The age-specific association between blood pressure and vascular disease has been studied mostly in high-income countries, and before the widespread use of brain imaging for diagnosis of the main stroke types . We aimed to investigate this relationship among adults in China.512 891 adults (59% women) aged 30–79 years were recruited into a prospective study from ten areas of China between June 25, 2004, and July 15, 2008. Participants attended assessment centres where they were interviewed about demographic and lifestyle characteristics, and their blood pressure, height, and weight were measured. Incident disease was identified through linkage to local mortality records, chronic disease registries, and claims to the national health insurance system. We used Cox regression analysis to produce adjusted hazard ratios (HRs) relating systolic blood pressure to disease incidence. HRs were corrected for regression dilution to estimate associations with long-term average  systolic blood pressure.During a median follow-up of 9 years (IQR 8–10), there were 88 105 incident vascular and non-vascular chronic disease events (about 90% of strokes events were diagnosed using brain imaging). At ages 40–79 years (mean age at event 64 years [SD 9]), usual systolic blood pressure was continuously and positively associated with incident major vascular disease throughout the range 120–180 mm Hg: each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease (HR 1·31 [95% CI 1·28–1·34]) and ischaemic stroke (1·30 [1·29–1·31]), but the association with intracerebral haemorrhage was about twice as steep (1·68 [1·65–1·71]). HRs for vascular disease were twice as steep at ages 40–49 years than at ages 70–79 years. Usual systolic blood pressure was also positively associated with incident chronic kidney disease (1·40 [1·35–1·44]) and diabetes (1·14 [1·12–1·15]). About half of all vascular deaths in China were attributable to elevated blood pressure , accounting for approximately 1 million deaths (<80 years of age) annually.Among adults in China, systolic blood pressure was continuously related to major vascular disease with no evidence of a threshold down to 120 mm Hg. Unlike previous studies in high-income countries, blood pressure was more strongly associated with intracerebral haemorrhage than with ischaemic stroke. Even small reductions in mean blood pressure at a population level could be expected to have a major impact on vascular morbidity and mortality.UK Wellcome Trust, UK Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, Chinese Ministry of Science and Technology, and the National Science Foundation of China. In 2013, WHO set global targets for the control of non-communicable diseases, including a 25% relative reduction in the prevalence of elevated blood pressure by 2025.Meta-analyses of prospective studies have demonstrated the importance of moderate differences in blood pressure for risk of ischaemic heart disease and stroke,Evidence before this studyWe did a literature search to identify articles from prospective studies in China that reported on the association between blood pressure and chronic disease. We searched PubMed for articles published between Jan 1, 1960, and March 1, 2017, using the terms “blood pressure” (or “hypertension”) and “prospective study”  and “China” (or “Chinese”). We used search terms in English but did not apply any language restrictions. The reference lists of relevant articles were also reviewed. We identified numerous small prospective studies (<50 000 participants) but few large studies, and the largest of these had less than half the number of vascular events than this study. All identified studies reported positive associations between blood pressure and vascular disease , but most examined effects on mortality only and did not correct for regression dilution bias. Furthermore, the larger prospective studies tended to pre-date the routine use of brain imaging required to reliably differentiate the main stroke types . As such, although blood pressure is an established cause of vascular disease, uncertainty remained about the strength of its association with the major types of vascular disease in China.Added value of this studyThis large prospective study reliably quantifies the age-specific associations between blood pressure and major vascular and non-vascular chronic diseases in men and women in China. For each decade of age at risk (40–79 years), there were positive, log-linear associations between systolic blood pressure and risk of ischaemic heart disease, ischaemic stroke, intracerebral haemorrhage, and the aggregate of all major vascular diseases, with no evidence of a threshold down to at least 120 mm Hg. Overall, each 10 mm Hg higher usual systolic blood pressure was associated with an approximately 30% higher risk of ischaemic heart disease and of ischaemic stroke, but the association with intracerebral haemorrhage was about twice as steep. Usual systolic blood pressure was also positively associated with chronic kidney disease and diabetes, but not with cancer , liver cirrhosis, or chronic obstructive pulmonary disease; the causal relevance of these positive associations with non-vascular chronic disease remains unclear.Implications of all the available evidenceOur study showed stronger associations between blood pressure and vascular disease than have previous prospective studies in China. The magnitude of the age-specific associations between blood pressure and ischaemic heart disease was similar to those reported in previous large meta-analyses of prospective studies. In contrast to these meta-analyses, however, the present study found strong evidence that, throughout middle age and into old age, there were steeper associations for intracerebral haemorrhage than ischaemic stroke. It was estimated that about half of all vascular deaths in China were attributable to elevated blood pressure , accounting for around 1 million deaths (age <80 years) annually; given the strength of the associations between blood pressure and vascular disease, even small reductions in mean blood pressure at a population level would be expected to have a major impact on vascular morbidity and mortality.Reliable classification of the main stroke types requires brain imaging,Hence, although blood pressure is an established cause of vascular disease, uncertainty remains about the strength of its association with the main stroke types and with ischaemic heart disease in China. Furthermore, studies in western populations have reported strong positive associations between blood pressure and risk of several non-vascular diseases, including chronic kidney disease, diabetes, and certain cancers, but such associations have not been reliably assessed in China.Details of the study design and survey methods have been reported previously.After participants had sat for at least 5 min, blood pressure was measured twice using a UA-779 digital sphygmomanometer . If the difference between the two measurements was more than 10 mm Hg for systolic blood pressure, a third measurement was taken. Only the last two readings were recorded, and the mean of these readings was used in all analyses. Sphygmomanometers were supplied centrally, calibrated daily, and only used by trained fieldworkers. Repeat measurements of blood pressure were obtained from a random sample of 19 788 participants (approximately 5%) about 3 years after baseline  using procedures identical to those used in the baseline survey. Repeated blood pressure measures were used to correct prospective analyses for the regression dilution bias that results from the inaccuracy with which a single measurement of an exposure at baseline characterises an individual's usual level.Deaths were identified by electronic linkage to local mortality records, supplemented by annual reviews of local residential registers to check for completeness. Non-fatal events were identified from local chronic disease registries  and from claims to the national health insurance system, which has almost universal coverage in all study areas. The underlying causes of death and hospital diagnoses were coded in accordance with the International Classification of Diseases 10th revision  or diastolic blood pressure (<40 mm Hg or ≥150 mm Hg), those with no follow-up in the age range 40–79 years, and those with a (self-reported) history of vascular disease at baseline . For prospective analyses of each non-vascular disease, participants with a history of the relevant disease at baseline were excluded  for the associations between systolic blood pressure and first occurrence  of major vascular disease , chronic kidney disease, type 2 diabetes, cancer, liver cirrhosis, or chronic obstructive pulmonary disease. Major vascular disease was further classified into ischaemic heart disease , stroke types , and other vascular diseases.HRs were adjusted for sex, education, area, smoking, alcohol intake, and body-mass index (BMI). An additional term was fitted that allowed the HR in each decade of age to be estimated as the geometric mean of the HRs in the first and second half of that decade, which avoids any assumptions as to whether the proportional associations of risk to usual systolic blood pressure are similar in different decades of age. The log HRs for a 10 mm Hg higher systolic blood pressure were obtained by fitting systolic blood pressure as a continuous variable in men and women separately for each decade of age at risk . Age-specific and sex-specific HRs were then corrected for age-specific and sex-specific regression dilution ratios to give the HR for a 10 mm Hg higher usual systolic blood pressure , and comIn categorical analyses, participants were divided into five groups according to baseline systolic blood pressure . HRs were calculated relative to the lowest systolic blood pressure group, and plotted against mean usual systolic blood pressure in each of these groups ; the 95%d × (RR – 1)/RR, where Pd represents the proportion of all vascular deaths in a given systolic blood pressure group  and RR, the relative risk, is approximated by the group-specific HR  relative to the lowest systolic blood pressure group.Assuming causality of the association between blood pressure and vascular mortality, we estimated the fraction of deaths attributable to elevated systolic blood pressure by PThe funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. BL, SL, RCl, ZC, and LL had full access to the data and analyses and had final responsibility for the decision to submit for publication.Of 512 891 participants, we excluded two with missing information, 110 with extreme systolic blood pressure, 62 with extreme diastolic blood pressure, 488 without follow-up in the age range 40–79 years, and 23 104 with a baseline history of vascular disease. By Jan 1, 2016, 37 289 (7·3%) participants had died and 4875 (1·0%) participants were lost to follow-up.2 (SD 3·4), and 26 393 (5·4%) participants had diabetes . Among men, 123 902 (62·0%) were current smokers and 67 693 (33·9%) consumed alcohol at least weekly, but only 6616 (2·3%) women were smokers and 6017 (2·1%) consumed alcohol at least weekly. Overall, mean systolic blood pressure was 130·6 mm Hg (SD 21·0), and 17 623 (3·6%) participants reported current use of blood-pressure-lowering medication.Among 489 125 participants included in the main analyses, the mean age at baseline was 51 years (SD 10) and 289 224 (59·1%) were women . Overall2 higher BMI), and was inversely associated with level of education and residing in an urban area. At resurvey, about 3 years after the baseline survey, the overall regression dilution ratio for systolic blood pressure was 0·6, but it was slightly lower  in men than women, and in older than in younger individuals , 42 662 incident major vascular disease events occurred, including 4450 cases of ischaemic heart disease, 29 343 of ischaemic stroke, 6011 of intracerebral haemorrhage, 1572 of other (or unspecified) stroke, and 1286 of other vascular events. About 90% of stroke cases were diagnosed for stroke type with brain imaging (CT scan or MRI), as estimated from a detailed review of the medical records of a representative subset of cases. Additionally, there were 21 044 incident cases of cancer, 12 241 of diabetes, 8478 of chronic obstructive pulmonary disease, 1940 of chronic kidney disease, and 1740 of chronic liver disease.For each decade of age at risk, usual systolic blood pressure was positively and log-linearly associated with risk of major vascular disease throughout the systolic blood pressure range examined, with no evidence of a threshold down to at least 120 mm Hg . The HRsvs 1·23 [1·19–1·28]) and for fatal than non-fatal ischaemic stroke (1·47 [1·40–1·55] vs 1·30 [1·29–1·31]), but there were no such differences for intracerebral haemorrhage.The associations between usual systolic blood pressure and ischaemic heart disease, ischaemic stroke, and intracerebral haemorrhage were also approximately log-linear throughout the systolic blood pressure range examined . OverallOnly 4% of strokes were classified as other or unspecified type, and the strength of these associations with usual systolic blood pressure was similar to that for ischaemic stroke . For theFor vascular mortality at ages 40–79 years, each 10 mm Hg higher usual systolic blood pressure was associated with about a 50% higher risk of vascular death .Our study showed stronger associations between blood pressure and vascular disease than have previous prospective studies in China, largely because those studies did not correct for within-person variability in blood pressure (regression dilution bias).These differences might, in part, reflect the high rate of brain imaging in this study. The use of brain imaging for diagnosis of stroke types was less common before the mid-1990s and, hence, it is possible that there was substantial