Long-term effect of biliopancreatic diversion on blood pressure in hypertensive obese patients

BACKGROUND: The weight loss surgically induced by gastroplasty or gastric banding has only a transitory effect on the arterial hypertension of the severely obese patients, and a prevalence of hypertension similar to that of controls has been reported 8 years after the operation. METHODS: We studied the effects of biliopancreatic diversion in a series of 73 severely obese patients with preoperative hypertension throughout a 10-year follow-up period. Body weight dropped from 135.5 kg to 84.8 kg and remained substantially unchanged during the entire 10-year period, hypertension resolved in 41 subjects within the first postoperative year and the resolution rate increased slightly and progressively with time: at 10 years only 15 subjects were still hypertensive. Mean systolic and diastolic blood pressure (BP) value decreased within the first postoperative year as well as the pulse pressure (mean +/- standard deviation from 168 +/- 25 to 143 +/- 22 mm Hg, from 105 +/- 18 to 88 +/- 13 mm Hg, and from 65 +/- 16 to 50 +/- 13 mm Hg, respectively) and remained essentially unchanged throughout all the follow-up; 10 years after surgery the systolic BP and pulse pressure values (127 +/- 14 mm Hg and 42 +/- 6 mm Hg, respectively) were significantly lower than those observed at shorter term. CONCLUSIONS: In severely obese patients with arterial hypertension, the weight loss determined by biliopancreatic diversion in most cases is accompanied by the normalization of BP, which remains into physiological range until very long term.     

Differential effect of weight loss on insulin resistance in surgically treated obese patients

PURPOSE: To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. METHODS: Eighteen nondiabetic patients with severe obesity (mean [+/- SD] body mass index: 53.5 +/- 9.0 kg/m(2)) and 20 sex- and age-matched lean subjects (body mass index: 23.8 +/- 3.0 kg/m(2)) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass, or biliopancreatic diversion, and were restudied at 5 to 6 months and again at 16 to 24 months postsurgery. RESULTS: At baseline, patients were hyperinsulinemic (194 +/- 47 pmol/L vs. 55 +/- 25 pmol/L, P < 0.0001), hypertriglyceridemic (1.56 +/- 0.30 mmol/L vs. 0.78 +/- 0.32 mmol/L, P < 0.0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 +/- 4.4 micromol/min/kg fat-free mass vs. 52.0 +/- 10.1 micromol/min/kg, P < 0.0001) as compared with controls. Weight loss by the two procedures was equivalent in both amount (averaging -53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 +/- 6.0 micromol/min/kg at 5 months and 33.7 +/- 11.3 micromol/min/kg at 16 months, P < 0.01 vs. baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 +/- 12.4 micromol/min/kg, P = 0.72 vs. controls) and increased further at 24 months (68.7 +/- 9.5 micromol/min/kg, P < 0.01 vs. controls) despite a persistent obese phenotype (body mass index: 33.2 +/- 8.0 kg/m(2)). CONCLUSION: In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass), but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity.     

Long-term normalization of insulin sensitivity following biliopancreatic diversion for obesity

OBJECTIVE: Assess insulin sensitivity and metabolic status of obese patients with stable weight loss at long term following biliopancreatic diversion (BPD). MATERIAL AND METHODS: The study was carried out in 36 nondiabetic severely obese patients undergoing BPD. Serum concentration of glucose, insulin and leptin were determined prior to and at 2 y following the operation. Insulin sensitivity was calculated according to the homeostatic model assessment (HOMA IR). RESULTS: At 2 y following BPD, weight loss in all subjects corresponded to a marked drop in serum leptin concentration and improvement of insulin sensitivity within physiological range. Following the operation, HOMA IR values were positively correlated with serum leptin concentration independently of body mass index values. DISCUSSION: The stable weight loss following BPD at long term is accompanied by a complete reversal of the preoperative insulin resistance. Serum leptin concentration and HOMA IR data were positively related only postoperatively, suggesting that the action of factors that could influence the relation between leptin and insulin action in the obese status can be reverted.     

