Blood Pressure (BP) is not well controlled and factors that predict BP control are not well identified in Lebanon. Improvement of hypertension management requires an understanding of patients’ characteristics and factors associated with uncontrolled BP. This national, multicentric, observational prospective study was designed to determine the predictors of BP control in patients followed up to 6 months.I-PREDICT study was conducted on 988 patients with newly diagnosed or uncontrolled hypertension. Socio-demographic and clinical characteristics were analyzed. The level of agreement between doctors’ perceptions on BP control status and JNC VII guidelines was analyzed.The predictor associated with poor BP control was diabetes . The predictors associated with better BP control at month-6 were the early control of BP at month-1  and combination therapy prescribed at baseline and month-1 . In the sub-group of diabetes, the predictors that were associated with better BP control at 6 months were following diet at V1  and BP control at V2 . The predictors that were associated with poor BP control at 6 months were middle economic class  and upper economic class .versus month 1 . Additional analysis showed poor agreement between the doctors’ perceptions on BP control status and the guidelines.The rate of BP control was significantly higher at month 6 Reaching an early BP control and combination therapy were significant predictors of better BP control, whereas diabetes was a significant predictor of poor BP control. A poor agreement between JNC VII guidelines and clinical practice was observed. I-PREDICT study identified factors that can be targeted for improving BP control. High blood pressure is a major risk factor for cardiovascular diseases, it is estimated to account for 13% of deaths worldwide. FurtherIn developing countries including Lebanon, the high prevalence of hypertension and poor hypertension control are important factors in the rising epidemic of cardiovascular disease. In Lebanon, around 39% prevalence of hypertension is reported among the general population. LebanonThe main challenge about hypertension is the number of patients who are not in control of their BP. If left uncontrolled, hypertension can lead to coronary artery disease, an enlargement of the heart and eventually heart failure. The numGlobally, the low BP control rates have been difficult to explain, given the number of apparently well-tolerated medications available for the management of hypertension. Factors related to access to care, medical practice patterns, patient education, poor compliance to prescribed treatment and patient cardio-metabolic profile have all been proposed as barriers to BP control–18. HoweFurther identification of patients at risk of poor control can lead to targeted interventions to improve management of hypertension. Besides, in order to improve the BP control rate in the population with hypertension, a more complete understanding of the predictors of BP control is essential.The following study (I-PREDICT) is a national, multicentric, observational, prospective cohort survey which aimed to identify the predictors of BP control in hypertensive Lebanese patients followed up to 6 months. The secondary objectives were to identify the predictors after 1 month of follow-up and to evaluate the number of hypertensive patients who are and are not at goal at months 1 and 6.From April 2010 to November 2010, a national, multicentric, observational, prospective cohort survey was conducted on 1079 patients, with newly diagnosed or uncontrolled hypertension on previous medications, in 107 centers all over Lebanon. Participating centers were either private clinics or hospitals based outpatient clinics.Institutional review board  approved the study protocol and the study was performed in compliance with Good Clinical Practices.One hundred seven (107) randomly selected physicians from across Lebanon were invited to participate in the study. Their number was determined based on the sample size and the recruitment period. Each physician was requested to enroll the first 10 eligible patients who met the eligibility criteria and gave written informed consent. Eligible participants for this survey were men and women 18 years old or above with newly diagnosed hypertension or uncontrolled hypertension on medications. Exclusion criteria included pregnancy, lactation, secondary hypertension or participation in another study.Hypertension was considered uncontrolled if BP was more than 140/90 mm Hg in hypertensive patients and more than 130/80 mm Hg in hypertensive patients with diabetes and chronic kidney disease. Those thresholds were based on the latest report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VII) and the guidelines for the management of arterial hypertension of the European Society of Hypertension, 20.Case report forms in English were used to collect patients’ data, from the physicians, over 6 months follow-up after enrolment in the study. Data were collected at baseline and during two follow-up visits when performed by the patients. The information included the following: dates of visits, verification of the eligibility criteria, systolic and diastolic blood pressures, whether the patient is newly diagnosed with hypertension or not, co-morbidities , lifestyle , medical treatment for hypertension and number of prescribed antihypertensive medication. The survey also obtained data on patient’s gender, weight, height, waist circumference, educational level, marital and socio-economic status assessed by the investigator, home blood pressure monitor  and knowledge of the patient of his target blood pressure.This study is purely observational of real-life practices, therefore no specific method of evaluation was defined. Physician’s therapeutic decisions and patients’ assessment were based on usual real-life practices.BP was measured by the available blood pressure device. Although, we do realize that using an automatic device is an objective method of BP assessment but in line with the study design, we didn’t impose any specific tool in order not to introduce any bias in the “real-life” assessment.2). Normal weight was defined as having a BMI of 18.5–24.9 kg/m2, overweight of 25.0–29.9 kg/m2 and obesity as BMI ≥ 30 kg/m2, as defined by the World Health Organization (WHO) classification of 2004 was was22] wA total of 1079 patients in 107 centers all over Lebanon were recruited in this survey of whom 988 were eligible for the statistical analysis  of the patients were men and 45% (N = 445) were women. The percentages of patients with newly diagnosed hypertension 2. The average waist circumference was 98.42 ± 16.02 cm.At baseline, out of 988 patients, the mean systolic BP was 166.74 ± 37.74 mm Hg, and the mean diastolic BP was 94.01 ± 9.18 mm Hg. The mean BMI was 28.75 ± 4.08 Kg/mTable There is a significant difference in the geographic distribution of diabetic versus non-diabetic patients such that patients in Beirut are more likely to be non-diabetic (p = 0.002). Additionally there is a significant difference in the educational levels of diabetic patients versus non-diabetic patients where non-diabetic patients are more likely to have higher educational levels (p = 0.022). Details are shown in Table Regarding co-morbidities, 41.27% were smokers. Dyslipidemia and diabetes were more frequently present with percentages of 57.39% and 39.27% respectively. Co-morbidities of patients at baseline are detailed in Table There is no significant difference between diabetic versus non-diabetic patients; such that the mean systolic and diastolic blood pressure, weight and waist circumference were comparable between the two subgroups.At baseline, the majority of patients received a combination therapy (71.3% vs. 28.7% on monotherapy) and this observation was maintained same across visits. Details on distribution of anti-hypertensive medication is detailed in Table In multivariate analysis, a number of factors were found to be associated with BP control in hypertensive patients at the follow-up visits (months 1 and 6) .The predictors that were associated with better BP control at month 6 were the early control of blood pressure at month 1  and combination therapy at baseline and month1 . Patients treated with combination therapy at baseline and month 1 had a better BP control at month 6 compared to those being treated with monotherapy at baseline.No significant association with blood pressure control was found for educational level, following diet, exercising, smoking, dyslipidemia, myocardial infarction, atrial fibrillation, chronic kidney disease and new diagnosis of hypertension.In the sub-group of diabetes, the predictors that were associated with better BP control at 6 months were following diet at V1  and BP control at V2 . The predictors that were associated with poor BP control at 6 months were middle economic class  and upper economic class .versus month 1 (P = 0.00).The percentages of patients who had controlled blood pressure at months 1 and 6 were respectively 44.08% and 67.52%. The rate of BP control was significantly higher at month 6 The measurement of agreement between doctors’ perceptions on BP control and JNC VII guidelines showed a poor agreement between the two parameters at the follow-up visit at month 1 (kappa < 0) whereas it was fair at the follow-up visit at month 6 (kappa = 0.26) according to Landis and Koch characterization’s.I-PREDICT survey is the first study that attempts to identify the predictors of BP control in the Lebanese population nationwide. It identifies diabetes as a predictor of poor BP control in subjects with hypertension. This is consistent with findings from previous studies that showed a higher predilection for uncontrolled BP in diabetic patients, 23–26. Moreover, early control of blood pressure is known to improve BP to a significant extent over time, 33, 34.This study also showed that combination therapy had a statistical advantage in terms of BP control . Patients who stayed on combination therapy by the time of the third follow-up visit at month 6 had a better BP control when they were already taking a combination therapy at baseline and month 1 as compared to those being treated with monotherapy at baseline. Several studies have shown that combination therapy may improve control rates of BP–37. In a2. Also, almost near 4 in 10 patients were smokers. These findings display the importance of pressing the need for lifestyle modification in hypertensive patients in Lebanon, since smoking abstinence and weight loss have shown to be key players in BP control[The results of the study show also that the study population tends to be overweight as the mean BMI was 28.75 ± 4.08 kg/m control.Follow-up results showed a significantly larger population reaching control at 6 month (67.52%) as compared to month 1 (44.08%). The overall BP control rate, after 6 months, in this cohort, is higher than international studies’ rates, 38, 39.BP outcomes according to JNC VII guidelines stratification was used throughout the analysis. The results of kappa statistics regarding the level of agreement between physicians’ perception and guidelines showed poor to fair agreement according to Landis and Koch’s classification. Such level of agreement reflects a gap between clinical practice and international guidelines. Factors related to insufficient access to guidelines at the point of care, insufficient information technology systems, especially for the small or solo practices, in addition to the culture, beliefs and habits of physicians and guidelines development have all been proposed as barriers to physician adherence to guidelines. In factWe acknowledge several limitations of the study. First, a sampling bias might have occurred at two levels: physicians’ selection and patients’ selection, which may affect the generalization of our results to the whole Lebanese population. Second, assessment of BP control was based on the measurement of diastolic and systolic BP at the clinic visit. People with hypertension often experience a spike in BP when the reading is taken in a physician’s office, leaving doctors with inaccurate information to determine the course of treatment and the status of BP control. To account for this “white coat effect”, researchers found significantly greater accuracy when several BP readings were combined from measurements taken at home or in the doctor’s office–44.Finally, some studies have shown that advancing age is the foremost reported predictor factor of poor BP control, 45, 46.I-PREDICT survey has the merit to be the first national study involving a large number of centers across a developing country. The results of this survey are informative as they suggest early control of BP and combination therapy as predictive factors of better BP control, and diabetes type 1 and 2 as a predictor of poor BP control in the population. Patients with these characteristics may represent important factors to target for better control in clinical practice. Clearly, our study may contribute to closing the knowledge gap on the predictors for BP control in Lebanon. Another positive finding is that rate of BP control in our cohort was high compared to international studies. Nonetheless, several approaches are to be applied in order to improve physician adherence to clinical practice guidelines. Physicians can play a key role in implementing any comprehensive, national program to improve hypertension management in Lebanon, but their assessment should be more objective and based on guided criteria in order to avoid subjectivity and medical inertia, 48.


