Hypertension (HTN) is a significant global health problem, responsible for 7.5 million deaths each year worldwide. The prevalence of HTN is increasing in the pediatric population likely attributed to the increase in childhood obesity. Recent work has also shown that blood pressure (BP) tends to track from childhood to adulthood including BP-related target organ damage. In the last 25–30 years, pediatric use of ambulatory blood pressure monitoring (ABPM) has been expanding mainly in the setting of initial elevated BP measurement evaluation, HTN therapy efficacy follow-up, and renal disease. However, there are many clinical areas where ABPM could potentially be used but is currently underutilized. This review summarizes the current knowledge and the uses of pediatric ABPM and explores clinical areas where it can be very useful both to detect HTN and its longitudinal follow-up. And thus, ABPM could serve as a critical tool to potentially prevent early cardiovascular mortality and morbidity in wide variety of populations. With solid data to support ABPM’s superiority over clinic BP measurements and these clinical areas for its expansion, ABPM should now be part of standard of care in BP evaluation and management in pediatrics. The prevalence of hypertension (HTN) in children and adolescents ranges from 1 to 5% while prehypertension has been reported as high as 10% with rates of both HTN and prehypertension increasing over the past two decades  Proper aElevated BP in children and adolescents is often found during routine well child examinations or sports participation physicals. The National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents defines HTN in the Fourth Report as average systolic BP (SBP) and/or diastolic BP (DBP) ≥the 95th percentile for age, gender, and height on three or more occasions . PrehypeIn order to overcome the limitations of clinic BP measurements mentioned above, ABPM has been in use in children and adolescents in the last 25–30 years , 16. A d(1)BP is considered normal if clinic BP < 90th percentile, mean awake and sleep SBP and DBP < 95th percentile, and awake and sleep SBP and DBP loads are all <25%,(2)WCH is when clinic BP ≥ 95th percentile and mean awake and sleep SBP and DBP < 95th percentile, and awake and sleep SBP and DBP loads are all <25%,(3)Prehypertension is when clinic BP ≥ 90th percentile or >120/80 and mean awake and sleep SBP and DBP < 95th percentile, and awake or sleep SBP or DBP load is ≥25%,(4)MH is when clinic BP < 95th percentile and mean awake or sleep SBP or DBP > 95th percentile, and awake or sleep SBP or DBP load is ≥25%,(5)Ambulatory HTN is when clinic BP > 95th percentile and mean awake or sleep SBP or DBP > 95th percentile, and awake or sleep SBP or DBP load is 25–50%, and finally(6)Severe ambulatory HTN is when clinic BP > 95th percentile and mean awake or sleep SBP or DBP > 95th percentile, and awake or sleep SBP or DBP load is >50%. These diagnosis categories are found in a table in the AHA 2014 Update  because there are no normative data for this age group, and this age group is unlikely to tolerate the frequent BP measurements. Currently, indications for ABPM include confirming the diagnosis of HTN, evaluating for white coat hypertension (WCH) and masked hypertension (MH), assessing effectiveness of antihypertensive medication, and determining if symptoms can be attributed to drug-related hypotension . There aAdult ABPM studies have consistently reported superiority of ABPM parameters over clinic BP in predicting mortality, cardiovascular events, and target organ damage such as left ventricular hypertrophy (LVH) –22. In cTable There is fairly extensive adult literature, which demonstrates that HTN is associated with poorer cognitive performance including learning and memory, executive functions; and visuospatial, visuoconstructional, psychomotor, and perceptual abilities, and chronic uncontrolled HTN predicts cognitive decline over time . More reIn summary, the above published studies suggest that proper diagnosis of HTN by ABPM in children and adolescents has the potential to prevent and/or to treat target organ damages, in particular, the heart, the arterial vessels, and the central nervous system, which may not be possible with clinic BP measurements alone.White coat hypertension in children and adolescents may be fairly common as studies have reported a wide range of prevalence of 13–52% of children with elevated clinic BP measurements –43. ABPMThe prevalence of MH in general pediatric population has been reported to be just under 10% , 46 and One of the most important populations to properly diagnose HTN is children with CKD as HTN is a well-known modifiable risk factor for progression of CKD , 50–52. Hypertension implication in the renal transplant children and adolescents is similar to CKD population including its high prevalence, cardiovascular significance, and prognosis of allograft. When ABPM was used in renal transplant patients, prevalence of MH was found to be around 25–45%, and prevalence of uncontrolled HTN among treated patients ranged between 18 and 82% with median prevalence of 53% suggestive of the importance of routine use of ABPM in post-renal transplant population . Last, tThus, based on these published reports in CKD and post-renal transplant children and adolescents, the use of ABPM appears to be critical in their longitudinal follow-up not only to properly detect HTN but also to treat their HTN to slow down the progression of CKD or to preserve their allograft function.Ambulatory blood pressure monitoring is not only an effective way to properly diagnose HTN at the onset but it is also an effective way to determine the efficacy of HTN therapy. Seeman et al. demonstrated that nearly half of the pediatric patients on antihypertensive medications were found to have uncontrolled HTN by ABPM parameters. In addition, 35% of this study population had reclassification of controlled or uncontrolled HTN after having ABPM from their original classification based on clinic BP measurements, and the prevalence of LVH was significantly higher in uncontrolled HTN group compared to controlled HTN group . SimilarAmbulatory blood pressure monitoring’s superiority at detecting treatment-induced BP changes compared to clinic BP measurements makes it ideal for its use in pediatric antihypertensive medication clinical trials. Using the ESCAPE trial cohort, Gimpel et al. showed that SD of ABPM responses were up to 39% smaller than those of clinic BP measured responses. Using power analysis, they showed that depending on the magnitude of the aimed BP reduction, sample size could be reduced by 57–75% with the use of ABPM, which would be critical in reducing the number of hypertensive subjects receiving placebo drugs .The use of ABPM in children and adolescents has become more prevalent especially when evaluating to distinguish sustained HTN from WCH for elevated clinic BP measurements and in patients with kidney diseases including CKD and post-renal transplantation as discussed in the previous section. However, there is a wide spectrum of clinical areas where ABPM is not routinely used currently and where it could be very useful in detecting hypertensive patients. Table Coarctation of aorta is one of the more common causes of secondary HTN in pediatrics and makes up about 2% of all children and adolescents with HTN . More reThe literature on the use of ABPM is scarce in non-renal solid organ transplantation. Because of the frequent uses of glucocorticoids and nephrotoxic agents such as calcineurin inhibitors and higher prevalence of CKD, HTN has been reported to be significantly higher than the general pediatric population in liver, intestinal, and heart transplantation –67. In tSimilarly, survivors of hematopoietic cell transplantation patients have been reported to have higher risk of HTN from multifactorial etiologies including the use of glucocorticoids, nephrotoxic medications including calcineurin inhibitors and various chemotherapy agents, total body irradiation, graft versus host disease, and kidney injury , 73. In Ambulatory blood pressure monitoring also appears to be promising tool in following pediatric patients with type I diabetes mellitus (T1DM). Children with T1DM were frequently found to have ABPM confirmed HTN with most of them being nocturnal HTN suggestive of the important role of ABPM in this population . PerhapsOne of the more common comorbidity of obesity and obesity-related HTN is obstructive sleep apnea, and the use of ABPM appears to be helpful in this population. In a tertiary care hospital-based population, there was an independent association between apnea–hypopnea index and nighttime SBP and mean arterial pressure adjusting for adiposity variables suggestive of children with moderate-to-severe obstructive sleep apnea having higher ABPM parameters compared with children who were primary snorers . SimilarThere are relatively common conditions in children and adolescents known to increase the risk of HTN including polycystic ovary syndrome, William syndrome, Neurofibromatosis type I, and Turner Syndrome. Single centered studies in each of these conditions have identified higher detection rates of HTN by ABPM compared to clinic BP measurements –85. WomeIn summary, there are a relatively large number of clinical areas discussed in this section where ABPM is currently underutilized but should be used routinely to detect MH and to follow BP longitudinally in order to prevent and to delay the onset of cardiovascular disease in growing number of high risk children and adolescents with chronic conditions. The 2016 European Society of HTN guidelines for the management of high BP in children and adolescents recommends ABPM for pediatric patients with diabetes mellitus type 1 and 2, CKD, solid organ transplants including renal, liver and heart, and severe obesity with or without sleep disordered breathing .Traditional practice in pediatrics for a new diagnosis of HTN often included extensive evaluation of secondary causes of HTN including laboratory investigation, imaging studies, and target organ damage assessment, most often echocardiogram. A cost analysis at a pediatric HTN clinic where the protocol was to perform ABPM on all patients with stage I HTN clinic BP measurements found projected saving of $2.4 million for every 1,000 patients given their WCH rate of 46% . The cosThere are some limitations in our current knowledge and clinical use of pediatric ABPM. The most glaring is the need for more comprehensive normative ABPM data , 90. TheAmbulatory blood pressure monitoring monitor availability in pediatric clinics is currently suboptimal. Based on a recent on-line survey among pediatric nephrologists at centers belonging to the Midwest Pediatric Nephrology Consortium in North America, 94% of the survey responders were at centers where ABPM was available, but 57% of responders stated that patients sometimes had to wait to have ABPM as monitors were not available at the time of the visits. This inconvenience is likely attributable to approximately 75% of survey responders practicing at centers owning <10 monitors (publication in press). Last, another potential barrier is the cost to start an ABPM program and its income potential. One ABPM monitor along with the software costs around $3,500–$4,000. In the United States, many government-based and other private health insurances either do not cover or have fairly low reimbursement rate for ABPM for children despite the cost effectiveness mentioned above and ABPM published guidelines starting in 2008. It is estimated that 190–200 ABPM studies would need to be performed to recover the initial starting cost (The health and economic burden of HTN is unquestioned worldwide. Based on recent data to suggest BP tracking from childhood to adulthood with target organ damages, earlier and proper diagnosis of HTN by ABPM is vital in the first step to prevent and to delay cardiovascular consequences of HTN. By properly identifying children and adolescents with WCH, ABPM can also reduce the number of children and adolescents undergoing unnecessary medical tests and experiencing adverse effects from unnecessary therapy. Routine use of ABPM appears to also save costs to the health-care system. Pediatric ABPM studies in the last 25–30 years are starting to demonstrate its superiority in target organ outcomes over clinic BP measurements. In addition, there are multiple clinical areas where ABPM use is currently infrequent, but its use may be very valuable in longitudinal care of many children and adolescents with chronic conditions. Figure CP and YM performed comprehensive literature search, drafting and editing of manuscript, final approval of the version, and agreed to be accountable for all aspects of the work.