Joint statement of the European Association for the Study of Obesity and the European Society of Hypertension: obesity and difficult to treat arterial hypertension

Obese patients are prone to arterial hypertension, require more antihypertensive medications, and have an increased risk of treatment-resistant arterial hypertension. Obesity-induced neurohumoral activation appears to be involved. The association between obesity and hypertension shows large inter-individual variability, likely through genetic mechanisms. Obesity affects overall cardiovascular and metabolic risk; yet, the relationship between obesity and cardiovascular risk is complex and not sufficiently addressed in clinical guidelines. The epidemiological observation that obesity may be protective in patients with established cardiovascular disease is difficult to translate into clinical experience and practice. Weight loss is often recommended as a means to lower blood pressure. However, current hypertension guidelines do not provide evidence-based guidance on how to institute weight loss. In fact, weight loss influences on blood pressure may be overestimated. Nevertheless, weight loss through bariatric surgery appears to decrease cardiovascular risk in severely obese patients. Eventually, most obese hypertensive patients will require antihypertensive medications. Data from large-scale studies with hard clinical endpoints on antihypertensive medications specifically addressing obese patients are lacking and the morbidity from the growing population of severely obese patients is poorly recognized or addressed. Because of their broad spectrum of beneficial effects, renin-angiotensin system inhibitors are considered to be the most appropriate drugs for antihypertensive treatment of obese patients. Most obese hypertensive patients require two or more antihypertensive drugs. Finally, how to combine weight loss strategies and antihypertensive treatment to achieve an optimal clinical outcome is unresolved.     

The treatment of hypertension in obese patients

Hypertension causes a significant disease burden in all racial and ethnic groups and is directly attributable to excess weight in most cases. The relationship between increasing body mass index and hypertension prevalence has been recognized for decades. Epidemiologic studies clearly demonstrate the correlation between body weight and blood pressure in obese and lean populations. Most patients with hypertension are overweight or obese, and loss of excess weight lowers blood pressure. Although the epidemiologic relationship is clear, the understanding of mechanisms linking hypertension and weight gain is still evolving. Lifestyle modifications and specific pharmacologic agents address many of the known mechanisms; however, blood pressure remains difficult to control in obese hypertensive patients. This review highlights the association of obesity and hypertension, identifies potential mechanisms for this association, and describes nonpharmacologic and pharmacologic strategies that offer potential benefits for the obese patient with hypertension.     

Sibutramine in overweight/obese hypertensive patients

Obesity and hypertension are closely associated risk factors for cardiovascular disease. An increase in body mass index is commonly associated with an increase in blood pressure and weight reduction is recommended as the principal intervention in the obese hypertensive patient. Sibutramine therapy, as part of a programme of diet and exercise, can help achieve marked weight reduction and improve metabolic and other cardiovascular risk factors. In hypertensive patients, weight loss induced by sibutramine has also been found to reduce blood pressure. Studies have shown that in the obese, well-controlled hypertensive patient, sibutramine is a safe and well-tolerated therapy offering the many clinical benefits associated with weight reduction in this high-risk population.     

Basal GLP-1 Levels in Morbidly Obese Patients following Biliopancreatic Diversion Surgery

Background: Previous studies addressing the changes of glucagon-like peptide-1 (GLP-1) concentrations in morbidly obese patients after bariatric surgery have demonstrated conflicting results. The aim of the present study was to investigate the changes in serum GLP-1 levels 9 months after biliopancreatic diversion in morbidly obese patients without diabetes mellitus. Methods: A sample of 40 morbidly obese patients without diabetes mellitus was enrolled. Biochemical and anthropometrical evaluations were conducted at basal and 9 months after surgery. Results: The mean patient age was 46.6 ± 13.1 years, and the mean preoperative body mass index (BMI) was 47.1 ± 18.1. A significant decrease in BMI, weight, waist circumference, fat mass, glucose, LDL cholesterol, total cholesterol, and triglyceride levels was observed after 9 months. Serum basal GLP-1 levels did not change after surgery (0.65 ± 0.18 ng/ml vs. 0.66 ± 0.17 ng/ml; n.s.). Postsurgical correlation analysis showed a negative association between basal GLP-1 and HDL cholesterol (r = -0.57; p < 0.01). Conclusions: Fasting GLP-1 concentrations did not change after massive weight loss with biliopancreatic diversion in morbidly obese patients without diabetes mellitus.     

