The purpose of this study was to investigate changes in peripapillary microvasculature using optical coherence tomography angiography (OCTA) in systemic hypertension (HTN) patients. This was a cross-sectional study. Based on the duration of HTN, seventy-eight HTN patients were divided into two groups.  and 90 control subjects. All subjects underwent 6 × 6 mm OCTA scan centered on the optic nerve head. We analyzed peripapillary vessel density (VD) and perfusion density (PD) in superficial capillary plexus among three groups. The average ganglion cell-inner plexiform layer (GC-IPL) and retinal nerve fiber layer (RNFL) thicknesses of HTN group 2 were thinner than those of the control group . HTN group 2 showed lower peripapillary VD and PD than the control group. However, there were no differences between HTN group 1 and the control group in OCT and peripapillary OCTA parameters. In HTN patients, the peripapillary VD, PD and GC-IPL, RNFL thicknesses correlated significantly. OCTA showed that the peripapillary VD and PD were lower in HTN patients with a duration ≥10 years compared with those of normal controls. Peripapillary microvasculature was correlated with the RNFL and GC-IPL thicknesses. HTN duration should therefore be considered when evaluating peripapillary microvasculature using OCTA. With advances in medical technology, the life expectancy has been extended, and the number of patients with HTN has increased.Cardiovascular disease is one of the more common causes of death in developing country, and hypertension (HTN) is the most common treatable risk factor. According to a US study, approximately 68 million (31%) of patients ≥18 years of age are reported to have HTNUncontrolled HTN can cause vascular changes in many organ systems, such as the brain, heart, kidneys, and eyes, due to elevated arterial pressure and increased peripheral resistance. Vascular changes in the eye can be directly visualized using funduscopy. Arteriolar narrowing is a hallmark of hypertensive retinopathy (HTNR), and the narrowing being characterized as either focal or diffuse. This occurs when the systemic blood pressure rises to maintain constant blood flow by autoregulation of the retinal circulation. The destruction of the inner blood-retinal barrier and vascular endothelial structure can then lead to cotton wool spots, retinal hemorrhage, and intraretinal lipid deposits.4, Furthermore, in previous optical coherence tomography angiography (OCTA) studies, foveal microvascular perfusion was decreased, which correlated with GC-IPL thinning in patients with HTN6.Funduscopy, optical coherence tomography (OCT), and fluorescein angiography (FA) may be helpful in the diagnosis and evaluation of retinal pathological changes in HTN. In our previous OCT study, the ganglion cell-inner plexiform layer (GC-IPL) and peripapillary retinal nerve fiber layer (RNFL) thicknesses were lower in chronic HTN and relieved HTNR patients than normal controlsWe assumed that RNFL thinning in patients with HTN should be related with peripapillary microvascular changes. We therefore analyzed changes in peripapillary microvasculature in patients with HTN using OCTA, and identified the associations between OCT and peripapillary OCTA parameters.This retrospective, cross-sectional study was approved by the institutional review board of Chungnam National University Hospital, and was conducted to the tenets of the Declaration of Helsinki. The requirement for obtaining informed patient consent was waived by the institutional review board of Chungnam National University Hospital due to the retrospective nature of the study. The medical records at the Chungnam National University Hospital inclusive were reviewed to identify HTN patients who visited retina clinic.7 at Chungnam National University Hospital. They underwent regular follow-up for blood pressure control, and all participants were well-controlled blood pressure for at least the past year. The participants were divided into three groups: control group , HTN group 1 , and HTN group 2 . We excluded HTNR using fundus photography of patients in the HTN groups. One eye from each participant was included. Only one eye was randomly selected if both eyes were eligible. In the power calculation using G*Power 3.18, the power of the average peripapillary VD and PD were 0.970 and 0.967, respectively.Diabetic patients were excluded because diabetes significantly affects the inner retinal layer and microvasculature. HTN was diagnosed as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHgThe exclusion criteria were systemic diseases other than HTN and hyperlipidemia, glaucoma, optic nerve disorders, a best-corrected visual acuity (BCVA) < 20/25, intraocular pressure (IOP) > 21 mmHg, high myopia [axial length (AL) ≥ 26.0 mm or spherical equivalent (SE) > −6 diopters], and a history of intraocular surgery.All patients underwent slit-lamp biomicroscopy, BCVA, SE, IOP, and AL using an IOL master, fundus photography, dilated fundus examination, OCT, and OCTA.OCT examination was performed using a spectral domain OCT . The skilled examiner performed all imaging. Central macular thickness (CMT) and GC-IPL thickness were analyzed using a macular cube scan. Average RNFL thickness was analyzed using an optic disc cube scan. We excluded with signal strength (SS) less than 7 or poor centration or segmentation error in OCT scans.OCTA imaging was acquired using the Zeiss Cirrus HD-OCT with Angioplex, with a light source at 840 nm and an A-scan rate of 68 KHz. We used only scans without segmentation errors and motion artifacts and with SS greater than 9. The superficial capillary plexus (SCP) images were segmented with an internal limiting membrane and the inner plexiform layer and the deep capillary plexus (DCP) was segmented with an inner nuclear layer and the outer plexiform layer.The optic disc centered 6 × 6 mm OCTA scans were acquired to evaluate peripapillary microvasculature. A 6 × 6 mm scans were acquired containing 350 × 350 scans each, and B-scans were repeated twice at each cross-section. Vessel density (VD) and perfusion density (PD) are defined as follows; VD means total length of perfused vasculature per unit area in a region of measurement and PD means the total area of perfused vasculature per unit area in a region of measurement. The AngioPlex software automatically displays the measured value of the SCP according to the subfield of the ETDRS. We only studied SCP because the built-in software provided automatically quantified values of SCP only. We analyzed the peripapillary VD and PD of the average and quadrants of the inner ring, outer ring, and full area Fig. . We inclStatistical analysis were performed with SPSS version 22.0 . For statistical analyses, BCVA values were transformed to the logarithm of the minimum angle of resolution (log MAR) values. One-way ANOVA with Bonferroni’s post-hoc test and the chi-squared test were applied to compare the clinical characteristics, OCT, and OCTA parameters among groups. To determine the relationship between peripapillary OCTA and OCT parameters, Pearson’s correlation was used. P < 0.05 was considered statistically significant.p < 0.001). There were no significant difference among the three groups in age, sex, laterality, BCVA, SE, IOP, AL, and SS of OCTA images , Seventy-eight eyes from HTN patients (38 in HTN group 1 and 40 in HTN group 2) and 90 control eyes were enrolled in the study. The durations of HTN were 4.2 ± 2.4 years in HTN group 1 and 16.3 ± 5.8 years in HTN group 2 (p = 0.135). The GC-IPL and peripapillary RNFL thicknesses showed statistically significant differences in the three groups . Using Bonferroni’s test, the GC-IPL and RNFL thicknesses in HTN group 2  were lower than those of the control group . However, there were no differences between HTN group 1 and the control group  and PD  in HTN patients . However, age, female sex, BCVA, SE, IOP, AL, mean arterial pressure and CMT were not correlated with the average peripapillary VD and PD. Multivariate regression analysis showed that clinical factors such as age, IOP, sex, BCVA, SE, and mean arterial pressure were not significant factors affecting the average peripapillary VD and PD  in the fellow eye of patients with one eye affected with CNV20.Systemic HTN affects the structure and function of blood vessels, and HTN changes are systemic risk factors for cardiovascular disease21, and the grade of HTNR is associated with mortality22. thus, evaluation of retinal changes in HTN patients is clinically important.HTNR is one of the markers of target organ damage in the initial evaluation of HTN patients23.Elevated blood pressure results in various changes to the retinal vasculature. These changes are classified as arteriolar changes  and retinal lesions  caused by blood-retinal barrier damage. Hayreh reported that hypertensive changes in the eye affect not only the retina but also the choroid and optic disc26.Funduscopy has been used to diagnose HTNR. However, if there is only arteriolar narrowing during an early stage, it may be difficult to detect these changes using only a fundus examination. Several studies have therefore been conducted to quantitate and differentiate these changes. Fundus photography has been used to measure decreases in retinal arteriolar diameter and the arteriole-to-venule ratio, and has revealed such decreases in high blood pressure patients when compared with normal subjects27. In our study, there was no difference in the CMT, but the GC-IPL and RNFL thicknesses were different among the three groups, and those of HTN group 2 was thinner than the control group. In an animal study using rhesus monkeys, the RNFL thickness decreased with chronic arterial hypertension28. In addition, previous studies reported that the inner retina during ischemia is more vulnerable to hypoxia, which is consistent with our previous research30. This reduction in inner retinal thickness may be associated with hypertensive retinal ischemia, such that chronic microvascular disorder is associated with slow inner retinal thinning. Similar to diabetic retinal neurodegeneration, it is possible that hypertensive changes can occur in patients without retinopathy. These were not observed using funduscopy, but there was still the possibility of microvascular damage. However, studies using OCT provide limited information on retinal capillary circulation.OCT is widely utilized for the diagnosis and treatment in retinal diseases and glaucoma. It can distinguish ten retinal layers with high resolution, and has the advantage of quantitatively evaluating the thickness of each layer. In HTN patients without retinopathy or glaucoma, thinning of the GC-IPL and peripapillary RNFL was reported6. In addition, patients with poorly controlled blood pressure showed a greater decrease in the retinal capillary density compared with patients whose blood pressure is well controlled31.The recently developed technique OCTA has no side effects from contrast agents, in contrast to FA, and has the advantage of being able to measure blood flow and the vascular density in SCP and DCP, separately. There have been many reports on the quantitative analysis of retinal vascular changes and ischemia in diabetic retinopathy, as well as on retinal venous occlusion and glaucoma. Recent studies with OCTA have shown decreased foveal microvascular parameters, increased foveal avascular zone areas in patients with chronic HTN, and relived HTNR. Because of the association between the microvasculature and inner retinal layer thickness, inner retinal thinning may be associated with retinal microcirculationTo our knowledge, there has been no previous study on changes to the peripapillary microvasculature according to HTN using OCTA. We found that the average peripapillary VD and PD of the inner ring, outer ring, and full area were different among the three groups. The peripapillary VD and PD of HTN Group 2 were lower than those of normal controls. We evaluated associations