Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis.2 and urine albumin:creatinine ratio (uACR) >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin–angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD.UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor–neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but <60 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol.Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized . The mean eGFR was 34.0 mL/min/1.73 mUK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD. Chronic kidney disease (CKD) affects between 2 and 17% of the general population (depending on the country) , 4. ReniThe natriuretic peptide (NP) system is a neurohormonal system that has a variety of potentially beneficial functions, including natriuresis, diuresis, vasodilatation and counterregulation of RAS , 10. TheAs NEPi and ACEi both inhibit bradykinin degradation, their combination is associated with substantially elevated bradykinin levels that cause unacceptable rates of angioedema . ARBs doIn a 5/6 nephrectomy model, treatment with combined NEP/RAS inhibition was associated with greater reductions in proteinuria and glomerulosclerosis compared with RAS inhibition alone , 16. MicThe United Kingdom (UK) Heart and Renal Protection III(HARP-III) trial (ISRCTN11958993) was designed to provide information on the short-term efficacy , tolerability and safety of sacubitril/valsartan among patients with CKD. The trial will also assess the effects of sacubitril/valsartan on albuminuria, blood pressure and biomarkers of kidney and cardiac damage.UK HARP-III is a double-blind, multicentre, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily versus irbesartan 300 mg one time daily among at least 400 participants ≥18 years of age with stages 3 and 4 CKD. Irbesartan 300 mg was selected as the comparator, as it has been shown to reduce the risk of ESRD among patients with diabetic kidney disease and is licensed for the treatment of proteinuric CKD , 21. Par2 with a uACR >20 mg/mmol or eGFR ≥20 but <45 mL/min/1.73 m2 (regardless of uACR). The exclusion criteria were designed to identify patients for whom the safety of sacubitril/valsartan or irbesartan may have been a concern. The full eligibility criteria are shown in Figure To fulfil the inclusion criteria, patients need to be ≥18 years of age and have either an eGFR ≥45 but <60 mL/min/1.73 mAfter relevant ethics [Nottingham Research Ethics Committee 2 (13/EM/0434)] and regulatory approvals had been obtained, sites were established in UK renal units. Site staff identified potentially eligible patients from hospital electronic databases, mailed these individuals an invitation letter and a copy of the patient information sheet and called them ∼1 week later to discuss the trial in more detail, answer any questions they might have and to see whether they were interested in participating. Those individuals interested in participating were invited to attend a screening visit.At the screening visit, eligibility was assessed and written informed consent was obtained from eligible individuals. All data were recorded directly into a bespoke Internet-based electronic case report form system. Relevant details of their medical history  were recorded by trained research nurses and their height, weight and blood pressure were measured. Blood pressure was measured and recorded three times using an Omron M6 automated digital sphygmomanometer after sitting for at least 5 minutes. Willing and eligible patients entered the pre-randomization run-in phase. Samples of blood and urine were sent to the local hospital laboratory for confirmation of eligibility. If the results were considered inaccurate (e.g. haemolysed sample) by the local study staff the samples could be repeated once, but if the results did not confirm eligibility the participant was withdrawn from the run-in phase.51Cr-EDTA technique, although if this was not available at the site, other methods (99mTc-DTPA or iohexol) could be used with the agreement of the coordinating centre. In willing participants, a 24-hour collection of urine for albumin and sodium quantification was also obtained.The aims of the pre-randomization run-in phase were (i) to ‘wash out’ any ACEi prior to introduction of NEPi, (ii) to allow a comparison of the acute effects of the study treatments on GFR and (iii) to reduce the rate of post-randomization discontinuation of study treatment and to produce a consequent improvement in the trial's statistical sensitivity . FollowiParticipants were not eligible for randomization if the mean of their second and third measurements of systolic blood pressure was <110 mmHg (or <130 mmHg with symptoms of hypotension) or if they reported an adverse event they believed to be related to their run-in treatment. Participants who remained willing and eligible were then randomly allocated in a 1:1 ratio to receive either sacubitril/valsartan or irbesartan. Participants were randomized by an Internet-based system using a minimization algorithm to ensure balance of important predictors of renal progression, including age, sex, systolic blood pressure, eGFR, uACR and the presence or absence of diabetes mellitus.At the randomization visit, run-in treatment was collected and willing and eligible participants were issued two bottles of study treatments: one containing sacubitril/valsartan 97/103 mg or placebo tablets and the other containing irbesartan 150 mg or placebo capsules (therefore a double-dummy technique to protect blinding). Participants were initially instructed to take one tablet and one capsule daily in the morning . Blood and urine samples were collected for the local analysis of creatinine, electrolytes, liver function tests and uACR and others were prepared for central analysis  for the remainder of the trial. If relevant, a reason for discontinuation or dose reduction is recorded. Participants prescribed contraindicated medications  have their randomized treatment stopped. Weight and blood pressure are measured (three times after sitting for at least 5 minutes) at all visits. In both treatment groups, blood pressure is to be controlled according to the Kidney Disease: Improving Global Outcomes guidelines , with thAt each follow-up visit, blood and urine samples are sent to the local hospital laboratory for creatinine, electrolytes, liver function tests  and uACR. In addition, at the 3-, 6- and 12-month visits, samples are also taken for central analysis. EDTA samples are centrifuged and the plasma aliquoted into Cryovials, which are stored locally  at or below −20°C prior to transfer to the central laboratory in Oxford, UK, where they are stored at −80°C. The main plasma analytes measured at the central laboratory are creatinine, cardiac and inflammatory biomarkers and the urine analytes include albumin and markers of tubular damage and function  , 26. ComStudy sites were established in 24 renal units in the UK. Between November 2014 and January 2016 a total of 620 patients attended the study screening visits and 566 (91%) entered the pre-randomization run-in  mg/mmol. Central laboratory assays will be conducted at the end of the study. About half of randomized participants had either glomerular [111 (27%)] or diabetic [83 (20%)] kidney disease and 165 (40%) patients reported diabetes mellitus at baseline. The median 5-year risk of ESRD  and the tolerability and safety of the drug compared with irbesartan in people with CKD. The trial will also provide information on the effects of sacubitril/valsartan on albuminuria, blood pressure and other biomarkers of both kidney and cardiac function. These results are important because sacubitril/valsartan has now entered routine clinical practice as a treatment for heart failure with reduced ejection fraction (HFrEF) , and manLarge randomized trials of interventions to slow the progression of CKD are required since currently available treatments do not prevent ESRD in all patients with CKD. Although ACEis and ARBs reduce the risk of progression of proteinuric diabetic and non-diabetic kidney disease, their effect  is moderate. For example, in proteinuric diabetic kidney disease, irbesartan reduced the risk of ESRD, doubling of creatinine or death from any cause by 20% compared with placebo {hazard ratio [HR] 0.80 [95% confidence interval (CI) 0.66–0.97]; P = 0.02}, but this composite outcome still occurred in nearly one-third of those allocated irbesartan (and 14% reached ESRD) during the mean 2.6 years of follow-up –33. NeprMost patients with CKD do not progress to ESRD , but areNEPi has the potential to improve both renal and cardiovascular outcomes among patients with CKD. The UK HARP-III trial will provide important information on the efficacy, safety and tolerability of sacubitril/valsartan in people with CKD. Results are anticipated in 2017.Supplementary DataClick here for additional data file.


