Randomized trial of effect of bariatric surgery on blood pressure after 5 years

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

Randomized Trial of Effect of Bariatric Surgery on Blood Pressure After 5 Years.

BACKGROUND: Obesity represents a major obstacle for controlling hypertension, the leading risk factor for cardiovascular mortality. OBJECTIVES: The purpose of this study was to determine the long-term effects of bariatric surgery on hypertension control and remission. METHODS: We conducted a randomized clinical trial with subjects with obesity grade 1 or 2 plus hypertension using at least 2 medications. We excluded subjects with previous cardiovascular events and poorly controlled type 2 diabetes. Subjects were assigned to Roux-en-Y gastric bypass (RYGB) combined with medical therapy (MT) or MT alone. We reassessed the original primary outcome (reduction of at least 30% of the total antihypertensive medications while maintaining blood pressure levels <140/90 mm Hg) at 5 years. The main analysis followed the intention-to-treat principle. RESULTS: A total of 100 subjects were included (76% women, age 43.8 ± 9.2 years, body mass index: 36.9 ± 2.7 kg/m2). At 5 years, body mass index was 36.40 kg/m2 (95% CI: 35.28-37.52 kg/m2) for MT and 28.01 kg/m2 (95% CI: 26.95-29.08 kg/m2) for RYGB (P < 0.001). Compared with MT, RYGB promoted a significantly higher rate of number of medications reduction (80.7% vs 13.7%; relative risk: 5.91; 95% CI: 2.58-13.52; P < 0.001) and the mean number of antihypertensive medications was 2.97 (95% CI: 2.33-3.60) for MT and 0.80 (95% CI: 0.51-1.09) for RYGB (P < 0.001). The rates of hypertension remission were 2.4% vs 46.9% (relative risk: 19.66; 95% CI: 2.74-141.09; P < 0.001). Sensitivity analysis considering only completed cases revealed consistent results. Interestingly, the rate of apparent resistant hypertension was lower after RYGB (0% vs 15.2%). CONCLUSIONS: Bariatric surgery represents an effective and durable strategy to control hypertension and related polypharmacy in subjects with obesity. (GAstric bypass to Treat obEse Patients With steAdy hYpertension [GATEWAY]; NCT01784848).

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension: A Randomized Clinical Trial

Hypertension is a leading cause of cardiovascular mortality (1). Its unfavorable impact is potentially explained by several factors, including the asymptomatic nature of this condition, poor medication adherence, and high burden of comorbid conditions, including obesity (1, 2). Hypertension occurs mostly in persons with excess weight and is often poorly controlled in patients with obesity (3, 4), and pharmacologic treatment of obesity has modest impact on blood pressure (BP) reduction (5). Bariatric surgery is the most effective method to treat obesity (6 ­ 8). Although recent research efforts have focused on metabolic improvement and diabetes resolution (9 ­12), growing interest has been devoted to evaluating the effects of this surgery on hypertension (13­15). The GATEWAY (Gastric Bypass to Treat Obese Patients With Steady Hypertension) trial focused on hypertension and included patients with mild obesity (body mass index [BMI], 30 to 34.9 kg/m2 ) and those with a BMI greater than 35 kg/m2 per current guidelines. The 1-year results showed that patients with coexisting obesity and hypertension were able to reduce or completely discontinue their antihypertensive medications after surgery, while maintaining a controlled BP and a similar 24-hour BP profile (16, 17). However, midterm effects of bariatric surgery on office and 24-hour BP measurements in a broad population of patients with obesity and hypertension remain uncertain. Here, we present the 3-year results from the GATEWAY trial. METHODS The GATEWAY trial is a randomized, nonblinded, single-center, investigator-initiated clinical trial performed at Heart Hospital in Sa˜ o Paulo, Brazil. Study design (18) and 1-year results (16) were previously pub lished; the full protocol, approved by the Research Ethics Board at the Heart Hospital (HCor), and the statistical analysis plan are available in Supplements 1 and 2 (available at Annals.org). The follow-up period for the primary end point was 12 months, but we prespecified that all patients would be scheduled for a 3-year and 5-year extension study. Here, we present the 3-year outcomes.

Three-Year Outcomes of Bariatric Surgery in Patients With Obesity and Hypertension : A Randomized Clinical Trial.