between OCT and peripapillary OCTA parameters in HTN patients. The peripapillary VD and PD showed a correlation with the GC-IPL and RNFL thicknesses. The decreased GC-IPL and peripapillary RNFL thickness might be associated with decreased peripapillary microvascular circulation. In the present study, the HTN duration did not correlate with the GC-IPL and RNFL thicknesses, but was correlated with the peripapillary VD and PD. It is presumed that the peripapillary microvasculature was more sensitive to the duration of HTN than the inner retinal thickness.33. Because of the cross-sectional study, we could not investigate these parameters in detail. Previous studies33 used scanning laser Doppler Flowmetry and fundus photography, so additional studies with OCTA may be needed. Third, a further longitudinal study of temporal sequencing between decreased GC-IPL and RNFL thicknesses and retinal microvasculature should be conducted, and the DCP and choroid investigated, as they may be affected by HTN. Finally, we only analyzed SCP, not DCP and choriocapillaries. However, previous studies have shown that projection artifacts may affect quantitative analysis of DCP and choriocapillaries, and Enders et al.34 reported that 75% of deep retina images were shown projection artifacts. Further studies on the changes of DCP and choriocapillaries using projection-resolved OCTA will be needed.This study has some limitations. First, in this retrospective, cross-sectional study, it was difficult to identify the occurrence of previous hypertensive events. In general, if there is no acute rise in blood pressure, visual symptoms do not occur, and ophthalmic examinations are often not performed. We excluded patients in HTNR with cotton wool spots, retinal hemorrhage, and severe arteriolar narrowing, thereby minimizing the effect of these on peripapillary OCTA parameters. Second, anti-hypertensive medications and kidney functioning (low estimated glomerular filtration rate levels) could affect the retinal microcirculationOur study excluded systemic diseases other than HTN. It is important to investigate the only effects of HTN on peripapillary microvasculature. In addition, we studied changes in peripapillary optic nerve head perfusion in HTN patients for the first time. Overall, the strength of this study was its characterization of the relationship between peripapillary microvasculature and the RNFL and GC-IPL thicknesses.In conclusion, this study showed that the peripapillary VD and PD were lower in HTN patients with a duration of ≥10 years, and the peripapillary VD and PD showed a correlation with RNFL and GC-IPL thicknesses. Based on the findings in this study, the effects of HTN duration should be taken into account when evaluating the peripapillary microvasculature using OCTA.Supplementary Table 1.


The relationship between electrocardiographic evaluation and circadian blood pressure (BP) variation in young and middle-aged hypertensive patients remains unknown.A total of 171 hypertensive patients were included in the study. First, patients were divided into a young and middle-aged group and an elderly group. The two groups were then separately classified into three subgroups on the basis of circadian variation of BP as dippers, non-dippers and reverse-dippers. The electrocardiographic evaluation was calculated from 12-lead electrocardiography (ECG).QTc intervals were shortest in the dippers and longest in the reverse-dippers in the young and middle-aged group . QTc interval was found to be an independent risk factor for the non-dipper BP pattern  and reverse-dipper BP pattern  in young and middle-aged hypertensive patients. No significant differences in other ECG parameters were found among the three subgroups in the young and middle-aged group.Our study suggested that QTc interval might serve as a risk factor for non-dipper BP pattern and reverse-dipper BP pattern in young and middle-aged hypertensive patients. To prevThere have been several studies investigating the association between electrocardiographic evaluation  and the circadian variation of BP , 9, 10. 22.1This single-center study retrospectively included hypertensive patients admitted to the Cardiology department at the first Affiliated Hospital of Soochow University who simultaneously underwent ECG and ABPM from January 2017 to January 2019. Hypertension was defined as previously diagnosed hypertension, currently using antihypertensive drugs, office-measured systolic BP (SBP)/diastolic BP (DBP)≥140/90 mmHg, 24h ABPM SBP/DBP≥130/80 mmHg, daytime (or awake) ABPM SBP/DBP≥135/85 mmHg or nighttime (or sleep) ABPM SBP/DBP≥120/70 mmHg, 12. BodThere were only two extreme-dippers meeting the above inclusion and exclusion criteria. Due to the limited numbers, the two extreme-dippers were not included in our study. In the end, a total of 171 patients were included in the study. They were first divided into two groups, the young and middle-aged group and the elderly group. Then, the above two groups were separately classified into three subgroups on the basis of circadian variation of BP, as dipper, non-dipper and reverse-dipper.2.2ABPM was performed to record the circadian variation of blood pressure in all included patients by an ABPM 6100 device . The cuff was placed on the right arm of patients. Patients were asked to keep their daily routine and stay calm when feeling the inflation of cuff. During the daytime (8:00AM to 11:00PM), BP was measured every 15 minutes. During the nighttime (11:00PM to 8:00AM), BP was measured every 30 minutes. Only recordings with more than 70% of valid BP measurements were included in the final analysis. The means of SBP and DBP were calculated at 24 h, awake and sleep. The nocturnal dip rate was calculated as follows: (%) 100× [1− (average night SBP/average awake SBP)]. Then, the circadian variation of blood pressure status was defined as: extreme-dipper , dipper , non-dipper  and reverse-dipper  [2.3All patients included in the study underwent a resting 12-lead ECG  with a 25mm/s paper speed and 10 mm/mV height. Heart rate and frontal QRS-T angle were obtained directly from ECG reports. The QT intervals were measured using a software program . Then we recorded the longest QT interval from all limb and precordial leads and QTc interval was calculated using Bazett’s formula. QTc int2.4Baseline demographic, clinical and laboratory data were collected from the hospital medical records and case collection and scientific research system for clinical cardiology (CCSSSCC). Peripheral blood samples were drawn from patients when they were in a fasting state. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other biochemical parameters were determined at the Biochemistry Department in the first Affiliated Hospital of Soochow University.2.5Statistical analysis was performed using IBM SPSS for Windows version 25.0 . Continuous variables were tested for a normal distribution using the Shapiro-Wilk test. Continuous variables with a normal distribution were defined as mean±standard deviation (SD), while continuous variables without a normal distribution were defined as median . Continuous variables were compared using the one way analysis of variance (ANOVA) or the Kruskal-Wallis test, if appropriate. If the results of ANOVA were statistically significant, post-hoc Bonferroni test was performed. If the results of Kruskal-Wallis test were statistically significant, the results of pairwise comparison were corrected by Bonferroni correction. Categorical variables, defined as percentages, were compared using the χ2-test or the Fisher’s exact test, if appropriate. To assess the correlation between continuous variables, Pearson’s correlation coefficients were calculated. To explore the relationship between relevant variables and circadian blood pressure rhythm, multivariate logistic regression analyses were applied. For all analyses, values of P less than 0.05 were regarded to be statistically significant.Ethical issues: Our study was in accordance with the principles outlined in the Declaration of Helsinki and approved by the ethics committee of Soochow University.Informed consent: Informed consent has been obtained from all individuals included in this study.3In the end, a total of 171 patients were included in our study. The baseline demographic and clinical characteristics are shown in The laboratory and electrocardiographic variables of the study population are shown in the Age, QTc interval, TpTe, frontal QRS-T angle, K and creatinine were included in the multivariate logistic regression analysis. Age and QTc interval were found to be significantly different when comparing reverse-dipper BP pattern with dipper pattern or non-dipper BP pattern with dipper pattern . QTc intTo investigate whether there were associations between age or indices of ABPM and QTc in the young and middle-aged patients, Pearson’s correlation coefficients were calculated . QTc int4ABPM, which records the variation of blood pressure in 24h, has attracted more and more attention in recent years. Due to its higher reproducibility than office-measured blood pressure, ABPM has been proposed as a clinical tool to confirm office-measured hypertension diagnosis in several international guidelines . Based oQTc is one of the most widely used ECG parameters to assess ventricular repolarization. Previous studies have revealed that abnormal prolongation of QTc interval was correlated to ventricular arrhythmia and sudden cardiac death, 19, 20.In our study, the main finding was that QTc interval was significantly longer in non-dippers and reverse-dippers than in dippers in young and middle-aged hypertensive patients. However, QTc was similar among dippers, non-dippers and reverse-dippers in elderly patients with essential hypertension. What’s more, QTc interval duration was negatively correlated with the decline rate of nocturnal SBP in young and middle-aged hypertensive patients. Last but not least, QTc interval and age were found to be independent risk factors for non-dipper BP pattern and reverse-dipper BP pattern in young and middle-aged hypertensive patients.The relationship between QTc interval and circadian BP variation might be explained by LVH and impaired autonomic nervous system functions. Loss of normal nocturnal BP drop is correlated to left ventricular hypertrophy. Ivanovic et al demonstrated that LVH was most prevalent among reverse-dippers compared to dippers, non-dippers, extreme-dippers . HypertrIn our study, the correlation between QTc prolongation and blunted nocturnal blood pressure drop was observed in young and middle-aged patients but not in elderly patients. Older age itself is a risk factor for QTc interval prolongation . ElderlyTanriverdi et al demonstrated that frontal QRS-T angle was smaller in patients with dipper hypertension than in patients with non-dipper hypertension . On the In our study, heart rate was significantly different among dippers, non-dippers and reverse-dippers in elderly patients with essential hypertension. Moreover, heart rate was lowest in revere-dippers and highest in non-dippers in elderly hypertensive patients, which was inconsistent with previous studies , 28. TheRecently, the Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares (MAPEC) study found that the reduction of sleep time SBP and correction of blunted night blood pressure drop through a night time antihypertensive treatment strategy can most efficiently lower the risks of stroke and cardiovascular diseases , 30. In 5Our study suggests that there is a correlation between QTc interval and the circadian variation of blood pressure in young and middle-aged hypertensive patients but not in the elderly. We found that QTc interval is a risk factor for non-dipper and reverse-dipper status in young and middle-aged hypertensive patients. What’s more, QTc interval is negatively correlated with decline rate of nocturnal SBP. The finding of our study may help to explain the conflicting results of previous studies.