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Aim: Activation of the sympathetic nervous system is common in resistant hypertension (RHT) and also in chronic kidney disease (CKD), a prevalent condition among resistant hypertensives. However, renal nerve ablation lowers blood pressure (BP) only in some patients with RHT. The influence of loss of nephrons per se on the antihypertensive response to renal denervation (RDNx) is unclear and was the focus of this study.Methods: Systemic hemodynamics and sympathetically mediated low frequency oscillations of systolic BP were determined continuously from telemetrically acquired BP recordings in rats before and after surgical excision of ∼80% of renal mass and subsequent RDNx.Results: After reduction of renal mass, rats fed a high salt (HS) diet showed sustained increases in mean arterial pressure (108 ± 3 mmHg to 128 ± 2 mmHg) and suppression of estimated sympathetic activity (∼15%), responses that did not occur with HS before renal ablation. After denervation of the remnant kidney, arterial pressure fell (to 104 ± 4 mmHg), estimated sympathetic activity and heart rate (HR) increased concomitantly, but these changes gradually returned to pre-denervation levels over 2 weeks of follow up. Subsequently, sympathoinhibition with clonidine did not alter arterial pressure while significantly suppressing estimated sympathetic activity and HR.Conclusion: These results indicate that RDNx does not chronically lower arterial pressure in this model of salt-sensitive hypertension associated with substantial nephron loss, but without ischemia and increased sympathetic activity, thus providing further insight into conditions likely to impact the antihypertensive response to renal-specific sympathoinhibition in subjects with CKD. The frequent association between chronic kidney disease (CKD) and treatment resistant hypertension (RHT) leads to a high incidence of adverse renal and cardiovascular outcomes, reflecting the likely, although not well studied, reciprocal potentiation of these conditions on the severity of the hypertension and its progression . High lesalt-sensitive, volume overload hypertension associated with loss of functional nephrons mimics the clinical situation of patients with CKD and RHT who commonly have inappropriately high levels of salt intake and hypertension that is frequently resistant to pharmacological therapy  and use of antihypertensive medications that alter sympathetic activity and, therefore, undoubtedly contribute to the variable BP response to RDNx in clinical trials.The overarching impetus for conducting the present study was to investigate the role of the renal sympathetic nerves in mediating the hypertension associated with reduced renal function. The remnant kidney model used in the present study has been the mainstay in the investigation of the pathogenesis of CKD and hypertension associated with reductions in functional nephron number . Surgica therapy . In contt kidney . In the t kidney . Howevert kidney  and it iThus, we tested the hypothesis that regional-specific abrogation of sympathetic outflow to the kidneys by RDNx chronically lowers BP in this salt-sensitive model of hypertension. A unique experimental approach in this study was that BP was measured continuously over several weeks to allow precise longitudinal determinations of changes in BP throughout the development of the hypertension and, moreover, during the immediate and subsequent days after RDNx. Furthermore, from the analysis of sympathetically mediated BP oscillations, along with inhibition of central autonomic outflow with clonidine, we determined whether increased sympathetic drive to non-renal targets play a role in mediating the salt-sensitive hypertension. These approaches allowed for a mechanistic evaluation of the role of the sympathetic nervous system in mediating salt-induced hypertension associated with reductions in the number of functional nephrons.ad libitum access to food and water, and were acclimatized for at least 3 weeks before the experimental protocols. Animals were fed a standard rodent diet containing either 0.8% NaCl , 0.1% NaCl , or 4% NaCl  . Surgical procedures were conducted under isoflurane anesthesia (2–3%). Tetracycline (2 mg/mL in drinking water) was administered for 3 days after each surgical procedure. All experiments were performed in accordance to the European Directive 2010/63/EU on the Protection of Animals Used for Scientific Purposes, the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes  and the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Research Ethics Committee of the Grigore T. Popa University of Medicine and Pharmacy, Iași.Eight adult male Sprague-Dawley rats (28–32 weeks of age) were obtained from the National Research Institute “Cantacuzino” . Rats were housed in a temperature (21–23°C) and humidity-controlled environment with a 12 h light/dark cycle, with TM, Becton Dickinson, Sparks, MD, United states) was guided from the left iliac fossa through a 1 mm incision of the abdominal muscle layer toward the inguinal area. The solid-state pressure sensor was tunneled through the tubing (which was then removed) and a length of ∼3 cm was advanced into the femoral artery with the pressure sensing tip in the aorta, below the emergence of the renal arteries. The pressure sensor was then secured with silk threads placed around the femoral artery and at the emergence from the abdominal wall. Finally, the muscle layers were closed with silk sutures and the skin with stainless steel clips .For implantation of telemeters, incisions were made in the midline abdominal and left inguinal regions. The body of the telemetry transmitters  was secured to the right flank of the inner abdominal wall with silk sutures . A 2 cm piece of PE90 polyethylene tubing . Throughout the procedure care was taken to avoid any manipulation of the left renal hilum containing the renal nerves. Incisions were closed with silk sutures and wound clips after visual assessment to verify hemostasis.The left and right kidneys were accessed via two longitudinal paravertebral incisions extending 1.5–2 cm caudally from the last rib. This retroperitoneal approach was chosen as it allows access to the kidney with minimal interference with the perirenal fat pads containing the renal nerve fibers. Following right nephrectomy, the upper and lower poles of the left kidney were cut with a scalpel blade so that a total of 75–80% of renal mass was removed. Hemostasis was obtained by gentle application of GelasponThe left kidney stump was accessed through a 1.5–2 cm ventral abdominal paramedian incision. Fibrous tissue and intestinal loops adherent to the remnant kidney were carefully removed using fine tweezers under magnification by a stereomicroscope . The renal artery and vein were exposed and cleared of surrounding tissue. All visible nerve running along the renal artery and vein within an area extending from the aorta to the renal hilum were cut. Thereafter, the adventitial layer was gently stripped off the renal vessels and a 10% phenol/ethanol (v/v) solution was applied for at least 5 min to the vessels using damp fine cotton tips. Extensive care was taken to prevent any leakage of the phenol solution onto the remnant kidney or into the peritoneal cavity. Finally, the surgical area was flushed with warm saline to remove any residual phenol. Wounds were closed with silk sutures and metal clips.® built-in BP module  were averaged to compute mean arterial pressure (MAP) and heart rate (HR) every day from the continuous 7.00 AM to 6.00 AM recordings, excluding the 1 h necessary for daily animal care.Rats were placed on TR181 smartpads  for signal acquisition and wireless charging of the implanted telemeters. The individual 24-h BP waveforms were acquired continuously at a sampling frequency of 2000 Hz using a PowerLab 16/35 acquisition system  connected to a PC for storage and subsequent analysis. All individual cardiac cycles identified using LabChart® software. Power spectra were calculated for all artifact-free segments ∼1 min in duration  within every 23-h period, overlapping by 50% and windowed using a Hamming function, and finally averaged to yield daily BP spectra. Analysis of the direct BP signal was preferred over extraction of cardiac cycle-related variables such as the systolic BP as it avoided the inherent issues related to resampling for unequally spaced time-series. Since the frequency band between 0.25 and 0.75 Hz  contains BP oscillations originating from sympathetically driven variations in arterial vascular tone  was administered in the drinking water for 6 and 3 days, respectively, in doses reported to reduce BP under conditions of sympathetic activation . The lowAfter implantation of the telemeters, the rats were maintained on NS and monitored until the circadian rhythmicity of BP and HR was fully restored (10–14 days). Then, control hemodynamic variables were recorded while on NS. To assess the hemodynamic and neural responses to variations in salt-intake during normal renal function, the rats were then fed LS for 1 week, followed by 1 week of HS, before returning to LS. After 5 days on LS, the right kidney was removed and the poles of the left kidney were excised to produce a total reduction in renal mass of ∼75–80%. Then the rats were allowed to recover for 10 days before HS was initiated and maintained for 6 weeks. RDNx of the remnant kidney was performed after 2 weeks on HS, when BP levels were stable. Two weeks after RDNx, responses to clonidine were assessed. Finally, rats were again placed on LS until the end of the study. At weekly intervals throughout the study, the rats were placed in metabolism cages and urine was collected for 24 h in chilled containers at 4°C . Sodium concentration was determined in urine using standard techniques, as previously described . UrinaryDays 1–4, NS control(1)Days 5–11, LS(2)Days 12–18, HS(3)Days 19–24, LS(1)Days 25–39, LS(2)Days 40–53, HS(3)Days 54–67, HS + RDNx(4)Days 68–73, HS + RDNx + clonidine (300 μg/kg/day)(5)Days 74–76, HS + RDNx + clonidine (150 μg/kg/day)(6)Days 77–81, HS + RDNx (clonidine washout)(7)Days 82–92, LS + RDNxResults are expressed as mean ± SE. One-way repeated measures ANOVA followed by Dunnett’s multiple comparison test were used  to compare the following experimental periods.Daily hemodynamic responses during varying salt intake (Days 5–24) to NS control (Days 2–3); Weekly urine responses during varying salt intake to NS control.P < 0.05.Daily hemodynamic responses during (1) HS (Days 40–53) to LS (Days 38–39); (2) HS + RDNx (Days 54–67) to HS (Days 52–53); (3) HS + RDNx + clonidine and clonidine washout (Days 68–81) to HS + RDNx (Days 66–67); and (4) LS (Days 82–92) to HS + RDNx (Days 80–81). Weekly urine responses during (1) HS, HS + RDNx, and HS + RDNx + clonidine to LS + RDNx and (2) HS, HS + RDNx, and HS + RDNx + clonidine to HS + RDNx (week 1). Differences were considered statistical significant for Figure 1A, MAP remained at NS control levels (105 ± 2 mmHg) during both LS and HS, although MAP was 5 mmHg below control during LS recovery. This indicates little or no BP salt sensitivity when renal function was normal. While transient increases in HR  occurred during the initial days of LS, LF power  remained unchanged from control levels for the entire week of LS. In contrast, HS led to significant and sustained increases of HR and estimated sympathetic activity as reflected by high levels of LF power. After returning the rats to LS in preparation for unilateral nephrectomy and partial surgical ablation of the remaining kidney, all variables returned to values indistinguishable from control except MAP, as indicated above. Urinary sodium and volume excretion closely paralleled the varying salt intakes while urinary protein excretion remained unchanged (Table 1).As shown in Figure 1B). This hypertensive response was associated with a fall in HR  and estimated sympathetic activity , likely due to autonomic responses caused by pressure-induced baroreflex activation. Urinary sodium and volume excretion were significantly higher during the 2 weeks of HS compared to LS baseline while urinary protein excretion did not change significantly (Table 1).In contrast to the absence of changes in MAP with varying salt intakes when renal function was normal, after RRM MAP increased progressively during the first week of salt loading and plateaued during week 2 to levels ∼20 mmHg higher than LS baseline, clearly indicating salt sensitivity , while HR  and estimated sympathetic activity  increased concomitantly. However, these acute hemodynamic changes after RDNx were only transient as MAP recovered back to hypertensive levels, while HR and LF power decreased toward pre-denervation levels within a week and were stable thereafter. Urinary sodium and protein excretion remained at levels similar to the first week of HS + RRM while urinary volume excretion increased by ∼35% after RDNx (Table 1).During the first day after RDNx MAP fell dramatically by ∼24 mmHg, to levels similar to those recorded during LS intake  and significant bradycardia . However, MAP increased slightly , albeit not significantly. During the 3 days of clonidine dose tapering (150 μg/kg) and the following washout period, estimated sympathetic activity gradually returned to control levels while MAP remained stable at post-denervation hypertensive values. Rebound tachycardia occurred for the first 2 days after cessation of clonidine, before eventual recovery by the end of the washout period. No further changes occurred in urinary variables during clonidine administration when compared to the days preceding drug treatment (Table 1).As expected, administration of clonidine (300 μg/kg) led to sustained sympathoinhibition as reflected by marked suppression of sympathetically mediated oscillations of BP in the LF band . Along with the abrupt fall in MAP, estimated sympathetic activity and HR increased during this time . By the end of the LS recovery period, MAP and HR were significantly lower than the days preceding salt restriction while estimated sympathetic activity returned to baseline levels, once again showing salt sensitivity.During the initial 2 days of LS there were precipitous reductions in MAP (P < 0.001), indicating completeness of RDNx.Renal levels of norepinephrine measured at the end of the experiment (∼6 weeks after RDNx) were 21.7 ± 5.9 ng/g, approximately 90% lower than those of age-matched normal animals  RDNx lowered BP transiently but not chronically in this model of salt-sensitive hypertension, indicating that the renal nerves have little role in the long-term maintenance of the hypertension. (2) Global suppression of sympathetic activity with clonidine did not attenuate the hypertension. (3) Indirect measures of sympathetic activity are consistent with these BP responses in that they indicate that sympathetic activity is actually suppressed during RRM and HS.Because there is independent activation of the sympathetic nervous system in many patients with CKD and RHT, sympathetic overactivity is believed to play a causative role in hypertension and disease progression . Therefoafter salt-sensitive hypertension had developed but within a time frame in which there is at best only moderate glomerulosclerosis  this study was performed during the early stage of salt-sensitive hypertension, below the time frame necessary for appreciable hypertensive nephrosclerosis in this model ; (b) theper se, signals from the injured kidney, such as ischemia, may underlie the reflex sympathetic activation, which promotes hypertension in CKD. Therefore, systematic exploration of the degree of ischemic renal injury may provide a mechanistic basis for identification of CKD patients with sympathetically mediated hypertension, which are likely to benefit the most from sympatholytic therapies such as RDNx.These findings in a classical model of kidney disease  indicateIT designed and performed the experiments, analyzed the data, and drafted the manuscript. TL designed the experiments, performed the analytical measurements, analyzed the data, and reviewed the manuscript. BA performed the analytical measurements. DP designed the experiments, reviewed the manuscript, and provided the logistical support. DS designed the experiments, analyzed the data, reviewed the manuscript, and provided the logistical support. RI designed the experiments, performed the experiments, analyzed the data, ensured the funding, and drafted and reviewed the final manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Aging, hypertension (HTN), and other cardiovascular risk factors contribute to structural and functional changes of the arterial wall.To evaluate whether arterial stiffness (AS) is related to cerebral blood flow changes and its association with cognitive function in patients with hypertension.®. Carotid properties were assessed by radiofrequency ultrasound. Central arterial pressure and augmentation index were obtained using applanation tonometry. Middle cerebral artery flow velocity was measured by transcranial Doppler ultrasonography.211 patients (69 normotensive and 142 hypertensive) were included. Patients with hypertension were divided into 2 stages: HTN stage-1 and HTN stage-2. The mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA) and a battery of neuropsychological (NPE) tests were used to determine cognitive function. Pulse wave velocity was measured using the CompliorBoth arterial stiffness parameters and cerebral vasoreactivity worsened in line with HTN severity. There was a negative correlation between breath holding index (BHI) and arterial stiffness parameters. Cognitive performance worsened in line with HTN severity, with statistical difference occurring mainly between the HTN-2 and normotension groups on both the MMSE and MoCA. The same tendency was observed on the NPE tests.Hypertension severity was associated with higher AS, worse BHI, and lower cognitive performance. Hypertension was defined as BP ≥ 140/90 mmHg or current use of antihypertensive drugs. Patients with hypertension were divided into 2 stages according to BP levels or medication use . Three groups were comparatively analyzed: Normotension, HTN stage 1 and HTN stage 2. Controlled HTN was defined as BP levels < 140/90 mmHg with the use of antihypertensive drugs. Patients from the Hypertension Unit of the Heart Institute of the University of São Paulo Medical School were consecutively recruited from June 2013 to December 2015. The normotension group participants were recruited among patients without CV disease followed yearly at the Heart Institute as part of a protocol for cardiovascular assessment.Patients that met the following criteria were excluded: age < 18 years, overt cerebrovascular disease (previous stroke or transient ischemic attack), diabetes mellitus, smoking, arrhythmias, heart failure associated with left ventricular dysfunction, known neurodegenerative or psychiatric disease, and being illiterate. Educational level was assessed by the number of completed school years. The local ethics committee approved the protocol and all participants gave written, informed consent.Blood pressure measurement. Brachial systolic and diastolic blood pressure was measured using an Omron automatic device, HEM-705 CP model, on the right upper arm, with the subject seated, after 5 minutes of resting, following the recommendations of the VI Brazilian Guidelines on Hypertension.-Arterial stiffness. Carotid-femoral pulse wave velocity (cfPWV) was analyzed with a noninvasive automatic device, Complior , and carotid measurements (intima media thickness [IMT] and carotid diameter) were taken with a high-definition echo-tracking device  by an experienced observer blinded to the clinical condition of each participant. All measurements were taken between 1:00 and 4:00 p.m., with the patient in a recumbent position while awake. The PWV measurement technique has been described previously elsewhere.Transcranial doppler. Cerebral blood flow velocity measurements were performed with subjects in a recumbent position while awake with the head in a neutral position. BP was continuously recorded, noninvasively, through finger plethysmography  in the left arm positioned at heart level. Blood flow velocities were measured continuously in the middle cerebral artery (MCA) using a transcranial Doppler device equipped with a 2-MHz transducer , positioned in the temporal region.Blood pressure and cerebral blood flow (CBF) velocity data were continuously transferred to a computer for analysis. These data were obtained at a sampling rate of 200 Hz. All signals were visually inspected to identify artifacts or noise. The spicules were eliminated by the linear interpolation method, and a frequency of 20 Hz was used as the cut-off for filtering signals. The beginning and end of each cardiac cycle were identified, and the mean values of CBF velocities and BP were calculated, beat-to-beat.The data acquisition protocol followed a pattern to assess both static and dynamic cerebral autoregulation such that cerebrovascular parameters were taken at the beginning and the end of the following periods: rest (3 minutes), breath-holding test (30 seconds), and handgrip maneuver (3 minutes).The breath-holding test was performed according to Harrison and Markus' descriptions.