BACKGROUND: Midterm effects of bariatric surgery on patients with obesity and hypertension remain uncertain. OBJECTIVE: To determine the 3-year effects of Roux-en-Y gastric bypass (RYGB) on blood pressure (BP) compared with medical therapy (MT) alone. DESIGN: Randomized clinical trial. (ClinicalTrials.gov: NCT01784848). SETTING: Investigator-initiated study at Heart Hospital (HCor), São Paulo, Brazil. PARTICIPANTS: Patients with hypertension receiving at least 2 medications at maximum doses or more than 2 medications at moderate doses and with a body mass index (BMI) between 30.0 and 39.9 kg/m2 were randomly assigned (1:1 ratio). INTERVENTION: RYGB plus MT or MT alone. MEASUREMENTS: The primary outcome was at least a 30% reduction in total number of antihypertensive medications while maintaining BP less than 140/90 mm Hg. Key secondary outcomes were number of antihypertensive medications, hypertension remission, and BP control according to current guidelines (<130/80 mm Hg). RESULTS: Among 100 patients (76% female; mean BMI, 36.9 kg/m2 [SD, 2.7]), 88% from the RYGB group and 80% from the MT group completed follow-up. At 3 years, the primary outcome occurred in 73% of patients from the RYGB group compared with 11% of patients from the MT group (relative risk, 6.52 [95% CI, 2.50 to 17.03]; P < 0.001). Of the randomly assigned participants, 35% and 31% from the RYGB group and 2% and 0% from the MT group achieved BP less than 140/90 mm Hg and less than 130/80 mm Hg without medications, respectively. Median (interquartile range) number of medications in the RYGB and MT groups at 3 years was 1 (0 to 2) and 3 (2.8 to 4), respectively (P < 0.001). Total weight loss was 27.8% and -0.1% in the RYGB and MT groups, respectively. In the RYGB group, 13 patients developed hypovitaminosis B12 and 2 patients required reoperation. LIMITATION: Single-center, nonblinded trial. CONCLUSION: RYGB is an effective strategy for midterm BP control and hypertension remission, with fewer medications required in patients with hypertension and obesity. PRIMARY FUNDING SOURCE: Ethicon, represented in Brazil by Johnson & Johnson do Brasil.

Effects of bariatric surgery versus medical therapy on the 24-hour ambulatory blood pressure and the prevalence of resistant hypertension

Bariatric surgery is an effective strategy for blood pressure (BP) reduction, but most of the evidence relies on office BP measurements. In this study, we evaluated the impact of bariatric surgery on 24-hour BP profile, BP variability, and resistant hypertension prevalence. This is a randomized trial including obese patients with grade 1 and 2 using at least 2 antihypertensive drugs at maximal doses or >2 at moderate doses. Patients were allocated to either Roux-en-Y Gastric Bypass (RYGB) combined with medical therapy or medical therapy alone for 12 months. The primary outcome was the 24-hour BP profile and variability (average real variability of daytime and night time BP). We evaluated the nondipping status and prevalence of resistant hypertension as secondary end points. We included 100 patients (76% female, body mass index, 36.9±2.7 kg/m2). The 24-hour BP profile (including nondipping status) was similar after 12 months, but the RYGB group required less antihypertensive classes as compared to the medical therapy alone (0 [0­1] versus 3 [2.5­4] classes; P<0.01). The average real variability of systolic nighttime BP was lower after RYGB as compared to medical therapy (between-group difference, −1.63; 95% CI, −2.91 to −0.36; P=0.01). Prevalence of resistant hypertension was similar at baseline (RYGB, 10% versus MT, 16%; P=0.38), but it was significantly lower in the RYGB at 12 months (0% versus 14.9%; P<0.001). In conclusion, RYGB significantly reduced antihypertensive medications while promoting similar 24-hour BP profile and nondipping status. Interestingly, bariatric surgery improved BP variability and may decrease the burden of resistant hypertension associated with obesity. (AU)

Effects of Bariatric Surgery Versus Medical Therapy on the 24-Hour Ambulatory Blood Pressure and the Prevalence of Resistant Hypertension.

