Normal blood pressure (BP) follows a circadian rhythm, with dipping of BP at night. However, little has been done to show how the dipping groups vary amongst the White and Asian population at different periods of the year. This study aims to examine the pattern of nocturnal dipping between the White and Asian population, as well as to compare it to the different timings of the year, between summer and winter.Ambulatory Blood Pressure Monitor recordings were obtained from 220 patients, half were White patients obtained from Mercy University Hospital, Cork, Ireland and half were Asian patients from National Heart Centre, Singapore during the summer period from May to June and the winter period from October to December.Both the Irish and Singaporeans exhibit a decrease in total number of reverse dipper from summer to winter. However, the redistribution of reverse dipper was mainly to the dippers in Singapore, while in Ireland it was to both the extreme dipper and dipper.Irish seasonal changes also resulted in an increase in nocturnal diastolic pressure  and a change in the duration of dipping at night .Regardless of race or temperature, reverse dippers seem to decrease in winter. However, the racial differences dictate the redistribution of the fall in number of dippers. This has implications on how reverse dippers should be treated at different periods of the year. Blood Pressure (BP) dipping is defined as the difference in BP from average waking to sleeping measurement. BP follows normal circadian rhythm of dipping at night at about 10-15% as compared to the day. Night time dipping is further divided into 4 types, reverse dipper (<0%), non-dipper (0-10%), dipper 10-20%) and extreme dipper (>20%). The dip is thought to be affected by an inability to excrete sodium during the daytime [0% and exStudies have shown how different dipping status of blood pressure during the night time affects the prognosis of diseases -5. This This shows the importance in knowing the pattern of dipping in different races. With this knowledge, there should be an impact not only on the choice of the medications but also how clinicians should pay attention, not just to the reverse dippers but also other dippers during different seasons due to the tendency to convert to reverse dippers.Lianne et al. have shown the differences in night time blood pressure dipping between the Black and White populations . Other rThis study aims to elucidate the racial difference of nocturnal dipping in patients with a clinical diagnosis, or suspicion of hypertension. This research also attempts to elicit the difference in dipping status between summer and winter.By exploring the effect of racial differences on the types of nocturnal dip status, particularly between the White and Asian population, we will be able to provide clinicians with a better appreciation of the factors that influence the successful control of hypertension. Treatment would thus be more individualized, based on the races of each of the individuals.This is a retrospective cohort study where patients who were referred to Mercy University Hospital (MUH), Cork, Ireland and National Heart Centre (NHC), Singapore were considered for the study. Only patients who were purely hypertensive without any other comorbidity were included. Hypertensive patients that were selected for the study were randomly selected by a non-stratified method. Hypertensive patients refer to patients who have a systolic pressure greater than 140 mm Hg and diastolic pressure of 90 mm Hg on ABPM. Of which, people with the following conditions were excluded from the study: Type II Diabetes Mellitus; renal diseases such as renal stenosis and renal failure; endocrine disorders like Pheochromocytoma, Addison’s disease and Cushing’s disease.The diagnosis is made according to National Institute for Health and Care Excellence (NICE) guidelines of hypertension medications in both countries . Those tThe data being collected have been ethically approved by the Clinical Research Ethical Committee (CREC) of UCC and the Centralised Institutional Review Board (CIRB) of Singapore.Data on Systolic blood pressure, diastolic blood pressure are recorded by 24 hours Ambulatory Blood Pressure Monitor (ABPM). Race, age, gender, Body Mass Index (BMI), any present diagnosis, family history, anti-hypertensive or diuretic drugs that affects blood were recorded from the Citrix system and medical reports in Singapore and Ireland. Confounding factors include: Smoking or chewing tobacco; alcohol consumption; recreational drugs; age differences brought about by arterial stiffness and calcification, are controlled as well; occupations of different stress level and the number of working hours per week as higher level of stress will inevitably result in an increase in blood pressure. Comorbidities include Hyperlipidaemia and Ischaemic heart disease.The Ambulatory Blood Pressure Monitor used in Singapore was a Spacelabs Model 90217 while those used in Ireland were Meditech LTD ABPM-04, Medtech LTD ABPM-05 and Spacelabs model 90207. The MUH ABPM data were analysed using the DABL software system, DABL Health, Dublin, Ireland. The ABPM’s were programmed to record BP at thirty minutes intervals over the day time and the night time. Systolic and diastolic BP and heart rate (HR) values were averaged to each hour of the recording, over the daytime (from 08:00–20:00 hours), over the night time (from 01:00-06:00 hours), and over the entire 24-hour periods .The retrospective data were collected from the period of May to July and October to December 2013. 110 patients’ details were collected from each period amounting to 220 patients per country.Data are also expressed in terms of means with standard deviations using descriptive statistics or independent sample T test is used. The type of dippers will be assigned a number, for e.g. 1: Reverse dipper, 2: Non dipper, 3: Dipper and 4: Extreme dipper. Sexes and races will be keyed in through the same method as well. However, the duration of dipping and the values of systolic and diastolic pressure will be keyed in using the actual values.Data on temperature, humidity and other metereological data was be obtained from the Irish Meteorological Service (MET) and from the National Environment Agency (NEA) of the Singapore government.Data on the electricity consumption by household in Singapore was taken from the Energy Market Authority (EMA) of Singapore.A total of 220 patients were studied in Ireland and in Singapore. There were a total of 62 males and 43 females, 82 males and 28 females in Singapore during the May to July and October to December respectively. In Ireland, there were a total of 64 males and 46 females, 58 males and 52 females. The mean age, in years, in Singapore was 52.29 during the first period and 46.37 in latter, while in Ireland the mean age was 57.64 and 55.63. Unlike Ireland, Singapore experiences a relatively stable temperature from May to December . This isDuring the different seasons, there were changes in mean systolic and diastolic pressure dipping for both Ireland and Singapore as summarized in When the average sleeping blood pressure between the two countries in the two seasons were compared  and 2, iDespite the difference in temperatures and races, both the Irish and Singaporean populations showed relatively consistent changes in the type of dippers as seen in The results of this study show that there was not just seasonal link but also racial contrasts with the nocturnal dipping and the grouping in hypertensive patients. As seen in However, the systolic dip at night in Singapore was an unexpected change (p<0.05). In fact, the mean systolic dip changed a total of 2.6% as compared to 1.99% of Ireland. This could be due to many other variables which might have a greater effect on the systolic pressure. In the Irish population, there is an overall decrease in pulse pressure from 56.23 to 56.15 mm Hg while that in Singapore increased from 53.12 to 53.9 mm Hg.In addition, the duration of night time dipping between the two seasons in Ireland changed from 2.99 to 3.52 hours, while that in Singapore was only from 2.57 to 2.97 hours. The result could also be an underestimation of the true value of the dipping as the average age in the Irish population is slightly higher. The average age for the Irish population is 58 and 56 between summer and winter while that in Singapore is 52 and 46 . Age is Interestingly, even though there are no changes in seasons in Singapore, both Ireland and Singapore seem to show an overall drop in the number of reverse dippers. The reverse dippers were being reattributed to only the dippers in Singapore while in Ireland to the dippers and non-dippers . This woThis study is unique in the inclusion of two countries, Ireland and Singapore, one of which has no seasonal changes. It allows the use of a single country to act as a form of control. Many present studies in similar field only use a single country as a form of comparison. This study thus, allowed us to further test the hypothesis.Some limitation of the study involves the fact that as data are being collected from different countries, the Ambulatory Blood Pressure Monitor (ABPM) being used is different which might give rise to systematic errors. However, both centers used systems of ABPM monitoring that are well validated and should minimize measurement bias in the collection of individual blood pressure values.The strict selection on the population based on the exclusion and inclusion criteria as well as the small population of Cork city, resulted in a smaller than ideal population size. This also prevents the restriction of the age group, especially in Cork’s population. This is however offset by taking into account the confounding of arterial stiffness due to calcification with aging.Both countries are very different in terms of culture, demographics as well as diet and that the Asian population tends to be lower in BMI as compared to the Caucasian population. Despite the differences in diet, people in Singapore are also affected by a wide range of westernization i.e. increase frequency of indulgence in many western diets such as fast food, high salt diet etc., thus frequently resulting in them having hypertension. Unlike Ireland, Singapore does not have winter season, thus the amount of food consumption are also generally more constant as people tend to consume greater amount and saltier food during the winter as compared to summer. This would inevitably affect the overall blood pressure as well.However, despite the differences in diet, race and culture, the difference in BMI between both countries was modest. Furthermore, the results still showed similarities in the changes in the type of dippers between the two countries. This would suggest that the drop in reverse dipping during the winter season from summer was independent to any of the factors but purely due to the different periods of the year. The shift to other groups could, however, be affected by the different co-founders.The population of hypertensive subjects studied in the summer and winter cohorts in each country differed. This is a reflection of the collection of this data from a real world population. Although it would be preferable to study the same population in both phases this was not practical in view of the clinical demand for ABPM and the need to apply it in an environment of routine care. As the comparison of an entire cohort in the two countries seems to show how the season will affect the dipping status in people, this would perhaps, be amplified if the same cohort were used.Another limitation will stem from the fact that Singaporeans in general are mostly indoors in air-conditioned areas. During a hotter weather the air-conditioners will be used to reduce temperature. Irish on the other hand, will use heaters during the winter season and reduce the change in temperature due to any seasonal changes. In our population of non-night shift works the nocturnal BP recordings will almost exclusively be recorded in the patients’ homes. As a result, the changes in blood pressure might not accurately reflect the actual changes in the temperature changes due to different seasons as the air-conditioning and heating might lower the difference in changes of temperature due to the changes of weather. This might cause an underestimation of the actual change in blood pressure.In summary, it is difficult to obtain a single variable from two separate countries with different cultural influences. However, this research shows the pattern in changes of types of dippers in different races and the seasons. As reverse dippers are associated with a poor prognosis of cardiovascular diseases, clinicians have to pay attention to patients who might not present as a reverse dipper in non-winter seasons in particular patients from the dipper group in Singapore and both dipper and extreme dipper in Ireland. By taking the changes into consideration, clinicians will be able to control the changes in blood pressure more effectively in different races even when the seasons change through the control of dosages of medications prescribed. The change in blood pressure should also be taken into considerations when the patient travels into countries with different climatic environment.