Effect of orlistat-induced weight loss on blood pressure and heart rate in obese patients with hypertension

OBJECTIVE: To investigate the effects of long-term weight management with orlistat on blood pressure in obese hypertensive patients. DESIGN: A meta-analysis of data from five multicenter, randomized, placebo-controlled studies, conducted in Europe and the USA, was performed. PATIENTS: Obese adults [body mass index (BMI) 28-43 kg/m(2) ] with uncontrolled diastolic hypertension or isolated systolic hypertension (ISH) were eligible for inclusion. INTERVENTIONS: Following a 4-week placebo lead-in period, patients were randomized to orlistat 120 mg or placebo three times daily, in conjunction with a mildly reduced calorie diet for 1 year. MAIN OUTCOME MEASURES: Change in body weight was the primary efficacy parameter. Blood pressure, heart rate and systolic workload were assessed as secondary efficacy parameters. RESULTS: A total of 628 patients were included in the intent-to-treat (ITT) analysis. After 56 weeks, orlistat-treated patients had lost significantly more body weight than placebo recipients (8.0 versus 4.0%; P<0.001). Among patients with ISH, mean systolic pressure was reduced to a significantly greater degree after 1 year with orlistat compared to placebo (-9.4 versus -4.6 mmHg; P= 0.022). Similarly, reductions in mean diastolic pressure in patients with diastolic hypertension were greater with orlistat than with placebo (-7.7 versus -5.6 mmHg; P= 0.017). Weight loss of >or= 10% was associated with significant reductions in blood pressure, heart rate and systolic workload. CONCLUSIONS: Orlistat promotes clinically meaningful weight loss that is associated with significant reductions in blood pressure and heart rate, and may therefore have a role in the management of hypertension in overweight and obese patients.     

Morbid obesity, nonalcoholic fatty liver disease, and weight loss surgery

OBJECTIVE: This study examines the impact of biliopancreatic diversion, a malabsorptive variant of gastric bypass, on liver histology. METHODS: Liver samples were collected from 689 severely obese (BMI 47 +/- 9 kg m(2)) patients undergoing biliopancreatic diversion. Exclusion criteria included: history of hepatitis, exposure to hepatotoxic medications, prior weight loss surgery, and alcohol consumption greater than 100 grams per week. One group of 14 patients had cirrhosis in their initial biopsy. Eleven of those 14 patients underwent multiple biopsies to monitor their liver disease. A second group of 104 patients had re-operations and a second liver biopsy. A hepatopathologist conducted blind evaluations of all biopsy specimens looking for steatosis and fibrosis. RESULTS: All patients lost weight and showed improvement in their metabolic syndrome. Of the 104 patients undergoing re-operation with a second liver biopsy, 28 showed a decrease in severe fibrosis, while 42 patients developed mild fibrosis. On average, this group lost 38 +/- 18 kg over 41 +/- 25 post-surgical months. A sub-group analysis revealed an association between increased fibrosis and post-operative low serum albumin, diarrhea, pre-operative alcohol consumption, and menopausal status. The eleven patients with cirrhosis in their initial biopsy showed a reduction in their fibrosis grade (mean fibrosis grade from 5 to 3) during nine years of follow-up care. CONCLUSION: These findings indicate that significant weight loss after biliopancreatic diversion can improve liver histology in patients with advanced fibrosis.     