The incidence of obesity is increasing worldwide, especially in countries with accelerated economic growth. We determined the prevalence of and associations between overweight/ obesity and cardiovascular risk factors in pre-pubertal (seven- to 11-year-old) schoolchildren  in Luanda, Angola. Biochemical (fasting blood) and clinical examinations were obtained in a single visit. Data are reported as prevalence  and association .Prevalence of overweight/obesity was 17.7% (12.4–23.0%), high blood pressure (BP < 90% percentile) was 14.6% (9.7–19.5%), elevated glucose level was 16.7% (11.5–21.9%) and total cholesterol level < 170 mg/dl (4.4 mmol/l) was 69.2% (62.8–75.6%). Significant associations between body mass index (BMI) and systolic and diastolic BP  were found. No association between BMI and elevated glucose or cholesterol levels was found.The prevalence of cardiovascular risk factors was high in pre-pubertal schoolchildren in Angola and fat accumulation was directly associated with blood pressure increase but not with other cardiovascular risk factors. Cardiovascular disease (CVD) is the leading cause of death worldwide. Although its most overt manifestations, such as hypertension, myocardial infarction and stroke, appear more frequently in adulthood, there is growing evidence that the risk factors for these events can appear precociously in the course of life, even in childhood.1-3 Some studies suggest that the pathophysiological processes leading to the onset of CVD in earlier phases of adult life could be detected as early as the foetal period.46Hypertension and obesity are two cardiovascular risk factors with a high prevalence in the adult population in virtually all countries. Their incidence is occurring at increasingly younger ages; today, these conditions affect a significant proportion of children and adolescents.71113Obesity in adults has become a global pandemic, affecting both developed and developing countries.Following the overweight and obesity pandemic, an increased incidence of hypertension, type 2 diabetes and dyslipidaemia is to be expected.14The prevalence of dyslipidaemia in children and adolescents worldwide varies between 2.9 and 33%, depending on the cut-off points used and the age range of individuals included in the study.1619Obesity and cardiovascular risk factors tend to increase in countries with rapid economic and social transformation. Angola is an African country that has experienced rapid economic growth over the last 15 years, following the end of the civil war. However, no existing studies have examined cardiovascular risk in Angolan children. Therefore the aim of this study was to determine the prevalence and severity of cardiovascular risk factors in pre-pubertal schoolchildren in Luanda, Angola, and to determine the contribution of excessive body weight to these findings.A cross-sectional, observational and descriptive study was conducted in a sample of children enrolled in the first cycle of primary education in a public school in Luanda, the Angolan capital. The project was carried out after obtaining authorisation from the Provincial Directorate of Education, the Education Chamber of Rangel municipality and the directors of the school 5008 (Our Lady of Light).Consent for the involvement of the community in the study was obtained in meetings with the school staff, parents and/or guardians of the children and the children to clarify the study purposes and methods. The project was approved by the Independent Ethics Committee on Research of the Faculty of Medicine of Agostinho Neto University, following the standards procedures in human research in accordance with the Declaration of Helsinki.In the 2011 academic year, 1 015 students (aged five to 12 years) were enrolled in the Our Lady of Light school and 719 (70.8%) were eligible for the study (seven to 11 years). This school was chosen because it is near the Faculty of Medicine, where data were collected and because it is located in a neighborhood with most of the families belonging to the middle class.After meeting with parents or guardians, we sent an envelope containing an invitation letter and a questionnaire to a random subsample of 290 students. The questionnaire required completion for information on the conditions of birth and the child’s life, including pregnancy history, birth weight, period of exclusive breastfeeding, self-reported diseases, and sociodemographic information of the family. Information about birth weight and the duration of exclusive breastfeeding in addition to signing of the consent form were necessary for final inclusion in the project.Of the 290 questionnaires distributed, 248 (85.5%) were returned. Eleven children were excluded due to lack of essential information. Of the 237 selected, 23 did not appear at the venue for the examination. The set of examinations to investigate the presence of cardiovascular risk factors was performed on 214 children.All children were classified according to the Tanner scale,All study participants presented to the Laboratory of Functional Tests and Physiology of the Faculty of Medicine on a pre-scheduled morning in a fasting condition (10–14 hours). Examinations were performed from June 2012 to November 2013. A previous pilot study (March 2012) was performed on 30 children (not included in this study) to standardise the protocol and to train examiners. Sociodemographic data , physical activity and dietary habits were obtained in an interview with the child and the mother or guardian.Blood was collected by venipuncture of the forearm and processed on the same day by the Department of Biochemistry (Faculty of Medicine) to determine glucose, urea, uric acid, creatinine, total cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels. Only reagents of BioSystems SA  were used. Low-density lipoprotein (LDL) cholesterol concentration was calculated by the Friedewald formula for triglycerides < 400 mg/dl (4.52 mmol/l).Biochemical variables in the blood were classified according to the criteria established by the American Academy of Pediatrics and the American Heart Association .total cholesterol < 170 mg/d (< 4.4 mmol/l): acceptable; 170–199 mg/dl (5.15 mmol/l): borderline; ≥ 200 mg/dl (≥ 5.18 mmol/l): highLDL cholesterol < 110 mg/dl (< 2.85 mmol/l): acceptable; 110–129 mg/dl (2.85–3.34 mmol/l): borderline; and ≥ 130 mg/ dl (≥ 3.37 mmol/l): hightriglycerides (0–9 years) < 75 mg/dl (< 0.85 mmol/l): acceptable; 75–99 mg/dl (0.85–1.12 mmol/l): borderline; ≥ 100 mg/dl (≥ 1.13 mmol/l): hightriglycerides (10–19 years) < 90 mg/dl (< 1.02 mmol/l): acceptable; 90–129 mg/dl (1.02–1.46 mmol/l): borderline; and ≥ 130 mg/dl (≥ 1.47 mmol/l): highHDL cholesterol < 45 mg/dl (< 1.17 mmol/l): acceptable; 40–45 mg/dl (1.04–1.17 mmol/l): borderline; and < 40 mg/dl (< 1.04 mmol/l): low.21According to fasting blood glucose criteria, the children were classified as normoglycaemic (60–99 mg/dl) (3.33–5.49 mmol/l), glucose intolerant (100–125 mg/dl) (5.55–6.94 mmol/l) or hyperglycaemic (< 125 mg/dl) (< 6.94 mmol/l). No child was on treatment with insulin or oral hypoglycaemic agents.Body weight was obtained using a digital electronic scale  with 0.1-kg precision while fasting and after voiding. Children were barefoot and clothed with undergarments only. Height was measured using a fixed stadiometer with 0.5-cm precision. The child was placed on the central part of the scale platform with heels together, head and buttocks resting against the stadiometer and eyes looking toward the Frankfurt horizontal plane.2). Percentiles (P) of height, weight and BMI of each child were calculated as presented in https://www.bcm.edu/bodycomplab/.23The body mass index (BMI) was calculated by dividing body weight by height squared  and olecranon process . The waist (WC) and hip circumferences (HC) were measured with an inelastic tape with the child in a standing position and at the end-expiration phase. Measurements (0.1- mm precision) were obtained in front of a mirror to facilitate the tape positioning in the horizontal plane. WC was measured at the midpoint between the lower edge of the rib cage and the anterior superior iliac crest. HC was measured at the level of the great trochanter, circling the hip on the most prominent point between the waist and the thigh. The waist-to-hip ratio (WHR) was obtained by dividing WC by HC. The thickness of four skinfolds  was measured with a manual caliper (Sanny) with a precision of 1 mm.Body composition was obtained by tetrapolar bio-impedance with the Maltron BioScan Analyser . Two electrodes were placed on the dorsal surface of the radiocarpal joint and metacarpal of the right hand and the other two on the dorsal surface of the right foot  according to the manufacturer’s instructions. Body fat and percentage of body fat were used to indicate overall obesity.Blood pressure was measured with an automatic sphygmomanometer  in the sitting position in a comfortable room and after bladder emptying. The cuff size was chosen according to the circumference of the child’s arm and the manufacturer’s recommendation. Three measurements were taken on the left arm at two-minute intervals after a five- to 10-minute resting period. The forearm was supported on a flat surface at nearly 120° with the arm.Resting systolic (SBP) and diastolic blood pressure (DBP) and heart rate (HR) were determined as the arithmetic mean of the last two measures. Pulse pressure (PP) was calculated as the difference between SBP and DBP. The mean arterial pressure (MAP) was calculated from the formula [SBP + (2 × DBP)]/3. The blood pressure percentile was determined using available software (https://www.bcm.edu/bodycomplab/), which accounts for the gender, height and age of each child.Blood pressure was classified according to the WHO criteria.Continuous variables are expressed as mean ± standard deviation when normally distributed or as median and interquartile range when the normal distribution model was not accepted (Kolmogorov–Smirnov test). Comparison of two means was done with the Student’s t-test for normal variables, and comparison of two medians was performed with the Wilkinson test. The comparison of proportions of categorical variables in two or more groups was performed using the chi-squared test. Comparison of means in three or more groups was performed by one-way ANOVA followed by the post hoc Tukey’s test. The degree of association between continuous variables was obtained with Pearson’s correlation coefficient (r).A multivariate analysis (stepwise forward procedure) was used to indicate independent predictors of systolic and diastolic blood pressure. Gender, birth weight, age, height, body weight, body mass index, absolute and relative fat mass and lean mass  were included in the model as predictors. Co-linearity variables were automatically excluded from the model. Statistical analyses were performed using SPSS for Windows, version 20.0. The significance level for all tests was set at p < 5%.It can be observed  that mosWhile all biochemical variables were unaffected along BMI categories, except for triglycerides, which showed higher values in the obese group, a different pattern was observed in relation to blood pressure. An obvious gradient of increasing SBP and DBP values was observed from the underweight group to the obese group. SBP was statistically higher in the obese group compared with the underweight, normal and overweight groups, while the DBP was significantly different between the obese groups and the normal and underweight groups.Significant differences among other variables are shown in Prevalence of cardiovascular risk factors according to BMI classification is shown in Normal blood pressure values were found in 166 (83.8%) children and elevated values were found in 29 (14.6%) children. Simultaneous elevation