Purpose. To evaluate provider adherence to national guidelines for the treatment of hypertension in African Americans. Design. A descriptive, preexperimental, quantitative method. Methods. Electronic medical records were reviewed and data were obtained from 62 charts. Clinical data collected included blood pressure readings, medications prescribed, laboratory studies, lifestyle modification, referral to hypertension specialist, and follow-up care. Findings. Overall provider adherence was 75%. Weight loss, sodium restriction, and physical activity recommendations were documented on 82.3% of patients. DASH diet and alcohol consumption were documented in 6.5% of participants. Follow-up was documented in 96.6% of the patients with controlled blood pressure and 9.1% in patients with uncontrolled blood pressure. Adherence in prescribing ACEIs in patients with a comorbidity of DM was documented in 70% of participants. Microalbumin levels were ordered in 15.2% of participants. Laboratory adherence prior to prescribing medications was documented in 0% of the patients and biannual routine labs were documented in 65% of participants. Conclusion. Provider adherence overall was moderate. Despite moderate provider adherence, BP outcomes and provider adherence were not related. Contributing factors that may explain this lack of correlation include patient barriers such as nonadherence to medication and lifestyle modification recommendations and lack of adequate follow-up. Further research is warranted. Hypertension (HTN) is a medical condition that is characterized by high or uncontrolled blood pressure. Inadequate control of HTN can lead to more serious vascular conditions affecting the major blood vessels in the heart, brain, and body. Additionally, HTN and diabetes mellitus (DM) frequently coexist, which further increases the risk of developing vascular complications. Vascular complications are a group of disorders that affects the heart and blood vessels. Hypertension is a major risk factor for vascular disease including heart attacks and strokes . In 2008The physical and financial burdens of HTN are not unique to any one group of individuals. However, it has been well documented that African Americans (AAs) have a disproportionate burden of morbidity and mortality compared to Caucasians . Data coNumerous interventions have been documented to improve control of HTN in AAs. The aims of such interventions have been to reduce the barriers to better control. Provider-centered barriers are the focus of this study and include limited patient-provider communication regarding lifestyle changes, lack of adherence to established guidelines for HTN management, and resistance to change. In addition, systems barriers were assessed and include access to care, medication costs, and lack of healthcare coverage . Racial Patients often seek medical attention for chronic conditions from their primary care providers. Geographic location of this population and clinic locations can influence patient outcomes . RuralitAs previously mentioned, a major problem for rural communities is access to healthcare. Improving access to healthcare for rural America is a priority. The National Rural Health Association  has deveThe theoretical framework of Avedis Donabedian was used as a tool to guide this research. His framework was used to assess the quality of care provided in healthcare. The three components that form the foundation of this theory are (1) structure of care, (2) process of care, and (3) outcomes. The concept is grounded on the principle of healthcare outcomes as a result of the medical care provided by medical professionals .Donabedian  describA retrospective review of the EMR was conducted to identify hypertensive AA patients in a rural clinic who were seen from July 1, 2014, to August 31, 2014. A descriptive, preexperimental, quantitative method was used to evaluate the degree of provider adherence to national HTN guidelines in AAs living in a rural community. Inclusion criteria for the patients included  (a) age A sample of 62 participants met the inclusion criteria.The study was conducted at a multiphysician practice located in a rural community. The practice serves a population of 45,273, 63.8% of which are AAs . The praThe primary source data were selected from the EMR Centricity developed by General Electric Healthcare. An EMR is a digital or electronic version of a paper chart that contains the patient's medical history. A report was populated using the following criteria: (1) the practice site location, (2) race specified as black or African American, (3) birthdate on or after 01/01/1949 but before 01/01/1995, (4) appointment date on or after 07/01/2014 but before 09/01/2014, and (5) active International Classification of Diseases, Ninth Revision (ICD-9) codes containing 401 for hypertension. The EMR was reviewed to identify onset of HTN if feasible, provider selection of antihypertensive drugs for initial treatment, and additional drug choices. HTN was defined as a blood pressure ≥140/90 mmHg in the general population and >130/80 mmHg in hypertensive individuals with a comorbidity of DM in accordance with JNC 7 or patients taking antihypertensive medications. Patients who met the inclusion criteria were selected by convenience sample. A list of those patients was composed and each was assigned a research identifier. Potential participants were consecutively recruited and a sample size of 62 participants met the inclusion criteria. Demographic variables assessed included age, gender, marital status, and insurance coverage. Other variables that were considered include the following antihypertensive drug classes: (a) thiazide diuretics, (b) angiotensin-converting-enzyme inhibitors (ACEIs), (c) angiotensin II receptor blockers (ARBs), and (d) calcium channel blockers (CCBs). Evaluation of monotherapy and combination therapy was also performed.JNC 7  describDiagnostic measurements for the classification of HTN were performed based on JNC 7 guidelines . AccordiWith regard to follow-up, JNC 7 recommends a monthly follow-up office visit if blood pressure is not at goal and a follow-up office visit every 3 to 6 months if BP is at goal. Laboratory values for potassium and creatinine should be obtained 1 to 2 times annually and patients with a comorbidity of DM should have their urine microalbumin levels measured at least annually. Patients newly diagnosed with HTN should have a urinalysis, blood glucose, hematocrit, potassium, creatinine, calcium, and lipid profile drawn prior to beginning pharmacological treatment.JNC 7 recommends lifestyle modification education. Better outcomes have been found when lifestyle modification is incorporated into the plan of care. The following are the areas recommended for lifestyle modification: (a) weight loss, (b) following the Dietary Approaches to Stop Hypertension (DASH) diet, which consists of a diet rich in fruit and vegetables, low fat dairy products, and reduced intake of saturated and total fat, (c) adhering to sodium restrictions, (d) regular physical activity, and (e) limiting alcohol consumption.Statistical analyses were performed on the outcomes of blood pressure control in participants who were prescribed antihypertensive medications based on JNC 7 guidelines compared to those who were not and also on blood pressures that were at goal and those that were not. Additionally, outcomes of provider adherence to the guidelines were measured based on adherence to medication choice recommendations, documented lifestyle modification recommendations, laboratory studies, and follow-up for patients with HTN and HTN with a comorbidity of DM. Descriptive analysis was conducted using crosstabs, frequencies, and means comparison and reported as percentages to describe the results. Crosstabs were used to determine the number of times the recommended combination of a thiazide diuretic was used in combination with an ACEI or ARB. Frequencies were conducted to identify the percentage of patients not prescribed a TD or CCB as monotherapy. Further, the use of means comparison was to compare differences in BP outcomes in patients prescribed ACEIs compared to TDs as monotherapy. Additionally, a chi square analysis was performed to determine if there is a relationship between provider adherence and blood pressure outcomes.n = 40) of the providers in this study. Nurse practitioners (NPs) accounted for 35.5% (n = 22). Of the 29 patients with blood pressure at goal, a physician was the provider in 75.9% (n = 22) of the office visits while NPs provided care in 24.1% (n = 7) of the visits.Physicians accounted for 64.5% (The demographic characteristics of the 62 participants are described in n = 8) were on monotherapy and 87.1% (n = 54) were on combination therapy. Combination therapy is described as taking two or more medications. Those with a comorbidity of DM accounted for 53.2% (n = 33) of the 62 patients. JNC 7 guidelines suggest that patients with a comorbidity of DM should take ACEIs to decrease morbidity and mortality. Of the 33 diabetic patients, only 69.7% (n = 23) were taking ACEIs as recommended. TDs or CCBs were not prescribed in any of the eight patients on monotherapy. Of the 54 patients taking combination therapy, 87% (n = 47) were taking either a TD or CCB. In the patients studied, 53.2% (n = 33) of the 62 warranted medication adjustments as a result of uncontrolled blood pressure. Only 15.2% (n = 5) had medication adjustments, leaving 84.8% (n = 28) inadequately treated. One patient (1.6%) required a referral to a HTN specialist as a result of maximizing three different medication classes, including a TD. That patient was not referred.Drug therapy regimens are reported in n = 3) of them met their blood pressure goal despite not being on a TD or CCB. Of the 54 patients on combination therapy, 87% (n = 47) were on a TD or CCB as recommended by JNC 7. Of those 47 patients, 55.3% (n = 26) achieved goal blood pressures. A chi square test was used to determine if there is a relationship between being prescribed JNC 7 medication regimen and blood pressure outcomes. There was no significant relation between taking the recommended TD or CCB and blood pressure control .In the eight patients on monotherapy, 37.5% (n = 4) of the 62 patients had documentation of provider recommendations for the DASH diet and alcohol consumption. The DASH diet includes recommendations for limiting alcohol consumption. Weight loss, sodium restriction, and PA recommendations were documented in 82.3% (n = 51) of the patients.The categories examined under lifestyle modifications included DASH diet, weight loss, sodium restrictions, physical activity (PA), and alcohol consumption see . Only 6.n = 28) of the time in the 29 patients with controlled blood pressure. In the remaining 33 patients who required monthly follow-up due to uncontrolled blood pressure, providers were only 9.1% (n = 3) adherent to the recommendations.JNC 7 recommends follow-up every 3 to 6 months if BP is controlled. Providers were adherent to follow-up recommendations 96.6% (n = 39) of the 60 qualifying patients. In patients with a comorbidity of DM, JNC 7 recommends measuring annual urine microalbumin levels. Providers were 15.2% (n = 5) adherent to the guidelines in the 33 diabetic patients.Providers were adherent to obtaining laboratory tests prior to initiating treatment in 0% of the two patients with new diagnoses of HTN. The adherence rate for biannual laboratory tests in patients with historical diagnosis of HTN was 65%  and qualitative (descriptive) data were collected and analyzed to assess the current system and to identify areas for improvement. The practice guidelines of JNC 7 were used as performance measures for comparison.The JNC conducts and analyzes evidence-based studies periodically. Subsequently, JNC formulates recommendations based on those findings. The National Heart Lung and Blood Institute (NHLBI) traditionally has endorsed previous versions. Controversy surrounding the Eighth Report of the Joint National Committee (JNC 8) has led to NHLBI not endorsing JNC 8 . Other fThere are several main findings of this study. First, the first-line drug choice as monotherapy in the treatment of HTN in AAs should be TDs or CCBs, as recommended by JNC 7. While there were only eight patients receiving monotherapy, none of them were on TDs or CCBs, which indicates 100% nonadherence to the guidelines regarding monotherapy. In fact, the majority of the patients on monotherapy were on ACEIs, while the remaining were on ARBs. However, studies have found that ACEIs and ARBs are less effective in the AA population. These findings are consistent with the studies reviewed in the literature review for this study. One such study compared the effectiveness of ACEIs as monotherapy between AAs and Whites . Whites Less than half of the 62 patients in this study have at goal BP readings at the level recommended by JNC 7 despite moderate provider adherence. Similar findings were found in a previous study. Provider