A high prevalence rate of hypertension (HTN) and its subsequent serious complications made this disease a major health-treatment concern in many societies. The current study aimed to investigate the prevalence of hypertension and its associated risk factors in Fasa PERSIAN COHORT in south of Iran in 2019.t test, chi-square test, analysis of variances, Pearson correlation coefficient, and multiple stepwise regression were used to analyze the obtained data. Thereafter, the data was analyzed using SPSS software version 22, and P value < 0.05 was considered as statistically significant.This was an analytical-cross sectional study. The study population were the individuals covered by Fasa cohort. Information of the first phase of Fasa Persian cohort in south of Iran was used in this study. Independent P < 0.5).Out of 10,111 individuals included in the study, 5546 (54.86%) subjects were women and 4565 (45.16%) other were men. The overall prevalence rate of hypertension was estimated as 46.6%. In the present study, (16/1%) of the participants were with HTN stage 1, and (17/9%) of them were with HTN stage 2. The results show that there were significant positive correlations among HTN and age, BMI, HDL, TG, BUN, ALP, smoking, physical activity, cardiovascular diseases, diabetes, and renal failure (Prevalence of HTN in this study population is considerable. Therefore, it is suggested that health system should program some plans to prevent hypertension’s prevalence and eliminate its risk factors. A high prevalence of hypertension (HTN) and its subsequent serious complications made this complication a major problem of health system in many societies . HTN, asAccording to the opinion of American society of Hypertension (ASH) and International society of Hypertension (ISH), systolic blood pressure equal to and greater than 140 mmHg and diastolic blood pressure equal to and greater than 90 mmHg can be considered as HTN based on an average value obtained from accurate measurement of blood pressure for at least two times . The resIn eastern Mediterranean countries and Middle East, the prevalence of HTN in various assessments was reported to be between 17 and 39%, and rapid social and economic changes of these countries in recent decades resulted in a high prevalence of the HTN . The resSince HTN is considerably prevalent in most communities, and its prevalence in various regions varies due to demographic, cultural, and social factors. Since there is no study performed in Iran based on the results obtained from cohort data to date, and besides, due to the reason that the identification of risk factors of HTN will play important role in programming for better prevention, control, and treatment of this complication, this study aimed to investigate the prevalence of hypertension and its associated risk factors in Fasa PERSIAN COHORT in south of Iran in 2019.The current study was an analytical-cross-sectional study. The study population were the individuals covered by Fasa Cohort in south of Iran .The data used in this research were driven from the base-line survey of the PERSIAN  cohort Study (Fasa noncommunicable disease cohort study) . MoreoveIn addition, anthropometric indices (measurement of height-weight and waist circumference) as well as blood pressure measurement were used. In order to measure blood pressure, the average of two times measurement of blood pressure was considered as the criterion. Thereafter, in terms of the 2017 ACC/AHA guideline, the participants were divided into four groups as follows: those with systolic blood pressure less than 120 mmHg and diastolic blood pressure less than 80 mmHg were considered as normal blood pressure, those with systolic blood pressure of 120–129 mmHg and diastolic blood pressure less than 80 mmHg were considered as the elevated hypertension, the subjects with systolic blood pressure of 130–139 mmHg and diastolic blood pressure of 80–89 mmHg were considered as stage 1 hypertension, and finally those with systolic blood pressure equal to and greater than 140 mmHg and diastolic blood pressure equal to and greater than 90 mmHg were considered as stage 2 hypertension [t test, chi-square test, analysis of variances, Pearson correlation coefficient, and multiple stepwise regression were used to analyze the obtained data. Notably, the data were analyzed using SPSS software version 22, and P < 0.05 was considered as statistically significant.Independent All the participants gave written informed consent to participate in the study. The present study was conducted in terms of the principles of the revised Declaration of Helsinki, which is a statement of ethical principles that directs physicians and other participants in medical research involving human subjects. The participants were assured about their anonymity and confidentiality of their information. Moreover, the study was approved by the Institutional Research Ethics Committee of Fasa University of Medical Sciences, Fasa, Iran (code: IR.FUMS.REC.1398.063).Out of 10,111 participants, 5546 (54.86%) subjects were women and 4565 (45.14%) others were men. The average age of the participants was 34.48 ± 8.4 years old. Furthermore, the mean age of male subjects was 49.58 ± 9.4 years old. Accordingly, the youngest man was 35 years old and the oldest one was 87 years old. In female individuals, the mean age was 49.64 ± 9.58 years old, the youngest woman was 37 years old, and the oldest one was 79 years old. The mean of systolic blood pressure in male participants was 110.52 ± 17.56 and diastolic blood pressure was 74.36 ± 11.84. The mean of systolic blood pressure in female subjects was 136.00 ± 19.69 and diastolic blood pressure was 83.01 ± 11.52. The total means of systolic and diastolic blood pressure were 111.36 ± 18.51 and 74.65 ± 11.99, respectively (Table P < 0.05)  of the included subjects were with HTN stage 1, and (17/9%) of them were with HTN stage 2 Tables . Tables Hypertension is the most important and prevalent chronic disorder, which still remains a major health concern despite many medical progresses. Given the prevalence of this disease and its serious subsequent complications, the current study aimed to investigate the known risk factors for hypertension as well as studying their associations in study population of the Cohort in south of Iran in 2019.Number of adults with hypertension in Iran reached 9 million and 7 hundred thousand individuals in 2015, out of whom, more than 5 million and 2 hundred thousand were man and more than 4 million and 5 hundred thousands were woman. Number of individuals with HTN in Iran has also increased from 4 million individuals (2 million and 1 hundred thousand men and one million and 9 hundred thousand women) to more than 9.7 million in 2015. Correspondingly, the majority of this increase was resulted from an increase in population of Iran and increase in life expectancy of the Iranian population .The prevalence of HTN varies in various studies, which in part could be attributed to differences in time, region, and the population’s ethnics of the studies. However, these different numbers can also be resulted from a mistake or bias. As an example, in the sugar and lipid study of Tehran, the prevalence of HTN in old ages was reported to be about 47% , and in However, there are some studies that estimated this rate as 25% . In addiRegarding the effective factors on blood pressure, the most significant association was observed with blood pressure in univariate associations, BMI, BUN, diabetes, cigarette use, and breastfeeding duration.The study performed by Rao et al.  in IndiaThe study by Fawokan et al. , which iThe study by Anteneh et al.  have alsThe study by Patra and Bhise also investigated the factors related to HTN in India population and then reported general prevalence of HTN about 25%. Moreover, this study reported some factors associated with the disease as age, sex, marital status, habitat, socioeconomic status, unhealthy behaviors such as tobacco and alcohol, and a high BMI . The resThe results obtained from the study by Saju et al. in India and the study by Gao et al. in China showed a direct and significant relationship among smoking, lack of physical activity, diabetes, and ischemic heart disease and blood pressure. In addition, in the present study, the above-mentioned factors had significant relationships with blood pressure , 25. RabNumerous biochemical and nutritional indices were entered into the study, and for the first time, by comparing similar studies, all the medications related to HTN that might affect blood pressure status were investigated (potency of decrease and increase of blood pressure as a side effect). Afterward, they were entered in the multi-variate analysis to attenuate their effects on blood pressure. Regarding the analysis of blood pressure, in order to achieve more accurate results and to control the effects of high and low pressures on the results in some groups, regression analysis was used, and as the results show, some of the findings are fully consistent with findings of similarly performed studies. For example, BMI and/or waist circumference, which are known as indices of obesity, have almost played critical roles in most sex and blood pressure groups, and were considered as significant risk factors for blood pressure.Of course, it should not be neglected that waist circumference in similar previous studies was not used, and index of abdominal obesity that is represented by waist circumference, was neglected in other studies. While in our study, for SBP and DBP in women, after the modification of many known variables, waist circumference showed a strong association with HTN. As stated earlier in the other studies, diabetes is considered as a risk factor for HTN, and in this regard, blood sugar showed a strong association with HTN in our study.Alkaline phosphatase (ALP) is considered as an index of hepatic function that showed a considerable association with HTN specially SBP, which was also pointed in few studies. Regarding the variables related to dietary regimen, as expected, sodium is associated with HTN, and almost all the previous studies had consensus on it; however, an interesting point in our study was its weak association compared to other variables.While opposite to our expectation, calcium and potassium were pointed as anti-HTN factors in many studies and were considered as the components of DASH diet (Dietary Approaches to Stop Hypertension) , 28, theAnother component of DASH diet that is considered as a decreasing factor of HTN, is magnesium, which in our study was shown as a preventive factor, and ths is fully consistent with the findings of other studies , 30.Another considerable point in our study was breastfeeding duration in women, which is a risk factor for susceptibility to HTN, approximately opposite to the other studies that introduced breastfeeding as a preventive factor for HTN . AccordiAlthough the study by Struebe et al.  pointed This is the point that should be considered in further studies; however, average breastfeeding duration in our study was considerable as 86.4 ± 58.8 months compared to other studies. In this regard, the reason for this considerable and different finding might be due to the long duration of breastfeeding, which we know that it can consequently cause considerable health risks to mother due to mother’s reservoir loss.Strength of this study was that it is the first community-based cohort study performed in South Iran. One limitation of the study was that the 2017 ACC/AHA Guideline was used in the present study to stage blood pressure; therefore, it is recommended to use other guidelines in future studies and also to perform studies in other countries.The findings of the current study showed a high prevalence of HTN in the study population; therefore, it is necessary to perform the required programs by the managers and policy makers of the health treatment system with the aim of screening and identifying hazardous factors, promoting self-care behaviors and management, and controlling HTN. In addition, since HTN is affected by cultural, social, and economic factors, it is necessary to conduct some studies in other countries, especially in cohort format, to investigate the prevalence as well as hazardous factors of HTN.


