Fatty acid-binding protein 4 (FABP4), but not FABP1 (liver-type FABP), is ectopically induced in injured glomerular endothelial cells, and urinary FABP4 (U-FABP4) level is associated with proteinuria and renal dysfunction in a general population.The clinical significance of U-FABP4 was investigated in 81 patients  who underwent kidney biopsy.r = − 0.56, P < 0.01) and was positively correlated with age, blood pressure, triglycerides, proteinuria , plasma FABP4 and urinary FABP1 (U-FABP1) . Multivariable regression analysis showed that eGFR, proteinuria and U-FABP1 were independent predictors of U-FABP4. The level of U-FABP4, but not that of proteinuria, eGFR or U-FABP1, in minimal change nephrotic syndrome (MCNS) was significantly lower than the level in membranous nephropathy (MN) and that in diabetic nephropathy. Receiver operating characteristic curve analysis indicated that U-FABP4 level ≤ 0.78 μg/gCr predicted MCNS in patients who had nephrotic-range proteinuria with a high level of accuracy. When divided by the median value of U-FABP4 at baseline in 33 of the 81 patients who could be followed up, the yearly change (post–pre) in eGFR in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group (median: 11.0 vs. -5.0 mL/min/1.73m2/year).U-FABP4 was negatively correlated with estimated glomerular filtration rate (eGFR) (U-FABP4 level is independently associated with proteinuria and renal dysfunction in patients with glomerular kidney disease. A low U-FABP4 level may predict MCNS in patients with nephrotic syndrome and would be a useful biomarker for differential diagnosis of MCNS and MN, which are common causes of nephrotic syndrome.Supplementary information accompanies this paper at 10.1186/s12882-020-02122-y. Chronic kidney disease (CKD) and metabolic syndrome are critical issues against healthy longevity. Therefore, much attention has been paid to the associations between CKD and metabolic disorders including insulin resistance and dyslipidemia , 2. PrevThe etiology needs to be determined in each case of nephrotic syndrome for selection of therapy since the response to treatment differs depending on the glomerular kidney disease. Several clinical markers, including selectivity index , urinaryFatty acid-binding proteins (FABPs), a family of intracellular lipid chaperones, are proteins of about 14–15 kDa in size that can reversibly bind to hydrophobic ligands, such as long chain fatty acids, with a high affinity and coordinate lipid responses in cells –15. At lFABP4, known as adipocyte FABP (A-FABP) or aP2, is expressed in both adipocytes and macrophages and contributes to the development of insulin resistance and atherosclerosis , 18–20. This study conformed to the principles outlined in the Declaration of Helsinki and was performed with the approval of the institutional ethical committee of Sapporo Medical University (number: 28–2-58) and Teine Keijinkai Hospital (number: 2017–031). The present study was separately designed from a previous study , in whicA total of 87 consecutive patients  who underwent kidney biopsy in Teine Keijinkai Hospital during the period from November 2013 to April 2015 were enrolled. Samples of blood and urine were obtained before kidney biopsy during hospitalization. Six patients were excluded because volumes of stored urine samples were insufficient for analysis. After the exclusion, 81 subjects  were finally recruited in the present study. Most of the patients returned to client hospitals after kidney biopsy for routine management, and 33 of the patients underwent follow-up examination 1 year after the biopsy in Teine Keijinkai Hospital.2) = 194 × Cr(− 1.094) × age(− 0.287) × 0.739 . Level of proteinuria was quantified as protein-to-creatinine ratio in urine (g/gCr). Concentrations of FABP4 in plasma and urine and FABP1 in urine were measured using commercially available enzyme-linked immunosorbent assay kits for FABP4  and FABP1 . The accuracy, precision and reproducibility of the kits have been described previously [eGFR was calculated by an equation for Japanese: eGFR . Receiver operating characteristic curve analysis was performed to determine the inflection point at which the level of U-FABP4 provided the most sensitive prediction of MCNS in patients who had nephrotic-range proteinuria (≥ 3.5 g/gCr). The area under the curve (AUC) with the 95% confidence interval (CI) was determined, and the cut-off point was obtained by the Youden index [p value of less than 0.05 was considered statistically significant. All data were analyzed by using JMP 9.0.2 for Windows  and EZR [Numeric variables are expressed as means ± SD for normal distributions or medians (interquartile ranges) for skewed variables. The distribution of each parameter was tested for its normality using the Shapiro-Wilk W test, and non-normally distributed parameters were logarithmically transformed. Comparison between two groups was performed using Student’s t test for parametric parameters and the Mann-Whitney U test for nonparametric parameters. One-way analysis of variance and the Tukey-Kramer post hoc test for parametric parameters and the Kruskal-Wallis test and the Steel-Dwass post hoc test for nonparametric parameters were used for detecting significant differences in data between multiple groups. The correlation between two variables was evaluated using Pearson’s correlation coefficient. Multivariable regression analyses were performed to identify independent determinants of proteinuria, eGFR and U-FABP4 after adjustment of factors selected by stepwise regression analyses using Akaike’s Information Criterion (AIC), showing the standardized regression coefficient (β) and the percentage of variance in the object variables that the selected independent predictors explained , myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis (n = 3), focal segmental glomerular sclerosis (n = 2), diffuse mesangial proliferative glomerulonephritis (n = 2), diffuse endocapillary proliferative glomerulonephritis (n = 1), proteinase 3-myeloperoxidase-antineutrophil cytoplasmic antibody-associated glomerulonephritis (n = 1), membranoproliferative glomerulonephritis (n = 1) and tubulointerstitial nephritis (n = 1). Median levels of plasma FABP4 (P-FABP4), U-FABP4 and U-FABP1 were 20.4 ng/dL, 0.55 μg/gCr and 6.78 μg/gCr, respectively  are shown in Table R2 = 0.57).Logarithmically transformed (log) proteinuria was negatively correlated with eGFR and was positively correlated with age, systolic and diastolic blood pressures, total cholesterol, log triglycerides, log P-FABP4, log U-FABP4 and log U-FABP1 Table . StepwisR2 = 0.51).eGFR was negatively correlated with age, systolic blood pressure, log triglycerides, log proteinuria, log P-FABP4, log U-FABP4 and log U-FABP1 Table . StepwisR2 = 0.55).Log U-FABP4 was positively correlated with age, systolic and diastolic blood pressures, log triglycerides, log proteinuria, log P-FABP4 and log U-FABP1 and was negatively correlated with eGFR Table . StepwisThere were significant differences in levels of proteinuria Fig. a, eGFR b and U-Fn = 9), MN (n = 12) and DN (n = 4), which can be causes of nephrotic syndrome, there was no significant difference in levels of proteinuria , MN (n = 7), DN (n = 3), IgA vasculitis (n = 3), focal segmental glomerular sclerosis (n = 2) and membranoproliferative glomerulonephritis (n = 1), the AUC of receiver operating characteristic curve analysis for U-FABP4 level to predict MCNS was 0.92, and the cut-off point of U-FABP4 level by the Youden index was 0.78 μg/gCr , including MCNS (2/year)  was performed in 33 of the 81 patients. The patients were divided into two groups by the median value of U-FABP4 or U-FABP1 at baseline: low and high groups. The yearly change in eGFR, defined as the value at one-year follow-up minus the baseline value, in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group   and becaSince levels of P-FABP4 were comparable in MCNS and MN in patients with nephrotic syndrome . On the other hand, the yearly change in eGFR in the low U-FABP4 group was significantly greater than that in the high U-FABP4 group (Fig. 2/year, whereas that in the high U-FABP4 group was − 5.0 mL/min/1.73m2/year, suggesting deterioration of renal function. The low U-FABP4 group may have included kidney diseases with a high rate of response to treatment such as MCNS. Thus, the findings regarding the relationship between U-FABP4 and prognosis of eGFR are preliminary findings.It has been reported that U-FABP1 level is a marker of tubulointerstitial injury , 17 and The present study had several limitations. First, since the recruited subjects were only Japanese, the results of this study may not be directly extrapolated to other ethnic groups. Second, the possibility of a selection bias in the samples cannot be excluded since the study was conducted in a single facility. Third, the number of patients enrolled in the present study was small. A multicenter study with a large number of patients is needed for confirming the associations of U-FABP4 with clinical characteristics in patients with various kidney diseases. Especially, the number of patients with DN was small among patients with nephrotic-range proteinuria. Therefore, additional large-scale studies to investigate the association between U-FABP4 and DN are needed in the future. Finally, some of the drugs used for treatment, including steroids, immunosuppressive agents and renin-angiotensin system inhibitors, might have affected data for the change in eGFR as unadjusted confounding factors.U-FABP4 level is independently associated with proteinuria and renal dysfunction in patients with glomerular kidney disease. A low U-FABP4 level may predict MCNS in patients with nephrotic syndrome and may be a biomarker that is useful for differential diagnosis of MCNS and MN, which are common causes of nephrotic syndrome.Additional file 1: Figure S1. Comparisons of plasma FABP4 among kidney diseases. Figure S2. Comparisons of proteinuria, renal function and urinary FABPs among kidney diseases which cause nephrotic syndrome.


Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients.n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75 mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75 mg of ASA per day in a single antiplatelet therapy for 3 months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed.All patients  contains supplementary material, which is available to authorized users. Acetylsalicylic acid (ASA) is one of the most commonly used drugs in the secondary prevention of coronary arterial disease –3. NowadTherefore, the aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients with coronary heart disease and arterial hypertension.n = 114) were randomly assigned, in a blinded fashion , to one of the two study groups receiving 75 mg of ASA per day in a single antiplatelet therapy in the morning (n = 58) or in the evening (n = 56). To ensure compliance with taking ASA at the specific time, the patients were instructed by the researchers and each patient received a written schedule of drug administration. The control group included 61 patients with arterial hypertension, without coronary heart disease, and not receiving any antiplatelet drugs (Table The study included 175 patients (59 women and 116 men), aged 59.8 years who were admitted to the Department of Hypertension. The recruitment period was 21 months (from May 2015 to January 2017). From the recruited group, 114 patients had been diagnosed with coronary heart disease (confirmed by angiographic examination) and arterial hypertension prior to the enrolment and had been treated with 75 mg per day of enteric-coated ASA  in the morning. These patients . Ambulatory blood pressure measurements were carried out using an A&D 24-h ambulatory peripheral blood pressure monitor. The frequency of measurements was every 15 min between 7:00 and 22:00, and every 30 min between 22:00 and 7:00. Subsequently, mean arterial pressure (MAP) was calculated from the formula MAP = DBP + 1/3 (SBP – DBP) [mm Hg].Mean diurnal and nocturnal values of SBP and DBP were analysed. The percentage drop in blood pressure was calculated using the following equations:The night blood pressure fall was calculated as follows:Patients with normal NBPF (10–20%) were referred to as “dippers.” Patients with NBPF < 10% were classified as “non-dippers,” and patients with NBPF exceeding 20% were classified as “extreme dippers” , 31.The Verify Now Aspirin Test method was described in our previous manuscript published in the Cardiology Journal .p value for Kruskal-Wallis ANOVA was below 0.05—in such a case a use of different superscripts in tables was applied to denote statistically significant differences between compared groups. Changes in parameters in the individual groups during the first and second visit were analysed using the Wilcoxon signed-rank test—the parametric equivalent of the t test for related variables. Differences between two independent groups were tested with Mann-Whitney U test. Frequencies, expressed on a nominal scale, were analysed based on the Pearson chi-squared test. To evaluate differences in number of dippers, extreme dippers and non-dippers in each group at Visit 1 and Visit, the Fisher’s exact test was performed. A p value < 0.05 was considered significant.Statistical analyses were performed with Statistica, version 13.0. . Since the tested data had not met the assumption of Gaussian distribution , non-parametric methods were applied. The Kruskal-Wallis ANOVA test was used for evaluation of the differences in parameters between the three groups. The multiple comparison post-hoc Dunn’s test was performed in case p > 0.05, the Wilcoxon signed-rank test). More importantly, the studied groups did not differ significantly in the amount of administered drugs , and there was no change of medications during the study. The results of daytime, night time, and average 24-h BP parameters in the ABPM at the first and second visits are presented in Table p = 0.04). The laboratory results for each group at Visit 1 and Visit 2 are presented in Table S1. None of the considered parameters was altered in all groups except uric acid, which concentration at Visit 2 was increased in the group receiving ASA in the evening when compared with that at Visit 1 (Table S1).The basic demographical and clinical characteristics of studied groups of patients are summarized in Table The present study demonstrated the clinic blood pressure drop after 3 months of evening ASA administration in patients with arterial hypertension coronary heart disease who were already taking ASA. More importantly, the same has been confirmed in ABPM. There was a significant reduction in the average 24-h BP  and night blood pressure  in the ASA evening group compared with the ASA morning group and the control group. Interestingly, during the day hours, there was a statistically significant decrease in systolic, diastolic, and average 24-h BP in both groups: ASA morning and ASA evening. This could be due to the antihypertensive drugs used by patients on their own although the nocturnal BP drop found only in the evening group highlights a favourable chronotherapeutic effect of ASA and advocates its use at bedtime in subjects with arterial hypertension and coronary heart disease.The anti-hypertensive mechanism of ASA is not fully understood. During the night, there is a physiological drop in blood pressure, which causes a decrease in perfusion through the kidneys, and this is a signal for the activation of the renin-angiotensin-aldosterone (RAA) system. The beneficial effect of ASA administration in the evening can be explained by the effect of inhibiting the increase of RAA system activity, as well as the beneficial effects on the production of nitric oxide . Snoep eThe results published by Hermida et al., which refer to a group of 328 subjects with mild, non-treated hypertension, are concordant with the results obtained in the present study. In the referenced study, after 3 months of ASA administration in the morning and in the evening, in the ASA evening group a significant drop in blood pressure was obtained in clinical and ABPM measurements. ASA belongs to the group of non-steroidal anti-inflammatory drugs, which by inhibiting cyclooxygenase type 1 and type 2 causes an increase in blood pressure , 35. TheChronotherapy with ASA is poorly understood and contradictory reports have been published so far. In contrast to the results of the present study, Magen et al. described the anti-hypertensive effect of ASA after morning drug administration. They have shown that the addition of low-dose ASA to anti-hypertensive drugs in patients with hypertension and hypercholesterolemia may reduce both SBP and DBP as well as improve endothelial function, measured by the ability of the brachial artery to dilate . The proThrough the use of ABPM, this study draws attention to the effect of ASA not only on a single blood pressure measurement but also on the diurnal blood pressure profile. Compared with the ASA morning group, in the ASA evening group there was a significant increase in nocturnal blood pressure drop. Paradoxically, in the ASA morning group, there was a slight decrease in the NBPF value, which meant that the patients still had a non-dippers profile. This observation may be of clinical significance because for patients in whom the pressure drop at the night does not exceed 10–20% (non-dippers); there exists a greater risk of developing subclinical organ damage , 42. TheThere are number of hypothetical explanations for the observed night drop in BP following the bedtime administration of ASA. Firstly, it may be possible that the activity of COX in endothelium and other tissues is higher during the night, thus explaining the more profound effect of ASA on its inhibition. Secondly, if BP at night is associated with higher platelets activation, the anti-platelet action of ASA may explain the night time reduction in BP. Finally, there may be a difference in ASA metabolism between night and day, with higher ASA inactivation to salicylate during the day. Indeed, studies addressing the circadian rhythms on the kinetics of drugs indicate that their night time metabolism is usually significantly lower  ThereforThe present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients suffering from arterial hypertension and coronary heart disease who are not naïve to ASA.ESM 1(DOCX 24 kb)


Background and aim: Spinal anesthesia is the most common type of anesthesia administered for caesarean section and it is frequently associated with hypotension. When post-spinal hypotension is accompanied with bradycardia, the condition may become more complicated. Numerous pharmacological agents have therefore been tried for prevention of hypotension and 5HT3 antagonists are the latest in the armamentarium. However, studies have shown conflicting evidence regardings the effectiveness of 5HT3 inhibitors (ondansetron and granisetron) in preventing spinal hypotension. We have tried to address this controversy and also wanted to explore the adverse effects of granisetron on the foetus, if any.Materials and methods: Two hundred patients were included in the study and divided into two groups of 100 patients each. Group S patients received 5ml of 0.9% normal saline while Group G patients received IV granisetron 1mg (diluted to 5ml) 10 minutes prior to administration of spinal anesthesia. Analysis of variance (ANOVA) test was used for comparing the data, Student t-test was applied to compare the difference between the two means and Chi-Square test was used to test significance of difference of proportions.Results: The incidence of hypotension in Group S was 69%, whereas it was 37% in Group G (p<0.001), hence patients of Group S required a significantly higher (p=0.001) amount of mephentermine. Haemodynamic parameters were well maintained throughout the study period in patients of Group G. The neonatal outcome was assessed by Apgar score at 0 minutes, one minute, and five minutes after delivery, and it was comparable between the two study groups.Conclusion: Intravenous granisetron 1mg if administered before administering spinal anesthesia can effectively attenuate hypotension in parturients without any adverse effects on the mother and the neonate. The most commonly administered anaesthesia technique for conducting caesarean section is subarachnoid block (SAB). SAB, although considered safe, has a reported incidence of hypotension following the procedure as high as 20-40% in pregnant patients . SimilarOwczuk et al.  and SahoTherefore, this study was undertaken with the aim of addressing the ongoing controversy regarding effectiveness of granisetron in preventing hypotension following SAB in obstetric patients undergoing caesarean section. The primary objective was to assess the effectiveness of 1mg intravenous granisetron in prevention of hypotension and the secondary objective was to assess the effect of granisetron in preventing bradycardia following spinal anaesthesia in parturients undergoing lower segment caesarean section (LSCS).This was a prospective double-blind randomized controlled trial. A total of 200 healthy term parturients (between 20 - 35 years) undergoing elective caesarean section under spinal anaesthesia were included in the study. They were then divided into two groups with 100 patients in each group . Parturients not willing to participate in this study, presence of any contraindication for spinal anaesthesia, history of allergy to study drug, patients on serotonin agonists or antagonists, and presence of any co-existing diseases were excluded from the study.Parturients were randomized into one of the two groups using a computer-based random number generator. The study drugs were premixed to a volume of 5ml and presented as coded syringes to the anaesthesiologist who was not an investigator in the study. Group G patients received IV granisetron 1mg and Group S patients received IV 5ml of 0.9% normal saline. Both the groups received the allocated solution intravenously 10 minutes before spinal anaesthesia. All parameters were noted by an anaesthesiologist blinded to the group allocation. All parturients were kept fasting for eight hours and they were uniformly pre-medicated with ranitidine 150mg and metoclopramide 10mg orally on the morning of surgery with sips of water.Baseline/pre-spinal (T0) vital parameters of parturients including heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), and peripheral oxygen saturation (SpO2) were recorded in the operating room. Any fall in the systolic arterial blood pressure below 100mmHg or a fall in mean arterial blood pressure of more than 20% from baseline value was taken as hypotension and managed with intravenous mephentermine 6mg bolus. In the operating room, an IV line was secured with 18-G intravenous cannula and infusion of ringer lactate solution started. Routine standard monitors such as pulse oximetry, electrocardiography (ECG) and non-invasive blood pressure applied and monitored. Sub-arachnoid block was given in a sitting position with midline approach with a disposable 27 gauge Quincke spinal needle. After confirming the free flow of cerebrospinal fluid, 2.2ml of 0.5% hyperbaric bupivacaine was deposited in the subarachnoid space at the rate of 1ml over 10 seconds. Parturients were made supine after putting a sterile dressing over the skin at the lumbar puncture site. The time of intra-thecal drug deposition noted and the haemodynamic parameters were recorded. All the above-mentioned parameters were recorded at every two-minute interval till 20 minutes after SAB (T-1 T-2 T-3 and so on up to T-10) and then at every five minutes till the end of surgery (T-11 onwards) . All theAnalysis of variance (ANOVA) was used for comparing the data, Student t-test was applied to compare the difference between two means and Chi-Square test was used to test significance of difference of proportions.The patient characteristics like age, weight, height, body mass index were comparable in both the groups. The baseline haemodynamic parameters like the heart rate, systolic blood pressure, diastolic blood pressure, mean arterial blood pressure, and peripheral oxygen saturation was comparable in both the groups before giving spinal anesthesia.The incidence of hypotension in Group S (69%) was more than Group G (37%) Table  and the Use of mephentermine as vasopressor was also significantly higher in Group S as compared to Group G. None of the patients required atropine Table .On comparison of the trend of systolic blood pressure between the two study groups at different time points, the difference was significant at T3 (two minutes after SAB), T4 (eight minutes after SAB), T6 (12 minutes after SAB), T10 (20 minutes after SAB) and T12 (30 minutes after SAB); p-values at these time points are < 0.05 , the difference between the two groups was non-significant and DBP was better maintained in the granisetron group  showed that at T4 (eight minutes after SAB), T6 (12 minutes after SAB), T10 (20 minutes after SAB) and T12 (30 minutes after SAB), the difference in MAP between two groups was significant. . The mean arterial blood pressure after spinal anaesthesia was also significantly better maintained in Group G at different time points in comparison to Group S /There was no statistically significant difference (p = 0.101) in height of sensory block in parturients after SAB, i.e. parturients of both groups attained comparable height of sensory block. The surgical duration and amount of intraoperative blood loss between Group S and Group G were also comparable .Neonatal outcome depends upon Apgar score, which was also comparable between the two study groups at 0 minutes, one minute, and five minutes after delivery.Neuraxial anaesthesia remains the preferred choice for LSCS across the world and hypotension after SAB remains one of the most researched subjects in obstetric anaesthesia. Hypotension is the physiological consequence of spinal anaesthesia and can have potential deleterious maternal and foetal impact. Several methods are therefore being followed to treat hypotension after SAB like IV fluids, pharmacological agents, and physical methods like positioning. Over the last few years, different pharmacological agents are in use to treat post-spinal hypotension. Prevention of spinal hypotension in parturients where two lives are affected is a real concern for the anaesthesiologist and an effective and safe prophylactic pharmacological agent will be ideal for this purpose. With the introduction of 5-HT3 receptor antagonist in clinical practice, different authors started exploring these agents and since then the treatment options for spinal induced hypotension has been widened. Numerous articles have been published showing the efficacy of both ondansetron and granisetron for the purpose of management of post-spinal hypotension. However, a few studies have shown that granisetron is ineffective for this very purpose. We therefore tried to address this issue and have conducted a prospective, randomized, double-blind study with the aim to study the effectiveness of intravenous granisetron (1mg) in prevention of hypotension in parturients undergoing elective caesarean section under spinal anaesthesia.In our study we observed that 67% of parturients of Group S had hypotension after spinal anaesthesia whereas only 33% of parturients developed hypotension in Group G and this difference was statistically significant with a p-value <0.001  between the two study groups was comparable in the present study. After administering spinal anesthesia, the systolic blood pressure at different points of time was comparable between the two groups except for readings at the sixth minute, eighth minute, 12th minute, 20th minute, and 30th minute. Different authors studied the onset and duration of post-spinal hypotension and they observed incidence of hypotension after three minutes of SAB  and thisDiastolic blood pressure between the two groups was comparable throughout the study period except at the 30th minute, which indicated granisetron had a negligible effect on diastolic blood pressure as compared to systolic blood pressure. Both Lamichhane et al.  and SabeIn the present study, baseline mean arterial blood pressure between Group G and Group S was comparable. After giving SAB, the difference in mean arterial blood pressure between the two groups was significantly different at the eighth, 12th, 20th, and 30th minute, which was similar to change in systolic blood pressure between the two groups at the same time interval. Mean arterial blood pressure takes into account both systolic blood pressure and diastolic blood pressure. As diastolic blood pressure did not show significant difference between the two groups, the changes that occurred in systolic blood pressure were reflected in a similar way and we observed similar significant changes in mean arterial blood pressure. When use of mephentermine was compared we observed significant difference between the two groups at the sixth minute, eighth minute, 12th minute, and 20th minute. Khalifa et al.  found thIn our study the baseline heart was comparable in both groups. After SAB, heart rate trend showed non-significant difference between Group G and Group S throughout the study period. Our findings of change in heart rate were similar to Lamichhane et al. , MohammaIn our study we did not find any episode of significant bradycardia in either of the groups and therefore intravenous atropine was not needed. Lamichhane et al.  also didIncidence of hypotension after spinal anaesthesia is as high as 50-60%  in the oIn spinal anaesthesia when sensory block level attains T4 or above T4 dermatomal level it increases the incidence of hypotension in the obstetric population. As block level reaches at or above T4 dermatomal level, it leads to inhibition of cardiac sympathetic system which is an influencing factor on haemodynamic parameters in spinal anaesthesia . So moniSurgical blood loss also influences haemodynamic parameters and may lead to hypotension. Intraoperative blood loss along with SAB have an additive effect and may cause profound hypotension. We, therefore, explored the effect of intraoperative blood loss on incidence of post-spinal hypotension between the two groups. In our study we observed that mean intraoperative blood loss between the two study groups was also comparable.The Apgar score describes the condition of newborns immediately after birth and when properly applied, is a tool for standardized assessment . In the Subarachnoid block is still the most commonly performed anaesthesia technique for lower segment caesarean section. Incidence of post-spinal hypotension is high in parturients undergoing lower segment caesarean section. Intravenous granisetron 1mg if administered before SAB, besides being an effective antiemetic, can also be used to effectively attenuate hypotension in parturients without any adverse effects on mother and neonate.


