To evaluate the levels of malondialdehyde (MDA) and total antioxidant capacity (TAC) in the blood and aqueous humor of glaucomatous and nonglaucomatous patients. To measure the adenosine triphosphate/adenosine diphosphate/adenosine monophosphate (ATP/ADP/AMP) concentration as a biomarker of the blood energy charge potential.We examined 40 consecutive patients with primary open-angle glaucoma scheduled for cataract surgery. Twenty-six age-matched subjects scheduled for cataract surgery were enrolled as a control group. Blood and aqueous humor samples were collected at the time of surgery. MDA concentrations and blood nucleotides were measured with high-performance liquid chromatography. The TAC of the samples was estimated with the oxygen-radical absorbance capacity method.Blood and aqueous humor MDA levels in glaucoma patients  were significantly increased (p<0.001 for both) over those of the control group . In contrast, the control group presented significantly higher TACs than did the glaucoma group in both the blood  and aqueous humor . The control group (0.869±0.037) exhibited statistically significant (p<0.001) higher values of blood adenosine triphosphate/adenosine diphosphate (ATP-ADP) levels than did the glaucoma group (0.791±0.037).Our data further support the hypothesis that oxidative stress and decreased antioxidant defenses are involved in glaucoma. High-performance liquid chromatography appears to be an effective and sensitive method to detect altered levels of oxidative stress markers in glaucoma patients. Glaucoma is a progressive optic neuropathy that affects nearly 90 million people worldwide, and is the leading cause of irreversible blindness -3. It isThe study was approved by the institutional review board of the University Hospital Tor Vergata. The study followed the tenets of the Declaration of Helsinki. All participants provided informed consent after explanation of the nature and possible consequences of the study. The study group consisted of 40 consecutive patients with primary open-angle glaucoma  recruited from the Ophthalmology Unit of the Tor Vergata University of Rome Medical Hospital. Inclusion criteria for glaucoma patients were the following that the vertical cup/disk ratio was >0.5 and that there were typical glaucomatous defects at the visual field . None of the glaucoma patients had previous incisional or laser surgery.For comparison purposes, we also enrolled a control group consisting of 26 age-matched nonglaucomatous subjects .Glaucoma and control candidates were excluded from the study for any of the following reasons: smoking, diabetes, liver disease, severe nephropathy, cancer, collagen diseases, acute or chronic infections, fever, congestive heart failure, use of oral antioxidant supplements, and the presence of any other eye disease, such as age-related macular degeneration and diabetic retinopathy.Samples of blood and aqueous humor were collected from all participants on the day of surgery. Venous blood samples were drawn after an overnight fast. The samples were placed on ice and centrifuged within 1 h (3500 ×g at 4 °C for 15 min), and the supernatants were stored at −20 °C until analyzed. Aqueous humor samples (0.1–0.2 ml) were rapidly collected at the beginning of cataract surgery with a 27-gauge needle on a tuberculin syringe. Special care was taken to avoid blood contamination. Samples were immediately cooled and stored at −70 °C.4  was added to the blood samples to deproteinize erythrocytes. All samples were centrifuged at 20,690×g for 10 min at 4 °C, neutralized by adding 5 M K2CO3 in ice, filtered through a 0.45 μm Millipore-HV filter , and subjected to HPLC. The ion-pairing method was used for simultaneous direct determination of MDA and adenine nucleotide levels in 100 μl of a perchloric acid extract of each sample  and buffer B ). The gradient was as follows: 10 min, 100% with buffer A; 3 min, 90% with buffer A; 10 min, 70% with buffer A; 12 min, 55% with buffer A; 15 min, 45% with buffer A; 10 min, 25% with buffer A; 5 min, 0% with buffer A. A flow rate of 1.2 ml/min was maintained throughout each run, and the column temperature was maintained at 23 °C with the aid of water-jacketed glassware. The HPLC apparatus consisted of a Surveyor LC Pump  connected to a Surveyor PDA Detector  with a wavelength range of 200–300 nm. Data were acquired and analyzed with the ChromQuest program . Areas, retention times and absorbance spectra of the peaks of sample chromatograms were compared with those of freshly prepared ultrapure standards to determine the concentration of the various compounds at 267 nm (the upper limit of the MDA absorbance spectrum) and identify different metabolites. Hemoglobin and the percentage of hemolysis were calculated with standard techniques [Blood and aqueous humor were collected in sterile tubes. Ice-cold 1.2 M HClOh sample ,12. We uh sample ,12 with chniques  in a JasThe blood energy-state levels were determined by employing ATP, ADP, and AMP detected by HPLC, and the ECP was calculated according to the following formula:where  is the sum of the adenine nucleotide levels .The ORAC assay is based on the dose- and time-dependent decrease in the fluorescence intensity of β-phycoerythrin (β-PE) when oxidized by oxygen radicals . It measOur assay was performed with the original method described by Cao et al. , with a For continuous variables, data were compared between groups using the unpaired Student’s t-test. For categorical variables, comparison between groups was done using the chi-square test. Correlations of the independent variables age and sex with the dependent variables studied  were evaluated with the Spearman nonparametric test. Significance was set at p<0.05.The mean±SD age of the control group (74.0±8.3 years) and of the glaucoma group (75.3±9.1 years) did not differ statistically (Student’s t-test p=0.559). The male/female ratio of the control group (14/12=1.17) and of the glaucoma group (22/18=1.22) did not differ statistically (chi-square p=0.872). In the present study, we attempted to characterize the oxidative stress and total antioxidant capacities of blood and aqueous humor in glaucoma patients. Oxidative stress has long been involved in the pathogenesis of cataract . This isOur results suggest that glaucoma patients had significantly higher levels of MDA and lower levels of TAC in the blood and aqueous humor. Oxidants are highly reactive compounds with half-lives of a few seconds, and this seriously hinders their measurement, in vivo, in the eye . HoweverIncreased levels of oxidative agents have been found in the aqueous humor of glaucomatous patients, and in a recent study, MDA concentrations measured spectrophotometrically using a thiobarbituric acid-reacting substrate were found to be higher in the aqueous humor of glaucoma patients than in that of healthy controls . Our stuIt has been proposed that oxidative stress can damage the cells of the trabecular meshwork . The TM,Finally, the blood of our glaucoma patients exhibited significantly reduced energy charge potentials, compared with controls. The ATP/ADP level ratio represents the balance between energy-producing and energy-consuming reactions, and decreased values generally reflect insufficient production of ATP via the oxidative and phosphorylative activities of the mitochondria. Our finding indicates for the first time that in glaucoma patients, the blood energy supply is deficient and its reduction may be a primary event in the development of the disease.On the whole, these data indicate that altering the redox state and energy potential contribute to the development of glaucoma, although the mechanisms by which oxidative stress triggers this event have not been fully elucidated. Oxidative stress has been shown to induce cell death by targeting the mitochondria directly, which are both a major endogenous source and target of ROS . ReactivA large number of mechanisms are implicated in neuronal death in glaucoma and include glutamate excitotoxicity, nerve growth factor deprivation, ischemia, and autoimmune and oxidative damage ,28,29. TIn conclusion, this study demonstrates that HPLC is an effective, sensitive method for detecting altered levels of oxidative stress markers in glaucoma patients. Our results strongly suggest that an increase in free radical formation and a decrease in the antioxidant defense mechanism may play a role in the pathogenesis of POAG. We propose that the determination of blood oxidative stress, TAC, and ECP may be assessed by using HPLC to help understand individuals’ vulnerability to the disease.