High blood pressure is the leading modifiable risk factor for cardiovascular disease, and is associated with high morbidity and mortality and with significant health care costs for individuals and society. However, fewer than half of the patients with hypertension receiving pharmacological treatment have adequate blood pressure control. The main reasons for this are therapeutic inertia, lack of adherence to treatment, and unhealthy lifestyle . Cardiovascular risk and mortality are greater in hypertensive patients who are receiving treatment but have suboptimal control of blood pressure.This is a multicentre, parallel, 2-arm, single-blind (outcome assessor), controled, cluster-randomized clinical trial. General practitioners and nurses will be randomly allocated to the intervention group  or the control group . A total of 424 patients in primary care centers who use 2 or more antihypertensive drugs and blood pressure of at least 130/80 during 24-hambulatory blood pressure monitoring will be recruited. The primary outcome is systolic blood pressure at 12 months. The secondary outcomes are blood pressure control (<140/90 mm Hg); quality of life (EuroQol 5D); direct health care costs; adherence to use of antihypertensive medication; and cardiovascular risk .This trial will be conducted in the primary care setting and will evaluate the impact of a multifactorial intervention consisting of self-management of blood pressure, antihypertensive medications, and lifestyle modifications . Thus, new approaches must be developed that provide better management of high BP.Control of hypertension is a major challenge in primary health care, the setting where most such patients are diagnosed and treated. Hypertension has a high prevalence, but only about 45% of patients with hypertension achieve adequate blood pressure (BP) control.,2 It causes considerable morbidity and mortality because it increases the risk of myocardial infarction, stroke, kidney damage, and micro- and macro-vascular diseases. The main factors that prevent adequate BP control are therapeutic inertia (use of incorrect dosages and/oran inadequate combination of drugs), poor adherence to treatment, unhealthy lifestyle , and prescription of drug that induced hypertension , steroids, nasal decongestants, antidepressants, and oral contraceptives).Hypertension is the main treatable cardiovascular risk factor. and to improve adherence, several drugs should be combined in a single tablet.Many drugs are currently available for reducing BP, and a common strategy is to prescribe a combination of drugs that have different mechanisms of action, with optimization of the dosage of each drug. The optimal dose may be initially considered as 50% or more of the maximum tolerated dose (MTD) and the European Society of Hypertension (ESH/European Society of Cardiology (ESC) recommend the following nonpharmacological interventions for the control of high BP: restricted intake of salt and alcohol, weight loss, intensification of physical activity with a structured exercise program, use of the Dietary Approaches to Stop Hypertension (DASH) diet, high intake of fruit and vegetables, and potassium supplementation. Physical activity is also useful for the prevention, treatment, and control of hypertension, and several metanalyzes of randomized clinical trials showed that aerobic exercise can reduce BP. However, it is crucial to specify the frequency, intensity, time, and type (FITT) of exercise regimens.,11 Other studies support use of the DASH diet for lowering BP. This diet is rich in fruit, vegetables, fiber, and potassium, and has minimal fat and sodium.The most recent guidelines of the American College of Cardiology (ACC)/American Heart Association (AHA) In general, a patients awareness of the need for self-management can make a real difference in the control of a chronic condition. BP self-monitoring (BPSM) might close the gap between the doctors and patients expectations, lead to effective self-management, and enable the patient to play a greater role in managing the condition.In addition to pharmacological and nonpharmacological measures, new patient-centered initiatives are now considered essential for the control of hypertension. There is evidence that a patients self-management of a chronic disease can increase motivation, understanding and skills, quality of life, clinical outcomes, and the efficient use of resources.,17 which consisted of self-monitoring, self-management, and tele-monitoring of BP measurements, concluded that self-management significantly contributed to the control of hypertension in a primary care setting.Self-management of BP consists of starting or increasing the dosage of a medicine, based on agreement of the doctor and patient and in accordance with measurements from BPSM. The TASMINH and TASMIN-SR trials,Approximately, half of the patients treated for high BP do not achieve successful control of hypertension. Overall, patients with high BP constitute a heterogeneous group, and include undiagnosed secondary hypertension, undertreated patients, and patients whose treatment was not successful. Patients with uncontrolled hypertension have a higher cardiovascular risk (CVR), and thus require a more comprehensive approach to treatment. Self-management of medications that is based on self-monitoring can play a significant role, and has generated significant interest among researchers.The aim of this trial is to analyze the effectiveness of a comprehensive intervention, consisting of self-management and self-monitoring of hypertension, lifestyle modifications, and optimization of pharmacotherapy, on the control of BP in patients receiving 2 or more antihypertensive drugs.1.11.1.1To analyze the effectiveness of a multifactorial intervention consisting of optimized pharmacotherapy, BP self-monitoring, self-management of antihypertensive medications, and intensive changes in lifestyle, on the reduction of systolic BP at 12 months in patients with uncontrolled hypertension who were initially receiving 2 or more antihypertensive drugs.1.1.21.To analyze the effectiveness of the proposed intervention on:1.Achieving adequate systolic and diastolic BP values (<140/90 mm Hg) after 12 months.2.Quality of life, as measured by a validated Spanish language version of the EuroQol-5D.3.Reduction of baseline CVR by 10% or more when the baseline risk was low/moderate and by 25% or more when the baseline risk was high/very high.4.Adherence to the antihypertensive medication regimen, based on the registry in the prescription section of the electronic medical record of the patient (Medication Possession Ratio).5.Body mass index (BMI) and physical activity, as determined by the International Physical activity Questionnaire (IPAQ).6.Patient safety, in terms of hypertensive crises, number of hypotensive episodes that required an emergency department visit, and adverse effects associated with medications.7.Feasibility, acceptability, adherence, and fidelity of the intervention.22.1This is a multicenter, parallel, 2-arm, single-blind, cluster-randomized clinical trial. with pharmacological and non-pharmacological measures according to the 2018 ESC/ESH Guidelines for the Management of Arterial Hypertension.Fig. The control group will receive regular clinical care according to recommendations for treatment intensification by the Eighth Joint National Committee,2.22.2.11.Hypertensive patients aged 35 to 75.2.Use of 2 or more antihypertensive drugs.3.BP of 130/80 mm Hg or more during 24-hambulatory monitoring.4.Written informed consent.2.2.21.Dialysis or diagnosis of kidney failure.2.Myocardial infarction, coronary bypass surgery or coronary angioplasty, stroke, peripheral arterial disease, heart failure, advanced liver disease, or atrial fibrillation.3.Unable or unwilling to sign the informed consent document.4.Alzheimer disease, advanced dementia or life expectancy less than the follow up duration of the study.5.Indefinite institutionalization in a nursing home.6.Long-term treatment with corticosteroids.7.Secondary hypertension.8.2).Impaired kidney function based on albuminuria (>300 mg/24 h)or estimated glomerular filtration rate , where m is the mean number of observations per cluster and p is the intraclass correlation coefficient. Each participating GP will have approximately 10 patients, the expected intraclass correlation coefficient between clusters is 0.04, and the cluster design effect is 1.20. Consequently, the final target sample size is 424 patients (212 in each arm).Sample size calculation, based on a reduction of the SBP of at least 5 mm Hg (SD: 17 mm Hg) between groups, led to an initial estimate of 177 patients per group. Next, correction was applied for correlation among patients within clusters using the inflation factor 1 + 2.6GPs cannot be blinded to the intervention that seeks to modify their clinical practice, nor the researchers be blinded to the allocation of the GPs. However, the outcome assessor and the data analyst will be blinded to patient allocation.2.7Patients with GPs in the intervention group will receive a multifactorial intervention consisting of changes in diet, physical exercise, self-measurement of BP, and self-titration of antihypertensive medications. An educational session conducted by a nurse will teach patients to use a sphygmomanometer and step counter. A second session will provide information on diet and exercise.a)Diet: Patients will be asked to follow the DASH diet and to attend a workshop session that will be used to motivate them to adopt this diet. Patients will also learn about reading the labels of food products and consuming adequate portions of each food group.b) If the exercise is walking or running, patients will receive a step counter. Risks associated with physical activity will be evaluated and progressive training will be prescribed, considering heartbeat, distance, steps walked, and time. Study participants will report