Brachial blood pressure (finger photoplethysmography) and TCD waveforms were extracted at baseline and during the nadir blood pressure (BP) response to LBNP and analyzed using a modified Windkessel model to calculate indices of cerebrovascular resistance (Ri) and compliance (Ci). Compared with baseline, rapid-onset LBNP decreased MAP by 22 ± 16% and Ri by 14 ± 10% (both P ≤ 0.03). Ci increased  but MCAvmean  and CBF  were preserved. The results provide evidence that changes in both vascular resistance and compliance preserve CBF, as indexed by no significant changes in MCAvmean or DCS microvascular flow, during transient hypotension.The aim of the current study was to establish the interplay between blood flow patterns within a large cerebral artery and a downstream microvascular segment under conditions of transiently reduced mean arterial pressure (MAP). We report data from nine young, healthy participants  acquired during a 15-s bout of sudden-onset lower body negative pressure . Simultaneous changes in microvascular cerebral blood flow (CBF) and middle cerebral artery blood velocity  and a downstream microvascular segment, we used a novel combination of transcranial Doppler ultrasound of the MCA and optical monitoring of a downstream microvascular segment, respectively, under conditions of transiently reduced mean arterial pressure . A rapid increase in vessel compliance accompanied the maintenance of MCA blood velocity and downstream microvascular flow. Stability of cerebral blood flow across a range of perfusion pressures is achieved by adjustments in vasoactive properties in both the large arteries at the base of the brain , 2 and tThe ability to quantify dynamic flow patterns along the conduit-to-microcirculation segments of a cerebral vascular bed is limited in the conscious human due to the confines of the rigid skull –8. In maRecent advances in optical technologies, specifically the development of diffuse correlation spectroscopy (DCS) , make itIn addition to the expected but unmeasured continuity of dynamic flow patterns across the cerebrovascular bed, the potential mechanisms that underly this regulation remain incompletely understood, particularly in rapidly changing pressure. Whereas changes in vascular resistance (Ri) form the principle concept of control, recent modeling advances and experimental measures implicate dynamic changes in arterial compliance as well  that, whOur primary objective in this study was to establish the relationship between blood flow in the large middle cerebral artery (MCA), reflecting patterns affected by the entire vascular bed, and the corresponding flow in the downstream microvasculature under conditions of transiently reduced blood pressure. In addition, the potential roles played by Ri and Ci in these patterns were assessed. To complete this aim, we utilized simultaneous depth-enhanced DCS with TCD during a 15-s bout of rapid-onset lower body negative pressure (LBNP). We further combined the DCS measurements with depth-enhanced time-resolved near-infrared spectroscopy (trNIRS) to quantify changes in tissue oxygen saturation and cerebral blood volume. We tested the hypothesis that increases in Ci and reductions Ri in response to hypotension, would underly the maintenance of cerebral vascular bed perfusion and oxygenation.All procedures were approved by the Health Sciences Research Ethics Board (HSREB) at Western University (No. 112633) and Lawson Health Research Institute (No. 107985), adhering to the guidelines of the Tri-Council Policy Statement for research involving humans as well as those set forth in the Helsinki Declaration. Participants provided written informed consent following verbal and written explanation of the experimental procedures.n = 9) were subsequently included in the analysis. To control for potential influences of sex hormones on vascular function, female participants were tested during the luteal stage of menstruation (18 ± 2 day). Furthermore, participants reported to the Laboratory for Brain and Heart Health at Western University for testing following a 4-h fast (including caffeine) and 12 h of abstinence from alcohol consumption and physical activity.Ten healthy participants  were recruited. Before tests, participants completed a mandatory health history form to evaluate the inclusion/exclusion criteria. Participants were included if they reported being a nonsmoker with no prior diagnosis of cardiovascular disease, neurological disorder, diabetes, or hypertension. All subjects reported that they identify with their sex assigned at birth. One male participant was excluded as a result of insonation difficulties of the MCA from a poor temporal window. Therefore, a total of nine participants (2) and total hemoglobin (HbT), which is a marker of relative cerebral blood volume. The primary purpose of this study was to assess the coordination of macrovascular and microvascular perfusion of the brain during a hypotensive episode. The secondary purpose was to study the patterns of change in cerebrovascular resistance (Ri) and compliance (Ci) that support the macro-microvascular coordination. Our primary outcomes required the use of optical monitoring equipment  to measure microvascular hemodynamics and TCD to measure MCA and downstream microvascular hemodynamics. Due to limited space on the head, it was not possible to instrument the participants with trNIRS, DCS, and TCD simultaneously. Therefore, two protocols were performed in a randomized order : a TCD-DCS condition and a trNIRS condition. The latter was used to measure microvascular tissue oxygen saturation (StOTo create sustained but brief (15 s) bouts of orthostatic stress, participants were sealed from the waist down in an LBNP chamber. LBNP is a commonly used technique to mimic orthostatic stress while the participant remains in a supine posture. This technique is advantageous for the current study design, as it enables control over the intensity and timing of each bout of hypotension while minimizing movement of the participant. The latter is necessary for the highest quality data collection with optical monitoring technologies. Both the TCD-DCS and trNIRS conditions included one short (15 s) pulse of rapid-onset LBNP at −30 mmHg and another at −80 mmHg, followed by a 15-s recovery . To avoi2 , from which continuous heart rate (HR) was calculated. Finger photoplethysmography  provided continuous arterial blood pressure measurements at the finger that was calibrated against three manual sphygmomanometric brachial artery measures, and the 1-s delay in the analog output was accounted for before data analysis. Expired gas was sampled at the mouth for the measurement of partial pressure end-tidal COTo account for any psychosomatic influences on cardiovascular function, participants were asked to report their “feeling”  at baseline and immediately after each bout of rapid-onset LBNP, using an 11-point affect feeling scale.Cerebral blood velocity was measured as the instantaneous peak velocity in the right MCA (M1 segment) using TCD . The 2 MHz frequency ultrasound probe was placed on the transtemporal acoustic window and set to a depth of 47–55 mm. Ipsilateral carotid compression was used to ensure insonation of the MCA in each participant. The probe was then secured in place with a headband device to maintain insonation angle and position.mean.Doppler ultrasound and systemic variables were sampled at 1 kHz using a data acquisition system  and software  and stored for subsequent offline analysis. MCA pulse amplitude was calculated as the difference of each cardiac cycle’s MCA systolic peak and diastolic nadir. MCA pulsatility index was calculated as pulse amplitude divided by MCAvDiffuse correlation spectroscopy is an optical technique that uses near-infrared light to noninvasively measure microvascular flow . Unlike rSD) = 1 and 2.5 cm. DCS and TCD data were time-aligned within Labchart using a BNC-trigger connecting the DCS to the data acquisition software described earlier.DCS data were acquired at 4 Hz with an in-house built system , 13 consN), mean time of flight (<t>), and variance (V)  paired with a time-correlated single photon counting unit to record arrival times of individual photons, which are used to build a time-of-flight distribution of diffusely reflected photons DTOF; . Early aance (V) , 21. Becance (V) , 22.rSD = 3 cm using a 3-D-printed holder made of Flexible 80 A Resin . Diffusively reflected light collected by the detection fiber bundle was delivered to hybrid photomultiplier tubes . A time-correlated single photon counting unit  was used to record photon arrival times, and the corresponding DTOFs were built using LabView software. At the end of every study, the instrument response function (IRF) characterizing the time profile of the light source and detection system was measured using a custom-built light-tight box connecting the emission fiber to a detection probe with a separation of 9 cm. If necessary, a neutral density filter was placed in the box to avoid saturating the detector , all time courses were interpolated to 1 Hz resolution. Data are presented as percent change from the 6 s average immediately before starting LBNP. Further technical details regarding the data analysis for DCS and trNIRS are described elsewhere .a0, μs0', and an amplitude factor that accounts for laser power, detection gain, and coupling efficiency.Analysis of the trNIRS data is detailed in our previous works , 26, 27.N), the mean time of flight (<t>), and the variance (V). The moments were calculated by setting the lower and upper integration limits based on arrival times corresponding to 1% of the peak of the DTOF  for the two wavelengths individually.Next, each DTOF in the time series recorded at 760 and 830 nm was analyzed to calculate the first three statistical moments: the number of photons , each moment was multiplied by its corresponding sensitivity factor (a0(λ) and μs0'(λ) values. The μa(λ) time courses generated for 760 and 830 nm were converted to CHbO and CHb using:HbO(λ) and εHb(λ) are the molar extinction coefficients for oxy- and deoxyhemoglobin, respectively. Changes in StO2 were calculated by 2 and ΔtHb presented in the paper were derived from ΔV, which provides the greatest sensitivity to the brain.To convert the time courses of changes in a statistical moment into time-varying concentrations of oxy- and deoxy hemoglobin , was performed using the modified two-layer Beer–Lambert approach described by Baker et al. . This apa0 and μs0' at 832 nm), the coherence factor (β) determined from the average initial value of the baseline intensity autocorrelation functions, and average thicknesses of scalp (6 mm) and skull (8 mm) layers obtained from a previous study .Cerebrovascular Ci was calculated using a four-element lumped parameter modified Windkessel model. This model is described in detail elsewhere –32. Briet tests were used to assess the effect of LBNP intensity (TCD-DCS condition) on