Bariatric surgery is an effective strategy for blood pressure (BP) reduction, but most of the evidence relies on office BP measurements. In this study, we evaluated the impact of bariatric surgery on 24-hour BP profile, BP variability, and resistant hypertension prevalence. This is a randomized trial including obese patients with grade 1 and 2 using at least 2 antihypertensive drugs at maximal doses or >2 at moderate doses. Patients were allocated to either Roux-en-Y Gastric Bypass (RYGB) combined with medical therapy or medical therapy alone for 12 months. The primary outcome was the 24-hour BP profile and variability (average real variability of daytime and night time BP). We evaluated the nondipping status and prevalence of resistant hypertension as secondary end points. We included 100 patients (76% female, body mass index, 36.9±2.7 kg/m2). The 24-hour BP profile (including nondipping status) was similar after 12 months, but the RYGB group required less antihypertensive classes as compared to the medical therapy alone (0 [0-1] versus 3 [2.5-4] classes; P<0.01). The average real variability of systolic nighttime BP was lower after RYGB as compared to medical therapy (between-group difference, -1.63; 95% CI, -2.91 to -0.36; P=0.01). Prevalence of resistant hypertension was similar at baseline (RYGB, 10% versus MT, 16%; P=0.38), but it was significantly lower in the RYGB at 12 months (0% versus 14.9%; P<0.001). In conclusion, RYGB significantly reduced antihypertensive medications while promoting similar 24-hour BP profile and nondipping status. Interestingly, bariatric surgery improved BP variability and may decrease the burden of resistant hypertension associated with obesity. Clinical Trial Registration- URL: http://www.clinicaltrials.gov . Unique identifier: NCT01784848.

Does the RYGB common limb length influence hypertension remission and cardiometabolic risk factors? Data from the GATEWAY trial.

BACKGROUND: Although Roux-en-Y gastric bypass (RYGB) results in significant weight loss and cardiometabolic risk factors improvements; there is no consensus whether limb lengths may influence these results. OBJECTIVE: To evaluate the correlations between the common limb length (CLL) and hypertension remission rate, cardiometabolic risk factors, and nutritional parameters after RYGB. SETTINGS: Private Hospital, Brazil. METHODS: GATEWAY is a randomized trial designed to evaluate the efficacy of RYGB on hypertension improvement and other cardiometabolic risk factors in patients with grade I and II obesity compared with medical therapy. The follow-up was 1 year. We measured the entire bowel in all patients and used a 150-cm alimentary limb and a 100-cm biliopancreatic limb. Univariate logistic regression was used to estimate the relationship between CLL and hypertension remission. Pearson and Spearman correlation were used to evaluate the correlation between the CLL and the percentage changes of cardiometabolic risk factors and nutritional parameters. RESULTS: From 100 randomized patients, 45 were submitted to RYGB and completed the follow-up. Mean CLL was 466.3 ± 86.4 cm. Of patients, 55.6% from the RYGB group showed remission of hypertension. CLL length was not significantly associated with hypertension remission (odds ratio [95% confidence interval] for 50 units increase in CLL: .97 [.68; 1.38], P = .88). Consistently, we found no correlations between CLL and all changes in cardiometabolic risk factors and nutritional parameters. CONCLUSIONS: In a proximal RYGB, CLL does not influence hypertension remission, cardiometabolic risk factors, and nutritional parameters.

Effects of Bariatric Surgery in Obese Patients With Hypertension: The GATEWAY Randomized Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension).