misclassification of stroke types in some of the older studies included in these meta-analyses. By contrast, brain imaging was used to diagnose stroke types in about 90% of stroke cases in the CKB study. The greater use of brain imaging might also have allowed more non-fatal strokes to be identified than previously. There were shallower associations for non-fatal than fatal ischaemic stroke , and there is some evidence that both case fatality and the strength of associations with blood pressure might differ between the different aetiological subtypes of ischaemic stroke .Randomised controlled trialsGuidelines on the management of hypertension generally recommend initiating treatment in adults with an average systolic blood pressure of 140 mm Hg or more, or diastolic blood pressure of 90 mm Hg or more, and some recent randomised trials, in selected populations, have found benefit in initiating treatment at lower levels.Previous studies reported associations between blood pressure variability and risk of vascular disease independently of baseline systolic blood pressure,We observed significant positive associations between systolic blood pressure and chronic kidney disease and diabetes, but the causal relevance of these associations remains uncertain. Neither association is strongly supported by evidence from trials, and might well be accounted for by reverse causality or residual confounding. A large meta-analysisThe chief strengths of this study include the large number of disease events, high-quality measurements of blood pressure (including the training of technicians), and long-term follow-up of a wide range of clinically validated disease outcomes. The main findings support efforts to address the substantial burden of blood pressure on vascular disease in China, and indicate that even small reductions in mean blood pressure at a population level can have a substantial effect on disease risk: for example, 5 mm Hg lower usual blood pressure would prevent around 350 000 deaths per year among individuals younger than 80 years of age (and around 200 000 deaths at <70 years). The use of blood-pressure-lowering medication is low in China, and strategies to improve rates of awareness, detection, and treatment of individuals with hypertension are likely to be highly cost-effective, especially among those with existing vascular disease.40In conclusion, among men and women in China, higher levels of blood pressure were continuously and positively associated with higher risks of major vascular disease, with no evidence of a threshold down to at least 120 mm Hg systolic blood pressure and 75 mm Hg diastolic blood pressure. Unlike studies in western populations, blood pressure was more strongly associated with intracerebral haemorrhage than ischaemic stroke. There was also evidence of positive associations with some non-vascular chronic diseases, but the causality of these associations remains unclear. It was estimated that about half of all vascular deaths in China were attributable to elevated blood pressure, accounting for roughly 1 million deaths (age <80 years) annually; given the strength of the associations between blood pressure and vascular disease, even small reductions in mean blood pressure at a population level would be expected to have a major impact on vascular morbidity and mortality.


Controlling blood pressure (BP) leads to significant reduction in cardiovascular risks and associated deaths. In Ethiopia, data is scarce about the level and determinants of optimal BP control among hypertensive patients. This study aimed to assess the prevalence and associated factors of optimal BP control among hypertensive patients attending at a district hospital.A hospital-based, cross-sectional study was conducted among 392 hypertensive patients who were on treatment and follow-up at a district hospital. A structured questionnaire adopted from WHO approach was prepared to collect the data. Medication adherence was measured by the four-item Morisky Green Levine Scale, with a score ≥3 defined as “good adherence”. Blood pressure was measured, and optimal BP control was 0DEFined as systolic BP < 140 mmHg and diastolic BP<90 mmHg. Both binary and multivariable logistic regressions models were fitted to identify correlates of optimal BP control. All statistical tests were two-sided and a p values <0.05 was considered for statistical significance.The mean age of the participants was 58 years (SD±13 years). Over half (53.8%) were females. Three quarters (77.3%) of the participants were adherent to their medications. The overall proportion of participants with optimally controlled BP was 42.9%.Female sex (Adjusted Odd Ratio(AOR) = 1.94, 95% CI: 1.15, 3.26), age older than 60 years , consumption of vegetables on most days of the week , physical activity , and taking less than three drugs per day  were positively associated with optimally controlled BP. Poor adherence to medications , having asthma comorbidity  and use of top added salt on a plate  were negatively associated with optimal BP control.A higher proportion of hypertensive patients remain with un-controlled BP. Modifiable risk factors including poor adherence to medications, lack of physical exercise, adding salt into meals, being on multiple medications and comorbidities were significantly and independently associated with poor BP control. Evidence-based, adherence-enhancing and healthy life style interventions should be implemented. For instance, effective and sustained lowering of the BP of hypertensive patients by 2 mmHg reduces the risk of CVD events by up to 10% . SimilarAntihypertensive medication is one of the measures to manage hypertension. However, studies had shown that merely less than half of hypertensive patients on medications have optimal BP control –6, 9–14.This hospital-based cross-sectional study was conducted at Debre Tabor district hospital, Northwest Ethiopia. The hospital is located in Debre Tabor town (667 km north-west of Addis Ababa), South Gondar Zonal administration of the Amhara National Regional State (ANRS). Currently, the hospital has a catchment population of about 2.3 million people in the zone and nearby districts.Study participants were recruited, between March and May 2015, from the outpatient chronic illness follow up clinic of the hospital. All hypertensive patients aged 18 years or older on outpatient follow-up and anti-hypertensive medication therapy for at least 6 months were included in this study.The sample size of 416 was determined based on a 95% confidence interval around a percentage prevalence estimate of 43.6% controlled BP  with a 5A structured questionnaire that included variables on sociodemographic characteristics, medical history, and other previously validated tools including the WHO STEP wise approach to surveillance non communicable diseases , and theThe questionnaire was pre-tested on 20 hypertensive patients from the nearby health center and modified accordingly before the main study was begun. Four data collectors and a supervisor were collected data from both primary and secondary sources (patient interviews and record reviews). Training was given for 2 days and information exchange by telephone and close supervision by the principal investigator and supervisor were made on a daily basis. Coding and data cleaning were done (checking frequencies and cross-tab for each item).To ascertain blood pressure control, we undertook document review of patient’s charts and recorded the average of three BP levels measured over the preceding 6 months (one being the most recent).Optimally controlled BP was defined as an average systolic BP <140 and diastolic BP < 90 mmHg if the patient is younger than 60 years , 22 or aPatients with score of ≥3 (range: 0–4) on the 4-items Morisky Green Levine Scale self-reported measures of medication-taking behavior were assessed as having good adherence to medications, otherwise classified as non-adherent.Physical activity level of the respondents was categorized into no, low, or moderate. Patients were defined as having no physical activity if they do not perform any form of physical activity for at least 10 minutes. If a patient declares performing moderate activity per week for less than 5 times of each at least 30 minutes, or less than three times of each at least 20 minutes of vigorous activity per week, then he/she was defined as having low level of physical activity. Similarly, a moderate level of physical activity was defined as if the patient performed 3 or more days of vigorous intensity activity of at least 20 minutes per day or, 5 or more days of moderate intensity activity or, walking of at least 30 minutes per day. Top added salt on plate was defined as the addition of raw salt on meal during meal preparation.Data were entered using EPI INFO version 7 and analyzed by using SPSS version 20. Data were checked and cleaned for completeness and consistency of values and variables. Descriptive statistics were used to present data in text and tables. Both bivariate and multivariable logistic regressions were fitted to identify factors associated with optimal BP control. All variables with p-values up to 0.2 in the bivariate analysis were fitted in to multivariable logistic regression to control for the possible effects of confounding. Hosmer-Lemeshow goodness of test for the model was also checked. All statistical tests were two sided and variables which have significant association with the outcome variable were identified on the basis of AOR with 95% CI, p-values <0.05.Of the 397 eligible patients attending at the clinic in the three months of data collection, 392 participated in this study (response rate of 98.7%).The mean age of respondents was 58 years (SD±13 years) which range from 23–88 years. Three hundred eighty seven (98.7%) of the respondents were from Amhara ethnic group, 254 (64.8%) were currently married, 211 (53.8%) were females, and 372 (94.9%) identified themselves as followers of orthodox Christianity. About half of participants (49%) were unable to read and write, and two-thirds (69.4%) were urban dwellers. The median monthly family income of the respondents was 600 Ethiopian Birr (ETB) with inter quartile range of1129 ETB .Of all participants, 384 (98%) and 112 (28.6%) were eating cereal products and vegetables on most days of the week respectively. Two hundred forty six (62.8%) of the respondents were using Sesame oil for their usual meal preparations and a third of participants (32.1%) add salt when cooking or preparing food at home.Five patients (1.3%) were current smokers, and 48 (12.2%) reported that they drink alcohol on daily basis. Close to half of patients (44.4%) are classified as having moderate levels of physical activity.Of all respondents 72 (18.4%), 68 (17.3%), 30 (7.7%) and 26 (6.6%) have diabetes mellitus, cardiovascular diseases, asthma and chronic kidney diseases respectively. Eighty one (20.7%) of the respondents reported as they had family history of hypertension.Among the respondents 285 (72.7%) of the study subjects had been taking less than 3 types of drugs per day and 303 (77.3%) were classified as having good adherence to prescribed medications .The mean systolic and diastolic BP readings were 142.17 mmHg (±14.69 SD) and 87.74 mmHg (±8.69 SD). The overall proportion of optimally controlled BP was 42.9% .After adjustment for potential confounders ,female sex, age older than 60 years, consumption of vegetables on most days of the week, adequate physical exercise, and taking less than 3 drugs per day were significantly and positively associated with optimally controlled BP whereas poor adherence to medications, use of top added salt on a plate and having asthma comorbidity were significantly and negatively associated with optimal BP control.Females were twice  more likely to have optimal BP control as compared with males. Compared with younger patients (aged 18–40 years), those aged over 60 years were three times  more likely to have optimal BP control. Patients who consumed vegetables on most days of the week were two times  more likely to have optimally controlled BP as compared to patients who didn’t consumed vegetables on most days of the week. Compared to patients with no physical activity, those who did low and adequate level of physical exercise were three times  and five times  more likely to have optimally controlled BP respectively. Hypertensive patients who took less than 3 drugs per day were three times  more likely to have optimal BP control as compared to patients who took 3 or more drugs per day. Hypertensive patients who used top added salt on a plate was 80%  less likely to have optimal BP control as compared to patients who didn’t used. Hypertensive patients who have had asthma comorbidity were 67%  less likely to have optimal BP control as compared to non-asthmatic patients.Patients who were poorly adherent to their prescribed antihypertensive drugs were 82%  less likely to have optimal BP control as compared to those who were adherent to their antihypertensive drugs .Controlling blood pressure in people with hypertension to reduce cardiovascular morbidity and mortality is a major challenge public health problem in many developing countries including Ethiopia.This study revealed that only 42.9% of hypertensive patients had optimally controlled BP despite being on follow up at a hospital. This finding was in line with studies done in Adama Hospital Medical College Ethiopia (43.6%) , urban-rAge was another factor significantly associated with blood pressure control found in this study. Accordingly, hypertensive patients older than 60 years were three times more likely to control their blood pressure as compared to age group of 18–40 years. This finding is supported by study done in rural and urban communities in high, middle, and low income countries  and MacaEating foods high in