of both SBP and DBP was found in five children, while 16 showed an increase of only SBP and eight showed an increase of only of DBP. Hypertension was detected in nine children and pre-hypertension in 20, without significant difference between genders . Positive familial history of hypertension was identified in 132 (66.7%) children. However, this trait was not associated with the presence of elevated blood pressure in the studied population .Another cardiovascular risk factor investigated was dyslipidaemia. The frequency of this condition was quite high, with 69.2% of the sample having at least one lipid value out of the normal range for this age group. This finding was unrelated to gender  and BMI. The most common change in lipid profile was the presence of high total cholesterol levels, followed by an increase in LDL cholesterol and triglyceride levels. Low HDL cholesterol level was found in 9.1% of children, without a significant difference between genders.An inverse correlation between fat accumulation and HDL cholesterol level and glycaemia was also observed. In a multivariate linear regression, we observed that body weight (kg) was the only independent predictor of SBP (SBP = 0.402 × body weight + 90.8) while the fat mass (kg) was the only independent predictor of DBP (DBP = 0.759 × fat mass + 58.1).The increased incidence of CVD risk factors is a growing reality in children and adolescents, according to studies in several countries.1161824Our study shows that the prevalence of overweight and obesity was approximately 14% in the studied age group and that fat accumulation correlated with high blood pressure values. More importantly, we also showed an unexpected elevated prevalence of dyslipidaemia , which, according to our data, was not associated with fat accumulation.Similar to other studies in pre-pubertal children1625It was possible to confirm in this group of children that borderline or high blood pressure values were associated with fat accumulation, without significant differences if overall  or central obesity indices (WC) were considered. Some studies show a stronger association between DBP and central obesity. However, the small sample size and the relatively small number of obese and hypertensive children may have hampered such analysis.The prevalence of high blood pressure in our cohort was 14.6%(11.1% with pre-hypertension and 3.5% with hypertension), a figure similar to that found in other African countries such as Egypt,16According to our findings, it is likely that body fat accumulation during adolescence may contribute to increased blood pressure, thus contributing to early onset of hypertension in adults. Validating other findings,27Hypertension is a multifactorial disease and the pathogenesis of its relationship with fat accumulation is unknown. Sorof et al. showed that obesity-induced hypertension could be due in part to hyperactivity of the sympathetic nervous system, which is manifested as increased heart rate and blood pressure variability.Another link between increasing blood pressure in children and fat accumulation is the increased thickness of the intima–media layer of arteries, leading to increased peripheral vascular resistance. Wunsch et al. showed an increased intima–media thickness in carotid ultrasonography of obese children. After a long period of physical activity and substantial weight loss, blood pressure reduction was followed by a proportional reduction of the carotid intima–media thickness, as well as in other blood biochemical parameters.33Genetic and environmental factors have also been suggested to be linked to high blood pressure. Therefore we also investigated the association of high blood pressure in children with a familial history of hypertension. Despite the fact that 72.4% of children with high blood pressure reported a positive family history of hypertension, this association was not significant when compared with children with normal blood pressure and positive family history of the disease . Our data are consistent with those of Shi et al.Overweight and obesity is a huge health problem in developed countries, and its prevalence seems to increase rapidly in countries facing fast economic growth.35The obesity pandemic therefore predicts the rise in incidence of other diseases in the near future. For this reason, obesity should be viewed as one of the most pressing health problems faced by public health authorities this century.In our study, we detected excessive weight in 17.7% of the studied sample, most reaching BMI values compatible with obesity, without significant gender differences. These figures are similar to studies in countries such as Egypt,The high prevalence of dyslipidaemia detected in our study is also noteworthy. Interestingly, dyslipidaemias were not associated with either fat accumulation or high blood pressure. However, the lack of a statistically significant association should be viewed with caution, given the small sample size of children showing obesity and/or hypertension. Our results suggest, however, that development of these cardiovascular risk factors may depend on different predictors. Dyslipidaemias, however, may be detected precociously because they may produce early changes in vascular structure, facilitating the development of atherosclerosis.Studies have alerted us to the increase in incidence of dyslipidaemia in children and adolescents.35The cut-off point adopted in our study, however, was used to classify children from different genetic backgrounds and with different dietary patterns. The prevalence of dyslipidaemias found in our study [50% with total cholesterol levels > 170 mg/dl (4.4 mmol/l)] is higher than the values found in some studies3842Regardless of cut-off points, it is important to highlight the high prevalence of dyslipidaemia in children and adolescents. For some authors, the change is due to the development of insulin resistance, initially peripheral and later at the systemic level.Our study suggests that, similar to other countries in sub-Saharan Africa, the high prevalence of overweight and obesity and of other cardiovascular risk factor indicates a rapid epidemiological transition affecting not only adults but also children.The consequences of childhood dyslipidaemia on the cardiovascular health of adults was reported by Berenson et al.Our study has some limitations. Children from a single school were included, therefore our data cannot be translated to the overall population of Luanda. Since the school is located in a neighbourhood with families belonging to the middle class, it represents only the population attending public school with such characteristics. Moreover, the final sample (n = 198) was sufficient to determine a prevalence around 10% only, with an estimated error of 3.5% and power of 90%, making our study inadequate for subgroup analysis.We only included pre-pubertal children in the analysis to avoid the influence of adolescence in fat accumulation. In this group, the association between body fat and blood pressure can be observed without the well-known influence of sex hormones. Therefore, most of the analysis was conducted in the overall sample, increasing the robustness of the conclusions.Blood pressure was measured on a single day, which is insufficient to establish a diagnosis of hypertension and rather requires confirmation by additional measures. Our analysis, however, was conducted by considering blood pressure as a continuous variable.Finally, cut-off points used in this study were based on international references not validated for the Angolan population. However, by using such international standards, comparison with other studies was possible.Our study shows a relatively high prevalence of obesity in pre-pubertal schoolchildren in Angola and suggests a possible association between fat accumulation and high blood pressure in this age group. However, a causal relationship cannot be established in this study given its transverse design. The high prevalence of dyslipidaemia in the studied population deserves attention in future studies, which should aim to investigate potential causal relationships, including eating habits and genetic factors. Early monitoring of blood pressure and lipid profile is necessary for adoption of adequate prevention policies in the area of cardiovascular health.


Methods. 8,155 people were randomly selected to participate in the 2011 annual Health Examination Survey in Beijing. A 75 g oral glucose tolerance test (OGTT) was tested in 3760 subjects with fasting plasma glucose (FPG) ≥ 5.6 mmol/L. Of 3,760 subjects, 583 were also randomly selected to take OCT. The aim of the study was to investigate the prevalence and the risk factors of maculopathy detected by optical coherence tomography (OCT) in a Chinese population with diabetes or prediabetes.p < 0.001) and systolic pressure (p < 0.05) made significant contributions to DME. Stepwise regression analysis revealed that HbA1c and blood creatinine were significantly independent influence factors for central subfield thickness (CST) . In this study population, 21 (3.95%) patients had maculopathy. Eight patients had diabetes macular edema (DME) and the prevalence was 6.72% in diabetes patients and 1.51% in all subjects. Eleven patients had age-related macular degeneration (AMD) and the prevalence was 3.36% in diabetes patients and 2.07% in all subjects. Logistic regression model confirmed that elevated HbA1c ( High prevalence of maculopathy was found in patients with diabetes in a Chinese population. Maculopathy poses a significant public health problem in China with rapid rising trend of diabetes. Type 2 diabetes mellitus (T2DM) has become a major public health problem in China and in the world, affecting 21 million people globally. The prevalence of total diabetes and prediabetes in China has been 9.7% and 15.5% in 2010 [Maculopathy is the main cause of legal blindness in adults aged between 20 and 74 years in industrial nations . SeveralMaculopathy has traditionally been assessed by clinical examination, stereoscopic retinal photographs, and fluorescein angiography. Optical coherence tomography (OCT) is a convenient and noninvasive method of imaging the macula. It creates a thickness profile of the retina that mimics quite accurately the histological arrangement of the retina. It is a more objective and accurate method of diagnosing macular edema than clinical examination, even by experts . As the In the present study, we sought to determine the prevalence of maculopathy detected by OCT and investigate possible correlation of maculopathy with systemic risk factors in patients with diabetes and prediabetes in a population-based sample of Beijing residents.From July 2010 to March 2011, we conducted the 2011 Health Examination Survey in Beijing, a cross-sectional, population-based survey on chronic diseases and risk factors. Our study area was Changping, a rapidly developing district in Beijing with an area of 1,343.5 square kilometers and a permanent resident population of 1,660,500. Household sampling was performed by the Center for Disease Control and Prevention (CDC) of Beijing; 8,155 randomly selected households were eligible (occupants were of Chinese ethnicity and had resided in Changping for more than 6 months). All household residents 18–79 years of age were enumerated in each sampled household; then, using Kish's selection tables, one person was randomly selected. Of the 8,155 individuals, 8084 received baseline examinations including physical checks, fasting plasma glucose (FPG) measurements, renal and liver function tests, and a general health questionnaire obtained through face-to-face inquiry. Then, 3,760 subjects with FPG ≥ 5.6 mmol/L were invited to receive a 75 g oral glucose tolerance test (OGTT) and ophthalmic examination. According to the protocol of this study, which is part of the 2011 Health Examination Survey in Beijing, we applied cluster random sampling method to sample subjects. In this process, a random sample  of the total of 48 villages was selected, and then all subjects in each sampled village were included. Finally, 583 subjects (70.2%) out of 830 subjects took part in our OCT study. Of the 1,166 eyes (583 subjects), 119 eyes were excluded for any of the following reasons: (1) self-reported history of trauma or surgery; OCT signal strength < 40 and scans of suboptimal quality with standard deviation of center point of >10% were excluded. For analysis of the correlation of risk factors with CST, only one eye of each patient was used in the study. In the patients who had maculopathy, the eyes with maculopathy were chosen. If both eyes had maculopathy, the right eye was chosen. In the other patients, if both eyes were eligible, the eye with the greater number of OCTs available for review was chosen, and if this number was equal for the two eyes, the right eye was chosen. Thus, a total of 531 eyes (522 right eyes and 9 left eyes) in 531 patients underwent analysis.The study protocol was approved and monitored by the Ethics Committee of Beijing Tongren Hospital, Capital Medical University, and written informed consent was obtained from all participants at the time of examination.Plasma glucose was determined by the glucose oxidase method. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglyceride, urinary albumin, and blood creatinine were analyzed by enzymatic methods on a Hitachi 7600 analyzer using an enzymatic assay.In a standard 75 g OGTT, blood samples were collected from an antecubital vein after an overnight fast for the determination of plasma glucose and hemoglobin A1c(HbA1c) levels. After the fasting blood specimen had been taken, the OGTT was performed between 08:00 and 10:00 hours. Two hours later, a blood sample was obtained for the determination of postloading plasma glucose levels. All blood samples were sent for centralized analysis within 24 hours.HbA1c was measured in whole blood by a high-pressure liquid chromatographic assay . The normal range for HbA1c was 4.0–6.0%.FPG of ≥7.0 mmol/L or OGTT-2h plasma glucose (2hPG) of ≥11.1 mmol/L cases were classified as diabetes. Impaired glucose tolerance (IGT) was defined on the basis of FPG < 7.0 mmol/L, 2hPG ≥ 7.8, and <11.1 mmol/L. Impaired fasting glucose (IFG) was defined on the basis of FPG ≥ 6.1 and <7.0 mmol/L and 2hPG of <7.8 mmol/L. Of the total 531 subjects, 234 had normal glucose homeostasis, 178 had prediabetes (IFG and/or IGT), and 119 had diabetes.OCT fast macular scans were obtained by a trained technician from each eye of the participant using 6.0-mm OCT scans  with software system version 1.5. Fast macular thickness map scan protocol was followed to obtain 6 consecutive macular scans automatically in 3 concentric circles  .Three scans for each eye were obtained and the best quality one  was selected for analysis. Moreover, one retinal specialist carefully reviewed these scans for abnormalities such as vitreoretinal tractions, retinoschisis, and lamellar macular holes. Retinal thickness over the macula was automatically determined by the instrument software.DME was defined according to Afef Maalej's protocol . It diviThe people aged 50 years inclusive or older in the present calendar year were included in the AMD study. AMD was defined as dry AMD , drusen with RPE pigmentary abnormalities (areas of hyperpigmentation or hypopigmentation), geographic atrophy of the RPE in the absence of neovascular), and wet AMD (neovascular AMD) . Other mt-tests were used to compare means of continuous variables. Chi-squared tests were used to compare proportions. Statistical correlations were obtained via Pearson correlation tests. Logistic regression models were used to detect risk factors in subjects, one for DME and the other for AME. The clinical parameters included in the model were age, gender, systolic BP (SBP), diastolic BP (DBP) and body mass index (BMI), HbA1c, total cholesterol, TG, HDL-C, LDL-C, and blood creatinine. Stepwise regression analysis was used to detect influence factors for central subfield thickness (the thickness of the 1 mm concentric circles (CST)). For all statistical tests, p values of less than 0.05 were considered to be statistically significant.All statistical analyses were conducted with the software package SPSS version 17 . Baseline characteristics were expressed as means ± standard deviation for quantitative variables and as percentages for categorical variables. Student's In this study population, 21 (3.95%) patients (29 eyes) had maculopathy. Eight patients  had DME and the prevalence was 6.72% in diabetes patients and 1.51% in all subjects. OCT classification of DME in five types: type 1, focal macular thickening ; type 2, diffuse macular edema without cysts ; type 3, cystoid macular edema ; type 4, tractional macular edema ; type 5, serous retinal detachments . Eleven patients  had AMD, and the prevalence was 3.36% in diabetes patients, 2.07% in all subjects, and 4.55% in the people aged 50 years or older. Additionally, 2 patients (2 left eyes) had other maculopathy forms .p < 0.001) and systolic pressure  made significant contributions to DME. After adjusting for age, gender, BMI, HbA1c, systolic pressure, diastolic pressure, blood creatinine, and lipid, elevated age  made a significant contribution to AMD.Patients with DME rated significantly higher in 2 h PG, HbA1c, and blood pressure compared with no-DME patients . In DME p = 0.01) and blood creatinine (p < 0.001) were significantly independent influence factors for CST  with different biochemical parameters was also tested. As shown in  for CST .According to the 2011 Health Examination Survey in Beijing, the prevalence of DR in patients with diabetes and prediabetes was 9.9% and 1.2%, respectively . BesidesIn Europe, the prevalence of visual impairment due to DME is estimated to be 5.4% of people with diabetes . From a μm of the center of the foveal avascular zone or the presence of an area or areas of retinal thickening of at least 1 disc diameter within 1 disc diameter from the center of the macula [μm and is more sensitive and objective in detecting the change of macular status than binocular clinical examination. As a consequence, OCT examination should be the first choice to detect possible macular thickening not seen clinically, which has been termed subclinical DME [Clinically significant macular edema (CSME) was assigned in cases of the presence of retinal thickening or hard exudates associated with adjacent retinal thickening within 500 e macula . Retinale macula , 28. Befical DME . Sasaki ical DME . Elevateical DME . In our Further, there are 2.07% subjects who suffered from AMD and prevalence was 4.55% in the people aged 50 years or older. In the United States, AMD affects 7 million persons 40 years of age and older . China iOur study has several limitations. Firstly, subjects with trauma, surgery, and severe cataracts were excluded from the study, which may have led to an underestimation of the prevalence of maculopathy. Secondly, our results may be bias due to a limited number used in this study. In subsequent investigations, a larger sample size prospective study would be preferable. Thirdly, we did not use the invasive angiography to make a definitive diagnosis of maculopathy in this health examination survey. Finally, it is a cross-sectional study, and we cannot draw conclusions about cause-effect relationship between CST and the metabolic factors.In summary, the current study provides novel and vital data on the epidemiologic characteristics of maculopathy in a population-based sample of Chinese adults. DME and AMD are the most important reasons of maculopathy in Chinese population. Considering the high prevalence of diabetes and aging population in China, maculopathy poses a significant public health problem in China. Regular and periodic screening of it should be performed in those people.


Introduction: Noninvasive measurement of arterial stiffness by pulse-wave velocity (PWV) hasprognostic value in different sub groups of cardiovascular disorders. We aimed to measure thePWV in advanced heart failure (HF) patients with reduced left ventricular ejection fraction(LVEF) and investigate whether it has any prognostic significance in this group of patients.Methods: Between 2013 to 2015 patients with a diagnosis of advanced HF (LVEF ≤ 30%)scheduled for right heart catheterization (RHC) were included in our study. PWV was measuredbefore RHC in each patient using vascular explorer device (Enverdis GmbH) in catheterizationlaboratory. The patients were subsequently followed for 6 months and their hospitalization ordeath  were recorded.Results: A total of 50 patients (38 men) were enrolled. The mean (SD) of age was 45 (16) years.The mean PWV was 6.8 m/s. There was no statistically significant correlation between the PWVand the clinical, echocardiographic and RHC data. The PWV was not different in patients withor without composite of all-cause death/hospitalization . In this studycardiac output (CO) , pulse pressure (PP) and age  were independent predictors of composite of all-cause death/hospitalization.Conclusion: In patients with advanced systolic HF, PWV may not be a good prognostic factor anddoes not have any added value over previous well known prognostic factors. PWV is the gold standard method for measuring arterial stiffness.7It has been shown that vascular function is impaired in patients with heart failure (HF). Arterial stiffness or reduced aortic distensibility plays an important role in exercise intolerance of this group of patients.12 Some of these studies show that PWV is associated with peak VO2, level of pro-brain natriuretic peptide (BNP) and mortality in patients with HF including those with systolic HF.16Several studies have shown that the PWV is a predictor of cardiovascular and all cause of mortality in a variety of cardiovascular disorders.In this study, we sought to measure the PWV value in advanced HF patients with reduced left ventricular ejection fraction (LVEF) who were candidate for right heart catheterization (RHC) and investigate whether PWV had any association with prognostic factors in advanced HF patients.Between 2013 and 2015, among patients referred for RHC, 50 patients were consecutively enrolled according to following inclusion criteria: presence of advanced systolic HF with LVEF ≤ 30% with ischemic or non-ischemic etiology. The indications for RHC was pre-heart transplant evaluation and/or hemodynamic study in advanced HF patients.17Advanced HF was defined according to American college of cardiology/American heart association (ACC/AHA) and European guidelines as; a stage D HF patient who is highly symptomatic most of the times with truly refractory HF symptoms  despite guidelines directed medical therapies, frequent outpatient visits (≥ 2 visit per months) and recurrent hospitalization  for decompensation and fluid overload, arrhythmias and complications of HF .Exclusion criteria were as follows: Presence of any arrhythmias including atrial fibrillation (AF) and frequent premature ventricular contractions, acute coronary syndrome, significant valvular heart disease (VHD), congenital heart disease, chronic renal failure, hypo or hyperthyroidism, chronic obstructive pulmonary disease (COPD), diabetes mellitus (DM), and the history of nitrate consumption during the previous week . Patients with other indications of heart transplantation were also excluded. All patients were subsequently followed for 6 months and their re-hospitalization due to cardiovascular events or death was registered.18A comprehensive medical and drug history was taken and thorough physical