Mitochondria produce cellular energy but also free-radicals, which damage cells despite an array of endogenous anti-oxidants. In Northern Europe, the mitochondrial haplogroup J has been related to longevity in nonagenarians and centenarians but also with age-related disease. Hypertension is an important contributor to atherosclerotic-related diseases and its pathogenesis is associated with increased oxidative stress. In this study, we questioned whether J haplogroup octo/nonagenarians from the Belfast Elderly Longitudinal Free-living Elderly STudy (BELFAST) study showed evidence of protective blood pressure or anti-oxidant profile which might explain their longevity advantage. Briefly, in a cross-sectional study, community-living, mentally alert (Folstein >25/30), octo/nonagenarian subjects, recruited for good health, were enlisted and consented as part of the BELFAST study, for blood pressure, anthropometric measurements and blood sampling. DNA typing for mitochondrial haplotypes was carried out with measurements for enzymatic and non-enzymatic antioxidants. J haplogroup carriers showed lower systolic blood pressure and glutathione peroxidase activity (Gpx) with higher folate measurements. There was no change in urate, bilirubin, albumin or nutrition-related antioxidants-selenium or vitamins A, C and α and β carotene. BELFAST study mtDNA J haplogroup octo/nonagenarians showed lower blood pressure and reduced glutathione peroxidase activity and higher folate, but no change for other antioxidants. These findings are of interest in view of mtDNA J haplogroup’s association with increased age in some previous studies. Mitochondria undertake multiple critical functions in a cell. They are the chief source of efficient energy production in cells, converting glucose into numerous high-energy phosphate bonds which transform adenosine diphosphate (ADP) to adenosine triphosphate (ATP) along the electron cascade. In addition to generating much of the cellular energy, mitochondria regulate the cellular redox state, produce most of the cellular reactive oxygen species (ROS), buffer cellular Ca2+ and initiate cellular apoptosis. Mitochondria have limited protection from oxidative stress Wallace  and enerAs we age, the free radical theory of ageing Harman  suggestsR which has branching subgroups of U , V and H, T and J, and B. The mitochondrial haplogroups J and T therefore share the same sub-branch of R and are considered to have been inherited from one woman, who is thought to have belonged to the hunter–gatherers that colonised Europe thousands of years before the agricultural revolution moved across Europe.In animal studies, nuclear and mitochondrial genes seem to both have an influence on the rate of ageing and free radical burden. In mice with genetically increased enzymatic anti-oxidant catalase activity, there is evidence for reduced atherosclerosis and increased lifespan Cutler  and mito‘successful’ ageing. The Caucasian haplogroup J is characterised by the mutations T489C, A10398G, A1262G, G13708A plus the T4216C, A11251G and C15452A substitutions which are shared with haplogroup T. The J combination of mutations seem to confer a higher chance of achieving longevity than other mtDNA haplogroups in Northern Italians  octo/nonagenarians carrying the mitochondrial J haplogroup would show a better blood pressure and antioxidant phenotype as a part explanation of their good-quality longevity. We also carried out comparisons of the T mitochondrial haplogroup which shares a similar mitochondrial subgroup root as J, though a number of additional mutations define a separate branch.Elderly subjects were a consecutive mid-study cohort enlisted from the BELFAST study, aged 80–100 years of age Rea , who metSubjects were seen in their own homes by the trained research officer and nurse. Blood pressure was measured in a sitting position and after 5 min of rest using a mercury sphygmomanometer, following the recommendations of the British Hypertension Society. Systolic blood pressure and diastolic blood pressure were measured using Korotkoff phase I and phase V, respectively. Blood was collected from subjects at a morning visit and returned to Belfast City Hospital Laboratories within 1 h of collection for various analyses.GSH blood samples, freshly collected into metaphosphoric acid-containing tubes, were transported in liquid nitrogen and stored at −70 °C until analysis by High Performance liquid Chromatography.Gpx was measured in serum using a modification of the coupled assay of Paglia and Valentine as described by McMaster et al. Selenium in serum and whole blood was measured by atomic absorption spectrophotometer  as appropriate. Blood pressure and a number of related variables were also categorised and comparison made for T and non-T mitochondrial haplogroups. Logistic regression analysis and odds ratio (OR) was used to predict differences in blood pressure categories defined by mitochondrial groups J non-J and T non-T and multiple models were constructed and analysed to include variables significantly different or close to significance in t test or mwu or other analyses. A p value of <0.05 was regarded as significant.For each variable, values are expressed as mean and standard deviation (SD) or as medians for non-normal distributions. Subject age, biochemical variables, Gpx activity and the other antioxidants were categorised by J or non-J mitochondrial haplogroup status and analysed by Subject characteristics are described in Tables There were differences between the use of medications across J and non-J mtDNA haplogroups. It was more common for J mtDNA haplogroup carriers compared to non-J mtDNA haplogroups to be on no medication, overall 20 viz 10 %, respectively. Anti-hypertensive use was 32 vs 32 % respectively and aspirin use 0 vs 14 % was more common in non-J mtDNA haplogroup subjects compared to J mtDNA haplogroup subjects.With respect to smoking there was little difference in the categories of never, past and current smokers between J and non-J mtDNA haplogroup carriers with 40 vs 50 % of subjects in J and non-J mtDNA groups advising that they had never smoked, 20 vs 21 % saying they had smoked in the past and 20 vs 21 % saying they were current smokers.p = 0.02) for J haplogroup 122 [SD 14] compared to non-J haplogroups 136 [SD 18]. Diastolic blood pressure was also lower in J haplogroup octo/nonagenarians, 76 [SD 14] mmHg, compared with 82 [SD 12] mmHg, in non-J haplogroups Table p = 0.06). A similar pattern was represented across male and female, J and non-J haplogroups for both systolic and diastolic blood pressure, Fig. Mean systolic blood pressure across the octo/nonagenarian group was 132 [standard deviation (SD) 17] mmHg, with a significantly lower value .Systolic and diastolic blood pressure were not significantly different when categorised by mitochondrial haplogroups T non-T; systolic blood pressure 133 [SD 11] and 134 [SD 18] p = 0.03 and p = 0.01, respectively). There was no change in serum glutathione or selenium between J and non-J carriers.Glutathione peroxidase activity in serum and blood categorised according to J and non J haplogroup carrier is shown in Table The non-enzymatic antioxidants albumin, bilirubin and urate were not significantly different when subjects were categorised according to mitochondrial J haplogroup, Table χ2 and associated p values with Exp(B) as the odds ratio (OR), using J and non-J mitochondrial status as a dichotomous variable for prediction of blood pressure, Gpx and folate-variables previously noted to be significantly different between the J mitochondrial categories. For systolic blood pressure, J carriers were predicted to be likely to have lower blood pressure compared to non-J carriers by about 5 mms for each 100 mmHg  which appeared to the confirm findings from the preliminary comparative analyses. For the anti-oxidant glutathione peroxidise activity, J mitochondrial carriers were also predicted to have somewhat lower glutathione peroxidase activity  in agreement with previous findings. Folate by contrast showed a trend for higher values in J haplotype carriers . Multinominal logistic regression models 1, 2 and 3 were set up with J and non-J mitochondrial haplotype as the dichotomous variable to include the independent variables blood pressure, glutathione peroxidase activity and folate. Table χ2, p and r2 values and shows that while all models could predict the class of J or non-J mitochondrial haplotypes for all three independent variables, model 3 performed best in predicting class category for both blood pressure and glutathione peroxidase activity (p = 0.02). There was a suggestion that there may have been collinearity between glutathione peroxidase activity and folate though the r value −0.284 in the correlation matrix was not particularly high (data not shown).Logistic regression was used to further explore whether carriage of the J or the non-J mitochondrial haplotype by BELFAST octo/nonagenarians could predict blood pressure and associated anti-oxidant status since logistic regression does not depend on the normality of independent variables nor the linearity of relationships. Table The main finding in this cross-sectional study of BELFAST octo/nonagenarians, enlisted by Senieur protocol was that those who carried the mitochondrial J haplogroup had lower systolic blood pressure compared to non-J haplogroups, and this trend was also separately present in men and women who were octo/nonagenarians. Hypertension is the single most important risk factor for cardiovascular disease, stroke and Alzheimers disease, all of which contribute to early mortality, increased morbidity and poor quality ageing (Hajjar et al. There is increasing evidence that the various mitochondrial haplogroups have functional differences which seem likely to be related to reductions in ATP production, increased generation of reactive oxygen species and impaired calcium buffering Postnov , all of Higher glutathione peroxidase activity found in BELFAST octo/nonagenarians in association with higher blood pressure is in keeping with suggestions that oxidative stress plays an important patho-physiological role in the development of hypertension Ceriello . OxidatiThe molecular pathway linking mitochondrial haplogroups and mutations with mechanisms and function in hypertension has become a bit clearer as a result of these publications and the recent work by Luon et al. Albumin and bilirubin are the most abundant and important non enzymatic anti-oxidants in the body (Vítek and Ostrow Important limitations of this research are the cross-sectional nature of the BELFAST study and the numbers which may have reduced the power. However, 90 year olds are both the fastest growing sector of present day populations and the group about whom we know relatively little medically, socially and economically. It can be argued that they are of special interest because of their extreme age and because in this study they were well categorised by Senieur status (Rea et al. The findings in the BELFAST study are very preliminary but are potentially interesting. They will need to be replicated but do provide some support for the idea that carriage of the mtDNA J haplogroup may be associated with a lower blood pressure profile. The associated altered antioxidant profile, which has been identified could also play a role in a longevity phenotype (De Benedictis et al.