vegetables reduces blood pressure of hypertensive patients. The finding of this study showed association between eating vegetables on most days of the week and optimal BP control. Those hypertensive patients who ate vegetables on most days of the week were two times more likely to have optimal BP control as compared to patients who didn’t eat vegetables on most days of the week. The possible reason may be vegetables are good source of potassium and this result in decreasing blood pressure. Using top added salt on plate during meal preparation was significantly associated with blood pressure control in this study. Hence, patients who used top added salt on a plate were 80% less likely to have optimal BP control as compared to patients who didn’t use top added salt. This is similar with studies done in Macau, China  and SoutPerforming adequate physical activity have strong and independent role in reducing blood pressure. Consistent to what was previously reported from other sub-Saharan countries and southern China , 25, thiPresence of asthma in patients with hypertension can worsen the conditions of the patient. This study revealed asthma was significantly and independently associated with blood pressure control. Asthmatic hypertensive patients were 67% less likely to have optimal BP control than non-asthmatic hypertensive patients which is supported by a study in KwaZulu-Natal, South Africa . These mNumber of drugs had a significant association with blood pressure control. This study revealed those patients who took less than three drugs a day were three times more likely to have optimal BP control as compared to patients who took three or more drugs a day. This study is in line with studies done in KwaZulu-Natal, South Africa , and AdaThis study has the following limitations: Some key confounding variables such as physical and biochemical measurements were not included in the study. Self-reporting was used as the only method of measuring adherence and may have the disadvantages of recall bias. It is difficult to infer causation for some variables using a cross sectional study design.In conclusion, the proportion of hypertensive patients whose BP is optimally controlled was relatively low especially among male patients. Females, age group older than 60 years, vegetable consumption on most days of the week, adequate physical exercise, and taking less than three drugs per day were positively and significantly associated with optimal BP control whereas poor adherence to medications, having asthma comorbidity and use of top added salt on a plate were negatively and significantly associated with optimal BP control. Recognizing the fact that controlling BP reduces cardiovascular disease related morbidity and mortality, and prevents costly interventions, we recommend to policy makers in collaboration with stakeholders to develop strategies about the importance of lifestyle modifications, and adherence counseling to effectively control BP. Moreover, we suggest researchers to do further longitudinal studies that include physical and biochemical measurements to identify most important variables associated with blood pressure control and to look at the cause and effect relationship between variables and blood pressure control.Ethical clearance was obtained from Ethical Review Board (ERB) of Institute of Public Health, College of Medicine and Health Science, University of Gondar. Permission letter was obtained from the hospital’s chief executive officer. Informed verbal consent was held from each participant to review their medical records and use the data and participant involvement in the study was on a voluntary basis. Confidentiality of data was kept by using identification numbers rather than names and limiting access to the data.S1 Quest(DOCX)Click here for additional data file.S2 Quest(DOCX)Click here for additional data file.S1 Data(SAV)Click here for additional data file.


Microvascular dysfunction could be responsible for chest pain in patients without myocardial perfusion defects. We evaluated microvascular function using ultrasound-assessed coronary flow reserve (CFR) in patients with chest pain and normal myocardial perfusion scintigram. Secondly, we investigated association between cardiovascular parameters and decreased CFR in a sex specific manner.A total of 202 (128 women) non-diabetic patients with chest pain and suspected myocardial ischemia, but without myocardial perfusion defects on myocardial perfusion scintigram, were enrolled and underwent CFR examination and blood sampling. All patients were followed-up for cardiovascular events. We used a supervised principal component analysis including 66 variables such as clinical parameters, ongoing medication, coronary artery disease history, lipids, metabolic parameters, inflammatory and other cardiovascular parameters.During a median follow-up time of 5.4 years, 25 cardiovascular events occurred; . Average CFR of the study cohort was 2.7±1.2 and 14% showed impaired CFR<2.0. In an adjusted Cox regression analysis, CFR<2.0 independently predicted event-free survival . In the supervised principal component analysis high insulin resistance assessed by Homeostatic model assessment for insulin resistance was the strongest biochemical marker associated with decreased CFR. Interestingly, upon sex specific multivariable linear regression analysis, the association was only significant in men  while systolic blood pressure remained an independent predictor in women .In non-diabetic patients with chest pain without myocardial perfusion defects, low CFR has prognostic value for future cardiovascular events. Insulin resistance appears to be a marker for decreased CFR in men. Indeed, in the context of contribution of traditional risk factors in this patient population, the value of systolic blood pressure seems to be important in the women. Invasive coronary angiography as well as myocardial perfusion scintigram typically identifies obstructive coronary artery disease (CAD) . CoronarCMD is defined as impaired coronary flow reserve (CFR) due to functional and/or structural abnormalities of the microcirculation . Non-invThe presence of microvascular dysfunction has previously been shown more evident in women , but recWe performed a prospective observational study in 202 non-diabetic patients with chest pain without myocardial perfusion defects (128 women and 74 men), at the Sahlgrenska University Hospital, Gothenburg, Sweden between 2006 and 2008 .1c) level >48mmol/mol. All participants provided written informed consent. The study complies with the declaration of Helsinki and was approved by the local Ethics Committee at the University of Gothenburg, Sweden.All patients were referred to myocardial perfusion scintigram due to chest pain and suspect myocardial ischemia, of which 16.8% had previously known CAD. Patients with no sign of ischemic heart disease at the myocardial perfusion scintigram investigation were recruited for study participation within two weeks. All study participants underwent examination of CFR in the left anterior descending coronary artery performed by transthoracic color Doppler guided echocardiography. Previously known CAD was defined as previous coronary artery bypass grafting, percutaneous coronary intervention or myocardial infarction and was collected from patients’ medical records. Blood sampling for laboratory biomarker analysis were carried out after an overnight fast. All patients underwent a standardized interview of demographic data including medical history, smoking status and current cardiovascular medication. All participants provided written informed consent. Inclusion criteria were completed myocardial perfusion scintigram examination due to chest pain followed by transthoracic color Doppler guided echocardiography CFR investigation. Exclusion criteria were myocardial perfusion scintigram-verified ischemia, incomplete CFR investigation, any diabetes diagnosis, fasting plasma glucose ≥7.0mmol/L or glycosylated hemoglobin . Reversible myocardial ischemia was observed automatically by the software ECT-tool box. Severity of reversible myocardial perfusion abnormality and extent of ischemia were evaluated by an experienced physician and only patients scored as no sign of ischemia (score 0) on both criteria were recruited for study participation.Myocardial perfusion scintigram was conducted by a standard clinical two-day protocol. Gated-SPECT studies were performed using We performed a basic transthoracic echocardiography examination according to current recommendations , using SMedian follow up-time was 5.4 years (range: 4.6–6.0 years). Follow-up information on outcome was performed by a physician, blinded to the CFR results. Causes of death were examined by data from the Swedish National Board of Health Registry, further follow-up was completed by telephone interviews and confirmed through patient’s medical records. Study endpoint was cardiovascular event-free survival and time to most severe event was analyzed. Cardiovascular endpoint events were defined according to recommendations . Outcome1c by HPLC at the department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg. Impaired glucose homeostasis, assessed by homeostasis model assessment of insulin resistance (HOMA-IR) was calculated to estimate insulin resistance using the formula: fasting serum insulin (mU/l) x fasting plasma glucose (mmol/l)/22.5 [All study participants underwent an over-night fasting prior to blood withdrawal. The biochemical analyses were performed using commercially available kits according to the manufacturers' protocols; serum triglycerides and cholesterol , direct high density lipoprotein (HDL) cholesterol  apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) , cytokines and cell adhesion molecules , serum insulin . Circulating Interleukin-18 levels were analyzed with an enzyme-linked immunosorbent assay . Ultrasensitive Troponin-I was determined using microparticle-based immunoassays and single molecule counting technology  generating a LLoQ of 0.4 pg/mL, compared to typical hospital lab tests with a LLoQ at 100pg/mL). Plasma fibrinogen was determined at the Karolinska University Laboratory, University Hospital Solna, Stockhom, by an immunonephelometric method using Polyclonal Rabbit Anti-Human antibody  and analyzed on Beckman Coulter Immage 800 Immunochemistry System. Plasma Osteopontin was measured using a sandwich enzyme-linked immunoassay (R&D systems). Myoglobin, carbonic anhydrase III, fatty-acid-binding protein, glycogen phosphorylase BB, creatinine kinase MB isoenzyme and cardiac troponin-I were all measured in plasma using the cardiac array panel . Soluble L-selectin, soluble E-selectin and soluble P-selectin were measured in plasma using the adhesion array panel . Vascular endothelial growth factor A and epidermal growth factor in plasma were measured using the cytokine array panel . Plasma myeloperoxidase was analyzed by an enzyme-linked immunosorbent assay . Plasma glucose was measured using a photometric method and HbA/l)/22.5 . L-argin/l)/22.5 .Principal component analysis (PCA) was performed using Simca 13 . Before analysis, all data were scaled to unit variance and mean centered. In addition, variables with a max/mean-ratio >10, were log-transformed to increase equal leverage of all variables. This generated a data matrix consisting of 69 variables in 202 patients. To rank and illustrate what variables predicted CFR in this cohort, a supervised PCA was performed. PCA is a projection method that allows for a simultaneous comparison and illustration of the inter-variable relationship and contribution of all variables to an endpoint, in a non-biased manner. The dataset was subjected to an orthogonal projection to latent structures by partial least square analysis (OPLS), in which the variability not related  to what is predicted (CFR in this example) is filtered out . In the Deviations in sample size for the various statistical analyses were due to differences in the availability of clinical demographic data, as well as missing values in some analyzed biomarkers/parameters. We calculated the sample size based on the Cox PH one-sided superiority formula. With an overall event rate 15%, an alpha level 5% and 80% power, we need approximately 214 patients to estimate a hazard ratio (HR) of 3.0. Sub-group analysis was performed in a sex specific manner as well as between patients with and without event. The test of skewness was used to assess normal distribution. Demographic data is presented as mean±SD for normal distributed continuous variables and as frequency and percentage for categorical variables. Non-normally distributed variables are presented with their median and interquartile range. Difference between groups was tested using t-test or Mann-Whitney as appropriate, and a p-value <0.05 was considered statistically significant (2-tailed). Categorical data was analyzed by Pearson chi-square test. Kaplan-Meier curves are used to display survival. Hazard Ratio (HR) and 95% confidence intervals (CI) were analyzed by Cox regression models with CFR as categorical variable divided by the pathological cut off <2.0 in both univariate as well as multivariate analysis. Due to the limited number of events (n = 25) in the current study, we selected age and sex based on their known significant clinical value as risk factors to cardiovascular outcome. Furthermore, to study specific sex determinants of the dependent continuous variable CFR, we used multivariable linear regression analysis. Potential covariates tested in the multivariable analysis were selected based on its significant value in the OPLS analysis predicting the dependent parameter as well variables associated with sex specific characteristics. Variables most strongly related to CFR entered the multivariable model with a univariate cut-off value of