nadir responses (percent change) during −30 mmHg and −80 mmHg. The remaining variables were assessed using one-way repeated-measures ANOVAs with a fixed factor of time (10 levels: 3 s bins across 30 s) for LBNP trials at −80 mmHg. Post hoc testing for significant interactions and main effects was completed using Bonferroni’s (parametric) multiple-comparison corrections. All results are reported using the means ± SD. Statistical analyses were conducted using Prism, version 9 .Linearity and approximate normal distribution residuals were assessed qualitatively using visual inspection of Q–Q plots and formally tested with Shapiro–Wilk’s test. All variables, with exception of the ordinal Feeling Scale outcomes, met the assumptions of normality and were analyzed using a parametric approach. Friedman tests were used to assess the change in Feeling Scale responses. Student’s paired P ≥ 0.05 vs. baseline; mean (3.1 ± 2.6%), MAP (3.2 ± 2.3%), HR (3.8 ± 2.9%), and mean pulse amplitude, and Ci compared with rapid-onset LBNP at −30 mmHg .All subjects tolerated LBNP. Rapid-onset LBNP at −80 mmHg caused a small but not statistically significant decline in perceived feelings .No evidence of gender differences was discovered . This reduction . Heart rate increased between 6 and 15 s post-onset of LBNP  and remained elevated between 18 and 24 s (both P ≤ 0.045 vs. baseline). P = 0.05), although it is interesting to note that the variability was driven by two individuals with an 18 and 16 mmHg reduction due to apparent sporadic breaths. As designed, the short bout of LBNP allowed us to interrogate hemodynamic responses in the absence of significant changes in cardiac output  and stroke volume .Rapid-onset LBNP significantly reduced MAP , with thmean and microvascular CBF remained relatively constant throughout rapid-onset LBNP at −80 mmHg  in the presence of sustained systolic MCA blood velocity throughout . This corresponds to a 20 ± 20% increase in MCA pulsatility index (P = 0.03 vs. baseline). Relatedly, cerebrovascular Ci increased significantly between 7 and 15 s . trNIRS-derived HbT (P = 0.03); however, the conservative post hoc comparisons revealed no significant changes at any point in time.Both MCAveline; 2 G and HbTived HbT H tended This study utilized an emerging optical technology, DCS, combined with TCD to describe simultaneous cerebral macro- and microvascular responses to transient hypotension during a 15 s bout of LBNP. In agreement with previous studies , 33, 34,1) new evidence of preserved overall perfusion of the downstream microvascular segments and 2) further evidence of increased MCA compliance  was restored within ∼8 s following a rapid thigh-cuff induced 20% reduction in MAP . We have clarified the effect of these assumptions on DCS measures of flow in Shoemaker et al.. Althoug2 or HbT. Thus, this study demonstrates the utility of simultaneous, depth-enhanced optical and ultrasound measures of CBF to assess the cooperative and dynamic features of cerebrovascular regulation.The current study utilized rapid-onset LBNP to explore the hemodynamic responses of both the cerebral macro- and microvascular beds during a period of transient hypotension. This study produced the main finding that rapid increases in compliance during transient hypotension support a continuance of cerebral blood flow at the microcirculatory level. Specifically, our data revealed a rapid increase in cerebrovascular compliance during 15 s of rapid-onset LBNP with marked hypotension, with no significant change in macro- or microvascular CBF. The data are supported by no significant change in NIRS-derived measures or StOThe data that support the findings of this study are available from the corresponding author upon reasonable request. This work was funded through grants from the Canadian Institutes of Health Research (Grant No. 130391) and the Natural Sciences and Engineering Research Council of Canada (Grant No. R3592A02002 to K.S.L. and Grant No. RGPIN-2018-06255 to J.K.S.).L.S. and J.K.S. are relatives. None of the other authors have any conflicts of interest, financial or otherwise, to disclose.L.N.S., D.M., K.S.L., and J.K.S. conceived and designed research; L.N.S., D.M., A.S., and J.M. performed experiments; L.N.S., D.M., A.S., and J.M. analyzed data; L.N.S., D.M., K.S.L., and J.K.S. interpreted results of experiments; L.N.S. prepared figures; L.N.S. drafted manuscript; L.N.S., D.M., A.S., J.M., K.S.L., and J.K.S. edited and revised manuscript; L.N.S., D.M., A.S., J.M., K.S.L., and J.K.S. approved final version of manuscript.


Malaysia has the highest number of obese and overweight individuals in South-east Asia. The 2019 National Health & Morbidity survey found 50.1% of Malaysians to be overweight or obese with 30.4% being overweight and 19.7% being obese. This has led to the high rise of the bariatric surgeries demand and needs within the nation.To assess the level of fasting blood sugar (FBS), systolic, diastolic blood pressure, stop BANG score for obstructive sleep apnoea (OSA) and BMI (Body Mass Index) for the patients before and after bariatric surgeries (sleeve/gastric bypass) for a one year follow up period.The study was conducted among 1000 patients who underwent a single weight reduction surgery (sleeve/gastric bypass) by a single surgeon at the Cengild Medical Centre between January 2019 to January 2020. They were followed up for a one-year period through recording the parameters of fasting blood sugar (FBS), systolic, diastolic blood pressure, stop BANG score for obstructive sleep apnoea (OSA) and BMI (Body Mass Index). Study was conducted using universal sampling including all subjects visited the centre and a written consent was obtained from each participant. Descriptive statistics with mean was used and paired t-test was used for comparison and test the difference. The STOP-BANG acronym stands for: Snoring history, Tired during the day, Observed stop breathing while sleep, High blood pressure, BMI more than 35 kg/m2, Age more than 50 years, Neck circumference more than 40 cm and male Gender.The mean age of patients was 38 years old. Mean FBS for the patients one month before the operation was 10.42 mmol/L and 5.84 three months post procedure. The systolic blood pressure one month before the operation and 3 months after was 139.81 mmHg and 123.79 mmHg, while diastolic blood pressure was 86.84 mmHg and 81.07 mmHg respectively. BMI was reduced from 39.69 to 27.99 after one year from the weight reduction operation. All the above parameters showed a significant reduction between one-month pre operation as compared to 3 months and 12 months post operation and that improved the health parameters of the patients significantly.The weight reduction operations showed a significant reduction in the FBS, blood pressure, OSA scores and BMI at 3, 12 months after the operation These patients had better overall health after the significant reduction in these parameters. Malaysia has the highest number of obese and overweight individuals in South-East Asia . The 201Obesity has been proven to be a risk factor for major non-communicable diseases such as Type 2 Diabetes Mellitus (T2DM), coronary heart disease, hypertension, and cancers . Nyberg In the morbidly obese, diet and exercise alone are not enough to achieve significant weight loss. Bariatric surgery has proven to be an effective component of treatment for such groups. According to the American Society for Metabolic and Bariatric Surgery, bariatric surgery is indicated in patients with a BMI of >40, or >35 with one or more related co-morbidities such as T2DM, hypertension, and sleep apnea, among others . There was a 1% drop out on the 3 months follow up, 3% drop out by 6 months follow up and total 5% by the one year follow up.The majority of 98% of the respondents’ length of stay was of only one night and to be discharged the day after the surgical procedure, while the rest extended for 2 nights and there was less than 1% readmission.In that study the female were the majority with 81.4% as compared to 18.6% for males. The minimum age was 28 years old as compared to maximum age of 57 years old and the average of 38.2 years old. The average fasting blood sugar (FBS) one month before the operation was 10.42 mmol/L, and one day post operation was 6.21 mmol/L, 3 months at 5.84 mmol/L and 1 year at 5.11 mmol/L.The mean systolic blood pressure one month prior to operation was 139.81 mmHg while 3 months post operation was 123.79 mmHg and for the 12 months follow up post operation was 122.21 mmHg. Mean diastolic blood pressure one month before the operation was 86.84 mmHg while 3 months post operation was 81.07 mmHg and was 80.67 for the 12 months post operation follow up .The average Stop BANG score for obstructive sleep apnea (OSA) one month before the operation was 3.95 while 3 months post operation was 1.48 and for the 12 months post operation was 1.36.BMI results was the highlight being the concern of patients. Average BMI one month pre- operation was 39.69, and 33.81 at 3 months and 27.99 at 12 months . While tIn Those with DM, they used different treatments to control their blood sugar, and it was found that for 6.4% of them are using Insulin. While for the oral medications use, they were mainly using the Metformin (60.42%), Gliclazide (24.06%) and other medications (7.52%), while 8% were not on any diabetic medications.While the prevalence of hypertension was 68% and they were on the following medications: 55% of them on Amlodipine, 20% on Atenolol and 15% on others antihypertensive medications and 10% of them were not on any medications.The bivariate association and relation between these parameters a month before the operation as compared to the same variable 3 months and 12 months after the operation using the paired t test as can be seen in rd month after the operation (p< 0.001) and the mean difference between these 2 periods was 17.32 mmHg for systolic and 5.76 mmHg for the diastolic. The reduction shown to be significant also when comparing one month before the operation with 12 months post operation and between 3 months to 12 months post operation. At the beginning of the study, it was found that 68% of the respondents were with hypertension and 60% of them showed complete remission which is defined as being normotensive (BP <120/80) off antihypertensive medication, while 20% of them went into partial remission which defined as a prehypertension values (120-140/80-89) when off medication and the other 10% of them showed improvement which was defined as a decrease in dosage or number of antihypertensive medication or decrease in systolic or diastolic blood pressure (BP) on the same medication (better control) while, the last 10% of them showed unchanged readings in the blood pressure one year after the surgical procedure [The systolic and diastolic blood pressure showed a significant reduction between one month before the operation as compared to the readings on 3The mean difference of the Stop