) (Numerosos et al., A study of 37,017 patients with syncope in the period 2001–2009, without previous hospitalization for comorbidities, and with a control group of 185,085 individuals, demonstrated increased risk of all-cause mortality, stroke, cardiovascular hospitalization, device implantation, and recurrent syncope in healthy individuals after first admission for syncope (Ruwald et al., Regarding the recurrence of syncope, risk stratification cannot predict it. The incidence of recurrence of syncope was similar regardless of cause of syncope. Its rate was 0.3% in the first month, of 0.8% per month during the first year and 0.5% per month during the second year. On univariate analysis, predictors of recurrence were male sex, presence of prodrome and absence of palpitations (Ungar et al., Thus, prognosis is determined by the underlying etiology specifically the presence and severity of cardiac disease. And it is imperative to identify its cause and risk stratification for positive impact in reducing morbidity and mortality.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


People with prehypertension (120–130/80–90 mmHg) are at increased risk of progressing to hypertension. Recommendations for prehypertension include engaging in regular physical activity. We aimed to assess feasibility and acceptability and collect preliminary outcome data on ChiRunning for people with elevated blood pressure. ChiRunning is a commercially available running program based on the mindful movements of Tai Chi, which is aimed at decreasing injury by both increasing body awareness and modifying running form.We enrolled adults with elevated systolic (130–150 mmHg) or diastolic (80–100 mmHg) blood pressure in a 12-week pilot trial. Participants were randomized 2:1:1 to 8 weeks of: 1) intervention—a trainer-led ChiRunning group (n = 10); 2) active control—a trainer-led running group (n = 6); or 3) educational control—a self-directed running group (n = 6) and followed for 4 more weeks. The active control and educational control groups were combined for analysis.p = 0.04) but not in the control group . Self-reported running-related injury (i.e. discomfort leading to a decrease in running) was similar between groups  although self-reported running-related discomfort (i.e. discomfort that does not lead to changes in running) trended higher in the ChiRunning group .This study was feasible, meeting recruitment, retention and adherence goals, and acceptable to participants. Systolic and diastolic blood pressure did not change significantly over the study for either the ChiRunning or control groups. Changes in BMI over time were significantly different from zero in the ChiRunning group (ChiRunning appears to be a feasible and acceptable exercise program for people with elevated blood pressure. We did not find that ChiRunning had a significant impact on blood pressure or self reported injury, but did see a positive change in BMI over time. ChiRunning warrants further investigation in a larger trial.NCT01587183ClinicalTrials.gov Identifier:  High blood pressure, known as hypertension ≥140/90 mmHg), is a significant problem affecting one in three adults and was associated with 18.8 deaths per 1000 people in the United States in 2010 . Regular0/90 mmHgRunning may be a suitable form of exercise for people with prehypertension because it is typically vigorous, and more intensive activities have been associated with more cardiorespiratory fitness compared to less intensive activities , 11. In ChiRunning is a commercially available running program based on the mindful movement practices of Tai Chi. ChiRunning aims to prevent new and recurring injuries by decreasing loading forces on the body by teaching key features of running form, such as using a midfoot strike, reducing overstriding, and increasing cadence. Mindfulness and body awareness practices are also taught as part of the ChiRunning curriculum to both help identify early indicators of injury and to increase motivation .According to a recent American Heart Association statement, “alternative” approaches, including those that increase mindfulness and awareness, may be beneficial adjunctive therapies for prehypertension . MindfulIn this pilot study, we sought to establish feasibility and acceptability and to collect preliminary data on outcomes on a ChiRunning intervention versus control in participants at high risk of hypertension. Feasibility measures included meeting recruitment, retention, and adherence goals, and acceptability was determined through semi-structured participant feedback. The preliminary efficacy data that we collected included blood pressure and BMI over 5 time points  and self-reported incidence of running-related discomfort and injury over the 12 weeks of the study.For this randomized controlled pilot study, a statistician not affiliated with the study used computer generated random blocks of numbers and delivered them to study staff in sealed opaque envelops. Participants were randomly assigned to one of the following three groups with a 2:1:1 allocation ratio: 1) intervention—a trainer-led ChiRunning group (n = 10); 2) active control—a trainer-led running group (n = 6); or 3) educational control—a self-directed running group (n = 6). For the purpose of this article, the two control groups were combined to examine the effects of ChiRunning. Participants met for four training sessions . The study took place June through September 2012.We enrolled adults (age 18–70) living in the San Francisco Bay Area with elevated blood pressure. Participants were recruited using flyers and other print and online advertisements. After an extensive phone screen, eligible individuals were invited to an in-person study visit to have their blood pressure measured at the Osher Center for Integrative Medicine (OCIM).2, and 3) not currently taking blood pressure