BACKGROUND: Recent research efforts on bariatric surgery have focused on metabolic and diabetes mellitus resolution. Randomized trials designed to assess the impact of bariatric surgery in patients with obesity and hypertension are needed. METHODS: In this randomized, single-center, nonblinded trial, we included patients with hypertension (using ≥2 medications at maximum doses or >2 at moderate doses) and a body mass index between 30.0 and 39.9 kg/m2. Patients were randomized to Roux-en-Y gastric bypass plus medical therapy or medical therapy alone. The primary end point was reduction of ≥30% of the total number of antihypertensive medications while maintaining systolic and diastolic blood pressure <140 mm Hg and 90 mm Hg, respectively, at 12 months. RESULTS: We included 100 patients (70% female, mean age 43.8±9.2 years, mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up. Reduction of ≥30% of the total number of antihypertensive medications while maintaining controlled blood pressure occurred in 41 of 49 patients from the gastric bypass group (83.7%) compared with 6 of 47 patients (12.8%) from the control group with a rate ratio of 6.6 (95% confidence interval, 3.1-14.0; P<0.001). Remission of hypertension was present in 25 of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass, considering office and 24-hour ambulatory blood pressure monitoring, respectively, whereas no patient submitted to medical therapy was free of antihypertensive drugs at 12 months. A post hoc analysis for the primary end point considering the SPRINT (Systolic Blood Pressure Intervention Trial) target reached consistent results, with a rate ratio of 3.8 (95% confidence interval, 1.4-10.6; P=0.005). Eleven patients (22.4%) from the gastric bypass group and none in the control group were able to achieve SPRINT levels without antihypertensives. Waist circumference, body mass index, fasting plasma glucose, glycohemoglobin, low-density lipoprotein cholesterol, triglycerides, high-sensitivity C-reactive protein, and 10-year Framingham risk score were lower in the gastric bypass than in the control group. CONCLUSIONS: Bariatric surgery represents an effective strategy for blood pressure control in a broad population of patients with obesity and hypertension. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT01784848.

Effects of bariatric surgery in obese patients with hypertension: the GATEWAY randomized trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension)

BACKGROUND: Recent research efforts on bariatric surgery have focusedon metabolic and diabetes mellitus resolution. Randomized trials designedto assess the impact of bariatric surgery in patients with obesity andhypertension are needed.METHODS: In this randomized, single-center, nonblinded trial, we includedpatients with hypertension (using ≥2 medications at maximum doses or >2 atmoderate doses) and a body mass index between 30.0 and 39.9 kg/m2. Patientswere randomized to Roux-en-Y gastric bypass plus medical therapy or medicaltherapy alone. The primary end point was reduction of ≥30% of the totalnumber of antihypertensive medications while maintaining systolic and diastolicblood pressure <140 mmHg and 90 mmHg, respectively, at 12 months. RESULTS: We included 100 patients (70% female, mean age 43.8±9.2 years,mean body mass index 36.9±2.7 kg/m2), and 96% completed follow-up.Reduction of ≥30% of the total number of antihypertensive medicationswhile maintaining controlled blood pressure occurred in 41 of 49 patientsfrom the gastric bypass group (83.7%) compared with 6 of 47 patients(12.8%) from the control group with a rate ratio of 6.6 (95% confidenceinterval, 3.1–14.0; P<0.001). Remission of hypertension was present in 25of 49 (51%) and 22 of 48 (45.8%) patients randomized to gastric bypass,considering office and 24-hour ambulatory blood pressure monitoring...

Effects of gastric bypass surgery in patients with hypertension: rationale and design for a randomised controlled trial (GATEWAY study).

INTRODUCTION: Obesity and overweight are becoming progressively more prevalent worldwide and are independently associated with a significant increase in the risk of cardiovascular diseases. Systemic arterial hypertension is frequently found in association with obesity and contributes significantly to increased cardiovascular risk. We hypothesise that Roux-en-Y gastric bypass (RYGB) surgery, a procedure that effectively reduces body weight, can also positively impact blood pressure control in obese and hypertensive individuals. METHODS AND ANALYSIS: A unicentric, randomised, controlled, unblinded clinical trial. Sixty obese (body mass index between 30 and 39.9) and moderately well controlled hypertensive patients, in use of at least two antihypertensive medications at maximum doses or more than two in moderate doses, will be randomly allocated, using an online, electronic and concealed method, to receive either RYGB plus optimised clinical treatment (OCT) or OCT alone. The primary end point is the reduction of antihypertensive medication at 1 and 2 years of follow-up. Data analysis will primarily be conducted on an intention-to-treat basis. ETHICS AND DISSEMINATION: The study was approved by the local institutional review board that works in total compliance with the latest version of the Helsinki Declaration, the Good Clinical Practices (GCP), the 'America's Document' and the national regulatory laws. Before the beginning of any study-related activities, each study participant is asked to provide a signed informed consent. TRIAL REGISTRATION NUMBER: NCT01784848.