adherence to the guidelines overall was 76%. Mean BP values decreased but insignificantly concluding no correlation with provider adherence and attaining BP goals . In thisLifestyle modification, as an adjunct to pharmacologic therapy, has been associated with better BP control. Provider adherence to alcohol consumption and DASH diet recommendations was poorly documented. Detailed recommendations for the DASH diet and alcohol were only documented in 4 of the 62 EMRs. Adherence was high in the recommendations for physical activity, weight loss, and sodium restrictions. The smart plan is inclusive of these 3 recommendations, which was documented in 51 of the 62 patients.Patient adherence with adequate office visit follow-up has been known to yield better BP control. JNC 7 recommends an office visit follow-up every 3 to 6 months in patients with BP at goal and monthly visits for those who are not at goal. Provider adherence was evident in the 3-to-6-month follow-up population (97%). A monthly follow-up recommendation for those with uncontrolled BP was poorly represented in this study.Uncontrolled BP can lead to end organ damage such as renal insufficiency or failure, heart attacks, or strokes. Further, the medications used to treat HTN can have adverse effects on other organs. JNC 7 recommendations include a urinalysis, blood glucose, hematocrit, potassium, creatinine, calcium, and lipids in patients newly diagnosed with HTN before initiating therapy. Due to the limitations of the EMR, only 2 patients were identified as newly diagnosed. Of these patients, neither of them had laboratory testing performed prior to starting treatment. Diabetics should have their urine microalbumin level measured annually. Only 15% of diabetics had documented microalbumin levels within the preceding 6 months.There are several limitations to this study. Due to small sample size, variability and vagueness should be noted as limitations. For example, the finding of no documentation of patients receiving labs prior to the initiation of drug therapy may provide a greater impact and consistency in a larger sample size. A larger sample size would produce more detailed, robust, and explanatory assessments. Secondly, the study was conducted during only the summer months and over a short duration. Extending the study period and expanding the study to include fall or winter months may provide input for comparison to determine if seasons impact BP control.Despite evidence-based recommendations by JNC 7, provider adherence in AAs has room for improvement. Provider pharmacologic choices and lifestyle modification recommendations are major components to blood pressure control in this population. Thiazide diuretics are recommended as initial monotherapy and in combination therapy for African Americans. CCBs are recommended as an acceptable alternative to thiazide diuretics. CCBs are preferred over ACEIs because of the increased risk of stroke, myocardial infarctions, and other vascular conditions associated with ACEIs. Conversely, providers have demonstrated a preference in prescribing ACEIs and ARBS in monotherapy. Better adherence in prescribing a TD or CCB is seen in prescribing patterns for patients on combination therapy. Providers are not adherent to the monthly follow-up recommendations required for medication adjustment or specialist referrals when BP is not at goal. Lack of lifestyle modification documentation, specifically the DASH diet and alcohol consumption, is consistent with nonadherence to the JNC 7 guidelines. Although there appears to be no relationship between receiving the recommended medications and BP outcomes, more than half of the population did not meet BP goals.The principal factor assessed in the process of care was provider barriers. Specific components impacting provider barriers include access to JNC 7 guidelines, provider adherence to JNC 7 guidelines, recommendation of lifestyle changes, and follow-up. Provider adherence to the guidelines overall was poor. Lack of documentation, provider-prescribing habits, and lack of knowledge of up-to-date, evidence-based guidelines may be contributing factors. While there is a gap between evidence-based national guidelines and clinical practice to controlling HTN, all contributing factors, including physician, patient, and systems barriers , require


Objective. To investigate the effectiveness and safety of controlled venous pressure in liver surgery and further to compare the clinical outcomes of low central venous pressure by infrahepatic inferior vena cava clamping (IVCC) and intraoperative anesthetic control (IAC). Methods. Online databases including PubMed, Embase, Cochrane Library, Clinical trials.gov, and China biology medicine database were comprehensively searched. After identifying relevant studies out of the search results, quality assessment was performed according to the methods recommended by the Cochrane collaboration. And meta-analysis was performed by both direct comparison and indirect comparison. Results. Thirteen studies containing 1252 patients were included. Compared with control, controlled venous pressure significantly decreased central venous pressure, total blood loss, blood loss during transection, transfusion rate, and total incidence of complications. Further analysis of IVCC and IAC showed that there was no significant difference in aspects of main clinical outcomes. Conclusions. Controlled venous pressure significantly decreased central venous pressure and achieved improvement of bleeding control in liver surgery. It reduced total incidence of complications and chest infection, while it caused concerns about heart disorder. Although IVCC was not worse than IAC in therapeutic effect, a superiority between them still needs to be explored. As known, acute and long-term severe liver disease mainly including alcoholic and viral hepatitis can lead to an end-stage function failure. Besides, many uncontrolled chronic hepatitis patients will finally progress to be cirrhosis, which has a high risk to be malignant tumors . For theNearly 14% of the whole blood is stored in liver, so liver surgery is always associated with high volumes of blood loss. In order to control bleeding from inflow system of liver blood supply, surgeons need to perform Pringle maneuver or selective vascular occlusion , 6, and Many clinical studies were designed to investigate the effectiveness and safety of controlled venous pressure in liver hepatectomy, liver resection, and transplantation . HoweverOnline databases including PubMed (1966.01–2014.12), Cochrane Library (2014 Issue 12), Embase (1974.01–2014.12), and China biology medicine database (up to 2014.12) were systematically searched. Search terms were  AND (“liver surgery” OR “hepatic operation” OR “hepatectomy” OR “liver transplantation”). Medical subject headings, related articles function, and the references of reviews were also screened to widen the search results.The literature search results were firstly scanned by titles and abstracts, and eligibility for inclusion was further evaluated by reading full-texts by two reviewers independently . Clinical studies investigating the method of controlled venous pressure in liver surgery were eligible. Patients with severe hepatic disease and who were willing to undergo a hepatectomy, liver resection, and transplantation were participants. All the characteristics of participants and treatment were comparable between treatment group and control group, except for the additional intervention of controlled venous pressure. The main outcome measures to evaluate therapeutic effect were total blood loss and blood loss during transection. Secondary outcome measures were transfusion rate, liver transection time, central venous pressure, and incidence of complications.Two reviewers  extracted the information of the included studies, which mainly included author, publication year, group, cases, age, surgical procedures, and the data of outcome measures. Methodological quality of randomized controlled studies was assessed by using and modifying the methods recommended in the Cochrane handbook , which wI2 statistical test. Random-effect model or fixed-effect model was chosen according to the heterogeneity test results. Pooled risk ratios (RR), mean difference (MD), and standard mean difference (SMD), with their 95% confidence intervals (95% CI), were presented for effect size. Network meta-analysis was conducted by using ITC soft  .Further analysis of liver transection time indicated that there was no significant difference between the groups [I2 = 94%, MD = −2.40, 95% CI , P = 0.007, I2 = 68%, SMD = −0.64, 95% CI , P < 0.0001, I2 = 91%, SMD = −1.01 95% CI , P = 0.01, I2 = 38%, RR = 0.46, 95% CI , P < 0.0001, I2 = 0%, RR = 0.75, 95% CI , P = 0.003, I2 = 0%, MD = −0.24, 95% CI , P = 0.71, Compared with control, IVCC significantly reduced central venous pressure [P < 0.0001, I2 = 70%, SMD = −1.05, 95% CI , P < 0.0001, I2 = 39%, SMD = −0.97, 95% CI , P < 0.0001, I2 = 0%, RR = 0.56, 95% CI , P = 0.02, I2 = 0%, RR = 0.68, 95% CI , P = 0.0009, I2 = 25%, MD = −2.36, 95% CI , P = 0.22, Compared with control, IAC significantly decreased central venous pressure [MD = −4.00 95% CI , Due to insufficient numbers and cases of direct comparison, we also performed a network meta-analysis. Inverted funnel plots were adopted to evaluate publication bias. The results of transfusion rate, liver transection time, and total complications did not reveal asymmetry, indicating little possibility of publication bias .The meta-analysis included 13 high-quality studies comparing controlled central venous pressure with control in liver surgery, and it demonstrated a strong relationship between blood loss and outflow system of liver blood supply. Meanwhile, controlled venous pressure also had advantages in aspects of other clinical outcome measures.2O in central venous pressure, and meta-analysis of 10 trials in the random-effects model showed that the total blood loss was significantly reduced. To estimate the total blood loss, four of the analyzed studies collected blood in the container of the aspirator and weighed the soaked gauzes [2), and it further demonstrated a significant difference between the groups (P = 0.01).There was a significant reduction of 2.67 cm Hd gauzes , 17, 18,d gauzes , while td gauzes –16, 20 ad gauzes , and thed gauzes  calculatFurther analysis revealed that the transfusion rate was also significantly decreased in IVCC and IAC group, while only one study presented a detailed protocol of transfusion. Although the transfusion protocols between the centers were different and it might cause a heterogeneity, it may not influence the pooled results as the protocols were comparable between the groups in each study. Therefore, combining all the results mentioned above, controlled central venous pressure though IVCC and IAC really significantly improved the intraoperative bleeding control and reduced the blood loss and thus induced a lower transfusion rate.In aspects of other clinical outcomes, controlled venous pressure might also decrease operation time, while meta-analysis result of liver transection time revealed that there was no significant difference.P = 0.76), which might involve the opening of collateral circulation and increased blood and pressure in azygos vein from hemiazygos vein and accessory hemiazygos vein.For safety, controlled venous pressure achieved a lower incidence of complications mainly in IAC subgroup, and further analysis of diagnosis only found a significant difference in chest infection. Many concerns about abnormal homodynamic did not have significant differences between the groups, perhaps due to the optimal intraoperative anesthetic control . Liver fFurther comparisons between IVCC and IAC were conducted using both traditional meta-analysis and network meta-analysis. There was no significant difference in aspects of center vein pressure reduction, transfusion rate, and total complications, while different results existed in aspects of blood loss and operation time. Meta-analysis based on two trials revealed that IVCC significantly decreased total blood, blood loss during transection, total operation time, and liver transection time. Network meta-analysis showed that there was no significant difference between the groups. Besides, compared with IAC, IVCC was really easy to realize as it only needs to clamp the IVC briefly with a vascular clamp before the actual transection , 22. AltLimitations that existed in the meta-analysis were as follows. (1) For all the surgeries, surgeon's experience played important roles in clinical outcomes . We coulIn conclusion, controlled venous pressure significantly decreased central venous pressure and achieved improvement of bleeding control in liver surgery. It reduced total incidence of complications, while it caused some concerns about heart disorder. Although IVCC was not worse than IAC in clinical treatment efficacy, a superiority between them still needs to be explored in the future.