medication. Eligibility criteria were expanded and the recruitment period was extended (from 8 to 12 weeks) as the study team found these criteria as being overly restrictive and limiting enrollment. In the revised eligibility criteria: 1) the upper limit of SBP was increased to 150 mmHg and the upper limit of DBP to 100 mmHg, 2) BMI was increased to ≤35 kg/m2, and 3) participants currently taking blood pressure medication were permitted with permission of their physician.Our initial inclusion criteria were: 1) systolic blood pressure (SBP) in the range of 130-139 mmHg or diastolic blood pressure (DBP) in the range of 80-85 mmHg, 2) BMI ≤30 kg/mExclusion criteria included: inability to provide informed consent; any history of serious joint or lower limb injury precluding running as a reasonable exercise program; self-reported inability to run continuously for 5 min ; substance or alcohol abuse, mental health, or a medical condition that, in the opinion of investigators, would make it difficult to participate in the group training sessions; contraindications to moderate-intensity exercise; arrhythmia, alcoholism or other condition that makes accurate blood pressure measurement difficult; a diagnosis of diabetes, chronic kidney disease or other condition indicating tighter control of SBP; non-English speaking (group training was given in English); pregnant or planning to get pregnant during the study period; unwillingness or inability to commit to walk/running up to 30 min three times per week; plans to move from the area during the study time period; and currently exercising at vigorous intensity for greater than 90 min per week. The UCSF Committee on Human Research approved this pilot study and all eligible individuals signed a written, informed consent prior to enrollment.All participants received a pamphlet on the Dietary Approaches to Stop Hypertension (DASH) diet  at theirChiRunning: A Revolutionary Approach to Effortless, Injury-Free Running [ChiRunning is a manualized technique requiring certification for all trainers. The ChiRunning group met on Sunday mornings with the certified trainer for an initial 4-h session at week 0, and three more times for 2-h training sessions at weeks 2, 4, and 8. The material covered had two primary focuses: 1) learning specific components of running form, and 2) developing mindfulness and body awareness in the context of running. While each session contained some elements of both focuses, the first two training sessions focused on running form, the third on body awareness and mindfulness and the fourth training session was a review. During each training session, participants were video-recorded while running and received individualized coaching feedback on their running form. Participants met at OCIM for the first half of the session (lecture) and walked 2 blocks to a community center gymnasium for the second half (applied). Participants in the ChiRunning group were given the book  Running  and a meParticipants were randomly assigned to one of two control groups: 1) active control, an attention matched, group based training with a running coach, or 2) self-directed control, which provided extensive written materials on starting a running practice. The active control group met with a running coach (certified USA Track and Field and Road Runners Club of America) on Sunday afternoons for the same durations as the ChiRunning group. The format of each training session was an initial talk on a running-related topic, followed by questions and answers and a group walk/run. Because of the group walk/run, the training sessions were held at various running-appropriate locations around San Francisco. The talks covered running topics including goal setting, pace, mileage, warm-up/cool down, stretching, core strengthening, cross training, hydration and nutrition, and shoes. Study staff was present at training sessions to ensure adherence to the study protocol. The educational control participants received printed materials on the same running topics covered in the active control talks. The two control groups were combined for analyses given that the primary focus of this article is on ChiRunning and due to small cell sizes.Our primary outcomes included feasibility, acceptability and preliminary efficacy for the effect of ChiRunning on blood pressure and BMI. We assessed feasibility based on recruitment, retention, and adherence and acceptability based on participant feedback. Feasibility of recruitment was determined by meeting at least 75 % of our original goal of n = 40, feasibility of retention was determined by retaining 75 % of participants enrolled in the study. Adherence was calculated as the percent of runs and time running laid out in the training schedule that was completed by the participant based on their entries in the training diary. Participants were considered adherent if they met training requirements 75 % of the time. Participants were sent surveys to gauge acceptability of content delivery, training structure and coaches during and after the intervention. Preliminary efficacy outcomes included within-group changes and between-group differences in SBP, DBP, and BMI over the course of the study and self-reported running-related discomfort and injury.Participants in the control group scheduled study visits to OCIM during normal business hours to have their blood pressure taken for all five blood pressure measures. Out of convenience, participants in the ChiRunning group had blood pressure measurements taken before each of the four training sessions on Sunday mornings. The follow-up visit for the ChiRunning group was scheduled during normal business hours. For all blood pressure visits, participants were asked to sit quietly in a room by themselves for 10 min, after which a trained assessor took two blood pressure measurements two minutes apart using