their subjective degree of fatigue following physical activity.Physical exercise: Moderate aerobic exercise will be prescribed according to the patient's condition. Generally, moderate exercise for 50 to 60 minutes on 5 to 7 days a week will be recommended.c)Self-measurement of BP: Patients will receive a BP monitor and will be trained in its use. They will measure BP 3 times in the morning and 3 times in the afternoon during the first and third weeks of each month throughout the 12-month study. Patients will be asked to record their weekly average BP in a table. The patients will also record the use of all medications.d)Self-titration of antihypertensive medications: Self-adjustment of medications will be performed according to the following algorithm:1.For patients with uncontrolled hypertension receiving 2 antihypertensive drugsa)First Step: Check that the combination of 2 drugs includes 1 Angiotensin-converting-enzyme (ACE) inhibitor or Angiotensin II Receptor Blockers(ARB) + 1 thiazide (hydrochlorothiazide) or a thiazide-like diuretic , or 1 CCB . An exception is made if there is a specific reason to use another type of hypertensive drug (such as a beta blocker) due to angina, heart failure, myocardial infarction, control of heart rate, or attempting pregnancy. The dosage of each drug must be at least 50% of the MRD and the drugs should be administered as a single pill when possible.b)Second Step: Add a third drug to the previous combination, with the resulting combination including and ACE inhibitor (or ARB) + CCB + thiazide or a thiazide-like diuretic. This third drug is added at half the standard dose.c)Third Step: In patients with no hyperuricemia or diabetes, start increasing the dose of the diuretic up to 100% of the MRD. In patients with hyperuricemia or diabetes, the first medicine to be increased is the ACE inhibitor or ARB.d)Fourth Step: In patients over 60 years-old, the CCB is the second drug whose dose is increased. In patients under 60 years-old, the ACE inhibitor or ARB is the second drugs whose dose is increased.e)Fifth Step: The third drug whose dose is increased is the remaining drug .f)Sixth Step: When 3 drugs were each increased to the optimal dose and hypertension is still uncontrolled, 25 mg of spironolactone is added.2.For patients with uncontrolled hypertension receiving 3 antihypertensive drugsa)First Step: Check that the 3 drugs are an ACE inhibitor (or ARB) + CCB + thiazide (hydrochlorothiazide) or a thiazide-like diuretic . An exception is made for patients who receive specific treatments due to other diseases.b)Second Step: Increase the dose of each drug to at least 50% of the MTD, 1 drug at a time.c)Third Step: Apply the same rule described for patients receiving 2 antihypertensive drugs. In both cases, each increase of dosage occurs in intervals of 4 to 6 weeks.d)Patients whose GPs are in the control group will receive standard care for hypertension.2.8BP will be measured with the patient sitting, using a standardized automated sphygmomanometer (OMROM 7 intelli IT) and after a 5-minrest period. Three readings will be taken 2 minutes apart, and the average of the last 2 will be recorded. The cuff will be adjusted according to the perimeter of the arm and placed on the middle third of the upper arm. The patient will be comfortably seated, without crossing the legs, and with the arm resting on a table and placed at the level of the heart. The patient should be relaxed, have an empty urinary bladder, and have no recent smoking or ingestion of stimulating substances.2.92.9.1The primary outcome measure is the systolic BP at 12 months, measured according to ESH/ESC guidelines. Prior to measurements, patients will be instructed to not eat or smoke for 30 minutes and to sit quietly with the back supported and feet on the floor for 5 minutes. An oscillometric BP monitor (OMROM 7 intelli IT) will be used for 3 measurements using an appropriately sized cuff and with support of the bare arm.2.9.2The secondary outcomes are:1.adequate BP control (<140/90 mm Hg) after 12 months;2. measured with the EQ-5D, which has good validity and reliability for individuals with various health conditions and includes 5 dimensions  and a visual analogue scale (VAS) used by patients to report their perceived health status;quality of life,3. in which differences are defined as changes in the moderate SCORE values and high SCORE values that reduced their risk of a coronary event by 10% and 25%, respectively;clinically relevant changes in cardiovascular risk from baseline to 12 months, based on the REGICOR scale,4.adherence to the hypertensive medications, based on the Medication Possession Ratio (MPR) at 12 months;5.BMI at 6 and 12 months;6. at baseline and 12 months.physical exercise, measured with the International Physical Activity Questionnaire (IPAQ)2.9.3All serious adverse events, such as hypotension, syncope, bradycardia, electrolyte abnormality, fall, acute kidney injury, or acute renal failure, that are possibly related to the use of antihypertensive drugs will be monitored.2.9.4Estimated effects will be calculated by comparing the systolic BP (mm Hg) in the intervention and control groups at 12 months. Generalized mixed linear random effect models will be used to account for clustering at the level of GP, with adjustment for the baseline values. Subgroup analyses of effectiveness will be performed for the following patient groups: with vs. without diabetes mellitus; with moderate vs high cardiovascular risk; with vs without adherence to antihypertensive medications; and males vs females. The significance of differences in the baseline characteristics of the control and intervention groups will be analyzed using descriptive analysis and will include calculation of means and/or proportions with confidence intervals, and of standard deviations (to account for clustering).All analyses will be performed on an intention-to-treat (ITT) basis  and results will be reported according to the 2010 CONSORT guidelines.The relative and absolute risk reduction and number needed to treat (NNT) to prevent one patient from having uncontrolled hypertension (SBP≥140 or DBP ≥90) will be estimated. All estimates will include 95% confidence intervals. The NNT will be calculated as the reciprocal of the difference between the proportion of patients with BP control in the intervention and control arms.1 – CT) divided by difference in the mean effects of the 2 groups (E1 – ET): The health economic analysis will be performed by calculating the incremental cost-effectiveness ratio (ICER) at 12 months. Data will be systematically collected on the use of all resources, including inpatient care, consultations with health care providers, use of drugs, and laboratory tests. To measure these effects, EQ-5D scores will be used, and quality-adjusted life years (QALYs) will be determined. The ICER will be calculated as the difference in the mean costs of the 2 groups , heart failure, and hypertension, and found that clinical improvement and better disease control occur when patients develop the skills needed to manage their conditions.Medical self-management requires patients to develop specific preventive, management, and therapeutic skills. In particular, our intervention includes follow-up and management of signs and symptoms; education regarding drug dosage; changes in lifestyle; and maintaining regular contact with primary health care professionals for shared decision-making.Our intervention follows procedures used in previous medical self-management programs.It is particularly important to develop new and effective interventions for patients with uncontrolled hypertension, because these individuals have higher morbidity and mortality rates than patients with controlled hypertension. The participation of patients in management of their own hypertension adds a new dimension to the treatment of this condition. Our intervention, which is comprehensive and implemented in the primary care setting, consists of optimization of pharmacological treatment through self-monitoring and self-management of antihypertensive medications and encouraging patients to adopt healthier lifestyles, including intensification of physical activity and adopting the DASH diet.This study aims to improve the management of hypertension and addresses pharmacological and non-pharmacological measures that can be used to achieve this goal. The researchers are committed to implementing the intervention, advancing the understanding of this disease, and engaging the patients in the management of their hypertension.This protocol will provide new data on the use of a comprehensive approach in the primary care setting to control arterial hypertension.The authors would like to thank Begoña Enseñat, Encarnación Villegas, Paloma Diaz, Adelaida Coll, the Son Espases Hospital Clinical Laboratory and Biobanco IdISBa for organize the extraction, collection and conservation of the blood samples of patients. The authors would also like to thank Sebastià Mesquida for searching the eligible patients and theparticipant GPs of the study for recruitment, collecting data and delivering the interventions.FU, FR, JLlC, PLM and ALR are responsible for the original idea and design of the intervention; PLM, ARH, AEM, TRR and MLMS developed the educational material for the study; FUV, JPB, TRR, FRC, PDF, PBF and PLM contacted GPs and nurses in the primary care centres; FUV, PBF, JLC and ALR drafted the manuscript; AL, JLC, and MTQ are responsible for the management of the trial, data analysis and interpretation; BOO will organise the ABPM for the study patients and coordinate with the health centres. All authors  read the draft critically, made contributions, and approved the final manuscript. FU is the principal investigator, had full access to all data and takes responsibility for the integrity of the data and the accuracy of the data analysis.Alfonso Leiva orcid: 0000-0001-5306-8533.