Delayed graft function (DGF) is closely associated with the use of marginal donated kidneys due to deficits during transplantation and in recipients. We aimed to predict the incidence of DGF and evaluate its effect on graft survival.This retrospective study on kidney transplantation was conducted from January 1, 2018, to December 31, 2019, at the Second Xiangya Hospital of Central South University. We classified recipients whose operations were performed in different years into training and validation cohorts and used data from the training cohort to analyze predictors of DGF. A nomogram was then constructed to predict the likelihood of DGF based on these predictors.P < 0.05).The incidence rate of DGF was 16.92%. Binary logistic regression analysis showed correlations between the incidence of DGF and cold ischemic time (CIT), warm ischemic time (WIT), terminal serum creatine (Scr) concentration, duration of pretransplant dialysis, primary cause of donor death, and usage of LifePort. The internal accuracy of the nomogram was 83.12%. One-year graft survival rates were 93.59 and 99.74%, respectively, for the groups with and without DGF (The nomogram established in this study showed good accuracy in predicting DGF after deceased donor kidney transplantation; additionally, DGF decreased one-year graft survival.The online version contains supplementary material available at 10.1186/s12882-020-02181-1. Kidney transplantation has been successful and has saved numerous lives since the 1960s. Compared to regular kidney dialysis, kidney transplantation results in better patient quality of life and longer survival , 3, the Various potential factors affect the rate of DGF, including the induction strategy, donor criteria, and surgical process, among others. Our center utilizes expanded criteria donor (ECD) kidneys to address the shortage, which has also been recognized by the Organ Procurement and Transplantation Network (OPTN) in recent years . Kidney Data for consecutive patients who had undergone kidney transplantation surgery were collected at the Second Xiangya Hospital of Central South University. The study was approved by the Ethics Committee of the Second Xiangya Hospital of Central South University, which waived the requirement for informed consent due to the retrospective design. The inclusion criteria were (1) grafts obtained from DD, (2) surgery performed as single-kidney transplantation, (3) and patients with complete data. Patients with a history of kidney transplantation or who had received double-kidney transplantations or grafts from living donors were excluded. The term ECD was used to classify subsets of all DDs over 60 years and DDs aged 50–59 years with at least two of the following characteristics: history of hypertension, serum creatinine (Scr) concentration above 1.5 mg/dL, and DCD . Among mEligible patients who underwent surgery between January 1 and December 31, 2018, were included in the training cohort for the development of the nomogram; those who underwent surgery between January 1 and December 31, 2019, were included in the validation cohort.Hemodynamic instability will destroy the utility of organs if the kidney has a long WIT or hypotension, which may cause blood clots, affecting the appearance and texture of the kidney. When we found a kidney that was reddish in color or slightly tough in texture, we used LifePort to evaluate and improve its quality before making a decision. A flow of > 80 mL/min was the screening criterion of transplantation qualification . We chosAntithymocyte globulin (ATG) or interleukin 2 (IL-2) receptor antibody blockers with steroids were used as induction therapy according to the surgeons’ experience. As some surgeons only administered steroids and drugs for cases with a significant risk of infection, we classify immunity induction as “Yes” or “No” in Table DGF-related factors included donor and recipient factors. We collected donor data, including age, sex, height, weight, BMI, blood type, CIT, WIT, primary cause of death, terminal urine volume before organ harvest, terminal Scr concentration before organ harvest, intensive care unit (ICU) duration, hypotension history, cardiac arrest time, donation type, history of hypertension and diabetes, history of cardiopulmonary resuscitation (CPR), history of hepatitis C virus (HCV) and usage of LifePort. The kidney donor profile index (KDPI), as an influencing factor of graft survival and DGF in some centers –16, was Recipient indicators included sex, age, height, weight, BMI, preoperative Scr concentration, number of human leukocyte antigen (HLA) mismatches, preoperative plasma renin activity (PRA) level, dialysis type, pretransplant dialysis duration, surgery duration, and immunity induction history.P values < 0.05 were considered statistically significant. R software version 4.0 were used to graphically depict the impact of significant risk factors identified in the binary logistic regression and to develop the nomogram. We used the parameters of the odds ratios and β of the predictors to assess the likelihood of DGF.Statistical analyses were conducted using IBM SPSS Statistics for Windows, version 23.0. For univariate analysis, continuous variables were compared using unpaired, two-tailed t-tests; categorical variables were compared by χ2 or Fisher exact tests when data were sparse. Binary logistic regression was performed to assess the impact of significant DGF-related factors in univariate analysis. The internal predictive accuracy of the model was evaluated in the training cohort using the area under the receiver operating characteristic curve (AUC) derived from 10-fold cross-validation by the least absolute shrinkage and selection operator (LASSO). The validation cohort was used to perform external validation by logistic analysis and calibration curves were plotted to examine the calibration of the nomogram, accompanied by Hosmer–Lemeshow tests. One-year graft survival curves were generated using the Kaplan–Meier method and compared using log-rank tests.During the study period, 858 consecutive patients underwent kidney transplantation. Of these, 721 patients who met the inclusion criteria were enrolled, with 461 and 260 patients assigned to the training and validation cohorts, respectively . The recipients tended to be younger with just five people older than 60 years old; the median age was 37 years old. The percentages of young child donors (≤ 12 years) and aged donor (≥ 60 years) were 13.88 and 17.15%, respectively. The remaining significant (P < 0.05) variables were fitted to a binary logistic regression model. Continuous variables  from the Hosmer–Lemeshow test showed good calibration between predicted and observed DGF , 1-year graft survival was impacted by DGF, though no correlation with KDPI based on the log-rank test was found (P > 0.05). Due to the limited number of graft losses (n = 6), Cox regression was not performed.Patients from the training cohort were observed every 2 weeks during the first postoperative year. We found that 5 DGF and 1 non-DGF patients experienced graft loss. The 1-year graft survival rates were 93.59 and 99.74%, respectively, for the groups with and without DGF. A Kaplan–Meier plot of graft survival against DGF occurrence is presented in Fig. DGF is a common complication after kidney transplantation operations and is related to both short-term functional recovery and long-term survival of the transplanted kidney. Yarlagadda et al.  systematRisk factors related to DGF can be divided into donor factors and recipient factors, and the multiple interactions of these factors ultimately affect the recovery of graft function. Numerous studies have assessed the causes of DGF, yet there is no consensus to date. In our study, prolonged CIT and WIT were most strongly associated with DGF, consistent with previous reports –27. AddiAlthough immunity induction is an important step before surgery to avoid acute rejection, the use of ATG induction remains controversial. ATG may induce cytomegalovirus infections and hematological complications , 30. PopAlthough long-term graft survival is expected, numerous complicated factors can cause graft loss. The relationship between DGF and deceased graft survival has been demonstrated recently , 34. In Our nomogram is a simple and visual prediction model of posttransplant factors. Maier et al. investigated the relationship between DGF and posttransplant indicators of neutrophil gelatinase-associated lipocalin (NGAL), reporting that early assessment of serum and urinary NGAL could predict DGF . In theiThe present study applied a 10-fold cross-validation LASSO method to divide the data into 10 equal parts, with nine parts for the model and one part for validation. This process was repeated ten times to produce an accurate AUC.In addition to identifying patients at higher risk of DGF before surgery, our model may also be used as a clinical tool to reduce the risk of DGF. CIT should be controlled when possible; for example, shortening the harvest and patient preoperative preparation times would reduce CIT, which would help to decrease the incidence of DGF. More specifically, the model can be used as a strategy to select suitable donors and recipients by identifying reasonable matches between recipients’ conditions and CIT. Additionally, the model can guide immunosuppression induction for high-risk DGF donors identified by the nomogram .This study had some limitations. First, because this was a single-center study, the sample size was small and data were variable since. Second, the follow-up period of graft function was not long compared to 10–20 years. Finally, we did not provide solutions for predictors such as WIT. Future studies are needed to explore methods for shortening WIT and to investigate the factors influencing graft survival, as prolongation of graft survival is our ultimate aim.This study identified six risk factors as predictors of DGF, including donor CIT, WIT, terminal Scr, primary cause of death, and recipient duration of pretransplant dialysis. A visual nomogram with reliable accuracy was created for clinical use.Additional file 1: Figure S1. Flow diagram of patient screening.Additional file 2. Supplement 2.Additional file 3. Supplement 3.