Increased arterial stiffness is a risk factor of atherosclerosis and cardio-vascular complications. The aim of the study was to determine whether peripheral vascular function might be an early marker of impaired health status in patients with a single ventricle after Fontan procedure.Twenty five consecutive adults (11 women and 14 men) aged 24.7 ± 6.2 years after the Fontan procedure and 25 sex, age and BMI match healthy volunteers underwent physical examination, blood analysis, transthoracic echocardiography and noninvasive assessment of aortic stiffness. Augmented pressure and Augmentation Index (AIx) were both significantly elevated in Fontan when compared to the controls . There were no differences in pulse wave velocity (PWV), mean blood pressure (BP), brachial pulse pressure (PP), central: systolic BP, diastolic BP and PP. In Fontan group we find negative correlation between PWV and SatO2  and positive correlation with WBC , INR , TNFα , and postoperative time . AIx correlates positively only with age at surgery . Bilirubin level correlates positively with brachial PP  and central PP .2 = 0.32, p = 0.03).The multivariate model showed that SatO2  was the only independent predictor of PWV (RAdult Fontan patients have an increased arterial stiffness assessed by a noninvasive technique. Low arterial oxygen saturation postoperative time, age at surgery, white blood cells, TNFα and bilirubin level are associated with arterial stiffening in these patients. The combination of blood parameters of the hepatic function and noninvasive measurements of arterial stiffness could be helpful in comprehensive care of patients with Fontan circulation. Non-invasive measurement of vascular parameters is increasingly used to assess the risk of cardiovascular disease. It is considered that the loss of elasticity of the walls of the arteries, especially the aorta is a marker of the early changes that may lead to the development of atherosclerosis and its following complications  in healthy individuals . IncreasFontan operation is a widely used method of treatment of patients with single ventricle. The main goal of this procedure is the separation of the pulmonary and systemic circulation. The treatment is multistage and it results in the absence of subpulmonary ventricle. The blood flow through the lungs is effected due to the pressure gradient between the systemic veins and the left atrium and has non-pulsatile character ,8.A vast majority of the patients born with a functional single ventricle, who underwent Fontan surgery in early childhood, survive over 20 years . The lonThe present study was designed to evaluate the usefulness of the noninvasive measurement of arterial stiffness to determine whether peripheral vascular function might be an early marker of impaired health status in patients with a single ventricle after Fontan procedure. We also evaluated the impact of endothelial dysfunction and inflammation on parameters of arterial stiffness.The patients were recruited consecutively at the John Paul II Hospital in Krakow and enrolled into the study if they had had the Fontan operation, were ≥18 years old, and were clinically stable for at least 3 months before the study.The patients underwent physical examination, blood analysis, transthoracic echocardiography and noninvasive assessment of aortic stiffness. Medical histories were taken and they included demographic, anatomic data, previous interventions and medical therapy. The exclusion criteria were: arrhythmia, any acute illness, cancer, diabetes mellitus, hypertension, acute vascular event, alcohol abuse and pregnancy.Healthy subjects were not on any medication and had no history of cardiovascular or cerebrovascular disease.The institutional ethics committee approved the study protocol. All the participants signed informed consent before enrolling into the study.Assessment of the central hemodynamic data and aortic stiffness was performed by non-invasive examination of the peripheral arteries. Measurements were performed after 8 hours fasting, before medications, in the supine position, in a quiet room, with an air temperature of 22 ± 1°C . ShortlyCentral: systolic BP, diastolic BP, pulse pressure (PP), augmented pressure (AP) and augmetation Index (AIx) were obtained during the course of at least 12 seconds registration of the pulse wave graph at the radial artery and calculated by a validated generalized transfer function.AP is a parameter that determines the difference between the peak of the reflected wave from the periphery (P2) and the peak of the wave generated by the contraction of the left ventricle P1) (AP = P2 - P1 [mmHg]). AP describes the increase or decrease in the amount of pulse wave in the ascending aorta in relation to strengthening it by the wave returning from the periphery to the ascending aorta  and PP in the aorta. (AIx = AP/PP [%]), and speaks of the percentage change (increase or decrease) of the pressure in the aorta (pulse wave height) under the influence of the peripheral wave and it is dependent on the duration of the cardiac cycle, PWV in the vessels and the amplitude of the reflected wave. Because the value of AIx is influenced by heart rate, AIx was standardized for the heart rate of 75/min .Single ventricle ejection fraction (SVEF) was assessed by echocardiography  using a Simpson method. Oxygen saturation (SatO2) was measured noninvasively by pulse oximeter in room airBlood samples from a peripheral vein were drawn into tubes. All blood samples were obtained in the morning after an overnight fast. In patients using warfin, blood was drawn at least 5 days after drug withdrawal. Plasma levels of white blood cells (WBC), platelet count, red blood cells (RBC), hematocrit (HCT), hemoglobin (Hg), total protein, alanine aminotransferase (ALT), C-reactive protein (CRP), creatinine, bilirubin, gamma glutamylo transpeptidaza (GGTP) international normalized ratio (INR), N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) were assayed by routine laboratory techniques.Endothelin-1 level and tumor necrosis factor-alfa (TNFα) were determined by the ELISA method (R&D Systems).Continuous variables are expressed as mean ± SD. Categorical variables are described as counts and percentages. Patients after Fontan operation and controls were compared with the Mann Whitney U-test for the continuous variables and with the chi square test for categorical variables. Correlations between the individual parameters were calculated using the Spearman rank test. Factors that determine PWV were analyzed using multiple logistic regression. A p-value <0.05 was considered statistically significant. The statistical analyses were performed with the PQ Stat version 1.4.2.324 software.Of 35 patients who were assessed for eligibility, 10 subjects were excluded due to: age below 18 years of life (n = 1), lack of informed consent (n = 3), and arrhythmias (n = 6). The study population consisted of: 25 consecutive adults (11 women and 14 men) aged 24.7 ± 6.2 years who underwent the Fontan procedure in their childhood and 25 sex, age and BMI match healthy volunteers. The dominant cardiac malformation were: tricuspid atresia 12 (48%), pulmonary atresia with ventricular septal defect and transposition of great arteries 8 (32% ), double outlet right ventricle with hypoplasia of left ventricle 2 (8%), double inlet left ventricle 3 (12%). Modification of the Fontan operation included direct right atrium-pulmonary artery connection in 2 (8%) patients and total cavopulmonary connection (TCPC) by means of intraatrial lateral tunnel in the remaining 23 (92%) patients. The mean age at Fontan procedure was 4.6 ± 3.3 years. The mean follow-up time was 20.1 ± 5.2 years. The patients were in NYHA class I 5 (20%), NYHA II 18 (72%) and NYHA III 2 (8%). Six (24%) patients were treated with warfarin, 1 (4%) with enoksaparin, 15 (60%) with aspirin and 3 (12%) were taking inhibitor of angiotensin in a small doses. On the day of examination the patients did not take any medication.The Fontan patients had lower SVEF  and there were no differences in SBP, DBP, HR. Study population characteristic is shown in Table 9/μl; p < 0.001), Hg , HCT , GGTP , ALT , bilirubin , INR , TNFα , NT-proBNP , endothelin levels  and significantly lower platelet account . There were no differences in WBC, total protein, creatynin and CRP. The results are shown in Table In Fontan group we also find significant higher RBC . There were no differences in PWV, Mean BP, brachial PP, Central SBP, Central DBP, Central PP. The results are presented in Table In Fontan group we find negative correlation between PWV and SatO2  and positive correlation with WBC , INR , TNFα , and postoperative time . We did not find similar correlation in controls.Augmentation Index correlates positively only with age of surgery . Bilirubin level correlates positively with PP brachial  and Central PP .2 = 0.32, p = 0.03).To determine the independent effect of clinical and laboratory variables, the stepwise regression analysis for PWV as a dependent variable was performed. The multivariate model showed that SatO2  was the only independent predictor of PWV . The authors ,20 foundPrevious study showed that arterial oxygen saturation decreased in majority of adult Fontan patients . The reaAnother factor that may affect the biophysical properties of the aorta and therefore influence the wave reflection, arterial pressure augmentation and contribute to central and peripheral vascular dysfunction, is endothelial dysfunction. We find elevated endothelial level in Fontan patients. Jin et al.  has showOur study showed that also inflammation influenced arterial stiffness in adult Fontan patients. We find correlation between PWV and white blood cells and TNFα. There is limited data regarding the relationship of inflammation with arterial stiffness in patients with single ventricle. However, previous study demonstrated that increase in systemic inflammation is an independent predictor of future development of hypertension . The incLiver is the organ at great risk after the Fontan operation . HepaticSeveral limitations of this study should be acknowledged. The study group was small and heterogeneous with regard to type of surgery. Also medication administrated to the Fontan patients is not without an effect on the arterial stiffness. The patients in our study were taking medication such as ACE inhibitors - the drugs that decrease AIx . This maAdult Fontan patients have an increased arterial stiffness assessed by noninvasive technique. Low arterial oxygen saturation postoperative time, age at surgery and bilirubin level are associated with arterial stiffening in these patients. The combination of blood parameters of the hepatic function and noninvasive measurements of arterial stiffness could be helpful in comprehensive care of patients with Fontan circulation.The authors declare that they have no competing interests.LTP designed the study, collected the data, interpreted the data and drafted the article. HDO participated in the design of the study, collected data and helped to draft the manuscript. JP collected the data and interpreted the data. MO interpreted the data and helped to draft the manuscript. JK collected the data, interpreter the data, MK collected data. PP interpreted the data, helped to draft the manuscript and designed the study. All authors read and approved the final manuscript.