p<0.250. Possible co-linearity between the x-variables was tested using Spearman correlation coefficient test and a coefficient >0.7 were considered significant. The results from the linear regression analyses are presented as parameter estimates with 95% CIs. All analyses listed above were performed in SPSS .During a time period of two years, 202 non-diabetic patients with suspected myocardial ischemia, but without myocardial perfusion scintigram-verified perfusion defects (128 women and 74 men) were recruited for study participation. Of these, 74% of the patients displayed atypical chest pain, while 26% displayed typical chest pain symptoms in terms of effort angina. Demographic data and history of previously known CAD are presented in 2:24.9). The study population consisted of 34 patients with previously known CAD. In a sub analysis, excluding these patients, 13 major cardiovascular events remained. The pathological CFR cut off <2.0 were then fulfilled by 12% (n = 14) of the women and 12% (n = 6) of the men with an event rate of 25% (n = 5) in patients with CFR <2.0 and 6% (n = 8) in those with CFR ≥2.0, p = 0.002. In an over adjusted Cox regression model adjusting for CFR <2.0, age and sex, CFR remained a predictor of event-free survival, alongside sex (2:23.2).Previous studies have shown that CFR <2.0 predicts outcome in patients without obstructive CAD , 7. To vside sex , Fig 2B Reduced CFR per se is a composite biomarker reflecting multiple pathological processes, including flow limiting stenoses, high blood viscosity, increased endothelial adherence of leukocytes and reduced dilatory capacity of resistance vessels (i.e. vascular dysfunction) . These f1c, glucose, osteopontin and eosinophil counts were all negative predictors of CFR. None of the variables positively correlating to CFR (bars in the positive direction) were considered as significant, as the variability (95% CI) extended through the zero level.To rank and illustrate which variables predicted CFR in this cohort, a supervised principal component analysis (OPLS) was performed. From the distribution of patients along the principal component describing CFR, (i.e. the scores), it appeared that it was a slight skewness in sex distribution . AlthougThe differences in the inter-variable relationships in men and women illustrated in the OPLS discriminant analysis, suggested sex specific mechanisms behind CFR and thus we analyzed the data in a sex specific manner, performing a linear regression analysis in respective sex. For the multivariable analysis, co-linearity was found between HOMA-IR and insulin as well as ApoA1 and HDL. HOMA-IR and ApoA1 were selected for further analysis due to greater correlation significance level to CFR in univariate analysis. Upon the sex specific analysis only HOMA-IR remained an independent predictor of CFR in men  R squar Click here for additional data file.S1 Minimal Dataset(XLSX)Click here for additional data file.


Background. High blood pressure in adults is directly correlated with increased risk of cardiovascular diseases. Hypertension in childhood and adolescence could be considered among the major causes of this problem in adults. This study aimed to investigate the factors associated with hypertension among the adolescents of Jahrom city in Iran and also standard percentiles of blood pressure were estimated for this group. Methods. In this community-based cross-sectional study 983 high school students from different areas of the city were included using a multistage random cluster sampling method in 2014. Blood pressure, weight, and height of each student measured using standard methods. Data were analyzed by statistical software SPSS 16. Results. In total, 498 male and 454 female students were included in this study. Average systolic blood pressure of students was 110.27 mmHg with a variation range of 80.6–151.3. Average diastolic blood pressure was 71.76 mmHg with the variation range of 49.3–105. Results of this study indicated that there was a significant relationship between gender, body mass index, and parental education level with systolic and diastolic blood pressure of the students (P < 0.05). Conclusions. Body mass index was one of the most important changeable factors associated with blood pressure in adolescents. Paying attention to this factor in adolescence could be effective in prevention of cardiovascular diseases in adulthood.  Nowadays cardiovascular diseases are among the leading causes of death all around the world . Among tHypertension which usually occurs in adults is determined by different factors such as gender, weight, height, genetic, physiologic, lifestyle, diet, geographical conditions, and ethnicity , 5. AlsoSystemic hypertension is an indication of an underlying pathophysiology in childhood and adolescence which if not controlled effectively could be resulted to the increased risk of myocardial and cerebral infarctions in adulthood . StudiesHypertension in children is often asymptomatic and does not receive any particular treatment. Hypertension pharmaceutical treatment usually starts in adulthood, whereas high blood pressure (BP) has left its considerable damaging effect on vascular system and other organs of the body from childhood which are often irreversible . Many prForasmuch BP in childhood and adolescence is affected by different factors such as age, gender, height, weight, ethnicity, nutrition, geographic zone, stage of sexual development, and even fatal growth pattern. BP level and its changes vary in different populations. Many studies have reported prevalence of hypertension among children and adolescence from 1 to 16.6 percent –14.Studies done on children and adolescents have shown that different factors  are associated with BP in these groups . It shouThis study aimed to investigate factor associated with BP and also to determine its standard percentiles in adolescents of Jahrom city in southern Iran.This cross-sectional community-based study was done in Jahrom city of Iran in 2014. Jahrom with 220000 inhabitants is one of the most populated cities of Fars province (the fourth province of the country in terms of area and population) which is located in southern Iran.We used a multistage random cluster sampling method for sampling and accordingly 8 high schools  were selected from different areas of the city as clusters. Different educational levels (4 classes) were considered as strata and then we selected samples from these strata randomly. Finally 983 students including 498 male and 454 female students were selected.Necessary data were gathered from the entire participants who include age, gender, height, weight, systolic and diastolic BP, physical activity, and some demographic information. To measure the variables we used 6 public health technicians who were working under the supervision of a general physician.Age of the participants retrieved from their registration documents in the schools. We used a digital stadiometer (Seca 274) for measurement of height and weight of the students. In order to reduce error of measurement, the stadiometer was calibrated with a standard weight every day after using it. Weight of participants measured with an accuracy of 0.1 Kg. In order to increase the accuracy of measurement participants were assessed with minimum possible cloths and also they were asked not to wear shoes and hat.We used a digital sphygmomanometer (Omron M6 Comfort) to measure BP of which length of its cuff was at least 2.3 times more than arm circumference of participants. BP of students measured twice with an interval of 5 minutes in a sitting position. The average value of two measurements was considered as BP of participants. In order to increase reliability of the data, all of the BP measurements were done by one of the technicians using the same method. In all cases diaphragm of the stethoscope located on brachial artery, the cuff filled 30 to 40 mmHg more than expected systolic blood pressure (SBP), and then the air released by 3 mmHg in second. The appearance point of the first Korotkoff sounds was considered as SBP. In the cases that Korotkoff sounds were audible to 0 mmHg, the appearance point of forth Korotkoff sounds was considered as diastolic blood pressure (DBP). The sphygmomanometer and stethoscope were checked for likely error every day. Four team groups were trained to collect data by measurement height, weight, BP, and other variables.In order to increase measurement accuracy some advices were recommended including the following: all participants got rest in a calm and quiet place at least 5 minutes before BP measurement; to reduce the likely stresses all participants were informed about the process; to avoid the effects of dilated urinary bladder all participant were asked to dispose their urine before measurement if needed; the participants were asked not to use caffeine and any adrenergic stimulant such as eye and nose drops and should not be involved in a hard physical activity or severe exercise 1 hour before measurement.All of the participants were in healthy children situation, had not any known disease, and were not under any drug therapy plan. Suspected participants checked by the physician and cases with illnesses and comorbidities  were not included in sampling.This study was approved by the ethical committee of Jahrom University of Medical Sciences. All of the cases were informed about the study and participated with the consent.t-test was used to compare SBP and DBP with gender. One-way analysis of variance (ANOVA) was performed for finding out significance difference among mean of SBP and DBP with body mass index, father and mother education levels, regular physical exercise, and participants' education levels. P value less than 0.05 was considered statistically significant.Data were entered into the statistical software for windows (SPSS 16). The descriptive variables such as mean and standard deviations were used. After checking normality assumption by Kolmogorov-Smirnov test, independent M), coefficient of variation (S), and skewness (L) of the measurement distribution [Q-Q plot, Q tests, and worm plots [Smoothed gender specific reference plots showing 3th, 10th, 15th, 25th, 50th, 75th, 85th, 90th, and 97th percentiles were derived using LMS method  . SBP andribution . Models rm plots . The LMSIn this study 983 students from 8 high schools of Jahrom city were included. 50.56% (497) of the participants were male with the mean ± SD age of 16.3 ± 1.1 (range: 14.2–20.7) and 49.44% (486) of them were female with the mean ± SD age of 15.8 ± 1.2 (range: 13.8–19.8). Mean ± SD SBP of the students was 110.27 ± 11.44 mmHg (range: 80.60–151.3) and the mean ± SD DBP was 71.76 ± 8.61 mmHg (range: 49.3–105). Also, mean ± SD weight and height were 59.33 ± 13.3 (range 33.7–122.9) and 165.2 ± 7.8 (rang 138–189), respectively.Averages of SBP and DBP of the students in terms of gender, body mass index, parents' education level, physical activity, and student's education level are presented in Q statistic curves for L, M, and  S were within −2 and +2, and the detrended Q-Q plot indicated that the population was approximately normal. Figures After completion of the study the standard percentiles of BP were estimated for students of Jahrom city in both genders. The model was considered a good fit as per the shape of the worm plot; the Hypertension in adults could result in various complications imposing financial and nonfinancial burdens to individuals and societies . HyperteAccording to the results of this study average of SBP among the male students was 5.2 mmHg more than females, whereas the average of DBP among females was 2.5 mmHg more than males. Results of the studies that have evaluated the relationship between gender and BP are very different. Whereas many studies, such as Nielsen and Andersen in Denmark , Al-SendOn the other hand results of some studies such as de Rezende et al. in Brazil  and AtaeMany similar studies, in line with our findings, have confirmed a direct relationship between BMI and BP. Studies of Ribeiro et al. in Portugal , He et aFindings of this study suggested that there was no significant correlation between regular physical exercise and average of SBP and DBP among adolescents. Similar studies which have been done in this area have found conflicting results. Study of Strazzullo et al.  in AustrThis study showed that average of SBP and DBP of students was indirectly associated with the education level of parents, so that average of blood pressure was higher among the students whose parents had lower education levels. It is believed that parental education level is correlated with healthy dietary pattern and life style of students. Consumption of salt, sugar, and cooking oils which contain polyunsaturated fatty acids is higher among the families with lower health knowledge. This kind of nutrition pattern as well as lack of enough attention to regular appropriate physical activity could lead to hypertension in children and adolescents. Also it is assumed that some parents with lower educational level consider their children's overweight and obesity as a sign of health which will result in overnutrition of children.Hypertension among children and adolescents that is always asymptomatic is a leading risk factor of cardiovascular diseases in adults. Therefor detection and control of high blood pressure in this period are considered as an appropriate preventive approach to reducing complications in adults.Findings of this study indicated that different factors are associated with average of blood pressure in students. Body mass index is one of the main factors that is influenced by various determinants such as nutrition pattern, physical activity, and also heredity. Intervention strategies should focus on the most important factors that have been determined through these kinds of studies.