Death rates due to hypertension in low and middle income countries are higher compared to high income countries. The present study is designed to combine life style modification and home blood pressure monitoring for control of hypertension in the context of low and middle income countries.The study is a two armed, parallel group, un-blinded, cluster randomized controlled trial undertaken within lower income areas in Kuala Lumpur. Two housing complexes will be assigned to the intervention group and the other two housing complexes will be allocated in the control group. Based on power analysis, 320 participants will be recruited. The participants in the intervention group (n = 160) will undergo three main components in the intervention which are the peer support for home blood pressure monitoring, face to face health coaching on healthy diet and demonstration and training for indoor home based exercise activities while the control group will receive a pamphlet containing information on hypertension. The primary outcomes are systolic and diastolic blood pressure. Secondary outcome measures include practice of self-blood pressure monitoring, dietary intake, level of physical activity and physical fitness.The present study will evaluate the effect of lifestyle modification and peer support home blood pressure monitoring on blood pressure control, during a 6 month intervention period. Moreover, the study aims to assess whether these effects can be sustainable more than six months after the intervention has ended. Data reported from the World Health Organization (WHO) showed that hypertension caused approximately 13% of annual deaths worldwide in the year of 2004. Death rates due to hypertension in low and middle income countries are higher compared to high income countries [Despite availability of effective anti-hypertensive medications at affordable cost, the control of hypertension is still a major issue in both developed and developing countries in Asia . LifestyPatients' non-cooperation or lack of compliance to pharmacological and non-pharmacological treatment are identified as key barriers in hypertension management . A revieThe present study is designed to combine life style modification and home blood pressure monitoring for control of hypertension in the context of low and middle income countries. To our knowledge, this is the first study to explore the effect of peer support home blood pressure monitoring rather than an individual based approach. The outcome from this study potentially may assist in development of future public health intervention in a resource limited setting.Objectives of this study are to investigate the effect of lifestyle modification and peer support home blood pressure monitoring on blood pressure control, dietary intake, physical activity and fitness during asix-month intervention period. Moreover, we aim to assess whether these effects are sustained more than six months after the intervention has ended.The study is a two armed, parallel group, un-blinded, cluster randomized controlled trial undertaken within lower income areas in Kuala Lumpur. There are six community housing complexes in the study area. Of these four housing complexes will be randomly selected and allocated 1:1) to the intervention and control arm  calculator. Participants in the control group will receive a BMI calculator and a pamphlet developed by the study team which includes brief information on hypertension, healthy diet and physical activity.Residents of the selected community housings who were diagnosed as having (stage 1 to stage 3) hypertension by medical professionals will be recruited as participants for the study. The potential participants will be identified based on the household survey data which was carried out by the 'PARTNER' study team from the University of Malaya. This survey was a cross-sectional design and conducted between February to November 2012. Altogether, 833 households were recruited from total 4726 households of four Community Housing Projects by using simple random sampling method. From 833 households, 431 individuals with hypertension were identified.Inclusion and exclusion criteria of the study are as follows.Adults aged 18 years and above will be eligible for the study if they have been diagnosed as having hypertension (stage 1 to 3) by medical professionals, Malaysian citizen, able to speak Malay  or/and English, willing to participate in all aspects of the intervention and fit to do exercise. Participants who can do daily activities without limitations are defined as "Fit to do exercise". The potential participants will be screened by Physical Activity Readiness Questionnaire (PAR-Q) whether they are fit to do exercise or need further consultation with physician.Residents who are pregnant, participants of other clinical trials or plan to leave the area before end of the study period will be excluded.The sample size was calculated by assuming p < 0.05 as the significance level, 80% power and 1 to 1 as the ratio of unexposed to expose in sample. The calculation was carried by using the OpenEpi version 2.3.1 . On the Universal sampling method will be used to recruit the study participants. The 431 residents of the selected community housing complexes who were diagnosed as (stage 1 to 3) hypertension will be invited to the study. We will take all participants which fit with inclusion criteria and willing to participate to the study so that actual participants may be more than calculated sample size.The intervention is developed based on Social Cognitive Theory which includes social support, self-regulation and self-efficacy . There wPeer support groups, consisting of five persons per group will be formed based on the proximity of the residences. An Omron digital blood pressure monitor (HEM-7111) will be distributed to each group and participants will be trained by a state registered nurse on how to measure blood pressure and record the blood pressure reading in a log book.Dietary assessments of individual participants will be conducted by three dietitians using 7 days diet histories. These dietitians will be randomly assigned to participant groups to assess the food intake. The same principal dietitian will conduct six sessions of health coaching to the participants in the group. The content of health coaching will include diet modification according to the DASH (Dietary Approaches to Stop Hypertension)diet  and reduExercise demonstrations and training will be conducted by a certified trainer from the sport medicine department. The exercise demonstration will focus on strengthening and flexibility exercise. The participants will be recommended to do low to moderate level physical activity and exercise minimum 150 minutes per week. Brisk walking will be also recommended as aerobic exercise. An exercise compact disc (CD) will be provided to the study participants as a guide to do exercise on their own. The participants will also be trained to record their physical activity in a log book. A Body Mass Index (BMI) calculator will be provided to help them to check their own BMI.The following tools and measurements will be used to evaluate the effect of the intervention and compliance of the participants regarding lifestyle modification included in the intervention. The measurements will be taken at baseline, six months and twelve months for both groups.Systolic and diastolic arterial blood pressure will be measured by using Omron Automated Blood Pressure Monitor HEM-7211 which is recommended by the Malaysian Hypertension Association. The arterial blood pressure measurement will be done according to the standardized procedure recommended by World Health Organization . After aA booklet of self-administered questionnaires will be provided for the participants to be completed. Questionnaires include i) Socio-demographic characteristics, ii) Knowledge, awareness and treatment of hypertension, and iii) Global Physical Activity Questionnaire (GPAQ) and, iv) Socio Cognitive variables.The questionnaire for knowledge, awareness and treatment of hypertension is adapted from the questionnaire developed by World Health Organization . The queGPAQ is a tool developed by World Health Organization. It consists of 16 questions to measure the level of physical activity of each individual. The total score of physical activity will be expressed as METs . One MET is defined as the energy cost of sitting quietly, and is equivalent to a caloric consumption of 1 kcal/kg/hour. In order to calculate a person's overall energy expenditure, 4 METs will get assigned to the time spent in moderate activities, and 8 METs to the time spent in vigorous activities . The GPA7 Days Diet History is chosen for dietary assessment. The tool has been pre-tested with 20 subjects from the community housing complexes, 10 with hypertension and 10 without hypertension. The 7 Days Diet History will be conducted by trained dietitians. A diet history flip chart will be used as a supplementary tool to assist the study participants during the dietary evaluation and to help in estimating the portion size of the foods consumed .Height will be measured without socks and shoes by using a calibrated vertical Seca Portable 217 Stadiometer, to the nearest millimetre. Weight will be measured with light clothing using a Seca 813 digital electronic scale, to the nearest decimal fraction of kilogram. Body mass index (BMI) will be calculated as weight in kilograms divided by the square of height in meters. Body fat composition will be measured using a Tanita portable Body Composition Analyzer SC-240 MA. Waist circumference (WC) and hip circumference (HC) will be measured with a non-elastic Seca measuring tape, to the nearest millimetre. Position of waist circumference measurement will be done at a level midway between the lower rib margin and highest point of iliac crest with the tape all around the body in horizontal position [The "six minute walk test" will be conducted to measure cardiovascular endurance. The six minute walk test is a sub maximal measure of aerobic capacity -27. A caThe follow up will be at six months and twelve months for both intervention and control groups. The GPAQ questionnaire survey, 7 days diet history, blood pressure measurement and physical evaluation will be conducted at baseline, six months and twelve months. The log book kept by participants in the intervention group will be checked for completeness and errors after one month of the intervention and the record will be taken at three, six, nine and twelve months in order to check the compliance of self-blood pressure monitoring and home-based exercise, and whether they measured their blood pressured once a week or not.The primary outcomes will be systolic and diastolic blood pressure measured at zero month (enrolment), six months (end of intervention period), and twelve months (maintenance period). Secondary outcome measures include some Social Cognitive Theory variables related to self-efficacy and self-regulatory such as practice of self-blood pressure monitoring, and adherence of exercise. Other secondary outcomes will be dietary intake, level of physical activity and physical fitness in term of both cardio vascular endurance and muscle strength.The data analysis will be done by using Stata software (version 11: StataCorp). Bivariate analysis such as Chi-square tests , t test and ANOVA  and Mann-Whitney-U test (for continuous variable with skewed distribution) will be applied to compare the two groups with respect of socio-demographic characteristics, number of clinic visits, practice of self-blood pressure monitoring, blood pressure at the time of enrolment, dietary intake, level of physical activity and fitness.The primary outcome, change in systolic and diastolic blood pressure at six months and twelve months will be compared between and within the groups by using t test and ANOVA. If there are some differences in group characteristics, it will be adjusted by performing multivariate analysis of variance (MANOVA).Since the secondary outcomes such as numbers of self-blood pressure monitoring, dietary intake, body composition , level of physical activity and physical fitness are also continuous variables, these will be examined as per primary outcome. The normality of the continuous variables will be checked before analysis and proper transformation will be done if the data is not normally distributed. The level of statistical significance will be set at p < 0.05.In order to calculate nutrient intake, Nutritionist Pro™ Diet Analysis software will be used to analyse the diet record. It will focus mainly on energy, protein, fat, carbohydrate, sodium, dietary fibre and others. Based on the 7 days diet histories, the average energy consumed with macronutrients , protein (g), fat (g), saturated fat (g) and others) and micronutrients , iron (mg), vitamins and minerals) value will be calculated. All nutrient intakes will be transferred to the Stata software for final data analysis.Ethical approval was obtained from the Medical Ethics Committee, University Malaya Medical Centre (Reference Number: 944.18). The trial was registered at Iranian Clinical Trial registry (Reference Number: IRCT2013030512705N1). The control groups will be receiving all components of intervention after completion of the study.Hypertension is a major contributor to the growing global pandemic of