BANG score for obstructive sleep apnea (OSA) one month before the operation compared to 3 months and 12 months post operation was statistically significant of p value < 0.001, and the mean difference between 3 months and 12 months post operation was also statistically significant of p value 0.007. OSA was noticed among 415 (41.50%) of the respondents prior to the bariatric operation and then, it was demonstrated that 218 (52.53%) of them had remission in OSA after one year following bariatric surgery.The BMI also showed significant reduction when compare between the BMI a month before the operation which was 39.75 to 33.81 after 3 months and 27.99 after 12 months of the operation with p value <0.001 as can be seen in Regarding the complications trace during the one year follow up, it can be reported as follow; no major complication  been witnessed. Only minor complications happened and as the following: 4 cases with marginal ulcer diagnosed with upper endoscopy, nausea and vomiting requiring intravenous fluids (IVF) among 12 patients, 1 acute renal failure managed with IVF without the need of dialysis, 3 female patients with urinary tract infection managed with antibiotics, 3 patients with dehydration requiring IV hydration as an inpatient, 1 patient with vitamin B1 deficiency and 20 patients with severe anemia requiring IV iron infusion).In this study it was found the reduction in the DM, Hypertension, sleep apnea and the BMI were all significant as comparing before the bariatric surgeries and post the operation by different periods of follow ups. The basis for bariatric surgery aiming at accomplishing weight loss is the understanding that severe obesity is a disease associated with multiple health morbidities. This risk can be corrected or improved by successful weight loss in patients who were unable to achieve weight loss by non-surgical means .The mechanisms by which obesity raises the risk of developing hypertension are multifactorial, involving structural, functional, and hemodynamic changes within the cardiovascular system . One of Another explanation to that reduction in the blood pressure was that the surgically induced weight loss is associated with a noticeable reduction in renal and systemic inflammation and arterial hypertension . With reIn this study the remission for the hypertension after one year follow up was at level of 62% and that was close to other studies conducted on different places  the restSevere obstructive sleep apnea (OSA) is often seen among morbidly obese patients undergoing bariatric surgery. Snoring, STOP-Bang score ≥ 3, fatty liver, and high BMIs were significantly correlated with OSA. Dyslipidaemia and BMI were demonstrated to be associated factors for severity of OSA in this population . In our This prospective multicentred study also found similar result in which they found improvements in the OSA, that study was conducted through a standard overnight cardiorespiratory recording was conducted 12 months after bariatric surgery among 132 patients who had OSA diagnosed prior to operation. The prevalence of OSA decreased from 71% at baseline to 44% at 12 months after surgery (p < 0.001). OSA was cured in 45% and cured or improved in 78% of the patients, but moderate or severe OSA still persisted in 20% of the patients after the operation . Therefo1c lowering. Importantly, this is equally true for patients whose baseline BMI is below or above 35 kg/m2 [In our study the blood glucose level was one of the independent variables of concern which of interest to show the improvement in the blood glucose level after the bariatric surgery and that’s parallel with other studies and the following also considered Type 2 diabetes mellitus (T2DM) is the most studied metabolic disorder connected with obesity, with data demonstrating that improvement and remission of T2DM in patients with obesity is superior after bariatric surgery compared with conventional medical therapy. This further solidifies that bariatric surgery is now a part of some treatment algorithm for medical management of patients with resistant T2DM and severe obesity . A meta-35 kg/m2 . Randomi35 kg/m2 .For the study limitations, as it is a single centre study, the results are not generalizable, and we will recommend doing such a study among different centres to be able to do randomization selection to generalize the results.This study shows that bariatric surgery at a specialized referral center with dedicated upper gastrointestinal services does have improved outcomes as the decline in the FBS, blood pressure, OSA and BMI were all significant and that will support the conclusion of the effectiveness of the bariatric surgeries in managing the metabolic morbidities that been studied.


The prevalence of obesity, a preventable and reversible condition with a high impact on health, continues to rise, especially after the COVID-19 pandemic. Severe overweight is well recognized as a risk factor for diabetes and hypertension, among other conditions, that may increase cardiovascular risk. Obesity has grown simultaneously with a rise in the prevalence of chronic kidney disease, and a pathophysiological link has been established, which explains its role in generating the conditions to facilitate the emergence and maximize the impact of the risk factors of chronic kidney disease and its progression to more advanced stages. Knowing the mechanisms involved and having different tools to reverse the overweight and its consequences, bariatric surgery has arisen as a useful and efficient method, complementary or alternative to others, such as lifestyle changes and/or pharmacotherapy. In a detailed review, the mechanisms involved in the renal consequences of obesity, the impact on risk factors, and the potential benefit of bariatric surgery at different stages of the disease and its progression are exposed and analyzed. Although the observational evidence supports the value of bariatric surgery as a renoprotective measure in individuals with obesity, diabetic or not, randomized studies are expected to establish evidence-based recommendations that demonstrate its positive risk–benefit balance as a complementary or alternative therapeutic tool. The continuous growth in the prevalence of overweight, aggravated by the COVID pandemic , is caus2, has been rising over the past few decades, reaching a worrying figure of 650 million obese adults in the world in 2016  of >30 kg/m in 2016 . Between in 2016 , nephrol in 2016 .In addition, approximately 15% of United States adults (37 million people) are estimated to have CKD, with diabetes and hypertension being the most common causes. Other risk factors such as cardiac disease, family history of CKD, inherited kidney disorders, previous renal injuries, older age, and obesity are now recognized . In the Efforts to reduce the systemic, particularly the renal, effects of the overweight pandemic must be adopted seriously, using the best available tools, especially if the knowledge about the effects of obesity on the kidney and the benefits of its reversal is growing. Bariatric surgery techniques are emerging as the most successful weight loss strategies for adults with extreme obesity, and their application in patients with chronic kidney disease deserves to be validated.A definitive link between obesity and renal damage was established in 1923 by Preble , increas2) could increase or not the risk  activation, and eventually, renal inflammation . Two typMechanisms of damage in obesity-associated kidney disease involve hemodynamic , metabolic (dyslipidemia and adipokine dysregulation) and lipid nephrotoxicity  , and oxiAn obese state is characterized mainly by an increase in white adipose tissue and it is associated with a low-grade systemic inflammation through an increased release of pro-inflammatory products (TNF-α and IL-6) and a reduced effect of favorable adipokines (leptin and adiponectin) .The participation of inflammatory markers in the pathogenesis of glomerular hyperfiltration (a key element in the pathogenesis of kidney damage) deserves special mention since it opens a new avenue of pathophysiological studies that can provide diagnostic, prognostic, and therapeutic guidelines. There is published evidence showing that the activation of the NLRP3 inflammasome is an effect shared by obesity and insulin resistance . RecentlLeptin, the physiological satiety hormone secreted by adipose tissue, inhibits insulin synthesis and secretion, decreasing energy expenditure and food intake by stimulation of hypothalamic receptors . ObesityJust as it occurs for proinflammatory cytokines, something similar is observed for adipokines. A decrease in leptin and visfatin levels and an increase in adiponectin can be observed after successful bariatric surgery in patients with established CKD .Some authors have linked low levels of adiponectin to an increase in cardiovascular risk in obese and hypertensive individuals with renal damage , but oth2. This fact has been observed also in studies of twins with different BMI  database for the years 2010–2015 shows that the chance of developing CKD (adjusted for risk factors) and of reaching ESRD is lower in those with BS .Indeed, BS is the most effective therapeutic option for morbid obesity and has been shown to induce modification of multiple risk factors involved in the progression of CKD . MoreoveThere are many BS modalities, which are described later. The most frequently used has been the gastric bypass, but there is a trend to adopt the sleeve gastrectomy (SG) as the first choice  owing toAn adjustable silicone band is positioned around the top of the stomach after the esophagus to reduce its size as well as slow the passage of food through the restriction. With this surgical technique, approximately 30% of excess body weight is expected to be lost after 2 years of follow-up. Although this procedure is the one that people have most often heard of, it accounts for approximately 10% of bariatric procedures because it is deemed less effective than the others .In this case, the stomach is divided by stapling, which results in a ‘sleeve’-shaped stomach removing approximately 70% of it. Since parts of the stomach are removed, neurohormonal changes can be observed, such as decreased concentrations of Ghrelin, the hunger-stimulating hormone. This peptide is mainly produced by cells located in the gastric fundus, which is removed, and this can diminish appetite contributing to further weight loss. Approximately 60% of excess body weight is expected to be lost at 2 years after surgery .Two different types of gastric bypass are in use: the Roux-en-Y gastric bypass and the loop gastric bypass. In both techniques, a smaller stomach/pouch is made using staples. Then, a loop is shaped in the bowel, which forms a new way for the food to leave the stomach (shorter than before), which can subsequently cause some minor malabsorption contributing, together with the reduced volume of food, to an effective