Results: There were insignificantly reduced MMP-9levels of patients vs. controls, however, there was significant increase in MMP-9 levels associated with CC genotypes for(C-1562T) polymorphism compared with CT genotype (p=0.01). We found that at MMP-9 base position-1562, the frequencies of the genotypes CC and CT in Children on HD were 71.4% and 28.6% respectively while all our controls were of the CC genotype. The alleles frequencies of C and T in patients were 85.7% and 14.29% as compared to 100% and 0%, respectively in the controls. Significant decrease in vitamin D was observed in children on HD versus that in controls (p=0.008). Serum MMP9 levels and age were variables that were independently associated with CVD. Conclusions: MMP9 genetic polymorphism (C-1562T) affects MMP9alterations in ESRD children on HD and vitamin D deficiency is common in our HD pediatric patients who require attention in accordance with current practice guidelines. They probably require supplementation with higher doses of cholecalciferol.Background and objectives: Data concerning the concentration of matrix metalloproteinase-9 (MMP-9) and its functional polymorphisms in chronic kidney diseases (CKD) are conflicting. The present study aimed to evaluate the levels of MMP-9in children with end stage renal diseases (ESRD) on hemodialysis (HD) and to explore its association with MMP-9 polymorphism and vitamin D levels as an important risk factors for cardiovascular diseases (CVD). Methods: We studied 55 children with ESRD on hemodialysis and 18 healthy children served as controls. MMP-9 and vitamin D levels were measured by ELISA in serum of all patients and controls. Genotypes for MMP-9 polymorphism(C Patients with chronic kidney disease (CKD) and on hemodialysis (HD) treatment are at higher dramatic cardiovascular risk than the general population . Even miMatrix metalloproteinase (MMPs) are structurally related, zinc dependent proteins that disrupt the ECM and other non-ECM related substances . They arMMP-9 activity is highly dependent on its expression level , and fun-1562T (rs 3918242) polymorphism in the promoter region is of special interest.The MMP-9 gene has three major polymorphisms in the promoter, coding and untranslated regions . Of thesVitamin D is obtained from both the diet and upon exposure to ultraviolet light .Precursors of vitamin D2 or D3 are hydroxylated in the liver to form 25-hydroxyvitamin D [25(OH) D]. A second hydroxylation occurs primarily in the kidney, leading to formation of 1, 25-dihydroxyvitamin D  . Calcitriol regulates intestinal absorption of calcium, bone resorption, and renal excretion of calcium and phosphate. Significant alterations in renal function, such as those found in CKD, result in decreased activity of renal 1-alpha-hydroxylase , leadingin vitro studies indicate that vitamin D down-regulates MMP-9 production by TNF-α  D] concentration and serum inflammatory biomarkers. Low 25(OH) D concentrations are associated with elevated tumor necrosis factor-alpha (TNF-α) concentrations , and ranby TNF-α  and suppby TNF-α -25. Moreby TNF-α . Previouby TNF-α , 28.-1562T) and vitamin D levels in these children.The data on MMP-9 concentrations and its functional polymorphism in CKD patients are scarce and contradictory and concerns only adults. This study was undertaken to evaluate the level of MMP-9 in children with end stage kidney diseases (ESRD) on HD and to explore its association with functional MMP-9 polymorphism, children’s hospital, Cairo University were included in the study. Etiology of ESRD was as follows: hereditary nephropathies in 17 patients, obstructive uropathies in 13, glomerulopathy in 9, renal hypoplasia or dysplasia in 5, metabolic causes in 3 and was unknown in 8 cases. All patients were dialyzed using a polysulfone dialyzer, with bicarbonate dialysate, using a blood flow rate of 80-150 ml/min and are dialyzed 3 times per week using polysulfone membranes. The dialysate fluids were prepared from concentrated salt solutions and from bicarbonate powder in sealed containers. As recommended by the FDA, the water purification system combines a double softener with a double granular charcoal filter and a double reverse osmosis module in series. Inclusion criteria included children on regular HD treatment for not less than 4 months, using bicarbonate dialysate and free from apparent acute illness. Patients with severe illness or acute medical events were excluded.Patients had taken routine medications in a dialysis unit for at least 3 months, such as phosphate-binding agents, calcium carbonate (35 patients (81.40%), 500 mg/tablet  at a dose of 500-4000 mg/day, or calcium acetate (8 patients (18.60%), 500mg/tablet  at a dose of 1500-2000 mg/day. Patients with parathormone (PTH) level greater than 100 pg/ml or hypocalcaemia received daily rocaltrol (38 patients (88.37%), at a dose of 0.25-2 µg/day. Antihypertensive medications taken by the patients were as follows: calcium channel antagonists (n=36), angiotensin converting enzyme inhibitors (n=24) and B-blockers (n=6). Medication compliance was checked by questionnaires and re-enforced at each dialysis unit. An EPO 750-9000 IU/week, subcutaneous injection was administered to maintain hematocrit between 28% and 31%. Eighteen healthy age- and gender-matched children were recruited from the pediatric clinic of the National Research Centre (NRC) to serve as controls. Written consent was obtained from the parents of each patient. The study was approved by ethical committees of both NRC in Egypt and CPNT, Children hospital, Cairo University. All patients were subjected to full history taking and thorough clinical examination.We studied the prevalence of vascular disease in children with CKD according to the following criteria .Cardiac disease: the presence of primary dilated cardiomyopathy previously diagnosed clinically and by echocardiography.Peripheral vascular or cerebral vascular diseases: Cerebral vascular disease was suspected on clinical grounds, that is, rapidly developing signs of focal disturbance of cerebral function such as hemiparesis and hemi-sensory impairment. The diagnosis was confirmed by computed tomography or magnetic resonance imaging. Brain hemorrhage and subarachnoid hemorrhage were excluded.A patient was considered to have a vascular disease when at least one of these two defined vascular disease was present.A peripheral blood sample was obtained prior to the hemodialysis session from the venous part of the arteriovenous fistula using a specially selected disposable plastic syringe. The 3 ml blood was divided into 2 ml to be centrifuged and 1ml blood sample on EDTA for gene analysis. The 2 ml blood sample was transferred to a sterile plastic vaccutainer tube and then immediate centrifugation was done for 10 min at 5000 rpm at 4°C and the one on EDTA was stored at -20°C should be analysed within 6 mothns .If later analysis will be done the samples must be frozen at -70°C.All biochemical parameters were measured for all patients using an automatic biochemistry analysis. Serum 25-hydroxyvitamin D level was measured by ELISA  Patients were labeled vitamin D insufficient if the levels were between 20 and 30 ng/ml, and deficient if the levels were less than 20 ng/ml. We also subcategorized these patients to severe vitamin D deficiency if the level was less than 10 ng/ml.Serum MMP9 was measured by ELISA .-1562T) polymorphism was done for only 28 patients and 18 healthy controls because these were the available numbers of EDTA samples, also the SphI (Fermentas) enzyme used for digestion of PCR products digests only 10 samples and the budget of the research was not enough to analyze more cases.MMP9 gene analysis for the according to manufacturer’s instructions. DNA was stored frozen at −20°C until processed.DNA concentration was determined by Nano Drop 2000 c Spectrophotometer (Thermo Fisher) and diluted as100 ng/μl .Genomic DNA was amplified using polymerase chain reaction (PCR), amplification was carried out on a Veriti thermal cycler Applied Biosystems, USA, in a 25 μl reaction mixture containing 200ng genomic DNA, 12.5 μL master mix using Taq DNA Polymerase (Applied Biosystems), 5 p mol each primers 5′-GCC TGG CAC ATA GTA GGC CC-3′ (sense) and 5′-CTT CCT AGC CAG CCG GCA TC-3′ (antisense). Samples were initially denatured at 95°C for 3-min, followed by 35 cycles of 95°C for 1-min, 65°C for 45-s, 72°C for 45-s, and a final extension step of 72°C for 7-min. PCR products were analyzed by 1.5% agarose gel electrophoresis, stained with ethidium bromide and a fragment of 435 bp was visualized in ultraviolet transilluminator (Biometra).PCR products were digested with SphI (Fermentas) in a volume of 20 μL containing Digestions were made in a thermal cycler plate at 37°C. Finally, the optimal digestion parameters selected were 1 μg DNA and 1 U enzyme during 2-h of incubation. Fragments were separated in agarose 1.5% stained with ethidium bromide. The C allele was not cut by SphI giving a fragment of 435 bp and the T allele was cut into fragments of 247 and 188 bp.SPSS for Windows, version 15.0 computer program was used for statistical analysis. Data are represented as the mean ± SD and as frequency and percentages accordingly. A p value of less than 0.05 was considered statistically significant. The t--test was used to compare between 2 independent means. Chi-square and Fisher’s exact tests were used to compare between independent proportions. Pearson correlation coefficient “r” was used to measure the linear relationship between different continuous variables. Multiple regression analysis was performed to assess the influence of risk factors on CVD and binary logistic regression was performed to assess the influence of MMP-9 alleles on CVD. Power analysis was used to calculate the minimum sample size required to accept the outcome of a statistical test with a particular level of confidence. A sample size of 20 will give us approximately 80% power  to reject the null hypothesis of zero correlation. We used power calculations performed by the Power and Precision program (Biostat) to determine the number of chromosomes required to detect a significant difference between the polymorphism frequency in the reference population and the expected frequency. Power commonly sets at 80%; however, at that level, a polymorphism would be missed 20% of the time. The Hardy- Weinberg equilibrium (HWE) assumption was assessed for case and control groups by comparing the observed numbers of different genotypes with those expected under HWE for the estimated allele frequency and comparing the Person goodness-of-fit statistic with a 2 distribution with 1 degree of freedom.P=0.01). We also noted a significant increase in creatinine (P=0.0001), cholesterol (P=0.0027), triglycerides (P=0.0001), and significantly decreased HDL-cholesterol levels (P=0.0001) in patients vs. controls. MMP-9 levels were insignificantly reduced in patients as compared to controls. SD was greater than the mean value of Alkaline Phosphatase for the patients group and the TPC group in Table P=0.0085).Detailed characteristics of patients and controls are shown in Table ol P=0.007, triglyThe characteristics of the patients by vascular access type are summarized in Table -1562T gene polymorphism in patients and controls is displayed in Table P=0.3 for both genotypes and alleles).The distribution of genotypes and alleles of MMP-9 C-1562T polymorphism, we had statistically significant increase in MMP-9 levels in CC genotypes patients compared to CT genotypes patients (P=0.01) as shown in Table As the patients were divided according to the genotypes for the Cp=0.97) or vitamin D  .The correlation between vitamin D and MMP-9 levels with different variables in HD patients are shown in Table .There isP=0.023) and age . (Table P=0.05).Multiple linear regression analysis demonstrated that the risk factors for CVD in patients on HD were serum MMP9  bear an overwhelming risk of CVD . The vaset al  in each group because of not experiencing the following conditions; mutation, immigration /emigration, natural selection or sexual selection.et al  D status to myopathy and adverse cardiovascular outcomes and also to the rate of progression of renal insufficiency in CKD -44. In tet al . Serum MMP9 levels and age were variables that were independently associated with CVD. Our findings also suggest that vitamin D deficiency is common in our HD pediatric patients and they probably require supplementation with higher doses of cholecalciferol Further studies on supplementation are recommended to define optimum dose schedules.Conclusion, our findings support the concept that MMP-9 genetic polymorphism affects MMP-9 changes in ESRD patients on HD. Where ESRD patients with CC genotypes for the C


The complex interplay between obesity and hypertension has been a matter of interest and debate for a long time. In the last decade several new insights into the pathophysiology linking obesity and hypertension have led to a better understanding of the mechanisms that beneath this association: insulin resistance, activation of the renin-angiotensin-aldosterone system (RAAS), dysfunctional adipose tissue and deregulated synthesis of adipokines, increased activity of the sympathetic nervous system, overproduction of inflammatory cytokines and obstructive sleep apnea are among some of these factors . TogetheIt is also worthwhile to note that obesity is one of the most frequent causes of resistant hypertension, and identification of major hemodynamic abnormalities may help shorten the time to achieve blood pressure control and reduce global cardiovascular risk .While invasive procedures are not adequate for ambulatory patients, non-invasive monitoring may be easily implemented using accurate and reproducible techniques like impedance cardiography . Previou2) and respective grades: grade 1 with BMI between 30 and 34.9 Kg/m2, grade 2 with BMI between 35 and 39.9 Kg/m2 and grade 3 with BMI ≥ 40 Kg/m2. The study was approved by the Ethics Committee of Centro Hospitalar de Lisboa Central. All patients had been diagnosed with primary hypertension and no cases of secondary hypertension were included. All the patients selected had on the day of the exam AP > 100/60 mmHg under anti-hypertensive treatment; as we only based in one ICG exam per patient we excluded the one’s that at the time of the test were hypotensive, mostly because they might develop hemodynamic adaptation to lower levels of AP. Uncontrolled AP was defined as systolic AP ≥ 140 mmHg and/or diastolic AP ≥90 mmHg on the day of examination. Limitations for ICG were also observed and patients with severe aortic insufficiency, permanent pacemakers, atrial fibrillation and ventricular extrasystole were not included in this analysis. Even if the situations of high BMI may constitute a technical limitation to the ICG test, we did not exclude patients with grade 3 obesity. In the literature we can see that the ICG test is not extensively validated in patients whose weight is above 342 pounds [We performed a retrospective analysis of 202 patients who attended our Hypertension Clinic and performed an ICG test for one of the two following clinical criteria: as part of the initial work-up at the Hypertension Clinic or follow-up of variations in hemodynamic variables after adjustments in anti-hypertensive therapy. All the patients were followed at our department, agreed to perform the exam and gave informed consent to participate. The exam was performed as outpatients and the ICG exams were not selected based on any time frame. Definition of obesity was based on World Health Organization criteria  was defined as (10 x supine stroke volume)/ supine pulse pressure and systemic arterial compliance index (SACI) as (10 x supine cardiac index)/ supine pulse pressure. A SACI < 0.1 suggested arterial stiffness.http://www.euro.who.int/en/health-topics/noncommunicable-diseases/obesity/data-and-statistics) for the prevalence of overweight and obesity for European Union countries of 30–70% and 10–30%, respectively, we saw that in our sample the proportion of overweight (38%) and obesity (37%) was very similar, not approximating the distribution of BMI in the population, reason why we performed weight adjustment of the variable BMI. Statistical analysis presents values for the different hemodynamic variables for “normal weight”, “overweight” and “obesity” and also for the three grades of obesity. T-test was used to compare “non-obese”  and “obese patients” and obese patients with “controlled” and “uncontrolled hypertension” . Finally, using logistic regression analysis analysis and weight-adjusted hemodynamic variables  we searched for predictors of uncontrolled hypertension in obese patients. The level of significance was defined to p < 0.05.Considering sample size and distribution of patients through the different categories of weight classification, with under-representation of patients with grade 2 and 3 obesity, we performed weight adjustment using SPSS 17 . With this statistical approach we aimed to correct for the lack of representativity of specific patient groups, namely patients with grade 2 and 3 obesity. Considering also estimates from the World Health Organization (2: 46 patients (22.7%) had BMI between 20 and 24.9 Kg/m2, 78 (38.6%) between 25 and 29.9 Kg/m2 and in 75 patients (37.1%) BMI was ≥30 Kg/m2. According to gender the average values of BMI were 28.5 ± 4.5 Kg/m2 for men and 29.5 ± 5.4 Kg/m2 for women (p < 0.001). Seventy one patients (35.1%) had systolic AP ≥140 mmHg and 45 patients (22.3%) diastolic AP ≥90 mmHg. BMI correlated with diastolic AP  but the association was stronger for systolic AP . There was also a positive correlation between obesity and uncontrolled AP , although this correlation was weak.One hundred patients were male (49.5%) and average age 54.6 ± 13.9 years. Average systolic and diastolic pressures were 136.5 ± 22.4 mmHg and 82.9 ± 5.1 mmHg, respectively. The average BMI was 28.9 ± 5.1 Kg/mNo adverse effects secondary to the ICG procedure were reported.p > 0.05) between normal weight and overweight patients we observed that differences became more pronounced with increasing BMI. In this way, when comparing non-obese  with obese we observed an increase in CI (p < 0.001), LCWI (p < 0.001) and SVRI (p < 0.001) but reduction in SACI (p < 0.001) (Table Table 1) Table .Table 1VHowever, we also noted that these variations were neither progressive throughout the 3 grades of obesity nor statistically significant and, even if we observed an increase in stroke volume and cardiac output with increasing BMI, these changes reflect mainly a greater body surface area and inherently a physiological larger cardiac output. Besides, the small number of patients with grade 3 obesity limits the interpretation of these variations throughout the three grades of obesity (Table p < 0.001), CI (p < 0.001) and SVRI (p < 0.001) (Table p < 0.001) and LCWI (p < 0.001). In multivariate analysis (Table To further characterize AP in obese patients and hemodynamic factors associated with poor blood pressure control we searched for differences between patients with controlled and uncontrolled HT (≥140/90 cut-off) using only weight-adjusted variables. After univariate analysis we found that uncontrolled obese patients had greater BMI . The differences were significant between non-obese and obese and became even more pronounced when the cut-off ≥140/90 mmHg was established. In this regard, decreasing SVRI, which is an indirect measure of cardiac afterload, should be part of the anti-hypertensive regimen using agents like blockers of the renin-angiotensin-aldosterone system (RAAS) and calcium channel blockers.The SVRI values, with a normal range between 1970 and 2390 Remarkably, however, SVRI was not predictive of uncontrolled HT in the obese patient in multivariate analysis. Although it is expected that vasoconstriction contributes to high levels of blood pressure, several reasons may explain why we didn’t observe that in our cohort: the increase in AP levels was not paralleled by the increase in SVRI and the absence of knowledge on current anti-hypertensive medication, specially with drugs that interfere with arterial tonus, does not to allow to interpret the heterogeneity of SVRI values found. However, it is also recognized that a blunted reduction of peripheral resistance, despite the increased stroke volume and CI, is a common finding in obesity , 16 thatConsidering SACI, we observed lower levels in the obese hypertensive, especially in the patients with uncontrolled AP and, in multivariate analysis, this variable was predictive of uncontrolled AP. Lower levels of SACI, representing an indirect measure arterial stiffness, were associated with greater risk of blood pressure ≥ 140/90 mmHg. Considering that SACI results from the ratio of CI and pulse pressure it is reasonable to expect, especially in those with higher levels of blood pressure, higher values of pulse pressure and, concomitantly, lower levels of SACI.2. Nevertheless, variations of TFC may be very sensitive and consistent with volume expansion [It is also worthwhile to note that obese patients, in general, and those with uncontrolled blood pressure had lower values of TFC. Although these data do not point to hypervolemia as a determinant factor to high blood pressure in this cohort, the absence of data concerning use of diuretics limits the interpretation of these values. In the model of multivariate analysis we didn’t included this variable, as expressed in Kohm and not adjusted to