To propose a new test to evaluate the autonomic nervous system in patients with syncope: Multimodal Monitoring for Diagnosis of Dysautonomia (MMDD). We included 21 patients with syncope  and 21 with no-syncope subjects  to perform a test of nine 2-min stages: four while resting and four during active testing of autonomic response. Transcranial-Doppler, electrocardiogram, and photoplethysmography blood pressure pulse-to-pulse monitoring, allow registering six variables from the Middle Cerebral Artery and four from the Cardiovascular System. We analyze each variable's mean differences in each stage and its change when they pass from one stage to another with the T and Z tests. To understand the significance of the change, we use a logistic regression model for a certain subgroup of variables. Since we have a small dataset, we use the bootstrap technique to infer the general behavior that characterizes a syncope. Our data confirm differences between syncope and non-syncope patients during MMDD stress stages 2, 4, 6 and 8. Bootstrap and multivariate logistic regression allow us to identify which sets of variables in each of these stages of the MMDD are sufficiently sensitive to recognizing syncope. MMDD protocol can recognize a syncope patient with some confidence by detecting subtle changes in the autonomic nervous system. This protocol encourages us to continue to study the effectiveness of MMDD protocol allowing a new approach to future research. Dysautonomia, defined as changes in the functioning of the autonomic nervous system that negatively affect health status, has manifestations ranging from symptoms located in some part of the body or transient and occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases1. Syncope, the most common event to translate dysautonomia, is defined as a state of transient loss of consciousness of rapid onset, short duration, and spontaneous recovery due to a transitory state of cerebral hypoperfusion that leaves no neurological sequelae3.4. In 50% of the cases, the clinical history allows us to identify the causes of syncope5; however, in the rest, diagnosis of the primary and less understood forms of syncope are elusive6.In the Framingham study, at least 3% of men and 3.5% of women between 30 and 62 years old, had an episode of syncope through 26 years follow-up7. Due to its complexity, we find several proposals to evaluate the Autonomic Nervous System (ANS) in patients with syncope, most of which study the reactivity of the heart and blood pressure in response to maneuvers such as Valsalva, deep breathing, isometric hand contraction with a dynamometer, orthostatism test, thermal test and, more recently, the analysis of heart rate variability9. In 1985, Ewing proposed a battery using some of these elements for the study of diabetic autonomic neuropathy, which is in use today10.The phenomenon of syncope occurs because of a state of transient global cerebral hypoperfusion that, independently of the mechanism that initiates it, responds to a decrease in the activity of vasoconstrictor neurons and an increase in the parasympathetic activity of cardiomotor neurons11. To consider positive this test of a passive movement against gravity, the syncope or, at least, the dysautonomic symptoms that precede it, must be triggered, using blood pressure and heart rate as explanatory variables12. The TT considered a non-invasive procedure associated with few complications. However, historically, new pharmacological tests with nitroglycerin and isoproterenol have been added15, as well as other maneuvers, such as carotid massage and compression of the eyes16, to enhance the test gives TT a certain degree of intervention, most of them are out of use. Even if passive movement in this test eliminates the abrupt changes in heart rate and blood pressure of the regular bodily activity, this type of mobility rarely happens in everyday life.The Tilt Table Test (TT) is in use since 1986 to understand and classify patients with sincope18, and active orthostatism19. The technique of the measurement of the Pulse of Transit Time using the electrocardiogram and photo-plethysmography by infrared light allows recording the arterial blood pressure in each heartbeat21. TCD and other different ways of recording beat-to-beat pressure have added to the TT protocol22.Transcranial Doppler (TCD) allows studying changes of cerebral blood flow of the Middle Cerebral Artery (MCA) with passive position changes23. That is why we do not consider the TT as a gold standard.Even considering these statements, the validity and usefulness of TT is debatable as, until now, the induction of syncope or premonitory symptoms of syncope are mandatory to determine when the test is positive. Also, indications for a TT test are limited and appear to have questionable sensitivity and specificity24. In this protocol, we recorded ten physiological variables during nine stages in different body positions. We aim to demonstrate that our results, obtained by simple statistical analysis (logistic regression and bootstrap technique), can generate numeric values in people that differentiate who may have syncope.According to our hypothesis, subtle body movement causes changes in the autonomic nervous system that can be recorded with multimodal monitoring. The data obtained can be analyzed and amplified using, from simple statistics to complex mathematical models. Our team created a free mobility protocol called Multimodal Monitoring for Diagnosis of Dysautonomia (MMDD)3. All patients had a cardiological review to discard any cardiological condition related to syncope. All patients had a normal electroencephalogram, glucose tolerance test, and imaging studies  to rule out any other neurological conditions related to loss of consciousness. We also included 22 control subjects with no syncope or any other state of transitory loss of consciousness matched for age and gender as controls to achieve two homogeneous groups. For both groups, we excluded patients with an apparent potential cause of syncope or a concomitant condition that could affect the Autonomous Nervous System (ANS). We did not include two patients for the final analysis, one in the syncope group and his equivalent from the control group, because of incomplete data.We obtained data from 22 consecutively treated patients in the neurology outpatient clinic of Médica Sur Hospital, Mexico City, between July 2015 and January 2016, whose motive for consultation and diagnosis was a first-ever syncopeWe performed all the procedures before noon in a closed room with a temperature between 23 ºC and 24 °C. In preparation for the process, we requested the patients to have a light breakfast and, to stop medications that could interfere with the results 48 h before their visit.We used a Sonara TCD monitoring equipment with two 3 MHz Doppler ultrasonic probes and the respective tailored headband  and a Somno-Touch wrist monitor .We start the procedure placing four electrodes on the patient's chest to obtain the electrocardiogram recordings and one infrared digital sensor for the photo-plethysmographic recording of pulse curve, oxemia, and beat to beat blood pressure (mm Hg). At the same time, two 3 Hz Doppler ultrasonic probes fixed with a headband to record, using a transsphenoidal approach, the blood flow velocity (cm/s) of the Middle Cerebral Artery (MCA) on both sides.Once the sensors and devices are confirmed to be working correctly, the test begins.MMDD includes nine positions Fig. . Stages With the return to a horizontal position, we measure the capacity of the variables to recover to the basal state. We decided to set a 2-min time for each stage as we consider this a reasonable time to detect the ANS's adaptive changes.Through mathematical modeling, we compare and analyze the subtle behavioral differences in the variables between patients and controls to sustain that the MMDD is significantly plausible from the statistical point of view.With these resources, it was possible to obtain a continuous record of the following variables of each heartbeat: Cerebral Blood Flow (CBF) variables: Systolic velocity of the MCA (Peak-vel.), Mean velocity of the MCA (Mean-vel.), End Diastolic Velocity of the MCA (EDV), Pulsatility Index (PI), Resistance Index (RI), and Systolic/Diastolic MCA velocity index (SD). Cardiovascular variables: Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), and these data allow us to calculate Mean Blood Pressure (MBP) during the procedure. With the electrocardiogram record, we obtained the R-R time used to calculate the Heart Rate (HR) and to rule out cardiac rhythm alterations during the procedure.We used a specially created software to insert the obtained data in our database automatically and sorted in the different stages using XLSTAT version 15.28 and the programming language R version 3.5.3 (2019-03-11) for statistical proposes.Under the hypothesis that the variables follow a normal distribution (Kolmogorov–Smirnov test), we used the T and Z tests to compare the demographic characteristics between the two groups and be able to consider the samples as comparable. To analyze the variables, we initially took the averages of the physiological variables for subjects with syncope and non-syncope of each two-minute stage. We ran a hypothesis test to determine if there is statistical evidence that the groups are different. Subsequently, the difference between the value of one stage j and the next stage j + 1 is taken, where j = 1, 3, 5, 7, and 9 are at rest and j = 2, 4, 6, and 8 are tested. The resulting value had the suffix "D"  added. We calculated the average D value of the contiguous stages of syncope and non-syncope in each two-minute periods and carried out a hypothesis test to determine the presence of statistical evidence of differences. Finally, with these D values, we constructed a logistic regression model to understand the contribution of the variables with position changes to the description of syncope.We included data of 42 people out of 44 with the 10 variables with the suffix D in the 9 position changes.25.Since the dataset is small, we used the bootstrap method with replacement in order to understand the underlying randomness in the sample. We divided the data into two subsets: training data , and test data For the moment of the cardiac cycle: during the systole , during diastole  and during intermediate moments .By its functional relationship: brain , , systemic , and .We selected subsets of variables for constructing the logistic regression under the following criteria:1, x2, and x3 correspond to some of the mentioned combinations. The response variable y is binary, where y = 1 is syncope and y = 0 is no syncope.The equation of the logistic regression:0, β1, β2, and β3, the p-value corresponding to the hypothesis that a coefficient is zero. We defined the capacity of the logistic regression to classify (distinguish syncope from no syncope) by the area under the ROC curve.We recorded the values of the coefficients βMMDD is carried out using non-invasive procedures and accepted in common clinical practice. To protecting patient privacy throughout the project, the manuscript and databases do not contain names or personal data. Given that it is a non-interventionist trial, retrospective work using information from a database of consecutive cases, the ethics and research committee of Hospital Médica Sur authorizes its implementation, the use of numerical data and the publication of this article without the need of informed consent. We testify that this work is original and is not currently considered for publication elsewhere. Partial data from this work was presented (poster session) at the 24th World Neurology Congress 2019, and a version of the abstract was published in the Journal of the Neurological Sciences 405(2019):314. 10.1016/j.jns.2019.10.1413.We studied 21 patients with a first-ever syncope  and 21 control subjects . In the group with syncope, six subjects smoked, one had moderate alcohol intake and four had controlled high blood pressure. In the control group, seven subjects smoked, four had moderate alcohol intake and four were hypertensive, one of them without treatment. We found no significant demographic differences or risk factors between the control group and the group with syncope, so we infer that both are comparable. The data, according to the tests, can be considered a normal distribution throughout the protocol.CBF variables: Mean-vel. in stage 6 , and in stage 8 . Peak-vel. in stage 8 (80 vs 94 p = 0.011). EDV showed a difference in four stages: stage 2 , stage 4 (27 vs 33 p = 0.038), stage 6 , stage 8 . PI, RI and SD values did not show significant differences.Cardiovascular variables, significant differences: HR in stage 6 , SBP in five stages: stage 2 , stage 4 , stage 6 , stage 8 (111 vs 132 p = 0.033) and stage 9 (109 vs 123 p = 0.003). DBP in stage 2 (70 vs 76 p = 001) and in stage 8  . From the 7 to 8 stage, we observe the major difference between the two groups for Mean-vel., Peak-vel., EDV, SBP and DBP variables. At 5–6, the PI and HR variables were different. At 6–7, PI, and at 8–9 were Mean-vel. and Peak-vel.  in the change from stage 1 (of rest) to stage 2 (of test) with three groups of variables Fig. . The sigThe variation of the negative sign in change 1–2 to positive in change 2–3 of the variables SBP.D, DBP.D and MBP.D, shows that the values generated by the MMDD are sensitive enough to observe the patient’s syncope when going from rest to test and vice versa. If the patient with syncope is at rest and undergoes a test, the change of their physiological variables must be the opposite when they return to a basal state . To understand the results, we evaluated the statistical significance of the sign from the coefficients of the regression, Fig. Figure While performing bootstrap with 