weight loss. Expected weight loss is approximately 60%–70% of the excess at 2 years post-surgery .Surgery is considered a successful method to reduce appetite, and deciding which procedure is better for some people may be easy, but not for others. It is very effective in reducing weight, showing additional benefits in T2DM, high blood pressure, obstructive sleep apnea, and high cholesterol; other conditions, including osteoarthritis, skin conditions, and hormone-related problems such as polycystic ovary syndrome/subfertility, are likely to benefit, in addition to many others .The first beneficial effect of BS was shown in diabetic patients  with a 6Following surgery, a weight loss of 25% can be maintained for the long term. The glucose-lowering effects rely on the effect of peripheral insulin resistance, but several interesting mechanisms, independent of weight loss, have been proposed as participants in the renoprotective outcome .Indeed, evidence is growing that changes in gut hormones (such as GLP-1), intestinal microbiome, plasma bile acids, and nutrient-sensing mechanisms may participate in the long-term benefits , 76, altMetabolic surgery, by reducing increased intraabdominal pressure, improves renal vein pressure, increases renal blood flow, and normalizes GFR, plasma renin activity, and aldosterone levels, all of them involved in proteinuria . BS has Experimental data from animal models show that in parallel with improvements in weight and metabolic control, BS improved the kidney itself reducing fibrosis, inflammation, and oxidative stress at a transcriptomic level , 83.A meta-analysis based on observational studies shows an improvement in albuminuria/creatininuria, both weight and blood pressure independently. With respect to GFR, the main demonstrated effect is a reduction in individuals with hyperfiltration and an increase in those with reduced eGFR .A systematic review and meta-analysis of observational studies about the positive impact of BS on renal outcomes  showed rChanges in body surface area, after the surgery, induce problems in the interpretation of changes in measured GFR in individuals with preserved renal function  with theThe main effect of BS has been demonstrated in a reduction in the GFR of hyperfiltrating patients . The sysHowever, it may be more important to demonstrate if it may reduce the risk of developing CKD. A problem observed after the readout of the renal outcomes in the available published literature is that many of the manuscripts have shown short-term results. A systematic review  explorinThe impact of BS on risk factors of CKD was evidenced early after the introduction of the technique and is well described in a meta-analysis reported in 2014 . With reFor hypertension, remission, defined as a blood pressure less than 140/90 without medications, was obtained in 38% of cases with gastric bypass  and 17% with a gastric band (prospective cohorts). Confirming the positive effect, in adolescents, it induced remission of high blood pressure in 75% of subjects .An improvement in dyslipidemia has also been found, with a remission rate of 60% after gastric bypass and 23% after the gastric band .The impact of BS may be observed in patients without diabetes also; observational studies have shown a reduction in albuminuria and risk of ESKD after a follow-up of 18 years . In CKD,In patients with moderate and high baseline CKD risk categories, BS is associated with an improvement in the CKD risk itself, in a large proportion of patients followed for up to 7 years. These findings support the introduction of CKD risk in presurgical evaluation for bariatric surgery . A retroMetabolic surgery has been shown to reduce the likelihood of CKD progression and improve kidney function in observational studies , but theA recent retrospective study  of the UThe CKD preventive effect of BS may be quantified from the data observed in the SOS study where a 47% of reduction in CKD stages 4 and 5 after a median 10 years follow-up was described. The protective effect was greater in patients with a baseline UACR > 34 mg/mmol, needing to treat 4 patients to prevent 1 case of CKD, stages 4 or 5 . Data frAlthough in observational studies, surgery shows improvements in creatinine-based renal outcomes, long-term studies using other filtration markers less dependent on body mass are needed .Renal protection induced by BS may last up to 9 years in patients with or without decreased baseline kidney function, hypertension, and diabetes . The besThe results of randomized, controlled trials in patients with well-defined and staged CKD powered to detect surrogate endpoints of disease progression  or, evenA meta-analysis of eight studies (six retrospective studies) including 766 patients with CKD of ≥3 described eGFR and/or creatinine improvement in 63% of the cases, independent of the surgery technique used, blood pressure, BMI, or presence of diabetes . Only onAlthough it has been reported that individuals with a lower preoperative eGFR experience less weight loss after BS, others have found that preoperative renal function may not have an independent impact on postoperative weight loss in patients with eGFR of ≥30 mL/min . On the More advanced stages of CKD do not appear to be statistically associated with an increased risk of early postoperative complications . StudiesParadoxically, in patients in dialysis, morbid obesity is protective if it is accompanied by muscle mass gain , 108. HoBetter selection criteria to submit patients to BS, which include the severity of obesity, goals , patients preferences, and tolerance to the risk, are also necessary .Obesity may impede access to kidney transplantation , 115. InMeta-analysis has shown that patients with obesity after renal transplants have a higher risk of delayed graft function, risk of death, biopsy-proven acute rejection, and allograft loss . Patient2 with cardiovascular and metabolic comorbidities and without previous bariatric procedures (Some authors suggest that surgery should be considered 6–12 months after transplantation for patients with a BMI of >35 kg/mocedures .The intervention, whether performed before or after the transplant, is effective and safe, and the time to do so must be individualized for each patient .The pharmacological effect of BS on immunosuppressive regimens must be tailored because potential changes in drug disposition after the anatomical and functional changes in the gastrointestinal tract  need to Perisurgical complications are higher in patients having both obesity and renal disease , 121, anLong-term problems vary with the surgical technique used . MechaniAn important matter is that 1/3 of the patients submitted to BS may experience suboptimal results or significant weight regain in the first few postoperative years . PsycholAn important issue in the therapy of obesity and its consequences is the persistence and duration of its effects. Although there is little doubt about the superiority of surgery over non-invasive therapies in terms of effectiveness, RCTs are expected to compare surgery treatment in addition to pharmacotherapy versus lifestyle changes and pharmacotherapy alone to help in deciding rationally the best recommendation in CKD, established or at risk of it. A synergic effect between surgery and medical therapies exists .The most important point is an eventual change in the CV risk. Here, the best studies have been done using RYGB showing, at 7 years of follow-up, a reduction in adjusted mortality of 40%, mainly attributed to a reduction in diabetes-associated cardiovascular events . But theThen, the targeted use of metabolic surgery to improve the cardiovascular and renal risks must be balanced against the undesirable short and long-term risks and sequelae of the procedure, which can be of particular concern to patients with CKD .The lack of randomized clinical trials, low follow-up rates, and poorly reported data regarding co-morbidities and quality of life in many of the studies indicate that these findings should be interpreted with caution.The use of multitarget therapies with appropriate education and combinations of SGLT2 or GLP-1 agonists with RAS blockade and BS could obtain more integrated management of the inflammatory state and modulate adipocyte cytokines, in order to obtain the best renal protection .Taking all of the above into account, if an increment in urinary albumin excretion is found in a patient with obesity, it is mandatory to intervene to reduce overweight, control hypertension, diabetes, and dyslipidemia with all the available tools to prevent future chronic renal damage .The author confirms being the sole contributor of this work and has approved it for publication.This work was supported by the Programa de Especialización en Medicina Interna, Facultad de Medicina, Universidad Austral de Chile.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The hypertensive index may be a more sensitive marker of treatment effect than assessing blood pressure measurements alone. The use of such scoring systems in future trial design may allow more accurate reporting of the effects of interventions for hypertension.A key limitation in assessing the therapeutic impact of non-pharmacological approaches to treating hypertension is the method of reporting outcomes. Reducing the medications required to achieve the same blood pressure may be reported separately to a reduction in the blood pressure without change in medication, and thus lessen the reported beneficial impact of treatment. This study aims to derive a novel scoring system to gauge the therapeutic impact of non-drug treatment of hypertension by utilising a combination of excessive blood pressure and the number of anti-hypertensives into a combined score—the hypertensive index (HTi). The hypertensive index was empirically derived based on the systolic blood pressure and number of antihypertensive drugs, and applied retrospectively to a cohort undergoing intervention for renovascular hypertension. Subgroup and receiver operating characteristic analyses were used to compare the HTi to traditional methods of reporting outcomes. Following intervention (99 patients), 46% had improvement in both medication load and blood pressure, 29% had benefit in blood pressure without reduction in medication load, 15% had reduction in medication load without significant change in blood pressure and 9% showed no benefit in either parameter. The HTi was superior in detecting benefit from intervention compared with measuring blood pressure or medication load alone (AUC  The magnitude of this impact is demonstrated in a recent large-scale analysis of randomised trials that found a 5 mm Hg reduction of systolic blood pressure reduced the risk of major cardiovascular events by about 10%4.Hypertension is the most important single modifiable risk factor for many cardiovascular diseases such as ischaemic heart disease and stroke, in addition to contributing to other long-term sequelae including