Cardiovascular disease is one of the main causes of death in the United States, and hypertension is a primary risk factor. Therefore, the primary causes of hypertension need to be identified so they may be addressed for treatment. The purpose of this study was to compare blood pressure with hemodynamic values and identify factors that may explain blood pressure differences between a cohort of healthy normotensive younger and older women.2, normal electrocardiography response at rest and during exercise, nonsmokers, and no use of medications known to affect cardiovascular or metabolic function. Body composition measured by dual-energy X-ray absorptiometry. Hemodynamic values measured by non-invasive pulse wave velocity through radial artery tonometry. Markers of inflammation measured through blood sample analysis.Participants were 49 young (age: 33.8 ± 5.9) and 103 old (age: 65.8 ± 4) who were non-hypertensive, had no previous history of heart disease or type 2 diabetes, body mass index less than 30 kg/mP < 0.001), systolic blood pressure (SBP) (P = 0.001), large artery elasticity (P = 0.005), small artery elasticity (P < 0.001), systemic vascular resistance (P = 0.004), total vascular impedance (P < 0.001), estimated cardiac output (P < 0.001), and tumor necrosis factor-⍺ (TNF-⍺) (P < 0.001). Using ANCOVA the difference in SBP between age groups was no longer significant after adjusting for small artery elasticity (P < 0.001) and TNF-⍺ (P = 0.041).Significant differences exist between young and old groups in %fat (These data demonstrate that blood pressure and vascular hemodynamic measures differ significantly between young and old women independent of body composition. Furthermore, these differences may be explained by the inflammation marker TNF-⍺ and/or small artery elasticity. Hypertension is a primary risk factor for cardiovascular disease (CVD) and even a slight increase in blood pressure can heighten the risk for developing CVD . ArteriaCVD is known as a “silent killer” due to the asymptomatic development starting as early as the first decade of life, thus it is important for medical professionals to identify valid and reliable techniques to assess and track the progression of CVD . PreviouTherefore, it is important to compare blood pressure with vascular hemodynamic values between younger and older women that are healthy and normotensive. Thus, the primary purpose of this study was to identify factors that may explain blood pressure differences between a cohort of healthy normotensive younger and older women. The result of which would identify if these blood pressure differences may be explained by differences in markers of inflammation, body composition, or arterial elasticity.This is a secondary analysis of two studies designed to evaluate free living energy expenditure. This data analysis consisted of 49 females aged 21–46, and 103 females aged 60+. The two groups of females were divided into young and old groups based on age. Inclusion requirements for participants were non-hypertensive (systolic blood pressure [SBP] < 140 or diastolic blood pressure [DBP] < 90 mmHg), no previous history of heart disease or type 2 diabetes, normal electrocardiogram (EKG) response at rest and during exercise, nonsmokers, and no use of medications known to affect cardiovascular or metabolic function. Preliminary screening for study inclusion also included a physical examination, dual-energy X-ray absorptiometry, and a 12-lead EKG. Participants were excluded from the study if they were hypertensive or dual-energy X-ray absorptiometry assessment revealed osteoporosis. The study was approved by the Institutional Review Board for Human Use at the University of Alabama at Birmingham. All women provided informed consent prior to participating in the study.Body composition was measured by dual-energy X-ray absorptiometry . The scans were analyzed with the use of ADULT software, version 1.33 (Lunar Radiation).Hemodynamic values such as SBP and DBP, large artery elasticity (LAE), small artery elasticity (SAE), estimated cardiac output (ECO), systemic vascular resistance (SVR), and total vascular impedance (TVI) were all measured by non-invasive pulse wave velocity analysis through radial artery tonometry . Participants were placed in the seated position, with a solid-state pressure transducer array (tonometer) placed over the radial artery of the dominant arm to record the pulse contour. The waveform from the tonometer was calibrated by the oscillometric method. Once a stable measurement was achieved, a 30 s analog tracing of the radial waveform was digitized at 200 samples per second. Before, during, and after the waveform assessment, an automated oscillatory blood pressure measurement was taken on the contralateral arm. The first maximum waveform observed represented the action of the arteries following cardiac ejection and reflects the large arteries, whereas the second rebound wave reflects compliance of the smaller arteries. SVR was calculated as the mean arterial pressure divided by the ECO. TVI was determined from the modified Windkessel model evaluated at the frequency of the measured heart rate at rest [Systemic inflammation was measured by serum levels of TNF-α, interleukin-6 (IL-6), and C-reactive protein (CRP) through blood sample analysis. TNF-α was analyzed using the high-sensitivity ELISA kit . IL-6 was assayed using the high-sensitivity ELISA kit . CRP was assayed with the high-sensitivity ELISA kit .P <  0.05. Simple Pearson correlations were also used to examine associations of weight, BMI, %fat, SBP and DBP, as well as LAE and SAE, SVR and TVI, ECO, and the proinflammatory cytokine levels CRP, TNF-⍺, and IL-6 for the young and old groups. An analysis of covariance (ANCOVA) was performed to explain differences between SBP and age with %fat, LAE, SAE, and levels of TNF-⍺, CRP, and IL-6.Data was analyzed using the Statistical Package for the Social Sciences . Means and standard deviations for anthropomorphic and hemodynamic measures, LAE, SAE, SVR, TVI, ECO, and proinflammatory cytokine levels, CRP, TNF-⍺, and IL-6 were reported and assessed by one-way analysis of variance (ANOVA) with a significance value of P < 0.05). No significant differences were observed between the age groups in weight, height, BMI, DBP, CRP or IL-6.Differences between body composition, vascular measures, and markers of inflammation are presented in Table Results from ANCOVA are shown in Table P < 0.05). SBP was positively associated with DBP, SVR, and TVI, while an inverse association was found between SBP and LAE and SAE (P < 0.05). LAE and SAE were positively associated with ECO, and inversely associated with SVR and TVI (P < 0.05). TNF-⍺ was positively associated with %fat, SBP, SVR and TVI, but an inverse association was seen between TNF-⍺ and LAE, SAE, and ECO (P < 0.05).Pearson correlation analysis between variables are shown in Table P < 0.05). BMI was not seen to have these same associations in the young group. SBP was negatively associated with LAE and SAE (P < 0.05) in the old group but this relationship was only seen between SBP and LAE in the young group. %Fat was positively associated with CRP in the young group, while %fat was positively associated with IL-6 in the older group (P < 0.05). TNF-⍺ was significant with SBP, DBP, LAE, SVR, and TVI in the older group. This significance was not seen in the young group suggesting that inflammation may have a greater affect in the older population.Tables Due to the rise in prevalence of hypertension in the older population , and theStudies have shown body composition measures to be strong predictors of arterial stiffness in young adults  and a reThe ability of the arteries to perform properly and maintain regular blood flow and pressure can be hindered due to aging or other factors such as kidney disease, diabetes, atherosclerosis , 29 or hTNF-⍺, IL-6, and CRP have all been shown to be associated with CVD, and of those, TNF-⍺ has been shown to be the most correlated with arterial elasticity, vascular resistance, and blood pressure . Of the The association between aging and blood pressure is complex. It is well known that aging –9 and otn = 49) and old (n = 103) women, and 3) the use of state-of-the-art methods to assess body composition, hemodynamic measures, and inflammation markers. This study also provides clinical significance for the development of gender specific hypertension intervention. As previously stated, to the authors knowledge this is one of the first studies to look at differences in blood pressure and vascular measures in women alone. This study offers insight for health professionals to better monitor hypertension emergence in women by detecting the above mentioned risk factors early. The primary limitation of this study was the lack of aerobic fitness level inclusion, which could play a role in the prevalence of inflammation and arterial elasticity. Future research would be needed to investigate the relationship between fitness levels, systemic inflammation, and blood pressure differences between younger and older women.Overall strengths of this study include 1) strict inclusion requirements, 2) a large population size of young (These data demonstrate that blood pressure and vascular hemodynamic measures differ between young and old women independent of body composition. These differences may be at least partially explained by the inflammatory marker TNF-⍺ and SAE. Therefore, monitoring of these values in women as they age may help to detect the risk for emergence of hypertension.