-1), where Vfa is the MCA mean blood velocity at the end of the apnea period, and Vra is the resting (baseline) MCA mean blood velocity, and s-1 denotes per second of apnea.Breath-holding index (BHI): BHI was calculated as the percentage increase in the MCA mean blood velocity registered during apnea, divided by apnea time in seconds ([(Vfa – Vra)/Vra] × 100 x sHandgrip maneuver: This was performed with a dynamometer in the right hand of the subject. To calculate the force applied during the maneuver, the participants were instructed to squeeze the dynamometer 3 times, with an interval of 10 seconds between maneuvers, using the maximum force of muscle contraction. The values were used to calculate the mean maximum contraction force. In the experiment, the patient squeezed the dynamometer for 3 minutes, exerting an effort corresponding to 30% of the mean maximum contraction force, in line with previous publications.The MMSE is a commonly used 30-point scale for assessing cognitive function based on orientation, registration, attention and calculation, recall, language, and praxis. MMSE administration was performed according to existing standards.The MoCA is a rapid screening instrument to identify mild cognitive impairment (MCI).-Procedures and descriptions of the neuropsychological tests used in this study have been published elsewhere.We computed scores for global cognition , language (BNT), memory , executive functioning , visuospatial abilities (mean z-score of REY-C and CDT), attention (mean z-score of FDST and TMT-A), and processing speed (DSST). Z scores were calculated using normotension as the reference group.t-test and Mann–Whitney U test, when applicable. Categorical data are expressed as percentages. Analysis of variance (ANOVA) was used with Bonferroni post hoc comparisons among the study groups. The Kruskal–Wallis test was used for categorical variables. Pearson's coefficient was used for bivariate correlations between BHI and arterial stiffness properties and multivariate step-wise analysis was performed. Statistical significance was set at 5%.Statistical analysis. Data were analyzed with SPSS for Windows 21.0. The distribution of the data was determined using the Kolmogorov-Smirnov test. Continuous variables are expressed as mean and SD or as median and range if not normally distributed and were analyzed by the independent-samples This study aimed to evaluate AS and BHI in a healthy population compared against patients with hypertension of different levels of severity. Baseline characteristics are presented in Cerebral blood flow velocities and breath-holding index are presented in Arterial properties according to blood pressure level are presented in On bivariate analysis, there was a negative correlation between BHI and arterial stiffness properties, respectively: PWV , Alx , Alx75 , cSBP , and cDBP . On multivariate analysis, only Alx75 independently and negatively predicted breath-holding index, showing that for every 1 unit increase in Alx there was a 0.012 decrease in BHI .On bivariate correlation between cognitive and cerebral parameters, BHI was positively associated with better performance on cognitive tests , suggesting that patients with lower blood pressure had better cerebral vasoreactivity (CVR) and performed better on cognitive function evaluation.The main finding of this study was that the patients with severe hypertension had higher arterial stiffness, lower breath-holding index, and lower cognitive performance. This finding suggests that hypertension severity is associated with higher arterial stiffness that may lead to impaired cerebral vasoreactivity and lower cognitive performance. The arterial system gradually stiffens, because of the combined effects of ageing, high blood pressure, and other vascular risk factors.,The mechanisms linking large-artery stiffness and manifestations of (silent) cerebral small-vessel disease are complex and not well understood.Moreover, contrary to large-artery stiffness, the role of small-artery stiffness has been studied less extensively.,Structural and functional changes of the arterial wall, caused by aging and cardiovascular risk factors, result in decreased elasticity and increased stiffness of the arteries.,CVR was associated with cognition, as assessed by the MMSE and MoCA, in older adults, including those with normal BP, HTN-1, and HTN-2, and was lower in HTN-2 patients than in subjects with normal BP and HTN-1 patients. A reduced CVR is known to be correlated with microangiopathy severity, which increases vascular resistance.,The associations we found between arterial stiffness and lower breath-holding index were most pronounced in persons with more severe hypertension. Evidence suggests that in the presence of hypertension, structural and functional changes of the arterial wall occur earlier.Our data suggest that within this group of subjects with severe hypertension, those with stiffer large arteries are more prone to having reduced cerebral vasoreactivity and lower cognitive performance.On the other hand, the HTN-1 group had a higher rate of controlled BP and better cognitive performance in comparison to the HTN-2 group. Whether the antihypertensive treatment may have influenced the cognitive performance in this group is unclear.So far, there is no convincing evidence from the trials identified that blood pressure lowering in late-life prevents the development of dementia or cognitive impairment in hypertensive patients with no apparent prior cerebrovascular disease.,-Seven randomized, double blind placebo-controlled trials have evaluated the benefit of antihypertensive treatments on cognition. Three of these found positive results in terms of prevention of dementia (SYST-EUR)In conclusion, severe hypertension was associated with higher arterial stiffness, worse breath-holding index, and lower cognitive performance. This scenario infers that hypertension severity is linked to higher arterial stiffness and lower vasoreactivity response, which may be associated with greater cognitive function decline in patients with chronic hypertension.First, our study sample was relatively small, and given the cross-sectional study design, association does not imply causation. Accordingly, our observations need confirmation in longitudinal and adequately powered studies. Second, our study was carried out in a select group of patients with hypertension referred to a university hospital, limiting the generalizability of our findings to other populations.,One limitation of the TCD method is related to the structure of the temporal window. The temporal window, where the TCD ultrasound probe is placed, thickens with age, making recording more difficult. A population-based study reported that 25% of the participants were lost because an adequate TCD signal could not be obtained, especially in older women.


Hypertension is as prevalent in many developing countries, as in the developed world and is the leading cause of cardiovascular morbidity and mortality in Africa. The control of hypertension in this resource limited setting is inadequate, a situation that translates into poorer outcomes in form of increasing incidences of stroke, heart failure, kidney failure and therefore early cardiovascular death.This was a chart review of all the patients seen during the months of September 2012 to February 2013. We determined the level of blood pressure control, basic investigations documented as well as the choice of hypertensive treatment among patients attending a hypertension clinic in a national referral hospital, Mulago.Of the 741 patients whose charts were reviewed the median age was 60 years, Inter quartile range (IQR) was 51–71. Six hundred forty-two (86.6%) were females. Blood pressure (BP) control defined as BP lowering to at least 140/90 was seen in only 198 (26.7%) patients. Biophysical measurement documentation was very low especially for waist and hip circumference at 0.3%. Majority of patients, 476 (64.2%) had at least one documented investigation for the complications of hypertension. Only 103 (13.9%) had all investigations documented in their charts. The investigations included; complete blood count (CBC), urinalysis, renal function tests (RFTs), Chest X-Ray (CXR), echocardiography (Echo) and electrocardiography (ECG). The commonly documented investigations were RFTs (45.5%), ECG (45.2%) and Echo (44.2%). The commonly prescribed anti hypertensive medications were; Angiotensin receptor blockers (ARBs)/Angiotensin converting enzyme inhibitors (ACEI) (72.74%), calcium channel blockers (72.3%) and thiazide diuretics (68.6%). Majority of patients were receiving three anti hypertensive medications 313 (42.2%), with 149 (43.6%) of these, on an ACEI/ARB, a calcium channel blocker and a thiazide diuretic.Blood pressure control is suboptimal in a tertiary clinic setting at Mulago hospital and documentation of investigations is inadequate. ARB/ACEI, Calcium channel blockers and thiazide diuretics were the commonly prescribed anti hypertensive medications. There is a great need to investigate for renal and cardiac complications as well as exploring reasons for inadequate blood pressure control and consider appropriate interventions to avert bad outcomes. Hypertension affects about one billion people and is estimated to cause 4.5% of current global disease burden , 2. TherThere is evidence that the diagnosis and control of hypertension is crucial in decreasing disability and mortality . A meta Blood pressure elevation is usually a multifactorial condition, and therefore it is almost impossible to normalize pressure by targeting only one mechanism. In addition, drug therapy directed at any one component routinely evokes counter regulatory responses that reduce the magnitude of response. Clinical trials have documented that achieving BP targets is usually not possible with a single agent. In the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial , only 26Blood pressure targets and choice of drugs are dependent on co-morbidity or presence of any target organ damage and so in the routine screening for patients with hypertension it is pertinent that some tests are done , 14.There has been documented poor BP control among community studies . HoweverIn an attempt to improve patient care in our hypertension clinics, we determined the level of blood pressure control, basic investigations documented and the choice of hypertensive treatment among patients attending the tertiary hypertension clinic Mulago national referral hospital.This was a chart review of all the patients seen through the months of September 2012 to February 2013.The study was conducted at the hypertension clinic in the medical out patients’ department of Mulago National referral hospital. The hospital is located in Uganda’s capital—Kampala and doubles as the teaching hospital for Makerere University College of health sciences. This clinic runs every Monday except on public holidays. The clinic is run by physicians, medical doctors and nurses plus support from the laboratory and pharmacy. About 80–100 patients are reviewed on a given clinic day.We used the records book at the hypertension clinic to get a list of all the patients that attended the clinic through the months of September 2012 to February 2013, their files were retrieved and data was abstracted using a pretested tool. The team that collected data was trained before data was abstracted. The data abstraction form was piloted and adjusted to get the required information. The data collected included: socio-demographics , co-morbidities including diabetes mellitus, obesity, chronic kidney disease, stroke and clinical characteristics such as blood pressure, weight, height, and