end organ damage, chronic kidney disease (CKD), cognitive impairment/dementia and mortality6.Hypertension that is resistant to treatment occurs in 10–20% of patients. Partly this may relate to poor compliance with up to ½ of newly diagnosed hypertensives stopping their antihypertensive medications by 6 months, and up to one quarter of patients not taking any of their antihypertensive medications. This poor adherence to prescription may be attributable to various factors including polypharmacy, adverse effects, and the difficulty in accepting lifelong treatment for an asymptomatic disease. Therefore it is unsurprising that there is interest in non-drug treatments for hypertension5. However, a key limitation in assessing the therapeutic impact of a device is the method of reporting outcomes, as a beneficial impact may be measured either in terms of absolute blood pressure change or by the impact on the number of drugs required. Reducing the number of medications to achieve the same blood pressure may be reported separately to a reduction in the systolic blood pressure with no change in medication, and thus lessen the reported beneficial impact of the treatment. This problem was seen in the ROX CONTROL trial, that randomised 83 patients to either standard care or insertion of AV coupler7. They found that whilst the device led to a reduction in blood pressure of 27/20 mmHg, 25% of patients in the coupler group decreased their antihypertensives whilst 30% of the control group had an increase in medications. Thus, intention to treat analysis of the blood pressure changes alone may have masked the true extent of beneficial effect.There are several differing approaches to devices to treat hypertension including renal artery stenting, renal denervation, vagal nerve stimulation, carotid body ablation, and arteriovenous fistula formation8. However this pragmatic approach fails to accommodate for a difference between those requiring single-agent or multi-agent treatment to maintain a specific blood pressure. In addition, the indiscriminate use of a set blood pressure equivalent of 10 mmHg is arbitrary, with few single agent randomised controlled trials achieving this measure of reduction, and an unknown efficacy of multi-drug regimens of varying type9.There have been few previous attempts to describe ‘treated blood pressure’ in the literature. One recent example, the Genome-Wide Association Study on blood pressure and Hypertension (GWAS), used a composite measure by supplementing the systolic blood pressure by 10 mmHg if a patient was prescribed any number of antihypertensive drugsThe aim of this study was to derive a novel scoring system to gauge the therapeutic impact of non-drug treatment of hypertension by utilising a combination of excessive blood pressure (> 120 mmHg) and the number of anti-hypertensives into a combined score—the hypertensive index (HTi).A retrospective analysis was performed of all patients who had received non-pharmacological intervention  for the treatment of renovascular hypertension in a defined geographical area in the West of Scotland (population 2.4 million) across 3 centres between 2010 and 2022.A database of patients with mechanical intervention performed for hypertension was used and augmented by a word-search of the radiology information system in which all imaging and interventions are reported. Case-notes were reviewed, and data obtained.Data extracted included patient demographics as well as the indication for intervention and the systolic and diastolic blood pressure measurements before intervention and at the point of discharge following intervention. The number of prescribed antihypertensive medications was recorded at each of these time periods. 2 patients who died in the immediate perioperative period were excluded from this analysis.11. Measurements relating to blood pressure and medication load before and after intervention in each study were collected to facilitate calculation of the HTi in each study cohort.For comparative analysis, published data from two multi-centre studies of renal artery stenting were accessedA novel marker of excessive blood pressure and medication load was empirically derived based on the systolic blood pressure and number of antihypertensive drugs.The number of antihypertensive medications was supplemented by a factor of 1 to allow calculation of the hypertensive index in those requiring no antihypertensive medications.A subgroup of patients who did not achieve significant blood pressure change was then assessed using the Hypertensive Index to evaluate for a more sensitive measure of treatment effect.Receiver operator characteristic (ROC) analysis was used to compare the HTi against conventional measurements .Various iterations of the HTi formula were tested to assess changes in the sensitivity and specificity depending on the blood pressure measurement component; including mean arterial pressure, diastolic pressure and pulse pressure.To compare the Hypertensive Index against the GWAS method, pre- and post-intervention scores were calculated for each patient and the reduction in these scores compared. Scores pertaining to the GWAS method were calculated by the addition of 10 mmHg to the patients’ systolic blood pressure if they were prescribed any antihypertensive drug. ROC analysis was used to compare the efficacy of each in determining whether intervention had been ‘successful’.11. Mean pre- and post-stenting HTi scores calculated for each cohort, and their outcomes compared.Further analysis was performed to assess the potential utility of the pre-intervention HTi in predicting the impact of treatment. The published data from two multi-centre studies of renal artery stenting were analysed12.‘Significant change’ in blood pressure was defined as a reduction in systolic blood pressure of ≥ 20 mmHg, or diastolic blood pressure of ≥ 10 mmHgFor the purposes of ROC analysis, ‘successful intervention’ was defined by a significant change in blood pressure without additional antihypertensive medications, or by any reduction in medication load without an increase in blood pressure.Data was collated using Microsoft Excel (Version 16.53 © Microsoft 2021). Statistical analysis was performed using RStudio . Data distribution was assessed using Shapiro-Wilks Test. Means were compared by Paired T-test, Welch Two-Sample T-test or Mann–Whitney U Test as appropriate.13.All participants provided written informed consent and all study procedures were in concordance with the Declaration of Helsinki, 1975 (revised 2000). Formal ethical approval was not required as per national legislation produced by the Health Research Authority99 patients were treated for hypertension with an intervention in the time-period studied, with a median age of 63 years (IQR 53–74). Only 5 patients were non-white, an equal number were males and females, and the underlying aetiology was atherosclerotic renal artery stenosis (ARAS) in 86%. The interventions performed included RA angioplasty (n = 16), RA stent (n = 78) and unilateral nephrectomy in 5 cases for renal artery occlusive disease not amenable to endovascular treatment. 4 additional patients in whom it was not possible to fully revascularize or remove an ischaemic kidney were analysed separately.Renal artery intervention across the entire group led to a substantial reduction in systolic and diastolic blood pressure and prescribed antihypertensive medications at the point of discharge. Blood pressure fell from 185/91 to 142/77 mmHg, plus a reduction in drug therapy from 3.2 medications to 1.8 , there was no significant change in the Hypertensive Index Fig. . SimilarReceiver operating characteristic (ROC) analysis showed that the Hypertensive Index was superior to blood pressure measurements or medication load alone in identifying a successful intervention Fig. .Figure 6The addition of alternative combinations including diastolic blood pressure, mean arterial pressure and pulse pressure failed to improve the sensitivity of the HTi in identifying beneficial change Fig. .Figure 78. Whilst the GWAS method outperformed blood pressure or medication load alone, it had a smaller area under the curve (AUC) than the Hypertensive Index , it is a practical and pragmatic measure of hypertension severity. This may require refinement if ongoing studies of lower total doses of multiple drugs or single polypharmacy pills are successful. To date however, single and additive medication prescription remains the basis of antihypertensive regimens. In addition, the effectiveness of the overall regimen is the basis of the HTi, and thus achieving better blood pressure control will outweigh an increase in the number of medications, e.g., comparing 145 mmHg on 2 tablets (HTi of 75) rather than 130 mmHg on 4 tablets (HTi of 50).15, with an arbitrary value of 10 mmHg used as an average impact on systolic blood pressure. As the HTi uses data from each individual patient—measured blood pressure and prescribed medication load, it provides a more direct, individualised, and nuanced measure of the effect of intervention on blood pressure that measures the differing impact of medication on individual patients.A comparison of the HTi to another method (GWAS) demonstrated a better performance. However, this would require a larger sample size to determine if this difference is clinically relevant. It is notable however, that the alternative methodology of describing ‘treated blood pressure’ was based on estimation of variance components applied to a pre-existing datasetThere is a recognised limitation in the lower end of the HTi with an achieved systolic blood pressure of 120 leading to a score of 0, irrespective of the number of medications employed. This is due to there being no excess risk from increased blood pressure. Similarly, a blood pressure lower than 120 will achieve a negative score, which itself be a marker of risk or over-treatment.10. Applying this measure to the individual data may be revealing. The next step would require validation, ideally by prospective use in larger randomised controlled trials of blood pressure treatment, and its utility in predicting the risk of cardiovascular events should be investigated.Whilst the findings are encouraging, the study cohort is small, and would ideally be replicated in larger data series, for example using a dataset from a large well-recognised RCT. The HTi, when applied to the mean measures of blood pressure and medication load in the CORAL trial, demonstrated that the predicted impact of treatment would overall be very low—as observed in the trialIn conclusion, this study describes a novel scoring system which combines excess blood pressure and medication load into a single combined score. This may be a more sensitive marker of treatment effect than assessing blood pressure measurements alone. The use of such scoring systems in future trial design may allow more accurate reporting of the effects of interventions for hypertension.


