When lifestyle-based interventions fall short, physicians may consider pharmacotherapy and surgical interventions for the management of obesity hypertension, according to a scientific statement published in Hypertension.

The statement endorsed by the American Heart Association (AHA)—led by the AHA Councils on Hypertension; Arteriosclerosis, Thrombosis, and Vascular Biology; Lifestyle and Cardiometabolic Health; and Stroke—reviewed weight loss strategies for the prevention and treatment of hypertension. According to recent data, upwards of 45% of US adults are living with hypertension, making this a crucial issue to address.

“Hypertension is a major cause of increased mortality, chronic kidney disease, and cardiovascular disease,” the authors wrote, “Increased body weight and obesity are major risk factors for and often occur with hypertension; thus, intentional weight-loss strategies represent ideal targets to reduce risk for chronic diseases and mortality in individuals with overweight/obesity and hypertension.”


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The Scientific Statement began with a review of the impact of obesity-specific hypertension, including target organ damage of the vasculature, heart, kidneys, and brain. Authors cited recent evidence from a large-scale, cohort studies that demonstrated a “clear dose-response relationship” between adiposity and incident heart failure, coronary heart disease, and stroke.

“Weight loss achieved through dietary changes and increased physical activity are the cornerstones of treatment for high blood pressure that’s related to being overweight,” said Michael E. Hall, MD, MS, FAHA, associate division director for cardiovascular diseases at the University of Mississippi Medical Center in Jackson, said in a press release.2 “However, these lifestyle behaviors are often not sustained over the long-term Th[is] scientific statement suggests medical and surgical strategies [that] may help with long-term weight and blood pressure improvement, in addition to heart-healthy diet and physical activity.”

Obesity leads to both extracellular fluid volume expansion and increased blood flow in numerous tissues, which in turn causes increases in venous return and cardiac output. Renal tubular sodium reabsorption also occurs, due to elevated renal blood flow and glomerular filtration rate during obesity development. Three major factors— renin angiotensin-aldosterone activation, sympathetic nervous system activation, and kidney compression via visceral, retroperitoneal, and renal sinus fat—all contribute to increased sodium reabsorption.

Visceral obesity has also been tied to inflammatory response within adipose tissue and organs, due to the activation of resident macrophages, macrophage infiltration, and proinflammatory cytokine secretion. A number of chronic inflammatory and metabolic disorders in people with obesity have been shown to interact with elevated blood pressure and cause oxidative stress, endoplasmic reticulum stress, and blood vessel, heart, and kidney mitochondrial dysfunction.

Recommendations across multiple domains of weight loss for blood pressure management are outlined below.

Dietary Management

According to statement authors, a number of published national guidelines recommend consumption of a heart-healthy diet—either alone or as part of a holistic healthy lifestyle—for the control of hypertension, management of weight, and risk reduction of cardiovascular disease (CVD). These guidelines emphasize dietary pattern-based approaches to weight management, rather than a focus on individual food and nutrients, to prevent CVD. The most well-established of these dietary patterns are the Mediterranean Diet and the DASH (Dietary Approaches to Stop Hypertension) diet.

In a 2019 Cochrane review, researchers demonstrated that the Mediterranean diet had a “significant beneficial effect” on both systolic and diastolic blood pressure (-3.0 mmHg and -2.0 mmHg, respectively), while a meta-analysis of randomized controlled trials demonstrated that Mediterranean-based diet interventions also reduce body weight and body mass index (BMI; -1.8 kg and -0.6 kg/m2, respectively).

Research has indicated that the DASH diet provides a more “robust” blood pressure-lowering effect. A meta-analysis inclusive of 24 randomized controlled trials indicated the strong effect of the DASH diet on reducing systolic and diastolic blood pressure by -7.6 mmHg and -4.2 mmHg, respectively. Combined with weight loss and exercise interventions, this diet was associated with “significantly greater” blood pressure reductions compared with the DASH diet alone (-16.1/9.9 mm Hg vs -11.2/7.5 mm Hg).

Independent of dietary pattern, data have shown that low-sodium consumption benefits blood pressure and hypertension control. Specifically, a meta-regression analysis of 133 randomized controlled trials showed that a 2300 mg/day reduction in sodium intake decreased systolic and diastolic blood pressure by 7.7 mmHg (95% CI, -10.4 to -5.0) and 3.0 mm Hg (95% CI, -4.6 to -1.4).

In addition to tailored diet composition plans, investigators have also evaluated the timing of eating and the role that plays in weight loss and blood pressure control. Small clinical studies in a population of patients with metabolic syndrome indicate that intermittent fasting practices “may produce modest reductions” in both systolic and diastolic blood pressure—reductions similar to those achieved via weight loss through other focused interventions.