waist–hip circumference.The investigations included: Renal function tests (RFTs), electrolytes, urinalysis, echocardiography, electrocardiogram (ECG) and Chest X-ray.We also obtained information on the type of drugs prescribed to the patient.An individual was classified to have sub-optimal pressure control if his/her blood pressure measurement was ≥140/90 mmHg on the last clinic visit. A missed appointment was defined as coming back to the clinic more than one week after a scheduled appointment.Data were collected manually and captured into Epi-data before it was transferred to STATA version 12 for analysis. Categorical variable are expressed as percentages and continuous data as median with their corresponding inter quartile range. Logistic regression was done to determine factors associated with blood pressure control. Statistical significance was set at p < 0.05.This research project was approved by the research and ethics committee of Mulago national referral hospital.Of the 741 charts reviewed; 642 (86.6%) belonged to female subjects; the median age was 60 years Inter quartile range IQR (51–71). More than two-thirds 548 (74%) of patients were 50 years and above.Blood pressure control as defined as at least 140/90 was seen in only 198 (26.7%) of the patients whose charts were reviewed. Blood pressure control was better among female patients. Age was comparable among patients with good blood pressure control and those not controlled Table .Ninety patients (12.2%) had documented co-morbid conditions. Stroke was in 14 (1.9%), Human immunodeficiency virus (HIV) infection was documented among 17 (2.3%), diabetes 11 (1.5%), asthma 11 (1.5%), arthritis 8 (1.1%), dyslipidemia 4 (0.5%) and benign prostatic hypertrophy in 4 (0.5%). Other conditions documented at very low frequency were renal disease, deep venous thrombosis, obstructive pulmonary disease, hyperthyroidism and peptic ulcer disease.The proportion of patients with biophysical measurement was very low especially for waist–hip circumference Table . Weight While the majority of patients had at least one documented investigation 476 (64.2%), only 103 (13.9%) had all the expected investigations documented in their charts. The expected investigations included CBC, urinalysis, renal function test, chest X-ray, echocardiogram and electrocardiography. The commonly documented investigations included RFTs (45.5%), ECG (45.2%) and Echo (44.2%) , with 149 (47.6%) of these on an ACEI/ARB, a calcium channel blocker and a thiazide  0.32 (0.16–0.62) and 0.17 (0.08–0.37) respectively compared to monotherapy (Table Other medications used included cardiac aspirin (23.4%), lipid lowering drugs (2.8%) and furosemide (5.3%).Almost half of the patients 348 (47.7%) did not keep their appointments. There was no difference in blood pressure control between those that kept appointments and those that did not keep appointments OR 1.03 95% CI (0.74–1.43) p = 0.858.Hypertension contributes to a high burden of disease and increased outpatient attendance for non communicable diseases. In Uganda specifically at the national referral hospital, the hypertension clinic is one of the busiest clinics with 80–100 patients reviewed each clinic day. Management of hypertension is aimed at controlling blood pressure to avert damage to end organs and thus improve quality of life for individuals with hypertension. In this study we found blood pressure control (as defined by a BP < 140/90 mmHg) at 26.7% which is inadequate in a country that has a high burden of hypertension , 18.In this clinic, there were older people than the young, 49.7% of patients were 60 years old and above with only 5.7% below 40 years of age. This can be partly because in the young cause of hypertension is mainly renal disease (secondary hypertension) and these patients are reviewed in the renal clinic which independently runs on a different clinic day .Hypertension control was comparable across age groups but this is different from what has been revealed from community studies that found better control among patients less than 50 years . BorzeckOur finding illustrates a poor control compared to what Musinguzi et al. found in a community study, blood pressure control among those on treatment was achieved by 52 (35.9%) . The posDocumentation of biophysical measurements and investigations was exceedingly poor in this hypertension clinic Table . It is nUrinalysis to check for micro-albuminuria can easily be done to screen for renal disease and plan management. Our study reveals that only a third of the patients (32.8%) had a urinalysis done. According to a study done by Nabbaale et al. in the same settings, 39.5% newly diagnosed hypertensive patients were found to have microalbuminuria . This imMajority of our patients were taking more than one drug for their blood pressure control, with 42.2% taking three drugs. Despite having several patients on more than one drug we still had poor BP control in this clinic setting. According to the Eighth Joint National Committee (JNC 8) , the recBlack patients with hypertension and renal disease are recommended to take ACEI or ARBs according to the African American Study of Kidney Disease and Hypertension (AASK) . PatientWe found that majority of patients on monotherapy were taking beta blockers, this is not in line with the guidelines. Beta-blockers are not recommended for the initial treatment of hypertension because their use resulted in a higher rate of cardiovascular death, myocardial infarction, or stroke . Beta-blThis finding of low blood pressure control prompts us to consider other modalities that can contribute to better blood pressure control. There have been studies that have shown that renal denervation may be a cost effective approach compared to medical management in management of resistant hypertension , 28. TheThis was a retrospective chart review study; we could not ascertain why control is low however we describe the magnitude of the problem and highlight key gaps in documentation. we cannot conclude that tests were not done since we went by what was documented but this clearly demonstrate that we have room to improve and make the care for our patients better.Evaluation for a hypertensive patient ought to be comprehensive to identify risk factors, co-morbidity as well as stratify patients to risk categories and plan appropriate treatment. In a clinic setting there is opportunity to make management of hypertension better and consequently avert the bad outcomes that are associated with poor blood pressure control.Blood pressure control is suboptimal in a clinic setting at Mulago hospital and documentation of basic investigations is inadequate. ARB/ACEI, Calcium channel blockers and thiazide diuretics were the commonly prescribed anti hypertensive medications. There is an urgent need to explore reasons for suboptimal control and institute measures to avert cardiovascular complications that are associated with poor blood pressure control.Evaluation for a hypertensive patient ought to be comprehensive to identify risk factors, co-morbidity as well as stratify patients to risk categories and plan appropriate treatment. Protocols have to be put in place and implemented for better patient care. In a clinic setting there is opportunity to make management of hypertension better and consequently avert the bad outcomes that are associated with poor blood pressure control.


The surfaces of the human body are heavily populated by a highly diverse microbial ecosystem termed the microbiota. The largest and richest among these highly heterogeneous populations of microbes is the gut microbiota. The collection of microbes and their genes, called the microbiome, has been studied intensely through the past few years using novel metagenomics, metatranscriptomics, and metabolomics approaches. This has enhanced our understanding of how the microbiome affects our metabolic, immunologic, neurologic, and endocrine homeostasis. Hypertension is a leading cause of cardiovascular disease worldwide; it contributes to stroke, heart disease, kidney failure, premature death, and disability. Recently, studies in humans and animals have shown that alterations in microbiota and its metabolites are associated with hypertension and atherosclerosis. In this review, we compile the recent findings and hypotheses describing the interplay between the microbiome and blood pressure, and we highlight some prospects by which utilization of microbiome-related techniques may be incorporated to better understand the pathophysiology and treatment of hypertension. The human microbiota is a mixed community of microorganisms composed of bacteria, viruses, archaea, and eukaryotic microbes that coinhabit the human body surfaces . The colMultiple studies have shown that each body site is characterized by unique ecological communities of microbial species  and eachHypertension is a global public health problem and contributes to the burden of heart disease, stroke, kidney failure, premature death, and disability. It is considered the most prevalent modifiable cardiovascular disease (CVD) risk factor. High blood pressure affects 1.13 billion people worldwide. In the US, 75 million American adults (29%) suffer from high blood pressure, which is around one out of three adults . GloballRecently, multiple animal and human studies have examined the relationship between the gut and the oral microbiome and blood pressure –11. ThesOur microbiota is highly dynamic and continuously changing. This is in part a reflection of age-related changes like growth and development, where the highest variation takes place during childhood but later decreases with age . NewbornMicrobiota composition is also determined by the physical characteristics and chemical properties of the site that is being colonized . TherefoRecent breakthroughs in high-throughput Next Generation Sequencing techniques, summarized in Figure Those tools have tremendously contributed to our current knowledge about the microbiota and their metabolites , 27. In Firmicutes and the Gram-negative Bacteroidetes  contribute to the fermentation of dietary plant polysaccharides or fibers, indigestible oligosaccharides, non-digested proteins, and intestinal mucin in order to produce SCFAs   . In addiutyrate) .Firmicutes and Proteobacteria, along with Bacteroidetes, Actinobacteria, and Fusobacteria totaling upwards of 95% of all identified oral microbiota  bacteria, such as Prevotella and Porphyromonas, have been associated with periodontitis and halitosis , sustenance , and worsening/progression of hypertension . Here, we provide an overview of the proposed hypotheses linking the microbiota to blood pressure, Figure Researchers have described a less rich and diverse microbiota in hypertensive compared to control subjects . SCFAs al-carnitine, a TMA abundant in red meat, by the intestinal microbiota results in the production of TMAO and accelerates the development and progression of atherosclerosis in mice (Another indirect connection between the gut microbiome composition and hypertension derives from the role of the gut microbes in the metabolism of choline and phosphatidylcholine to trimethylamine (TMA), which is further metabolized to the pro-atherogenic species, TMAO . Koeth a in mice . Recentl in mice . The res in mice . It is iVagal nerve stimulation and blocking sympathetic derive prevent breakdown of the intestinal lumen–blood barrier and enhance epithelia cell barrier function , 