cardiovascular diseases and stroke. It is also one of the main non communicable diseases in Malaysia that are becoming an economic burden of the nation . By realOur intervention is in line with national strategy and approach for prevention and control of hypertension. Previous studies showed that adherence to the "Dietary Approaches to Stop Hypertension (DASH) diet" alone can reduce both systolic and diastolic blood pressure ,18. Our We selected a low income urban community as population of interest in order to reduce existing disparities in health status and access to health care across population sub-groups. Previous research conducted in the study area showed that prevalence of hypertension and other cardiovascular risk factors are higher compared to the nation-wide study. The health system in Malaysia is heavily financed by the Government and all citizens can enjoy financial and geographical access to health care . HoweverOne of the expert recommendations to improve hypertension management in Asia is to increase awareness of hypertension, enhance treatment adherence and promote home blood pressure monitoring . PositivHowever, to obtain a blood pressure monitor is a big challenge since more than half of our study population have an average household income less than 2,000 MYR which equivalent to (USD 605). The purchase of a reliable quality digital blood pressure monitor would cost about 10% of household income which is generally considered as catastrophic health care expenditure . Our stuWe expected that after completing intervention, the participants of our study could benefit by increasing awareness of healthy diet and physical activity, adopting healthy life style and improving self-management of hypertension. The proposed intervention would ensure the self-efficacy and self-regulation of regular blood pressure monitoring, healthy diet choice, and maintaining physical activities and exercise with peer social support. There would be a promising possibility that our intervention is widely replicable and adopted as a model of community based approach for combating hypertension in low and middle income countries.The authors declare that they have no competing interests.TTS, HAM and AMN conceived the study and designed the interventions. AB and LJM gave input on method and statistical analysis. NAA, FMH, NT and MD conducted the pilot testing of the study tools. All authors were responsible for the drafting of this paper and approved the final manuscript.


A seeming paradox of sickle cell disease is that patients do not suffer from a high prevalence of systemic hypertension in spite of endothelial dysfunction, chronic inflammation and vasculopathy. However, some patients do develop systolic hypertension and increased pulse pressure, an increasingly recognized major cardiovascular risk factor in other populations. Hence, we hypothesized that pulse pressure, unlike other blood pressure parameters, is independently associated with markers of hemolytic anemia and cardiovascular risk in sickle cell disease. We analyzed the correlates of pulse pressure in patients (n  =  661) enrolled in a multicenter international sickle cell trial. Markers of hemolysis were analyzed as independent variables and as a previously validated hemolytic index that includes multiple variables. We found that pulse pressure, not systolic, diastolic or mean arterial pressure, independently correlated with high reticulocyte count  and high hemolytic index  in patients with homozygous sickle cell disease in two multiple linear regression models which include the markers of hemolysis as independent variables or the hemolytic index, respectively. Pulse pressure was also independently associated with elevated serum creatinine , and with proteinuria . These results from the largest sickle cell disease cohort to date since the Cooperative Study of Sickle Cell Disease show that pulse pressure is independently associated with hemolysis, proteinuria and chronic kidney disease. We propose that high pulse pressure may be a risk factor for clinical complications of vascular dysfunction in sickle cell disease. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses. Findings from the landmark Cooperative Study of Sickle Cell Disease (CSSCD) revealed that sickle cell disease (SCD) patients, particularly those affected by HbSS, have lower systolic and diastolic blood pressure values compared to age, sex and race-matched normative values.Multiple hypotheses have been formulated over the following years to explain the paradox of a population affected by severe endotheliopathy and vasculopathy and accelerated organ damage, yet largely spared from systemic hypertension. Possible explanations have taken into consideration the role of anemia, resulting in increased cardiac output with compensatory decreased vascular resistance, hyposthenuria leading to sodium loss, decreased blood viscosity of oxygenated sickle blood at low hematocrit levels, and the role of compensatory increases in cyclooxygenase-2, endothelial nitric oxide synthase, placenta growth factor and other endothelial-derived factors.Elevated pulse pressure has recently emerged as an independent predictor of cardiovascular outcomes and prognostic factor for death in patients at high risk of cardiovascular morbidity and mortality such as aging patients and those affected by advanced chronic kidney disease.Hemolysis in SCD causes endothelial dysfunction via multiple mechanisms, and both hemolysis and endothelial dysfunction may be independently linked to elevated pulse pressure. High plasma levels of free hemoglobin from hemolyzed RBC lead to nitric oxide depletion and reactive oxygen species formation which cause impaired vascular relaxation and increased arterial stiffness.The study population and design have been described in detail elsewhere.Local institutional review boards (University of Pittsburgh IRB PRO07060076) approved the protocol and written informed consent was obtained and approved by the IRB . This study is an analysis of data from the walk-PHaSST trial.2 = 175 × (serum creatinine)-1.154 × (age)−0.203 ×  × (1.212 if African American)).All screening study subjects were evaluated by histories of clinical events and lifetime treatments, physical examination, laboratory screening, transthoracic Doppler echocardiography, and the six-minute walk test. Blood pressure was obtained according to the standard method at each site with the cuff placed in the forearm and the patient seated. Routine laboratory tests including complete blood count, serum chemistry profile, lactate dehydrogenase (LDH), urinalysis, urine albumin, and urine creatinine from samples taken at the subject's screening visit were performed in the local laboratories of the participating institutions. Echocardiography was performed at the participating institutions and read centrally in the National Heart, Lung and Blood Institute echocardiography core laboratory. Cardiac measurements were performed according to American Society of Echocardiography guidelines.2 and albuminuria <30 mg/g creatinine; stage 1 – eGFR ≥ 90 ml/min/1.73 m2 and albuminuria ≥ 30 mg/g creatinine; stage 2 – eGFR 60–89 ml/min/1.73 m2 and albuminuria ≥ 30 mg/g creatinine; stage 3 – eGFR <60 ml/min/1.73 m2.Patient characteristics are presented as median and interquartile range (IQR) or number and percentage of participants with a given characteristic, and associations with hemoglobin genotype were assessed using the Wilcoxon two-sample test and the Pearson chi-square test of independence. A hemolytic component variable was derived using principal component analysis from four markers of hemolysis - LDH, aspartate aminotransferase (AST), total bilirubin, and reticulocyte percent - as described elsewhere.Associations of patient characteristics with pulse pressure were assessed using Spearman correlation coefficients and linear regression analysis, log-transforming continuous variables as necessary to normalize skewed distributions. Regression coefficients were tested for significant differences from zero by the t-test. For the final models, variables were entered in a stepwise approach if they had a significant univariate association with pulse pressure. All statistical analyses were performed using SAS, version 9.1  and Stata, version 11.1 .Most patients enrolled in walk-PHaSST had either HbSS or HbSC and were analyzed separately. We are reporting their baseline characteristics as these are not available from prior walk-PHaSST published reports . As expeWe next conducted a univariate analysis of pulse pressure and multiple clinical and laboratory markers in patients with HbSS and HbSC disease . In HbSSIn HbSC patients, a different pattern of pulse pressure correlates emerged. In this group, pulse pressure was positively correlated with age and BMI. There was no correlation with markers of hemolysis and although, similarly to HbSS patients, there was a positive correlation with creatinine , there wIn both HbSS and HbSC groups pulse pressure was positively correlated with TRV.A complete list of all univariate correlations is reported in We conducted a multiple linear regression analysis to determine which of the variables that emerged as significant by univariate analysis were able to cross-sectionally predict the blood pressure variables  in the regression model. The following pairs of variables could not be entered into the model simultaneously due to their high correlation, so we fitted separate models for each of them: reticulocytes and hemolytic component; creatinine and estimated glomerular filtration rate; and proteinuria and urine albumin-to-creatinine ratio. For brevity, we are only reporting the results of the regression analysis for pulse pressure for HbSS and HbSC patients, separately.As shown in In model 1, where the hemolysis markers LDH, AST, total bilirubin, and reticulocyte proportion were coded as individual variables, the reticulocyte proportion emerged as a predictor of pulse pressure, together with TRV ≥ 3.0 m/sec, hemoglobin oxygen saturation, creatinine and proteinuria. In model 2, the hemolytic component emerged as a significant predictor of pulse pressure in the regression model. Model 3 and 4 were fitted with the urine album-to-creatinine ratio replacing proteinuria and showed similar results.In hemoglobin SC patients, creatinine (model 1) and estimated glomerular filtration rate (model 2) and ferritin (both models) were the only predictors of pulse pressure .Pulse pressure is emerging as an important risk factor for end-organ damage and cardiovascular morbidity and mortality in many conditions  than normative controls, a difference observed for all age groups and both sexes.As other studies have shown,We also found a significant association between BMI and pulse pressure in HbSC patients, but not in HbSS patients. In HbSC patients, we also observed an interaction of gender and BMI, with associations of BMI with pulse pressure observed in males but not in females (data not shown). BMI has been positively correlated with pulse pressure in other populations without SCD,Finally, we found significant independent associations between hemoglobin oxygen saturation and pulse pressure in HbSS patients and ferritin and pulse pressure in HbSC patients. We hypothesize that the inverse relationship between hemoglobin oxygen saturation and pulse pressure in HbSS patients may be either the result of increased cardiopulmonary disease burden in patients with high pulse pressure, as also shown by the association with elevated TRV, or worse anemia secondary to hemolysis. As shown in The main limitation of our study is that the walk-PHaSST clinical cohort was not designed to specifically evaluate baseline systemic blood pressure in SCD patients. Thus, data on the history of hypertension or use of antihypertensive medications are not available for our population. The use of principal components analysis to derive a hemolytic component variable from several correlated variables all related to hemolysis is an additional limitation because of potentially important associations that could have been missed by using a data reduction technique such as PCA. Finally, eGFR and creatinine are relatively poor markers of kidney function in sickle cell disease due to glomerular hyperfiltration and increased creatinine excretion by the proximal tubule in this disease. It is, unfortunately, not possible to infer which patient subsets may have experienced worse hyperfiltration and the confounding effect of this phenomenon, although it is safe to assume that glomerular hyperfiltration decreased with increasing age in our population. Associations of eGFR with pulse pressure did not, however, change after adjustment for age. Our results are also strengthened by the availability of values of proteinuria and albumin to creatinine ratio in a subset of patients. These are recognized valuable screening tools of kidney dysfunction by the recently published sickle cell guidelines.In summary, our results show that pulse pressure is closely linked to hemolysis in SCD and suggest that it may be an important predictor of cardiovascular risk. Longitudinal and mechanistic studies should be conducted to confirm these hypotheses. Moreover, measurement of pulse wave velocity may provide further information on arterial stiffness and its relationship to pulse pressure and microvascular dysfunction in SCD.