Physical Activity Management

Existing evidence in the literature indicates that both physical activity and exercise training reduce obesity, blood pressure, and obesity hypertension. While current data indicates that a weight loss as small as 2% to 3% can improve CVD risk factors, current recommendations suggest that clinically significant weight loss—defined as 5% to 10%—within a 6-month period leads to more profound improvements in CVD risk factor reduction.

Exercise training also plays a significant role in blood pressure management, independent of weight, according to results of a meta-analysis of 93 randomized controlled trials showing that both exercise training and medications effectively lower blood pressure.

A 5% to 10% loss of body weight may lead to a more than 5 mmHg and more than 4 mmHg reduction in systolic and diastolic blood pressure, while 10 kg of weight loss has the potential to lower systolic blood pressure between 5 and 20 mmHg. While physical activity of less than 150 minutes per week produces “no to minimal” weight loss, upwards of 150 minutes (150-225 minutes/week and 225-420 minutes/week) can produce between 2 and 3 kg and 5 and 7.5 kg of weight loss, respectively.

Between 200 and 300 minutes per week of physical activity is required for long-term weight maintenance.

There is increasing evidence from numerous intervention studies suggesting that a reduction in sedentariness can lead to a reduction in both systolic and diastolic blood pressure ranging from 1 to 16 mmHg.

“Although dietary modification, exercise, and associated weight loss are effective strategies for reducing [blood pressure], recidivism rates for hypertension are high among those receiving such lifestyle interventions,” the authors wrote, citing a review of prospective trials that found that the beneficial effects of weight loss on blood pressure are “significantly diminished or reversed over time.”

While blood pressure increases is typically related to the “common occurrence” of weight regain, there are data indicating that these recurrent increases are at least partially independent of regain of weight. Results of a study evaluating the body’s response to an 800 calorie per day diet for 9 weeks showed that although both body weight and ambulatory systolic blood pressure declined among participants, mean 24-hour systolic blood pressure rose to 40% of the initial response over a 6-month period of full maintenance of weight loss.

Pharmacotherapy Management

Among patients with limited response to lifestyle modifications alone, those with a BMI ≥30 kg/m2 or 27 kg/m2 with weight-related comorbidities like hypertension, pharmacotherapy may be considered. However, obesity pharmacotherapy is “intended for use as an adjunct to diet and exercise,” according to the authors.

There are 4 FDA-approved drug short-term therapeutic options for pharmacotherapy weight loss management: phentermine, diethylpropion, phendimetrazine, and benzphetamine, which all have “a close structural and mechanistic relationship” with amphetamines.

FDA approved-long term therapies include orlistat, phentermine/topiramate extended release, naltrexone/bupropion, and liraglutide 3.0 mg.

Weight loss within the first 3 to 4 months of pharmacotherapy initiation is, according to authors, the “most consistent predictor of 1-year response to these drugs,” and can be used to guide decision making in terms of pharmacotherapy continuation. For patients who experience sustained weight loss and who tolerate these drugs well, there may be a benefit associated with long-term pharmacotherapy for obesity.

Long-term effects of these medications on blood pressure are mixed and are the result of numerous factors, including differing mechanisms of action, weight loss efficacy, and study populations. Randomized controlled trials have demonstrated a “slight decline” in blood pressure in patients randomly assigned to orlistat, phentermine/topiramate, and liraglutide vs placebo at 1 year—thought to be mediated by weight loss. However, in trials with patients randomly assigned to naltrexone/bupropion vs placebo, slight increases in blood pressure have been recorded.

There are safety considerations with any pharmacotherapy, including pharmacotherapy for obesity. Common side effects include constipation, dizziness, dry mouth, and insomnia, as well as increased blood pressure related to the drug’s mechanism of action. The safety profile of orlistat is generally favorable, although the drug is generally poorly tolerated due to loose stools and fecal urgency when patients are not adherent to a low-fat diet.

Surgical Management

In 2016, there were 216,000 metabolic surgeries performed in the US, including sleeve gastrectomy (58%), Roux-en-Y gastric bypass (RYGB; 19%), adjustable gastric band surgery (3%), and biliopancreatic diversion with duodenal switch (0.6%). More than 98% of these metabolic procedures are performed laparoscopically; perioperative major morbidity is less than 5%, mortality is less than 0.2%, hospital stay is typically 1 to 2 days, and recovery is typically between 2 and 4 weeks.

Current indications for surgical weight management include patients with a BMI ≥40 kg/m2 or ≥35 kg/m2 with comorbidities; patients must be psychologically stable and have no active substance abuse. Those who have type 2 diabetes and BMI ≥30 kg/m2 are candidates if they do not have good glycemic control on reasonable medical therapy. Surgeries should be performed at centers with a multidisciplinary team: bariatric surgeon, endocrinologist/diabetologist, cardiologist, anesthesiologist, and dietician with expertise in both obesity and diabetes care.