The cognitive impact of changes in late-life blood pressure is less clear. We aimed to investigate the association between late-life blood pressure changing pattern and risk of cognitive impairment.Using data from the community-based Chinese Longitudinal Healthy Longevity Survey, change in systolic (SBP) or diastolic (DBP) blood pressure was calculated as the difference between follow-up and baseline, cognitive impairment was defined based on both the Mini-Mental State Examination and education level. The generalized additive model with penalized spline and multivariate logistic regression model were used, respectively, to examine the associations between continuous and categorized blood pressure changes with cognitive impairment at the follow-up wave.A total of 8493 Chinese elderly without cognitive impairment were included, with mean (standard deviation) age 80.6 (10.7) years. U-shaped associations between late-life blood pressure changes and risk of cognitive impairment were found, with only stable optimal blood pressure related to the lowest risk. For participants with baseline SBP around 130–150 mmHg, the adjusted odds ratio was 1.48 (1.13–1.93) for increasing follow-up SBP (> 150 mmHg), 1.28 (1.02–1.61) for decreasing follow-up SBP (< 130 mmHg), compared to stable follow-up SBP (130–150 mmHg). For participants with relative lower baseline DBP (< 80 mmHg), increasing their DBP to 80–90 mmHg during follow-up was associated with lower cognitive impairment risk (0.73 (0.58–0.93)), compared to steady low follow-up DBP (< 80 mmHg). Sex-specific analysis suggested that men were more vulnerable in term of SBP change.Adhering to a stable optimal level of blood pressure in late-life is related to lower risk of cognitive impairment in Chinese elderly.The online version contains supplementary material available at 10.1186/s12877-021-02479-1. Although blood pressure management has been served as a viable strategy for primary dementia prevention, controversies persist regarding the association between blood pressure and the risks of cognitive impairment and dementia –3. StudiAn improved understanding of the evolving relationship between changes in late-life blood pressure and cognitive functioning must be established before recommendations can be made concerning blood pressure targets for lowering the risk of dementia in older adults . The ChiThe CLHLS is a nationally-representative longitudinal cohort study conducted among older Chinese adults with more details reported elsewhere . By usinAfter having the participant rested for 5 minutes, arterial blood pressure (systolic blood pressure (SBP); diastolic blood pressure (DBP)) was measured with a mercury sphygmomanometer on the right arm at the heart level of the seated position by research assistants in the participant’s house. If the subject cannot remain in the sitting position, the arm is placed by the bed when measuring in the supine position. If when the supine position, the upper arm is below the heart level, then a pillow can be placed under the upper arm. The mercury sphygmomanometer must be calibrated before measurement . The meaCognitive function was measured by the Chinese version of Mini-Mental State Examination (MMSE) in each wave, which is a 14-question scale that includes 5 domains: orientation, registration, attention and calculation, recall, and language with a total score ranging from 0 to 30. The survey was administered in the participants’ homes by trained interviewers from the local centers for disease prevention and control and university students , 16.2 (kg/m2). Education status was dichotomized according to whether the participant ever received formal education. Economic income was classified as “high” and “medium or low” by the question “Compared with other locals, how do you think about your economic position?” Smoking status was classified into current, past or never, and alcohol consumption (current vs former/never) was assessed by the question “Do you currently drink alcohol?”. Additionally, we defined healthy diet habit as reporting consuming fresh fruit and vegetable every day, regular exercise as a positive answer to the question “Do you do any of the following exercise at present? jogging, playing ball, running or Qigong”. We defined good visual status as the participant was able to identify the direction of a break in a circle. Comorbidity was defined as participants having more than one of self-reported doctor-diagnosed diseases . Information on covariables was missing for only up to 4.8%, no imputation method was used.Baseline covariates were collected using a structured questionnaire, including sociodemographic characteristics, health behaviors and disease history. Body mass index (BMI) was calculated as weight/heightChanges in blood pressure between two sequential visits  were calculated as the absolute difference, with cognitive impairment determined at the follow-up wave Fig. . We firsThen, based on previous evidence , 17, 18,Finally, multiple logistic regression analysis was performed to estimate the corresponding odds ratio and 95% confident interval for different change patterns of blood pressure during 3-years interval associated with risk of cognitive impairment, using the stable category as reference. Three different models were fitted here: Model 1, crude model without any adjustment; Model 2, adjusted for sociodemographic and lifestyle confounders, including age, sex, BMI, income, diet, exercise, smoking status, alcohol consumption, visual status, comorbidity, and cohort , 20; ModTo test the robustness of the main findings, we performed the following analyses: (1) excluding participants with follow-up interval < 2.5 years or > 3.5 years; (2) excluding participants who had self-reported doctor-diagnosed hypertension to clarify the potential confounding caused by antihypertensive treatment; (3) using MMSE decline ≥4 points to define cognitive impairment ; and (4)A total of 8493 participants were included in the final analyses , the mean (SD) age was 80.6 (10.7) years, 4396 (52%) were women, and most (93%) were Chinese han. More than half of the participants were lived in rural area and received no formal education. During the 3-years follow-up, the blood pressure level was increased for SBP (from 134.0 to 135.9 mmHg), and declined for MMSE score (from 27.1 to 23.8)  with the corresponding crude incidence rate of cognitive impairment calculated within each cross-tabulated category. As shown in Fig. After conducting multiple logistic regression to adjust potential confounders, we found significant relationships between changes in blood pressure and risk of cognitive impairment Table . ResultsThe associations between changes in blood pressure and risk of cognitive impairment remained relatively the same among men and women, but lost significance for certain changing patterns. Also, men were more vulnerable in term of SBP change compared to women Figure S.Findings were consistent in the sensitivity analyses Tables S and S5. This large-scale population-based study examined the associations between changes in late-life blood pressure and cognitive impairment. The results of our study indicated that U-shaped associations between late-life blood pressure changes and cognitive impairment, with only stable optimal blood pressure level related to the lowest risk. Sex-specific analysis suggested that men were more vulnerable to SBP change.The deleterious influence of midlife blood pressure and hypertension on late-life cognitive function has been strongly suggested, while the cognitive impact of late-life blood pressure is much less clear with null , 24, U-sTwo former studies , 18, alsThe potential sex difference between hypertension and cognition has also not been fully understood . A previOur study has some unique and useful features. The most important feature is that based on the large-scale population-based cohort, we thoroughly investigated the association of different late-life blood pressure changing patterns with cognitive impairment among older Chinese. A sex-specific analysis was also conducted. Taken together, our study filled in certain knowledge gap about late-life blood pressure and cognitive function. On the other hand, there are still some limitations. Firstly, the validated data of incident dementia was unavailable in this cohort, using cognitive impairment defined by MMSE and education level as the outcome of interest might induce misclassification. Poor health status, usually indicated by frailty index, has been a critical confounder among geriatric research , here weOur findings suggest that adhering to stable optimal blood pressure in late-life is related to lower risk of cognitive impairment in Chinese elderly.Additional file 1: Figure S1. Flowchart of the study population. Figure S2. Heatmaps of sex-specific unadjusted incidence rates of cognitive impairment by patterns of blood pressure during 3-years follow-up. Table S1. Sex-specific 3-years risk of cognitive impairment by changes of blood pressure. Table S2. 3-years risk of cognitive impairment by changes of blood pressure, excluding participants with follow-up interval < 2.5 years or > 3.5 years. Table S3. 3-years risk of cognitive impairment by changes of blood pressure, excluding participants who had self-reported doctor-diagnosed hypertension. Table S4. 3-years risk of cognitive impairment by changes of blood pressure, using MMSE decline ≥4 points to define cognitive impairment. Table S5. 3-years risk of cognitive impairment by changes of blood pressure, further adjusted for baseline depression.


The role of endogenous mammalian cardiotonic steroids (CTS) in the physiology and pathophysiology of the cardiovascular system and the kidneys has interested researchers for more than 20 years. Cardiotonic steroids extracted from toads or plants, such as digitalis, have been used to treat heart disease since ancient times. CTS, also called endogenous digitalis-like factors, take part in the regulation of blood pressure and sodium homeostasis through their effects on the transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) in renal and cardiovascular tissue. In recent years, there has been increasing evidence showing deleterious effects of CTS on the structure and function of the heart, vasculature and kidneys. Understanding the role of CTS may be useful in the development of potential new therapeutic strategies. Cardiotonic steroids are a group of steroid hormones that circulate in the blood and are excreted in the urine. They are divided into two groups by their chemical structure: cardenolides (plant-derived) and bufadienolides . Cardenolides have a five-membered unsaturated lactone ring attached to the steroid nucleus at position 17 and bufadienolides have a doubly unsaturated six-membered lactone ring . CardenoThe biosynthesis of endogenous CTS in humans remains poorly understood. Biosynthesis of ouabain and dihydro-ouabain has been demonstrated in human cultured adrenocortical cells .Until recently, it was believed that CTS act mainly as inhibitors for the ubiquitous transport enzyme called sodium–potassium adenosine triphosphatase (Na/K-ATPase) . Na/K-AT+ and K+ pump, has also an additional, signaling function. Na/K-ATPase acts as a receptor for CTS and takes part in the cell signal transduction pathways [It is now believed that Na/K-ATPase, apart from its role as a Napathways . It has pathways . It is cNa/K-ATPase is composed of three subunits: alpha, beta and FXYD . The alpApart from the physiological role of CTS in the regulation of sodium content, blood volume and pressure, CTS also take part in the pathological adaptation resulting in hypertension. Experiments in animals show that the infusion of ouabain or marinobufagenin, at concentrations similar to endogenous levels, leads to an increase in blood pressure ,22. IncrThe relationship between salt, and especially salt-sensitivity, and blood pressure is well known, and has been demonstrated by several large clinical trials, such as the International Study of Salt and Blood Pressure (INTERSALT)  and the Observations from studies, both in animals and humans, have shown that an increased salt intake associates with elevated MBG levels. Studies, both in rats by Fedorova et al.  and in h2+ transporters, including NCX1 and SERCA, which promote a long-term arterial Ca2+ gain and sequestration in the sarcolemmal reticulum and lead to the long-term elevation of blood pressure [CTS can also act on Na/K-ATPase as a hormone that stimulates its signal transduction. It was observed in rats, in vivo and in primary cultured human and rat artery