Plasma PTX3 levels in CHF patients with cardiac events were significantly higher than in event-free patients (p < 0.001). We determined the normal upper limit of plasma PTX3 levels from the mean + 2 SD value of 64 control subjects (3.64 ng/mL). A Kaplan-Meier analysis revealed that patients with increased PTX3 (≥3.64 ng/mL) were at a higher risk for cardiac events than those without increased PTX3 (p < 0.01). A multifactorial Cox proportional hazards model showed that increased PTX3 (≥3.64 ngImL) was an independent risk factor for cardiac events in CHF patients (hazard ratio (HR) = 4.224, p < 0.01; 95% CI: 1.130–15.783). Plasma PTX3 levels are a long-term independent predictor of prognosis in patients with CHF.The aim of this study was to investigate the long-term prognostic value of pentraxin-3 (PTX3) in patients with chronic heart failure (CHF). 377 patients were prospectively followed up for 3 years to determine cardiac events including cardiac death or rehospitalization for worsening heart failure. The plasma PTX3 levels were significantly higher in CHF patients than in healthy subjects ( Chronic heart failure (CHF) is the end stage of many types of cardiovascular diseases, and the prognosis of patients with CHF is very poor. CHF is a leading cause of hospital admissions and death in developed countries , and CHFIn recent years, studies have shown that inflammation is related to CHF and that plasma C-reactive protein (CRP) levels are associated with the prognosis of CHF patients –4. PentrWe recently demonstrated that plasma levels of PTX3 were significantly higher in patients with stable coronary artery disease (CAD) after drug-eluting stent (DES) implantation and that these elevated levels of PTX3 were significantly and independently associated with the prevalence of major cardiovascular events (MACE) after DES implantation . MoreoveAll of these data were obtained in developed countries such as Japan and various European countries, and the causes of CHF in these countries differ from the causes of CHF in developing countries. To our knowledge, no data have been published about the association between PTX3 and CHF in developing countries. China is the largest developing country in the world; thus, data from China are likely to be valuable.This study was designed to assess the efficacy of plasma PTX3 levels for the prediction of long-term cardiac events in CHF patients in China.Between June 2010 and December 2011, we prospectively enrolled 406 patients with CHF who were admitted to Ningbo Yinzhou People's Hospital, Medical School of Ningbo University. Sixty-four age- and gender-matched healthy subjects from our medical examination center served as the control group for determining normal plasma levels of PTX3. These subjects were diagnosed as normal by physical examinations, chest X-ray, electrocardiogram, and echocardiography.Two cardiovascular specialists confirmed all recruited CHF patients. The diagnostic criteria for patients with CHF included the following: (1) underlying heart disease; (2) dyspnea and edema of the lower limbs as well as other symptoms of heart failure; (3) abnormalities in at least one of the following objective indicators: etiological factors, the anatomy of the heart, and the cardiac function index (as assessed by chest X-ray or echocardiography). The inclusion criteria included the following: (1) impaired heart function (NYHA classes II to IV) on admission; (2) left ventricular ejection fraction (LVEF) ≤45%; and (3) impaired heart function (NYHA classes I and II) before discharge. Exclusion criteria included patients with renal dysfunction (serum creatinine >1.5 mg/dL), severe hepatic or lung disease, chronic or acute inflammation, and malignant disease. Patients who experienced myocardial infarction (MI) during the month prior to enrollment were also excluded.This study was approved by the Ethics Committees of Ningbo Yinzhou People's Hospital, and all patients provided written informed consent.In this study, demographic and clinical data, including age, gender, heart rate, diabetes mellitus, hypertension, hyperlipidemia, smoking, a previous history of myocardial infarction, NYHA class, and LVEF on admission, were collected from in-hospital medical records and patient interviews.Venous blood samples were collected from patients on the second morning after admission under fasting conditions to measure levels of serum hsCRP and plasma PTX3. Whole blood was immediately collected into a tube containing ethylenediaminetetraacetate (EDTA) and then centrifuged at 2000 ×g for 15 min at room temperature; the plasma was kept frozen at −80°C until analysis. Plasma PTX3 concentrations were measured by enzyme-linked immunosorbent assay  as reported previously . This asNormal PTX3 levels were determined based on the upper limit of plasma PTX3 levels from the mean + 2 SD value in control subjects.A total of 377 patients underwent clinical follow-up  for three years after enrollment. The primary endpoint was cardiac events, which were defined as cardiac death or rehospitalization for worsening heart failure. A review of medical records and follow-up telephone interviews were conducted to survey for cardiac events among the enrolled patients. Reviews of the follow-up case notes were performed by two of the authors (Wang Chunming and Chen Guozhong) who were blinded to the PTX3 levels. All deaths were considered to be from cardiac causes unless an unequivocal noncardiac cause could be established.t-test or linear regression analysis; categorical variables were compared using the χ2 test. If data were not normally distributed, the Mann Whitney U-test was used. Cox proportional hazard regression analysis was used to determine which variables were significantly related to cardiac events. Only variables with p values less than 0.05 in the univariate Cox regression analysis were entered into the multivariate Cox regression analysis. The hazard ratio (HR) and 95% confidence intervals (CIs) are presented. The log-rank test was performed to obtain the Kaplan-Meier probability estimates. A value of p < 0.05 was considered significant.All data analyses were performed using SPSS, version 18.0 . Continuous data are expressed as the mean ± SD, and skewed variables are presented as the median value. Continuous variables were analyzed using unpaired Student's p < 0.01) and increased significantly with advancing NYHA functional class (p < 0.01).The plasma level of PTX3 in control subjects  was 2.58 ± 0.53 ng/mL, but the corresponding value was 3.42 ± 0.88 ng/mL in the CHF patients . As shown in p < 0.001) compared with those without a cardiac event. Patients with a cardiac event had a higher prevalence of NYHA class >II and a higher heart rate and age (p < 0.001), but they showed decreased use of angiotensin converting enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) (p < 0.05)  cardiac events, including 54 (14.3%) cardiac deaths and 98 (26.0%) rehospitalization cases for worsening heart failure. Patients with a cardiac event had higher concentrations of PTX3, high-sensitivity C-reactive protein (hsCRP), and cardiac troponin (cTnI) ( < 0.05) .p = 0.039) as well as higher concentrations of hsCRP and cTnI (p < 0.001) compared to patients without increased PTX3  from the mean + 2 SD value in 64 control subjects (2.58 ± 0.53 ng/mL). Patients with increased PTX3 (≥3.64 ng/mL) had a higher prevalence of NYHA class >II (sed PTX3 .p < 0.05), rehospitalization for worsening HF (p < 0.001), and cardiac events (p < 0.001). Kaplan-Meier analysis also showed that the probability of cardiac events, cardiac death, and rehospitalization was significantly higher in the high-PTX3 group than in the low-PTX3 group  (As shown in nk test) .p < 0.001), heart rate (p = 0.003), and hsCRP (p = 0.016) were significantly associated with cardiac events over the three-year period based on univariate Cox regression analysis , cTnI , NYHA class >II , and age  were independently associated with cardiac events over the three-year follow-up period. hsCRP was not independently associated with cardiac events over that same time period  or LVEF, which are strong predictors of CHF prognosis, due to insufficient data. Therefore, a multicenter trial with a large study population derived from different developing countries that includes BNP and LVEF data is necessary to validate the clinical importance of PTX3 in the future.In conclusion, PTX3 could be considered as a universal risk factor and was more reliable than CRP in CHF patients. Measuring plasma PTX3 levels may substantially improve the risk stratification of CHF patients.


Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function.In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates.During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 : 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables  both sTNFRs remained independently associated to outcomes . A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1.sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease. Chronic kidney disease (CKD) has been linked to increased risk for cardiovascular disease and mortality independent of traditional cardiovascular risk factors . This haSoluble tumor necrosis factor receptor 1 (sTNFR1) and soluble tumor necrosis factor receptor 2 (sTNFR2) are the circulating forms of their membrane bound counterparts (mTNFR1 and mTNFR2) which are essential for tumor necrosis factor alpha (TNFα)-signalling via different pathways. Interaction between TNFα and both mTNFR leads to a pro-inflammatory stimulus via activation of nuclear factor kappa B (NF-κB) or activator protein 1 (AP-1), while only mTNFR1 contains a death domain through which signalling leads to apoptosis . The solIn contrast to TNFα, which failed to be associated to mortality or cardiovascular events in CKD , both ciIn the present study, we evaluated the predictive value of sTNFR1 and sTNFR2 for the risk for all-cause mortality or cardiovascular events in a population with advanced CKD . Evaluating outcome in advanced CKD minimizes the influence of eGFR on outcomes and on the concentration of the evaluated marker. This may allow to generate hypotheses on the contribution of other important mechanisms in the pathophysiology of CKD, such as inflammation, while reducing the impact of their intrinsic association to kidney function.This study was approved by the local Ethics Committee  and performed in accordance to the Declaration of Helsinki. Written informed consent was obtained from all participants.All non-transplanted CKD patients stage 4 and 5 not on dialysis, attending the Nephrology outpatient clinic and included in the biobank sample collection of the Nephrology Department of the Ghent University Hospital between January 2011 and August 2012, were included in this study (n = 131). Samples were processed immediately after collection and stored at—80°C. Outcomes were registered prospectively.2 (kg/m2), mean arterial pressure (MAP) as the sum of 1/3 of the systolic and 2/3 of the diastolic blood pressure and pulse pressure (PP) as the difference between systolic and diastolic blood pressure. Estimated glomerular filtration rate (eGFR) was calculated based on the creatinine-based CKD-EPI formula . Twenty-nine patients (22.1%) died (cardiovascular (n = 3), malignancy (n = 3), infection (n = 7), ESRD (n = 1), unknown (n = 15)) and 11 (8.4%) had a first non-fatal CVE (ACS (n = 1), PTCA (n = 4), CABG (n = 2), stroke (n = 4)), of which 5 patients died subsequently during follow-up. Seven events occurred after the start of RRT, which was initiated in 35 patients during follow-up. Baseline clinical characteristics and biochemical parameters of the entire population and those with and without event are presented in sTNFR1 and sTNFR2 were strongly correlated  . Linear In univariate Cox proportional hazards analysis, sTNFR1  and sTNFR2  were associated to adverse outcomes. Older age, a higher CRP, a lower albumin concentration, a history of cardiovascular disease and diabetes mellitus also showed an association . Kaplan In multivariate models, sTNFR1 and to a smaller extent sTNFR2 remained significantly associated to outcome. In the first model  after adWhen including also albumin in this multivariate model, sTNFR1  remained significantly associated to adverse outcome, while sTNFR2 was not. Albumin itself was not a significant covariate.In summary, after adjustment for significant clinical covariables, sTNFR1 and sTNFR2 remained independently associated to increased risk of death or cardiovascular events. This association was stronger for sTNFR1 than for sTNFR2 .Eighteen of the eighty patients without diabetes had an adverse event (22.5%). Patients, having an event, were older , had a higher CRP , had more often a history of malignancy  and were less likely to start RRT during FU (5.6% (n = 1) vs. 29% (n = 18), p < 0.05). There were no differences for the other clinical variables listed in In the subgroup of diabetes patients (n = 51), only sTNFR1 and not sTNFR2 concentrations were significantly higher in the patients reaching the composite endpoint  . In univThis study evaluated the value of sTNFR1 and sTNFR2 as biomarkers for their association to the composite endpoint of all-cause mortality or first non-fatal cardiovascular event in a cohort with advanced CKD irrespective of the underlying etiology. The main finding of this study is that sTNFR1 and sTNFR2 are associated to adverse outcome, even after adjustment for clinical covariables, such as age, gender, eGFR, CRP. The association with outcome was stronger for sTNFR1 than for sTNFR2. In the subgroups of patients without and with diabetes only sTNFR1 was after adjustment associated to outcome.2) minimized the impact of eGFR on outcome, which was confirmed by the lack of association to adverse outcomes  and also reported previously . sTNFR1 Constitutively, both sTNFRs are released from cell membranes by shedding ,25 or asThe limitations of the study are: the results cannot be generalized to all CKD stages, since we restricted the evaluation to CKD stage 4 and 5 intentionally to evaluate both receptors in a narrow range of eGFR, which also resulted in a rather small population. Furthermore, based on our results it is not yet possible to draw conclusions on the potential use or incremental value of these markers in clinical situations. Nevertheless, the study unravelled convincing correlations between sTNFRs and outcomes even after adjustment for confounders such as eGFR or diabetes. Hence our data underscore the relationship of TNFRs, with hard clinical outcomes irrespective of underlying kidney disease and the presence or absence of diabetes. The fact that especially sTNFR1 was consistently associated to different outcomes in advanced CKD as shown in this study as well as in community-based and specific high risk populations such as post-myocardial infarction, offers a strong argument in favour for its further evaluation in larger CKD cohorts.S1 TableData are presented as means ± standard deviation or medians with interquartile range between square brackets. For binary variables, frequencies with percentages between brackets are given. MACE: major adverse cardiovascular event, N = number of patients, M: male, BMI: body mass index, MAP: mean arterial pressure, PP: pulse pressure, HR: heart rate, eGFR: estimated glomerular filtration rate, CVD: history of cardiovascular disease, DM: diabetes mellitus, AHT: arterial hypertension, RRT: start of renal replacement therapy during follow-up, CRP: C-reactive protein, TNFα: tumor necrosis factor alpha, sTNFR1: soluble tumor necrosis factor receptor 1, sTNFR2: soluble tumor necrosis factor receptor 2.(DOC)Click here for additional data file.S2 TableHR: Hazard ratio, CI: confidence interval. In bold, variables with p-value < 0.05, included in the multivariate model. sTNFR1: soluble tumor necrosis factor receptor 1, sTNFR2: soluble tumor necrosis factor receptor 2, TNFα: tumor necrosis factor alpha, CRP: C-reactive protein, eGFR: estimated glomerular filtration rate, MAP: mean arterial pressure, PP: pulse pressure, BMI: body mass index, CVD: history of cardiovascular disease, DM: diabetes mellitus, AHT: arterial hypertension.(DOC)Click here for additional data file.S3 TableData are presented as means ± standard deviation or medians with interquartile range between square brackets. For binary variables, frequencies with percentages between brackets are given. MACE: major adverse cardiovascular event, N = number of patients, M: male, BMI: body mass index, MAP: mean arterial pressure, PP: pulse pressure, HR: heart rate, eGFR: estimated glomerular filtration rate, CVD: history of cardiovascular disease, DM: diabetes mellitus, AHT: arterial hypertension, RRT: start of renal replacement therapy during follow-up, CRP: C-reactive protein, TNFα: tumor necrosis factor alpha, sTNFR1: soluble tumor necrosis factor receptor 1, sTNFR2: soluble tumor necrosis factor receptor 2(DOC)Click here for additional data file.S4 TableHR: Hazard ratio, CI: confidence interval. In bold, variables with p-value < 0.05, included in the multivariate model. sTNFR1: soluble tumor necrosis factor receptor 1, sTNFR2: soluble tumor necrosis factor receptor 2, TNFα: tumor necrosis factor alpha, CRP: C-reactive protein, eGFR: estimated glomerular filtration rate, MAP: mean arterial pressure, PP: pulse pressure, BMI: body mass index, CVD: history of cardiovascular disease, DM: diabetes mellitus, AHT: arterial hypertension.(DOC)Click here for additional data file.