Accurate assessments of intravascular fluid status are an essential part of perioperative care and necessary in the management of the hemodynamically unstable patient. Goal-directed fluid management can facilitate resuscitation of the hypovolemic patient, reduce the risk of fluid overload, reduce the risk of the injudicious use of vasopressors and inotropes, and improve clinical outcomes. In this paper, we discuss the strengths and limitations of a spectrum of noninvasive and invasive techniques for assessing and monitoring intravascular volume status and fluid responsiveness in the perioperative and critically ill patient. The ability to assess intravascular volume is an essential part of perioperative care and the management of perioperative hemodynamic instability. Insufficient intravascular volume can result in decreased oxygen delivery to tissues and organ dysfunction, while fluid overload states can contribute to the development of edema and organ dysfunction, including respiratory failure. The injudicious use of vasopressors and inotropes in the hypovolemic patient can be hazardous and increase the risk of a poor outcome.Euvolemia describes a state of normal body fluid volume that allows adequate filling of the cardiac chambers and, in turn, makes it possible for the heart to produce a cardiac output that can meet the organism oxygen demand. In the setting of euvolemia, neither diuresis nor fluid administration is necessary. Fluid responsiveness describes the ability of the heart to respond to filling volume variations, modifying its stroke volume and consequently the cardiac output. From a patient management perspective, fluid responsiveness determines the extent to which circulatory homeostasis can be maintained with fluids alone versus the need for inotropes or vasopressors. An understanding of both concepts derives from the Frank-Starling relationship describing the changes in cardiac stroke volume in response to changes in cardiac preload. The ascending portion of the Frank-Starling curve will correspond to the fluid responsive phase of resuscitation, as seen with an increase in the cardiac output. Once the left ventricle reaches the plateau phase of the curve, fluid administration will not improve the cardiac output any further; it may lead to the adverse effects related to fluid overloading, such as hydrostatic pulmonary edema. Two concepts are relevant to assessments of fluid status in perioperative and critical care. In a broad sense, if euvolemia is the goal of fluid use in resuscitation, then fluid responsiveness reflects the process of working toward establishing euvolemia. In evaluating the various techniques for analyzing fluid status, it is helpful to contrast their utility in predicting fluid responsiveness versus euvolemia and to consider how these relative strengths and weaknesses may be paired with different clinical situations to yield accurate and meaningful information. Methods of interpreting intravascular volume range from clinical assessments such as inspection of veins and passive leg raising, to more invasive methods such as central venous and pulmonary artery catheterization, to newer technically intensive methods such as echocardiography and analysis of flow parameters.nil per os (NPO) status and use of inhalational agents and positive pressure ventilation early in a case are usually indicative of relative hypovolemia, and anesthesiologists typically respond by increasing the volume of infused fluids. Blood loss and release of inflammatory mediators can also reduce blood volume, preload, and vascular tone in latter phases of an operation, when, again, additional boluses would likely be given with careful assessment of the blood pressure response. Only extremes of body water can be predicted by clinical examination. Tachycardia and hypotension and loss of skin turgor are associated with frank hypovolemia in unanaesthetized adults, while tenting of skin and sunken eyes and fontanels can be found in infants. The ability to detect hypervolemia is more dependent upon cardiac pathology where smaller grades of fluid excess can produce findings such as rales, a third heart sound, oxygen desaturation, jugular vein distension, and peripheral edema. In operative patients, experienced clinicians can often predict hypovolemia from the clinical situation. Fluid deficits resulting from a patient's passive leg raising test (PLR) delivers a reversible endogenous fluid challenge by increasing venous return resulting from elevating the legs to 45 degrees in a supine patient and evaluating its effect on blood pressure and heart rate. One simple described way to perform PLR is by using the pivotal motion of the bed to transfer a 45 degree recumbent patient into a horizontal position with supine trunk and elevated legs [Depending on patient position and access, examination of neck veins and passive leg raising test can yield useful information. The ted legs . This teted legs  and has ted legs  and esopCVP is the measurement of pressures within the thorax in the superior vena cava (SVC) and serves as a reasonable surrogate for the corresponding right atrial pressures. CVP is the most widely used technique for measuring intravascular volume in critically ill patients . The CVP pressure tracing consists of three positive waves  and two negative waves (x and y). The CVP is specifically measured at the “z” point of the CVP tracing which corresponds to the leading edge of the c wave . At this2. The two important findings of the study were that only 4.5% of the patients with a CVP more than 10 mm Hg responded to a fluid challenge, also of the patients who had increase in CO, 42% had a simultaneous increase in blood pressure. Therefore, the two conclusions from the study were that patients with a CVP of more than 10 mm Hg were poor responders to volume infusion and that 10 mm Hg may represent euvolemia in most individuals. Second, blood pressure increase was not a good indicator of cardiac response to a fluid challenge [In our experience, single point estimates of CVP are of limited clinical value unless they are low (<5 mm Hg) and confirm an existing suspicion for hypovolemia. Trends and their correspondence to clinical evidence of organ function and perfusion help to create a more meaningful picture of fluid needs and euvolemia. The standard for testing volume responsiveness is to give a fluid challenge. This involves giving fluids to increase the CVP by 2 mm Hg and then determining whether it increased the CO . In a sthallenge .The Society of Critical Care Medicine's Surviving Sepsis protocol recommends to fluid resuscitate a septic patient to a target CVP goal of 8–12 mm Hg and 12–15 mm Hg in a mechanically ventilated patient . Though The discussion above applies to use of jugular and subclavian veins. If these sites are not available, femoral vein line pressures have been shown to be a good substitute for CVP. In various studies in spontaneously breathing and ventilated patients, inferior vena cava pressures have been shown to be around 0.5 mm Hg lower than the SVC pressures on average and rarely more than 3 mm Hg different . Though A healthy person can have a CVP less than zero in upright position and still have an adequate CO and be euvolemic. Conversely, CVP can be high in a patient with poor ventricular function and low cardiac output or with a good ventricular function and volume overload . As illu2) with a single device. ScvO2 values of more than 70% are consistent with an adequate cardiac output and perfusion status, although this relationship is true only with adequate hemoglobin levels and stable oxygen requirements (VO2) of the body. The early goal-directed therapy for severe sepsis and septic shock has ScvO2 monitoring as an integral part of the resuscitation goals [2.Another distinct advantage of central venous catheterization is the ability to obtain simultaneous measurements of pressure or pressure change and central venous saturations , the catheter is in continuity with the left ventricle. With some minor gradients in between structures, as long as the catheter is the West Zone III of the lung and no mitral valve pathology is present, the following relationship exists.When pulmonary vascular resistance is not elevated, the PA diastolic pressure approximates the pulmonary artery wedge pressure (PAWP) and provides a useful estimate of LVEDP without having to advance and wedge the catheter. Pulmonary artery catheters can also be used to measure mixed venous saturations and CO via the Fick principle by analysis of blood aspirated from the catheter's distal port. Typically, most CO measurements are made by electronic analysis of a thermal wash-out curve of fluid of a known temperature detected proximally at the point of injection and distally at a thermistor located 4 cm from the catheter tip. Continuous measurement of CO is accomplished with catheters containing an additional thermal filament and a computation module. The latter system requires occasional set-up time and calibration. Data from either of these catheters can be used to derive right ventricular ejection fraction (REF) and right ventricular end-diastolic volume (RVEDV). Thus, in addition to titration of fluids, the impact of inotropes, vasoconstrictors, and other interventions can be measured and followed. Low REF has been found to be helpful in identifying myocardial depression and as a marker of poor prognosis in septic patients . In cardAs with the CVP, PAWP measurements are dependent on myocardial compliance. Multiple studies on ICU patients have shown that PAWP in acute illness correlates poorly or inconsistently with left ventricular end-diastolic volume (LVEDV) –17. Comp2), [2 was achieved by dopexamine infusion [For most of the past three decades, use of the PAC was based on the uncontested assumption that targeted improvement of physiologic parameters to supranormal endpoints is a desirable strategy. This approach began in the early 1970s when Shoemaker and colleagues described a pattern of higher ventricular performance, oxygen delivery, and oxygen consumption which predicted survival in trauma patients . Subsequ2), ). A simiinfusion , and a linfusion . 2 [2 delivery index of ≥600 mL/min/m2 in another [2 and VO2 were attempted [per se in high-risk surgical patients [Using the PAC to facilitate increased oxygen delivery in medical and surgical ICU patients was the next natural step. However, therapy designed to achieve such supranormal values had no effect in one study where therapy was targeted to achieve a supranormal CI and normal SvO2 , did not another , did notttempted , and, fittempted . In the patients , patientpatients , and adupatients . In the patients . Use of PACs has fallen over the last ten years due to the factors cited above, as well as due to higher complication rates , frequenAt present no study has demonstrated a positive association between PAC use for fluid management and survival . Many ofCardiac output and blood pressure interact with the respiratory system in a predictable manner according to the relationships indicated in It is well recognized that pulsus paradoxus, or an inspiratory fall in systolic blood pressure by more than 10 mm Hg, is seen in critically ill patients with hypovolemia. With hypovolemia, the myocardium is at the steep portion of the Frank-Starling curve, so any minor variation in the preload with inspiration or expiration can cause appreciable changes in CO and blood pressure. Some rather direct and accurate inferences regarding intravascular volume can be made from analysis of arterial pressure waveforms and Doppler analysis of aortic blood flow. Ironically, while positive pressure ventilation is used, the accuracy of pressure-based measures of fluid responsiveness such as CVP is highly debated, while flow-based measurements achieve their highest accuracy. Indices of intravascular fluid and preload assessment derived from positive pressure ventilator-induced arterial blood pressure changes include systolic pressure variability, the respiratory systolic variation test, stroke volume variability, and respiratory changes in arterial pulse pressure.The range of blood pressure  during a single positive pressure breath is defined as SPV. The baseline systolic pressure is taken using a short apneic period. SPV has 2 components, delta up and delta down, corresponding to the difference between the baseline and the peak amplitude during early expiration and at end inspiration, respectively. SPV refers to the sum of delta up and delta down or the total amplitude variation .Beside intravascular volume status, SPV and its two components can be affected by a multitude of factors which include arrhythmias, chest wall and lung compliance, abdominal pressure, method of ventilation , and myocardial function –46. All espiratory systolic variation test uses the slope obtained by the minimal systolic BP during a ventilator maneuver involving four successive incremental positive pressure breaths [Respiratory change in arterial pulse pressure (DPp) is defined as the difference in pulse pressure of the highest (Ppmax) and lowest magnitude (Ppmin) over several respiratory cycles, divided by the mean of the 2 values, expressed as a percentage. In one study, a DPp of 13% differentiated fluid responders from nonresponders [Stroke volume variability is an index that is based on beat-to-beat variability in the arterial pulse during the respiratory cycle [Other methods of analyzing fluid responsiveness from respiration-induced changes in arterial pulse waves have been described and validated. The r breaths . Greater breaths . Respirasponders . Stroke ry cycle . While all of these parameters can be measured manually via printouts from raw arterial pressure waves, a number of commercial systems discussed below provide automated analysis and trending along with means of measuring cardiac output. The PiCCO system  derives volumetric parameters from arterial waveforms via a set of algorithms termed pulse contour analysis. The latter method, first described by Wesseling et al., computes the end-diastolic to end-systolic change in pressure over systemic vascular resistance (SVR) . The beaIn principle, the monitor could indicate fluid responsiveness via pulse variability with mechanical ventilation as a stand-alone monitor, but, with calibration, an additional wealth of information is available. Unlike the PAC, the injectate signal is collected at one of the large arteries outside of the thorax  and thus measures transpulmonary blood flow. Mathematical analysis of the transpulmonary dilution curve can be carried out further to derive actual fluid compartments within the thorax. Two of the derived parameters, extravascular lung water (EVLW) and global end-diastolic volume (GEDV), are of particular interest. Both GEDV and the related intrathoracic blood volume (ITBV) are volumetric preload parameters in contrast to the more commonly used pressure-derived