myocytes, that a sustained exposure of arterial myocytes to ouabain activates an α2 Na/K-ATPase-mediated protein kinase (PK) signaling cascade. This leads to an increased expression of Capressure . In the pressure . It has pressure . Grigoropressure . All thepressure .Strauss et al. demonstrated that in young adults, MBG excretion is also associated with an increased blood pressure  and arteConsidering the above, MBG may become an early biomarker of increased cardiovascular risk.Increased levels of cardiotonic steroids, such as MBG or ouabain, have been documented in a variety of cardiovascular disease states, among others, in congestive heart failure ,29 and mChronic kidney disease (CKD) increases cardiovascular (CV) risk immensely. CV disease is the leading cause of death in CKD and end-stage renal disease patients. However, the nature and pathophysiology of CV disease in CKD is complex and both classical  and non-classical  factors take part. It was shown that both rats receiving MBG  as well as rats after partial nephrectomy  developed a very similar increase in cardiac weight and fibrosis, increased systemic oxidative stress and a decrease in left ventricular vasorelaxation. It was also discovered that these changes were attenuated if rats were immunized against MBG. It is worth to say that only rats after partial nephrectomy had an increased aldosterone concentration and the administration of MBG in rats without nephrectomy did not influence serum aldosterone concentration. These data show that MBG’s effects on the heart are not mediated via increasing the aldosterone synthesis . SpironoInteresting data were shown in the analysis by Strauss et al. in the African-PREDICT study, performed in a young population (aged 20–30 years), free of detected cardiovascular or other chronic diseases. They found a positive, blood pressure-independent association of the left ventricular mass normalized for body surface area, the most sensitive estimate of subclinical cardiac target organ damage, with 24-hour urinary MBG excretion in young adults with excessively high levels of MBG excretion. These findings suggest that elevated levels of MBG, particularly in women, may increase the risk of the development of future cardiovascular disease . It is aSalt sensitivity is, as a cardiovascular risk factor, independent of blood pressure  and it i


There was an improvement in depression levels and a decrease in IL-4 and IL-5 in the IS and in the EBC in both groups. Our results suggest that an educational intervention can bring benefits concerning the control of inflammation, lung function alterations, quality of life and levels of depression in asthmatic patients. Registration: ClinicalTrials.gov; NCT03655392.This study aimed to evaluate the clinical evolution, functional parameters and inflammatory activity of asthma in patients who submitted to an educational intervention. 58 adult patients over 18 years of age with partly controlled and uncontrolled asthma were randomized into an intervention group (IG) (N = 32) and a control group (CG) (N = 26) and evaluated for 12 weeks. The Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Asthma Quality Life Questionnaire (AQLQ) and Beck Depression Inventory (BDI) questionnaires were applied. Spirometry, exhaled nitric oxide (NO), exhaled breath condensate (EBC) and induced sputum (IS), measurement of the peak flow and symptoms were performed. The IG patients received an educational activity for 30 min applied by a nurse. Statistical analysis: analysis of variance with repeated intragroup measures. IG presented a decreased number of eosinophils in IS and IL-17A in EBC, an increase in the percentage of FEV Chronic inflammation in asthma is a consequence of the participation of several mediators that lead to influx of inflammatory cells and airway remodeling as a consequence of goblet cell metaplasia, excessive subepithelial collagen deposition, airway smooth muscle hyperplasia, and increased vascularity. These characteristic features are orchestrated mainly by Type 2 (Th2) cells and cytokines5.It is estimated that approximately 358 million individuals worldwide are affected by asthma8. The correct use of these drugs is associated with better efficacy and fewer collateral effects related to therapy9.Thus, the main goal of asthma treatment is to reduce inflammation in the airways and consequently control the disease and its symptoms. Asthma treatment includes inhaled corticosteroids (ICS) and long-acting bronchodilators (LABA), and, more recently, for severe asthma, biologicals that target Th2 mediators. Factors contributing to an uncontrolled asthma are poor adherence and inappropriate inhaler technique. Studies have found that most patients do not use their inhalation device correctly11.Inhaled corticosteroids are the basis of treatment for most cases of asthma. Their constant use is associated with an improvement of symptoms and a reduction of morbidity and mortality related to disease13.Several studies showed that poor adherence to asthma medications and inadequate inhaler technique were associated to difficult-to-control asthma. The asthma education program is considered one of the fundamental pillars for adherence and proper treatment of the disease. It is estimated that more than half of patients treated for asthma do not have adequate adherence to the prescribed medication or do not perform the treatment properly14. Melani et al. observed that critical errors in the inhalation technique were observed in 36% of the patients with chronic airflow obstruction15.A review of interventions for inhaler techniques concluded that most of the studies showed that an intervention improved inhaler technique when assessed by a checklist or dichotomously; and that it was true for both children and adults with asthmaWe believe that an educational intervention aims at better comprehension on asthma care, including environmental control, adherence to medication use, and correct use of the inhalation device. These interventions can improve clinical, functional and inflammatory parameters of asthma. Thus, the objectives of this study were to assess asthma control, quality of life, levels of depression, lung function and inflammatory parameters of patients with asthma before and after an educational intervention.https://clinicaltrials.gov/ct2/show/NCT03655392).This study was a prospective, randomized, controlled trial approved by the Hospital Research Ethics Committee of the University of Sao Paulo (protocol number: 11496/14); the recruitment and protocol was carried out between 2015/2017. It was registered at ClinicalTrials.gov, registration number NCT 03,655,392, first registered in 03/28/2018 (retrospectively recorded)  for at least 1 year; increase in FEV1 of > 12% and > 200 ml from baseline 10–15 min after 400 mcg Salbutamol; dose of ICS stable in the last 8 weeks before recruitment; and nonsmokers or ex-smokers less than or equal to 10 pack-years. Subject characteristics are summarized in Table Adults between 18 and 69 years of age with clinical diagnosis of asthma16.Exclusion criteria: clinical asthma diagnosis and upper respiratory tract infection less than 30 days before; systemic steroids within 4 weeks of enrollment; pregnancy; other lung or uncontrolled chronic disease and chronic obstructive pulmonary disease (COPD) according to the Global Initiative for COPD (GOLD)Individuals were recruited after regular medical visits in outpatient clinics, by the researchers and physicians, after routine outpatient medical care. The study protocol was explained to the possible participant, and signed informed consent was requested within 28 days (T0). Subjects were followed for 56 days at three visits every 4 weeks (day 0 = T1 (baseline), day 28 = T2 and day 56 = T3) 19 and Beck Depression Inventory II (BDI II)20. After, individuals underwent spirometry for the collection of exhaled breath condensate (EBC) and induced sputum (IS). All these data were collected from both groups at the three study visits .At the first visit (T1), the patients were randomized in the order of inclusion in a 1:1 ratio for the IG (intervention group) or CG (control group) groups. The symptom diary and a manual and portable peak flow meter  were delivered to all patients. Then, they answered the following questionnaires administered by a blind investigator: Asthma Control Test (ACT)Additionally, IGs were submitted to educational intervention at all three visits  and received phone calls every 2 weeks, reinforcing the educational content and the date of return. CGs were only advised as to the date of return and received phone calls 2 days before to confirm attendance.2 and a simplified explanation of this disease and its main characteristics, guidance on inhalation technique using illustrations, a script and an explanatory leaflet.Educational intervention was applied by a trained nurse in a 30-min session. Its main objective was to verify whether the patient was using the ICS properly and, if necessary, to teach the correct inhalation technique. It included the asthma education components recommended in the Global Initiative for Asthma (GINA) main reporthttp://www.incor.usp.br/sites/incor2013/videos/asma-dpoc/). Environmental control was also briefly addressed, and IG subjects were guided on measures to avoid exposure to allergens and irritants.Skills for correct medication inhalation from a metered-dose inhaler and for peak flow measurement were taught and practiced. The inhalation technique was explained and demonstrated to the patients. As a complementary material, a four-minute explanatory video addressing the correct inhalation technique was shown . At each new visit (T2 and T3), patients returned the symptom diary and the annotation of the peak flow values.The symptoms of asthma and peak flow measurement were recorded in a diary of symptoms already used by patients in hospital outpatient clinics17. To evaluate clinical parameters, the ACQ-7 was applied21 considering the week before patients fill it out.To access the level of asthma control, the ACT questionnaire scores were used22. A minimal clinically important difference (MCID) of 0.5 was used. The MCID indicates the minimal difference in mean scores that is regarded as important23.Asthma quality of life was assessed using the AQLQ; a higher score indicates a better quality of life24.The BDI was used to assess depression levels, it’s a scale that has been used to evaluate related symptoms of depression in the last 4 weeks. The higher the score, the worse the severity of the symptoms25; a Koko spirometer  was utilized.Spirometry was also performed at the three study visits and was analyzed according to the acceptability and reproducibility criteria recommended by ATS/ERS (2005)Peak expiratory flow (PEF) measurement was performed after NO (nitric oxide) collection and after each inhalation. The patients were also instructed to perform this measurement three times, twice a day, morning and evening, before the use of the ICS, and to note down the three measurements in the symptom’s diary.27. Patients were asked to inhale 400 μg Salbutamol via a metered-dose inhaler 20 min before induction and then inhaled hypertonic saline (3% NaCl) for 7 min; peak flow and symptoms were evaluated before and after each inhalation. A Devilbiss Ultraneb 99  ultrasonic nebulizer was used.Sputum was induced by standard methodology28. The patients were instructed to blow into a Mylar balloon with an expiratory pressure supported in 12 cm H2O and a stable flow of 200 ml/s. This procedure and analysis were performed by a blinded investigator.The measurement of FeNO  was performed by chemiluminescence (Sievers 280) according to the recommendations of the ATS29. A condenser  cooled to − 20 °C for at least thirty minutes was used. The individuals were instructed to perform oral breathing using the mouthpiece of the equipment and with the aid of a nasal clip.EBC  was collected for 15–20 min in the current volume to measure cytokines30 was utilized. The tests were performed according to the manufacturer’s guidelines; the samples were analyzed in an ELISA reader .The levels of interleukin (IL)-4, IL-5 and IL-17A were quantified in IS supernatant and EBCs. ELISA (enzyme-linked immunosorbent assay) Descriptive analysis was performed on all patient data . Differences between groups were analyzed using Student’s t test, chi-square and one-way repeated measures analysis of variance (ANOVA). Intragroup analysis was compared by means of repeated measurement ANOVA. The confidence interval was 95% (p < 0.05). A statistical package was used for tests —descriptive