Rationale. Renal dysfunction has a serious impact on the natural evolution of liver cirrhosis. Treatment and prognosis may be improved if an early diagnosis could be established, and specific therapeutic interventions would be applied. Although RIFLE and AKIN classifications have been successfully implemented in the clinical practice of Nephrology and Intensive Care Units, these did not provide major improvements in patients with liver cirrhosis. In the last decade, various biomarkers of kidney injury have been assessed, and Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the most promising and most studied novel biomarker. Objective. To offer a brief evaluation on current data on the utility of this biomarker in patients with liver cirrhosis. Methods and results. We have searched through current literature and analyzed all significant full text articles on this topic. Discussions. NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies to confirm this observation are needed.Abbreviations: ADQI = Acute Dialysis Quality Initiative, AKI = acute kidney injury, AKIN = Acute Kidney Injury Network, ATN = acute tubular necrosis, CKD = chronic kidney disease, Cys C = cystatin C, GFR = glomerular filtration rate, HRS = hepatorenal syndrome, IAC = International Ascites Club, IL-18 = interleukin-18, KIM-1 = kidney injury molecule-1, L-FABP = liver-type fatty acid-binding protein, LT = liver transplantation, MDRD6 = Modification of Diet in Renal Disease 6, NAG = N-acetyl-β-D-glucosaminidase, NGAL = Neutrophil Gelatinase-Associated Lipocalin, pi-GST = pi-glutathione S-transferase, PRA = prerenal azotemia, RBP = retinol binding protein, RRT = renal replacement therapies, SCr = serum creatinine, SLKT = simultaneous liver and kidney transplant, UO = urine output, γ-GT = γ-glutamyl transpeptidase  AKI occurs in up to 19-20% of hospitalized patients with liver cirrhosis and among the most frequent causes are prerenal azotemia (PRA), hepatorenal syndrome (HRS), and acute tubular necrosis (ATN), with prevalence rates estimated around 68%, 25%, and 33%, respectively . Reports have shown that approximately 1% of cirrhotic patients with azotemia suffer from progressive parenchymal renal disease secondary to hepatic viral infections, immune or metabolic disorders  .Kidney dysfunction is a complex and common event in patients with liver cirrhosis. Although novel treatments have shown some promising results . The term “Acute Kidney Injury (AKI)” is used to describe the abrupt decline of the renal function indicated by a boost in serum creatinine level of >50% from baseline, or by an upward trend in serum creatinine level of ≥26.4 µmol/ L (≥0.3 mg/ dL) in less than 48 hours. Chronic Kidney Disease (CKD) can be defined by an estimated glomerular filtration rate (eGFR) below 60 ml/ minute for more than 3 months, by using the Modification of Diet in Renal Disease 6 (MDRD6) formula (this is considered the most accurate creatinine-based formula in cirrhotic patients). Acute chronic kidney disease manifests as an overlapping of AKI on pre-existing chronic renal disease according to the previous definitions for AKI and CKD .In 2011, after a joint debate, members of the Acute Dialysis Quality Initiative (ADQI) and the International Ascites Club (IAC) developed a new collection of diagnostic criteria for an improved evaluation of kidney impairment in liver cirrhosis [Table 1 [7].Gathered together in Vicenza  in May 2002, the members of ADQI group elaborated a new set of diagnostic and classification criteria for AKI: the RIFLE classification (published in May 2004). This classification system includes three classes for severity  and another two classes for outcome  defined by perturbations in serum creatinine, glomerular filtration rate or urine output as described in AKIN classificationTable 2 [7].After a meeting in Amsterdam (September 2005), the Acute Kidney Injury Network (AKIN) group developed a new set of criteria for AKI known as the AKIN classification (published in March 2007). This improved the classification system which consisted of 3 stages of severity and was based only on changes in serum creatinine (2 measurements within 48 h) and urine output as shown in 9]. Fagundes et al. observed that a combination between AKIN classification and traditional criteria for kidney impairment might provide a better assessment of risk in patients with liver cirrhosis, compared with AKIN criteria alone [10].A common limitation of both classifications systems is their inability to provide any information on the cause of the renal dysfunction in liver cirrhosis. Existing data cannot support the superiority of AKIN classification to traditional criteria regarding risk prediction in patients with liver cirrhosis and renal failure  tend to lead to an overestimation of GFR by using creatinine-based formulas. In the setting of AKI, after a renal insult takes place, a steady state must be reached in order to accurately estimate the GFR by using serum creatinine. Most commonly, serum creatinine levels are assessed by using Jaffe reaction, which may interfere with bilirubin levels [11] therefore, the enzymatic method for the determination of creatinine would be more appropriate in these scenarios. Besides these shortcomings, serum creatinine does not have the ability to differentiate among the causes of renal impairment [4]. Despite the fact that it lacks in accuracy, particularly in the setting of liver cirrhosis, serum creatinine is our current marker for kidney dysfunction, and it is widely used. In patients with liver cirrhosis and CKD, decreased hepatic synthesis of creatinine and significant loss of muscle mass [12]. Modern techniques using genomics and proteomics have identified several candidates for the role of kidney biomarkers such as: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), liver-type fatty acid-binding protein (L-FABP), cystatin C (Cys C), N-acetyl-β-D-glucosaminidase (NAG), α1/ β2-microglobulin, γ-glutamyl transpeptidase (γ-GT), retinol binding protein (RBP), pi-glutathione S-transferase (pi-GST), etc. [12].The distinction among the main forms of renal impairment is a crucial step because the outcomes and the management are very different. This challenge has led to a continuous research in this area and to the discovery of new markers of kidney dysfunction. These novel biomarkers are usually small molecules (e.g. proteins or enzymes), that are released into the systemic circulation or urine as a result of changes in glomerular filtration rate, tubular cell injury or inflammatory cell infiltration [13] and can be found in the circulation as three different structural isomers: a monomer (25-kDa), a homodimer (45-kDa), a heterodimer (135-kDa) [14]. NGAL was first discovered inside the specific granules of neutrophils, but further studies revealed that it is secreted by various cells of the body: epithelial cells , neutrophils, monocytes/ macrophages, adipocytes [15]. There is a low baseline production of NGAL that maintains its serum concentration to around 20 ng/ mL, but various stimuli that induce epithelial damage can increase this baseline level [14]. Due to these factors, among the scenarios with an elevated production of NGAL are sepsis, malignancy, chronic kidney disease, pancreatitis, chronic obstructive pulmonary disease, endometrial hyperplasia, urinary tract infection [12]. Increased levels of NGAL can be identified in plasma and urine starting 2-4 hours after a kidney injury, resulting from alterations in glomerular filtration and tubular reabsorption and also by increased secretion in tubular epithelial cells [12]. Serum NGAL levels seem to be directly correlated with urine NGAL levels, therefore, a urine NGAL/ serum NGAL ratio may prove to be a better marker of renal impairment [23].Neutrophil gelatinase-associated lipocalin (NGAL), also described as lipocalin-2 or human neutrophil lipocalin, is one of the most commonly studied novel biomarkers. By its affiliation to the lipocalin superfamily, this small glycoprotein has a specific shape that provides an ability to bind and transport different molecules [3], after cardiac surgery [16-19], after contrast agent administration [20], sepsis [21], trauma patients [22].The utility of NGAL as a biomarker of renal impairment has been tested in various clinical situations, in both adult and pediatric populations: critically ill patients [23-29]. The purpose of our review is to present a synthesis of the current data regarding the potential applicability of NGAL in daily practice in patients with liver cirrhosis and renal dysfunction. In order to have a better interpretation, we have divided the existing data on this topic, according to different applications of this biomarker in patients with liver cirrhosis. All the studies showed higher levels of NGAL and other markers studied in patients with liver cirrhosis and renal impairment compared with patients without renal dysfunction [23] conducted a small study investigating various methods of assessing glomerular filtration rate and the predictive values of proteinuria and kidney injury biomarkers in AKI development. From a small cohort of 34 patients with liver cirrhosis, eighteen (53%) were diagnosed with AKI. Serum NGAL concentration and Cystatin C-based formulas for the estimation of GFR were good early predictors of AKI, with AUROC values of 0.74 (0.51–0.97), P = 0.04 and 0.72 (0.52–0.92), P = 0.02 respectively. In terms of risk assessment, Slack and his colleagues [24] were among the first to study the role of urinary NGAL in patients with liver cirrhosis and renal impairment. One of the results of their study was the ability of uNGAL to discriminate between different types of AKI. By using only one uNGAL measurement at hospital admission, the group of researchers was able to divide patients with AKI into three categories: prerenal azotemia (low levels), hepatorenal syndrome (intermediate levels) and intrinsic AKI (high levels).Verna et al. [25] evaluated the utility of two urinary biomarkers of kidney damage . A total of 160 hospitalized patients with liver cirrhosis were divided into three cohorts: non-ascitic patients (n = 42), ascitic patients without renal impairment (n = 50), and ascitic patients with renal impairment (n = 68). Levels of both urinary NGAL and urinary IL-18 were significantly higher in patients with ascites and renal impairment compared to the other two groups. Also, both urinary biomarkers were able to differentiate between causes of AKI, with highest levels in ATN , intermediate levels for HRS , and the lowest levels in prerenal azotemia . In patients with liver cirrhosis and CKD, the researchers reported medium values of uNGAL (232.63±41.31 μg/ g creatinine) and uIL-18 (582±98.24 μg/ g creatinine), ranged between those of prerenal azotemia and HRS groups.A cross-sectional study conducted by Qasem and his colleagues [26] evaluated the utility of different biomarkers of kidney damage as differential diagnosis tools for AKI in 188 cirrhotic patients. The subjects were separated into three major groups depending on the form of AKI: prerenal azotemia (PRA), hepatorenal syndrome (HRS), acute tubular necrosis (ATN). A set of new and traditional urinary biomarkers was assessed: neutrophil gelatinase-associated lipocalin, interleukin-18, kidney injury molecule-1, liver-type fatty acid binding protein, fractional excretion of sodium and albumin. Urinary markers of kidney injury were substantially elevated in patients with liver cirrhosis and AKI induced by ATN.In a multicenter study, Belcher et al. [27] evaluated the value of urinary NGAL levels in the differential diagnosis of renal impairment in a cohort of 241 patients with liver cirrhosis. Only 84 patients had a grade of impaired kidney function, with higher urinary NGAL levels than the rest of the cohort (patients with and without ascites). Patients with ATN had the most elevated levels of urinary NGAL compared to those of patients with other etiologies of AKI, chronic kidney disease (CKD), and HRS (P < 0.001). For a better interpretation of the results, patients with HRS were divided in three categories  with the highest values of uNGAL in the first two groups (median and IQ range 391(72–523) vs. 147(83–263) vs. 43(31–74) μg/ g creatinine). Despite significantly raised levels found in patients with renal impairment, plasma NGAL was not useful in distinguishing between the causes of kidney dysfunction in patients with liver cirrhosis. Fagundes and colleagues [28] studied the differences in plasma and urine NGAL levels in 64 cirrhotic patients and 23 control subjects. Results of the study showed the highest values of plasma NGAL in patients with type 1 HRS, with statistically significant differences compared to patients with type 2 HRS and compensated liver cirrhosis. Urinary NGAL levels showed the same trend, with greater values in type 1 HRS, intermediate values in type 2 HRS, and low levels in patients with stable liver cirrhosis and controls, without significant differences between type 1 HRS and type 2 HRS patients. Patients with stable liver cirrhosis showed approximately the same values of plasma and urinary NGAL as the control subjects.Gungor et al. [28] revealed a higher mortality rate in patients with HRS, correlated with plasma NGAL levels  and urine NGAL levels .In their study, Gungor and his colleagues [29] evaluated the clinical importance of urinary NGAL in the setting of liver cirrhosis and infections. Their study included 132 hospitalized patients with liver cirrhosis and infections and three measurements for uNGAL were carried out at the time of infection diagnosis, on day 3 and day 7. Markedly elevated levels of uNGAL were found among 65 patients clinically diagnosed with AKI, compared to non-AKI patients , and an even more significant difference was observed between persistent AKI group (n = 4) and transient AKI group (n = 25) . Patients diagnosed with type-1 HRS showed lower values of uNGAL, therefore this urinary biomarker may have the ability to distinguish type-1 HRS from other causes of persistent AKI . High uNGAL levels measured when infection diagnosis was established, were good predictors for the development of a second infection during hospitalization and for the 3-month mortality rate. Baretto et al. . In the pre-transplant setting, kidney damage biomarkers could recognize patients with structural renal impairment in need of simultaneous liver and kidney transplant (SLKT). These novel biomarkers could be of assistance in the pre- and post-transplant evaluation of patients with liver cirrhosis. Some studies indicated that NGAL and other new biomarkers are good prediction tools for early post-transplant AKI and tacrolimus-induced AKI in patients with liver transplantation (LT) , but in the future, a classification that associates the AKIN criteria and kidney injury biomarkers levels can be very useful because the cause of kidney dysfunction plays an important role in the prognosis cirrhotic patients.A “modified” AKIN classification may now be the best solution [By including these biomarkers in the clinical management of AKI, we could identify more accurately patients with underlying structural kidney damage and apply the appropriate treatment.NGAL and other new kidney injury molecules may be useful in patients with liver cirrhosis, particularly in identifying structural kidney dysfunction, but larger validation studies are still needed to confirm this observation. AcknowledgementsThis paper was published under the frame of European Social Found, Human Resources Development Operational Programme 2007-2013, project no. POSDRU/159/1.5/S/133377.All authors have made substantial and equal contributions to this manuscript.