Effects of gastric bypass surgery inpatients with hypertension: rationaleand design for a randomised controlledtrial (GATEWAY study)

Obesity and overweight are becomingprogressively more prevalent worldwide and areindependently associated with a significant increase inthe risk of cardiovascular diseases. Systemic arterialhypertension is frequently found in association withobesity and contributes significantly to increasedcardiovascular risk. We hypothesise that Roux-en-Ygastric bypass (RYGB) surgery, a procedure thateffectively reduces body weight, can also positivelyimpact blood pressure control in obese andhypertensive individuals.Methods and analysis: A unicentric, randomised,controlled, unblinded clinical trial. Sixty obese (bodymass index between 30 and 39.9) and moderately wellcontrolled hypertensive patients, in use of at least twoantihypertensive medications at maximum doses ormore than two in moderate doses, will be randomlyallocated, using an online, electronic and concealedmethod, to receive either RYGB plus optimised clinicaltreatment (OCT) or OCT alone. The primary end pointis the reduction of antihypertensive medication at1 and 2 years of follow-up. Data analysis will primarilybe conducted on an intention-to-treat basis.Ethics and dissemination: The study was approvedby the local institutional review board that works intotal compliance with the latest version of the HelsinkiDeclaration, the Good Clinical Practices (GCP), the‘America’s Document’ and the national regulatory laws.Before the beginning of any study-related activities,each study participant is asked to provide a signedinformed consent.

Glycemic control after stomach-sparing duodenal-jejunal bypass surgery in diabetic patients with low body mass index.

BACKGROUND: Bariatric surgery frequently results in the resolution of type 2 diabetes mellitus (T2DM). One of the many factors that could explain such findings is the duodenal exclusion of the alimentary tract. To test this hypothesis, a surgical model that induces glycemic control without significant weight loss would be ideal. In the present study, we evaluated the early metabolic changes that occur in overweight diabetic patients after laparoscopic duodenal-jejunal bypass (DJB) and determined the factors associated with success in T2DM resolution. The setting was a private practice. METHODS: A total of 35 patients (20 men and 15 women) were included in the present study. The mean preoperative body mass index was 28.4 ± 2.9 kg/m(2). DJB was performed in all patients, and the anthropometric data and blood samples were collected at baseline (preoperatively) and 3, 6, 9, and 12 months after surgery. Success was defined when patients reached a glycated hemoglobin level of <7% without diabetic medication. RESULTS: T2DM remission was observed in 14 (40%) of 35 patients. No differences in the homeostasis model assessment insulin resistance index levels and patient weight were observed before and 12 months after DJB surgery. Gender, duration of T2DM, previous use of insulin, preoperative homeostasis model assessment insulin resistance index, and C-peptide levels were not significant predictive factors of success or nonsuccess. The only factor that significantly predicted postoperative positive outcomes was a waist circumference reduction of ≥ 7% compared with baseline within the first 6 months after surgery. CONCLUSION: DJB improves glycemic control; however, it does not increase insulin sensitivity in overweight diabetic patients. These changes were observed without significant weight loss.

Long-long limb Roux-en-Y gastric bypass is more efficacious in treatment of type 2 diabetes and lipid disorders in super-obese patients.

BACKGROUND: Super-obese patients can achieve adequate weight loss with long limb Roux-en-Y gastric bypass (RYGB). These patients, however, might need longer intestinal limbs to control co-morbidities such as type 2 diabetes, lipid disorders, hypertension, sleep apnea, and gastroesophageal reflux disorder. METHODS: A total of 105 patients with a body mass index of > or =50 kg/m(2) were randomly divided into 2 similar groups regarding sex, age, and number of co-morbidities. All underwent laparoscopic Roux-en-Y gastric bypass. In group 1, the length of the biliary limb was 50 cm and the length of the Roux limb was 150 cm. In group 2, the length of the biliary limb was 100 cm and the length of the Roux limb was 250 cm. RESULTS: The follow-up for both group was 48 months. Diabetes was controlled in 58% of group 1 and in 93% of group 2 (P <0.05). Lipid disorders improved in 57% of group 1 and in 70% of group 2 (P <0.05). No statistical difference was found in the control or improvement of hypertension, sleep apnea, or gastroesophageal reflux disorder. The excess weight loss was faster in group 1 but was similar in both groups at 48 months (70% in group 1 and 74% in group 2), with no statistical difference. CONCLUSION: Patients with longer biliary and Roux limbs achieved greater type 2 diabetes control, greater lipid disorder improvement, and showed a trend toward faster excess weight loss.