For infants undergoing complex cardiac surgery, hemodynamic management after cardiopulmonary bypass (CPB) is challenging because of severe myocardial edema, vasomotor dysfunction and weak tolerance to a change in blood volume. More importantly, the lack of availability of equipment for advanced monitoring, such as transesophageal echocardiography or transthoracic echocardiography, restricts the accurate assessment of hemodynamics.2) after CPB in a low-weight infant who had normal blood pressure and oxygen saturation before surgery. Epinephrine and milrinone were administered with cerebral oximetry monitoring rather than blood pressure measurements because cerebral oximetry was more responsive to treatment than blood pressure. Under the guidance of cerebral oximetry, the infant was successfully weaned from CPB and recovered after surgery without adverse neurological events.This is a case of severe hypotension and non-detectable pulse oxygen saturation (SpO2 monitoring during the CPB weaning period, cerebral oximetry provides an index for assessing brain perfusion and valuable guidance for appropriate inotropic treatment.For infants who develop refractory hypotension and failure in SpO For an infant undergoing complex cardiac surgery, hemodynamic management after cardiopulmonary bypass (CPB) is challenging because of severe myocardial edema, vasomotor dysfunction and weak tolerance to a change in blood volume . More imA female infant aged 2 months, weight 2.7 kg, height 50 cm, diagnosed with ventricular septal defect (VSD), atrial septal defect (ASD) and severe pulmonary hypertension was scheduled for VSD repair under CPB. The preoperative TTE examination revealed a VSD of 9 mm and an ASD of 8 mm. The past medical or family history was unremarkable.2) 39.5 mmHg, oxygen partial pressure (PO2) 218.8 mmHg and haemoglobin 82.4 g/L. TEE monitoring was not performed due to no available probe for an individual weighing less than 3 kg. Arterial blood pressure was 64/40 mmHg, and the SpO2 signal was good and the reading was 100% prior to surgery. Anesthesia and surgical repair were performed routinely. The operative site was exposed via a median sternotomy, then CPB was built successfully after injection of 1125 U heparin and cannulation at the aorta root, superior vena cava and inferior vena cava, with infusion of cardioplegia solution containing potassium. The core body temperature was maintained at 32 ~ 33 °C during CPB. The ASD and VSD were patched during 88 min of aortic cross-clamp period. The results of arterial or venous blood gas analysis during surgery are shown in Supplementary file Table .General anesthesia was induced by 0.5 mg midazolam, 5 μg fentanyl, 5 mg rocuronium and 7% sevoflurane. An endotracheal tube with an inner diameter of 3 mm was intubated using direct laryngoscope. After tracheal intubation, the infant was ventilated to normocapnia with an inspired oxygen fraction 0.5 by a fresh gas flow of 2 L/min of oxygen and air. Anesthesia was maintained with sevoflurane inhalation, intravenous infusion of remifentanil and injection of fentanyl and rocuronium as required. Invasive arterial blood pressure was continuously monitored through the left radial artery. The patient had a 5F double-lumen catheter placed in the right internal jugular vein for central venous pressure monitoring and medication. The arterial blood gas analysis after intubation (before surgery) was: pH 7.34, carbon dioxide partial pressure , but no significant increase in blood pressure occurred. A systolic blood pressure below 50 mmHg is insufficient for satisfactory perfusion of body organs. As CPB had been completed and the aortic cannula removed, pressure detection at aortic root was not performed. Cerebral oximetry  was applied to the left side to evaluate cerebral perfusion and revealed a cerebral tissue oxygen saturation (SctO2) of 35.7%.After the aortic clamp was released, sinus rhythm was restored spontaneously at a rate of 120 to 130 beats per minute and the electrocardiogram showed ST segment elevation. Intravenous infusions of epinephrine and nitroglycerin were administered at a dose of 0.05 μg/(kg·min) and 0.5 μg/(kg·min), respectively. When bypass withdrawal was attempted, sustained hypotension and low saturation of blood oxygen occurred. The systolic blood pressure ranged between 40 ~ 50 mmHg and a SpO2, poor cardiac output was considered as the likely cause. Therefore, the rate of epinephrine infusion was increased to 0.12 μg/(kg.min) and milrinone was infused intravenously at a rate of 1 μg/(kg.min). After 20 min of inotropic treatment, the SctO2 increased gradually from 35.7 to 61%, and photoplethysmography measurements from the finger and ear were now detectable and SpO2 increased to 98%, but notably without a significant increase in blood pressure. Given the acceptable cerebral tissue oxygen saturation and SpO2, no further treatment was performed to increase blood pressure. When the infant transferred to the pediatric intensive care unit, the SctO2 was about 56%, with a SpO2 of 99% and arterial blood pressure 48/29 mmHg. Epinephrine was infused at a rate of 0.1 μg/(kg.min) and milrinone at 0.5 μg/(kg.min). Arterial blood pressure, SpO2 and SctO2 readings are shown in Fig. Given the low blood pressure, low arterial blood oxygen saturation, and the low SctO2 or TEE assisted hemodynamic measurements in an infant who developed a severe low blood pressure. Even though little increase of blood pressure occurred after treatment with a high dose of epinephrine and milrinone, an acceptable level of SctO2 was achieved. After delayed sternal closure, the infant was discharged from hospital without any discernible neurological complications. This case, which integrated the practical use of cerebral oximetry, raised several important issues worthy of discussion.In this report, we have described a case of cerebral oximetry measurements during CPB weaning and the medication administered without available SpO2 monitoring has been widely used to estimate the balance between oxygen supply and consumption in cerebral tissue to a depth of about 15 mm [2 is associated with postoperative cerebral injury, neurocognitive dysfunction, a prolonged hospital stay and increased cost [Cerebral tissue is highly vulnerable during CPB for its weak tolerance to hypoxia, even for a short period of time. Thus, cerebral injury is a common complication after cardiac surgery , 4. As ased cost .2 and hemoglobin levels, are commonly used to augment cerebral oxygen supply. In addition, intravenous anesthesia, hypothermia or anti-epileptic medication, are also options to decrease oxygen consumption of cerebral tissue [The value of SctO2 is determined by two main factors, oxygen supply and oxygen consumption . Changesl tissue , 6, 8.2. Given the severe myocardial edema, the reduction in blood pressure and SpO2 was mainly interpreted as being caused by a decrease in cardiac output. Therefore, epinephrine was first administrated, but had little effect on blood pressure [2 monitoring, 0.5–1 μg/kg milrinone was administered tentatively to increase cardiac output. Even though the blood pressure remained low after treatment, the SctO2 value was significantly increased.In the present case, the depth of anesthesia and the head position was unremarkable. Severe hypotension and myocardial edema were the main manifestations after CPD, accompanied by systemic hypoxia and a low SctOpressure . Due to 2. Holmgaard et al., reported that at a fixed cardiopulmonary bypass pump flow rate of 2.4 L/min/m2, targeting a high MAP (70–80 mmHg) by norepinephrine produced more frequent and pronounced cerebral desaturation than a low MAP (40–50 mmHg) during bypass [2 level remains to be debated. Several studies have also shown the discrepancy in the effects of epinephrine and other vasoconstrictors such as phenylephrine on SctO2 [2 in the present case, the controversy remains to be resolved.It is likely that low blood pressure is an important cause of poor cerebral perfusion, based on the formula: cerebral perfusion pressure = mean blood pressure - intracerebral pressure. Increasing blood pressure is listed as the first parameter to consider for cerebral desaturation by proposed algorithms . Howeverg bypass . Similarg bypass , 12. Theon SctO2 , 14. Eve2 was not measured before anesthesia or surgery, the normal range or target of therapy for this infant was unclear. Multiple studies have been conducted to determine the normal range of SctO2 [2 ranged from 56 to 82% with a median of 73%, which was affected by the hemoglobin concentration [2 changes referring to baseline rather than absolute values are preferred in clinical practice or research studies [2, shown by the parallel increase in SctO2 and SpO2. But it should be noted that a large discrepancy between SctO2 and somatic tissue oxygen saturation was demonstrated in previous studies in adult surgical patients [However, because the baseline level of SctOof SctO2 , 16. Kusntration . Nonethe studies , 18. Furpatients .2 monitoring failure, cerebral oximetry is applicable for evaluating and directing hemodynamic management. Appropriate treatment is based on meticulous analysis among the variables of blood volume, cardiac function, mean blood pressure, hypoxia, anemia, and so on. A further study will be necessary to evaluate the effects vasoconstrictor-induced increase in blood pressure on SctO2 and the underlying mechanisms.In conclusion, for an infant with difficult CPB weaning, especially one with a low cardiac output resulting in SpOAdditional file 1: Table S1. Measurements of arterial blood pressure, SpO2 and SctO2, also shown in Fig. Additional file 2: Table S2. Results of blood gas analysis during surgery. 08:12 anesthesia induced; 09:40 surgery started; 10:28 CPB started; 10:43 aorta cross-clamped; 12:11 aorta clamp released; 12:50 CPB ended; 15:25 surgery ended. A, arterial blood; V, venous blood.