Risk factors associated with many chronic diseases can be improved through regular physical activity. This study investigated whether cross-sectional associations between physical activity, assessed by the Exercise Vital Sign (EVS), and cardiometabolic risk factors can be detected in clinical settings.We used electronic records from Kaiser Permanente Southern California members  to examine the association of EVS category with blood pressure, fasting glucose, random glucose, and glycosylated hemoglobin. Adults aged 18 years or older with at least 3 EVS measures between April 2010 and December 2012, without comorbid conditions, and not taking antihypertension or glucose-lowering medications were included. We compared consistently inactive (EVS = 0 min/wk for every measure) with consistently active (EVS ≥150 min/wk) and irregularly active (EVS 1–149 min/wk or not meeting the consistently active or inactive criteria) patients. Separate linear regression analyses were conducted controlling for age, sex, race/ethnicity, body mass index, and smoking status.Consistently active women had lower systolic  and diastolic  blood pressure than inactive women. Active men had lower diastolic blood pressure than inactive men. Consistently active patients  had lower fasting glucose than consistently inactive patients. Consistently active and irregularly active men and women also had favorable random glucose and HbA1c compared with consistently inactive patients.Routine clinical physical activity assessment may give health care providers additional information about their patients’ cardiometabolic risk factors. During the past 60 years, many studies have demonstrated that regular physical activity reduces illness and death from numerous diseases, including coronary heart disease ,2, hyperMost of the relevant literature includes adults who have been recruited into some type of study on the basis of strict selection criteria, limiting the generalizability of results to those responding to recruitment efforts . Few stuIn 2009, Kaiser Permanente Southern California (KPSC) created and implemented an Exercise Vital Sign (EVS) to be assessed, along with height, weight, and blood pressure, at every adult outpatient visit . This stKPSC is an integrated health care system that serves approximately 3.6 million residents in Southern California at 14 medical centers and more than 200 medical offices. Racial/ethnic makeup, neighborhood education, and household income are generally similar to that of the area population, with marginal underrepresentation of people with very low income and those with high education . In addiThe study period was from April 1, 2010, through December 31, 2012. Inclusion criteria were adults aged 18 years or older as of April 1, 2010, who were health plan members during this time , and had at least 3 outpatient visits during the study period with an EVS measurement on each of these visits .We also required that patients not have any major comorbidities and that all outcomes were abstracted from outpatient settings rather than hospitals or emergency departments. Physical activity and cardiometabolic risk factors can be altered by diseases or chronic conditions, which may mask true associations that we would not be able to detect. This requirement ensured that we would select a generally healthy population. Presence of comorbid conditions was assessed with a modified Charlson comorbidity index , which u2), being pregnant during the study period, and having a body temperature above 99.9 degrees on a particular visit, which may indicate an illness and may affect both MVPA and blood pressure. In addition, patients could not be taking antihypertensive medications or glucose-controlling medications. We added these exclusions because the medications may mask possible effects from MVPA , consistently physically inactive , and irregularly physically active  were created for this study.The EVS has been described in detail elsewhere . BrieflyBlood pressure was also measured at every KPSC outpatient visit by trained medical assistants or nurses. After a 5-minute seated rest, blood pressure was measured using standard procedures with the arm supported at heart level. An automated sphygmomanometer, Welch Allyn Connex series , was used; if the measure was elevated (≥140/90 mm Hg), a second measurement was taken. Results were recorded in the EMR. All blood pressure measurements taken during the study period were averaged to create a mean blood pressure for each individual.All laboratory tests and results were tracked through a laboratory management system, which was incorporated into the patient’s EMR. Because of varying clinical practices across the region, patients may have had a combination of fasting blood glucose, random blood glucose, and HbA1c in their records. All were measured from a blood draw from the antecubital region of the arm by a phlebotomist at a KPSC laboratory. The reference laboratories at KPSC were all Clinical Laboratory Improvement Amendment certified. All results during the study period were averaged for each patient and used for analysis.2) and weight (kg) were measured at each outpatient visit, values were recorded in the EMR, and BMI was calculated. All values obtained for each patient during the study period were averaged for the analyses.Date of birth , race/ethnicity, and sex were obtained from electronic membership files. Smoking status was obtained from self-report during outpatient visits and recorded in the EMR. Height (mP < .001), so results are presented stratified by sex. We calculated 95% confidence intervals (CIs) around the regression coefficients. Analyses were conducted using SAS Enterprise Guide 4.3 (SAS Institute Inc).Descriptive data were derived from frequency counts for categorical variables and means and standard deviations (SDs) for continuous variables. Separate multivariable linear regression models were conducted using systolic blood pressure, diastolic blood pressure, fasting glucose, random glucose, and HbA1c as the outcomes. Each analysis included the main predictor of physical activity status  and controlled for age, sex, race/ethnicity, BMI, and smoking status. The inactive group was the reference for the analyses. Analyses were also run with a sex*activity interaction variable because the descriptive data suggested differences in the exposure for some of the outcome variables. The interaction term was significant  who met study criteria. Fasting glucose information was available for 401,635 patients, random glucose for 218,506, and HbA1c values for 158,653. Mean (SD) age was 44.2 (14.5) years . ApproxiP < .001), and results indicated a greater magnitude of difference in systolic and diastolic blood pressure for consistently physically active women than for consistently physically active men and for irregularly active women than for irregularly active men.Consistently physically active women had lower systolic  and diastolic  blood pressure than did inactive patients . IrregulP < .001). For all 3 glucose measures, consistently physically active women had a greater magnitude of difference than did the consistently active men . Similarly, the magnitude of difference for the irregularly physically active women was greater than the irregularly active men for fasting glucose, random glucose, and HbA1c.Fasting glucose was lower for consistently physically active women  and irregularly active women  than that for consistently inactive women. The same was true for men; consistently active men  and irregularly active men  had lower fasting glucose than did those who were consistently inactive . SimilarOur results demonstrate that, using the EVS as a measure of MVPA, generally healthy, consistently active, and irregularly physically active patients of both sexes have lower diastolic blood pressure, glucose, and HbA1c levels than patients who are consistently physically inactive. Consistently active and irregularly active women also have lower systolic blood pressure. For glucose and HbA1c, the most favorable values were for consistently physically active patients. Consistently active and irregularly active women had a greater magnitude of difference for all the cardiometabolic variables compared with similarly active men.The associations we observed were modest and cross-sectional. However, even a small improvement in cardiometabolic risk factors has a profound impact on population health. Cook et al estimated that a 2 mm Hg reduction in diastolic blood pressure would decrease the US prevalence of hypertension by 17% and reduce the risk of coronary heart disease and stroke by 6% and 15%, respectively ,19. ThisThe difference in fasting glucose (approximately 3%) we found between the consistently physically active and consistently inactive patients is comparable to findings from lifestyle interventions in populations at risk for future cardiometabolic disease. Randomized trials of weight loss, dietary patterns, and physical activity interventions reported reductions of a similar magnitude for intervention compared with control group participants –23. For The random and fasting glucose and HbA1c results were graded, with favorable values among patients who were irregularly physically active compared with those who were consistently inactive and the most favorable values among patients who were consistently physically active. These results were not noted for blood pressure in which irregularly active women had blood pressure reductions similar to those of consistently active women. Although the exact amount of physical activity needed to produce blood pressure reductions has not been identified, it is recognized that a low amount of physical activity can improve blood pressure . In contWe cannot explain why the magnitude of differences between the consistently active and consistently inactive patients was greater for women than for men. Other studies reported stronger correlations between physical activity and 2-hour glucose levels in men compared with women   and incrOur study has many limitations. It was cross-sectional, which limits the ability of making causal inferences. However, a multitude of investigations have demonstrated the effects of physical activity on blood pressure and glucose levels. The significant effects may not be clinically meaningful, given our very large sample size. The study population had to have had at least 3 outpatient visits during a 2.5-year period, which may make them substantively different from other generally healthy patients who have lower health care use. There are limitations with self-reported physical activity that have been noted elsewhere . In partIn conclusion, consistently physically active and irregularly active patients, as assessed by the EVS, have lower diastolic blood pressure, glucose, and HbA1c levels than patients who are consistently physically inactive. On a population level, the associations we observed were comparable with those needed to reduce the risk of coronary heart disease, stroke, and diabetes. If health care providers would routinely assess the physical activity of their patients and refer those who are physically inactive to effective physical activity programs, it may reduce the burden of future chronic diseases.