The mechanisms driving improved blood pressure control following metabolic surgery are “multifactorial, complex, and not well understood” at the current time. Reductions in blood pressure have occurred as early as 1 week postoperatively—well before any significant weight loss—indicating a potential role of neuroendocrine mechanisms. Increases in incretin glucagon-like peptide-1 have been observed postoperatively, and the sympathetic nervous system may also play a part.

Systematic reviews of observational data indicate that metabolic surgery may improve hypertension. One review, including 136 studies and 22,094 patients, saw an overall 63% resolution of hypertension; procedure-specific reductions were 68%, 43% and 83% for RYGB, adjustable gastric band, and biliopancreatic diversion, respectively. Similarly, over a 10-year median follow up of the Swedish Obese Subject study, investigators saw a significantly greater reduction in both systolic and diastolic blood pressure in patients who underwent RYGB vs nonsurgically treated obesity management.

Currently, the GATEWAY Trial (Gastric Bypass to Treat Obese Patients With Steady Hypertension) is the only controlled trial of a metabolic surgery that evaluated blood pressure as a primary endpoint. A total of 100 patients with a BMI 30 to 39.9 kg/m2 treated with maximum doses of ≥2 antihypertensive medications were randomly assigned to receive either RYGB plus medical therapy or medical therapy alone. At 12 months, the RYGB group was more likely to experience the primary outcome: a ≥30% reduction in the total number of blood pressure medications while maintaining an office blood pressure ≤140/90 mmHg (83.7% vs 12.8% in medical therapy alone).

Data from the U.S. Nationwide Inpatient Sample indicated a total in-hospital morbidity rate of 9% and mortality risk of 0.1%, representing the significant decrease in perioperative morbidity and mortality associated with metabolic surgeries since the introduction of minimally invasive surgery. Perioperative complication rates are “approximately equivalent” to those associated with laparoscopic cholecystectomy, laparoscopic appendectomy, or hysterectomy.

Pediatric Prevention

Among children with obesity, there is a 2-fold increased risk of incident hypertension; those with severe obesity have a greater than 4-fold increased risk.

“Prevention of weight gain and obesity is paramount to prevent cardiometabolic diseases, including hypertension and subsequent heart, kidney, and brain diseases,” the researchers wrote, nothing that in children and adolescents, BMI and weight are correlated strongly with increases in blood pressure. “Comprehensive and coordinated efforts, including multidisciplinary strategies across health care systems, research programs, advocacy, education, media, and consumer organizations, are necessary.”

Factors such as parental obesity and hypertension, a history of hypertensive diseases in pregnancy, and genetic causes of early-onset diabetes require further investigation, as they may play important roles in obesity and hypertension development throughout life.

Future Research

There are numerous areas for future research. These include, but are not limited to:

  • New strategies and science-based guidelines needed to prevent childhood obesity and hypertension;
  • Evaluating if intentional weight loss plus pharmacotherapy or metabolic surgery in childhood and early adulthood can prevent hypertension and target organ damage later in life;
  • The optimal amount of time clinicians should wait before recommending aggressive weight management strategies;
  • The harms of pharmacotherapy for obesity or metabolic surgery in older adults; and
  • Minimal and maximal tolerated doses for reducing sitting time to lower blood pressure.

Randomized controlled trials evaluating metabolic surgery vs pharmacotherapy to reduce the risks of chronic kidney disease, heart failure, and stroke are also needed.

“Intentional weight loss strategies…are important ways to reduce [blood pressure] in individuals with obesity that may attenuate the risks of hypertension and related diseases,” the researchers concluded. “However, these lifestyle modifications are difficult for many patients to maintain, and rates of weight regain are high. Evidence-based treatments such as pharmacotherapy and [metabolic surgery] can also be used to treat obesity and, as a result, lower blood pressure.”

Disclosures: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

References

  1. Hall ME, Cohen JB, Ard JD, et al; for the American Heart Association Council on Hypertension; Council on Arteriosclerosis, Thrombosis, and Vascular Biology; Council on Lifestyle and Cardiometabolic Health; and Stroke Council. Weight-loss strategies for prevention and treatment of hypertension: A scientific statement from the American Heart Association. Hypertension. Published online September 20, 2021. doi:10.1161/HYP. 0000000000000202
  2. Meds, surgery may help obesity-related high blood pressure if diet, exercise fall short [news release]. American Heart Association; Dallas, TX. Published September 20, 2021. Accessed September 20, 2021.