Pelvic and lower junctional hemorrhage result in a significant amount of trauma related deaths in military and rural civilian environments. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infra-renal (zone 3) Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) are two options for resuscitation of patients with life threatening blood loss from and distal to the pelvis. Evidence suggest differences in the hemodynamic response between AAJT and zone 3 REBOA, but fluid management during resuscitation with the devices has not been fully elucidated. We compared crystalloid fluid requirements (Ringer’s acetate) between these devices to maintain a carotid mean arterial pressure (MAP) > 60 mmHg.n = 6) or zone 3 REBOA (n = 6) were then applied for 240 min. Crystalloid fluids were administered to maintain carotid MAP. The animals were monitored for 30 min after reperfusion.60 kg anesthetized and mechanically ventilated male pigs were subjected to a mean 1030 (range 900–1246) mL  haemorrhage. AAJT  in zone 3 REBOA  compared to AAJT  to maintain target carotid MAP. Release of the AAJT required vasopressor support with norepinephrine infusion for a mean 9.6 min (0.1 µg/kg/min), while REBOA release required no vasopressor support.Zone 3 REBOA required 7.2 times more crystalloids to maintain the targeted MAP. The AAJT may therefore be considered in a situation of hemorrhagic shock to limit the need for crystalloid infusions, although removal of the AAJT caused more severe hemodynamic and metabolic effects which required vasopressor support. Trauma is a major global health issue contributing to about 10% of overall mortality and an annual worldwide death of more than 5.8 million people . HemorrhResuscitative endovascular balloon occlusion of the aorta (REBOA) and the Abdominal Aortic and Junctional Tourniquet (AAJT) are devices with the potential to control hemorrhage from the lower body including the pelvis by closing off arterial inflow –10. OcclA recent animal study described improved blood pressure support when resuscitating with whole blood and fresh frozen plasma compared to crystalloids when comparing the AAJT and REBOA in a pooled group. The AAJT and REBOA animals did not differ in hemodynamics, metabolic responses or survival . In contA large volume of crystalloids is an independent factor for increased morbidity and mortality in trauma patients. Fluid resuscitation of patients with impending or manifest hemorrhagic shock should replace sufficient blood volume to maintain cardiac output and end-organ perfusion while preserving blood coagulation and oxygenation. Crystalloids address the first of these parameters while having a negative impact on coagulation and oxygen transportation , 18. No This study was approved and conducted in accordance with the Swedish regional ethics approval board for animal research S3-15), and included four phases: animal preparation, hemorrhage, intervention (AAJT or zone 3 REBOA) and reperfusion  was adjusted to PaCO2 4.7–5.5 kPa. Initial ventilator settings were: inspiratory oxygen fraction 21%; peak inspiratory pressure 16 cm H2O and peak expiratory end pressure 4 cm H2O. Anesthesia was maintained by continuous infusion of ketamine 25 mg/kg/h (Ketaminol Vet 100 mg/ml), midazolam 0, 0485 mg/kg/h (Midazolam Hameln 1 mg/ml) and fentanyl 3.5 µg/kg/h (Fentanyl B. Braun 50 µg/ml). A fluid bolus of 500 ml Ringer’s acetate was given after induction of anesthesia to adjust baseline fluid-balance discrepancies and then continuously throughout the experiments with 3 ml/kg/h to replace insensible losses.Castrated, crossbred male pigs (54–65 kg) were pre-medicated with 150 mg tiletamine/zolazepam (Zoletil 100 Vet) and 6 mg medetomidine (Domitor) and placed supine on a standard operating table. 100% O2). The left carotid artery was surgically exposed and used for hemorrhage, hemodynamic monitoring and collection of blood samples. A suprapubic urine catheter and 12 EKG electrodes were placed to monitor heart rate, the occurrence of arrhythmias and to verify euthanasia. The AAJT was pre-positioned and left in place unbuckled. In the REBOA animals, a 7F introducer  was placed via the femoral artery using Seldinger-technique.A 7.5 F Swan-Ganz pulmonary artery catheter (Edwards Lifescience) was introduced in the surgically exposed right external jugular vein and used for core temperature, cardiac output (CO) and mixed venous oxygen saturation  or zone 3 REBOA . After completion of hemorrhage the AAJT was inflated (300 mmHg) or a 15 mm balloon  was positioned in the infra-renal aorta guided by anatomical measurement on the skin from the site of vascular access to aortic bifurcation before insertion and inflated with 8 ml NaCl. We have verified anatomical measurement as a robust method of estimating the level of the balloon in our earlier experimental series [0 was defined as when the AAJT or REBOA balloon was fully inflated. Complete data collection started at T0. Total occlusion of aortic blood flow was verified by loss of a pulse wave and no blood flow in a percutaneous arterial catheter placed distally to the devices, non-measurable noninvasive blood pressure on the hind leg, non-measurable heart rate (HR) and pulse-oximetry from the tail probe.Animals were assigned to groups AAJT application . Standard deviations were calculated from pilot studies. For five animals in the AAJT group, a secondary analysis of previously published data was performed [Hemodynamic performance and fluid administration were continuously registered and arterial blood gases and hemoglobin were collected. Arterial pressure was measured between 0–200 mm Hg and monitored as maximum (systolic), mean  and minimum (diastolic). The following calculations were used for hemodynamic parameters: Stroke volume (SV) = CO/HR, SVR = 80 × (MAP−CVP)/CO . Primaryp < 0.05 was considered significant. All data are expressed as mean ± SD. Two-way ANOVAs with multiple comparisons tests were used for iv fluids, hemorrhage volume, hemodynamic- and metabolic parameters. Student’s unpaired t-test was used for norepinephrine.All statistical analyses were made by GraphPad Prism version 7.03 for Windows (GraphPad Software). Baseline characteristics displayed differences for MAP which was higher in the AAJT group and heart rate which was higher in the REBOA group Table . Average20 in the AAJT and T40 in the REBOA group , the framework for ethical animal research. However, as a consequence, the short observation time after reperfusion was also a major limitation. A longer intensive care phase would allow for assessments of organ function and general physiologic consequences including inflammation, coagulation and renal failure. The increased vasopressor need after removal of the AAJT is likely caused by redistribution of blood from the ischemic vasculature distal to the AAJT together with a reperfusion injury with ensuing inflammatory response and capillary leakage. It is unclear how and to what extent these mechanisms contribute, and an assessment would require a longer follow-up, which would also allow for investigations of postoperative fluid management. Future studies should therefore include a longer reperfusion phase, covering the first 24 h.2 within a normal range, and adjustments in ventilatory pressures were made accordingly. Future studies may investigate CVP in relation to the devices in spontaneous ventilation. Finally, the positive pressure mechanical ventilation was also a limitation since the effect on cardiac preload possibly differs between the interventions. Future studies may compare the impact of positive pressure ventilation and spontaneous ventilation when applying AAJT and zone 3 REBOA.We did not assess central venous pressure (CVP). To correctly assess the central venous blood volume indicated by CVP, the intra-thoracic pressure from positive pressure ventilation should have been equal between groups. The AAJT applies pressure towards the diaphragm causing higher ventilator pressures to maintain adequate tidal volumes and gas exchange in the lungs, which is why CVP likely was related to ventilatory pressures. In this study, the animals were mechanically ventilated to maintain etCOZone 3 REBOA required 7.2 times more crystalloids to maintain the targeted MAP. The AAJT may therefore be considered in a situation of hemorrhagic shock to limit the need for crystalloid infusions, although removal of the AAJT caused more severe hemodynamic and metabolic effects which required vasopressor support.