10,000 iterations, we assigned a sign. We gave statistical value when at least 70% of the cases resulted in same-sign coefficients, and 70% of the corresponding p-values were below 0.1. We consider that logistic regression is a good classifier if the area under the ROC curve for 70% of generated ROC curves by the bootstrap procedure is at least 0.7. From our simulation with 10,000 iterations, we created Table As shown in Table Respect to the area under the ROC curve, in the groups , we saw a good performance during 1–2, 2–3, 3–4, 4–5 and 7–8. For the group  in 1–2, 2–3, 3–4, 5–6 and 7–8, and in the group  in 1–2, 2–3, 7–8.26. In another work, they use mathematical tools to understand the physiological changes in patients with syncope using the mathematical idea of entropy to analyze the ANS complexity before the moment of a syncope using passive movement in the TT27.Technological advances in the last three decades have been extraordinary. We consider it convenient to search for new options to study patients with ANS disorders. We share this concern with other teams; in a recent paper, using the Calgary scale to stratify the risk of syncope in test subjects, positivity was when compared using the Bruce protocol of the stress test added with 300 mcg of sublingual nitroglycerin to identify the patients with syncope. Although the acquisition of the variables happens during a mobility test, the positive result is given by evoking syncope using a pharmacological challenge10, we designed the MMDD: a free mobility test that resembles daily life conditions and allows the study of newly available technology, the ANS's behavior in patients with syncope.In our opinion, the study of syncope and conditions of the ANS requires changes in paradigms. Inspired by the works of Ewing in 198528, TCD monitoring and other methods to assess the state of CBF autoregulation30, to obtain in each beat four variables of general circulation  and six variables of CBF .In this way, we use pulse-to-pulse blood pressure records with pulse transit timeWe also consider the activities we submit our patients to during the study to be close to real-life situations. As we use mathematical modeling to characterize patients with dysautonomia, we do not require to evocate syncope as a criterion of positivity.31 to perform up to 10,000 iterations to understand the behavior of the changes of the variables in each change of position through logistic regression. The sign of the coefficients in the logistic regression describes changes suffered by physiological variables induced by changes in position from one stage to another. Considering the groups of the variables mentioned above, we could estimate the probability of suffering a syncope. For this paper, we focus only on analyzing the signs to understand how the changes are in the physiological variables and then give a description of a "standard" patient with syncope. Table In the first statistical analysis, we showed the different means of the variables in each stage of the study between patients with syncope and the control group. Later, using the means between the different D values in the stages, we verified the difference in change suffered by the variables between positions, which is again, different between patients with syncope and the control group. These differences allow us to confirm the hypothesis that, through the MMDD, we obtain data to distinguish ANS's behavior in patients with syncope. We took advantage of the bootstrap technique32. In our study, the variable SBP showed a relevant differentiator between patients with syncope and the control group during almost all the test stages. Moreover, the change between SBP and DBP when moving from one stage to another has a characteristic behavior in patients with syncope at 5–6 and 6–7, wherein some cases one increases and the other decreases, since SBP has no a predominant sign. This observation of different signs shows a "paradoxical" behavior in SBP and DBP interaction with patients without syncope  and in stages 5–6 and 6–7. This is corroborated with logistic regression by showing the significance of changing this variable when interacting with others. During the change at 5–6 (from lying to standing), the resulting coefficient for HR has a positive sign  and in 6–7 (from standing to rest) a negative sign , associated with the sign in SBP, that is, at 5–6 h increases and SBP decreases, which indicates syncope.In neurally mediated syncope and postural orthostatic tachycardia syndrome (POTS), the chronotropic response of the heart is not related to the vasopressor response and may even be paradoxical with the CBF response, suggesting a central control disorder of the latter36. It is valid for calculating CBF autoregulation's lower limit and sensitive to changes in perfusion pressure in healthy patients30. Our focus is to study the relationship between systemic circulation and its influence on CBF. With our method, we found differences in the CBF variables at various moments of the test. For example, EDV patients with syncope are significantly different from those with non-syncope it in all stages of our test: Mean-vel in the standing position and while effort, and Peak-vel at the time of the effort, and differences during 7–8 and 8–9 changes, which are recovery phases. One of the most outstanding findings in this work happens while reviewing the signs of the CBF coefficients: we observed the alternating signs of Peak-vel., Mean-vel, and EDV as the three variables interact. Mean-vel and Peak-vel., for example, have an alternation (opposite). It is possible to see how the patient with syncope modifies these variables in changes of "every day" positions. These changes are a mathematical representation of the behavior of the CBF variables during the test.In cerebral syncope and disorders of the ANS, it is fundamental to consider cerebral vascular reactivity. Different authors have used TCD to study cerebral autoregulation in both animal and human experimentsWe demonstrate the feasibility of using the MMDD to detect subtle physiological changes during a free mobility trial. As it shows notable differences between patients with and without syncope, we were able to establish the hypothesis that these differences distinguish the behavior of ANS and CBF in patients with syncope.Through the bootstrap technique, we efficiently performed a multivariate logistic regression study and reviewed the joint behavior of different variables while changing position. The changes of sign in the coefficients of a multivariate logistic regression model from stage to stage describe an individual with syncope. The sign direction is an indicator of what kind of change would be expected in some physiological variables for a "standard" syncope. Thus, meanwhile studying a new patient with MMDD, the certainty that a new patient has syncope increases when the more coincidences exist with our results. This hypothesis is subject to research in our group.Furthermore, once demonstrated that our analysis permits understanding some particular subtle characteristics of syncope, we are currently testing modifications to the protocol to increase its sensitivity and specificity, and we are working on a clustering model and developing artificial intelligence to propose a new approach for the study of patients with dysautonomia.


Exploring an alternative to improve the clinical management of hypertension, we tested the hypothesis that food supplementation with coconut oil (EVCO), alone or combined with aerobic exercise training, could exert an antihypertensive effect (primary outcome) in patients with stage 1 hypertension. Forty-five hypertensive volunteers of both genders participated in a placebo-controlled clinical trial. The volunteers were submitted to 24-hour ambulatory blood pressure monitoring, analysis of blood pressure variability (BPV), measurement of serum malondialdehyde (MDA) and nutritional assessment. Results indicate that EVCO consumption had no adverse effects. The supplementation did not increase the caloric intake compared with placebo, and the dietary constituents were similar between groups, except for the saturated fats, especially lauric acid. The analysis of blood pressure indicated absence of antihypertensive effect of EVCO alone or combined with physical training. Furthermore, no effects on blood pressure variability and oxidative stress were observed in the supplemented hypertensive patients. Thus, despite the results observed in pre-clinical studies, the current clinical study did not provide evidence to support the use of coconut oil as an adjuvant in the management of hypertension in humans. The impact of hypertension on health continues to rise despite the advances in antihypertensive drug development by the pharmaceutical industry. In 2018, data from the American Heart Association indicated that 40.6% of deaths from cardiovascular disease in the U.S. were related to hypertension [Non-pharmacological approaches have been important adjuncts in the treatment of hypertension. Nutritional strategies such as using antioxidants and regular exercise have been shown to be beneficial ,4,5, butIt has been demonstrated that coconut oil can increase high-density lipoprotein, improving the lipid profile ,8, and iHowever, there are no reports on the effects of coconut oil supplementation in relation to the cardiovascular system in humans. Studies that focus on the relationship of coconut oil consumption with physiological variables of interest such as BP and BP variability can elucidate the potential of coconut oil as an adjuvant alternative in the clinical management of hypertension. Thus, we tested the hypothesis that coconut oil supplementation, isolated or combined with physical training, could exert antihypertensive effects in patients with stage 1 hypertension.Hypertensive patients were recruited to participate in this placebo-controlled study. Patients with stage 1 systemic arterial hypertension (mild hypertension) were included. This degree of hypertension is characterized by levels of systolic blood pressure between 140 and 159 mmHg and/or diastolic blood pressure between 90 and 99 mmHg [https://www.openepi.com ) and, as a result, a minimum of seven subjects for each group was obtained, considering a confidence interval of 95% and a statistical power of 80%. Our study included 51 hypertensive patients who were allocated by simple random distribution (1:1) using a freely available website ). These patients were followed up in the experimental groups: group supplemented with extra-virgin coconut oil—EVCO; group supplemented with placebo; group supplemented with EVCO plus physical training (EVCO-training); and group supplemented with placebo plus physical training (placebo-training). Six patients did not complete the treatment protocol and were excluded. Two of them were from the EVCO group . The patient in the training group dropped out of the study, and the other patient started pharmacological treatment by decision of the cardiologist on the study team. The remaining four losses were from patients supplemented with the placebo intervention (one from the trained group and three from the untrained group). The patient in the trained group had to move from the study city, and the other three dropped out the study. Considering blood pressure analyzes, two records were excluded (one from the placebo group and one from the EVCO group) because they did not reach more than 80% of the valid measures after 24-hour monitoring. Thus, we had the following experimental groups: EVCO, n = 14; Placebo, n = 11; EVCO-training, n = 11; and Placebo-training, n = 9, The sample size was based on the outcome of reduced systolic blood pressure obtained by Perona et al. , consideThis is a randomized, single-blinded, placebo controlled clinical trial. Patients were initially submitted to 24-hour ambulatory blood pressure monitoring according to VI Brazilian guidelines for hypertension . Blood cCocos nucifera L.) [The patients receiving EVCO or placebo were instructed to intake 10 capsules a day within the main meals as follows: three during the breakfast, four during lunch and three during dinner. The EVCO groups received 10 mL/day (1 mL in each capsule) of EVCO (fera L.) . Both pr® frequency meter model M200 , and supervised by rating of perceived exertion [The training protocol consisted of four weeks of aerobic training , three times per week, lasting 60 min, of moderate intensity (50% to 70% heart rate reserve) . A one mexertion .