examination and transthoracic echocardiography was performed by an expert cardiologist. The NYHA function class of each patient was determined by evaluating each patient at rest and different activities including dressing, walking, and climbing the stairs. The scores given to each patient ranged from I (no symptoms) to IV (symptoms at rest).19 using a commercial GE Vivid 7 with a three-MS variable frequency harmonic phased array transducer just before performing RHC.A complete 2-dimensional (2D) color Doppler echocardiogram was performed in each subject in accordance to the American Society of Echocardiography RecommendationsLVEF was measured by Simpson’s method. The early diastolic mitral flow velocity (E), early diastolic annular velocity (E’) and E/E’ ratio were measured using standard Doppler imaging. To assess right heart function, the right ventricular tissue Doppler peak myocardial velocity (RVsm), tricuspid annular plane systolic excursion (TAPSE) and tricuspid regurgitation gradient (TRG) were measured.PWV was measured just before RHC using Enverdis vascular explorer device (Enverdis GmbH) by an expert cardiologist who was blinded to the patient characteristics. The room was quiet with stable temperature and each patient remained in a resting supine position at least for 10 minutes before the measurement.The RHC was performed in catheterization laboratory with 7F balloon tipped pulmonary artery catheter. All measurements were acquired with the patients in supine position and breathing room air at end expiration. The following variables were measured in each patient: mean pulmonary capillary wedge pressure (PCWP), systolic and diastolic pulmonary artery pressure (PAP), mean PAP, right ventricular systolic pressure (RVSP), right ventricular end diastolic pressure (RVEDP) and mean right atrial pressure. The cardiac output (CO) was calculated by estimated Fick method and cardiac index (CI) was calculated by dividing the CO to body surface area (BSA). Stroke volume (SV) was obtained by dividing the CO by heart rate. Brachial blood pressure was measured via a mercury sphygmomanometer in a supine position and after 10 minutes of rest. The pulse pressure (PP) was calculated by subtracting systolic and diastolic blood pressure. The aortic compliance was calculated by dividing the SV to PP.t test, analysis of variance (ANOVA), Mann-Whitney U test and chi-square test were used as appropriate. Pearson correlation coefficient (r) or Spearman rank correlation coefficient (rho) was also used to show linear correlations between PWV and hemodynamic measures. Binary logistic regression was used for multivariate analysis. Values of P < 0.05 was considered significant.IBM SPSS statistics 19 for windows  was used for all statistical analyses. At first all data were assessed for normal distribution using Kolmogorov-Smirnov test. Quantitative variables were expressed as mean  and qualitative data were expressed as number . To compare different variables student A total of 50 eligible patients (12 women and 38 men) were enrolled in our study. The mean (SD) of age was 45 (16) years, between 16-72 years. Non ischemic dilated cardiomyopathy was comprised 28 (56%) of the patients and the rest had ischemic cardiomyopathy.The most common etiology for non-ischemic dilated cardiomyopathy was idiopathic dilated cardiomyopathy (26 patients) and the etiology in 2 patients was peripartum cardiomyopathy. The mean (SD) of LVEF was 21.8 (8.9).In this study, PWV was used for assessment of aortic stiffness. The mean (SD) of PWV was 6.8 (3.3) m/s.P values)In this study there was also no significant relationship between the PWV and echocardiographic and/or hemodynamic measures  were observed in 29 (58%) patients.Seven patients died and 22 patients were admitted due to decompensated HF.As was expected, the patients with lower LVEF and compromised right ventricular function showed worse outcome.For the assessment of the adjusted associations between composite of all-cause death/hospitalization and other predictors which had been detected in bivariate analysis, a logistic regression model with backward elimination method was applied. The predictors applied in this model included; age, NYHA class, LVEF, systolic blood pressure, RA pressure, mean PAP, PCWP and CI.P = 0.02, odds ratio = 0.944, 95% CI = 0.897-0.993) as well as NYHA class  were shown to be independently associated with composite of all-cause death/hospitalization.In multivariate logistic regression model, lower age  may not be a useful prognostic factor in patients with advanced HF who are on guideline directed medical therapy.25 Bonapace et al13 demonstrated that arterial stiffness is a good predictor of peak Vo2 in patients with dilated cardiomyopathy. Sakuragi et al15 and Kaji et al16 found a significant relationship between pro-BNP level and aortic stiffness. Demir et al3 assessed 98 ischemic cardiomyopathy patients with LVEF ≤35% and NYHA functional class III-IV and revealed a cut off value of 11.06 m/s for PWV as a prognostic factor and predictor of mortality in these patients. Regnault et al14 investigated 306 patients of EPHESUS trial. They showed that PP and decreased PWV contribute to cardiovascular outcome. In their study, the mean of PWV was more than 11 m/s.The prognostic significance of arterial stiffness has been investigated in many cardiovascular disorders including HF.3 study. The lower values of PWV in our study population may be an explanation for the lack of relationship between PWV and prognostic factors including death and rehospitalization. The PWV more than 11 m/s has been correlated with prognosis in similar studies and the mean PWV was 6.8 m/s in our study.In the present study we could not find any relationship between PWV and known HF prognostic factors including LVEF, NYHA class and hemodynamic measures. The mean PWV in our study was markedly lower than those observed in similar studies and only 4 patients showed the cut point of 11 mentioned in Demir et al27Although, it has been shown, PWV is increased in patients with HF whether LV function is impaired or preserved, there was no study reporting the fact that arterial stiffness was investigated in advanced HF. On the other hand, it has been shown that all known cardiovascular pharmacological approaches are capable of decreasing arterial stiffness. The influence of some drugs is uniform which means the drug group definitely improves arterial stiffness and some drugs have prevailing effect that means the drug group improves arterial stiffness in the majority of studies. In this regard, angiotensin converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs), calcium channel blockers and spironolactone have uniform effect on arterial stiffness and beta-blockers and statins have prevailing effect.28 Mahmud et al29 and Shahin et al7 showed ACEIs significantly decrease PWV and arterial stiffness and this effect is independent of their decreasing blood pressure effect. These studies suggest that the effect of these drugs in decreasing mortality in HF patients is through decreasing arterial stiffness.REASON  study was the first study in which the long term influence of ACEIs on arterial stiffness was evaluated. They showed the combination of perindopril/indapamide was efficacious in reducing systolic blood pressure as well as PWV.27Beta-blockers have been shown to affect central pulsatile hemodynamics and arterial stiffness by reducing heart rate. The heart rate reduction influences the viscoelastic properties of the arterial wall.30The spironolactone proved to reduce PWV and arterial stiffness when adjusted for blood pressure, compared to bendrofluazide. The beneficial effect of spironolactone in this regard was also observed in patients with non-ischemic dilated cardiomyopathy.All of our study population was treated with a combination of ACEIs or ARBs and beta blockers as well as spironolactone for a long time which could be an explanation for lower PWV in them. The favorable effect of guideline directed medical therapies with ACEIs/ARB, beta blocker and spironolactone on arterial stiffness may modulate the prognostic value of PWV.3 the influence of pharmacological therapies on arterial stiffness and different study population can be an explanation for the different findings of our study. It seems that the arterial stiffness has exerted its maximal effects on the heart in advanced HF and at this stage may not have prognostic significance any more.Although the drug history has not been mentioned in most of the similar studies including the study done by Demir et al,The selection of advanced HF patients as study population is the strength of this study, however, there are some limitations. The main limitation of this study was relatively small sample size, particularly in that group with higher NYHA class. The second limitation was relatively short follow up duration and at last in this study we did not assess the Pro-BNP level as a prognostic factor.In conclusion, although PWV is a good surrogate for arterial stiffness, it may not be a good prognostic factor in patients with advanced HF. The PWV is not correlated with hemodynamic findings and do not have any added value over previous well known prognostic factors such as CO and NYHA class in patients with advanced HF.The authors declare that they have no competing interests.The study was approved by the ethic and research committee of Rajaie cardiovascular medical and research center and informed consent was obtained from all the participants.We would like to thank Raymand Rad Company for their kind support in this study and in particular Mr. Karimi. We would also like to thank Dr. Nick Austin for language editing of our paper.


In recent years, the feasibility of near-infrared spectroscopy to continuously assess cerebral autoregulation has gained increasing interest. By plotting cerebral oxygen saturation over blood pressure, clinicians can generate an index of autoregulation: the cerebral oximetry index (COx). Successful integration of this monitoring ability in daily critical care may allow clinicians to tailor blood pressure management to the individual patient’s need and might prove to be a major step forward in terms of patient outcome. It was initially promoted as a brain monitor in cardiac surgery and neonatal intensive care, but its use has been extended to various non-cardiac surgeries and critical care settings. Some recent reviews provide excellent detail on the principles of NIRS and its current clinical practice patterns3.Near-infrared spectroscopy (NIRS) has been adopted in clinical practice for over three decades now. Based on a similar principle as pulse oximetry, it allows continuous, non-invasive, real-time monitoring of cerebral oxygen saturation  during changes in cerebral perfusion pressure (CPP). The classic curve of cerebral autoregulation represents the autoregulation plateau and the lower and upper limit of autoregulation  .4. At the extremes of blood pressure , myogenic vasoactivity capacity is no longer able to accommodate these changes, and CBF becomes pressure-passive; CBF decreases when MAP moves below the LLA and increases when MAP is above the ULA.Using data from 11 human studies, derived from young patients with few comorbidities, Lassen described an autoregulatory plateau between mean arterial blood pressures (MAPs) of 50 and 150 mm Hg, over which CBF remained constant by active myogenic control of small cerebral arteries and arterioles5. It is now accepted that CBF regulation is determined by many more factors than blood pressure alone. A variety of physiological and biochemical mechanisms may interact and lead to a complex entity of vascular reactivity in which the relative regulatory role of each component remains largely unknown7. It has also been acknowledged