parameters from CVP and PACs. Changes in GEDV have correlated better with changes in stroke volume than with changes in CVP . The abiAn investigation of postoperative cardiac surgery patients showed that CO derived by PAC and transpulmonary method is clinically comparable . The advSimilar measurements using transpulmonary lithium dilution and detection by an ion selective electrode are the basis of another commercial system providing continuous CO and pulse wave analysis, the PulseCO  . The conAnother recently introduced system called FloTrac/Vigileo  has also been designed to function without external calibration. Instead individual demographic data  are used with arterial waveform analysis to calculate CO, the principle being that SV is proportional to pulse pressure (PP). In addition, the FloTrac can also calculate SVV, and if a central venous catheter is present, SVR and central venous saturation can be obtained. Like the LiDCO rapid, the FloTrac features ease of use and requires only an arterial catheter . A studyPressure Recording Analytical Method (PRAM)  is another device that estimates CO from the area under the arterial pressure wave. No external calibration is required as with FloTrac. A study in hemodynamically stable children comparing Doppler echocardiography found PRAM reliable, though more validation studies are required .From its initial use in outpatient settings in 1970s, echocardiography has found its place in all inpatient settings, ranging from the operating rooms to the intensive care unit (ICU). Different modalities of ultrasound include transthoracic echo being most noninvasive and portable, while the more invasive nature of esophageal Doppler and transesophageal echo is well tolerated in anesthetized patients. Nevertheless, all echographic techniques spare the patient the complications related to vascular access and indwelling devices. Also, in contrast to the PAC which is dependent on pressure measurements to make volume determinations, echocardiography relies on direct visualization of the cardiac anatomy and flow dynamics. Moreover, in patients where causes of circulatory failure overlap, echocardiography provides the ability to evaluate structural abnormalities , contractility (ejection fraction), besides assessment of intravascular volume. Improved image quality with portable study echo machines in the last decade has made TTE a popular tool for intravascular fluid assessment in the ICU. More recently, its use has been advocated in the perioperative settings due to its ability to provide quick, noninvasive functional and fluid assessment. Right heart preload can be reliably obtained by direct measurement of the inferior vena cava diameter (IVC) variations with respiration  and alsor = 0.17, P = .45) and dIVC [In mechanically ventilated patients, IVC variations with respiration (Delta DIVC) of 12% differentiated patients who responded with increased CO to a fluid bolus from nonresponders . In anotand dIVC . In spitBesides cardiac anesthesia, TEE is now used routinely in other complex and long surgeries , especially among patients with known cardiac pathology. In our operating rooms, the quick availability of TEE machines makes this a first-line diagnostic modality for experienced users when unexpected hemodynamic instability is encountered. For general use, the main focus is on intravascular volume status assessment and overall cardiac function. In the ICU, TEE is recommended when diagnostic information cannot be adequately obtained by TTE . LimitatAs with TTE for IVC measurements to determine preload, TEE can be used to measure SVC collapsibility. Volume expansion was found to decrease SVC collapse, decrease RV stroke volume variation, and increase CI in a study in 22 mechanically ventilated ARDS patients with septic shock . A collaBoth TTE and TEE allow visual estimation of ventricular volume. Ninety percent of the stroke volume is obtained by ventricular shortening in the short axis . TherefoUsing the Doppler principle to calculate blood flow velocity in the aorta, EDM can be used to provide minimally invasive continuous CO monitoring. EDM comprises of a small, thin, flexible probe with a Doppler transducer at the tip, inserted 35 cm into the esophagus, and has a tolerability similar to a nasogastric tube . A contiWhile nearly emerging devices for fluid management have sought to first establish themselves as similar to the “gold standard” PAC, the initial studies of EDM are relatively unique in their attempt to associate a positive clinical outcome with device use. In postsurgical patients, hypovolemia is a notorious cause of splanchnic hypoperfusion, prolonged hospital stays, and even increased mortality in moderate- to high-risk surgical patients –84. Withelectrical bioimpedance. With electrical velocimetry (EV), all measurements are made via four ECG electrodes applied along one side of the patient's body. A small amplitude alternating current is applied to one pair of electrodes, while the other detects the change in electrical signal through the cardiac cycle. When blood moves forward through the ascending aorta during ventricular ejection, red cells tend to align more along the body's long axis, and create less impedance of electrical signals traveling along the same vector. Thus, from analysis of the electrical signal during the cardiac cycle, velocity and flow time parameters are generated and used to calculate stroke volume and cardiac output. An analogous method for evaluation of cardiac output is based on estimation of blood flow via analysis of r = 0.97) was found between EV and cardiac output measurements made by the Fick method (using direct measurements of VO2) in children with congenital heart disease, and EV measurements correlated well with Doppler measurements made via transesophageal echo in cardiac surgery patients [Comparisons between EV and thermodilution cardiac output measurements show a good level of agreement over a wide range of outputs in adult cardiac surgery patients and critically ill adults , 87. An patients , 89.Limitations to EDM use are similar to TEE. In addition, severe aortic regurgitation, severe lung disease, altered thoracic blood flow, and presence of intra-ortic balloon pump can alter accuracy of EDM . Resuscitation of the hypotensive patient in the perioperative setting can be challenging. Accurate and timely assessment of fluid status and fluid responsiveness are cornerstones in the management of the hypotensive patient. Both hypovolemia and hypervolemia can be harmful. Goal-directed fluid management can result in the appropriate use of fluids, vasopressors, and inotropes, resulting in improved patient outcomes. Invasive, noninvasive, static, and dynamic monitoring methods have strengths and limitations. Continual monitoring of unstable patients through the resuscitation period utilizing a combination of techniques can improve the utility of hemodynamic information, improve the accuracy of assessments of volume status, and improve patient outcomes.


Uncontrolled blood pressure (BP) is a significant contributor of morbidity and even mortality in type 2 diabetes (T2D) patients. This study was done to determine the significant determinants of uncontrolled blood pressure in T2D patients in Malaysia.st January 2009 to 31st December 2009, data from 70 889 patients with Type 2 diabetes was obtained from the Adult Diabetes Control and Management Registry for analysis; 303 centers participated in the study. Their demographic characteristics, the nature of their diabetes, their state of hypertension, treatment modalities, risk factors, and complications are described. Based on their most recent BP values, subjects were divided into controlled BP and uncontrolled BP and their clinical determinants compared. Independent determinants were identified using multivariate logistic regression.Between 1The mean age of patients at diagnosis of diabetes was 52.3 ± 11.1 years old. Most were women (59.0 %) and of Malay ethnicity (61.9 %). The mean duration of diabetes was 5.9 ± 5.6 years. A total of 57.4 % were hypertensive. Of the 56 503 blood pressure (BP) measured, 13 280 (23.5 %) patients had BP <130/80 mmHg. Eighteen percent was on > two anti-hypertensive agents. Health clinics without doctor, older age (≥ 50 years old), shorter duration of diabetes (< 5 years), Malay, overweight were determinants for uncontrolled blood pressure (BP ≥130/80 mmHg). Patients who were on anti-hypertensive agent/s were 2.7 times more likely to have BP ≥130/80 mmHg. Type 2 diabetes patients who had ischaemic heart disease or nephropathy were about 20 % and 15 % more likely to have their blood pressure treated to target respectively.Major independent determinants of uncontrolled BP in our group of T2D patients were Malay ethnicity, older age, recent diagnosis of diabetes, overweight and follow-up at health clinics without a doctor and possibly the improper use of anti hypertensive agent. More effort, education and resources, especially in the primary health care centres are needed to improve hypertensive care among our patients with diabetes. The profile of blood pressure (BP) management in Type 2 diabetes mellitus (T2D) patients has generally been unsatisfactory until about two decades ago ,2. In 19Patients with diabetes are especially vulnerable to hypertensive injury. The coexistence of hypertension has a significant impact of the poor prognosis for patients with diabetes because of its effect on the micro and macro vasculature. These include impaired autoregulation of blood flow in the microcirculation, the non-dipping of nocturnal BP owing to autonomic dysfunction, increased pulse-wave velocity and ventricular-vascular mis-coupling from premature stiffening of the abdominal aorta by elastic fibres glycation -9. The aClearly there is convincing evidence on the benefits of effectively treating T2D patients who have hypertension. However, we have no national data on this aspect of the problem and neither do we know how effective we have been in dealing with the problem. We therefore set out to assess the care these patients have been given and in particular, the variables that had a significant impact on the uncontrolled blood pressure. We hoped that the results will shed some light on the problem and guide policy-makers in developing appropriate strategies for prevention and for the proper allocation of health resources to this area of diabetic management.st December 2009, 3140 (4.4 %) were lost to follow-up (defaulted appointment for > one year) and 203 (0.3 %) patients had passed on.This was a cross-sectional study using data extracted from the Adult Diabetes Control and Management (ADCM) Registry in 2009. It represents 70 889 T2D patients from 289 health clinics and 14 hospitals and from 8 of the 15 states in the country and 2 Federal territories. These represent 22.1 % of the health clinics and 9.6 % of the hospitals in the country. It has been estimated that these patients represent 5.2 % of the total number of diabetics in these areas 70889/1368590)  and lipid profile control .Mean levels were compared using the Student’s t test for unpaired samples and proportions compared with Chi square test. The normality of each variable was first tested by histogram and confirmed by Kolmogorov-Smirnov test. A two-tailed P value of < 0.05 was considered to be significant.Having grouped the patients into controlled and uncontrolled BP using the latest mean BP values, logistic regression was used to determine the significant clinical determinants. The significant determinants were then identified and fitted into a multivariate logistic regression model using the stepwise method with uncontrolled BP as the dependent variable. Multicolinearity between the variables were checked with correlation matrix and inspected for the magnitude of the standard error (SE). None of the variables correlated with each other, r < 0.2 and SEs were all within 0.001 to 5.0. All data was analysed using STATA version 9.Of the 70 889 patients with T2D analysed, most were women (59.0 %) and Malays 62 %) Table . The mea2 = 19.14, p < 0.001), this association was not seen for ADA, diet therapy and HbA1c levels.The variables that determined good control of BP on univariate analysis were, the type of health clinic, ethnicity, age group, duration of diabetes, BMI, HbA1c, targets of lipid profiles and use of anti-hypertensive agent , double  or ≥ triple anti-hypertensive agents .Of interest was that those who were being treated for hypertension did not have their blood pressure control on target Figure  This wasOf the 41 286 (58.2 %) patients on anti-hypertensive agents, angiotensin-converting enzyme inhibitors (ACEI) (63.9 %) were the most prescribed, followed by calcium channel blockers (CCB) (37 %) beta-blockers (36.5 %) and diuretics (23.4 %). The use of specific anti-hypertensive drug classes had been assessed and reported elsewhere .Health clinics without a doctor, older age (≥ 50 years old), shorter duration of diabetes (< 5 years), non-Indians , overweight, being on anti-hypertensive agents and having poor lipid profile LDL-C > 2.6 mmom/L) were predictors for uncontrolled blood pressure (BP ≥130/80 mmHg). Patients who were on anti-hypertensive agent/s were 2.7 times more likely to have uncontrolled BP. T2D patients who had IHD or nephropathy were about 20 % and 15 % more likely to have their blood pressure treated to target, respectively . It was not the case in reverse when treating these lipid profiles and HbA1c to targets, we noticed that a large proportion of T2D patients were still not at BP target (about 75 %). Therefore, simultaneous management of all these risk factors is most cost-effective via BP lowering effort. Sever P et al reported a potential synergy between the use of amlodipine-based blood pressure lowering agent and lipid lowering agent (atorvastatin 10 mg) in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) which comprised 10 305 patients with about a quarter of them were with diabetes mellitus . There w %. It waOf the demographic characteristics, we found that those who were > 50 years old, recently diagnosed with diabetes, overweight (and obese) and of Malay ethnicity were more likely to have uncontrolled BP and require closer monitoring. The high proportion of Malays was probably a reflection of the population distribution in Malaysia with Malays being the dominant race. It has been shown that a combination of T2D, resistant hypertension and obesity was related to autonomic imbalance (heart rate variability) and circadian disruption of the sympathetic and parasympathetic tones during day and night periods. These effects may contribute to the observed increased risk of cardiovascular morbidity and mortality . PreventThe way in which our patients were being treated with hypertensive agents appears to be less than satisfactory. More than half of the patients were on two or more drugs and despite this; good control has not been achieved. Granted that most patients with T2D diabetes may require combination therapy  but the Therefore the education of the physicians managing these patients, the use of proper combinations, attending to the individual needs of the patient and adherence to guidelines are ways in which this area can be improved . Thus, tNot surprisingly, BP control among the T2D patients was better at the health clinics where a doctor was present when compared to those without. Rohana D et al has shown convincing evidence that in Malaysia, where the clinics were manned by a M&HO or family physician, the care was significantly better . The solThere may be other factors that may have contributed to the poor control of hypertension. Concentration on the glycaemic control (HbA1c) at the expense of the hypertension could be one factor ,40. InadThe limitations of our study are recognized. The sample studied may not have been representative of the country. Not all hospitals or health clinics were involved in the survey. Furthermore, 20 % of the blood pressure recordings were missing . A largeT2D patients who were older, recently diagnosed, obese and having care at a health clinic without a doctor were more likely to have uncontrolled BP. These patients can be clearly identified and therefore preventive measures should concentrate on this group of patients. The inappropriate use of anti-hypertensive agent may be another identifiable reason for the poor control of hypertension. Investment in these areas in terms of appointment of trained physicians to health clinics and drawing up proper guidelines in their management of hypertension, especially in improving physician prescribing capability, should be a priority in order to reduce the unfavourable consequences of hypertension in our patients with T2D.T2D, Type 2 diabetes; BP, Blood pressure; HDS, Hypertension in Diabetes Study; NNT, Number needed to treat; QALYs, Quality-adjusted life-years; ADCM, Adult Diabetes Control and Management; CRF, Case record form; FMS, Family medicine specialists; ADA, Anti-hyperglycaemic agents; LDL-C, Low density lipoprotein-cholesterol; TG, Triglyceride; HDL-C, High density lipoprotein-cholesterol; CVD, Cerebrovascular disease/stroke; IHD, Ischemic heart disease; ED, Erectile dysfunction; BMI, Body mass index; ACEI, Angiotensin-converting enzyme inhibitors; CCB, Calcium channel blockers.The authors declare that they have no competing interests.MI & CBH collected data; CBH drafted the manuscript; MAB & CBH, performed statistical analysis. All authors read, edited and approved the final manuscript.


Septic shock is characterized by altered tissue perfusion associated with persistent arterial hypotension. Vasopressor therapy is generally required to restore organ perfusion but the optimal mean arterial pressure (MAP) that should be targeted is uncertain. The aim of this study was to assess the effects of increasing MAP using norepinephrine (NE) on hemodynamic and metabolic variables and on microvascular reactivity in patients with septic shock.2), using near infrared spectroscopy (NIRS), with serial vaso-occlusive tests (VOTs) on the upper arm. We also evaluated the sublingual microcirculation using sidestream dark field (SDF) imaging in 6 of the patients.This was a single center, prospective, interventional study conducted in the medico-surgical intensive care unit of a university hospital. Thirteen patients in septic shock for less than 48 hours who required NE administration were included. NE doses were adjusted to obtain MAPs of 65, 75, 85 and (back to) 65 mmHg. In addition to hemodynamic and metabolic variables, we measured thenar muscle oxygen saturation (StOP<0.05) and mixed venous oxygen saturation . Oxygen consumption (VO2) remained stable, but blood lactate levels decreased. There was a significant increase in the ascending slope of StO2  after VOTs. SDF imaging showed an increase in perfused vessel density  and in microvascular flow index .Increasing NE dose was associated with an increase in cardiac output (from 6.1 to 6.7 l/min, In this series of patients with septic shock, increasing MAP above 65 mmHg with NE was associated with increased cardiac output, improved microvascular function, and decreased blood lactate concentrations. The microvascular response varied among patients suggesting that individualization of blood pressure targets may be warranted. Septic shock is characterized by an alteration in tissue perfusion associated with persistent arterial hypotension - generally defined as a systolic arterial pressure of less than 90 mm Hg  - despit2) in 10 patients with septic shock. Bourgoin and colleagues [2) and cutaneous microvascular flow; however, the authors found no significant effect on the microcirculation when using sidestream dark field (SDF) imaging techniques. Using the same SDF imaging techniques and a similar protocol with MAP at 65, 75, and 85 mm Hg, Dubin and colleagues [In septic shock, fluid resuscitation is insufficient to restore hemodynamic stability, so that vasopressor therapy is typically required to restore organ perfusion. Recommendations suggest that a mean arterial pressure (MAP) of around 65 mm Hg should initially be targeted . There illeagues  observedlleagues  showed tlleagues  reportedBecause of these unsettled controversies, we studied the hemodynamic, metabolic, and microcirculatory effects of an increase in NE dose in patients with septic shock. Our hypothesis was that increasing MAP by increasing NE doses would improve microvascular function in patients with septic shock.This was a single-center study conducted over a 1-year period and approved by the local ethics committee of Erasme University Hospital . Informed consent was obtained from all patients or their closest relative.We studied 13 adult patients who had had septic shock for less than 48 hours. All patients had an arterial catheter, a central venous catheter, and a pulmonary artery catheter (Swan-Ganz) in place. All patients required an NE infusion for arterial hypotension resistant to fluid therapy, supported by a change in pulse pressure (ΔPP) of less than 13% [NE doses were adjusted to maintain a baseline MAP of 65 ± 2 mm Hg. After stabilization, basal measurements were performed twice, 15 minutes apart ('baseline 1 and 2'), and the NE doses were increased to obtain an MAP of 75 ± 2 mm Hg; patients were allowed to stabilize for 30 minutes before taking measurements ('increasing 1'). NE doses were then increased to reach an MAP of 85 ± 2 mm Hg within 15 minutes, and the measurements were repeated after another 30-minute stabilization period ('increasing 2'). NE doses were then decreased to return to an MAP of 65 ± 2 mm Hg, and another stabilization period of 30 minutes was allowed before the final measurements ('baseline 3'). During the protocol, no other change in treatment was allowed.2), arterial partial pressure of oxygen (PaO2), hemoglobin concentration, arterial hemoglobin saturation (SaO2), mixed venous hemoglobin saturation (SvO2), and blood lactate concentration. Vascular resistances were calculated by standard formulas. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score [We measured temperature, heart rate, cardiac output, systemic and pulmonary arterial pressures, central venous pressure (CVP), pulmonary artery occlusion pressure, and ΔPP. Arterial and venous gases were obtained to determine pH, arterial partial pressure of carbon dioxide (PaCOI) score  and the I) score  were cal2). A vascular occlusion test (VOT) [2 and global tissue hemoglobin (THI). The descending slope of the StO2 and the nirVO2I (the reverse descending slope multiplied by the average THI during the first occlusion minute) [2). The ascending slope of the StO2 and the reactive hyperemia reflect microcirculatory reactivity .In each patient, we used near-infrared spectroscopy (NIRS)  ,17 to evst (VOT)  was used minute)  estimateIn six patients, we also assessed the sublingual microcirculation using the SDF imaging technique  . Descriptive statistics were computed for all study variables. To verify the normality of the distributions of continuous variables, histograms and normal quantile plots were examined and the Kolmogorov-Smirnov test was used. Continuous variables are presented as mean  if normally distributed and as median (25% to 75% interquartile range) if not normally distributed. Categorical variables are presented as number and percentage. To analyze the time courses of the hemodynamic, metabolic, or NIRS parameters, we used analysis of variance for repeated measurement followed by paired 2 was 70%, and ΔPP was less than 13%  without significant changes in heart rate (Tables 2 increased from 70.6% (67.9% to 73.2%) to 75.9% (71.7% to 80.1%) (P <0.05). DO2 increased but VO2 remained stable. Blood lactate concentrations decreased.Cardiac output increased from 6.1 L/minute (5.4 to 6.8 L/minute) at baseline to 6.7 L/minute (5.9 to 7.6 L/minute) at an MAP of 85 mm Hg (e Tables  and 3. S2I.The ascending slope increased from 110.6%/minute (80.0 to 141.2%/minute) at baseline to 176.9%/minute (121.6 to 232.2%/minute) at 85 mm Hg  may partly explain the significant differences.Microcirculatory alterations have been demonstrated in sepsis  and are 2 was not affected by the different arterial pressure levels and remained lower than in a healthy population [2 suggests that NIRS changes were not the consequence of the increase in cardiac output. The ascending slope of the StO2, the delta between StO2 at baseline and at the hyperemia peak, and the ratio between the two areas under the curves can be used to estimate capillary reactivity. In our study, although delta StO2 and the ratio between the areas under the curves did not change, the StO2 reperfusion slope increased when the arterial pressure was increased by NE, indicating some improvement in microvascular reactivity. To compare our variables with values found in other NIRS studies during sepsis, we can express the StO2 recovery slope results in percentage per second [2 can be estimated from either the descending StO2 slope - which shows the rate of tissue VO2 at the onset of hypoxia - or the nirVO2I [2 during the first minute of hypoxia weighted by the conversion rate of oxyhemoglobin into deoxyhemoglobin during this period. None of these variables changed, indicating that increasing NE dose has no effect on the local tissue VO2 despite the microvascular recruiting reflected by the rise in StO2.StOpulation . The absr second ,19. The Our study also showed an improvement in microvascular reactivity, evaluated by NIRS, related to the changes in arterial pressure during sepsis. As expected, there was some interpatient variability. Our data are in line with the observation that correction of severe hypotension (MAP of less than 65 mm Hg) by NE administration in patients with septic shock resulted in improvement in microvascular reactivity measured by NIRS . It is, We also used SDF techniques to study the sublingual microcirculation in 6 of the 13 patients. There was an increase in the proportion of all perfused vessels and of perfused small vessels. The changes were not significant, but these parameters evolved from abnormal values at baseline - as expected in patients with sepsis - to almost normal values when the MAP was increased to 85 mm Hg. Almost all large vessels were perfused, and this is expected when the probe is properly applied without too much local pressure . Although the changes in small PVD were not significant, there was a significant increase in the global PVD , which probably can be explained by the increase in the proportion of small perfused vessels. Finally, the MFI showed variable values between patients but was mainly sluggish at baseline and increased toward a normal flow at higher MAP values. Accordingly, increasing arterial pressure above 65 mm Hg in septic shock may have beneficial effects on perfusion and flow in the microvessels in patients with septic shock.2, and DO2 but no significant changes in renal perfusion. It should be noted that their period of observation was quite long. Moreover, these data are in contradiction to the work of Deruddre and colleagues [Our results contradict those of some previous studies ,9,11, bulleagues , who replleagues  used SDFlleagues , in whicOur study has several limitations. First, we included a relatively small number of patients, as did other studies -12, and In the treatment of patients in septic shock, increasing MAP above 65 mm Hg with higher doses of NE can result in increased cardiac output, improved microcirculatory function, and decreased lactate concentrations. The present observations challenge the commonly heard statement that an MAP of 65 to 70 mm Hg is adequate for most patients with septic shock and suggest that microvascular studies may be helpful to define the optimal target in a given individual. The microvascular response is variable between patients and suggests that personal adaptation of the MAP is needed. Additional studies should be carried out to develop criteria for determining an individually adapted arterial pressure threshold and to evaluate the long-term effects of this strategy.