Primary Hypertension (HT) is the most prevalent cardiovascular disorder worldwide and is accompanied by significant morbidity and mortality.The present study aimed to investigate the kinetics of orthostatic Blood Pressure (BP) in primary hypertensive patients during the change from supine position to standing position as well as during the standing position using the Orthostatic Test (OT).This prospective study included a group of 107 primary hypertensive patients . Orthostatic systolic BP (Ortho SBP) was recorded for 10 minutes at the rhythm of 3 measurements per minute and was compared to the values of supine systolic preorthostatic (Preortho SBP). According to the changes in Ortho SBP, three subgroups of primary hypertensive patients were selected as follows: Subgroup A: Ortho SBP was higher than mean Preortho SBP by 10 mmHg or more. Subgroup B: Ortho SBP was lower than mean Preortho SBP by 20 mmHg or more. Subgroup C: -20 mmHg < (Ortho SBP - Preortho SBP) < + 10 mmHg.The kinetics of each group was then recorded.In this study, the prevalence of subgroups A, B, and C was 27.1%, 15.9%, and 57.0%, respectively. In subgroup A, the adrenergic peripheral sympathetic alpha response was 20% during the OT.Hypertensives with very similar supine SBP behavior could exhibit widely different Ortho SBP. Thus, careful and effective treatment of hypertensives requires careful consideration and assessment of orthostatic BP. Arterial Hypertension (HT) is defined as Systolic Blood Pressure (SBP) ≥ 140 mmHg and/or Diastolic Blood Pressure (DBP) ≥ 90 mmHg, measured in supine position -4. In thAccording to the American Autonomic Society and the American Academy of Neurology , OH is dThe present study aims to investigate the kinetics of the Ortho BP in primary hypertensives during the change from supine to standing position and during the standing position, using the Orthostatic Test (OT).This prospective study was conducted on 107 primary hypertensive patients referring to the unit of exploration of the Autonomic Nervous System (ANS) in the cardiology service A at Ibn Sina Hospital in Rabat. The study was approved by the Ethics Committee of Ibn Sina Hospital after a thorough analysis. Also, written informed consents were obtained from all the patients before the tests. Each patient also completed a form recording the presence or absence of various significant functional signs.The inclusion criteria of the study were BP equal to or higher than 140/90 mmHg measured in supine position, mild to moderate primary HT, and not having received complete treatment or not having been treated at all.On the other hand, the exclusion criteria of the study were suffering from severe, secondary, or complicated HT and being under any anti-hypertensive treatment.OT allows the study of changes in BP and Heart Rate (HR) that occur during transition to active standing compared to supine position.The test was performed in the morning, after fasting and under no anti-hypertensive treatment within at least 48 hours. BP and HR were monitored using a Dynamap  and a screen of posting , respectively. The basal systolic BP and HR were measured on both arms on a The hypertensive patients were then classified into the following three subgroups:-Subgroup A: Ortho SBP was higher than mean Preortho SBP by 10 mmHg or more.-Subgroup B: Ortho SBP was lower than mean Preortho SBP by 20 mmHg or more.-Subgroup C: -20 mmHg < (Ortho SBP – Preortho SBP) < +10 mmHg.The changes in Ortho SBP were assessed during 10 minutes and the results were reported for each subgroup.Peripheral sympathetic consecutive stimulation to orthostatic stress usually increases the BP. Thus, we can estimate the adrenergic peripheral alpha sympathetic nerve response according to the following formula:A 10 - 15% increase in adrenergic peripheral sympathetic response is considered as normal. Besides, adrenergic peripheral sympathetic response higher than 15% is normally considered as hyperactive. Finally, a sympathetic response lower than 10% is considered as sympathetic impairment -13.In this study, we aim to work only on adrenergic peripheral alpha sympathetic response related to BP. HR is going to be investigated in further studies.Descriptive statistics included range, mean, and standard deviation for continuous variables and frequency and percentage for categorical ones. Categorical and normally distributed continuous variables were compared using Chi-square test and independent t-test, respectively. Additionally, the SBP changes during OT were compared using Friedman test. P values < 0.05 were considered as statistically significant. All the analyses were performed using the SPSS statistical software, version 15.0 .In this study, the mean age of the patients was 55.82 ± 11.35 years ranging from 39 to 80 years. In addition, 61.7% of the participants were female.The mean basal HR was 75.5 ± 13.2 beats/minute ranging from 65 to 87 beats/minute. In addition, the mean Preortho SBP was 150.0 ± 6.2 mmHg ranging from 147 to 163 mmHg. Besides, the mean Ortho SBP was 177.5 ± 17.3 mmHg ranging from 135 to 220 mmHg, excluding the patients with OH. The prevalence of subgroups A, B, and C was 27.1%, 15.9%, and 57.0%, respectively .th minute. Even in the 10th minute of the test, the increase was +13.3 mmHg. In particular, orthostatic HT was maintained  had orthostatic HT  out of whom, 69% (20/29) were female. The mean Preortho SBP was 148.1 ± 10.7 mmHg ranging from 141.6 to 155.2 mmHg. Besides, the mean Ortho SBP was 164.5 ± 2.7 mmHg ranging from 162 to 168 mmHg. In this subgroup, in comparison to Preortho SBP, the mean Ortho SBP increased and reached the maximum value in the first minute of OT (+20.0 mmHg) and thereafter decreased gradually throughout the OT. For example, increase in the mean ortho SBP was +16.4 mmHg in the 5intained .In subgroup B, 17 hypertensive patients had OH , 59% of whom (10/17) were female. The mean Preortho SBP was 163.4 ± 7.2 mmHg ranging from 160 to 167 mmHg. In addition, the mean Ortho SBP was 137.5 ± 11.2 mmHg ranging from 128 to 143 mmHg. In this subgroup, in comparison to Preortho SBP, the mean Ortho SBP decreased in the first minute of OT (-20.3 mmHg) and continued to decrease throughout the whole OT. The change was -36.2 mmHg in the 5th minute and -38.4 mmHg in the 10th minute. OH was maintained throughout the test .In subgroup C, 61 hypertensive patients had no significant changes in Ortho SBP , 62.3% of whom (38/61) were female. The mean Preortho SBP was 153.1 ± 8.4 mmHg ranging from 146 to 160 mmHg. Besides, the mean Ortho SBP was 150.0 ± 4.2 mmHg ranging from 145 to 156 mmHg. In this subgroup, the mean SBP increased slightly during the first minute of orthostatism (+1.67 mmHg), but decreased throughout the whole OT. The change was -5.16 mmHg in the 5th minute and -9.3 mmHg in the 10th minute .Measurement of the adrenergic peripheral sympathetic alpha responses during the OT showed an average increase of 20.0%. The normal response was supposed to be around 10% in the subgroup with orthostatic HT.The present study aimed to investigate the kinetics of SBP in hypertensives during the change from supine to standing position and during standing position by using OT. Among the cardiovascular ANS tests, OT is a simple, non-invasive, and reproducible one involving the measurement of BP and HR during upright posture.In this study, we reported the mean of the Ortho SBP values. Comparing Ortho SBP to the mean basal supine SPB, three subgroups of primary hypertensive patients were selected.In subgroup A, in comparison to Preortho SBP, the mean Ortho SBP increased and reached a maximum value in the first minute of OT (+20.0 mmHg), but decreased gradually throughout the OT. In this subgroup, the orthostatic HT was maintained during the OT. Orthostatic HT refers to an increase in the BP in an upright posture. This clinical condition has been understudied and is often underappreciated in clinical practice.In subgroup A, elevation of orthostatic BP was related to the increase in sympathetic response, as described in the literature -18. HT iIn addition, spectral analysis techniques provide important information regarding the alterations of the nervous control of essential HT and allow highlighting an increase in sympathetic activity , 25.The exact causes of sympathetic overactivity in hypertensives are only partially known. The hereditary factor has been much studied. Thus, for example, similarities found only in monozygotic twins compared to fraternal twins lead to the assumption that this factor has indeed a role in the genesis of this hyperactivity , 27. BesBiochemically, measures of radiotracers of the norepinephrine passage in plasma are well suited to study the pathophysiology of increased activity of the sympathetic nervous system in HT . Thus, tAlso, same studies have found higher levels of noradrenaline in cerebrovascular circulation in the patients with primary HT compared to the healthy subjects, suggesting that an underlying increase in the central nervous system norepinephrine could form the basis of increased sympathetic impulses , 28.The discovery of an autonomic imbalance in hypertensive patients not only helps to identify the mechanism of HT, but also to understand the pathophysiology of the cardiovascular system due to HT through metabolic, trophic, rheological, and hemodynamic consequences , 24.Elevation of sympathetic activity increases BP, being responsible for cardiac, renal, and vascular stimulation, respectively increasing, cardiac output, fluid retention, and vascular resistance with hypertrophy of vascular smooth muscle cells .Prognosis of HT depends on the reduction of sympathetic hyperactivity. It is desirable to develop antihypertensive treatment by acting as well on the sympathetic overactivity, as already mentioned by some authors , 33-36.Lenski M et al. showed that Catheter-based renal denervation (RDN) reduced local and whole-body sympathetic activity and BP in the patients with resistant HT. However, safety concerns exist regarding the development of orthostatic dysfunction after RDN. In addition, RDN reduced syncopes in the patients with resistant HT three months after the treatment .On the other hand, Schlaich and Krum indicated that RDN was associated with a substantial and presumably sustained BP reduction .In this work, OH was found only in 17 hypertensive patients. This subgroup represented the smallest subgroup (15.9%) of the three study subgroups. However, this prevalence was not negligible. OH appears early in the OT and worsens thereafter. Masuo et al. showed that OH was present in 20% of hypertensive patients and 4% of normotensive subjects .The mechanism of OH in hypertensive patients suggests impaired baroreflex function in favor of central or peripheral neuropathy affecting the afferent and/or efferent ways . In thesWhen OH occurs in hypertensive patients, antihypertensive attitude becomes difficult because treatment of OH aggravates HT and vice versa. Overall, considering the severity of OH, therapeutic measures depend on the severity of OH in addition to the importance of high BP values.Hypertensive patients with very similar supine SBP behavior can exhibit widely different ortho SBP. This has important consequences for both diagnosis and treatment of hypertensives. Overall, careful and effective treatment of hypertensives requires careful consideration and assessment of orthostatic BP.