Management of hypertension in overweight and obese patients: A practical guide for clinicians

The association between obesity and cardiovascular disease is well established, and up to 60% of overweight or obese patients have hypertension. Dietary interventions associated with modest weight loss are effective in controlling blood pressure and in reducing use of antihypertensive drug therapy in overweight and obese patients. However, long-term maintenance of weight loss is achieved only in a small proportion of patients. Orlistat and sibutramine may help to achieve and maintain weight loss but may not be sufficient to control blood pressure in overweight and obese hypertensive patients. Consequently, antihypertensive drug therapy is often necessary in addition to weight loss interventions. Few studies have investigated different antihypertensive drugs, specifically in overweight and obese patients with hypertension. Based on studies involving obese and nonobese patients, first-line treatment options include a diuretic alone or an angiotensin-converting enzyme (ACE) inhibitor alone. If monotherapy is inadequate for blood pressure control, combination therapy with diuretic and ACE inhibitor and/or combining either of these drugs with a calcium channel blocker are reasonable treatment options. Additional studies to further clarify the management of these patients are warranted.     

Pulse wave velocity in patients with obesity and hypertension

Pulse wave velocity was measured in 27 obese and 25 nonobese patients with sustained essential hypertension. Pulse wave velocity was significantly increased in obese patients in comparison with nonobese patients. The result was independent of age, sex, and level of blood pressure. In the overall population, a significant positive correlation (r = 0.85; p less than 0.001) was observed between the degree of obesity and pulse wave velocity. A study of partial correlation coefficients indicated that the levels of glycemia, cholesterolemia, and triglyceridemia did not influence the relationship. After body weight was reduced, blood pressure decreased and arterial compliance increased. The results show that in patients with sustained essential hypertension: pulse wave velocity and obesity are strongly related independent of age, sex, blood pressure, and associated metabolic disorders and body weight reduction is associated with an improvement of arterial distensibility and compliance.     

Aldosterone studies in obese patients with hypertension

Ten patients with hypertension and obesity were studied during a program of weight loss on an unrestricted sodium diet. The study showed that weight loss during the ten month period was accompanied by a significant decrease in urinary aldosterone, tetrahydroaldosterone -3-glucuronide and plasma renin activity values. It was also demonstrated that successful reduction in body weight was associated with a reduction in blood pressure. It is postulated that blood pressure reduction in obese patients during weight reduction may depend on decreases in aldosterone and plasma renin activity. The reduction in levels of tetrahydroaldosterone-3-glucuronide is due to an energy related depression of the glucuronidation process caused by carbohydrate deficiency. It is postulated that the lowered rate of metabolism of aldosterone as measured by the diminished formation of the metabolite tetrahydroaldosterone-3-glucuronide is an important determinant of blood pressure status during weight reduction.     

Therapeutic Considerations in the Treatment of Obesity Hypertension

Obesity, now recognized as an independent risk factor for cardiovascular disease, is closely associated with hypertension. Complex mechanisms link increasing body weight with increasing blood pressure. Treatment of the obese patient with hypertension requires consideration of physiologic changes related to obesity hypertension. Lifestyle modification, including weight reduction and increased physical activity, can directly influence blood pressure levels and improve blood pressure control in obese, hypertensive patients. Clinical trials are needed to determine the most effective antihypertensive drugs for the obese, hypertensive patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity hypertension, but additional long-term studies are needed to support their safety and efficacy.     

Therapeutic considerations in the treatment of obesity hypertension

Obesity, now recognized as an independent risk factor for cardiovascular disease, is closely associated with hypertension. Complex mechanisms link increasing body weight with increasing blood pressure. Treatment of the obese patient with hypertension requires consideration of physiologic changes related to obesity hypertension. Lifestyle modification, including weight reduction and increased physical activity, can directly influence blood pressure levels and improve blood pressure control in obese, hypertensive patients. Clinical trials are needed to determine the most effective antihypertensive drugs for the obese, hypertensive patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity hypertension, but additional long-term studies are needed to support their safety and efficacy.     