®, version 3048/16, Porto Alegre, Brazil). The nutritional parameters of total energy intake, carbohydrates, total proteins and fats, saturated fatty acids (including lauric acid), unsaturated fatty acids, intake of sodium and antioxidants were selected for analysis.The dietary intake of each patient was assessed by a three day food recorder, two representing the weekday diet and one representing the weekend diet. The average food consumption over the three days was used for nutritional assessment. The analysis was performed by a nutrition professional using a nutritional software  for 20 min. Four hundred and fifty microliters of supernatant was removed and mixed with 0.6% thiobarbituric acid and incubated at 90 °C for 1 h. Then, absorbance at 532 nm was measured. A standard curve was generated using 1,1,3,3-tetrametoxypropane. Results were expressed as nmol/mL.To evaluate lipid peroxidation, serum samples were collected to measure levels of malondialdehyde (MDA) determined by TBARS assay . After bSerum was used to determine total cholesterol, triglycerides, low density lipoproteins (LDL-cholesterol), high density lipoproteins (HDL-cholesterol) and glucose using colorimetric standardized commercial kits . Non-HDL-cholesterol is calculated by subtracting HDL-cholesterol from total cholesterol.Cardios® device . The equipment was programmed to perform measurements every 15 min during the waking period and every 30 min during sleep, according to the recommendations of the 4th Guidelines for Ambulatory Blood Pressure Monitoring and 2nd Guidelines for Residential Blood Pressure Monitoring [® model HBF-514C, Shiokoji Horikawa, Shimogyo-ku, Kyoto, Japan). Body mass index was calculated using the formula weight/(height)2.The BP was measured for a period of 24 h using a Dyna MAPA + nitoring . The datt Student test. For the other analyses, a one-way ANCOVA corrected by age was performed with repeated measurements, followed by Bonferroni post-test. The data were expressed as means and standard deviation and the significance level was adopted with p < 0.05. The effect size values were expressed by the partial eta square (η2).The analysis of normality was performed by Shapiro-Wilk test. Non-normal variable  was log-transformed from their original values. In the nutritional analysis, a comparison between means of the diet components the placebo and EVCO periods was made by unpaired p = 0.134), carbohydrate intake (252.8 (200.1–305.5) vs. 213.2 (177.9–248.4) g; p = 0.278) and total fats intake (69.1 (56.7–81.5) vs. 55.7 (40.5–70.8) g; p = 0.161). However, considering the fractions of saturated fats (29.3 (23.5–35.1) vs. 18.5 (12.0–24.8) g; p = 0.017) and the amount of lauric acid (4.64 (4.50–4.77) vs. 0.20 (0.07–0.34) g; p<0.001) ingested in periods of coconut oil and placebo supplementation, respectively, a greater amount of saturated fats and lauric acid is observed for patients supplemented with coconut oil. For the other dietary constituents evaluated  there was no significant difference between the periods of supplementation with EVCO and placebo (data not shown). In addition, no adverse effects  were observed or reported in relation to the use of 10 mL/day of EVCO during the 30-day period, suggesting that this pattern of dietary supplementation is fully safe in humans.The records obtained from the food diaries of the patients supplemented with coconut oil or placebo indicates that there was no difference in the energy intake (1961 (1700–2222) vs. 1678 (1450–1905) kcal; plus training (2. 63 ± 0.10 vs. 2.20 ± 0.14); and Placebo plus training (2.21 ± 0.12 vs. 2.29 ± 0.17); p = 0.644 and η2 = 0.009). However, there is an interaction effect between time and group that appears to be promoted as a function of a decrease between initial and final MDA concentrations among patients who were supplemented with EVCO and trained (p = 0.015 and η2 = 0.227) (There is no EVCO-induced effect on serum MDA concentrations (nmol/mL) assessed after the experimental intervention compared to control intervention (EVCO (2.22 ± 0.10 vs. 2.24 ± 0.13); Placebo (2.27 ± 0.11 vs. 2.32 ± 0.15); EVCO = 0.227) .plus training (10.2 ± 0.57 vs. 9.58 ± 0.53) and Placebo plus training (9.40 ± 0.64 vs. 9.56 ± 0.60)); and ARV–MAP: ; EVCO plus training (6.57 ± 0.34 vs. 6.07 ± 0.29); and Placebo plus training (6.37 ± 0.40 vs. 6.71 ± 0.33))  and average real variability (ARV), showed that supplementation with EVCO was not effective within the assessed groups: SD–MAP: (EVCO (9.27 ± 0.54 vs. 8.73 ± 0.510); Placebo (8.90 ± 0.65 vs. 9.60 ± 0.60); EVCO ± 0.33)) .in natura coconut oil and its main isolated constituent, lauric acid, were able to evoke antihypertensive effect in spontaneously hypertensive rats and vasorelaxant effect in superior mesenteric artery, respectively [Original preclinical studies provided evidence that both ectively ,14. It wClinical studies with specific subpopulations and testing non-pharmacological alternatives are essential. Thus, considering the preliminary research, this was the first trial designed to assess the effects of EVCO in patients with systemic arterial hypertension. So, this study represents an effort to test an unknown outcome on the use of coconut oil in humans. In addition, we highlight the fact that the present study controlled precisely (through supplementation with capsules) the amount of EVCO effectively ingested. An important proportion of the studies that focus on this natural product did not properly control the amount of EVCO ingested; instead, it was included in meal preparation, without precise delimitations of its consumption ,26. Our Regarding the primarily investigated outcome, there was no antihypertensive effect associated with supplementation with EVCO in patients with stage 1 arterial hypertension tested in this study, unlike what was evidenced in the preclinical study with an animal model of essential hypertension . ClinicaWith regards to the difference in response evoked by coconut oil supplementation between pre-clinical and clinical studies, it is prudent to consider the distinctions inherent to each experimental model that was used in each study. The two studies involve specimens with different structure and metabolism and also with different experimental conditions. In the preclinical study, the dose of coconut oil administered was 2 mL per day for animals weighing between 200–300 g. Based on this dosage, if this was extrapolated for use in adult humans (average weight 70 Kg), an amount that would exceed 500 mL of EVCO per day would be necessary . The dosAlthough no effect on blood pressure was observed, a possible effect of EVCO on the autonomic function of patients was investigated. Two main factors motivated this experimental approach. First, in the pre-clinical study it was seen that, besides the antihypertensive activity, the supplementation with EVCO was associated with a reduction in oxidative stress and with an improvement in the baroreflex response in the treated animals . Second,Blood pressure variability is not a physiological variable routinely accessed in clinical practice, although according to Hsu et al. , it is rIn addition, through the antioxidant potential of several coconut oil constituents ,46 and tIn fact, the effectiveness of this antioxidant property inherent to EVCO has been attributed almost exclusively to animal models. Nevin and Ramajohan  showed tIn conclusion, the supplementation with EVCO did not have an antihypertensive effect in patients with stage 1 hypertension. It also showed no effectiveness on blood pressure variability and oxidative stress levels in humans. Thus, although coconut oil supplementation (10 mL/day) was shown to be safe as a nutritional approach and without significant impacts on the caloric load intake, it was not able to reproduce the effects obtained in an experimental model of hypertension when translated to hypertensive patients. Finally, it should be ratified that complementary studies are necessary to determine if doses different from the current trial can evoke additional or diverse effects.


Despite efforts to combat hypertension by pharmacotherapy, hypertension control rates remain low. Lifestyle modifications of individuals diagnosed with hypertension have prospects for the prevention and control of hypertension. This study assessed the effect of modifiable lifestyle factors on blood pressure control among adults in urban Accra.  In this cross-sectional study, 360 diagnosed hypertensive patients who were ≥18 years old, selected from two secondary-level referral hospitals in the Greater Accra Region, were interviewed. Demographic information, diet components, and exercise assessments as well as blood pressure measurements were taken. Chi-squared tests and binomial logistic regression were used to determine the association between demographic and lifestyle factors with blood pressure control. Area under the receiver-operator curves (AUROC) was used to identify lifestyle factors predicting optimal blood pressure control among patients diagnosed with hypertension.  Approximately 54.2% of participants had no knowledge of either causes or complications of hypertension. Similarly, 52.5% of patients that had not achieved blood pressure control lacked knowledge of causes or complications of hypertension. Longer time since diagnosis of 2–5 years (AOR = 0.08 (95% CI: 0.01–0.47)) and 6–10 years (AOR = 0.08 (95% CI: 0.01–0.50)) and diets, mainly composed of meat (AOR = 0.13 (95% CI: 0.02–0.70)) and starch (AOR = 0.14 (95% CI: 0.03–0.79)), predicted poor blood pressure control compared to patients diagnosed within a year and diets without meat and starch as main components, respectively. Additionally, engaging in some physical activity of 30 minutes to one hour (AOR = 5.64 (95% CI: 2.08–15.32)) and more than an hour ) predicted blood pressure control.  