analysis, differences between groups and intragroup, sample calculation) and SPSS 20.0 (odds ratio (OR) and chi-square). To calculate the odds ratio, the rates of change were compared between the groups (IG/CG) at different times of assessment: T1–T2, T2–T3, T1–T3 .31. The sample size calculation took into account a minimum mean difference of 67% for eosinophils, with an expected difference in means of 8 and a standard deviation of 10, test power of 80% and alpha of 0.05, thus resulting in a requirement of 13 patients in each group.Sample size estimates were based on the estimated effect of the intervention on eosinophils in induced sputum according to a previous studyPlataforma Brasil), number CAEE 25319213.5.0000.0068 (http://plataformabrasil.saude.gov.br/login.jsf).This study was approved by the HCFMUSP Research Ethics Committee, protocol number 639.895 in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki. The study was registered and approved according to the country’s standards on the Brazil Platform  and CG (n = 70). During the protocol, 76 patients lost follow-up, 29 from IG and 44 from CG. The claimed reasons for that were: lack of time to participate, other health treatments not related to this study, difficulties to get into hospital, change of address or employment, difficulty in missing work for treatment, among other reasons. Three patients were removed from IG because they presented a slight respiratory discomfort after inhalation with hypertonic saline solution. One patient was removed from CG for emotional disorder. After completing the protocol, we excluded 6 patients from IG for insufficient samples. At the end, 58 patients completed the entire study (IG n = 32) (CG n = 26) , we found an improvement in IG patients when comparing T1 with T2 or T3 moments . In the CG, we found improvements only in T3 compared to T1 (*p = 0.006)  and peak flow. In CG, patients reported more days free of cough at T3 when compared to T2 (*p = 0.028) (Table 1/FVC before and after bronchodilator in IG or CG (Table IG presented an increase in FEV1 before (p = 0.009) and after bronchodilator (p = 0.004) in T2 and T3 when compared to T1 CG . According to cellularity in endotype (induced sputum), most patients had paucigranulocytic asthma (69%) compared to neutrophilic, eosinophilic and mixed endotypes (p = 0.027*)  compared to T1 in the IG (*p = 0.034)    through the odds ratio and chi-square test among the 3 study visits , including clinical, functional and inflammatory parameters Table .Table 4O1 before BD among T1–T3 ; FEV1 after BD among T1–T2  and T1–T3 ; ACQ between T1 and T3  , T2–T3  and T1–T3 ; FEVIn the present study, we found that asthmatic patients with the disease partly controlled and uncontrolled who underwent an educational intervention showed improved clinical control of asthma, pulmonary function, markers of airway inflammation, and quality of life and decreased levels of depression.We showed the importance of an educational activity for a short period of time. This has led to a better lung function, decreased inflammation and levels of depression, and a better quality of life. This improvement occurred even without changing the previous pharmacological treatment of the patients, thus showing the importance of the educational approach in the management of asthma.33, asthma-related hospitalizations, emergency department visits and unscheduled doctor or clinic visits, missed work/school days, and night awakening35. The use of inhalation devices promotes a high concentration of medication in the airways, more rapid onset of action, and fewer systemic adverse effects than systemic delivery. For this to happen, the correct use of the inhalation device must be learned and maintained. In this context, skills training to use inhaler devices effectively are essential in an individualized self-care plan for asthma patients2.An effective guided asthma self-management education may help patients and reduce morbidity36. Boulet et al. showed significant improvements after an educational program, such as a reduction in unscheduled visits, inappropriate use of medications and an increase in FEV1 in mild to moderate asthmatic patients after 1 year of follow-up37. In another study, asthmatic and COPD patients showed better clinical control and lung function after submitting to a 6–8 follow-up educational program38. In our study, we also found an increased FEV1 after one (before and after bronchodilator) and 2 months (after bronchodilator) of educational intervention follow-up, that is, the improvement of this parameter after the educational activity.Some previous studies have shown that educational activities and self-management related to asthma features have been associated with better control of the disease in both adults and children39. They found that both groups that received an educational program presented increased scores on perceived control asthma questionnaires, although scores in the SMS group were higher than those in the traditional educational program39. Continuing medical program education in asthma care was shown to improve parent-reported provider communication skills, the number of days affected by asthma symptoms, and asthma health care use40.Lv et al. compared an SMS with a traditional educational program and an outpatient ordinary service (control group)43 and the negative effects of uncontrolled asthma on patients' quality of life44. In our study, asthmatic patients from IG presented better quality of life after 1 and 2 months (T2 and T3) of protocol intervention. Janson et al.36 showed that individualized asthma self-management education resulted in a decrease in nighttime awakenings, improved perceived control of asthma, better adherence to treatment, and improved clinical parameters of the disease and quality of life.Other authors have evaluated quality of life as an auxiliary measure of asthma treatment and its control38 also did not find differences between groups after an educational intervention regarding proper use of ICS in ACT scores. França-Pinto et al. did not show a difference in ACQ after an aerobic training program of asthmatic patients, although they presented a better quality of life and better scores of depression27. However, when the effect of the educational intervention was compared between the groups (IG and CG) through the odds ratio and chi-square test among the 3 study visits  we observed a significant difference in the percentage of ACQ between T1 and T3.However, we did not observe differences when comparing ACT and ACQ scores in either group. In the same way, Maricoto et al.One strength of our study is that even the CG presented more cough-free days and better IL-4, IL-5, and depression levels after the protocol. We hypothesized that these positive results could be motivated by the use of peak flow to fill a diary of symptoms and by some calls received from a health professional; thus, it was enough to help them feel self-confident to better manage the disease.46. Plourde et al.47 validated the BDI, one of the most widely used questionnaires to screen depression in health research areas50, to be used in asthmatic adult patients.Depression is an important asthma comorbidity and has been associated with worsening disease control in adultsWe found better depression scores in the IG after 1 month (T2) of educational intervention and after 2 months (T3) in the CG. When invited to participate in a survey, the participant’s attention is focused on the subject in question, that is, to have more health care. It is possible that the fact of having applied questionnaires about your illness, quality of life, depression, may have influenced further reflection and self-care, generating some positive results even in patients in the control group.51.Stoop et al. carried out a study with people with diabetes, asthma or COPD and the subjects answered questionnaires after 3, 6, 9, 12 and 18 months. The intervention group received a 12-month stepped care treatment and monitoring of symptoms. The control group received usual care plus monitoring by filling in a postal questionnaire every 3 months. Eighteen months post screening, the difference in symptoms of depression between intervention and control group was not significant anymore52. Some studies have associated FeNO with eosinophilia in asthmatic patients54. However, according to GINA2, this measure has not been established as useful for ruling in or ruling out a diagnosis of asthma; among other factors, it is not elevated in some asthma phenotypes, such as neutrophilic asthma55. The majority of our patients had paucigranulocytic asthma, which may explain the decreased values of FeNO after educational intervention  made recommendations on the use of novel therapies for severe asthma, specifically biologics for type 2 high asthma, such as the anti-IL-5 mepolizumab and reslizumab, the IL-5 receptor antagonist benralizumab and dupilumab, the IL-4 and IL-13 α-chain receptor antagonist. Those biologics showed efficacy for severe uncontrolled eosinophilic asthma phenotypes, particularly for those with severe corticosteroid-dependent asthma59. Thus, decreasing the levels of these cytokines with only a short-term educational intervention can bring benefits to patients.Another mediator related to eosinophils and the inflammatory process of asthma is Th2 cytokines, such as IL-4 and IL-5In the IG group, it has already been possible to observe with one month of educational intervention an improvement of inflammation, seen through the reduction of IL-4 and IL-5, both as evaluated by IS and EBC; this reduction was also observed after 2 months of intervention. In the CG, although there has been a decrease of these parameters, this reduction only occurred after 2 months. CG presented a decrease in these cytokines but they did not present improvement in other parameters that could represent disease control, such as lung function, the number of eosinophils and quality of life. Although these cytokines are involved in asthma pathogenesis, other mediators are also important to achieve the control of asthma symptoms.60. Barczyk et al. also presented a correlation of increased levels of IL-17 in asthmatic patients with bronchial hyperreactivity61. Camargo et al. showed that therapy with anti-IL-17 could be used to control the inflammatory process in an exacerbated asthma model62. In addition, Fattahi et al. found that lower levels of IL-17 + cells in asthmatic patients were associated with atopy and ICS use63. We observed decreased expression of IL-17A at EBC only in IG, suggesting a possible pathway to explain reduced inflammation in these patients.Although allergic asthmatic features are linked to Th2 cytokines, recent studies have associated Th2 with Th17 cytokines. Bullens et al. found an increase in the expression of IL-17 mRNA in the sputum of asthmatic patients compared to healthy controls64; however, its use has already been described as potentially harmful for differential cell analysis66. This procedure may have influenced the analysis of cytokines, a fact that was observed only after the freezing of samples. Another factor to be considered is the sample size, which could be expanded in future studies. It should also be considered that the CG may have influenced some of the results despite not having received the educational intervention in the first two visits. The fact that CG participated in the research may have influenced the results in a beneficial way and may have inferred some of the results. Despite these limitations, our study has several strengths. We showed that an educational intervention performed for a short period of time, applied by a trained professional, can produce benefits to patients in relation to inflammation, lung function, quality of life and depression levels.We believe that one of the limiting factors of this study may have been the use of dithiothreitol (DTT) for processing sputum supernatant. It is indicated for better preparation of slidesIn summary, we showed that an educational program directed to asthmatic patients in addition to physician care has an important role in disease control. Identifying patients’ needs, beliefs and behaviors can indicate where improvements should be focused to help people and plan future interventions. In this study, this benefit was evidenced by a reduction in airway inflammatory markers, such as IL-4, IL-5, IL-17A, FeNO and lung function, which consequently resulted in better quality of life and decreased depression levels. Finally, we suggest that health educational programs should be part of asthma management.