65. SanResearchers have proposed a brain–gut–bone marrow axis in which sympathetic activity to the bone marrow induces mobilization of hematopoietic stem cells . In thisAnother intriguing hypothesis involves the role of the gut microbiota in the enterohepatic circulation of steroids. Using antibiotic therapy, the bacterial flora of rats was modified to interrupt the enterohepatic circulation of steroids excreted in bile. Antibiotic and corticosterone were administered simultaneously to these animals. After 5 days, rats receiving both steroids and antibiotics had an average elevation of 9.2 mmHg in their blood pressure compared with 24.6 mmHg in rats given steroid alone. These findings are consistent with the possibility that metabolites of steroids, when reabsorbed in the enterohepatic circulation, contribute to the physiological response to exogenous steroids . FurtherLactobacillus helveticus as the predominant microorganism, indicated that antihypertensive effects and angiotensin-I converting enzyme inhibitory peptides are present in sour milk  plays a key role in the bile acid synthesis; when activated, it exerts negative feedback to control bile acid synthesis . Gut micvia SCFAs, as both acetate and hetanoate were higher in the R to S transfer group , and 2–3.5 mmHg increase in blood pressure  have equally contributed to the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Among Kazakh-Chinese population in Xinjiang province of China, prevalence of obesity and hypertension were 40.1% and 50.3% respectively, the highest across all ethnic groups residing in this pastureland. Despite this, there remained a dearth of information regarding the association between the anthropometric measures  and indicators for hypertension control  among them.A cross-sectional study was conducted in Xinjiang to determine the distribution and inter-relationships of the anthropometric measures and indicators for achieved BP control as well as their predictors among hypertension patients of Kazakh-Chinese ethnicity. Out of 550 randomly selected patients, 516 completed the interview, anthropometry and BP assessments.a = 0.152, p = 0.001) and duration of hypertension  with achieved level of SBP as well as BMI  with DBP. Age  and WHtR  were positively and WC  was negatively associated with PPI. Increasing age , female gender  and 5years’ duration of hypertension  were negatively associated with ABI. After adjustment for socio-demographic variables, hypertensive patients with (reference = without) abdominal obesity had 93% (p = 0.013) higher odds of missing the target BP control.In the sample population, average SBP, DBP and PP were 156.26±24.40mmHg, 87.55±14.73mmHg and 68.71±19.39mmHg respectively. Bivariate analysis identified age, gender, education, duration of hypertension, WC and BMI being factors influencing the achieved levels of BP. Adjusted multiple linear regression models elicited positive associations of age (βAnthropometric measures and indicators for blood pressure control among Kazakh-Chinese patients were far beyond normal. Several anthropometric measures appeared useful for monitoring BP. Using them, regular screening and consequent targeted intervention were required urgently to control hypertension among Kazakh-Chinese. Hypertension is regarded as one of the major contributing factor for the global burden of diseases. WorldwiPulse pressure index (PPI) is a relatively novel estimate of arterial stiffness defined as “pulse pressure/systolic pressure”. The valfor the management of arterial hypertension issued by the European Society of Cardiology (ESC) and European Society of Hypertension (ESH) did include ABI as a parameter for early detection of peripheral artery diseases(PAD). Further assuming 20% non-response 550 eligible subjects were required to be recruited for the study.Information on SBP level (158±22 mmHg) among Kazakh-Chinese hypertensive patients measured in an epidemiological investigation in Xinjiang during 2010 participants were categorized into three groups: obese (BMI ≥30), overweight (25≤BMI< 30) and normal/ underweight (BMI<25). Abdominal obesity was determined based on both WC as well as Waist-to-hip ratio (WHR = WC in cm/hip circumference in cm). Men with WC≥102cm and women with WC≥88cm were considered as having abdominal obesity while abdominal overweight meant 94cm≤WC<102cm in men and 80cm≤WC< 88cm in women. WC<94cm in men and WC<80cm in women were considered normal[According to the JNC-8 the 2014 guideline, the targets for the general population aged≥60 years were defined as: “SBP<150mmHg and DBP<90mmHg”. In the erweight ≤BMI< 30 ed normal, 27. Added normal.All analyses were conducted using SPSS version 20.0 . The resAmong 550 randomly selected eligible subjects, 516  completed the interview along with the clinical examination and anthropometric measurements. The overall response rate was 93.82%. The mean age was 58.14±12.05 years. Mean BMI was found to be 27.77±4.80 and mean WC was 97.56±13.07. Only 34.5% were receiving regular medical treatment for hypertension at the time of the survey. BP of 72.7% patients never reached the target level. Among participating patients, an average SBP was 156.26±24.40mmHg, DBP was 87.55±14.73mmHg and the PP was 68.71±19.39mmHg. In addition, 15 individuals suffering from diabetes, 6 individuals had chronic kidney disease, 64 had coronary heart disease, 7 suffered from cerebral stroke, 3 individuals had both diabetes and coronary heart disease while 2 individuals had cerebral stroke combined with coronary heart disease.Older age groups had higher SBP than <50years aged . Again 60–70 years old patients had lower DBP than 50–60 years’ group . PPI was increasing, but ABI was decreasing with advancing age. SBP and PPI of females were higher than males . BP control was marginally better among men than women (28.0% vs. 26.7%). Patients who did not attend high school had higher SBP than those who had high school or higher level of education . SBP and PPI of full-time employed subjects were higher than the part-time workers . Those who were having hypertension for ≥5years had higher SBP and ABI than those suffering from <5 years . SBP, DBP, PPI, and ABI did not vary significantly across the categories of complication and treatment of hypertension. Also, there was no statistical significance for the variation in the proportion of patients for whom targeted control of BP across the strata of received treatment (p = 0.756). 2, obese subjects had higher DBP and lower PPI (p<0.01). SBP and DBP were increasing with increase in WC, WHR and WHtR. Compared those with normal WC, patients having abdominal obesity (based on WC) had higher SBP and DBP . (Compared to those with BMI<25kg/mp<0.01). a = 0.152, p = 0.001) and duration of hypertension  had positive associations with SBP. Patients with higher BMI had more DBP . PPI was associated negatively with WC  and positively with age  and WHtR . Age , gender  and duration of hypertension  were negatively associated significantly with ABI.  was found to be associated positively with achieved BP levels through control measures .Kazakh-Chinese community is the second largest ethnic minority group in Xinjiang. They live in the mountains, eat cheese and meat more with less intake of vegetables and fruits. Such unhealthy food habit was likely to increase the risk of obesity, hyperlipidemia and hypertension in this population. Thus it was not surprising that among Kazakh-Chinese residents of Xinjiang province, based on prior findings, 50.3% were suffering from hypertension and 40.1In the current study, also, the observed burden of general 29.46%) and abdominal obesity (61.82%) were very high among Kazakhs. Corroborating with several prior studies, anthropometric measures like BMI, WC, WHR and WHtR were positively associated with achieved BP level. Generally, the predictive roles of anthropometric indicators in BP control vary across population. Regzedmaa et al.46% and  observedGrowing bodies of evidence suggested elevated SBP to be a strong and direct predictor for mortality among hypertensive patients aged >50 years, 32. In High DBP had been found previously to be associated with higher likelihood of organ damage among patients aged <50 years, 33. In It was also revealed that SBP, DBP and PPI were higher among women than men, while the case was reverse for ABI. Thus, contradicting with some prior observations, this stit as a better indicator than PP for the assessment of cardiovascular outcomes[Determination of PPI, through BP measurement, was found to be rapid. Previous research also established  outcomes. To the  outcomes, childre outcomes and larg outcomes. ExplanaABI measurement had widely been recommended for PAD screening. AbnormaAfter adjustment for age, gender, duration of hypertension and medication, hypertensive patients having abdominal obesity were 1.9 times likely to fail to achieve the target BP through the existing control program. Thus it appeared that prior screening and monitoring of WC might help in identification and then targeted intensification of intervention among patients having abdominal obesity, to improve their chances of achieving BP control.The study had some important limitations. First, hypertensive patients of Kazakh ethnicity were recruited for this study through a community-based sampling which could have missed some patients not residing locally for study (younger ones) or jobs elsewhere. Thus, further efforts should be made using multiple strategies to make the sample more comprehensive in future. Non-inclusion of any healthy control group could also be viewed as another limitation of this study that involved only the hypertensive patients. Besides, in order to ensure the reliability, 34 subjects with incomplete data were excluded, which might have limited the generalizability of the findings of this study to some extent in addition to the age-related issue. Alike any observational study with cross-sectional design, the observed associations should not be interpreted as causal and any effort to extrapolate the results beyond the study sample to be made with caution. Owing to the very small number of diagnosed cases of non-communicable diseases in the study sample, determination of the association between anthropometric measures and BP control among those specific cases was not possible. Last but not the least, our study did not collect detailed information on high blood pressure treatment.Observed values for the hypertension related indicators including SBP, DBP, PP and PPI as well as anthropometric measures like BMI, WC, WHR and WHtR were far beyond the normal ranges among hypertensive patients of Kazakh-Chinese ethnicity in Xinjiang pastureland. Subjects having higher anthropometric measures like BMI, WC, WHR, and WHtR, were more likely to end up with higher achieved levels of SBP, DBP, PP and PPI through efforts for hypertension control. After adjustment for the potential socio-demographic confounders, BMI and WHtR appeared to be independent risk factor for having higher DBP and PPI levels respectively. WC was also found to be associated positively with odds of having uncontrolled hypertension among Kazakh-Chinese residents of the study area. Thus for better effectiveness, hypertension control programs in this part of China, need to include anthropometric screening and targeted intervention for the identified population susceptible for poor BP control.S1 Dataset(SAV)Click here for additional data file.