body surface area, doesn’t reflect volume/mxpansion . The usexpansion –21 and axpansion , 23.There are limitations to this work since its retrospective nature and several relevant data missing. One of the most important in this context concerns information on current anti-hypertensive medication on the date of the ICG examination, which we were not able to fully collect due to technical problems concerning data archives and lack of data on waist circumference and abdominal obesity. BMI, although reflecting weight excess and being the basis for obesity grading, does not allow to identify patients with predominantly central adiposity. The evidence in the literature regarding the pathogenic role of abdominal fat is vast and the contribution of insulin resistance, oxidative stress and deregulated synthesis of hormones by adipose tissue for cardiovascular disease is well documented –28. In oIn obese patients, trends in CI and SVRI are clearly distinct from the one’s we found in lean subjects (which presented a predominance of increased SVRI in spite of CI) and it would be important to investigate if central obesity is associated with extreme values of the considered hemodynamic variables or, in alternative, with variations in other parameters that would impose changes in anti-hypertensive therapy. It should also be mentioned that when considering abdominal obesity, in addition to waist circumference, other elements should also be taken into consideration, namely the differential composition of abdominal fat  and the proportion of fat-free mass. While some studies support the importance of fat-free mass as a major determinant of the variations in SV and CO to accomplish with greater metabolic demands in the obese patient , 29 otheIt is also important to refer two other limitations: first, patients with cardiac arrhythmias were excluded from this study and, in the general hypertensive population they represent a large proportion of patients. In this regard, as the study of hemodynamic in this specific subset is unreliable with ICG, non-invasive determination of CI and SVRI is compromised in these patients. Second, when classifying patients with controlled versus uncontrolled HT we based exclusively on the values of AP obtained in the day of examination. Information about number of medications in each group, time of follow-up in the Hypertension Clinic or time to achieve blood pressure control would better describe the differences between the two groups.Tailored anti-hypertensive therapy for the obese patient should focus in the balance between CI and SVRI in each patient. In our cohort, anti-hypertensive drugs aimed to modulate cardiac index, mainly beta-blockers, and decrease SVRI like inhibitors of the RAAS and calcium channel blockers seem the most appropriate to control blood pressure. Increased levels of CI contribute to higher risk of uncontrolled HT in the obese, situation in which adjustment of drugs that reduce hyperinotropy may improve and shorten time to blood pressure control.


The metabolic syndrome describes a clustering of risk factors—visceral obesity, dyslipidaemia, insulin resistance, and salt-sensitive hypertension—that increases mortality related to cardiovascular disease, type 2 diabetes, cancer, and non-alcoholic fatty liver disease. The prevalence of these concurrent comorbidities is ~ 25–30% worldwide, and metabolic syndrome therefore presents a significant global public health burden. Evidence from clinical and preclinical studies indicates that glucocorticoid excess is a key causal feature of metabolic syndrome. This is not increased systemic in circulating cortisol, rather increased bioavailability of active glucocorticoids within tissues. This review examines the role of covert glucocorticoid excess on the hypertension of the metabolic syndrome. Here, the role of the 11β-hydroxysteroid dehydrogenase enzymes, which exert intracrine and paracrine control over glucocorticoid signalling, is examined. 11βHSD1 amplifies glucocorticoid action in cells and contributes to hypertension through direct and indirect effects on the kidney and vasculature. The deactivation of glucocorticoid by 11βHSD2 controls ligand access to glucocorticoid and mineralocorticoid receptors: loss of function promotes salt retention and hypertension. As for hypertension in general, high blood pressure in the metabolic syndrome reflects a complex interaction between multiple systems. The clear association between high dietary salt, glucocorticoid production, and metabolic disorders has major relevance for human health and warrants systematic evaluation. The metabolic syndrome describes a concurrence of interrelated abnormalities, including visceral obesity, dyslipidaemia, insulin resistance, and hypertension. Each of these features independently carries significant cardiovascular risk. In combination, the risk is amplified, and all-cause mortality increases: metabolic syndrome predicts the development of type 2 diabetes, cardiovascular disease, cancer, and non-alcoholic fatty liver disease . AlthougMetabolic syndrome is more useful as an epidemiologic tool for analysing cardiovascular risk than it is as a clinical entity requiring specialist management above and beyond management of individual components. For example, hypertension is one of the cardinal features of metabolic syndrome, but the origins of high blood pressure are obscure and lost in the complexity of the syndrome. Clearly metabolic syndrome captures a cluster of pathophysiological features that are individually accepted as “pro-hypertensive”: renal dysfunction and sodium retention , vasculaThis review focusses on covert glucocorticoid excess and the role of local glucocorticoid metabolism by the isozymes 11β hydroxysteroid dehydrogenase types 1 and 2 (11βHSD1 and 11βHSD2). 11βHSD1 and 11βHSD2 are products of distinct genes and members of the dehydrogenase/reductase superfamily. Here, the preclinical and clinical data connecting the activity of these enzymes to blood pressure homeostasis is discussed, concluding by addressing the potential therapeutic relevance to the management of patients with the metabolic syndrome.zona fasiculata of the adrenal cortex in response to ACTH, described as the hypothalamic-pituitary-adrenal axis (HPAA). In peripheral tissues, particularly adipose, liver, skeletal muscle, and kidney, glucocorticoids can be regenerated from inactive 11-keto derivatives  by 11βHSD1  are determined by the balance between synthesis and clearance, and by the high-affinity binding of glucocorticoids to circulating corticosteroid-binding globulin. Glucocorticoids are synthesised in the SD1  suggestive of aldosterone excess and in mice ACTH induces increased renal transcription of aldosterone-response genes such as C, scnn1 . As expeC, scnn1 , but theC, scnn1 , or if pC, scnn1 . In miceC, scnn1 , and in C, scnn1 . GR antaC, scnn1 .11βHSD1 is highly expressed in the key metabolic tissues of liver, adipose, pancreas, and skeletal muscle. The role of 11βHSD1 in metabolism has been extensively studied from a cellular basis in individual tissues through to impact upon an integrated metabolic system •. A consIt is of course challenging to ascribe absolute causality of hypertension in a complex disorder, and several studies show that non-adipose 11βHSD1 activity contributes to blood pressure control. Human genetics studies associate the gain of function rs846910 SNP in the HSD11B1 promotor with blood pressure in non-obese people –45. ThisThe kidney contributes to long-term blood pressure control through the pressure natriuresis, an integrated tubular-vascular response that stabilises extracellular fluid volume . 11βHSD1The mechanistic relationship between increased 11βHSD1 activity and disorders of metabolism provided a strong driver for development of pharmacological inhibitors. Preclinical studies showed that 11βHSD1 inhibitors lower systemic blood pressure in obese spontaneously hypertensive rats . A bloodMineralocorticoid over-activity is often considered a major factor in the hypertension of glucocorticoid excess. Activation of MR by glucocorticoids is normally restricted by the presence in certain cells of 11βHSD2, which convert MR-active glucocorticoids to MR-inactive metabolites. 11βHSD2 is highly expressed in the kidney, defining the aldosterone-sensitive distal nephron, and here, the activity of the enzyme is certainly important for blood pressure control. Congenital or acquired deficiency in 11βHSD2 causes the syndrome of apparent mineralocorticoid excess , presenting with salt retention, potassium wasting, and hypertension .Hsd11b2 expression [Renal 11βHSD2 activity is regulated by glucocorticoids. It is downregulated following adrenalectomy and restored by corticosterone replacement . Such repression . Studiespression  due to dpression . Renal 1pression ••. Thus,pression  and discIn common with other Mendelian disorders, high blood pressure in AME is thought to originate in the kidney . Renal thsd11b2 heterozygote null mice, and salt-sensitive hypertension was prevented by GR blockade with RU486 rather than by MR blockade with spironolactone [Mechanistically, null mutations in HSD11B2, or inhibition of the enzyme by glycerrhetinic acid such as found in liquorice , would polactone , 73. Theolactone . It may olactone . MR and The physiological ramifications of MR/GR interaction are not clear, but it is likely that aldosterone and glucocorticoids normally have mutually reinforcing roles. In a collecting duct cell line, for example, aldosterone activation of MR controls sodium transport during circadian cycles . If aldoConditions associated with increased circulating or intracellular glucocorticoids are common and often associated with hypertension. The metabolic syndrome exemplifies the complexity of glucocorticoid-dependent hypertension: clinical investigation and studies in experimental models demonstrate impairment of all the major homeostatic systems controlling blood pressure Fig. . A unify