Background and Purpose: Optimal periprocedural management of blood pressure during mechanical thrombectomy (MT) remains controversial. This study aimed to investigate the relationship between the duration of blood pressure drops during general anesthesia and the outcomes in large vessel occlusion (LVO) patients treated with MT.Methods: We retrospectively reviewed our prospectively collected data for LVO patients treated with MT between January 2018 and July 2020. Intraprocedural mean arterial pressure (MAP) was recorded every 5 min throughout the procedure. Baseline MAP minus each MAP value recorded during general anesthesia was defined ΔMAP. Cumulated time (in min) and longest continuous episode (in min) with ΔMAP more than 10, 15, 20, 25, and 30 mmHg were calculated, respectively. Poor outcome was defined as 90-day modified Rankin score (mRS) 3–6. Associations between cumulated time of different ΔMAP thresholds and poor outcome were determined using binary logistic regression models.Results: A total of 131 patients were finally included in the study. After controlling for age, atrial fibrillation, baseline NIHSS, baseline ASPECTS, procedure duration of MT, and times of retrieval attempts, the results indicated that cumulated time of MAP drop more than 10 mmHg  and 15 mmHg  were independently associated with poor outcomes.Conclusion: Prolonged episodes of intraprocedural MAP lowering were more likely to have poor outcomes in LVO patients following MT with general anesthesia, which might be helpful in guiding intraprocedural hemodynamic management of patients under general anesthesia. Reperfusion therapy with mechanical thrombectomy (MT) has been a standard treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) . Neverthpost-hoc analysis of randomized controlled trials found that critical BP thresholds and durations during MT, with MAP <70 mmHg for more than 10 min, are linked with poor outcomes  had CT angiography (CTA)-confirmed LVOs presenting within 6 h of symptom onset, including the internal carotid artery, the middle cerebral artery (M1 or M2), and the basilar artery. Patients presenting at the hospital 6–16 h after symptom onset were included if they met the criteria described in the DEFUSE-3 trial . PatientWe retrieved demographic, clinical, laboratory, and radiological data including age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Alberta Stroke Program Early CT Score (ASPECTS), baseline systolic blood pressure (SBP), and diastolic blood pressure (DBP) parameters, as well as comorbid conditions such as history of smoking, hypertension, diabetes mellitus, atrial fibrillation, and congestive heart failure.MT under general anesthesia is our center's standard procedure. Only in a few cases when the anesthesiologist could not arrive at the angio-suite in time, MT under conscious sedation was selected. For the purpose of reducing the heterogeneity of study subjects, we excluded patients with conscious sedation. All data from the anesthesiology reports were collected from the beginning of anesthetic induction until awakening. The current guidelines from American Heart Association/American Stroke Association guidelines recommend to maintain BP ≤ 180/105 mmHg during and for 24 h after procedure . Baseline MAP minus each MAP value recorded during general anesthesia was defined as ΔMAP. As our main measure of the different ΔMAP duration during general anesthesia, cumulated time (in min), and longest continuous episode (in min) with ΔMAP more than 10 mmHg, while a cutoff value of 15, 20, 25, and 30 mmHg were also calculated, respectively.via a structured telephone interview by two certified neurologists with clinical experience for 8 and 13 years, respectively  scores of 2b or 3; a good outcome was defined as mRS score 0–2, and a poor outcome was defined as mRS score 3–6 at 90 days. At 90 days, an outcome assessment was performed with each patient ectively –18.t-test or a Mann-Whitney U-test was used for the continuous variables, depending on the normality of the distribution. Associations of each ΔMAP duration parameter with clinical outcomes were determined using binary logistic regression models adjusted by baseline characteristics with a P < 0.1 in univariate analyses, respectively. All statistical analyses were performed using SPSS, Version 22.0 . A P < 0.05 was considered statistically significant.The patients were dichotomized according to the functional outcome. Clinical characteristic and imaging profiles were summarized as mean ± SD or median (25th−75th percentile) for quantitative variables depending on the normality of the distribution and as frequency (percentage) for categorical variables. The Fisher exact test was used to compare the dichotomous variables between two groups, whereas an independent sample 2-tailed n = 10), conscious sedation (n = 23), and lost to follow-up (n = 1). Of the patients included, the mean age was 67.2 ± 13.0 years, and 46 (35.1%) were female. The median NIHSS score on admission was 19 , mean time from onset to reperfusion was 460.4 ± 206.1 min and median procedure duration was 124.5 ± 59.2 min.A total of 131 patients were finally enrolled after excluding patients due to TICI 0–2a after the procedure  of patients experienced a drop in MAP during general anesthesia. The mean MAP drop (ΔMAP) was 19.5 ± 14.1 mmHg.P = 0.002), had a higher frequency of atrial fibrillation , higher baseline NIHSS score , smaller baseline ASPECTS , longer procedure duration , and underwent more retrieval attempts  than those with good outcome.As shown in P < 0.001), the cumulated time of MAP dropping more than 15 mmHg , and the cumulated time of MAP dropping more than 20 mmHg  were longer in the poor outcome group. There were no significant differences in other variables including baseline BP. After controlling for age, atrial fibrillation, baseline NIHSS, baseline ASPECTS, procedure duration of MT and times of retrieval attempts, we found the results indicated that cumulated time of MAP drop more than 10 mmHg  and 15 mmHg  were independently associated with poor outcomes (The cumulated time of MAP dropping more than 10 mmHg (110.2 vs. 71.0 min, outcomes . For allIn this study, our findings suggest that prolonged episodes of lower MAP compared with baseline are related to a higher likelihood of poor outcome in LVO patients following MT with general anesthesia.A drop in BP during general anesthesia is a common phenomenon in LVO patients receiving MT, which are thought to occur mainly during the induction phase of general anesthesia. The incidence of this phenomenon reported by recent research is about 87% . SimilarConsidering that the SBP or DBP variables are more susceptible to be influenced by measurement errors and short BP fluctuations, we thus specifically chose the MAP instead of the SBP or DBP variables. Moreover, in the setting of arterial non-compliance or stiffness, SBP and DBP often move in the opposite direction, especially in an increasingly aging population . MAP refInterestingly, we found that only a cutoff value of 10 and 15 mmHg in intraprocedural MAP drop were independently associated with poor outcome. A previous study demonstrated that a fall in MAP of >40%, that is, ~40 mmHg, during endovascular therapy from baseline is an independent predictor of worse functional outcomes in LVO patients under general anesthesia (The major difference between our study and other previous studies is that our observation index is the duration of BP drops, not merely the extent of BP drops. Theoretically, BP elevation may be a natural response of the organism to persistent vessel occlusion in the acute ischemic stroke phase, in order to increase the perfusion of salvageable tissue and to minimize the ischemic damage , 27. MaiLimitations include the study being performed in a single center and with small number of cases. We collected data prospectively, which has the potential of selection bias. Second, we recorded the BP values only every five min during the procedure. It would be more informative to record BP every 2 or 3 min or even every min. Third, the site of LVO occlusion may also have played a role in the bias of the hemodynamic data as BP pathophysiology and optimal approach of management could be largely different between anterior and posterior circulation strokes. Fourth, inclusion criteria provide heterogeneity in baseline profiles of patients. We enrolled LVO patients within 6 h of symptom onset between January 2018 and April 2018. Afterwards, patients presenting at the hospital 6–16 h after symptom onset were also included according to the criteria of DEFUSE-3 and DAWN trial. Fifth, we did not explore the impact of different anesthetic drugs and doses on BP and clinical outcome, which are worthy of further study. Sixth, we had no standardized protocol for general anesthesia or intubation, which may lead to selection bias.Prolonged episodes of intraprocedural MAP lowering were more likely to have poor outcome in LVO patients following MT with general anesthesia. Every 1 min extension in duration of ΔMAP more than 10 and 15 mmHg before recanalization increased the odds of poor outcome by an estimated 1.3 and 1.1%, respectively. Larger prospective studies are warranted to confirm our results and give further insights in periprocedural BP management of AIS patients.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Human Ethics Committee of Zhejiang Provincial People's Hospital. The patients/participants provided their written informed consent to participate in this study.CX: substantial contributions to study design, data collection for the whole trial, data analysis, interpretation of data, and drafting and revising the manuscript for intellectual content. GL: substantial contributions to study design, cleaning and analyzing the data, and revising the manuscript for intellectual content. ZZ, TJ, and NL: data acquisition, interpretation of data, and revising the manuscript for intellectual content. HM: intraprocedural data collection for the whole trial and revising the manuscript for intellectual content. SY: image data collection for the whole trial and revising the manuscript for intellectual content. ZY: writing the statistical analysis plan. YG: monitoring data collection for the whole trial and revising the manuscript critically for intellectual content. ZS: developing study concept/design, study supervision, interpretation of data, revising the manuscript critically for intellectual content, and final approval of the version to be published. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.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.