There is growing attention to how unfounded beliefs about biological differences between racial groups affect biomedical research and health care, in part, through race adjustment in clinical tools. We develop a case study of the Eighth Joint National Committee (JNC 8)'s 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults, which recommends a distinct initial hypertension treatment for Black versus nonblack patients. We analyze the historical context, study design, and racialized findings of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) that informed development of the guideline. We argue that ALLHAT's racialized outcomes emanated from a poor and artificial study design and analysis weakened by implicit assumptions about race as biological. We show that the acceptance and utilization of ALLHAT for race correction arises from its historical context within the “inclusion-and-difference paradigm” and its indication of the inefficacy of angiotensin-converting-enzyme inhibitors for Black patients, which follows from the enduring, yet, refuted slavery hypertension hypothesis. We demonstrate that the JNC 8 guideline displays the self-fulfilling process of racial reasoning: presuppositions about racial differences inform the design and interpretation of research, which then conceptually reinforce ideas about racial differences leading to differential medical treatment. We advocate for the abolition of race adjustment and the integration of structural competency, biocritical inquiry, and race-conscious medicine into biomedical research and clinical medicine to disrupt the use of race as a proxy for ancestry, environment, and social treatment and to address the genuine determinants of racialized disparities in hypertension. But aimed at providing patient-centered care, they worry that they may harm patients by ignoring race or disregarding race-adjusted clinical tools.Racial disparities in cardiovascular disease (CVD) and guidelines recommending distinct hypertension treatment by race are often cited to claim that racial groups are biologically real entities, that race should be taken as primary health information, and that the current push to acknowledge race as a social construction is “political correctness” run amok in medicine.3 The urgency around this dilemma has intensified as emerging data demonstrates that even when racialized hypertension treatment guidelines are widely used, they do not appear to reduce racial disparities in hypertension control.4This paper focuses on one such example of race adjustment, hypertension management guidelines, which commonly assert that angiotensin-converting enzyme (ACE) inhibitors are not as efficacious and should not be prescribed as initial antihypertensive therapy for Black patients.5 The investigators argue, “Race differences in group blood pressure responses to monotherapy with ACE inhibitors are an inaccurate means of predicting the magnitude of BP-lowering with an ACE inhibitor in individual patients of either race because of the near-complete overlap of the BP response distributions of Blacks and whites, and because a significant portion of the race difference in BP response is attributable to factors that vary at the level of the individual.”5 Indeed, physicians cognizant of and focused on reducing demonstrated racial inequities in hypertension6 are correct to be skeptical of race-based medical recommendations as a mechanism for their mitigation.Furthermore, drug treatment outcomes seem to vary more within than between racial groups, demonstrated by a study comparing the blood pressure (BP) outcomes of Black and white hypertensives on ACE inhibitor monotherapy.This article is a theoretical analysis and conceptual critique of the Eighth Joint National Committee (JNC 8) Evidence-Based Guideline for the Management of High Blood Pressure in Adults. We examine the origins of distinct treatment guidelines that so many lean on as a paradigmatic case. In this case, we assert that the race-specific components of the JNC 8 guideline and their primary evidence basis, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), demonstrate racialized thinking that is cognitively and institutionally self-affirming rather than based in good evidence. We analyze five interlocking issues in ALLHAT's design and analysis and show that ALLHAT's racialized outcomes, as well as their uptake by JNC 8, were a product of the racial worldview (RWV).We offer a historical analysis of the conception of a Black patient-specific physiology, which is rooted in the debunked but perpetuated slavery hypertension hypothesis and part and parcel of the inclusion and difference paradigm. Furthermore, we illustrate that this case study exemplifies a self-fulfilling prophecy of racial reasoning, in which assumptions about racial difference inform the design and interpretation of research which then serve to reinforce ideas about racial differences leading to differential medical treatment. Finally, we call for a rejection of racial essentialism in biomedical research and clinical treatment and an embrace of biocritical inquiry, structural competency, and race-conscious medicine, which aim to parse out and address the specific social and structural determinants of racial inequities in hypertension.3 There are several commonly prescribed drugs to treat hypertension; this article will focus on the medications tested in ALLHAT: thiazide-type diuretics, calcium channel blockers (CCBs), and ACE inhibitors,7 each of which have different biological mechanisms.Hypertension is defined as of 2017 by the American College of Cardiology and the American Heart Association as having systolic pressure greater than or equal to 130 mmHg and/or diastolic pressure greater than or equal to 80 mmHg.8 CCBs prevent the entrance of calcium into the cells of the heart and arteries, decreasing the strength of heart contractions and relaxing blood vessels to lower BP.9 ACE inhibitors work in the renin-angiotensin-aldosterone system (RAAS).10 Normally, after renin converts angiotensin to angiotensin I, the ACE converts angiotensin I to the vessel-narrowing angiotensin II (its active form). ACE inhibitors inhibit this ACE enzyme.10 Without ACE inhibition, angiotensin II increases BP by constricting the blood vessels, and impacts greater levels of aldosterone, causing more water and sodium reabsorption and increasing blood volume as well as pressure.10Thiazide-type diuretics inhibit sodium and water reabsorption in the kidney, decreasing fluid volume to diminish BP.11 As kidney function worsens, the RAAS is upregulated with increases in the release of renin and downstream products, which can lead to or worsen hypertension.12 Thus, ACE inhibitors and angiotensin receptor blockers (ARB), both of which work within the RAAS, or a combination of these drugs and CCBs and diuretics are commonly recommended as initial treatment for patients with hypertension who suffer from CKD.11Hypertension is seen in most patients with chronic kidney disease (CKD) and can both lead to and result from CKD, which is defined by decreased kidney function, measured through estimated glomerular filtration rate (eGFR), or kidney damage, often indicated by the presence of protein in the urine.2The JNC 8 Evidence-Based Guideline for the Management of High Blood Pressure in Adults, published in 2014, and a major focus of this article, was aimed at offering evidence-based recommendations to clinicians for managing hypertension. The guideline follows the logic of other racialized clinical decision-making tools in distinguishing drug treatment recommendations for the “general nonblack” versus the “general Black population.”2 Through recommendation eight, which cites the African American Study of Kidney Disease and Hypertension Study,13 the guideline recommends that patients with CKD and hypertension, “regardless of race or diabetes status,” be treated with “an angiotensin-converting enzyme inhibitor (ACEI) or ARB to improve kidney outcomes.”2It specifies that while nonblack patients should be treated initially with a “thiazide-type diuretic, calcium channel blocker, angiotensin-converting enzyme inhibitor, or angiotensin receptor blocker (ARB)” according to recommendation six, Black patients should be treated initially only with a thiazide-type diuretic or CCB, based on recommendation seven.14 This concept of a Black patient-specific physiology, defined by high salt sensitivity and low plasma renin, is commonly cited as an explanation for why ACE inhibitors are not as effective for Black patients, since ACE inhibitors lower BP by inhibiting the enzyme that acts on angiotensin I, the product of renin.15–17 The historical underpinnings of this supposition will be delineated later. Although the JNC 8 guideline does not explicitly call upon this supposed racialized physiology, its recommendations, which assert ACE inhibitors are not an appropriate first-line therapy for Black patients, follow this same logic.Significantly, as previously described, ACE inhibitors operate in the RAAS. There is a common idea in biomedical research that Black folks are predisposed to low concentrations of renin, the enzyme that converts angiotensin to angiotensin I in the RAAS or RAS, and therefore decreased plasma renin activity (PRA).* Indeed, JNC 8 recommends ACE inhibitors for all patients with CKD, regardless of race. These conclusions are essential and will be expanded on later in the context of the guideline and study on which this article focuses.In terms of CKD, the upregulation of the RAAS  commonly seen with this disease may lead to the conclusion that Black individuals with CKD, whose renin levels are bolstered, become good candidates for drugs that inhibit the RAAS, including ACE inhibitors.2 This article focuses on this trial, a National Institutes of Health (NIH) National Heart, Lung, and Blood Institute funded study which began in August of 1993 and was completed in March 2002. ALLHAT was groundbreaking at the time of its design in its comparison of classically used diuretics with the more novel CCB and ACE inhibitor drugs in terms of “fatal coronary heart disease (CHD) incidence” as well as other CVD events.7The evidentiary basis for recommendation seven—which explicitly recommends a differential initial hypertension treatment based on race—comes from the outcomes of the ALLHAT.18 Ultimately, ALLHAT reported several significant race-specific results based on secondary outcomes pointing to the inefficacy of lisinopril, the ACE inhibitor, for Black patients. These results, including a decreased reduction of systolic blood pressure (SBP) and increased relative risk (RR) of stroke and combined CVD for Black patients using lisinopril, the ACE inhibitor, as compared to chlorthalidone, the diuretic, informed the JNC 8 recommendations.17ALLHAT initially defined its primary outcomes as “combined fatal CHD or nonfatal myocardial infarction” and its secondary outcomes as “all-cause mortality, fatal and nonfatal stroke, combined CHD , and combined CVD  , and peripheral arterial disease).”7 Indeed, the Protocol articulates the disproportionate burden of hypertension for Black Americans and thus the ramifications of the study for Black folks. Focused on testing the more expensive CCBs and ACEIs against cheaper diuretics partially due to a dearth of comparative studies attentive to hypertension and CHD reduction, the Protocol also explicitly states that the cost consideration is important for Black patients.7ALLHAT's influence based on a racialized subgroup analysis is unsurprising as its intentions were specifically racialized from its inception. In ALLHAT's Protocol, the third listed rationale for the ALLHAT study is the “Importance of Comparing Antihypertensive Agents in African-Americans.”7 The end of the protocol states, “… given the relative lack of clinical trials information in African-Americans, they should be heavily represented in the current trial so that the results will be directly applicable to them. For these reasons, the population for this trial will be at least 55% African American,” demonstrating the principal investigators' hypothesis of the existence of racialized distinctions in drug efficacy and aim to include an ample number of Black participants to ensure that any such differences are produced.7ALLHAT asserts that it is essential for Black patients, whom they posit as more often low-income with decreased access to medical care, to know whether cheaper drugs such as diuretics are as efficacious as CCBs and ACEIs.post hoc analysis and reformulation of the study question; (3) artificial study design; (4) overstatement