a mercury sphygmomanometer . Weight discomfort (RRD). Self-reported discomfort that did affect the duration or intensity of the run was considered to be more severe and classified as running-related injury (RRI) [Running-related discomfort and injury were based on entries in the training diary. Self-reported discomfort that did not affect the duration or intensity of the run was considered running-related ry (RRI) .t-test with a two-sided probability of Type 1 error = 5 % and probability of a Type 2 error = 20 %, with our recruited n = 22, we were able to detect a very large between group effect of d ≥ 1.26.Given that this pilot was to establish feasibility and acceptability and collect preliminary outcome data, our study was not powered to detect small to medium-sized effects. Based on power calculations for an independent samples t-tests with equal variances for within-group comparisons and independent samples t-test to examine between-group differences. Fisher’s exact test was used to compare categorical data. We used a linear mixed model to estimate the slope (change over time) and to compare slopes between groups. Discomfort and injury incidence were calculated as new RRD or new RRI reported per 100 h of running, and 95 % confidence intervals were calculated based on a Poisson distribution. We considered p ≤ 0.05 to be statistically significant, although p ≤ 0.1 was considered to be a meaningful trend given the pilot nature of this study. All statistical analyses were performed using Stata 12 Statistical Software: College Station, TX: StataCorp LP.We used paired 2.Figure Based on recruitment, retention, adherence and participant feedback, we determined that the study design and materials were both feasible and acceptable. By revising eligibility criteria we were able to increase recruitment to an acceptable rate. We retained 19 (86 %) participants through study completion. Two participants dropped out after the first training session, one (ChiRunning) for a pre-existing foot problem, and one (active control) due to a scheduling conflict resulting from a new job. Another participant (active control) dropped out after the third training session due to an illness unrelated to running. The three participants that dropped out had baseline measures similar to participants completing the study.p = 0.78). Sixteen of the 18 (89 %) responding participants felt they received the tools necessary to maintain their running practice and 14 (78 %) thought that their blood pressure had improved or would improve based on the training they had received as part of the study.Of the 13 participants in the two trainer-led groups, 11 (92 %) attended at least 3 of 4 training sessions and gave the trainer a mean score of 4 out of 5 for the quality of the teaching. Of the 19 participants completing the study, 14 (73 %) completed at least 75 % of the scheduled runs and 17 (89 %) submitted a training diary that was at least 75 % complete. Participants completed an average of 89 % of the scheduled runs in both groups, and 85 % and 80 % of scheduled time in the ChiRunning and control groups, respectively (There were no significant changes in either group between baseline (week 0) and post intervention (week 8), or between baseline and follow-up week 12)  for blood pressure, authors reported a positive effect for participants with hypertension but mixed findings for prehypertension . Our parp = 0.042), suggesting that a larger study may favor the ChiRunning group for changes in BMI.Changes in BMI between baseline and post intervention and baseline and follow up were in the right direction for both groups Table . While tGiven the sensitivity of blood pressure to external factors  BMI may be a more stable indicator of efficacy and we may see changes in blood pressure with longer follow up. Such a change was seen in a study of 115 prehypertensive participants over 6 months where increased fitness and decreased waist circumference independently predicted a decrease SBP .p = 0.54).Both the ChiRunning and control group spent similar amounts of time running and had similar proportions of participants with self-reported RRD and self-reported RRI Table . Injury p = 0.06). This may have been the effect of increased awareness leading to increased sensitivity for RRD, which may play a significant role in injury prevention. In another study, an association between increased age and decreased injury led authors to speculate that age was acting as a proxy for older participants having more experience with “the language of their body” and not necessarily the age of their body per se [not necessarily indicative of a higher injury rate, rather it could indicate a lower threshold for body sensing and by promoting early prevention measures, this sensing may lead to decreased injury over time.There was a trend of higher self-reported RRD in the ChiRunning group (y per se . Increasy per se . Thus, sDue to the pilot nature of our study, there were limitations that also need to be considered. One of the objectives was to refine procedures. As part of the intervention refinement, adjustments to the protocol were made throughout the study, and inclusion criteria were revised. Other areas for procedural refinements in a future study were identified, namely a potential bias associated with the timing of blood pressure measurement. In addition, due to the pilot nature of the study, our sample size was small, and thus the study was not powered to detect many significant effects.ChiRunning appears to be a feasible and acceptable training technique for people with elevated blood pressure. We did not find that ChiRunning had a significant impact on blood pressure or self-reported injury, but did see a positive affect on BMI. Teaching ChiRunning may be effective for improving blood pressure but warrants further investigation in a larger trial.