Although diabetic kidney disease (DKD) could affect up to one-third of patients with diabetes mellitus (DM), these patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD. Several potential predictors of nondiabetic kidney disease (NDKD) have been proposed, but there are no definitive indications available for kidney biopsy in diabetic patients.  We designed a single-center, cross-sectional, and retrospective cohort study to identify clinical and laboratory factors associated with a diagnosis of NDKD after native kidney biopsy in diabetic patients and to investigate differences in time to end-stage kidney disease (ESKD) in patients with a diagnosis of DKD and NDKD.  Of 142 patients included in our analysis, 89 (62.68%) had a histopathological diagnosis of NDKD or mixed NDKD + DKD. Patients in the NDKD group had significantly lower HbA1C, lower prevalence of diabetic retinopathy (DR), and less severe proteinuria, and there was a lower proportion of patients with nephrotic syndrome; the DKD group had significantly lower proportion of patients with hematological conditions. In the multivariate binary logistic regression, only absence of DR and presence of a hematological condition significantly predicted NDKD after adjustment for age and sex. Time to ESKD was significantly higher in patients with NDKD or mixed forms than in those with DKD.  After a careful selection, more than half of kidney biopsies performed in diabetic patients can identify NDKD . Absence of DR and coexistence of a hematological condition  were strong predictors of NDKD in our cohort. The global burden of diabetes mellitus (DM) has substantially increased in the last decades, mostly due to a rise in the prevalence of type 2 DM secondary to obesity and the metabolic syndrome . ApproxiDiabetic patients can develop kidney diseases different from DKD, or these conditions can superimpose on DKD; since clinical presentation is generally nonspecific (kidney dysfunction and proteinuria), clinicians are less prone to perform diagnostic kidney biopsy in these patients and could erroneously provide a presumptive diagnosis of DKD, limiting the access to specific treatments. The indication to kidney biopsy in a patient with DM and kidney dysfunction and/or proteinuria represents a clinical conundrum, and several studies have attempted to identify clinical and laboratory factors associated with a histopathological diagnosis of nondiabetic kidney disease (NDKD) in order to restrict biopsy to patients with a high probability of being candidates to different therapeutic interventions. Clinically accepted predictors of NDKD in diabetic patients are the absence of DR, sudden onset of nephrotic syndrome or nephrotic-range proteinuria, short duration of diabetes, microscopic hematuria , and low glycated hemoglobin levels . HoweverThe performance of kidney biopsy in diabetic patients has also been proved to provide prognostic information; indeed, patients with DKD have been reported to have shorter renal survival compared to patients with NDKD –9. AlthoThe aim of our study was to investigate the clinical and laboratory factors associated with a diagnosis of NDKD in a cohort of patients with DM who underwent kidney biopsy on clinical indication. We also investigated differences in renal and patient survival among patients with DKD or NDND.We designed a single-center, retrospective, cross-sectional, and cohort study to identify clinical and laboratory factors associated with a histopathological diagnosis of NDKD after native kidney biopsy in diabetic patients  and to investigate differences in time to ESKD in patients with a diagnosis of DKD and NDKD after kidney biopsy. We enrolled all adult patients with a diagnosis of type I or type II DM who underwent diagnostic native kidney biopsy on clinical indication at the Nephrology and Dialysis Unit, University Hospital of Modena, Modena, Italy, from January 1, 2010, to April 30, 2020. The study was approved by the local ethical committee (“Comitato Etico dell'Area Vasta Emilia Nord” (protocol no. 252/2020)).Data were collected from clinical charts and histopathological reports; patients with incomplete clinical or laboratory data or with inadequate samples in kidney biopsy were excluded from the analysis. The following clinical variables at kidney biopsy were considered: age, sex, body mass index (BMI), blood pressure, presence of nephrotic syndrome, acute kidney injury, need for dialysis, type of diabetes, presence of DR, diabetes duration, presence of hematological conditions, and history of cardiovascular diseases . Laboratory data at biopsy included the following: serum creatinine and estimated GFR (eGFR) according to the CKD-EPI equation, 24 h proteinuria or proteinuria/creatininuria on a single-void urine sample, serum albumin, presence of microhematuria, serum cholesterol levels, serum complement levels (C3/C4), antinuclear antibody (ANA) and antineutrophil cytoplasm antibody (ANCA) positivity, antiphospholipase A2 receptor (PLA2R) positivity, viral serologies for hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV), and glycated hemoglobin (HbA1C). Nephrotic syndrome was defined as the combination of proteinuria of more than 3.5 g per day, hypoalbuminemia (less than 3.5 g/dl), and edema. Acute kidney injury was defined according to the KDIGO criteria . We defiRenal biopsy was performed on clinician discretion, and indications included the following : nephrotic syndrome , subnephrotic proteinuria in patients with a DM duration of less than 5 years, rapidly progressive kidney dysfunction with or without urinary abnormalities, and acute kidney injury without convincing clinical explanation. Histological examination, performed by one of two expert nephropathologists, was conducted on light microscopy for Bouin medium-fixed paraffin-embedded tissue with standard staining and immunofluorescence analysis for fresh frozen tissue with standard antisera; electron microscopy analysis was performed in a minority of cases on clinician indication and if dedicated material was available. Histological features of DKD were diffuse mesangial sclerosis with or without nodule formation and glomerular basement membrane thickening; supportive features were tubular basement membrane thickening (in nonatrophic tubules), presence of glomeruli (fibrin caps and capsular drop), and arteriolar hyalinosis.t-test, Kruskal–Wallis test, and chi-square test as appropriate. Univariate binary logistic regression was used to identify independent factors predictive of NDKD; a multivariate logistic regression model adjusting for age and sex was then developed including all variables with p < 0.1. Differences in time to ESKD  and death among the DKD group and the NDKD and mixed DKD + NDKD group were estimated with the Kaplan–Meier method with log-rank test.Statistical analysis was performed using GraphPad Prism (version 6.01) and SPSS (version 23) software. Continuous data were reported as median and interquartile range or mean and standard deviation as appropriate and discrete data as absolute number and relative percentage; data were compared with Student's We screened 203 diabetic patients who underwent diagnostic kidney biopsy at our center; after exclusion of biopsies performed in kidney-transplanted patients and of cases with insufficient material for a diagnosis, 142 patients were included in our analysis. Of them, 53 patients (37.32%) had a diagnosis of DKD in kidney biopsy, 28 (19.72%) of NDKD with mixed DKD, and 61 (42.96%) of isolated NDKD see . ClinicaEighty-nine diabetic patients received a main histological diagnosis different from DKD . The most frequent diagnosis in the NDKD and NDKD + DKD groups was membranous nephropathy (19.1%), hypertensive renovascular disease (8.99%), chronic nephropathy—not otherwise specified (7.87%), membranoproliferative glomerulonephritis (not further specified) (6.74%), and IgA nephropathy (6.74%). The complete list of diagnosis in the NDKD and NDKD + DKD groups is depicted in Twenty patients had a hematological condition, mostly benign; the majority of them (85%) had a diagnosis of MGUS, 2 had MM, and 1 had MBL; 2 patients with MGUS also had cryoglobulinemia (of unspecified type). Histological diagnosis obtained from kidney biopsy of the 20 patients with hematological conditions and NDKD is reported in To identify independent predictors of NDKD in kidney biopsy, we tested several factors in a preliminary univariate analysis. The following variables were included in the final multivariate model: diabetes duration, nephrotic syndrome, DR, hematological condition, and HbA1C. After adjustment for age and sex, only the absence of DR and the presence of a hematological condition maintained significance in predicting the specified outcome see .n = 45) developed ESKD during follow-up. We encountered a higher proportion of patients needing RRT in the DKD group  with respect to the NDKD  and the mixed groups ; four patients  were on dialysis at the time of kidney biopsy. Time to ESKD was significantly shorter in the DKD group, as shown by the Kaplan–Meier curves in p=0.0008). We did not identify difference in patient survival comparing the two groups . We found that the absence of DR and the presence of a hematological condition were the strongest predictors of NDKD as a main histopathological diagnosis.Nephropathy represents a frequent microvascular complication of DM, with up to one-third of patients being reported to develop DKD in the course of their life. Nevertheless, these patients can develop other types of kidney disease, which require a different diagnostic and therapeutic approach, and the frequency of these conditions in diabetic patients is reasonably expected to grow with the steady increase in the prevalence of DM worldwide.With the present study, we showed that, in a carefully selected population of diabetic patients, over a half received a histological diagnosis of kidney pathology different from DKD, allowing for a more precise diagnostic and prognostic classification and, in a relevant proportion of cases, opening the opportunity for specific treatments. Regarding this aspect, our findings are in line with those from a recent study from Spain including more than 800 diabetic patients (mostly Caucasians), where NDKD and mixed NDKD + DKD were diagnosed, respectively, in 49.6% and 10.8% ; similarRegarding the histopathological findings in the NDKD and mixed NDKD + DKD groups, in our cohort, the most frequent diagnosis was membranous nephropathy . This appears somewhat conflictive with the data from the aforementioned larger Spanish court , where hDiabetes duration and levels of HbA1C have been reported as important predictive factors for DKD in previous studies ; neverthSimilarly, the degree of proteinuria and the presence of nephrotic syndrome, although significantly different among the groups we examined (with patients with DKD presenting with higher proteinuria and more frequent nephrotic syndrome), did not predict NDKD in the multivariate analysis. Regarding this aspect, similar results were reported from Sharma et al. . This fiDiabetic patients with NDKD have been reported to show a slightly higher prevalence of microhematuria, especially with dysmorphic erythrocytes, and this factor has been claimed as a potential predictor of NDKD . We did Serological tests, such as markers of chronic viral infections, autoimmunity, and serum complement levels, are often used in clinical practice to refine the indication to kidney biopsy; this is considered especially useful in patients with metabolic conditions such as diabetes and hypertension, which can per se lead to kidney dysfunction and urinary abnormalities. Nevertheless, in our study, groups did not differ for positive autoimmune  or viral serologies . We acknowledge that the relatively low number of patients under study could complicate the identification of small differences between groups; however, similar results were obtained in a previous study involving a larger cohort . Even ifConversely, our data suggest that the absence of DR in a diabetic patient with kidney dysfunction and urinary abnormalities substantially strengthens the indication to kidney biopsy. In our cohort of diabetic patients, the absence of DR significantly predicted NDKD. Indeed, it has been previously reported that DR has a high sensitivity for predicting DKD , and in We believe that the most relevant finding of our study is the association between the presence of a hematological condition and NDKD in kidney biopsy, which has not been clearly reported before. The occurrence of kidney diseases associated with hematological conditions, especially monoclonal gammopathies, in the absence of symptomatic MM or chronic lymphocytic leukemia is increasingly recognized . The terWe also highlighted a faster progression of CKD in patients with DKD, compared with those with NDKD or mixed forms. This has been previously reported  and is lOur study has several limitations. Importantly, an inherent selection bias is evident since patients who were presumed to have a high probability of DKD were excluded a priori, not being offered kidney biopsy. Nevertheless, our data represent an insight into the common practice of clinical nephrologists and could apply to the population of diabetic patients who are considered for kidney biopsy. We also acknowledge that our study was monocentric, with a retrospective design and including a relatively small number of patients, factors limiting the generalizability of our findings.In summary, our study confirms that, if carefully selected, more than a half of kidney biopsies performed in diabetic patients can identify NDKD . The strongest predictors of NDKD in kidney biopsy in our cohort of diabetic patients were the absence of DR and the coexistence of a hematological condition , and clinicians should maintain a low threshold for kidney biopsy if these characteristics are met. Patients with DKD progressed more rapidly to ESKD than patients with NDKD or mixed forms; aggressive supportive therapy to slower the progression of CKD should be warranted if DKD is identified in kidney biopsy.