of drug differences; and (5) selective uptake of evidence. Here, we are artificially simplifying and separating the different components for the purpose of accessibility.We argue that the differential racial recommendations crafted by JNC 8 and informed by ALLHAT are shaped and discredited by five interlocking issues in ALLHAT's design and analysis and the incorporation of outcomes into JNC 8; namely (1) poorly defined categories/measures; (2) 19–21 It was “not a hard end-point” and there were “no standard, preset criteria for the diagnosis” or follow-up for HF as compared to other outcomes, including stroke and myocardial infarction; rather, “it was determined by the investigator with only a tiny minority of events undergoing independent adjudication.”19–21First, ALLHAT used poorly defined categories and metrics. Although ALLHAT's outcomes were used to create racialized clinical recommendations, ALLHAT never defined its racial categories or what race was meant to encapsulate . This point will be expanded on later. Furthermore, HF, one of the components of combined CVD, was likely variable in its diagnosis.19Moreover, 90.2% of participants were undergoing treatment for hypertension before the study, and many were likely taking commonly prescribed diuretics. For participants who switched from diuretic therapy to a nondiuretic therapy such as ACE inhibition, there may have been some effects of withdrawal, including HF.20 In terms of primary outcomes and “all other hard mortality end points,” there were no statistical differences found; demonstrating that “the newer drugs were at least as effective in the all-important category of saving lives and saving heart attacks, as were diuretics” for all patients.20Second, ALLHAT's ultimate analysis diverged sharply from its initial study question and used secondary outcomes to make its conclusions. ALLHAT's first goal was comparing amlodipine, a CCB, and lisinopril, an ACE inhibitor, with chlorthalidone, a diuretic (the standard at the time).20 But ALLHAT was not designed to be a first-step study, because as mentioned before, 90.2% of all participants were already taking hypertension medication, with no “washout” period before starting the study drug.20 For these patients, there was also no record of the length of consumption of the previous drug or consideration of BPs before the start of any medication.20 One critique went so far as to argue that this design of the study “precludes the possibility of answering the newly formulated research question.”21Instead of publishing this conclusion, however, ALLHAT pivoted to formulate a new question regarding the optimal first-step therapy for hypertension.20 Indeed, there were no significant racialized differences found for the primary outcomes of combined fatal CHD or nonfatal myocardial infarction for any drugs.Furthermore, ALLHAT applied its secondary end-points, especially RRs of stroke and combined CVD (which included HF and stroke outcomes), to produce the racialized conclusions used by JNC 8, although secondary end-points are normally “collected mainly for hypothesis generation and the elucidation of possibilities for further studies.”14 Diuretic usage in the lisinopril group was prohibited if BP goals were not met. Instead, ALLHAT enforced usage of the beta-blocker atenolol or clonidine or reserpine in combination with the ACE inhibitor lisinopril.20 The allowance of only these add-ons, which also suppress renin, compared to CCBs or diuretics which would certainly be used clinically, as well as the study's “failure to restrict salt” disadvantaged the lisinopril group, especially since “high salt diets minimize the antihypertensive effects” of ACE inhibitors.20 Comparatively, 40% of the chlorthalidone (diuretic) group also used the beta-blocker atenolol which “works synergistically with diuretics”  without any subgroup analysis on the effect of atenolol on the study's outcomes.20Third, ALLHAT's study design was artificial and not aligned with clinical applications of the study's drugs.† BP differences can hugely impact risk of stroke as well as other outcomes related to morbidity and mortality.19 For stroke , the reported RR was 1.40  for Black folks and 1.00  for nonblack folks.17The authors of ALLHAT acknowledged the potential faults of their design which “led to a somewhat artificial regimen … of step-up drugs in the ACE inhibitor group,” and “may have contributed to higher BPs in the ACE inhibitor group, especially in the Black subgroup.”18 due to an artificial regimen creates a much greater overlap of CIs between groups with a supposedly distinct drug response.Accounting for the 13–16% difference in RR (that the ALLHAT authors surmised could have been caused by higher SBP in the lisinopril group)17 The overlap of the CIs from 1.09 to 1.13 means no statistically significant difference between racial groups can be inferred. Furthermore, HF ‡ alongside stroke events were two factors largely “responsible for the higher rate of combined CVD in the lisinopril group.”19 The validity of information on stroke events was impacted by the artificial study design, and as mentioned earlier, HF was likely variable in its diagnosis due to missing criteria.Fourth, the lisinopril versus chlorthalidone stroke RR was not the only example of an overstated difference between Black and nonblack patients in terms of these two drugs. For combined CVD, the RR was 1.19  for Black folks and 1.06  for nonblack folks.§ it was still recommended as a first-line therapy for Black patients because “there were no differences in other outcomes  between a CCB and a diuretic.”2Finally, JNC 8 ultimately formulated its racialized recommendation seven through selective uptake of ALLHAT outcomes. It is essential to note that, according to JNC 8, while “a CCB was less effective than a diuretic in preventing heart failure in the Black subgroup of this trial,”2 Thus, the JNC 8 guideline deems the disparate outcomes between Black and nonblack patients reported by ALLHAT for an ACE inhibitor versus a diuretic as essential enough to discourage the former drug as a first line therapy for Black patients—but not the disparate outcome between Black and nonblack patients for a CCB versus a diuretic.Comparatively, ACE inhibitors were not recommended for Black patients as “a thiazide-type diuretic was shown to be more effective in improving cerebrovascular, heart failure, and combined cardiovascular outcomes compared to an ACEI in the Black patient subgroup.”22 We have no reason to think that something similar is at play here, rather we advance a cultural explanation. This is a case of the RWV23 becoming a self-fulfilling prophecy in biomedicine.We have shown that the ALLHAT study, and the way it was incorporated into the JNC 8 guidelines, was deeply flawed. ALLHAT produced the idea of a significant difference between Black and nonblack people in drug response and influenced a differential clinical guideline. Given the flaws, we pointed out in its evidence basis, which are not deeply buried or obscure, what explains the persistence of the racialized guideline? In the case of the race-based drug BiDil, Jonathan Kahn has shown the financial interests at play.23 The RWV encourages us to think of Black and white as coherent biological categories, to always assume we will find biological differences between them, and to assume that variation within racial categories is relatively trivial while differences between categories are significant. Smedley and others have traced how this worldview emerged and became part of our cultural bedrock23–26—even as racial grouping is demonstrated not to be a natural or accurate biological construct.27–30The RWV was theorized by anthropologist Audrey Smedley as an ideological/cognitive framework that holds that biology is the most important way to understand human differences, and that the groups we think of as racial are primarily biological in nature—while social and economic causes of differences exist, there are crucial underlying biological differences.Although science is supposed to be a process by which fallacious ideas are steadily falsified, theoretical frameworks structuring questions, perceptions, and evaluations rarely are overcome with data alone.31 This Act dictated that the NIH “shall ensure that [trials are] designed and carried out in a manner sufficient to provide for valid analysis of whether the variables being studied in the trial affect women or members of minority groups, as the case may be, differently than other subjects in the trial.”32The RWV has long preceded biomedical research, but sociologist Steven Epstein has shown how it became concretely institutionalized within biomedicine through the NIH Revitalization Act of 1993.31 But good intentions without a critical perspective on how to think about and analyze racial difference can lead, as they have here, to a treatment paradigm that builds on racist cognition.Essentially, the Act instructed NIH-funded studies (including ALLHAT) to find and publish race-specific medical differences. Crucially though, it was not motivated by racial animus, but rather a push from members of marginalized groups to be represented (nonexploitatively) in biomedical research—a form of racial justice.33 as the assumption of racial difference colors study design, execution, data interpretation, and results presentation in ways that confirm the original assumption. This can be seen across several problems we identified in the previous section. For example, the reliance on secondary outcomes that pointed toward racial difference when the primary outcomes did not do so and the overstated interpretation of overlapping CIs, alongside JNC 8's acceptance of these practices, are puzzling without the overarching search for racial difference conditioned by the RWV.In the case of ALLHAT and JNC 8, questions were asked, research was framed, and data were evaluted in a racialized framework, and thus, results were interpreted as confirming the idea that inherent racial differences are driving the inequity in hypertension burden, demanding differential treatment regimen. The RWV becomes a self-fulfilling prophecyis. As Gravlee et al. have argued, in most studies, race is a poorly defined proxy that simultaneously evokes genetic ancestry/heterogeneity; differences in socioeconomic status (SES), opportunities, and health care access; racist treatment; and behavioral and lifestyle differences.35 This is reflected in ALLHAT and JNC 8, where the racial disparity was marked, but its character or cause never clarified. ALLHAT asserted as its motivation for including Black patients their potential inability to afford drugs aside from diuretics—a SES difference.7 But otherwise, blackness is medically undefined and implicitly stands in for a biological difference. Whether that difference is inherent, developmental, or due to later-life environmental factors is never stated.What underlies these faulty assumptions and animates the RWV in this case? First, is the vague and ambiguous way that race is conceived and operationalized. This has two parts: how groups are identified and defined (considered second) and what race 18 from which study participants were recruited. Moreover, the Black populations within each study location are greatly genetically heterogeneous; members are not biologically uniform.37 Of the 19.1% of the study categorized as Hispanic, 65.6% self-identified as “white Hispanic” but were excluded from the “white” category (and placed in the “other” category) in at least one article comparing baseline characteristics of participants in different treatment groups, while the 17.4% of Hispanic participants who identified as “Black Hispanic” were grouped with other Black participants.38The other part of the vague invocation of race was the lack of critical interrogation of how racial groups were defined and how individuals were assigned to them. There is no biological coherence to their racial category definitions. ALLHAT used a “self-described Black” subgroup, but blackness is constructed and defined differently among the locations 30 Indeed, socially constructed racial grouping was implied to be biological throughout ALLHAT's study design and analysis—and its results seem to imply that disparities in hypertension and drug treatment response are rooted in inherent differential biology between racial groups.No justification was offered for this decision, but it fits with the “one drop rule” for U.S. racial designation which defines whiteness in terms of ancestral “purity” and blackness in terms of any amount of Black ancestry.not included in