Patients with fibromyalgia syndrome (FMS) have a nonspecific postural balance disorder and a greater prevalence of falls. Objective: to clarify which aspects of maintaining balance are associated with the impact of the disorder and with balance confidence. Methods: A total of 182 persons with FMS agreed to participate in this study. After re-evaluation, 57 fully met inclusion criteria: age 40–70 years and moderate-severe impact of the illness according to the Fibromyalgia Impact Questionnaire (FIQ). All participants underwent a posture control analysis with a stabilometric platform, an evaluation of the perception of verticality and an exploration of the vestibular system via functional tests. Additionally, they self-completed questionnaires about balance confidence, central sensitization, pain catastrophizing, kinesiophobia, dizziness and days with episodes of instability. Results: The FIQ was associated with central sensitization and dizziness, which explained 56% of its variance (AdjR2 = 0.566), while days with instability, kinesiophobia and dizziness also explained more than half of the variance of the balance confidence scale (AdjR2 = 0.527). A high percentage of positive responses was found for functional tests (>50%) and a high dispersion in the stabilometric parameters. Conclusion: the detection of factors susceptible to intervention, such as disability due to dizziness, takes on special relevance in patients with FMS. Fibromyalgia syndrome (FMS) is a disorder principally characterized by chronic generalized pain, with increased sensitivity to pain with a low pain threshold, which is normally accompanied by non-restorative sleep, tiredness, rigidity, instability, cognitive difficulties, and mood disorders . FMS affRecent studies have shown that patients with FMS present with a nonspecific postural balance disorder and an increased prevalence of falls . The magThe uncertainty of balance tests has hampered the finding of a characteristic dysfunctional pattern for this pathology. The scarce data are unclear, however, appear to suggest that these patients present with poor integration of visual and vestibular afferents with a sensorimotor preference when balancing, causing a deficient balance system ,8,9. TheFalls prevention requires multiple rapid automatic corrections coordinated by the central nervous system; a process that appears to be affected in fibromyalgia . No consSome studies have found an association between disability and worse scores on different balance assessments in patients with FMS ,5,8. NevThis study aimed to clarify which variables, among functional balance tests, stabilometry and perception of verticality variables and central sensitization, pain catastrophizing, kinesiophobia and disability due to dizziness are related to the impact of the disease—the severity of symptoms measured with the fibromyalgia impact questionnaire (FIQ)—and with the confidence of these patients in their own stability measured with the activities-specific balance confidence (ABC) scale.An observational descriptive cross-sectional study was conducted in a sample of patients diagnosed with FMS who were recruited from the Fibromyalgia Association of Jaen city (AFIXA) from January to May 2019. Telephone contact was made with 264 possible participants who received detailed information regarding the study; of these, 182 agreed to participate. An in-person interview at the association was organized with each and they were re-evaluated to confirm that they met the inclusion criteria: aged 40–70 years, fully met the diagnostic criteria for fibromyalgia as described by the 2016 American College of Rheumatology (ACR), moderate to severe impact on quality of life, at the time of the interview, according to the categories described by the FIQ with a score equal to or greater than 50. Exclusion criteria were as follows: (a) cognitive impairment impacting ability to fill out the scales and questionnaires, (b) musculoskeletal surgical intervention in the preceding six months and/or acute traumatic pathology to the inferior limb(s), (c) musculoskeletal disease with deformity of the inferior limbs, (d) diagnosed with vestibular, visual and/or auditory pathology, and (e) neurologic illness that could be the cause of a balance disorder. A total of 70 participants met all the criteria, presenting with a moderate/severe limitation in quality of life at the time of inclusion, and a final 57 persons completed the whole study protocol. A flowchart showing the selection of participants in presented in The research protocol was approved by the Ethics committee of the University of Jaen and was designed and conducted in accordance with the Ethics code of the World Medical Association for studies including human participants (Declaration of Helsinki). All participants were provided with written informed consent to obtain voluntary agreement to participate in the study.All participants were given a dossier of self-administered questionnaires. An examination of the vestibular system was performed based on a battery of functional tests, along with a stabilometric analysis, and an evaluation of the perception of verticality using a virtual reality system. Data collection was carried out on the premises of the University of Jaen.Demographic and anthropometric data such as sex, age, education level, occupation, civil status, height, weight, body mass index (BMI) were collected by well-trained interviewers.The impact of the disease and disability of the symptoms was measured with the FIQ  and consBalance confidence was recorded using thectivities-specific balance confidence scale (ABC-16) . This isThe variable “number of days with episodes of instability” was recorded by an experienced researcher, who asked participants to answer the following question: “How many days of the last week have you suffered episodes of instability?”, understanding these episodes, such as those situations where some of the following symptoms occur: sensation of movement or spinning (vertigo), feeling of lightheadedness or fainting (presyncope), sensation of insecurity when walking, feeling of floating or dizziness, changes in vision, blurred vision or disorientation. Response options range from zero (no day of the week) to seven (every day of the week). The conceptualization of episodes of instability was described by Horak .The presence of central sensitization was measured with the central sensitization inventory (CSI) . The CSITo assess pain catastrophizing the pain catastrophizing scale (PCS) was used . The PCSThe fear of movement was measured with the Tampa scale for kinesiophobia (TSK) . The TSKTo evaluate disability due to vertigo the dizziness handicap inventory (DHI) was used . This isThe perception of verticality was measured using the subjective visual vertical (SVV) test using a virtual reality device . The SVVTo record static balance the Romberg test was done on a stabilometric platform with pressure resistant sensors  with a 400 x 400 mm surface and an acquisition frequency of 30Hz with FreeStep© Standard 3.0 software . Using this system, displacement of the center of pressure (CoP) is detected, similar to the center of gravity, in different situations of sensorial conflict . This postural evaluation test was conducted using the same methodology used in other studies . The patIn terms of the functional evaluation of static and dynamic balance and neuromotor function, 7 function tests were conducted which assessed the function of the different structures and systems involved in postural control. These tests are classified in 3 analysis subscales: (a) standing balance/static balance: assessed with the Romberg test, sensitized Romberg test , and theContinuous variables were described using means and standard deviations, whereas the categorical variables were described using frequencies and percentages. The Kolmogorov–Smirnov test was used to verify normal distribution of the continuous variables. The possible associations between different study variables were explored via bivariate analyses, using Pearson’s correlation for continuous variables and T-student for categorical variables. Variables with a significant association and showing a greater degree of association in the bivariate analysis were introduced stepwise into a multiple linear regression model for each of the study variables. The criteria to keep a variable in the multivariate model was obtaining a p < 0.05, and for its exclusion a p > 0.10. To calculate the effect size the coefficient of multiple correlation, R, was used. To measure the percentage of the variance predicted by the multiple regression model, the corrected or adjusted R2 was used. According to Cohen , R2 can Data handling and analysis were conducted using the statistical package for social sciences (SPSS) version 21 . A level of confidence of 95% was used (p < 0.05). . The sample had a mean age of 55.56 years (SD = 7.97) and a mean BMI of 28.68 kg/m2 (SD = 5.26), indicating overweight. Ninety-three percent were women and seven percent men. No association was found between these characteristics of the sample and the study variables. Fifty-seven patients met the inclusion criteria and completed all the planned study tests. The sociodemographic and most relevant clinical factors of the study sample are presented in Table 1The impact of fibromyalgia as measured with the FIQ questionnaire and had a mean total score of 68.69 (SD = 13.97); a moderately severe impact on quality of life. Balance confidence, measured with the ABC scale, obtained data showing moderate balance confidence levels, with a mean score of 58.05 (SD = 22.34). The majority of our sample (61.4%) obtained confidence scores lower than 67%, indicating a substantial risk for falls.Participants reported a mean of 4.28 (SD = 2.16) days with episodes of instability in the preceding week, noting feelings of fear of movement with a moderately-high level on the TSK , and a moderated degree of catastrophic thoughts on the PCS questionnaire . On the other hand, the presence of high central sensitization was observed  and a moderate disability related with a perceived severe sensation of vertigo reported in the DHI questionnaire . The stabilometric measurements related with CoP displacements showed values particularly high during the recordings made with open eyes (OE) and even more so, as expected, with closed eyes (CE). The functional tests that evaluate balance showed elevated percentages of positive results . The highest percentages of vestibular symptom response were obtained in the static balance test, the sensitized Romberg test and in the one-leg standing time tests; with values around 50% when the test was performed with open eyes and 90% when performed with closed eyes .In the rest of the dynamic balance and gait balance functional tests, equally high percentages of positive results  were obtained and exceeded 40% of the total sample .The bivariate analysis did not find an association between the FIQ and the ABC and these categorical variables. This study intended to analyze dynamic and static balance impairment in persons with FMS who present with a moderate level of impairment from the disease. Our results showed a frequency of impairment between 50% and 90% with tests performed with closed eyes, including the one-leg standing time test and other static balance tests, and a frequency higher than 40% of patients with impaired dynamic and gait balance. These data are consistent with other studies that also found a prevalence in these types of patients of around 50% ,6. In teThe participants of this study were mostly women (93%) with a mean age of 55.56 years. The majority had a secondary level of education, were married or in a stable relationship, and actively employed at the time of data collection. The sociodemographic distribution of our sample was therefore similar to that of other studies with patients diagnosed with FMS. Nevertheless, no correlation was found between the sociodemographic data of the sample  and the study variables. One of the most important impairments of fibromyalgia is its impact on quality of life. In this study a FIQ > 50 was established as part of the inclusion criteria, resulting in a sample with a moderately–severe degree of impact on quality of life. The mean total score obtained with the FIQ was 68.508 (SD = 15.83), similar to those obtained in recent studies such as Correa-Rodríguez et al. , which rSelf-confidence is considered a psychological characteristic and has received a lot of attention in the treatment of diverse chronic illnesses , among wFibromyalgia is associated with balance impairment and an increased frequency of falls . No singRecent studies ,8,34, haAccording to Pérez-de-Heredia-Torres et al.  patientsOn the other hand, a strong association was found, significant and inverse, for days with episodes of instability, kinesiophobia, and the perceived severity of vertigo on the ABC scale, identifying them as predictive factors of the latter and explaining 52.7% of its variability. Balance confidence can be interpreted as the degree of trust with which patients perform specific and daily tasks without losing balance. This study has some limitations to consider. First, as it is a cross-sectional study of a correlational nature, we were unable to analyze and observe in a sequential manner the evolution of the study variables and thus obtain more conclusive data on the causal relationships between FMS and balance impairment, in addition to observing the process of change in any of the variables studied. Second, the small sample size, may have resulted in obtaining of data with less statistical significance for some variables of our study. However, due to the exploratory nature of the study, in terms of the high number of variables included in the analysis, very relevant information has been provided in the relationships between variables that had not previously been associated in the literature in this study population. The relevance of this study is based on the analysis of variables are predictors of the impact of FMS. Variables associated with confidence in balance are also analyzed. This study highlights that disability due to dizziness on daily life is significantly related to the impact of the disease and balance confidence. This is a previous step to introduce intervention programs for patients with FMS. Finally, this study delves into the already known relationship between impaired balance and fibromyalgia.Based on these results, future studies should include larger FMS population with lower levels of FIQ to analyze whether this condition affects this association between variables, as well as new studies that analyze the efficacy of a vestibular rehabilitation program to the impact of FMS.The disease severity (measured with FIQ) in patients with a moderate-severe impact of FMS was associated with central sensitization (CSI) and the impact of dizziness on daily life (DHI), which explained 56% of its variance, while days with episodes of instability, kinesiophobia (TSK) and dizziness on daily life (DHI) also explained more than half of the variance of the balance confidence . A high frequency of positive results in functional balance tests and a high variability in the scores for stabilometric variables were found. The detection of factors susceptible to intervention, such as disability due to dizziness and vertigo, takes on special relevance in patients with FMS as it is significantly related to the impact of the disease and balance confidence.