that autoregulation may be altered in specific diseases  and in specific conditions 12.13. In this study, we managed hypertension with one of three different vasodilating drugs: sevoflurane, sodium nitroprusside (SNP), or nitroglycerin.cO2, suggesting impairment of cerebral autoregulation.This description of cerebral autoregulation has been widely accepted and has been propagated in many textbooks, and, even today, most caregivers feel confident with a MAP within the presumed autoregulation range. However, already in 1997, the validity of this concept was criticized15. Therefore, the practice of applying a fixed blood pressure threshold in an individual patient is risky, and tighter pressure control is mandatory16.In response to all of these confounders affecting cerebral vascular reactivity, the limits of autoregulation and the shape of the autoregulation curve may vary enormously and unpredictably 14,15. Even with an impaired autoregulation curve, there might be an optimal blood pressure in the middle of the autoregulation curve at which the autoregulatory function is most robust  and a real-time estimate of CBF. Although theoretically CPP should be plotted, this requires invasive monitoring of intracranial pressure (ICP) (CPP = MAP − ICP). Therefore, without access to ICP monitoring and without an increased ICP, ABP is considered a valid substitute for CPP.17.For the assessment of CBF, no convenient means of measuring CBF currently exist, so surrogates of CBF are being used. Recently, the various indices of autoregulatory function were extensively examined in adults with traumatic brain injury (TBI)cO2 is considered a reliable surrogate of CBF. When ScO2 is correlated with MAP, an index of autoregulatory vasoreactivity, the cerebral oximetry index (COx), is generated. Blood pressure in the autoregulation range is indicated by a COx that approaches zero; that is, there is no correlation between ScO2 and MAP. A COx approaching one indicates a strong correlation between the two signals and has to be interpreted either as impaired autoregulation or as MAP being beyond the limits of autoregulation . However, this practice was challenged by data showing a lower incidence of cardiac and neurologic complications when targeting a higher MAP (>80 mmHg) during CPB31. The time and magnitude that MAP spent below the LLA were higher for patients who developed acute kidney injury compared with patients without acute kidney injury, although absolute blood pressure values were equal between the two groups28. A significant association was also found between blood pressure excursions below the LLA and major morbidity 29. A recent study demonstrated that a blood pressure below the optimal MAP based on COx monitoring was associated with an increase in postoperative plasma GFAP , which is a brain-specific injury biomarker30. However, on the other hand, simply raising blood pressure might result in a MAP above the ULA, which also predisposes to cerebral injury. Horiet al. demonstrated that the sum of the product of the magnitude and duration of MAP above the ULA was associated with increased risk for delirium in cardiac surgery patients31.In some recent studies, it has been demonstrated that MAP variations outside the autoregulatory range, not the absolute MAP values, were associated with adverse outcomes32. Management at or close to the optimal CPP has been shown to be associated with better outcomes in patients with TBI34. Since an in-depth discussion of cerebrovascular autoregulation monitoring in neurocritical care is beyond the scope of this article, we refer the interested reader to some excellent reviews39.Patients with brain injuries constitute another population at high risk of impaired autoregulation. A consensus statement from the Neurocritical Care Society and the European Society of Intensive Care Medicine suggested that continuous monitoring of cerebral autoregulation might help guide ABP and CPP targets to ‘optimal’ levels in patients with TBI and might contribute to prognostication40. However, in conditions of brain injury, tissue composition may vary substantially , resulting in changes in light absorption and scattering. Accurate quantification of ScO2 and data quality could be questioned in this setting41.One methodological aspect of autoregulation monitoring with NIRS in the setting of neurosurgery and neurointensive care requires close attention. NIRS technology is based on sending near-infrared light through the tissues, where it is attenuated because of a combination of absorption and scattering. It is a prerequisite that the quantity of light scattering remains constant during the measurements and that changes in attenuation result solely from changes in absorptionWhile at first view defining COx might seem simple and easy to perform at the bedside, some major barriers have to be faced.cO2 is determined by arterial blood oxygen content, cerebral oxygen consumption, oxygen-tissue diffusivity, and CBF. It has been assumed that, if all other parameters which influence ScO2 are kept constant, changes in ScO2 are due to changes in CBF and therefore that those two parameters can be interchanged. Although one might question this approach, the problem remains that to date there is no continuous real-time methodology to quantify CBF.The use of NIRS for quantifying cerebral autoregulation is based on some assumptions, and this continues to be a major point of discussion. S® software . The ScO2 signal and the MAP signal are captured longitudinally . Filtering of both signals is performed to limit analysis to the frequency of slow waves (0.05–0.003 Hz), which are relevant to autoregulation and exclude confounding wave components such as respiratory and pulse frequencies. A sliding analysis window of a 300-second period updated every 10 seconds runs across the signals, and the ScO2 and MAP data within these windows are plotted against each other, incorporating 30 data points for each calculation. The linear regression line for these data is computed, and the Pearson correlation coefficient is obtained. The process repeats as the analysis window scans over the signals in incremental steps, resulting in a continuous COx measurement.In most studies, COx is determined by using ICM+® then fits a U-shaped curve through the COx values plotted versus MAP. The optimal MAP can be identified at the point with the lowest COx.To calculate the optimal MAP, the COx values are binned in 5 mmHg blood pressure increments. The first and last MAP bins, as well as bins which contain less than 2% of data points, are discarded. ICM+42. The binned data are generally noisy in a clinical environment, which may be device-specific  or physiological in nature . This becomes even more important when very few bins contain data points, such as early in a procedure when the complete picture of the COx plot has not yet built up, or when blood pressure is relatively stable. Montgomeryet al. demonstrated that the data in their raw format  are feasible for monitoring cerebral autoregulation, and they hypothesized that their method might be particularly useful in noisy environments42.However, owing to the granular nature imposed on the bin-aggregated data, binning makes it difficult to produce a robust automated algorithm to assess autoregulationcO2 and MAP (time-domain approach). However, it could be argued that cerebral autoregulation is a complex physiological system and that simple correlation analysis does not cope with the complex interplay and the time-varying aspects of the different physiological mechanisms43. Coherence and transfer function analyses have also been used to quantify cerebral autoregulation45. Caicedoet al. analyzed four different measurement models used for cerebral autoregulation assessment . Although Caicedoet al. proposed transfer function gain as the most robust method when used for cerebral autoregulation studies, correlation was also considered a robust method, despite some restrictions related to time delay46.The current methodology for analysis of cerebral autoregulation includes either a time-domain or a frequency-based approach. The most common method is to calculate the correlation coefficient between S47. So autoregulation is not an on–off phenomenon, in which correlations between CBF and MAP jump from zero (intact autoregulation) to one (impaired autoregulation), and this makes the interpretation of autoregulation data rather cumbersome.Varying definitions to decide between intact and impaired autoregulation are found in the literature. Generally, a COx of less than 0.3 is considered consistent with intact autoregulation and the MAP with the lowest COx is considered the optimal MAP. However, noise on the data may impede the identification of intact and impaired regions. A further complication for the assessment of autoregulation is that, owing to interpatient variability, no specific threshold will apply to everyone. Moreover, it has been postulated that the flat part of the autoregulation curve is never really horizontal, but slightly tiltedcO2 response to natural slow variations in blood pressure. However, the natural blood pressure variations may not be strong enough to challenge CBF. An alternative approach is to induce blood pressure variations  and measure the concomitant response of ScO2. However, it has been demonstrated that CBF dynamics are driven by the rate of change in blood pressure rather than absolute pressure per se; therefore, the precipitous change in pressure might elicit autoregulatory reactions that would not be seen with gradual changes in pressure50.One approach to assess cerebral autoregulation is to monitor the S14 and an autoregulation plateau which may be very narrow15. The clinical implication is that CBF might fluctuate as blood pressure fluctuates, exposing the patient to the risk of decreased cerebral flow and potential ischemia when blood pressure is relatively too low and conversely to the risk of increased cerebral flow and increased ICP when blood pressure is relatively too high. Since the individual limits of autoregulation are unknown, it is likely that empiric blood pressure management will result in patients having a MAP outside the autoregulatory range for at least part of the surgery or stay in intensive care. If autoregulation monitoring can individualize blood pressure targets, it could provide a more effective means for preventing ischemia–reperfusion injury than the current standard of care.Despite the emerging availability of bedside physiology monitors, blood pressure targets remain mostly empirically chosen during critical care management. Efforts at preventing cerebral injury have emphasized the importance of maintaining a ‘normal blood pressure’ to ensure adequate perfusion of the brain. Hence, often medications are given to increase blood pressure in order to restore cerebral perfusion. However, as discussed before, the position and the shape of the autoregulation curve may have shifted away, with LLAs and ULAs which vary greatly and unpredictablyWith the sophistication of signal processing and online analysis software, the challenge lies in the successful integration of ‘optimal MAP’ and autoregulation monitoring into daily critical care management.The next steps will be to study the autoregulation in different clinical situations and to clarify whether incorporation into therapeutic management protocols leads to an improved cerebral outcome.Progress in perioperative and critical care will depend on moving away from broad assumptions and ‘one size fits all’ physiological targets. In the near future, real-time cerebral autoregulation monitoring may provide clinicians with the opportunity to individualize blood pressure targets and might direct critical care management to the individual patient’s need.