Body weight changes are associated with significant variations in blood pressure (BP). Body mass modifications may, therefore, influence hypertension control in primary care.Patients with a history of essential arterial hypertension were observed for 12 months. Anthropometric data and clinical BP were evaluated at the time of the recruitment and after 12 months of follow-up. The association between (body mass index) BMI change and BP control was analyzed by logistic regression.2 was negatively associated with uncontrolled hypertension at the end of the follow-up . A similar association was observed in overweight patients . A BMI increase of at least 1 kg/m2 was associated with a significantly higher odd of uncontrolled hypertension in obese  and overweight patients .Sixteen thousand five hundred and sixty-four patients were recruited, while 13,631 patients  finished the 1-year follow-up. In obese patients, a BMI decrease by at least 1 kg/mWeight loss is inversely associated and weight increase is positively associated with the probability of uncontrolled hypertension in obese and overweight hypertensives. Arterial hypertension is a major global public health problem. It is estimated that more than 1 billion people suffer from arterial hypertension and its prevalence is expected to rise in the coming decades –5. DespiThere is a large body of evidence suggesting that the risk of developing arterial hypertension and body weight (BW) increase/obesity is mutually interdependent –17. The Although weight reduction is recommended in the guidelines as an essential part of non-pharmacological management of hypertension, it is often neglected by both patients and primary care physicians . Thus, tSince weight increase is associated with increase in systolic and diastolic blood pressure, we hypothesize that increase in weight may impair the effectiveness of arterial hypertension therapy and could result in higher proportion of patients with uncontrolled hypertension in primary care. We conducted prospective observational study in which the primary goal was to assess the presence of uncontrolled hypertension at the end of the 1-year follow-up period and to assess an effect of weight increase and decrease on the uncontrolled hypertension as a primary endpoint.2 and overweight as BMI of 25.0–29.9 kg/m2. Significant weight reduction was defined as a decrease in BMI by at least 1 kg/m2 and significant weight increase as an increase in BMI by at least 1 kg/m2.We conducted partial data analysis from the MIRROR Slovakia Study, which was a nation-wide prospective observational study. The primary goal of the study was to assess the mode and efficiency of antihypertensive therapy in primary care during a 1-year follow-up of patients with known history of essential arterial hypertension. The subanalysis focused on the relationship between BMI changes and the level of hypertension control during the 1-year follow-up. Its primary goal was to assess the effect of weight increase and decrease on the uncontrolled hypertension as a primary endpoint. Patients in the MIRROR Slovakia Study were recruited proportionally from all parts of Slovakia by general practitioners and internists. They had medical histories of arterial hypertension, regardless on the niveau of hypertension control, and were older than 18 years. The exclusion criteria included a history of oncologic disease except total remission, pregnancy, thyrotoxicosis, a history of hypercorticism or therapy by corticoids, liver cirrhosis, malabsorption syndrome, and end-stage kidney disease. All patients signed an informed consent. At the recruitment and 1-year follow-up visits, the weight and height of the volunteers were obtained. Body mass index (BMI) was calculated as the BW in kilograms divided by the square of the height in meters. BP was measured by a certified automated sphygmomanometer after 5 min of rest in a sitting position on both arms three times, separated by 1 min interval. The mean value  for each arm was calculated, and the higher mean value was used as definitive clinical BP. The target values for hypertension control were determined according to the 2013 European Society of Cardiology/European Society of Hypertension (ESC/ESC) guidelines [During the follow-up, the general practitioners and internists were free to change the pharmacologic antihypertensive therapy and/or recommend regime and diet changes; however they were instructed to adhere to recommendations of ESC/ESH guidelines and were also strictly instructed to provide the same level of medical attention to each patient . Accordi p values of less than 0.05 were considered as statistically significant. For the statistical analysis, the SPSS version 20 of Windows was used.The descriptive data were provided as mean ± standard deviation. The statistical significance of the differences in the means of quantitative variables was assessed using ANOVA with Tukey posts hoc test. Normal distribution of quantitative variables was verified using Kolmogorov–Smirnov test. Qualitative variables were compared using Chi-square test. The statistical significance of the association between BMI change and arterial hypertension control status at the end of the follow-up (uncontrolled hypertension represented the primary endpoint) was assessed using binary logistic regression analysis. Age, baseline systolic and diastolic blood pressure, creatinine, and number of minimal effective doses of antihypertensive drugs at the beginning and at the end of the follow-up were included in the analysis as possible confounders. Cohorts with no significant BMI change were used as reference groups for test purposes. Differences withThe study was approved by an ethical committee of Ministry of Health of Slovak Republic.Sixteen thousand five hundred and sixty-four patients were recruited, while 13,631 patients  finished the 1-year follow-up and their data were available for analysis. Eight hundred and twenty-seven patients died and 2106 patients were lost to follow-up. At the end of the follow-up, 4162 (65.7%) men had no significant BMI change; 1489 (23.5%) had BMI decreased; and 685 (10.8%) had BMI increased and of women 4651 (63.8%) had no significant BMI change; 1634 (22.4%) had BMI decreased; and 1010 (13.8%) had the BMI decreased according to study criteria. The baseline characteristics of the cohorts are displayed in Table 2, 56.1% of overweight men, and 61.4% of obese men (Table 2 (54.2%) but not between overweight women and women with BMI < 25 kg/m2 , diastolic blood pressure (DBP), creatinine, and doses of antihypertensive therapy at the beginning and at the end of the follow-up as possible confounding variables , pregnancy, thyrotoxicosis, liver cirrhosis, malabsorption syndrome, and end-stage kidney disease were excluded. However, there was a possibility that in some patients, these conditions might develop during the follow-up. Also, the possibility of significant worsening of glomerular filtration rate during the follow-up was not ruled out.Patients in our study differ in terms of antihypertensive therapy. Moreover, the pharmacological therapy was modified in a substantial number of patients during the follow-up. To decrease the effect of possible differences in pharmacological therapy as a confounding factor, the doses of antihypertensive therapies administered at the baseline and at the end of the follow-up were included in the logistic regression analysis as a possible confounder. All the patients were followed up on a regular basis of 3 months, and the general practitioners were strictly instructed to provide the same level of medical attention to each patient. However, there is a possibility of difference in the frequency of therapy modification.Also, the duration of the follow-up period should be considered. Our patients were observed for the period of 1 year; thus, it was not possible to assess the long-term effect of weight loss. A previous study on obese patients who underwent bariatric procedure has shown that BP increased again on pre-surgery values during 8-year follow-up . HoweverMost previous studies used body weight change as an indicator of weight loss. We used delta BMI rather than delta body weight, because BMI is a function of body adiposity .2 was associated with lower risk of uncontrolled hypertension at the end of 1-year follow-up in patients with obesity and overweight. This emphasizes the importance of BW control in the management of cardiovascular risk in patients with arterial hypertension, and it should be considered as an unavoidable recommendation in the complex treatment of arterial hypertension in obese and overweight individuals. On the other hand, weight increase by at least 1 kg/m2 during 1-year follow-up enhanced the risk of uncontrolled hypertension compared to maintaining approximately the same weight. It is suggested that weight loss or at least stabilization of BW may improve the control of hypertension in obese hypertonics and in overweight hypertensive patients.In our large observational prospective study, it has been shown that BW reduction by at least 1 kg/m


Prednisone dependence in asthma is usually described based on clinical and spirometric characteristics. It is generally believed that these patients have frequent exacerbations and lose lung function rapidly because of uncontrolled airway eosinophilia.The objectives of this study are to report the effect on asthma exacerbations and the change in lung function over time in prednisone-dependent asthma when severe asthma is managed using a protocol that aims to maintain normal sputum cell counts.A retrospective survey of patients prospectively assessed in a university tertiary care asthma clinic.52 patients  were followed for a median period of 5.4 years (min–max: 0.2–35.2). Monitoring with the aim of keeping sputum eosinophils below 3% resulted in higher doses of corticosteroids  than at baseline and this was associated with predictable adverse effects. Despite the disease severity, 10 patients (19%) did not require LABA for symptom control. Most importantly, over the period of follow-up, there were only 0.3 eosinophilic exacerbations/patient/year. Overall, there was an increase in FEV1 over the period of follow-up (mean +84.6 ml/year) rather than an expected decline.Monitoring of eosinophils in sputum enables to maintain symptom control and preserve FEV1 in patients with severe prednisone-dependent asthma. Asthma management guided by sputum cell counts has been shown to reduce eosinophilic exacerbations , 2 and i1 and on exacerbations in patients with prednisone-dependent asthma who were referred to this clinic.The recent experience from the British Thoracic Society Severe Asthma program suggest that the clinical outcomes of patients with severe asthma are better if they are managed in specialized asthma centres than in general clinics . A sever1 was >65% of predicted. Symptoms of cough, wheeze, chest tightness, dyspnea and sputum production were documented on a 7-point Likert scale (1 being worst and 7 being best). Tools to assess “asthma control” and “asthma-specific quality of life” were not available when the first patients were recruited into this program. Sputum was induced and processed according to the methods described by Pizzichini et al. [This was a retrospective descriptive chart review of patients with a physician-confirmed diagnosis of