Background. Estimation of glomerular filtration rate (eGFR) from biomarkers has evolved and multiple equations are available to estimate renal function at bedside. Methods. In a random sample of 119 Uruguayans ), we used Bland and Altman's method and Cohen's kappa statistic to assess concordance on a continuous or categorical (eGFR < 60 versus ≥60 mL/min/1.73 m2) scale between eGFRcys (reference) and eGFR derived from serum creatinine according to the Modification of Diet in Renal Disease (eGFRmdrd) or the Chronic Kidney Disease Epidemiology Collaboration equations (eGFRepi) or from both serum cystatin C and creatinine (eGFRmix). Results. In all participants, eGFRmdrd, eGFRepi, and eGFRmix were, respectively, 9.7, 11.5, and 5.6 mL/min/1.73 m2 higher (P < 0.0001) than eGFRcys. The prevalence of eGFR <60 mL/min/1.73 m2 was the highest for eGFRcys (21.8%), intermediate for eGFRmix (11.8%), and the lowest for eGFRmdrd (5.9%) and eGFRepi (3.4%). Using eGFRcys as reference, we found only fair agreement with the equations based on creatinine (Cohen's kappa statistic 0.15 to 0.23). Conclusion. Using different equations we reached clinically significant differences in the estimation of renal function. eGFRcys provides lower estimates, resulting in higher prevalence of eGFR <60 mL/min/1.73 m2. The glomerular filtration rate (GFR) is the most widely used indicator of overall renal function. The GFR can be measured by clearance of an ideal, usually exogenous, filtration marker such as inulin, iothalamate, EDTA, diethylene triamine pentaacetic acid, or iohexol. The clearance of endogenous markers such as creatinine or blood urea nitrogen can overestimate or underestimate the GFR. All these methods have the drawback to be complex and require 24-hour urine collection, which is not always practicable in day-to-day clinical practice. A more pragmatic approach is to estimate GFR from equations based on serum creatinine , 2.More recently, experts proposed cystatin C as an alternative to creatinine . CystatiCompared to GFR measurement based on the renal clearance of exogenous markers, estimated glomerular filtration rate (eGFR) is more precise if derived from both cystatin C and creatinine levels in serum . This obn = 22) or because they had not yet completed the physical examination (n = 8). Thus, the number of participants analysed statistically totalled 119.GEnotipo Fenotipo y Ambiente de la HiperTension en UruguaY (GEFA-HT-UY) is a prospective cohort study started in April 2012 conducted by the Unidad de Hipertensión Arterial, Hospital de Clínicas Dr. Manuel Quintela, Universidad de la República, Montevideo, Uruguay . The EthThe examinations took place at a field centre located within the neighbourhood. Trained observers administered a standardised questionnaire inquiring into each participant's medical history, smoking and drinking habits, and intake of medications. They measured blood pressure according to the European guidelines. After participants had rested for 5 minutes in the sitting position, the observers obtained five consecutive blood pressure readings (phase V diastolic pressure) to the nearest 2 mm Hg, using mercury sphygmomanometers. Standard cuffs had a 12 × 24 cm inflatable portion, but if upper arm girth exceeded 31 cm, larger cuffs with 15 × 35 cm bladders were used. Pulse pressure is the difference of systolic minus diastolic blood pressure. Mean arterial pressure is diastolic pressure plus one-third of pulse pressure. For analysis, the five blood pressure readings were averaged. Hypertension was an office blood pressure of at least 140 mm Hg systolic or 90 mm Hg diastolic or use of antihypertensive drugs. The observers measured body height to the nearest 0.5 cm with a pliable measurer and the participant standing against the wall. Participants wore light indoor clothing without shoes for body weight measurements. Body mass index was weight in kilograms divided by square of height in meters. Venous blood samples were obtained after at least 12 hours fasting and were kept at 4°C and within 2 hours period were analysed for serum levels of cystatin C, creatinine, cholesterol, and glucose. Diabetes mellitus was the use of anti-diabetic drugs or a fasting glucose ≥ 126 mg/dL (7 mmol/L).After the participants had rested 15 min in the supine position, we recorded during an 8 s period the radial waveforms at the right side by applanation tonometry. We used a high-fidelity SPC-301 micromanometer  interfaced with a computer running SphygmoCor software, version 8.2 . We discarded recordings when the systolic or diastolic variability of consecutive waveforms exceeded 5% or the amplitude of the pulse wave signal was less than 80 mV. We calibrated the radial pulse wave on the brachial blood pressure . From thA) and from the suprasternal notch to the femoral sampling site (distance B). Pulse wave travel distance was calculated as distance B minus distance A. Pulse transit time was the average of 10 consecutive beats. Pulse wave velocity was the distance in meters divided by the transit time in seconds , Delanaye and colleagues report that the prevalence of eGFR below 60 mL/min/1.73 m2 using eGFRcys, eGFRmdrd, eGFRepi, and eGFRmix was 4.7%, 13.0%, 9.8%, and 5.0%, respectively  and 1999–2002 ), observed slightly higher eGFR using cystatin C than creatinine equations (102.9 versus 99.4 mL/min/1.73 m2). However, in line with our results, the proportion of subjects with eGFR below 60 mL/min/1.73 m2 was larger if derived from cystatin C than creatinine (5.5% versus 4.7%). More recently, Tsai and colleagues  and 0.39 [eGFRcys versus eGFRepi]) ) . In thisHow to explain the discrepancies between cystatin C and creatinine based equations? We first discarded all potential sources of preanalytical and analytical errors. We analysed creatinine in fresh serum samples and cystatin C in samples that were kept frozen at −80°C. Over a period of 10 years, a decay in cystatin C levels occurs using a particle-enhanced nephelometric assay (PENIA) . Such decys had elevated risk of death, cardiovascular disease, and heart failure and had an elevated risk of kidney failure [P < 0.001) if they were categorized based on eGFRcys (32.1%) than on eGFRepi (5.7%) with a similar but not significant trend among the few diabetics patients. However, when computing IDI and NRI we did not observe significant differences between the various estimates of eGFR for hypertension or diabetes (P ≥ 0.24). In accordance with previous reports [P = 0.27) and age (P < 0.0001), systolic blood pressure (P < 0.01), cholesterol (P = 0.004), aortic pulse wave velocity (P < 0.0001), and the central augmentation index (P < 0.0001) increased with lower categories of eGFRcys . Table S4 summarize the computations of the eGFR according to racial parental background of the participants.