Dyslipidemia is often detected in patients with chronic kidney disease (CKD). Previous studies of the relationship between lipid profiles and kidney function have yielded variable results. We aimed to investigate the correlation between serum lipid levels and kidney function evaluated by measured glomerular filtration rate (mGFR) in Chinese patients with CKD.A cross-sectional study was conducted on 2036 Chinese CKD patients who had mGFR. Linear regression analysis was performed to evaluate the correlation between different serum lipid levels and mGFR, while logistic regression analysis was used to investigate the association between CKD stages and the risk of different types of dyslipidemia.2. After adjusting for some confounders , serum triglyceride level showed a negative correlation with mGFR  in linear regression analysis, and CKD stages were positively related to the risk of hypertriglyceridemia  in logistic regression anlysis.The mean age was 55 years and the mean mGFR was 63 mL/min/1.73mSerum triglyceride level is independently association with mGFR. Patients with reduced kidney function are more likely to have higher serum triglyceride levels. Further longitudinal, multicenter and well-conducted studies are needed to provide more evidence. Chronic kidney disease is recognised as a major health problem worldwide. The disease affects 10–16% of the general population in Asia, Europe, and the USA and is thDyslipidemia leads to atherosclerosis, and is considered to be an important risk factor for CVD ,8. Accel99mTc-DTPA) renal dynamic imaging method, from January 2005 to December 2014 at the Third Affiliated Hospital of Sun Yet-sen University, Guangzhou, China. Patients were excluded for any of the following reasons: 1) younger than 18 years old; 2) taking lipid-lowering therapies; 3) with missing data on factors hypothesized to be associated with GFR. 2036 patients were included and staged according to the National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines [th 2011 by telephone or letters to get their informed consent, and got approval of ethical review exemption from the medical ethics committee for participants who were unable to contact. Written informed consent was obtained from all the participants after July 25th 2011. The participants specifically consented to participate in this study and to have their medical records used in research.The cross-sectional study was conducted among Chinese CKD patients with mGFR assessed by a technetium 99m diethylene-triaminepentaacetic acid (2). The blood pressure measurement was performed by well-trained doctors using a calibrated desktop sphygmomanometer  while the participants were seated and rested for at least 5 min.Information about the age, gender, smoking status, the history of hypertension and diabetes mellitus, and medication use of the participants was collected from their medical records. Weight and height were measured. Body mass index (BMI) was calculated as weight (kg) divided by height squared , using a Millennium TMMPR SPECT with the General Electric Medical System . The details had been described previously [The measured GFR (mGFR) was obtained by a eviously . Serum aAll data used in this study was collected as part of standard clinical care. We did not collect any data from patients specifically for this study. The patient data was anonymized before they were accessed by the researchers.Different types of dyslipidemia were defined by the 2007 Guidelines for Prevention and Treatment of Dyslipidemia in Adults in China [P value less than 0.05 indicates a significant difference. All statistical analyses were performed using SPSS software .Continuous variables were presented as the mean and standard deviation (SD), and categorical variables were presented as numbers and percentages. We began with un-adjusted linear regression analysis to evaluate the correlation between different serum lipid levels and mGFR, and models adjusted for age, gender, BMI, a history of diabetes, fasting glucose, a history of hypertension, systolic blood pressure(SBP), diastolic blood pressure (DBP), smoking status, hemoglobin, serum potassium, serum albumin, and serum uric acid. Logistic regression analysis was used to investigate the association between CKD stages and the risk of different types of dyslipidemia: unadjusted models first, and then models adjusted for the same factors mentioned above. 2. There were 1159 (56.9%) participants with a history of hypertension and 939 (46.1%) with a history of diabetes. 289 (14.2%) of them were current smokers. The mean levels of HDL-C, LDL-C, TG and TC were 45.60±23.94, 109.44±47.50, 180.40±168.08 and 186.20±61.18 mg/dL, respectively.P for trend were < 0.001 and 0.013, respectively). We performed linear regression analysis between levels of different serum lipid components and mGFR as continuous variables. The results shown in P were 0.023 and < 0.001, respectively). However, after adjusting for risk factors, only triglyceride showed a negative correlation with mGFR .As shown in P for trend was < 0.001), while the incidence of hyper LDL cholesteremia and hypercholesteremia varied inversely . Logistic regression model was used to investigate the association between different types of dyslipidemia and CKD stages, and CKD stage 1 was used as reference. In the unadjusted model, CKD stages were positively related to the risk of hypo HDL cholesteremia . In the multi-variables adjusted model, CKD stages were positively related to the risk of hypertriglyceridemia . These results are shown in Renal dysfunction is usually accompanied by increased levels of triglyceride-rich apoB-containing lipoproteins and decreased levels of apoA-containing lipoproteins–12. In tThe relation between kidney dysfunction and dyslipidemia is still far from fully understood, but some possible pathogenetic connections have recently been revealed. The first mechanism may be altered metabolism of lipoproteins. As shown in kinetic studies of CKD patients with dyslipidemia ,23, therA major strength of our study is that we used mGFR to evaluate kidney function, which is more accurate than eGFR. Furthermore, this study involved four major types of dyslipidemia and adjusted the regression model by related risk factors. There are some limitations in our study. First, this is a cross-sectional study, which does not reveal the causal relation between serum lipid levels and mGFR. Second, our data represented a specific group of CKD patients in China. Finally, although we adjusted the regression model for 13 covariates that may be associated with mGFR, there are still some other unknown risk factors.In conclusion, serum TG level is independently association with mGFR. And further longitudinal, multicenter and well-conducted studies are needed to provide more evidence.S1 STROBE Checklist(DOC)Click here for additional data file.


To advance the study of variables associated with subclinical atherosclerosis in rheumatoid arthritis (RA) with special consideration for the degree of disease activity, age and gender.The carotid intima-media thickness (cIMT) and the presence of carotid atherosclerotic plaques along with clinical and biochemical characteristics were determined in 214 RA patients.2 = 3.8%) and that age was associated with cIMT . Interestingly, we observed a significant interaction between gender and age. Thus, the effect of age on cIMT was significantly increased (12%) in men compared with women . Moreover, adjusted multivariable linear regression analysis revealed that disease activity score (DAS28) was significantly associated with cIMT in women  but not men. In particular, women with high disease activity had a 0.079 mm increased cIMT compared with women in remission (p = 0.026). In addition, men in remission had a 0.134 mm increased cIMT compared with women in remission . Active patients did not exhibit differences in cIMT values. Furthermore, 43% of patients presented carotid plaques. The variables independently associated with carotid plaques were age, smoking, health assessment questionnaire, erythrocyte sedimentation rate and rheumatoid factor .Adjusted analysis reveals that men had a 0.059 mm significantly increased cIMT compared with women (p = 0.001; RIn our cohort of patients with RA, DAS28 and age are differentially associated with cIMT in men and women. Our findings could explain the contradictory results that have previously been published in the literature. Rheumatoid arthritis (RA) is a systemic autoimmune disease that mainly affects synovial joints and causes chronic pain, bone erosion and progressive disability. With a prevalence of up to 0.5–1% of the general population, RA is the most common chronic inflammatory disease . In addiThe assessment of RA patients with subclinical atherosclerosis by means of ultrasonographic determination of the carotid intima-media thickness (cIMT) and the presence of carotid plaques has been accepted as a good predictor of CV events . HoweverThe study population included all consecutive patients who visited via external consultations of the University Hospital Sant Joan de Reus and who fulfilled the diagnostic criteria of RA proposed by the American College of Rheumatology of 1987. We excluded patients older than 80 years and younger than 20 years and those with acute intercurrent diseases. Consistent with our Institution’s guidelines and the Helsinki Declaration, subjects were informed of the research nature of the study and provided written consent prior to participation. The study was approved by the clinical research Ethics Committee of the University Hospital Sant Joan. Patients were visited between the period of September 2011 and November 2014, and we performed blood collection and carotid ultrasound on the same day of the medical visit.Blood samples were collected from 214 patients who had fasted for at least 12 hours. Analytical determinations included the following: haemogram, general biochemistry, haemoglobin glycoside, thyrotropin, albumin, lipid profile  by enzymatic methods; apolipoproteins A1 and B by immunonephelometry; lipoprotein (a) by an enzyme-linked immunosorbent assay; and rheumatoid factor (RF), citrullinated anti-cyclic peptide antibodies (ACPA), antinuclear antibodies and inflammatory markers  by conventional methods. RF positive (RF+) was defined for values of RF>20, and positive ACPA (ACPA+) was defined for ACPA values>1.The presence of CV risk factors  and histories of previous CV events and the use of lipid lowering drugs, antidiabetic agents or antiplatelet drugs were collected. In addition to joint physical examinations of RA, measurements of body weight, height, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were obtained.As a measure of disease activity, the disease activity score (DAS28) was calculated according to the ESR. Pain was measured using the 0–10 visual analogue scale, and any disability was reported by the patient using the health assessment questionnaire (HAQ) index. The DAS28 variable was categorized as remission (DAS28<2.6), low activity (2.6≤DAS28<3.2), moderate activity (3.2≤DAS28≤5) and high activity (DAS28>5).To measure cIMT, we used a My Lab 50 X-Vision sonograph  with a linear array ultrasound probe small parts broadband transducer (5–12 MHz). We identified and digitally recorded the far wall of the common carotid artery  and the internal carotid artery  of the left and right carotid arteries. cIMT measurements were performed at the predefined points using ThickSoft image processing software (%). To reduce observer variability, a single operator obtained and measured the images. We averaged the measurements of three static images of left and right carotid arteries to obtain the mean cIMT. Carotid artery plaque was defined according to Mannheim consensus  as a focAll data were analysed using the statistical software SPSS, version 23. Continuous variables are presented as the mean (standard deviation) and categorical as the percentage . ANOVA was used to evaluate differences between groups followed by Bonferroni correction as a post hoc test. For categorical variables, the differences between the proportions were analysed using the chi-Squared test. Bivariate correlations were estimated using the Pearson correlation coefficient r. To estimate the cIMT variable, multiple linear regression was used with multivariate models. Multivariate logistic regression was used to estimate the presence of carotid plaques. We initially selected clinical relevant variables and known confounders for inclusion in the multivariable logistic regression analysis. The iterative process of variable selection was performed using stepwise logistic regression analysis. A p-value<0.05 was considered statistically significant.A total of 214 RA patients were included in the study. Crude analysis of the ultrasonographic variables showed, as expected, that age was highly correlated with cIMT  and that men presented significantly larger values of cIMT than women  . After aAdjusted multivariable linear regression analyses revealed that DAS28 was significantly associated with cIMT in women   and thatNext, regarding the presence of carotid artery plaques in RA patients, we observed that 43% had carotid plaques, with a significantly increased prevalence in men compared with women . FurtherIn our study, we evaluated the relationship of cIMT with disease activity in conjunction with age and gender in a sample of 214 patients with RA. We observed a complex relationship among these variables and cIMT. In particular, we observed that males with RA had increased cIMT values compared with women, but these differences were due to patients in remission. As the disease activity increased, these differences disappeared, and the cIMT values of women became similar to those of men. In addition, women with high disease activity exhibited significantly increased cIMT values compared with women in remission; this result was not observed in men. Although different studies have evaluated the association between DAS28 and cIMT, the results are inconclusive. Thus, both studies with significant associations ,23 and tIn addition, we observed a significant interaction between age and gender. We observed a 12% significantly more pronounced correlation of age with cIMT in men compared with women. To the best of our knowledge, these data are reported for the first time. These results suggest a more rapid rate of cIMT thickening in men with RA than in women as age increases. The adjusted model  for our In our study, we observed no significant association between the inflammatory variables  and serological markers  studied and cIMT. Several publications have reported significant associations between these variables ,23,28–34The association between classical lipid profile values  and subclinical atherosclerosis is not well determined. Although positive associations have been reported ; other sThe presence of carotid plaques is considered a good predictor of CV risk. In our study, 43% of RA patients had carotid plaques, which is slightly higher than the 33% described in a meta-analysis of 35 studies . In addiThe observed differences between some of the variables that are associated with cIMT and the presence of plaques could be explained if we take into account that cIMT and atherosclerotic plaques reflect different stages and pathophysiological processes of atherosclerosis ,52. ThuscIMT is an independent predictor of cardiovascular events and for this reason it has been considered as a tool to improve the estimation of cardiovascular risk. However, its application in the clinical practice is still a matter of debate and is limited by the lack of positive results in interventional studies and clinical trials aimed to correlate cIMT regression with the improvement in cardiovascular survival.In conclusion, in our cohort of patients with RA, disease activity measured according to DAS28 and age are associated with cIMT differentially in men and women. Our results may help to explain why DAS28 is not always associated with subclinical atherosclerosis. In addition, gender differences influencing cIMT could be justified by the increased incidence of RA in women and by factors intrinsic to the female sex that are external to the autoimmune disease itself  and could help clinicians to manage these patients.S1 File(TXT)Click here for additional data file.