Aim. To evaluate the relationship between creatinine clearance rate (CCR) and the level of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients and their correlations with HF severity. Methods and Results. Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. The following variables were compared among these three groups: age, sex, body mass index (BMI), smoking status, hypertension, diabetes, NT-proBNP, creatinine (Cr), uric acid (UA), left ventricular end-diastolic diameter (LVEDD), and CCR. The biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR varied significantly in the three groups, and these variables were positively correlated with the NHYA classification. The levels of NT-proBNP and CCR were closely related to the occurrence of HF and were independent risk factors for HF. At the same time, there was a significant negative correlation between the levels of NT-proBNP and CCR. The area under the receiver operating characteristic curve suggested that the NT-proBNP and CCR have high accuracy for diagnosis of HF and have clinical diagnostic value. Conclusion. NT-proBNP and CCR may be important biomarkers in evaluating the severity of HF. Chronic heart failure (CHF) is a disorder associated with high mortality and prolonged hospitalization; it affects more than 10 million people in the countries represented by the European Society of Cardiology . Over thThe natriuretic peptide family mainly includes A-type natriuretic peptide (ANP) or atrial natriuretic peptide, B-type natriuretic peptide (BNP) or brain natriuretic peptide, C-type natriuretic peptide (CNP), renal natriuretic peptide, and Dendroaspis natriuretic peptide (DNP). The ANP and BNP are mainly secreted by the atrium and ventricle, respectively, and have similar effects, which are natriuretic and can inhibit renin angiotensin aldosterone system, and BNP is useful as a principal biomarker for CHF –9. SinceHeart failure and renal dysfunction are closely related. The ventricular dysfunction caused by CHF may lead to a series of adaptive responses, such as the activation of neuroendocrine system, peripheral vasoconstriction, and reduced renal perfusion pressure. All these changes can cause renal dysfunction, and the deterioration of renal function further increases the capacity of the load of the heart and leads to a vicious circle. The natriuretic peptide system can be activated in both heart failure and severe renal insufficiency patients. Renal dysfunction is often present in CHF patients with reported CCR lower than 60 mL/min in up to 50% of patients , 14.Several studies have revealed that there is a relationship between NT-proBNP levels and clinical manifestations , 15, 16.The investigation complied with the principles outlined in the Declaration of Helsinki . The preThree hundred thirty-six consecutive symptomatic or nonsymptomatic Chinese heart failure patients for suspected myocardial ischemia scheduled for coronary angiography were recruited between July 2011 and October 2012 at the 6th People's Hospital affiliated to Shanghai Jiaotong University Medical College, Dalian Municipal Central Hospital Affiliated of Dalian Medical University, and General Hospital of Shenyang Military Area Command, China. Severity of CHF was clinically evaluated according to the NYHA classification.Two hundred and one Chinese patients were grouped according to the New York Heart Association (NYHA) classification as NYHA 1-2 and 3-4 groups and 135 cases out of heart failure patients as control group. Patients in NYHA class 1 showed cardiac disease but result in no limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. No cardiac disease, hypertension, or diabetes was diagnosed in control group.2 = weight (kg)/[height (m)]2) and blood pressure by standard methods.A fasting venous blood sample was obtained for measurement of fasting glucose and HbA1c. Patients with HbA1c levels ≥6.5% were diagnosed as diabetic, even without previous history of diabetes. Body weight and height were measured to determine the body mass index  for continuous variables, or as percentages (%) for categorical variables. Statistical analysis was performed using SPSS for Windows (version 13.0). Variables such as age, sex, and smoking status were adjusted by covariance analysis. Repeated measures one-way ANOVA was used to determine the significance of trends within groups, and further comparison between the two groups was done using least significant difference procedure (LSD). Numerical data was compared using the Chi-square test. Spearman single-factor correlation analysis and Spearman coefficient of rank correlation were used to evaluate linear relationship between biomarkers and NYHA classification. Logistic regression was used to identify independent risk factors for heart failure. Association between variables in NT-proBNP and CCR was examined using Pearson's correlation coefficient and linear regression. Receiver operating characteristic (ROC) curves were used to obtain the biomarker cut-off points for predicting the prevalence of angiographic heart failure. The respective areas under the curve (AUC), sensitivity, and specificity were compared between biomarkers and NYHA classification. A value of Fasting plasma glucose (FPG) was quantified by the glucose oxidase procedure and HbA1c was measured by ion-exchange high-performance liquid chromatography . Creatinine (Cr) and uric acid (UA) were measured by an enzymatic method with a chemical analyzer ; CCR was calculated using the Cockcroft-Gault formula. The chemiluminescence-based immunoanalytical system was used to determine plasma levels of NT-proBNP .Two-dimensional and Doppler echocardiography scans were performed using the HP77020A echocardiograph  to assess the left ventricular end-diastolic diameter (LVEDD).The baseline characteristics of the patients are shown in P > 0.05); the variables of male, hypertension, diabetes, NT-proBNP, CCR, Cr, UA, and LVEDD were significantly different among the three groups .There were no significant differences in age, BMI, and current smokers between any of heart failure groups and the control group . The NT-proBNP level increased from control group (78.83 ± 15.27) to NYHA class 1-2 group (1611.54 ± 171.24) to class 3-4 group (3162.19 ± 453.21). The value for CCR significantly decreased from control group (89.94 ± 16.39) to NYHA class 1-2 group (59.43 ± 19.57) and class 3-4 group (53.57 ± 17.41) (P < 0.01). The patients with history of hypertension and diabetes were higher in the NYHA class 1-2 and 3-4 groups than in the control group (P < 0.05), and there was no significant difference between NYHA class 3-4 and 1-2 groups  and age, male, BMI, current smokers, hypertension, diabetes, NT-proBNP, CCR, Cr, UA, and LVEDD as independent variables, the results showed that NT-proBNP and CCR were independent risk factors for heart failure .The Pearson correlation analysis was carried out to determine the relationship between variables of NT-proBNP and CCR in control and heart failure groups. r = −0.62, P = 0.00, In univariate linear regression analysis, CCR showed a significant negative correlation with NT-proBNP in the control and heart failure groups (The ROC curves for NT-proBNP and CCR as indicators of heart failure are shown in In this study, we observed that the variables, such as male, hypertension, diabetes, NT-pro BNP, CCR, Cr, UA, and LVEDD, were significantly different among all groups. Furthermore, we revealed that the biomarkers of NT-proBNP, Cr, UA, LVEDD, and CCR were positively correlated with the severity of heart failure.The NT-proBNP level significantly increased and the value for CCR significantly decreased from control group to NYHA class 1-2 to 3-4 group. The levels of NT-proBNP and CCR were closely related to heart failure and were independent risk factors for patients with heart failure. At the same time, there was a significant negative correlation between the level of NT-proBNP and CCR. The area under the ROC curve suggested that the NT-proBNP and CCR have high accuracy in the diagnosis of heart failure with clinical diagnostic value.Our findings are similar to the results of several previous studies where NT-proBNP plasma levels were closely related to the severity of heart failure . FurtherHeart failure and renal dysfunction often coexist as the visceral damage in one organ will result in the other organ's pathological changes accordingly. As two most important organs in the body, heart and kidney influence each other in the physiological and pathological processes, and the renal blood flow accounts for 20–25% of the total output of heart and plays an important role in regulating blood volume, blood vessels tension, and blood pressure change. In patients with heart failure, moderately elevated serum creatinine, without a history of chronic renal insufficiency, is often noticed. Therefore, our research focused on heart failure with no history of chronic kidney disease patients to observe the correlation between kidney index and cardiac function.Determination of endogenous CCR can effectively evaluate the glomerular filtration function. The CCR can determine the degree of renal impairment and whether glomerular filtration function was damaged. Previous studies have shown that renal insufficiency is the risk factor for prognosis of patients with myocardial infarction, cardiac insufficiency, and hypertension –21.Uric acid, a product of purine metabolism whose elevated concentration in CHF is a sign of damaged oxygen metabolism, is associated with the severity of cardiac dysfunction . There iLeft ventricular end-diastolic diameter is used to determine the abnormal changes of cardiac systolic function. Cardiac ischemia causes the interruption of coronary blood flow and decline of myocardial contraction ability. Cardiac contraction ability is closely related to the size of myocardial ischemic area. When ischemic area size exceeds 15%, LVEDD value increases. There is evidence to suggest that NT-proBNP levels may reflect increased left ventricular wall stress in the absence of cardiac ischemia; thus, in this study we observed that the LVEDD increased from control to NYHA class 1-2 to 3-4 group, associated with heart failure severity.