Endothelial-derived apoptotic microparticles (EMPs) play a pivotal role in endothelial dysfunction in hronic Heart Failure (CHF).The present study aimed to evaluate the association between EMPs and pro-inflammatory biomarkers, clinical status, and outcomes in the patients with ischemic CHF.This study was conducted on 154 patients with ischemic symptomatic moderate-to-severe CHF on discharge from hospital. The observation period was up to 3 years. Circulating NT-pro-BNP, TNF-alpha, sFas, and sFas ligand were determined at baseline. Flow cytometry analysis was used for quantifying the number of EMPs. All-cause mortality, CHF-related death, and CHD-re-hospitalization rate were examined. The data were analyzed using descriptive statistics, Receive Operation Characteristic Curve (ROC), and logistic regression analysis. Besides, P < 0.05 was considered as statistically significant.During a median follow-up of 2.18 years, 21 participants died and 106 subjects were hospitalized repetitively. The results showed a significant difference between the patients with a large number of EMPs (> 0.514 n/mL) and those with a low level of the biomarker (< 0.514 n/mL) regarding their survival. The number of circulating EPMs independently predicted all-cause mortality , CHF-related death , and CHF-related re-hospitalization .Among the patients with symptoms of CHF, increased number of circulating EMPs was associated with increased 3-year CHF-related death, all-cause mortality, and risk of recurrent hospitalization due to CHF. Recent studies have suggested that endothelial dysfunction is crucial for clinical manifestations of Chronic Heart Failure (CHF) , 2. It hThe present study aims to evaluate the relationship between EMPs and pro-inflammatory biomarkers, clinical status, and outcomes in the patients with ischemic CHF.This study was conducted on 154 patients  aging 48 to 62 years old with ischemic symptomatic moderate-to-severe CHF. CHF was diagnosed according to the current clinical guidelines . WrittenBefore enrollment of the patients into the study, their ischemic heart disease was verified through multispiral computed tomography angiography using Somatom Volum Zoom scanner  with two detector rows at the end of breathing . After pLeft Ventricular (LV) end-diastolic and end-systolic volumes were measured by modified Simpson’s method  using ACGlomerular Filtration Rate (GFR) was calculated using MDRD-6 formula .Blood samples were taken in the morning (at 7 - 8 A.M.) and poured into cooled silicone test tubes. The samples were processed according to the recommendations of the manufacturer of the utilized analytical technique.Circulating NT-pro-BNP level was measured by immunoelectro chemoluminescent assay using sets by R&D Systems (USA) on Elecsys 1010 analyzer . Moreover, the serum concentrations of TNF-alpha, sFas, and sFas ligand were determined in duplicate using commercially available enzyme-linked immunosorbent assay kits . Overall, 100 μL of the serum samples was assayed in parallel to determine the standard concentrations for each biological marker. The mean intra-assay coefficients of variation were < 10% of all the cases. The concentrations of Total Cholesterol (TC) and High-Density Lipoproteins (HDLP) were measured by fermentation method. On the other hand, Low-Density Lipoproteins (LDL-C) concentration was computed according to the Friedewald formula (1972). All the biomarkers were determined at baseline.EMPs were phenotyped through flow cytofluorimetry by phycoerythrin (PE)-conjugated monoclonal antibody against CD31  followed by incubation with fluorescein isothiocyanate (FITC)-conjugated annexin V  using high-definition fluorescence activated cell sorter methodology. The samples were incubated in the dark at room temperature for 15 min according to the manufacturer’s instructions. The samples were then analyzed on a FC500 flow cytometer (Beckman Coulter) after 400 µL annexin-V binding buffer was added. Overall, 500 thousand events were analyzed for each sample. Furthermore, the EMPs gate was defined by size, using 0.8 and 1.1 mm beads . CD31 + /annexin V + microparticles were defined as EMPs positively labeled for CD31 and annexin V (CD31 + /annexin V +) .All the statistical analyses were performed using the SPSS statistical software, version 22 . The data were presented as mean, Standard Deviation (± SD), 95% Confidence Interval (CI), median, and interquartile range. Student t-test or Shapiro–Wilk U-test were used to compare the main parameters of the patients’ groups. Additionally, Chi-square test and Fisher exact test were used to compare the categorical variables between the study groups. Moreover, the factors which could be potentially associated with circulating EMPs were determined by logistic regression analysis. Receive Operation Characteristic Curve (ROC) analysis was also performed to compare the cutoff points of the number of EMPs to the predicted values. Odds Ratio (OR) and 95% CI were calculated for all the independent predictors of patients’ survival. P < 0.05 was considered as statistically significant.During a median follow-up of 2.18 years, 21 participants died and CHF-related death was detected in 18 patients. Additionally, 106 subjects were hospitalized repetitively due to advanced CHF (17 cases in the dead cohort and 89 ones in the survived cohort). According to The median of EMPs circulating levels was 0.286 n/mL  and 0.673 n/mL  in survived and dead patients, respectively (P < 0.001). The concentrations of TNF-alpha, sFAS, and sFAS ligand were significantly lower in the survived patients compared to the dead ones . In addiThe study results indicated a direct relationship between the number of EMPs in plasma and NYHA functional class , sFAS/sFASl ratio , sFAS , TNF-alpha , sFASl , and NT-pro-BNP . Also, a weak association was observed between the number of EMPs and type 2 diabetes mellitus , multi-vessel lesion of coronary arteries , Е/Аm , Е/Em , gender , and TC . On the other hand, an inverse relationship was found between the number of EMPs and LVEF  and eGFR . Nevertheless, no significant association was observed between the levels of circulating EMPs and fasting plasma glucose, HbA1c, systolic and diastolic BP, premature CAD in family anamnesis, and medications in both cohorts .The optimum cut-off point for EMPs number in circulation was determined by the relative importance of the sensitivity and specificity of the test. ROC analysis showed that the cut-off point of EMPs number for cumulative survival function was 0.514 n/mL . BesidesMultivariate logistic regression was used to assess whether any combination of assays was able to better discriminate between the survived and dead patients. According to the results of logistic regression analysis, the main factors independently related to cumulative mortality and CHF-related rehospitalisations were EPMs, NT-pro-BNP, NYHA class, TNF-alpha, sFAS/sFAS ligand ratio, LVEF, type two diabetes mellitus, and three- and multi-vessel lesion. In addition, the number of circulating EPMs independently predicted all-cause mortality , CHF-related death , and CHF-related rehospitalization  . NYHA clUsing a stepwise model selection method for multivariable prediction model, we investigated the summary effect of any combinations of EMPs, NT-pro-BNP, TNF-alpha, sFAS/sFAS ligand ratio, and LVEF on all-cause mortality, CHF-related death, and CHF-related rehospitalizations . AccordiCirculating EMPs play a pro-inflammatory detrimental role in the vascular dysfunction that is a key mechanism in development and progression of a wide range of cardiovascular diseases . EMPs maAmong the patients with symptoms of CHF, increased number of circulating EMPs was associated with increased 3-year CHF-related death, all-cause mortality, and risk of recurrent hospitalization due to CHF. This also provides an additional explanation by which low-intensity inflammation that is suitable for CHF may contribute to development of endothelial dysfunction and might reflect a risk of unfavorable clinical outcomes irrespective of traditional biomarkers, such as NT-pro-BNP, NYHA class, and LVEF.The study was approved by the local Ethics Committee of State Medical University, Zaporozhye, Ukraine. The study was carried out in conformity with the Declaration of Helsinki.This study had some limitations. The authors believe that further studies should be conducted on a larger cohort of patients to improve the power of the study. Of course, these restrictions might have had no significant impact on the interpretation of the study results.