Surgical treatment of obesity

Opinion statement Obesity has emerged as one of the most complex and debilitating diseases affecting the world’s population. It is estimated that more than two thirds of Americans are overweight and more than 20% are obese. This disease is associated with many morbid conditions, including hypertension, coronary artery disease, hypoventilation, sleep apnea syndrome, diabetes mellitus, and an increased incidence of certain malignancies. Medical interventions for achieving and maintaining significant weight loss have generally failed, leaving surgery as the only effective treatment for durable weight loss. A number of surgical options are available today and can be grouped into two categories based on the mechanism of how the weight loss is achieved. Restrictive procedures include vertical banded gastroplasty (VBG), adjustable gastric banding (AGB), and Roux-en-Y gastric bypass (RYGB), although the latter does have some altered absorption as well. Largely malabsorptive procedures include biliopancreatic diversion (BPD) and biliopancreatic diversion with duodenal switch (BPD-DS). Whereas VBG has largely fallen out of favor due to inadequate long-term weight loss, the other procedures have proven successful in achieving and maintaining adequate weight loss. In addition, each has proven successful in reversing or ameliorating many of the comorbidities associated with obesity. RYGB is the most common procedure performed in the United States and is considered the gold standard. It has the best short- and long-term results for safety, efficacy, and durability, and it has been proven to be superior in results to those for AGB. In experienced hands, this technically challenging procedure can now be performed laparoscopically. This method has the same weight loss and health benefits as the open procedure while achieving all the added benefits of a minimally invasive approach. Long-term data seem to support the malabsorptive procedures as most effective in the superobese. All the procedures require compliance and long-term nutritional follow-up.     

Beneficial health effects of modest weight loss.

The medical effects of modest weight reduction (approximately 10% or less) in patients with obesity-associated medical complications were reviewed. The National Library of Medicine MEDLINE database and the Derwent RINGDOC database were searched to identify English language studies that examined the effects of weight loss in obese patients with serious medical complications commonly associated with obesity (non-insulin dependent diabetes mellitus (NIDDM or type II), hypertension, hyperlipidemia, hypercholesterolemia, and cardiovascular disease). Studies in which patients experienced approximately 10% or less weight reduction were selected for review. Studies indicated that, for obese patients with NIDDM, hypertension or hyperlipidemia, modest weight reduction appeared to improve glycemic control, reduce blood pressure, and reduce cholesterol levels, respectively. Modest weight reduction also appeared to increase longevity in obese individuals. In conclusion, a large proportion of obese individuals with NIDDM, hypertension, and hyperlipidemia experienced positive health benefits with modest weight loss. For patients who are unable to attain and maintain substantial weight reduction, modest weight loss should be recommended; even a small amount of weight loss appears to benefit a substantial subset of obese patients.     

Surgical intervention as a strategy for treatment of obesity

A very large number of weight-reducing surgical techniques have been developed over the last 25 years. Today only a handful of these techniques can be recommended. Gastric bypass, vertical banded gastroplasty, and variable banding can all be recommended although gastric bypass should be reserved for heavier patients. For the heaviest, biliopancreatic diversion or biliopancreatic diversion with duodenal switch might be considered. The controlled intervention study Swedish Obse Subjects has shown that most but not all cardiovascular risk factors are improved over 10 years by surgically induced weight loss. Quality of life as well as cardiac structure and function are dramatically improved. The average weight loss for gastric bypass and vertical banded gastroplasty was 16% after 10 years. No non-surgical treatment available today can achieve such results, not even over 2 years. Surgical treatment for obesity needs to become much more common, particularly in obese patients with metabolic disturbances.     