Zou and colleagues are publishing in this issue of The Journal of Clinical Hypertension, result of one of their studies in which they found that human corin genetic polymorphisms is involved in blood pressure control, more specifically in salt sensitivity. It is being published in this journal shortly after a literature review indicated another 18 genes were also involved in salt sensitivity, however corin gene. This dynamism of newly discovered genes shows the complexity of studying the genetic control of arterial hypertension and explains its known preliotropic characteristic. In this commentary, the study by Zou and colleagues is placed in the context of recent evidence on the genetics of high blood pressure and the future perspectives resulting from this and other studies are presented in the context of the clinical application of genetics in the prevention and treatment of high blood pressure. In this issue of The Journal of Clinical Hypertension, an article is being published that reports the results of a study conducted by Zou and 28 collaboratorsThese two works with multicentric characteristics are examples of the need for joint efforts to deal with the complexity of studying the interactions of more than 25 000 human genes. An example of the complexity of the genetic interaction to control blood pressure is well shown just in article published by Zou,Controlling blood pressure is even more complex when considering the plead of other biological mechanisms involved in blood pressure control, such as autonomic nervous activity,Despite a good and growing availability of antihypertensive drugs, as well as non‐drug therapies such as physical trainingThe discovery of genetic ‐ polymorphism dependence of responses to antihypertensive treatments, however, still does not seem enough. Because of the multifactorial nature of arterial hypertension, we must understand that the genome project represented only a starting point that provided us researchers with a basic tool to unravel how we can translate genetic knowledge into the treatment of arterial hypertension. While works such as those by Zou and colleagues While genomics is potentially promising in terms of contributing to the advancement of gene‐gene interaction, at the same time it suggests the need to advance to other areas of cell and molecular biology, such as epigenomics, transcriptomics, proteomics, and metabolomics. Epigenomics has the potential to clarify how environmental factors modify innate genetic tendencies to control blood pressure; transcriptomics, proteomics and metabolomics have the potential to indicate drug treatments that attenuate cellular responses promoted by genomic interactions associated with the pathophysiology of arterial hypertension, as drugs can act by stimulating or inhibiting transcription processes, micro RNA activity and protein formation involved in blood pressure control. Applications of pharmacogenomics can already be considered a plausible possibility to increase the antihypertensive success rate from clinical drug intervention, as argued in the review by Arnett and Claas.Advancing to the level of omics does not exclude the need for studies with single nucleotide polymorphism studies like the one by Zou and colleagues. Finally, while single nucleotide polymorphism studies offer the links (set of genes) that must be linked to understand the complex chain of genetic interaction involved in controlling hypertension, epigenomics can shed light on how the environment interferes with innate genetic programming to better explain this environment‐gene interaction; the proteomics, transcriptomics, and metabolomics can shed light on how we can interfere with cellular mechanisms through nutritional, pharmacological or lifestyle aspects so that we have a more complete mastery of this complex system of blood pressure control.The author has no competing interests.


Despite the availability of effective treatment, the control of hypertension remains insufficient. Telemonitoring in the management of hypertension would be an effective way to improve blood pressure control.The aim of our study will be to evaluate the effects of telemonitoring with antihypertensive treatment titration on blood pressure control in Tunisian patients with hypertension.Our trial will be a prospective, rater-blinded randomized controlled trial carried out with primary care physicians in the Sahel region of Tunisia. Patients will be eligible for enrollment if they are aged over 35 years, are newly diagnosed with hypertension, or are known to be poorly controlled on antihypertensive therapy. Participants will be randomly assigned in a 1:1 ratio to the telemonitoring arm or usual care arm. The telemonitoring arm will involve a weekly telephone call for the collection of the home blood pressure measurements, therapeutic education, and treatment compliance assessment as well as a monthly call for treatment titration and a side effect check. Randomization will be done via the use of an interactive web responsive system, and patients will be stratified by investigation center. Neither participants nor investigators will be masked to the group assignments. The primary outcome will be the change in mean 24-hour systolic blood pressure from baseline to the 6-month follow-up in the 2 groups. All randomized patients who attend the follow-up visit at 6 months and have no missing data for the primary outcome will be included in the analysis.Recruitment to the trial started in July 2020. The study was initiated with 17 primary care physicians. We expect the inclusion period to last for approximately 6 months. We expect to complete data collection by the end of 2021 and plan to disseminate the results subsequently.The HOROSCOPE  study will provide important new evidence that could shed some light on the feasibility and impact of telemonitoring and self-monitoring in a Tunisian population of patients with hypertension who consult primary care physicians.ClinicalTrials.gov NCT04607239; https://clinicaltrials.gov/ct2/show/NCT04607239DERR1-10.2196/26184 P<.001) and only 38.1% of patients with hypertension are aware of their hypertension [Hypertension is one of the main risk factors for cardiovascular disease and the leading cause for global morbidity and mortality ,2. Despirtension .The aim of the HOROSCOPE  study is to demonstrate the impact of telemonitoring on blood pressure control among patients with hypertension.The trial will address the following three main research questions: (1) does telemonitoring improve treatment compliance and blood pressure control in newly diagnosed or poorly controlled patients with hypertension, (2) does telemonitoring improve patients’ quality of life, and (3) does telemonitoring reduce the incidence of cardiovascular complications?Our trial will be a multicentric, rater-blinded, prospective randomized controlled trial. The allocation ratio between the intervention and control group will be 1:1. Randomization will be done via the use of an interactive web responsive system, and patients will be stratified by investigation center. Neither participants nor investigators will be masked to the group assignments. However, the cardiologist, who will interpret the results of the primary outcome, will be blinded.The study is expected to last for an overall duration of 12 months . The recruitment period will last for 6 months, and the follow-up interval will be 6 months.Patients with hypertension will be recruited from consultations with primary care general practitioners in the central region of Tunisia. The inclusion and exclusion criteria are outlined in Inclusion criteriaAged ≥35 years oldNewly diagnosed hypertensionPoorly controlled hypertensionOne single blood pressure value outside the expected range will not be taken as a definitive indicator of clinical deteriorationBlood pressure should be >140/90 mm Hg at screening for at least 2 visits to allow the inclusion of a patientExclusion criteriaOrthostatic hypotensionChronic renal failure (serum creatinine level: >200 µmol/L)Acute coronary syndrome, coronary revascularization, or stroke within the past 3 monthsKnown secondary causes of hypertensionPregnancyNew York Heart Association Class III or IV heart failure or left ventricular ejection fraction of <30%Dementia or any other cause that could prevent the implementation of remote monitoring (telemonitoring)Participants will be recruited directly from primary health care centers by general practitioners. Participants will be included during their visit to the outpatient clinic after the verification of their eligibility criteria. When patients meet the eligibility criteria, the investigator will provide them with a study information sheet. Patients showing interest in taking part in the study will be included.Material compensation will not be offered for participating in the study. Potential participants will be informed about the scientific benefits of their participation and will not be offered any other incentives. In order to obtain informed consent, the investigator will inform the participants about the possible benefits and potential side effects of participating in this study as well as the study duration. Patients will also be informed that their participation will be strictly voluntary and that they can withdraw from the study at any time without stating any reason. They will also be informed that withdrawing from the study will not affect subsequent medical assistance and treatment. Participants will be advised that their personal data will be used by other authorized health care professionals other than their treating physicians as part of the clinical trial. They will be given sufficient time to reflect extensively on their participation decision. The informed consent form will be signed and dated by the investigator following the signature of the participant. The consent form will be retained as part of the study records. A signed copy will be provided to each study participant. Overall patient flow throughout the study is depicted in A sample size of 199 subjects per group is required for 80% power, assuming a mean difference in the reduction of SBP of at least 5 mm Hg between the two study groups and an SD of 15 mm Hg. Considering a patient dropout ratio of 15%, the study will need to recruit 230 subjects in each group.Patients will undergo an initial baseline clinic examination, during which clinical measurements, demographic data, and past medical histories will be collected and electrocardiogram exams and biological examinations will be conducted.A validated blood pressure monitor  will be used for blood pressure measurements. After 1 month, a satisfaction questionnaire—the Medical Outcomes Study Short Form-12 questionnaire [Twenty-four–hour ambulatory blood pressure monitoring (ABPM) will be performed for all included patients to analyze their blood pressure profiles through the use of a Holter monitor . Ambulatory blood pressure measurements will be scheduled to acquire a blood pressure reading every 30 minutes from 6 AM to 10 PM and every 60 minutes from 10 PM to 6 AM. The cuff will be placed on participants’ nondominant arms. Of the 48 