P < 0.001). Blood glucose was linearly correlated to SPA, TOS, TAS, and OSI in control-2, case-1 and case-2 (P < 0.001). Serum creatinine was linearly correlated with SPA, TOS, TAS and OSI in control-2 and case-1 (P < 0.001). In case-2, serum creatinine was significantly correlated with SPA only (P < 0.001). Thus, the study concluded that SPA and oxidative stress significantly correlated with blood glucose and creatinine. SPA, TOS, TAS, and OSI can be used as biomarkers for diagnosis of kidney damage.Association of oxidative stress and serum prolidase activity (SPA) has been reported in many chronic diseases. The study was aimed at evaluating the correlation of glucose and creatinine to SPA and oxidative stress in patients with diabetic nephropathy (DN) and end stage renal disease (ESRD) concerned with T2DM. 50 healthy volunteers, 50 patients with T2DM, 86 patients with DN, and 43 patients with ESRD were considered as control-1, control-2, case-1, and case-2, respectively. Blood glucose, creatinine, SPA, total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) were measured by colorimetric tests. SPA, TOS, and OSI were significantly increased in case-1 and case-2 than control-1 and control-2, while TAS was significantly decreased ( Chronic kidney disease is one of the major health related issues of twenty-first century. Nephropathy constitutes a major microvascular complication of long term diabetes mellitus and it is the most common cause of end stage renal disease. It is categorized into five different stages. In stage one, the kidney function is normal and in stage two it is slightly reduced. Third and fourth stages are considered as incipient and overt diabetic nephropathy, respectively, while the last or fifth stage of diabetic renal disease is considered as end stage renal disease , 2. HypeProlidase EC 3.4.13.9) activity is reported as a marker for oxidative stress for many diseases, like diabetes, diabetic neuropathy, nonulcer dyspepsia, chronic liver diseases, erectile dysfunction, osteoporosis, and so forth –11. It c.9 activiThus, in the present study, we aimed to observe the correlation of blood glucose and creatinine to serum prolidase activity and oxidative stress in T2DM, diabetic nephropathy and in ESRD with T2DM, and assess the possibility of a new biomarker for the evaluation of kidney damage.This study was done at the Department of Biochemistry and Department of Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India. The study was ethically approved by institutional ethical committee and signed informed consent was taken from every subject.Total of 229 subjects of matched age and sex were selected. Out of 229, 50 subjects  who were patients of type-2 diabetes mellitus (T2DM) of ages between 25 and 76 (53.34 ± 14.68) years, 86 patients with diabetic nephropathy  of age range 28–76 (52.34 ± 12.89) years, 43 ESRD patients  caused by T2DM of age range 30−80 (57.34 ± 15.36) years old, and 50 healthy volunteers  of age 25–75 (52.64 ± 18.76) years old were included in the study. Healthy volunteers and patients with T2DM were considered as control-1 and control-2 group, respectively, whereas patients with diabetic nephropathy and ESRD were categorized as case-1 and case-2, respectively .Inclusion Criteria. Patients of T2DM, diabetic nephropathy, and ESRD attending outpatient department and admitted in the ward of nephrology, Sir Sunder Lal hospital, BHU, who agreed to participate in the study were included. Medical history, standard physical examination, and test of biochemical parameters  listed in Exclusion Criteria. Patients suffering from major infections like tuberculosis, HIV, and so forth, chronic heart failure, pregnant females, taking potent antioxidant, and history of alcohol intake were excluded from our study. Diabetic macroangiopathic complications  and acute myocardial infarction in diabetes groups were excluded.Venous blood was collected in 2 vials (EDTA tube and plane tube). Blood in the EDTA tube was used for the estimation of glucose and hemoglobin, while blood in plane tube was allowed to clot and serum was separated by centrifugation at 3000 rpm for 10 min at 4°C. Serum samples for the measurement of serum prolidase activity, total oxidant status (TOS), and total antioxidant status (TAS) were stored at −80°C. Samples were thawed to room temperature before every assay, and repeated thaw was avoided.2 in 6 mM tris HCl buffer), standard proline solution (650 μmol/L in 0.45 mol/L trichloroacetic acid), 94 mmol/L glycyl-l-proline solution (94 mmol/L Gly-l-Pro solution in 0.05 mol/L Tris HCl buffer containing 1 mmol/L of MnCl2 (pH 7.8–8.0)), and Chinard's reagent  was added to 593 mL of distilled water) were prepared.Diluting solution  the reaction was checked. Followed by 100 μL of diluted, nonincubated serum was added in control tube. After that centrifugation at 2000 rpm for 5 minutes supernatant was separated and 0.5 mL was used for proline estimation.The serum obtained from subjects were diluted six times with diluting solution and preincubated for 24 hours at 37°C for enzyme activation. The enzymatic reactions were carried out in two Eppendorf tubes and labeled as experimental and control. 100 For measurement of enzymatic reaction, four tubes were selected and labeled as blank tube, standard tube, experimental tube, and control tube. 1 mL of glacial acetic acid and 1 mL of Chinard's reagent were added in each tube. After this, 0.5 mL of supernatant was added in experimental tube and control tube. 0.5 mL of trichloroacetic acid (0.45 mol/L) was added in blank tube and 0.5 mL of standard proline solution was added in standard tube. All four tubes were incubated in water bath at 90°C for 10 minutes and optical densities (OD) were taken at 515 nm. Spectrophotometer was adjusted to zero with blank tube solution.S: standard tube absorbance, E: experimental tube absorbance, C: control tube absorbance, and [S]: substrate concentration in mmol/L (94 mmol/L).For the calculation of enzymatic activity we used the following Myara et al.  equationTAS and TOS of serum were determined by using automated measurement methods developed by Erel , 16.OSI values were calculated according to the following formula :(2)OSIEstiEstimation of clinical parameters like creatinine, blood glucose (fasting blood sugar (FBS), and two hours postprandial blood sugar (PPBS)) and urea were done by commercial kits . Hemoglobin was estimated by hematology autoanalyser and blood pressure was measured by mercury sphygmomanometer.t-test, ANOVA Student-Newman-Keuls test, and Pearson's correlation were used. P value less than 0.05, 0.01, and 0.001 were considered as significant, highly significant, and very highly significant, respectively. Sensitivity, specificity, and all other statistical calculations were done by use of software SPSS 16.0 version. Inter- and intraassay % of coefficient of variations (CV) was estimated for SPA (6.85 and 3.82%), TAS (8.45 and 4.12%), and TOS (7.38 and 3.89%).Parametric and nonparametric statistical methods, Student's Scr), fasting blood glucose (FBS), postprandial blood glucose (PPBS), systolic blood pressure, diastolic blood pressure, haemoglobin, and blood urea within and between groups  were significant , while differences of TAS for any other two groups were of significant value  was significantly decreased than in case-1, control-2 and control-1  (μmol H2O2 Eq./L) was significantly increased than in case-1, control-2, and control-1   was significantly increased than in case-1 (16.04 ± 7.58), control-1 (8.02 ± 4.21), and control-2 (10.58 ± 4.58) (P < 0.001), while nonsignificant correlation was observed between creatinine and TOS and TAS and OSI  and creatinine (Cr) with SPA, TOS, TAS, and OSI are tabulated in  and OSI .DN and ESRD both are different stages of kidney damage. Thus for prediction of kidney damage values of area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity for SPA, TOS, TAS, and OSI were tabulated in Out of the 229 patients enrolled for the study, 94 were females and 135 were males. As shown in P < 0.001)  . PatientP < 0.05) and increase in OSI was non-significant (P = 0.07), while TAS was non-significantly decreased (P = 0.091) in patients with T2DM than healthy volunteers , while increase in duration of diabetes negatively correlates with decrease in TAS . TOS at ≥16.64 μmol H2O2 Eq./L, TAS at ≤0.81 mmol Trolox Eq./L, and OSI at ≥10.24 were predicted 89.10% sensitivity with 60% specificity, 89.10% sensitivity with 2% specificity, and 80.60% sensitivity with 67% specificity for kidney damage (either DN or ESRD or both), respectively .This study revealed that serum prolidase activity and oxidative stress were significantly increased in patients with DN and ESRD than patients with T2DM and healthy volunteers. The same pattern was also obtained for T2DM with respect to healthy volunteers with significant differences. Blood glucose and creatinine were correlated to oxidative stress markers  and serum prolidase activity in patients with T2DM, DN, and ESRD. It is concluded that serum prolidase activity, TOS, TAS, and OSI at cutoff values ≥60.78 mmol Min


Pulmonary artery systolic pressure had a good correlation with TRAb , but was not related to free T4  and free T3 . To determine the important variables present in patients with Graves’ disease that may be related to pulmonary artery systolic pressure, 4 variables  were used in the multivariate analysis. In addition to PVR  and cardiac output , TRAb  emerged as a significant variable related to pulmonary artery systolic pressure. Thus, in addition to the effect of thyroid hormone on the cardiovascular system, autoimmune-mediated pulmonary vascular remodeling may play a role in Graves’ disease-linked elevated pulmonary artery systolic pressure.A link between hyperthyroidism and pulmonary hypertension has been reported, but the underlying mechanisms of these two conditions have not been clearly identified. The aim of this study was to determine the clinical correlates of pulmonary hypertension in patients with Graves’ disease. Among 50 consecutive patients with Graves’ disease referred for echocardiography, 18 patients (36 %) had pulmonary hypertension measured by continuous-wave Doppler echocardiography (pulmonary artery systolic pressure >35 mmHg). The patients with pulmonary hypertension had significantly higher pulmonary vascular resistance (PVR), cardiac output and thyroid-stimulating hormone receptor antibody (TRAb) compared to those without ( Characteristic clinical manifestations of hyperthyroidism are those resulting from the effects of thyroid hormone on the cardiovascular system , 2. CommThis observational study was performed in 59 consecutive patients with recently diagnosed Graves’ disease (within 12 weeks of diagnosis) recruited from the echocardiography laboratory of the Kochi Medical School Hospital. All the patients were referred to the echocardiography laboratory by physicians from the endocrinology outpatient clinic. The main inclusion criteria for enrolment were no history of heart disease , lung disease, liver disease, or collagen vascular disease. We excluded patients who were taking vasoactive drugs . Lung disease was excluded by chest radiography and careful chart reviews. Patient evaluation included a medical history, physical examination and laboratory studies. The diagnosis of Graves’ disease was made by the findings of sustained hyperthyroidism; serum-free thyroxine (T4) level >1.79 ng/dL, free triiodothyronine (T3) >4.0 pg/mL with concomitant decrease in thyroid-stimulating hormone (TSH) levels, elevated TSH receptor antibody (TRAb) levels (>2 IU/L ), increased blood flow in the thyroid gland on ultrasonography and a diffuse goiter. All samples were prepared and analyzed in accordance with the ethical recommendations of the hospital’s committee on human research and written informed consent was obtained from all subjects.Blood samples were collected from the antecubital vein within 24 h of the echocardiography. Serum albumin was measured by a dye-binding bromocresol green procedure and C-reactive protein (CRP) was measured by latex agglutination immunoassay using a JCA-BM2250 analyzer . White blood cells were measured by the direct current detection method using a Sysmex SE 9000 . Blood samples were also analyzed for free T4, free T3, TSH and TRAb by the electrochemiluminescence immunoassay using Modular Analytica E170 .Transthoracic echocardiography was performed with a Philips ultrasound iE 33 phased-array sector scanner  or a Sequoia 512  using a 3.75 or 2.5 MHz transducer by an experienced echocardiographer. Conventional M-mode and 2D echocardiographic measurements were performed in the standard manner . Dopplert test or the Mann–Whitney test for continuous variables and the Fisher exact probability test for discrete variables. Correlation coefficients between the 2 continuous variables were obtained using the linear regression analysis. Multiple regression analysis was performed to identify the variables independently related to pulmonary artery systolic pressure. A p value <0.05 was considered significant.Results are reported as the mean value ± standard deviation. Statistical analysis between the 2 groups was performed by the Student’s r = 0.74, p < 0.001)  and free T3 .Among 59 patients with Graves’ disease, pulmonary artery systolic pressure could not be determined in 9 patients 18 %) due to the absence of tricuspid regurgitation. Therefore, this study consists of 50 patients. Eighteen patients (36 %) had pulmonary hypertension (pulmonary artery systolic pressure >35 mmHg). There were no significant differences in age, gender distribution, cardiac output, free T4, free T3, TSH, creatine phosphokinase, CRP levels, cholesterol, serum albumin, white blood cells or incidence of medical therapy (beta-blocker and/or thiamazole) between patients with and without pulmonary hypertension (Tables 8 % due tp < 0.001) and cardiac output , TRAb  emerged as a significant variable related to pulmonary artery systolic pressure.To determine the important variables present in patients with Graves’ disease that may be related to pulmonary artery systolic pressure, 4 variables  were used in the multivariate analysis. From the analysis, in addition to PVR  due to the absence of tricuspid regurgitation. Nonetheless, data obtained by cardiac catheterization show that moderate or severe pulmonary hypertension is almost always associated with tricuspid regurgitation. Third, medical therapy was started in most of the patients at the time of cardiovascular evaluation because clinician judged it was necessary to start treatment. However, all the patients were in hyperthyroid state with elevated TRAb and remission is usually accompanied by decrease in TRAb activity.In conclusion, in addition to the effect of thyroid hormone on the cardiovascular system, autoimmune-mediated pulmonary vascular remodeling may play a role in Graves’ disease-linked elevated pulmonary artery systolic pressure.