Efficacy and safety of sibutramine in obese white and African American patients with hypertension: a 1-year, double-blind, placebo-controlled, multicenter trial

BACKGROUND: Obesity is a highly prevalent medical condition and is commonly accompanied by hypertension. This study assessed the efficacy and safety of treatment with sibutramine hydrochloride for promoting and maintaining weight loss in obese patients with controlled hypertension, including a subset analysis of African American patients. PATIENTS AND METHODS: Obese patients with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) between 27 and 40 and a history of hypertension controlled with a calcium channel blocker (with or without concomitant thiazide diuretic treatment) were randomized to receive sibutramine (n = 150) or placebo (n = 74) with minimal behavioral intervention for 52 weeks. African Americans constituted 36% of enrolled patients. Efficacy assessments were body weight and related parameters (BMI and waist and hip circumferences), metabolic parameters (serum levels of triglycerides, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol, glucose, and uric acid), and quality-of-life measures. Safety assessments included recording of blood pressure, pulse rate, adverse events, and reasons for discontinuation. RESULTS: For patients receiving sibutramine, weight loss occurred during the first 6 months of the trial and was maintained to the end of the 12-month treatment period. Among patients receiving sibutramine, 40.1% lost 5% or more of body weight (5% responders) and 13.4% lost 10% or more of body weight (10% responders) compared with 8.7% and 4.3% of patients in the placebo group, respectively (P<.05). Changes in body weight were similar among African Americans and whites. Sibutramine-induced weight loss was associated with significant improvements in serum levels of triglycerides, HDL-C, glucose, and uric acid. Waist circumference and quality-of-life measures also improved significantly in patients receiving sibutramine. Sibutramine-treated patients had small but statistically significant mean increases in diastolic blood pressure (2.0 mm Hg) and pulse rate (4.9 beats/min) compared with placebo-treated patients (-1.3 mm Hg and 0.0 beats/min; P<.05); these changes were similar among African Americans and whites. Most adverse events were mild to moderate in severity and transient. The most common adverse event resulting in discontinuation among patients receiving sibutramine was hypertension (5.3% of patients receiving sibutramine vs 1.4% of patients receiving placebo). CONCLUSIONS: In obese patients with controlled hypertension, sibutramine was an effective and well-tolerated treatment for weight loss and maintenance. Sibutramine-induced weight loss resulted in improvements in serum levels of triglycerides, HDL-C, uric acid, and glucose, and in waist circumference and quality-of-life measures. Blood pressure and heart rate increased by a small amount. Efficacy and safety profiles for sibutramine among African American and white obese patients with controlled hypertension were similar.     

The effects of weight reduction on blood pressure in 301 obese patients

The effects of weight reduction on blood pressure were assessed in 301 obese patients. Weight reduction was achieved by behavior modification, medication, or their combination and was associated with significant reductions in systolic and diastolic blood pressure. The weight reduction method was less important than the amount of weight lost in determining reductions in blood pressure. The greatest reductions in weight and blood pressure occurred during the first half of weight loss, suggesting that even brief treatment (ie, 8 to 10 weeks) may benefit obese, hypertensive patients. Despite repeated measurements, 36 patients who failed to lose weight showed no decrease in blood pressure. Although blood pressure rose during follow-up in patients who regained weight, it remained below baseline levels. These findings provide further support for weight reduction in the control of hypertension.     

Should Patients with Obesity and Hypertension be Treated Differently from Those Who Are Not Obese?

Obesity and hypertension frequently coexist. Measuring blood pressure (BP) accurately in obese patients is challenging and may require strategies that are less accurate, such as forearm cuffing or use of wrist cuffs. Pathophysiologic mechanisms of hypertension may differ between obese and non-obese individuals, which may result in differing effects of common BP-lowering medications. However, to date, there is insufficient trial data to recommend a different approach to medication selection based on body mass index. Additionally, the goal BP is generally not different between obese and non-obese patients. Weight loss should be emphasized for obese patients with hypertension, and interventions in addition to diet and exercise may include weight loss medications and bariatric surgery. Recognition and treatment of obstructive sleep apnea is also important.