To explore the risk factors for rebleeding in acute nonvariceal upper gastrointestinal bleeding patients with high-risk stigmata after endoscopic hemostasis and to develop a new scoring system for them.  A retrospective single-center study was conducted from January 2012 to June 2017. The logistic regression model was used to explore risk factors of poor clinical outcomes. Accuracy of new scoring systems was compared with Rockall score (RS) and Glasgow-Blatchford score (GBS) using receiver operating characteristics curve.  Two hundred nine patients were included. In multivariate regression analysis, systolic blood pressure, endoscopic hemostasis method, hemoglobin, blood urea nitrogen, and serum creatinine were identified as indicators for rebleeding. New scoring systems with 4 variables and 5 variables based on these 5 risk factors were chosen. The 4-variable scoring system outperformed GBS in predicting rebleeding while 5-variable scoring system outperformed RS and GBS in predicting rebleeding significantly. Score 2 was identified as the best cut-off of these 2 scoring systems.  Systolic blood pressure, endoscopic hemostasis method, hemoglobin, blood urea nitrogen, and serum creatinine were all associated with poor clinical outcomes. The new scoring systems had greater accuracy than RS and GBS in predicting rebleeding. Further external validation should be performed to verify the results. Acute upper gastrointestinal bleeding (AUGIB) is a common disease with an incidence of 100 to 180 per 100,000 adults . A systeSeveral scoring systems for ANVUGIB have been developed to assess the risk of patients. Rockall score (RS) is the first established and validated scoring system . The sysThe aim of this study was to explore the risk factors for rebleeding in ANVUGIB patients with high-risk stigmata after endoscopic hemostasis. Then, we aimed to develop new scoring systems for them and compared the new systems with existing systems retrospectively.Data were collected from consecutive patients found to have ANVUGIB with high-risk stigmata and received endoscopic hemostasis over a 5-year period, from January 2012 to June 2017, who were referred to Tongji Hospital in Shanghai, China. The ANVUGIB with high-risk stigmata was defined as spurting, gushing, oozing bleeding or nonbleeding visible vessel in the cases of peptic ulcers and spurting, gushing bleeding or nonbleeding visible vessel in the cases of other diseases.This was a retrospective study including all medical records. Admission history, clinical and laboratory data, endoscopic manifestation, endoscopic hemostasis methods, and clinical outcomes were recorded. All patients were treated with standard supportive treatment, fluid resuscitation, and high-dose acid suppression, 80 mg pantoprazole (iv), after endoscopic hemostasis.The following data were collected for each patient: demographic data, UGIB symptoms, history of UGIB and drug use, vital signs, laboratory results, endoscopic manifestation, endoscopic diagnosis, endoscopic hemostasis methods, and clinical outcome. The RS and GBS were calculated using the collected data for each patient.Among them, laboratory results consist of hemoglobin (HB), blood urea nitrogen (BUN), serum creatinine (Scr), aspartate transaminase (AST), alanine aminotransferase (ALT), and blood glucose.All endoscopic procedures were performed by experienced endoscopist who had experience in endoscopic examination and hemostasis. Endoscopic diagnosis of bleeding was classified into spurting hemorrhage, oozing hemorrhage, and visible vessel. As for peptic ulcer bleeding, the diagnosis was followed as Forrest classification. Endoscopic hemostasis consisted of monotherapy and multiple therapies combined. The monotherapy included thermal hemostasis using argon and mechanical hemostasis using titanium clip while multiple therapies combined was defined as submucosal epinephrine injection plus thermal or mechanical hemostasis. The endoscopic hemostasis methods were chosen based on the endoscopists' judgement.The clinical outcome of the current study was defined as rebleeding after endoscopic hemostasis. Rebleeding was defined as one or more signs of bleeding after primary bleeding stopped, including fresh hematemesis or hematochezia, melena with instable vital signs, or reduction in hemoglobin levels by 3 g/dL or more.http://www.medcalc.be).All analyses were performed using R language version 3.1.1 and MedCalc version 11.4.2.0  was used to identify independent indicators of the poor clinical outcomes. Continuous variables were converted into ordinal categorical variables based on quartile.To explore the risk of poor clinical outcomes for clinical data, the factors whose Then, the continuous variables were also converted into unordered categorical variables based on quartile in order to determine the risk of poor clinical outcomes for each quartile of laboratory data. The binary logistic regression analysis was applied with the lowest quartiles as reference. Model 1 was unadjusted. Model 2 was adjusted for risk factors obtained in final multivariate model for each clinical outcome.The scoring systems were made using all combinations of risk factors obtained. The cut-off of each laboratory data was identified using the intersection of the best 5 cut-offs for each clinical outcome. The best cut-off was based on Youden's index.The accuracy of the scoring systems to predict clinical outcomes was evaluated by receiver operating characteristics curves (ROC) with 95% confidence intervals. The areas under ROC curves (AUC) were compared using chi-square tests according to the method described by Delong et al. .P values were two-sided with P < 0.05 defined as statistical significance.All reported -three males and 36 females were studied, whose median age was 58. For the clinical outcomes, 38 patients bled one or more times after primary bleeding stopped and 44 patients had requirement of blood transfusion. Duodenal ulcer and gastric ulcer were the main causes of ANVUGIB. For endoscopic hemostasis, 172 patients accepted monotherapy consisting of 101 mechanical hemostasis and 71 thermal hemostasis. Thirty-seven patients received multiple hemostasis combined.A total of 209 patients were included in the study. As demonstrated in μmol/L, respectively. As for HB, the best 5 cut-offs for rebleeding were around 75 g/L or 85 g/L. Calculating the sensitivity and specificity of both cut-offs, the results showed too low sensitivity in cut-off 75 g/L (rebleeding sensitivity/specificity 0.47/0.86) and cut-off 85 g/L has better result (rebleeding sensitivity/specificity 0.58/0.75). Thus, HB < 85 g/L was finally selected as cut-off value. All of these 5 factors were weighted equally for simplicity.Totally, 5 factors were included in our new scoring systems based on the final multivariate regression model. The cut-off of continuous variables including HB, BUN, and Scr was identified using the intersection of the best 5 cut-offs based on Youden's index for each clinical outcome . In ordeμmol/L; BUN > 9.5 mmol/L; HB < 85 g/L; monotherapy) and 5-variable  scoring systems were the best score for predicting rebleeding. The cut-off 2 in 4-variable scoring system provided the high sensitivity (rebleeding 94.7%) and patients with score 0 had no risk for rebleeding. The cut-off 2 in 5-variable scoring system provided high sensitivity (94.7%) while patients with score 0 had no risk for rebleeding either.A total of 31 combinations were created and AUC of each was calculated. Among them, the set of variables (from 1 to 5) that yielded the highest AUC value is shown in P = 0.049) while 5-variable scoring system (AUC 0.79 (0.72–0.86)) outperformed both RS (P = 0.046) and GBS (P = 0.021) significantly ) performed as well as RS (AUC 0.70 (0.61–0.79)) and outperformed GBS (AUC 0.71 (0.62–0.8)) significantly  group and BUN (≤6.5 mmol/L) group in predicting rebleeding, but BUN (> 10 mmol/L) group had increased hazard of rebleeding. Moreover, Scr was not included in GBS, but it is really a key indicator for poor clinical outcomes. As an ordinal categorical variable, Scr was independent predictor for rebleeding in multivariate regression. As an unordered categorical variable, Scr (≥94 μmol/L) group had several risk of poor clinical outcomes compared with Scr (<94 μmol/L) group. After integrated analysis of logistic regression model and the best 5 cut-offs of each laboratory index, we adjusted the cut-off of these 3 laboratory data to most fit and easy-remembered status, which were different from the cut-off in GBS. SBPs were also indicators of patients' condition. A previous trial demonstrated that the shock index, HR/SBP, was independent predictor for high-risk stigmata and endoscopic intervention and the simple score consisting of shock index, BUN/Scr and “no daily use PPI one week before examination”, was superior to GBS [To make the cut-off well remembered and meet the clinical practicality, the cut-off of HB, BUN, and Scr was set as 85 g/L, 9.5 mmol/L, and 100 r to GBS . Howeverμmol/L,” and “Monotherapy”, performed as well as RS and outperformed GBS significantly in predicting rebleeding. Moreover, the cut-off 2 for this scoring system provided very high sensitivity and good specificity in predicting rebleeding. If the intensive treatment was only performed on scores of 2, 3, and 4, almost all of high-risk patients could receive special care to decrease the risk of rebleeding while about 45% clinical resource could be saved. The 5-variable scoring systems, which comprise of 5 variables, “SBP < 90 mmHg,” “HB < 85 g/L,” “BUN > 9.5 mmol/L,” “Scr > 100 μmol/L,” and “Monotherapy”, outperformed RS and GBS in predicting rebleeding. The cut-off 2 provided very high sensitivity in predicting rebleeding, but the specificity was lower than that of 4-variable scoring system. In these 2 scoring systems, the patients with a score of zero could be normally managed as they were less likely to suffer rebleeding after endoscopic hemostasis.The 4-variable scoring system, which consists of 4 variables, namely, “HB < 85 g/L,” “BUN > 9.5 mmol/L,” “Scr > 100 As we know, the difficulty of calculating and distrust led to the factor that doctors were unwilling to use risk score the guidelines recommended for management of UGIB patients. Our simple score, no matter 4 variables or 5 variables were reliable, was easy-remembered and easy-calculated.Despite the good performance of our new scoring systems, there were several limitations. One limitation was the small sample size. The small sample size makes it hard to draw a firm conclusion while many risk factors for clinical outcomes might be covered up. Moreover, the comparison of different endoscopic hemostasis methods such as thermal hemostasis versus multiple therapies combined and mechanical hemostasis versus multiple therapies combined was hard to achieve due to the small sample size. Another limitation is that our study is retrospective single-center clinical trial, which limits its reliability and generalizability potentially.In summary, SBP, HB, BUN, Scr, and endoscopic hemostasis methods were indicators for rebleeding in ANVUGIB patients with high-risk stigmata after endoscopic hemostasis. The 4-variable scoring systems we made were greater than GBS in predicting rebleeding significantly and 5-variable scoring systems we made outperformed RS and GBS in predicting rebleeding. However, larger multicenter prospective studies are needed to validate these conclusions and verify the new scoring systems thresholds that might be suitable for clinical decisions in the future.