Although hyponatremia is related to poorer outcomes in several clinical settings, its significance remains unresolved in kidney transplantation. Data on 1,786 patients who received kidney transplantations between January 2000 and December 2011 were analyzed. The patients were divided into two groups according to the corrected sodium values for serum glucose 3 months after their transplantations (<135 mmol/L vs. ≥135 mmol/L). Subsequently, the hazard ratios (HRs) for biopsy-proven acute rejection, graft failure, and all-cause mortality were calculated after adjustments for several immunological and non-immunological covariates. 4.0% of patients had hyponatremia. Patients with hyponatremia had higher risks for graft failure and all-cause mortality than did the counterpart normonatremia group; the adjusted HRs for graft failure and mortality were 3.21 (1.47–6.99) and 3.03 (1.21–7.54), respectively. These relationships remained consistent irrespective of heart function. However, hyponatremia was not associated with the risk of acute rejection. The present study addressed the association between hyponatremia and graft and patient outcomes in kidney transplant recipients. Based on the study results, our recommendation is to monitor serum sodium levels after kidney transplantations. The annual rate of kidney transplantation has steadily increased due to its proven survival benefit over other treatment options . More spHyponatremia is regarded as an important risk factor for high morbidity and mortality in several clinical settings . This reHerein, we first addressed the predictability of sodium levels on the graft and mortality outcomes in a large cohort who received kidney transplantations. Furthermore, its predictability remained significant independent of several immunological and non-immunological factors, all of which have been monitored in current clinical practice. The results indicate the necessity of adding serum sodium to the current monitoring system for kidney transplantations.The study protocol complies with the Declaration of Helsinki and received full approval from the institutional review board at the Seoul National University Hospital (no. 1406-125-591). The requirement of informed consent was waived by the board.Data on patients receiving kidney transplantation were obtained retrospectively from a cohort that consisted of patients from 2 tertiary referral centers . A total of 2,885 patients consecutively underwent kidney transplantations from January 2000 to December 2011. Patients were excluded from the analysis if they were younger than 20 years old (n = 181) or if they had received multiple organ transplantations , because these patients had a distinctive graft or patient survival rate compared with others. We obtained sodium levels 3 months after kidney transplantation with following reasons; we attempted to include patients with stable sodium statuses and exclude patients with potentially unstable statuses in the early period of transplantation. In particular, pre-transplant sodium levels were not considered because sodium levels are affected significantly by end-stage renal disease or dialysis . With thThe clinical parameters recorded included the following: age, sex, weight, smoking, hypertension, diabetes mellitus, history of cardiovascular disease, liver cirrhosis, history of tuberculosis, origin of end-stage renal disease, previous transplantation, donor type, ABO-incompatible transplantation, and the use of medications that have hyponatremia risk, such as thiazides, selective serotonin reuptake inhibitors, and anti-psychotic drugs. In addition to the serum sodium levels, the following laboratory data were considered: potassium, chloride, bicarbonate, hepatitis B virus surface antigen, anti-hepatitis C virus antibody, HLA mismatch, and donor-specific antibody. All the laboratory parameters were obtained when the patients were stable based on the medical reviews. Corrected sodium values for serum glucose were used in the study analyses, based on the following formula: corrected sodium = measured sodium + 0.016 × (serum glucose– 100) . The estt-test were used to compare the categorical variables and continuous variables, respectively. We divided the patients into the following two groups: normonatremia (135–145 mmol/L) and hyponatremia (<135 mmol/L). Survival curves were drawn using the Kaplan-Meier method. To compare the survival curves between the groups, the log-rank test was initially applied. To calculate the hazard ratios (HRs) of the outcomes, the Cox proportional hazard model was used, with and without the adjustments for the covariates. In the multivariate models, age, sex, estimated glomerular filtration rate, and covariates with P<0.1 in the univariate analysis were initially adjusted, and then all the covariates were adjusted. A P value less than 0.05 was considered significant. All analyses and calculations were performed using SPSS software .The data are presented as the means ± standard deviations for the continuous variables and as the proportions for the categorical variables. The chi-squared test and Student’s For the 1,786 subjects, the mean age was 43 years . Among tPs were <0.001 by the log-rank test), but the difference was not significant with acute rejection (P = 0.251). When the most common two causes for mortality  were only considered, the infectious mortality differed according to the presence of hyponatremia (P<0.001), but the cancerous mortality did not (P = 0.482). Subsequently, stepwise multivariate models were applied to calculate the adjusted HRs  patients died and 87 (4.9%) patients had graft loss. One hundred sixty-three patients (9.1%) had at least one episode of acute rejection in the 3 months after the kidney transplantation. The causes of death were as follows: infection (n = 21), cancer (n = 11), cardiovascular disease (n = 3), and others. The graft failures were attributable to acute rejection (n = 9), chronic rejection (n = 16), recurrence (n = 5), infection (n = 8), or non-compliance (n = 4); but most other cases could not clearly determined the cause of graft failure. sted HRs . The patWe further expanded our hypothesis to the other timeframes, such as baseline  and 6 months after transplantation. However, as stated in the method section, the baseline hyponatremia at the time of kidney transplantation was not associated with any transplant outcomes . When thP were 2.82 (1.178–6.762) and 0.020, respectively, for graft failure; HR and P were 3.99 (1.450–10.956) and 0.007, respectively, for mortality.Because heart function is related to the sodium level and to the mortality rate , we addiSerum sodium is broadly monitored in current clinical practice because an abnormal level is the most commonly found electrolyte disorder and it can result in poorer outcomes in several clinical settings. With this in mind, the present study has clinical implications on the following issues. First, the present data is the first report on the relationship between serum sodium and kidney transplant outcomes. Second, the relationships were not the same across the outcomes, wherein significance was primarily shown in the overall graft survival and mortality, not in the acute rejection. Finally, the sensitivity analysis  suggests that the relationship mechanisms may not depend on the heart function.The most common causes of death in kidney transplant recipients are infection and cardiovascular disease . HyponatGraft failure is attributable to both immunological and non-immunological factors . The preBased on the present data, monitoring post-transplant serum sodium levels may be needed to prepare clinicians for potentially poorer outcomes. However, the issue of hyponatremia correction is a separate matter. First, the current observational study design cannot provide any evidence for the intervention benefit. Second, recent studies have raised a question regarding whether the correction of sodium itself can reduce the mortality risk ,23. HypoThe present study has strength in the context of the large sample size, the solid statistical significance, and the long-term follow-up duration. Although the data are informative, this study has some limitations. First, as stated above, the study design, which involved observing correlations, limited the drawing of conclusions based on causality. However, the main aim of the present study was to determine the relationship itself; thus, the current design does not significantly hamper this aim. Second, we primarily considered Asians, but not other races; racial disparity in recipients’ state and outcome exists . Third, For the first time, the present study determined that hyponatremia was associated with poorer outcomes following kidney transplantations. Because current transplant outcomes remain suboptimal, it is essential to find additional factors related to poorer outcomes. In this respect, we believe that monitoring serum sodium and warning clinicians about hyponatremia may improve the transplant and patient outcomes. Future follow-up studies are needed to support the present findings and to address additional issues such as the underlying mechanisms and the correction of hyponatremia in kidney transplant recipients.S1 Data(XLS)Click here for additional data file.


P < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (P < 0.05) and plaque score on CA in these patients (P < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients ( Cardiovascular disease is one of the major causes of morbidity and mortality worldwide, especially among patients of chronic kidney disease (CKD) , 2. TherIt is believed that atherosclerotic changes in blood vessels in chronic renal diseases contribute significantly to the high cardiovascular morbidity and mortality. Morphological and functional abnormalities of the endothelium are considered as prodromal stage of atherosclerosis and early marker of CVD  that facRenal disease is associated with a graded increase in oxidative stress (OS) markers even in early CKD . OxidatiHowever, the relevance of malondialdehyde as a marker of oxidative stress which is generated by peroxidation of unsaturated fats as well as the role of matrix metalloproteinase-9 in atherosclerosis progression in patients (pts) with chronic kidney disease (CKD) not yet on dialysis compared to patients on peritoneal dialysis is less known, particularly with respect to cardiometabolic syndrome.The aim of this paper was to examine whether the serum concentration of malondialdehyde and matrix metalloproteinase-9 is involved in the process of atherosclerosis in patients with CKD not yet dialysis-dependent and those on peritoneal dialysis (PD) with signs of CMS.2) and patients on peritoneal dialysis for >6 months (22 pts). Antioxidants had not been taken by any subjects in the two groups. All PD patients underwent 4 to 5 dialysis changes with 2 liters of dialysis solution. The control group consisted of 20 age- and sex-matched healthy subjects.This cross-section study was conducted at the Clinic for Nephrology, Clinical Center University in Sarajevo, from June 2014 through December 2014. Fifty-two adult patients with CMS and chronic kidney disease were included in the study. The subjects were divided into CKD patients not yet dialysis-dependent , moderate atherosclerosis (AS1/2), and severe atherosclerosis (AS3)).2). Body weight for BMI in PD patients is measured with dry abdomen . The blood pressure (BP) was measured with mercury sphygmomanometer after 15 minutes of rest, according to recommendation by the British Hypertension Society [Kidney function was assessed by using estimated glomerular filtration rate (eGFR). Estimated glomerular filtration rate was performed using the MDRD  . Body ma Society . HyperteInformed consent was obtained from all participants and the local ethics committee approved the study.All serum samples were stored at −80°C until they were measured.The concentration of malondialdehyde (MDA) was analyzed at the Center for Cytogenetics and Molecular Medicine at the Medical Faculty in Sarajevo using a competitive enzyme immunoassay test (ELISA), which was performed with commercial kit for the assessment of the overall level of MDA . Reading of the results is carried out at 450 nm on a plate reader STAT FAX 2100, USA. The measurement concentration of MAD was expressed in nanograms per milliliter (ng/mL).The concentration of the enzyme matrix metalloproteinase-9 (MMP-9) in serum was quantified by ELISA at the Clinic for Immunology University Clinical Centre Sarajevo, according to manufacturer's instructions . Reading of the results is carried out by spectrophotometry at 450 nm (reader BIOTEK ELX50), with the correction wavelength at 540 nm or 570 nm. The measurement concentration of MMP-9 was expressed in nanograms per milliliter (ng/mL).The severity of carotid artery atherosclerosis was evaluated using the mean common carotid artery (CA), intima media thickness (IMT), and plaque score (PS). Carotid ultrasonography was used to evaluate the mean IMT and the PS. High-resolution B mode and color Doppler and pulse Doppler ultrasonography of both carotid arteries were performed with an ultrasound scanner  equipped with a 7.5-MHZ linear array transducer. Measurement was done by the same angiologist who was not familiar with the clinical status of the study patients. Patients were examined in the supine position with the head tilted backwards. After the carotid arteries were located by transverse scans, the probe was rotated 90° to obtain and record a longitudinal image of the anterior and posterior walls. The high-resolution images of the walls of the bilateral CA, internal carotid arteries (ICA), and carotid bulbs were examined according to recommendations of the American Society of Echocardiography Carotid Intima Media Thickness Task Force . The IMTThe PS was calculated by adding the maximal thickness in millimeters of plaques in each segment on both sides . The length of individual plaques was not considered in determining the PS.(1) without atherosclerosis (AS0): IMT less than 80% of the reference interval (RI), age- and gender-adjusted, with RI values obtained from previously published studies of monitoring, using the same ultrasound procedures;(2) mild atherosclerosis (AS1): IMT > 80% of the RI;(3) moderate atherosclerosis (AS2): the presence of carotid plaque, with no significant stenosis (PSV <125 cm/s);(4) severe atherosclerosis (AS3): the presence of carotid plaque with threatening stenosis (PSV >125 cm/s).The presence of atherosclerosis in CCA is estimated as recommended by the Mannheim consensus about atherosclerosis :(1) with t-test was used to compare the means of variable with normal distribution. Kruskall-Wallis test was used for statistical evaluation of more than 3 groups. The difference in median with interquartile range between two groups was analyzed by the Mann-Whitney test. Pearson's test was used to correlate data with normal distribution and Spearman's test for data with a skewed distribution. A multiple regression analysis was applied to define the independent connection serum concentration of MDA and MMP-9 with ultrasound parameters of CA.All data were expressed as the mean ± SD or as median and interquartile range. The distribution of variables was tested by the Kolmogorov-Smirnov and/or Shapiro-Wilk test. Student'sβ). P values of <0.05 were considered statistically significant. All statistical calculations were performed with the SPSS 16 software .The significant independent variables were determined according to their standardized effect, defined as regression coefficient/standard error of the regression . In our study, all observed CKD patients, dependent or not dependent on dialysis treatment, were hypertensive (BP ≥140/90 mm Hg), but significantly higher values of both systolic and diastolic blood pressure were registered in the group of patients on PD treatment compared to other CKD patients. Although there were no significant intergroup differences in serum triglyceride levels, all groups of patients had an elevated level of serum triglycerides .Basal characteristics of the anthropometric profile, blood pressure values, metabolic pattern, and serum concentration of MDA and MMP-9 in the whole group of CKD and PD subjects with CMS and in two subgroups of CKD with and without dialysis (PD) are presented in Depending on the stages of atherosclerosis our data showed significant changes in serum concentration of MDA and MMP-9 between the different subgroups of CKD nondialysis-dependent patients, as well as in patients on peritoneal dialysis .P < 0.05 and in AS3 53.9 (49.8–63.2) versus 74.3 (68.2–76.3) ng/mL; P < 0.05). There were no significant differences in serum concentration of MDA in the monitored PD and CKD patients without expressed atherosclerotic changes (AS0 20.6 (10.4–31.3) versus 24.1 (18.8–27) ng/mL; P > 0.05)  versus 40.3 (31.9–45.6) ng/mL;  > 0.05) .P < 0.05), whereas in stage AS3 serum MMP-9 concentration was significantly higher in PD patients in comparison with other CKD patients (P < 0.05). Such a relationship but lower concentration of MMP-9 in the serum was present in stage AS0 in both groups  ng/mL) compared to the CKD patients treated conservatively (425.2 (405.5–439.5) ng/mL)  (P < 0.01)  , as well < 0.01) .r = 0.762; P < 0.01)    and betw < 0.01) .P < 0.05), as well as plaque score on carotid arteries in these populations (P < 0.05). This model is able to explain 70% of the variance in the results of IMT (R2 = 0.765) and about 79% (R2 = 0.786) of the variation that occurs with the plaque score on carotid arteries in chronic kidney disease  and the absence of trusted signs of inflammation. Since peritoneal dialysis is intrinsic type of dialysis through the peritoneum as biocompatible membrane, this result also suggests the possible influence of peritoneal dialysis on oxidative stress.A few studies reported increased OS among PD patients, but other prooxidants  were measured, associated with hypoalbuminemic state or loss of residual renal function (RRF), and without comparing it with nondialysis CKD patients , 27, 30.Activity of MMP-9 is highly associated with the progression of CKD, diabetes, and coronary arterial disease , 34. ThiIn our study, no significant difference was found in the serum concentration of MMP-9 between CKD patients treated conservatively and PD patients, but the significant increase was found in the value of this biomarker within both groups with progression of atherosclerotic process. These findings are in line with the findings of Addabbo and associates, who have demonstrated that MMP-9 levels strongly correlated with carotid atherosclerosis burden irrespective of other factors in early, moderate, and advanced CKD .Our data also showed the decreased serum concentrations of MMP-9 in the stage AS1/2 of atherosclerosis in PD patients compared with CKD patients without dialysis treatment. Possible reason of such decrease is unknown. However, it is our belief that the decrease in MMP-9 concentration in AS1/2 stage of PD patients might occur due to the impact of peritoneal dialysis on MMP-9 serum concentration. MMP-9 was significantly higher in stage AS3 in PD patients compared with CKD patients treated conservatively. To our knowledge, the impact of peritoneal dialysis on the concentration MMP-9 has not yet been clarified. Some authors have demonstrated that the hemodialysis process leads to a reduction in plasma concentration of MMP-9 in some patients .A significant correlation of MMP-9 serum concentration with CA-IMT and plaque score was found in all monitored patients in this study. Also, in multiple regression model we confirmed a significant independent association of MDA and MMP-9 with these ultrasonography parameters characterizing arterial wall and atherosclerotic changes of carotid arteries.The need for identification of risk factors and serum markers of atherosclerosis in the process of early detection and prediction of risk for cardiovascular disease has attracted a lot of attention in recent years. The significantly lower levels of MDA in PD-CMS patients in comparison with CKD-CMS patients not yet dialysis-dependent and its increase with atherosclerosis progression, as well as obtained higher values of MMP-9 during progression of atherosclerosis especially in PD patients, could be a new contributing factor of our study.However, this study has certain limitations, such as the small number of respondents and a cross-sectional design of study. A question on the periodontal disease status of those patients was not included, although periodontal disease and kidney disease are highly associated and periodontal disease is alone associated with increases in MMP-9 . WhetherThe results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS. The study data also suggest that that factors mediating relationship between cardiometabolic syndrome, chronic kidney disease, and atherosclerosis can include malondialdehyde and MMP-9.