The study concludes that increased physical activity, abstaining from alcohol and smoking, increased intake of fruits and vegetables, and reduced intake of carbohydrates, meat, and fat have a positive influence on blood pressure control. Lifestyle modifying factors have a key role in complementing pharmacotherapy in hypertension control. Hypertension is universally acknowledged as a preventable and modifiable risk factor for cardiovascular disease . It is tThe increasing prevalence of hypertension in developed and developing regions is attributed to a number of factors. These include population growth and ageing, changes in diet, physical inactivity, increasing body mass index (BMI), and harmful use of alcohol . In deveAmong patients diagnosed with hypertension, the initiation and adherence to pharmacological treatment have been proven to help individuals attain optimal blood pressure (BP) control . NonetheControl rates of hypertension vary widely across and within populations. Various studies have reported rates of 1%–49% , 18–21. The identification of lifestyle factors associated with blood pressure control is necessary for improved chances of BP control outside of pharmacological treatment. Of the lifestyle modifications believed to contribute to both the prevention of hypertension and its control, dietary modification has been emphasized in several studies , 13, 17.The multifactorial nature of risk factors implies that preventive efforts are needed at patient, physician, and health system levels to reduce hypertension . The eviBeyond the prediction of high-risk individuals likely to develop hypertension, monitoring BP control is equally of value. In spite of the crucial role of lifestyle modification in controlling blood pressure, very limited evidence exists in Ghana on the extent to which lifestyle factors influence blood pressure control. This study aimed to identify the factors that influence hypertension control in adults on antihypertensive medication in urban Ghana. The purpose of this is to develop a lifestyle-based prediction model for hypertension control in a population of urban Ghanaian adults. The lifestyle factors measured in the study included physical activity, alcohol consumption, tobacco use, and diet.This was a descriptive, cross-sectional study at the outpatient hypertension clinics in two secondary-level referral hospitals in the Greater Accra Region of Ghana. Both hospitals serve urban populations and run hypertensive clinics on two days of the week.La Dadekotopon is an entirely urban municipality. It has an area of 36.3sqkm with a population of 183500. The household size is 3.6 persons/household. Malaria is the leading communicable disease in the municipality. Hypertension accounts for 20% of noncommunicable diseases. LEKMA Hospital is situated in the Ledzokuku Krowor Municipal Assembly. The Assembly has an area of 47.58sq.km with a population of 227,932. It has a household size of 2.8 but the average population per house is 10.4. Upper respiratory tract infections and malaria are the leading cause of communicable diseases. Hypertension is the commonest noncommunicable disease , 32.A total of 360 participants were interviewed in this study.Participants were eligible for the study if they were 18 years and older. They also needed to have been diagnosed as hypertensive with a systolic blood pressure (SBP) of at least 140 mm Hg and/or a blood pressure (DBP) of at least 90 mm Hg. They must have also been on antihypertensive treatment for no less than a year. Patients with coexisting medical conditions such as diabetes were included in the study once they met a blood pressure reading of or at least 130 mm Hg (SBP) and/or a blood pressure (DBP) of at least 80 mm Hg if they were diabetic.Patients with psychiatric conditions or previous hypertensive emergency as well as those on medication that affected blood pressure were excluded from the study. Pregnant women were also excluded from the study.z = 1.96, d = 0.05, prevalence of adherence to hypertension medication of 0.30 based on a study of urban adults in Accra [The sample size was estimated under the following assumptions: in Accra . The calA list of hypertensive patients given appointments for each day was obtained from the records department. Numbers were assigned to the individuals on the list. This list was deidentified and identification numbers were assigned to the individuals on the list to control for sampling bias. The numbers were randomly selected using Excel random number generation. After the selection, the names of individuals on the list corresponding to the selected numbers were contacted after they had seen the doctor to conduct the interview. An average of 50 to 60 patients was booked for each clinic day for both facilities with the facility with a higher caseload contributing 30–35 per day. In total, 220 participants were recruited from LEKMA and 140 were recruited from La Dadekotopon and the sample for each facility was proportional to size.A written informed consent (signed or thumb-printed) was obtained from each participant. Illiterate respondents nominated an independent witness to attest to the consent process. Consent was sought from participants by trained researcher after the study was explained to them. Participants were interviewed after they had completed their doctor's visit. Data was collected using an interviewer administered structured questionnaire composed of five  differenThe first section of the questionnaire recorded a minimum of two  and a maThe second section consisted of questions on the sociodemographics of participants including age in single years, sex of participant, level of education, and area of residence. Additional information on the participant's health and treatment collected information on the number of pills being taken and the presence of comorbid conditions. Comorbidities reported were verified from patient records.The third section examined patients' knowledge about hypertension, its causes, and complications as well as comorbidities and medications. A final knowledge score was obtained for each respondent. The respondents were scored on their knowledge of each domain: normal adult blood pressure and the number of causes of hypertension and complications of hypertension they knew. Scores of 0 represented no knowledge of either the causes or complications of high blood pressure. 1 represented knowledge of either the causes or the complications and scores of 2 represented those who knew both causes and complications of hypertension. Participants were considered as having “Good knowledge” for a score of 2, as “Moderate knowledge” for a score of 1, and “No knowledge” for a score of 0.In the final section, questions that measured lifestyle factors such as weekly exercise by duration, alcohol consumption in units, tobacco use and smoking history, and dietary habits were posed. Dietary components were assessed by a self-reported response of yes or no to the question “Is your diet largely based on Meat and fatty foods?” Similarly, the question was posed also for starchy foods, fruits, and vegetables, salt, or any others.t-test was used to compare means for continuous variables: age and alcohol in units. Cross-tabulations of client sociodemographic and lifestyle factors influencing hypertension control were undertaken. Descriptive analysis was conducted using Pearson's χ2 and Fishers exact test were appropriate. The hypertension control status of each client was determined by calculating the average of all SBP and DBP readings recorded. Blood pressure readings of 140/90 mmHg or less were classified as optimal control. Blood pressure control was coded as 0 for poor control and 1 for optimal control.Frequencies and proportions of the background factors by categories were done to describe the sample and show distribution. Means of continuous outcomes, age, and alcohol units consumed were estimated. The Binary logistic regression model was used in assessing the influence of lifestyle factors on hypertension control. In estimating the predictive effect of lifestyle factors on blood pressure control among patients recruited in the study, two nested models were fitted. Model 1 consists of only lifestyle factors and model 2 integrated both the lifestyle factors and sociodemographic characteristics. The performance of these two models was evaluated by the area under receiver-operating characteristic curve (AUROC) and Akaike information criterion (AIC). Background variables that were controlled for in the analysis were sex, age, education, knowledge, presence of comorbidity, and number of pills taken. All analyses were conducted in STATA and statistical significance was set at a 95% confidence level.Ethical clearance was sought from the Ghana Health Service Ethics Review Committee with approval number GHS-ERC: 037/12/17. Permission to conduct the research at Ghana Health Service facilities was also sought from the Greater Accra Regional Health Directorate and subsequently from the Municipal Health Directorates and Heads of both facilities.Among the sample of patients interviewed, females constituted a larger proportion (70%). The mean age of participants was 61.9 ± 0.6 years with ages ranging from 27 to 94 years. The average time since diagnosis for patients in this study was 7.6 ± 0.3 years. Among the 51% of participants who consumed alcohol, less than a unit of alcohol was consumed weekly and smoking history was reported in a few patients (8.9%). Less than half of the patients in this study were engaged in any form of weekly exercise activity, and carbohydrates were a major component of the diets reported (91%). Further details of the background characteristics of the participants are available in Assessing patient knowledge shows that approximately 54.2% of patients did not have any knowledge of hypertension or its causes and complications . Similarp < 0.05). Among patients with uncontrolled blood pressure, 52.5% did not have any knowledge on hypertension or its causes and complications (ications . Approxiications .p=0.005), 6–10 yrs since diagnosis (p=0.006), and diets with meat (p=0.017) and starch (p=0.025) as their main components predicted lower blood pressure control compared to patients diagnosed under a year and with diets without meat and starch as main components, respectively.To assess the lifestyle factors on blood pressure control among urban adults, two nested models were fitted. No significant difference in AUROC between the two nested models was observed; model 2, however, performed better with a larger area . p < 0.001) and more than one hour (p=0.006) predicted blood pressure control when controlling for sociodemographic and other lifestyle factors . Similarly, among those diagnosed over 6–10 years, the odds of controlled blood pressure were reduced .In this study, one out of every five patients on antihypertensive medication was able to attain control of their blood pressure—a finding consistent with the range of control estimated from other studies in Ghana –13. The This study found that more than half of participants did not have accurate knowledge of hypertension—a finding in support of evidence linking poor knowledge of hypertension to suboptimal blood pressure control –39. ThisWeekly exercise, comprising exercise activity of up to an hour or more, was identified to contribute to blood pressure control among diagnosed patients assessed. This finding is encouraging as evidence continually shows that the frequency of exercise is a significant predictor of hypertension control , 16, 26.In assessing the components of an individual's diet, the findings of this study indicate that patients with poor blood pressure control reported diets mainly composed of meats, fats, and starch. These are dietary components identified as not supportive of reducing blood pressure , 14, 16.Patient counselling has been shown to reinforce the importance of adhering to diets rich in fruits and vegetables and fat products . This beWithin this population of urban adults, alcohol consumption also did not have a significant effect on blood pressure control. This finding is at variance with other studies of alcohol use and hypertension in Ghana . It is pThis study demonstrates that a variety of lifestyle factors can reflect the hypertension control status of an adult patient. The findings of this study particularly show that modifiable factors, such as duration of exercise, alcohol intake, and dietary composition, were associated with BP control in patients on antihypertensive medication. These results are in agreement with the identified contribution of diet and exercise to blood pressure control in both men and women , 16, 43 Our study is not without limitations. Even though correlations were identified between starch, meats, and fats as main components of the typical diets assessed, a standard dietary assessment tool was not employed. Further studies utilizing such tools in dietary assessment among hypertensive patients would ensure comparability.A second limitation is that responses to exercise were subjective and self-reported. However, the use of well trained research assistants and to explain duration and intensity required for categorization ensured that responses obtained were as accurate as possible.The study concludes that, among patients diagnosed and on antihypertensive medication, increased physical activity, abstaining from alcohol and smoking, increased intake of fruits and vegetables, and reduced intake of carbohydrates, meat, and fat have a positive influence on blood pressure control. Lifestyle modifying factors have a key role in complementing pharmacotherapy in hypertension control. Lifestyle modifying factors should be an integral part of management of patients with hypertension.