asthma , and who were on a maintenance dose of at least 5 mg of prednisone daily for at least 6 months prior to the initial consultation, who were referred to a severe asthma clinic at the Firestone Institute in Hamilton, Ontario, between 1973 and 2008. Basic clinical and demographic data were documented. Pre-and post-bronchodilator reversibility were recorded according to the American Thoracic Society standards . Airway i et al. .6/g and neutrophils greater than 65%, the patients were treated with a broad spectrum antibiotic (zithromycin or amoxicillin + clavulanic acid for 5–7 days). Most importantly, the dose of steroid was not increased. Long-acting bronchodilators  were added to the inhaled steroids only after the bronchitic component was controlled and the patient continued to have shortness of breath or wheezing that required more than 2–4 puffs of short-acting bronchodilators daily. They were not added if spirometry did not show any worsening of airflow obstruction or if PC20 methacholine was greater than 8 mg/ml or had not worsened by more than one doubling dose. If the sputum eosinophil % was less than 1%, the dose of corticosteroids was reduced. Sputum was always rechecked with 6–8 weeks of any treatment change. Once the maintenance dose of steroid was identified, patients were left on this dose indefinitely and seen in follow-up on average twice a year at which time spirometry, sputum and blood counts, clinical asthma control and adverse effects of therapy were assessed by self-reported history. Methacholine airway responsiveness was also reassessed if patients reported an increase need for short-acting bronchodilators and the sputum cell counts were normal and if it was felt safe to perform the test . Adherence to prescribed medications was continuously assessed by checking the pharmacy records every year.Asthma was managed according to the protocol described by Jayaram et al. . BrieflyIf patients experienced any worsening of symptoms  they were instructed to call our research office. Patients were brought to the clinic within 72 h for a clinical assessment, spirometry, and collection of either spontaneously expectorated or induced sputum. They were phoned back the same evening or the next morning with instructions to change their medication dosages. If patients had seen their family doctor and had received either antibiotics or prednisone without being seen at our clinic, this information was documented in the clinic chart. All the demographic and clinical information was meticulously extracted by a research assistant (AAR) and verified by a research technologist (MK) after obtaining approval from the Hospital Research Ethics Board.1 (ml/year) were analyzed by multilevel linear regression using three time points  for each gender and smoking status separately. As a first step, individual FEV1s were regressed against time to find rates of change (ml/year) for each patient. In the second step of multilevel linear regression, the rates of change (ml/year) for each patient (dependent variable) were regressed with age and height as the independent variables. The final rate of change of FEV1 in a specific group e.g. males, females, smokers and nonsmokers was computed using the mean age and height of the respective groups. The analyses were carried out using SPSS (version 16). Since we did not have a comparison group of patients with milder asthma or patients with severe asthma who were not monitored using sputum cell counts, we plotted the rates of decline of our cohort against the data published by Ulrik et al. [t test. P-value was considered significant if <0.05.Baseline demographic and clinical data were summarized using descriptive statistics. The rates of change of FEVk et al.  for patiThe study included 52  patients. The baseline characteristics of all patients are tabulated in Table Sputum eosinophil counts were normalized in all patients within a median period of 5 months Table . This wa1 from baseline value to the time point when sputum quantitative assay became normal was 1201.24 ml/year (95% CI 199.31 to 2202.7 ml/year) while the rate of change (decline) from the time sputum was normal to the time when the patient was last seen was a modest −14.9 (95% CI 53.4 to −83.2) ml/year. The overall (baseline to when last seen) rate of change of FEV1 was 84.63 (95% CI −44.6 to 213.8) ml/year. The corresponding values in males were 970.53 (95% CI 178.5 to 1762.4) ml/year, −28.36 (95% CI −18.1 to −38.6) ml/year and the overall rate of change was 113.99 (95% CI 70.6 to 157.4) ml/year and for females were 1515.85 (95% CI −701.1 to 3732.7) ml/year, 3.44 (95% CI −115.7 to 122.6) ml/year and the overall rate of change was 44.59 (95% CI −95.6 to 184.8) ml/year. There were however no statistically significant difference between males and females in their rates of change of FEV1. The rates of change of FEV1 for male smokers were : from baseline to when sputum was normal 1433.13 (95% CI 199.3 to 2666.9) ml/year, from when sputum was normal to when last seen 6.09 (95% CI −113.1 to 125.3) ml/year and overall 227.31 (95% CI −91.9 to 546.5) ml/year and for females smokers were: from baseline to when sputum was normal 663.8 (95% CI −332.4 to 1660.0) ml/year, from when sputum was normal to when last seen 21.54 (95% CI −310.1 to 353.1) ml/year and overall 82.58 (95% CI −306.6 to 471.8) ml/year. The corresponding values for male nonsmokers were: 171.48 (95% CI −78.0 to 420.9) ml/year, −87.86 (95% CI −218.7 to 43.02) ml/year and −81.73 (95% CI −190.5 to 27.1) ml/year and for female nonsmokers were: 2105.74 (95% CI −1801.4 to 6012.9) ml/year, −9.09 (95% CI −35.3 to 17.2) ml/year and 18.28 (95% CI −11.4 to 47.9) ml/year. There were no statistical differences in rates of change of FEV1 between the genders when smokers and nonsmokers were analysed separately.The rate of change of FEVOver the 2 years prior to attending our clinic, the patients had reported an average of 1.9 exacerbations/patient/year that had responded to prednisone. Since sputum was not examined during these exacerbations, we cannot confirm that these were eosinophilic, but we assume they were as patients reported improvement in their asthma symptoms within 48–72 h of therapy. This was reduced to 0.3 eosinophilic exacerbations/patient/year over the course of the follow-up period. The average time of resolution of individual exacerbations was 4 days. We did not have accurate records of “non-eosinophilic” or “neutrophilic” exacerbations before their initial visit to our clinic. During the course of the follow-up, the patients had 1.2 neutrophilic exacerbations/patient/year that were treated with antibiotics.The median duration of the steroid optimization phase was 5 months (min–max 1–7 months). During this period, the median daily dose of prednisone was 10 mg  and the dose of inhaled corticosteroid was 1500 mcg of fluticasone equivalent. This dose was maintained for the duration of the follow-up period. Five patients required the dose of prednisone to be increased after the maintenance dose was established. Corticosteroids caused predictable adverse effects . Over the course of the follow-up period, 20 patients were also commenced on LABA. The median period to commencement of LABA was 2 years . 10 patients have not required LABA for symptom control as their asthma severity (and airflow obstruction) was largely driven by steroid-responsive luminal eosinophilic inflammation rather than by bronchodilator-responsive smooth muscle dysfunction.This retrospective study illustrates three important concepts. Firstly, when available, incorporation of timely measurements of sputum quantitative cytometry and airway hyperresponsiveness into routine clinical practice is feasible and effective in the management of severe prednisone-dependent patients with asthma. Secondly, this strategy can reduce exacerbations and preserve lung function albeit at the cost of adverse effects of glucocorticoids. Thirdly, recognition of the component of asthma that leads to severity can help to rationalize the inappropriate use of long-acting bronchodilators that are associated with asthma morbidity.1 over time that has been reported in patients with “eosinophilic severe asthma” [1 was positive when the rate was computed from the baseline value to the point when the airway inflammation (or the sputum quantitative assay) became normal (Fig. 1 thereafter, from the time sputum was normal to the time when the patient was last seen was a modest −14 ml/year which is clearly lesser than that reported in previous longitudinal asthma studies [1 in this study is possibly driven by the fact that most patients had an improvement in lung function when sputum became normal after intensive anti-inflammatory therapy and that too within a short span of time resulting in high rates of improvement in FEV1 with time. Comparison with a matched group of patients at the Firestone clinic with similar severity of asthma who were managed based on symptoms only would have certainly added strength to the study. Unfortunately, such data were not available to us. However, it is extremely unlikely that treatment based on symptoms alone would give results similar to treatment using a sputum strategy [To our knowledge, this is the first study that reports the preservation of lung function in patients with severe asthma. Not only did we not observe the expected decline in FEV asthma” , 15, butmal Fig. , whereas studies , 15–18. 1 between this study and that by Ulrik et al. We fully realize that these two studies are not entirely comparable given the differences such as patient population, management strategies, sampling strategies etc. [1 in asthmatics. However, methodological issues have led to wide variations in these observations resulting in a lot of heterogeneity in the reported rates of decline in FEV1. Rates of decrease of FEV1 have varied from 25.7 ml/year in severe asthma [1 either between the genders (Fig. Figure ies etc. . Howevere asthma , 31.5 mle asthma , 26.6 mle asthma , 28.4–39e asthma , to 16.1e asthma . In the A second important point that we would like to highlight in this report is that patients could be on high doses of corticosteroids and not necessarily require long-acting beta-agonists if the severity is driven by luminal inflammation rather than by smooth muscle dysfunction. This is not often appreciated in clinical practice nor is it emphasized in the guidelines. In our cohort, the use of long-acting beta-agonist could be delayed or withheld in a small proportion of severe asthmatics in whom there is the highest concern for their adverse effects . This alThe major limitation of our study is the retrospective nature of data collection that spans over 25 years, the absence of a comparator group, and the lack of precision in the definition of exacerbations prior to referral to our clinic. It is also plausible that some of the exacerbations may not have been reported to us during the period of follow up. We did not use any sophisticated method to assess compliance other than self reports and pharmacy logs.1 in these patients. The test is not intrusive and is acceptable to most patients [In conclusion, we recommend monitoring of eosinophils in sputum in patients with severe prednisone-dependent asthma as this strategy enables to maintain symptom control, reduce exacerbations and preserve FEVpatients . This stpatients  can be a