An LTI of less than 10% of the normal value (low LTI) indicates muscle wasting. Patients with low LTI (n = 40) tended to be diabetic, had significantly higher fat tissue index, urine protein creatinine ratio, and interleukin-6 and tumor necrosis factor-α levels, but had significantly lower serum albumin and hemoglobin levels compared with those with normal LTI. In multivariate linear regression analysis, age, sex, cardiovascular disease, and interleukin-6 were independently associated with LTI. Additionally, diabetes mellitus remained an independent predictor of muscle wasting according to low LTI by multivariate logistic regression analysis. We conclude that LTI has important clinical correlations. Determination of LTI may aid in clinical assessment by helping to identify muscle wasting among patients with stage 3–5 CKD.Muscle wasting is common and is associated with increased morbidity and mortality in patients with chronic kidney disease (CKD). However, factors associated with decreased muscle mass in CKD patients are seldom reported. We performed a cross-sectional study of 326 patients (age 65.8 ± 13.3 years) with stage 3–5 CKD who were not yet on dialysis. Muscle mass was determined using the Body Composition Monitor (BCM), a multifrequency bioimpedance spectroscopy device, and was expressed as the lean tissue index (LTI, lean tissue mass/height Body composition is one of the best indicators of overall health. Muscle wasting is common and progressive in patients with chronic kidney disease (CKD) and has important health consequences ,2. The tIn adults without CKD, a loss of muscle mass of 1% per year is expected ,9. HowevIn order to improve the prognosis of CKD patients, sarcopenia should be screened for and detected during mild to moderate stages of CKD, when the complications of reduced muscle mass may be reversible . Bioimpe2, as calculated by a simplified Modifications of Diet in Renal Disease (MDRD) equation. All patients received multidisciplinary CKD care, focusing on dietary salt and protein restriction, nephrotoxin avoidance, and strict blood pressure and glycemic control. Patients were excluded if they had a cardiac pacemaker or metallic implants, or were amputees. Patients were also excluded if they had malignancies or clinical conditions affecting body composition, such as liver cirrhosis, active inflammatory diseases, or any acute cardiovascular event during the three months before screening for inclusion.This was a cross-sectional study conducted in the Taipei Tzu Chi Hospital, Taiwan. This study complied with the Declaration of Helsinki and was approved by the Institutional Review Board (01-XD13-034). All participants gave written informed consent. Patients with prevalent stage 3–5 CKD who had been seen in outpatient clinics but who were not yet on dialysis were assessed for eligibility for inclusion if they were >18 years of age. CKD was defined on the basis of two  estimated glomerular filtration rate (eGFR) values <60 mL/min per 1.73 mFor each patient, a medical history was taken at the time of enrollment. Diabetes mellitus (DM) was defined as the current or past use of insulin and/or oral antidiabetic drugs. Hypertension was defined by a blood pressure ≥140/90 mm Hg or by receiving treatment with anti-hypertensive agents. The definition of cardiovascular disease (CVD) included coronary artery disease, as documented by coronary angiography or a history of myocardial infarction, class III to IV congestive heart failure, or cerebrovascular accidents. Smoking history was defined as any use of tobacco.Plasma levels of interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) , and N-terminal pro-brain natriuretic peptide  were determined using commercially available enzyme-linked immunosorbent assay kits according to the manufacturers’ instructions. Serum albumin levels were measured using a bromocresol purple (BCP) assay. Proteinuria was determined based on the urine protein-to-creatinine ratio (UPCR) assessed using the first morning void. Arterial stiffness was obtained by measuring the brachial-ankle pulse wave velocity (baPWV) using a VP-1000 analyzer .Body composition was assessed using the BCM device. Electrodes were placed on the hand and foot on the nondominant side of the body while the patient was in a supine position, and the results were available within 2 min. The BCM measures body composition by analyzing electrical responses at 50 different frequencies between 5 and 1000 kHz. The use of multiple frequencies enables the calculation of theoretical resistance values at zero and infinite frequencies by fitting a polynomial curve termed the Cole–Cole plot. The validity of the measurement can be assessed by the graphic representation of the curve. Only patients with at least one valid BCM measurement were included in the study.2), which was derived from the impedance data based on a three-compartment model  [Input parameters included the patient’s age, sex, height, and weight. Muscle mass was expressed as the lean tissue mass or lean tissue index  . The BCMdration) ,24. Patidration) ,23.t-test or the Mann–Whitney U-test was used to compare continuous variables. Categorical variables were compared by using a χ2 test. Univariate correlations between LTI and potential explanatory variables were assessed by Pearson’s correlation coefficient. Multivariate linear and logistic regression analyses were conducted with the LTI and the presence of muscle wasting  as dependent variables and potential predictors  as independent variables. A two-tailed p-value < 0.05 was considered statistically significant. Statistical analysis was performed using the computer software Statistical Package for the Social Sciences, version 20 .All of the variables were reported as the frequency and percentage for categorical data and as the mean ± SD or median and interquartile range for continuous data with or without a normal distribution, respectively. The study population was further divided into two subgroups according to low  or normal LTI. For all comparisons of baseline characteristics between the two subgroups, Student’s n = 8) or the initiation of chronic dialysis within the first month after enrollment (n = 4). The baseline characteristics of the remaining 326 patients, divided according to low or normal LTI, are presented in n = 148) of the study population had DM and 23.6% (n = 77) had pre-existing CVD. All patients had moderate to severe CKD . Patients in the low LTI group were more likely to have DM and a smoking history. Furthermore, patients with a low LTI had significantly higher levels of fat tissue index, UPCR, IL-6, and TNF-α but had significantly lower levels of serum albumin and hemoglobin.After the exclusion criteria were applied, 338 clinically stable patients were enrolled in the study. Twelve patients were excluded from the analysis due to loss of follow-up after the initial visit  and negatively associated with fat tissue index . Correlations between LTI and other variables are presented in r = 0.197, p < 0.001)     A and eGF< 0.001) B, and ne< 0.001) C and log< 0.001) D.R2 of the model = 0.454)  . In logi= 0.454) .We found that LTI was independently associated with age, sex, CVD, and IL-6. In addition, we observed that DM was an independent predictor of muscle wasting, defined as LTI being less than 10% of the normal value in the multivariate logistic regression model. Therefore, LTI has important clinical correlations and may aid in the clinical assessment of patients with stage 3–5 CKD.Several studies have shown that lean mass decreases with age in older adults without CKD ,26,27. OSarcopenia is common and occurs in all stages of CKD. Foley et al.  assessedWe found that DM was an independent predictor for muscle wasting in CKD patients in the present study. Insulin resistance has been identified as one of the most important metabolic challenges in patients with CKD. It is linearly correlated with decline in renal function  and is sLow-grade inflammation is common even in earlier stages of CKD, as evidenced by increased circulating levels of inflammatory markers such as C-reactive protein (CRP), IL-6, and TNF-α. After multivariate adjustment, IL-6 remained an independent predictor of LTI in our study, suggesting that the development of decreased muscle mass in CKD may be mediated by chronic inflammation. Muscle mass in long-term HD patients is inversely associated with inflammatory markers such as serum IL-6 and CRP levels ,41,42,43Some limitations of our study should be acknowledged. Because of the cross-sectional design of the study, causality cannot be established, and there remain some potential unknown or unmeasured confounding factors associated with LTI. Dietary intake was not assessed in this study. Decreased protein intake may be a risk factor for loss of lean mass in patients with CKD and should be studied further. The strengths of this study are that the BCM device is portable and relatively inexpensive, and that measurements are non-invasive, simple, rapid, and highly reproducible . MoreoveA better understanding of the factors associated with decreased muscle mass is needed to develop preventive strategies for muscle wasting in patients with CKD. Muscle mass, as measured by the BCM and expressed as the LTI, is strongly associated with age, sex, DM, CVD, and IL-6. The BCM may help to identify a high-risk group with decreased muscle mass among patients with stage 3–5 CKD. Control of inflammation and underlying comorbidities such as DM and CVD, in addition to appropriate nutritional, pharmalogical, and exercise interventions ,48, may