possible measurements, at least 32 (67%) must be available. Otherwise, ABPM will be repeated. The Holter monitor must not get wet , and usual activities must be maintained. After installing the Holter monitor, study participants can return to their usual activities. They will be invited to return to the clinic 24 hours later, so that we can collect the data from their monitors. The results will be interpreted by a cardiologist.Randomization will take place 1 month after participants’ inclusion, that is, after the collection of at least 32 interpretable ABPM measurements. All patients will be asked to attend 2 follow-up clinics within 6 months. The clinical follow-up data to be collected are detailed in Patients who meet the eligibility criteria will be randomly assigned to either of the study groups in a 1:1 ratio via the use of an interactive web responsive system.The study groups are as follows:Usual care group (control group): patients in this group will receive their antihypertensive treatment according to the usual approach during each consultation appointment made with the attending physicians.Telemonitoring group (intervention group): patients in this group will receive their usual care along with at-home self-monitoring, telemonitoring, and the titration of antihypertensive treatment.Participants randomized to the control group will receive usual care . In contrast to the intervention group, control group participants will not receive phone calls for therapeutic education, a treatment compliance assessment, treatment titration, or a side effect check. In cases of any worsening symptoms, patients will have to contact their general physician individually and independently.Participants randomized to the intervention group will receive therapeutic education, including information on diet, sleep, physical activity, and other lifestyle advice, from the research associate. Patients will also be provided with a validated blood pressure monitor (ROSSMAX X3), and they will be taught how to use the blood pressure monitor at home. Patients will be asked to measure their blood pressure 3 times in the morning and 3 times in the evening for 3 days per week.Once per week, the research associate will call the patients to check their treatment compliance and verbally collect the blood pressure measurements. Compliance evaluation will be conducted by asking the patients whether they have been taking their medication correctly every day on time for the past week. Patients will be asked to keep their empty treatment boxes. The remaining pills will be counted, and patient compliance will be assessed. The research associate will also remind patients about lifestyle and dietary measures. Subsequently, the research assistant will fill in the data entry fields in the electronic platform, which can be checked and validated by the investigators. Patients will be contacted every month via telephone by their attending physician for 6 months to titrate the antihypertensive treatment according to the data collected by the research associate. At day 90 and day 180, the medical visit will be conducted face-to-face. For the titration of antihypertensive medicines, the decision criterion will be the percentage of home blood pressure readings that meet the target. If at least 75% (375/500) of the readings since the last visit meet the blood pressure target, no changes in treatment will be considered. If less than 75% (375/500) of the readings meet the target, we will recommend readjusting the treatment. During the telephone follow-up calls, physicians will encourage participants to adhere to the treatment. Regardless of blood pressure control, if patients experience side effects, the involved antihypertensive drug will be stopped or changed, or its dose will be reduced.The target blood pressure will be based on the 2018 European Society of Cardiology and European Society of Hypertension Guidelines .The home blood pressure target will be ≤135/85 mm Hg, and the general practitioners’ office blood pressure target will be ≤140/90 mm Hg. The mean ambulatory blood pressure targets will be ≤135/85 mm Hg at daytime, ≤120/70 mm Hg at nighttime, and ≤130/80 mm Hg for 24 hours.t test or by its correction, as appropriate. The differences among the categorical variables will be evaluated with the Pearson chi-square test. All tests will be considered significant at the cutoff value of P<.05.Categorical variables will be expressed as frequencies and percentages, while continuous variables will be expressed as means with SDs. An analysis of variance will be performed to compare the two study groups in terms of the primary end point. The normality of continuous data will be assessed with the Shapiro-Wilk test. Furthermore, we will use a general linear model for repeated measures to compare the marginal means of Gaussian quantitative dependent variables before and after the intervention (a Bonferroni test will be considered). A nonparametric test (the Friedman test) will be used for the comparison of non-Gaussian quantitative variables before and after intervention. The Cochran Q test will be performed to compare binary dependent variables before and after intervention. Subgroup analyses will be performed by age (<65 years and ≥65 years), sex, and the severity of hypertension. Differences between continuous variables will be evaluated with a 2-tailed Student Data will be collected via an electronic data capture system  that is compliant with international data security requirements . Dacima Clinical Suite is authorized by the local body of personal data protection. The electronic case report form will be used to perform quality checks on the data  to increase the accuracy of the data. Double data entry will not be scheduled, as data will be directly captured in the electronic data system. Investigators and research assistants will use monitoring data tools as an audit trail for tracking the data modification log, data queries, and electronic signatures. Research assistants will use source document verification tools to ensure the accuracy of the collected data. Automatic alerts will be implemented to notify the responsible investigator about any data or protocol violations.Participants who do not have data on the primary outcome at the 6-month follow-up assessment will be labeled as those who are missing data for the primary outcome at this time point. A further sensitivity analysis will include participants with 1 missing measurement. The frequency (percentage) of losses to follow-up  after 6 months will be reported by randomized group and compared between the two groups. The availability of the outcome data for the primary and secondary outcomes will be summarized for the two randomized groups. The mixed-effects model implicitly accounts for data missing at random; however, the missing data mechanism will be explored. A logistic regression model will be used to explore any associations between baseline characteristics and the availability of data on the primary outcome. Any changes to the assumptions made in the primary analysis  will be considered in a sensitivity analysis.Our primary outcome will be the percentage of patients who exhibit a change of 10 mm Hg in average 24-hour SBP from baseline to the 6-month follow-up.The following will be our secondary outcomes:The percentage of patients who exhibit a change of 5 mm Hg in average 24-hour diastolic blood pressure from baseline to the 6-month follow-upThe percentage of patients who exhibit a change of 10 mm Hg and 5 mm Hg in average 24-hour blood pressure from baseline to the 6-month follow-upThe change in blood pressure load  percentaThe change in dipping  percentaThe percentage of patients taking more than 80% (400/500) of the antihypertensive medications at the 6-month follow-upThe percentage of patients with changes in mean 12-Item Short Form Survey scores from baseline to the 6-month follow-upClinical outcomes, including hospitalization rates and emergency room admissions related to high blood pressure, adverse effects, or other reasonsDefinitionsBlood pressure load: the percentage of abnormally elevated blood pressure readings, which is usually provided in the ambulatory blood pressure monitoring report. Normal values should be <40% ,15.Dipping: the difference between the mean systolic pressure during the day and mean systolic pressure during the night. This is expressed as a percentage of the daytime mean, and the accepted normal ranges between 10% and 20% .Full ethical approval for the trial was obtained from the local ethics committee of Monastir University of Medicine (reference number: IORG 0009738 N° 50/098060279). The study is registered on the ClinicalTrials.gov registry under the identifier NCT04607239.The electronic data capture system that was provided to the study is compliant with confidentiality requirements , and local regulatory authorization was obtained before starting the project. Personal data that are not relevant to the study will not be collected. Other personal data will be secured by obtaining specific rights for their use in follow-up monitoring only. Investigators and research associates will sign a confidentiality agreement before starting the project.The final data set will be extracted from the electronic data capture system along with anonymized personal data. The primary investigator will be responsible for access to the final data set for medical writing purposes. The Contract Research Organization team of Dacima is authorized to access the final data set to program statistical analyses and provide the final results of the project according to the statistical analysis plan. The primary investigator will be responsible for reviewing the data analysis and validating the final clinical study report.Recruitment to the trial started in July 2020. The data collection period is expected to last for approximately 12 months . The length of the study per patient will be 6 months. We expect to complete data collection by the end of 2021 and plan to disseminate the results subsequently.This paper describes the protocol for the HOROSCOPE study—a randomized controlled trial that will assess the impact of telemonitoring on the control of blood pressure. To our knowledge, this will be the first Tunisian study to compare telemonitoring to usual care in terms of the control of blood pressure. If telemonitoring is found to be successful, we will extend the study to other investigation centers throughout the Tunisian territory. We can, in the future, develop connected electronic devices that can send the results of blood pressure measurements directly to doctors.Randomized controlled trials are considered the “gold standard for evaluating the efficacy of different interventions in clinical research and constitute evidence for medical treatment” . By condA possible limitation is that enrolled patients may greatly vary in terms of their clinical profiles. In addition, subjects may feel overloaded by the daily measurements and questionnaires that need to be answered, which could result in dropouts. Another possible limitation is that the study population may not represent the overall Tunisian population.