comparisons. Cooper et al. compared rates of hypertension among US white and Black individuals and Caribbean Black individuals, but also included white Germans and Black Nigerians.39 Although US Black individuals had greater levels of hypertension than US white individuals, Cooper et al. found that white Germans had the highest and Black Nigerians the lowest. By including a wider range of groups, the hypertension gradient no longer appears to be a function of racial biology, but a more complex pattern of environmental exposures.39 Yet, analyzing hypertension solely from the point of view of US-based racial categories yields the appearance of a racial logic to the disparity in disease burden, which is another self-fulfilling prophecy.Crucially, however, this appearance may be contingent on who is 40 This so-called the Slavery Hypertension Hypothesis holds that during the slave trade, kidnapped Africans were taken from a homeland of salt scarcity and then experienced the Middle Passage voyage defined by “heat stress and salt and water deprivation” and salt loss from sweat, vomit, and diarrhea.40 This “rapid selection process attributed to high mortality during slave transport and slave labor” would, perhaps, have led to intense selection for “salt-saving renal-adrenal adaptations” that predisposed African Americans to hypertension.40There is an implicit framework used to explain this inequity, which is that Black people disproportionately suffer from hypertension because of an evolved predisposition to retain salt.14 This is conceptualized within the JNC 8 guideline: ACE inhibitors (which work in the RAAS) are not recommended as an initial therapy for Black hypertensive patients, until they have CKD, and their renin levels are presumably elevated to a level higher than “typical” for Black patients. The influence of the Slavery Hypertension Hypothesis becomes clear upon considering that although a CCB (which does not operate within the RAAS) also appeared to be less effective than a diuretic in ALLHAT's Black subgroup, JNC 8 still recommended CCBs as a first-line therapy for Black patients.This connects to the common idea in biomedical research that Black people are predisposed to low concentrations of renin, the enzyme that converts angiotensin to angiotensin I in the RAAS, and therefore decreased PRA.per se but a specific product of past racism. It holds that Black people were “intractably transformed, genetically mutilated,”40 which means that contemporary health inequity is not the result of current social forces or discrimination. So, it is a framework that features biological determinism while acknowledging racism but not demanding any antiracist action or social amelioration.The Slavery Hypertension Hypothesis has a specific appeal for health disparities researchers entangled in the RWV. First, it embeds the racialized disparity in hypertension burden and a supposed racialized differential response to ACE inhibitors in an appealing and intuitive evolutionary narrative. The narrative, further, has biopolitical appeal since it explains a racial difference as inherent and the result of natural selection, yet, not as an essential flaw of Black people 40–43 PRA levels have been shown to be variable within Black populations.**While the ideological logic of the Slavery Hypertension Hypothesis is strong, its evolutionary, genetic, and empirical basis is extraordinarily weak. Critics have shown that theorized patterns do not match contemporary population genetics or the historic landscape of West Africa.45 Yet, Black patients' presentation of low renin alongside salt sensitivity and higher BP has been reported by many sources as inherent.46A study with a diverse New York City sample investigating PRA variation by age, race, sex, and diabetic status found that, “Despite differences in renin associated with several characteristics, we have found that no demographic factor nor other commonly measured physical or laboratory characteristic, alone or in combination, can be used as a surrogate to predict PRA status. Instead, in all subgroups a wide distribution of PRA values is to be found.”As we have argued, racial reasoning has a circular logic that is difficult to disrupt. The RWV leads researchers to expect racial differences, and thus studies are designed and interpreted to produce such differences. The hypothesis marshaled to explain racial difference is grounded in the conceptual architecture of the RWV which is itself reinforced by the racial disparity that it produced. When the hypothesis is criticized on theoretical and empirical grounds, one can point to the hypertension disparity as justification that there must be some hidden biological factor to explain the situation. Offering Black and nonblack patients different treatment regimens is a logical outcome, even if the signal of differential drug response is largely a product of the expectation that it exists.47 But the racial realism that these folks fall back on as a safer option for protecting patients in fact may do the opposite—demonstrated, for example, by the studies cited earlier that showed differential drug prescription does not assuage disparities in CVD mortality4 and that the efficacy of ACE inhibitors on the individual level are not well predicted by the average response of the racial group to which a patient is assigned.5Some practitioners of medicine and public health have tried to sweep away the more radical implications of the social constructionist critique of race by asserting that health inequities are real and need attention and that a practical reliance on progressive ideals can harm patients.The “inclusion and difference” paradigm ushered in by the 1993 NIH Revitalization Act was preceded by deep concern especially from minoritized populations about scientific exploitation, science performed for the purpose of racial stratification, and complete exclusion from biomedical research. But this paradigm aimed at equity becomes dangerous in its reliance on a spurious assumption of inherent differential biology between racial groups and a mandate of intentional study of these differences to provide responsible treatment, with little focus on social determinants of health. This allows purely genetic explanations for unequal health outcomes to persist.The slavery hypertension hypothesis, a genetically deterministic explanation of disparity in hypertension burden, for example, does not assign culpability to patients' ongoing lived experiences and blames instead a singular and far-reaching point in history. It absolves practitioners of responsibility in assuaging the structural violence that may create disparate health outcomes between Black and white patients.Clinical guidelines rooted in this logic of race-based differential biology allow physicians to identify a racial health inequity and locate its purported salvation within the accepted medical milieu, by prescribing Black patients alternative medications. The idea that unequal health care access and the embodiment of the social exposome may be drivers of health disparities is much more disruptive to the RWV than the notion that race-specific drug prescriptions will moderate racialized disparities in CVD. Without the critical tools to conceptualize race effectively, researchers and clinicians can perpetuate pseudoscientific stereotypes with the possibility of medical harm.48 rightly so, by practitioners eager for alternative structures through which to treat their patients and grapple with inequity without using circular reasoning to delineate any demonstrated racial variation as due to inherent genetic differences. We advocate for several related approaches; namely, biocritical inquiry,49 structural competency,50 and race-conscious medicine.48 These concepts disrupt the practice of attributing differences in health and treatment outcomes to discrete biological characteristics of different racial groups.The JNC 8 guideline joins many examples of race corrective guidelines and tools being questioned,48 They contribute to a new scientific paradigm which considers specific genetic determinants of disease and how humans embody their sociopolitical environment, especially lived experiences of racism, and the consequential effects on health outcomes.Rather, they encourage an understanding of race as a social product of processes of racialization used to underwrite and justify colonization, dispossession, and enslavement, with effects that persist today.50Furthermore, structural competency advocates for engagement with interdisciplinary knowledge within medicine and asserts that “increasing recognition of the ways in which social and economic forces produce symptoms or methylate genes then needs to be better coupled with medical models for structural change.”51 For lighter-skinned Puerto Ricans, as SES increases, BP decreases, while the opposite trend is found for ‘Negro’ or dark-skinned Puerto Ricans. It is clear that the environment of ‘Negro’ Puerto Ricans is determined by social classification and SES, which together impact experiences of racism or microaggressions, psychosocial stress, and, ultimately, HBP.51 Gravlee's methodology is unique for its simultaneous engagement of genetic and social hypotheses.One powerful example of research informed by a biocritical approach is Dr. Clarence Gravlee's study on determinants of BP in Puerto Rico which finds that African ancestry (via genetic markers) is not associated with high blood pressure (HBP), but that social classification (shaped by skin color) is linked to HBP, through an interaction with SES.Many studies, including ALLHAT, fail to use a biocritical inquiry. Without defining or operationalizing race, they use it roughly as a proxy for genetic ancestry, environment, and social treatment, which blocks them from teasing out the specific structural factors that lead to health inequities.The ALLHAT researchers indicated their buy-in to the RWV as soon as they asserted the importance of a race-specific analysis (so that study results would be applicable to Black patients) in a biomedical research study testing drugs with different mechanisms. Also, JNC 8's rooting in the RWV is demonstrated through its (1) usage of ALLHAT's outcomes as the evidence basis for racialized recommendations despite its clearly problematic study design and analysis; (2) assumption, without genetic evidence or further investigation of other variables, that racial differences in the study were the product of differential biology that indicates distinct drug treatment based on race; and (3) selective uptake of outcomes to create guidelines aligned with historical notions of a Black patient-specific physiology characterized by low renin and salt sensitivity.52 Gravlee demonstrates that alternative approaches grappling with genetic and environmental factors are necessary for researchers and clinicians to measure, investigate, and understand the specific aspects of a person or group's environment that impact their health outcomes so that these can be mitigated.The self-fulfilling prophecy of racial reasoning is apparent here as the JNC 8 guideline further entrenches notions of immutable differential biology between racial groups which permeate biomedical research and clinical treatment. As Dr. Camara Jones puts it, “The ideology of race as a biologic determinant is bolstered when scientists fail to probe the basis of race-associated differences as though this basis were already completely understood.”48 we assert that the medical and public health fields need to look carefully at their practices and reevaluate previous findings through biocritical inquiry and the consideration of the impact of mediators, including structural factors, on commonly propagated racialized findings. We advocate for the incorporation of the highest standards of evidence and self-critical reflexivity to ensure that researchers and clinicians are not inscribing the RWV falsely into medicine.In accordance with other scholars,Notably, we are not suggesting a colorblind approach that ignores the impacts of racialization and racism on health outcomes. Rather, we believe that racial health inequities need to be addressed through a lens of justice. We champion a rejection of the status quo of racial realism that may only exacerbate inequity, and an embrace of structural competency and race-conscious medicine. We push for the conceptualization of the process of racialization as a tool of colonization and social stratification, the effects of which can become embodied through structural violence that clinicians and researchers have a responsibility to address.