• Increasing mean arterial pressure by norepinephrine during septic shock can increase cardiac output and improve microvascular flow and reactivity in stable resuscitated patients without modification of global oxygen consumption.• There is considerable interindividual variability in microvascular response, suggesting that the level of mean arterial pressure should be adapted to each patient.2: oxygen delivery; FCD: functional capillary density; MAP: mean arterial pressure; MFI: microvascular flow index; NE: norepinephrine; NIRS: near-infrared spectroscopy; nirVO2I: reverse descending slope multiplied by the average tissue hemoglobin index during the first occlusion minute; PP: pulse pressure; PVD: perfused vessel density; SDF: sidestream dark field; StO2: thenar muscle oxygen saturation; SvO2: mixed venous oxygen saturation; THI: tissue hemoglobin index; VO2: oxygen consumption; VOT: vascular occlusion test.CVP: central venous pressure; DOThe authors declare that they have no competing interests.AT participated in the design of the study and helped conduct the study, collect the data, perform the microcirculatory imaging and the statistical analyses, and draft the manuscript. DDB participated in the design of the study and helped perform the statistical analyses and draft the manuscript. JC and J-LV participated in the design of the study. RF, DRS, and KD helped conduct the study, collect the data, and perform the microcirculatory imaging. FST helped conduct the study, collect the data, perform the microcirculatory imaging and the statistical analyses, and draft the manuscript. All authors read and approved the final manuscript.


Conflicting reports support or refute an association between vitamin D deficiency with high levels of parathyroid hormone (PTH) and raised blood pressure or hypertension.To explore the associations of serum vitamin D and PTH levels with blood pressure and risk of hypertension in a Chinese population.A population-based cross-sectional study was conducted among 1,420 Chinese participants, aged 20–83 years, in 2010. Anthropometric phenotypes and blood pressure were evaluated. Serum lipids, 25-hydroxyvitamin D [25(OH)D] and PTH were measured.P>0.05). In logistic regression analyses, serum 25(OH)D levels were not associated with risk of hypertension in single and multiple regression models. One unit increments of natural log of PTH levels were significantly associated with risk of hypertension in the crude model  and model adjusted for age and sex . However, these associations were attenuated and became nonsignificant  after further adjustment for body mass index, current alcohol intake, current smoking, glomerular filtration rate and family history of hypertension.One thousand four hundred and twenty participants, including 566 women (39.9%), were evaluated in 2010. Four hundred and eighty seven were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The median concentrations of serum 25(OH)D and PTH were 22.0 ng/ml and 2.83 pmol/l, respectively. Serum 25(OH)D and natural log of PTH levels were not independently associated with blood pressure in a multivariable adjusted linear regression analysis of 1,206 participants not receiving antihypertensive treatment (Serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population. Hypertension is one of the important risk factors for cardiovascular disease, which is the major cause of morbidity and mortality worldwide. Vitamin D is known to regulate calcium and phosphate metabolism China, with a rapidly developing economy and large aging population, is experiencing a growing pandemic of hypertension We hypothesized that lower levels of vitamin D and higher levels of PTH are associated with blood pressure and the risk of hypertension in Chinese. 25(OH)D is the main storage form of vitamin D in the body and the most commonly used marker to evaluate vitamin D status. We conducted this cross-sectional study to evaluate the associations of serum 25(OH)D and serum PTH with blood pressure and the risk of hypertension in a Chinese population.The Ethics Committee of the Affiliated Hospital of Dali University approved the study protocol. All subjects gave written informed consent. The study complied with the guidelines in the Declaration of Helsinki.The present analysis was based on a cross-sectional study in the framework of comprehensive cardiovascular health examinations for all employees of a factory in Dali (25°N) of Yunnan Province, a small city in southwest of China. We invited all employees and retired workers to take part in this study from March to May 2010. Of the 1,643 eligible individuals, 1,443 (87.8%) agreed to participate in the study. In addition, 23 participants were excluded for inadequate blood sample to test 25(OH)D or PTH (n = 8), or lack of demographic data (n = 15). Thus, a total of 1,420 participants was included in the present analysis.− 1.154× −0.203×  One physician measured each participant’s blood pressure three times consecutively using an automatic blood pressure monitor (Omron HEM 7011), after the subjects had rested for at least 5 minutes in the sitting position. The three blood pressure readings were averaged for analysis. The same observer also administered a questionnaire to collect information on medical history, smoking habits, alcohol consumption and the use of medications. A trained technician performed anthropometric measurements, including body height, body weight, and waist and hip circumference. Hypertension was defined as a sitting blood pressure of at least 140 mmHg systolic or 90 mmHg diastolic, or as the use of antihypertensive drugs. Current smoking was defined as at least 1 cigarette smoked per day. Current alcohol intake was defined as consuming at least 1 drink per week. Body mass index was defined as a ratio of the body weight in kilograms to the square of the height in meters. Glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) Study equation as: GFR = 186× 125I RIA Kit, Stillwater, Minnesota, USA) in the Clinical Laboratory of the Affiliated Hospital of Dali University. The intra- and interassay coefficients of variance were 6.0% and 5.6%. Serum PTH assay was performed in the same laboratory by the chemiluminescence method . The intra- and interassay coefficients of variance were 3.9% and 6.0%.Venous blood samples were drawn after overnight fasting for the measurement of serum glucose, creatinine and total cholesterol. Serum was also stored at −30°C for measurement of 25(OH)D and PTH. Serum 25(OH)D was determined by radioimmunoassay . Because the distribution of serum PTH levels was skewed, PTH values were logarithmically transformed. Quantitative variables were summarized as mean and SD or median and interquartile range if the distribution of the variable was skewed. The differences between means were tested using the one-way analysis of variance (ANOVA). The differences between proportions were tested using the chi-square test. We restricted linear and logistic regression analyses to participants not receiving antihypertensive treatment to remove the influence of antihypertensive treatment on blood pressure. We performed unadjusted linear and logistic analyses in single regression and adjusted analyses in multiple regression after adjustment for age and sex , full adjustment for body mass index, current alcohol intake (yes/no), current smoking (yes/no), glomerular filtration rate and family history of hypertension. The interactions between serum 25(OH)D, natural log of PTH and other factors were examined by adding an interaction term to the linear regression analysis. One thousand four hundred and twenty participants included 566 women (39.9%). Four hundred and eighty seven participants were hypertensive (34.3%), of whom 214 (43.9%) received antihypertensive treatment. The prevalence of hypertension was 37.6% and 29.3% for men and women, respectively. The median concentrations of serum 25(OH)D and PTH for the entire group were 22.0 ng/ml and 2.83 pmol/l, respectively.P≤0.04). Compared with participants with lower natural log of PTH levels, those with higher natural log of PTH levels had lower serum 25(OH)D levels, higher systolic and diastolic blood pressure, higher pulse pressure, higher serum glucose and higher prevalence of hypertension, a greater body mass index and were older (P≤0.03).Characteristics of the 1,206 participants without antihypertensive treatment are shown in P>0.05) in linear regression analyses in the 1,206 participants without antihypertensive treatment both in unadjusted and adjusted models .Serum 25(OH)D levels were not statistically associated with either systolic or diastolic blood pressure . A one unit increment of natural log of PTH was significantly associated with a 1.78-fold increased risk of hypertension  in the crude model and a 1.41-fold increased risk of hypertension  in model adjusted for age and sex, respectively. However, when body mass index, GFR, current alcohol intake, current smoking and family history of hypertension were further adjusted, these associations were attenuated and became nonsignificant . Subgroup analyses stratified by gender yielded similar results.The main findings of our cross-sectional study are that serum 25(OH)D and PTH levels are not independently associated with blood pressure level or risk of hypertension in a Chinese population.et al.Our findings that serum 25(OH)D was not significantly associated with blood pressure level or risk of hypertension are consistent with some studies et al. et al.Our finding is in contrast to three Chinese studies. Lu The finding that serum PTH level was not associated with blood pressure level or risk of hypertension is in contrast to previous studies. Several studies have consistently demonstrated that higher levels of circulating PTH were associated with higher blood pressure or prevalence of hypertension Although we did not find any associations of serum 25(OH)D and PTH levels with blood pressure or risk of hypertension, previous experimental and population studies have provided several mechanisms to explain the relationships among vitamin D, PTH and blood pressure. Vitamin D may influence blood pressure by functioning as an endogenous inhibitor of the renin-angiotensin system (RAS) A strength of our study is its rapid completion, which minimized seasonal variation of serum 25(OH)D and PTH levels. In addition, there was only 1 participant on calcium supplementation and none received vitamin D supplementation. However, our study has to be interpreted within the context of its limitations. First, we did not collect information on physical activity, dietary vitamin D intake, and sunlight exposure. Second, we used only a single measurement of serum 25(OH)D and PTH. It can be questioned whether serum 25(OH)D and PTH levels measured at a single point in time reflects only recent exposure rather than long-term exposure. In addition, the participants were not selected randomly from the general population. Therefore, the results may not be generalized to the general population. Finally, our study was cross-sectional, and hence no causal inference could be taken.In conclusion, our study suggests that serum vitamin D and PTH levels are not independently associated with blood pressure or risk of hypertension in a Chinese population. Prospective population studies are needed to evaluate the role of vitamin D and PTH in the incidence of hypertension.


Prevention and control of hypertension are critical in reducing morbidity and mortality attributable to cardiovascular diseases. Awareness of hypertension is a pre-condition for control and prevention. This study estimated the proportion of adults who were hypertensive, were aware of their hypertension and those that achieved adequate control.We conducted a community based cross sectional survey among people≥15 years in Buikwe and Mukono districts of Uganda. People had their blood pressure measured and were interviewed about their social-demographic characteristics. Hypertension was defined as systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or previous diagnosis of hypertension. Participants were classified as hypertensive aware if they reported that they had previously been informed by a health professional that they had hypertension. Control of hypertension among those aware was if systolic blood pressure was <140 mmHg and diastolic blood pressure was <90 mmHg.The age standardized prevalence of hypertension was 27.2% (95% CI 25.9–28.5) similar among females (27.7%) and males (26.4%). Prevalence increased linearly with age, and age effect was more marked among females. Among the hypertensive participants, awareness was 28.2% (95% CI 25.4–31.0) higher among females (37.0%) compared to males (12.4%). Only 9.4% (95% CI 7.5–11.1) of all hypertensive participants were controlled. Control was higher among females (13.2%) compared to males (2.5%).More than a quarter of the adult population had hypertension but awareness and control was very low. Measures are needed to enhance control, awareness and prevention of hypertension. The epidemiological transition with increasing prevalence of chronic non-communicable diseases (NCDs) is already underway in sub-Saharan Africa Studies examining awareness and control of hypertension in Uganda and SSA are scarce, despite the reported increase in the prevalence of hypertension in the region The study was conducted among adults 15 years and above in urban and rural communities of Buikwe and Mukono districts of Uganda. Buikwe was carved out of Mukono district in 2009. These two districts neighbour Lake Victoria and lie between the two biggest urban areas of Jinja and Kampala . Together the two districts have a population of over 1,000,000 people . About 75% of the population are rural dwellers whose main occupation is agriculture. Mukono and Buikwe districts were chosen because of their strategic location between two major urban centers of Kampala and Jinja as well as the likelihood of having a large section of urban dwellers.This was a community based cross sectional study where data was collected through interviews and taking of physical measurements. The tool used for data collection was adapted from the World Health Organisation (WHO) stepwise approach to chronic disease risk factors surveillance (STEPS) The questionnaire enlisted social demographic and behaviour variables such as age, sex, place of residence, level of education, marital status, alcohol and tobacco smoking. Physical measurements conducted included the height, weight, and blood pressure. In addition a medical history was elicited regarding whether the individual had ever had their blood pressure measured, whether they have ever been told by a health professional that they have hypertension and whether they were receiving treatment for hypertension in the previous two weeks preceding the survey. The questionnaire administration and blood pressure measurements were carried out by trained research assistants from July through September of 2012 in people's homes. Data collection was conducted every day of the week including weekends and evenings when men in urban settings were more likely to be found at home.Blood pressure (BP) was measured on a single occasion using automated digital blood pressure monitor, model LD7 with appropriate cuff sizes. Three blood pressure measurements (at least 1 minute apart) were taken after 5 minutes rest with the participant seated, using a calibrated automated digital BP machine. For each participant's blood pressure, the mean of the three values was calculated to estimate their blood pressure. A participant was classified as being hypertensive if their mean systolic BP was 140 mmHg or higher, or if their average diastolic BP was 90 mmHg or higher, or if they were on anti-hypertensive treatment in the two weeks preceding the study or if they had previously been told by a health professional that they had hypertension or the combination of the above. Participants were classified as hypertensive aware if they reported that they had previously been informed by health professional that they had hypertension. Hypertensive aware participants were classified as being on treatment if they reported current use of drugs prescribed by a health professional which they had taken within the past two weeks prior to the study. Control was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg among people aware of their hypertension.A random sample of 111 villages stratified by residence status  was generated using a sampling frame of the 2002 Uganda National Census and Housing enumeration areas available from the Uganda Bureau of Statistics The study was approved by Makerere University School of Public Health institutional review board and the Uganda National Council of Science of Technology. Written informed consent was obtained from adult participants. For participants below the age of 18, assent and written informed consent were obtained from minors and their parents/guardians respectively. People diagnosed with hypertension were referred to health units.http://www.epidata.dk), cleaned and exported using Stata Transfer to STATA 10.0  for analysis. The prevalence of hypertension was age standardized using World Health Organisation (WHO) world population for people aged 15 years and above. In order to adjust for clustering, robust standard errors and cluster option in the STATA 10.0 software were utilized. We conducted stratified analysis by sex and classified outcomes variables according to residence, age, marital status, school attendance, alcohol consumption, tobacco smoking and Body Mass Index (BMI). To identify independent predictors of being hypertensive; age, residence, level of education, marital status, tobacco smoking, alcohol use and BMI were controlled for each other using multivariable logistic regression. The crude odds ratios (COR) were compared to adjusted odds ratios (AOR) and their 95% confidence intervals (CI). Awareness and control of hypertension was assessed by calculating proportions with their CI. For awareness the number of those who were aware was divided by those who were hypertensive. For control the numerator was those controlled and the denominators were those hypertensive, aware or on treatment. Significance for proportions was tested using a two tailed Pearson's chi-square test with Yates's collection. Linear trends between hypertension and age, education and BMI were assessed with Cochran-Armitage chi-square for linear trend. For all tests, a p-value of <0.05 was taken as statistically significant.Data that was collected by trained research assistants from July to September 2012 was field edited and checked for consistencies on a daily basis after each working day. Consequently, the data was entered in EpiData 3.02  were found at home and consented to participate in the study. Of those who consented 222 (7% of the women) were excluded because they reported being pregnant. Thirty three of the 4596 study participants (12 men and 21 women) were excluded from analysis because of missing data. Of the 4563 analysed 64.5% where females and 35.5% were males. More females were included because they were more likely to be found at home compared to men. No more data was collected about people not at home at the time of the survey.The overall prevalence of hypertension in our sample was 21.8%. The age adjusted prevalence was 27.2% and was similar among women and men [Female 27.7% (95% CI 26.1–29.3) and men 26.4% (95% CI 24.3–28.5)]. The prevalence of hypertension increased linearly with age overall  and the increase was more marked among women . Young wIn a multivariable logistic regression model that controlled for sex, age, education level, residence, marital status, tobacco smoking, alcohol consumption and BMI, the independent predictors of being hypertensive were age, residing in an urban area and being overweight or obese .Overall 1268  of the study participants had ever had their blood pressure measured. Females were more likely to have ever had their blood pressure measured compared to males [women 36.5% versus men 12.0%]. Among the 997 people that had hypertension 283  were aware that they have the disease and awareness was high among the women compared to males [women 37.4% versus men 12.4%]. Of those aware of the disease 142 (51.6% CI 45.7–57.4) were on treatment within two weeks of the interview and 93  had achieved control of the disease. More men (62.2%) than women (48.7%) were likely to be on treatment but the difference was not statistically significant . ControlAwareness increased linearly with age from 1.7% among those aged 15–24 to 38% among those aged more than 65 years . However, awareness was not affected by level of education . Although awareness was high in rural areas (29.7%) than urban areas (24.6%), this difference was not statistically significant .In a population based survey of adults 15 years and above conducted in the districts of Mukono and Buikwe in Uganda hypertension was very common with more than one in five of the people affected. The finding is consistent with studies conducted in other parts of the country as well as in sub-Saharan Africa which show the prevalence of high blood pressure ranging from 20% to 50% Despite the high prevalence of hypertension, awareness of the problem was very low at less than 30 percent. The low awareness could be explained by our study findings that showed only 27.8% of the population to have had their blood pressure ever measured. Awareness of hypertension largely depends on the capacity of the health system to provide diagnostic services for hypertension to the general population Among the people with hypertension less than 10% were controlled. Reasons for this very low level of control is that the majority of people with hypertension are not aware and even among those aware less than a half were receiving treatment. However, even among those receiving treatment only one in three had achieved control. A worrying global trend is that very low levels for control of hypertension are widespread in both low and high income countries Advantages of the present study were the large sample size stratified by sex and the use of a standardized protocol. However, the sample was not strictly representative, as more women than men were found at home and therefore more likely to be involved in the study Click here for additional data file.