Obesity, defined as a body mass index (BMI) of greater than or equal to 30 kg/m2, is a chronic disease affecting a large percentage of the US population. The prevalence of obesity among US adults was 42.4% between 2017 and 2018, with the highest rates among non-Hispanic Black (49.6%) and Hispanic (44.8%) people.1 The rate of obesity is considerably increasing in children and adolescents, representing a growing public health problem.2 Obesity is associated with an increased risk of developing hypertension (HTN) and other complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, heart disease, and certain types of cancers.2 The COVID-19 pandemic, with its stay-at-home orders and social isolation, escalated rates of obesity due to increased sedentary behaviors, consumption of calorie-rich "comfort" foods, and an increase in alcohol intake to combat psychological stressors.3
Approximately 45% of American adults have HTN, defined as systolic BP (SBP) greater than or equal to 130 mm Hg or diastolic BP (DBP) greater than or equal to 80 mm Hg.4,5 The prevalence of HTN is higher in men, older adults, and non-Hispanic Black people.6 HTN is a key modifiable risk factor for premature mortality, chronic kidney disease, and cardio- and cerebrovascular comorbidities (coronary artery disease, congestive heart failure, and stroke).5,7 Despite advances in medical therapy, only 50% of patients with HTN have controlled BP.7
The link between HTN and obesity is well established. One of the most influential and largest investigations into risk factors for chronic diseases among women, the Nurses' Health Study II, followed 80,000 women over 14 years and found that women with excess weight had almost five times the incidence of HTN compared with those of healthy BMIs.8 Although obesity contributes to development of HTN, the prevalence of HTN in patients with obesity is difficult to determine. In the Nurses' Health Study II, the incidence of HTN attributable to overweight (BMI 25-29.9 kg/m2) and obesity (BMI >=30 kg/m2) in women was approximately 40%.8 In the Framingham Heart Study, in which adults ages 35 to 75 years were followed for up to 44 years, overweight and obesity accounted for 26% of new HTN cases in men and 28% in women.9 Although excess weight increases the risk of HTN, it is well known that HTN is common in individuals with healthy BMIs as well. In addition, not all patients with overweight or obesity have HTN, meaning that factors other than elevated body mass (for example, genetic makeup) contribute to development of high BP.10
In addition to being a risk factor for HTN, obesity is often implicated in difficult-to-control and resistant HTN, where BP remains above the goal level despite treatment with three or more different antihypertensives.5 The combination of obesity and HTN produces a synergistic deleterious effect on blood vessels, paving a path to target organ damage in the heart, brain, and kidneys.11
Pathophysiology of obesity-related HTN
Excess weight increases risk of HTN.10 Notably, visceral and retroperitoneal adiposity are more strongly associated with HTN than subcutaneous fat.10 The mechanism of obesity-related HTN involves complex interactions among hormonal, renal, and neuronal pathways. Free fatty acids and adipokines that are released from adipose tissues cause increased sympathetic nervous system activity, which in turn leads to arteriolar vasoconstriction.10,11 Chronic hypoxemia due to obstructive sleep apnea, which is a common comorbidity in patients with obesity, also potentiates sympathetic stimulation, resulting in increased BP.10-12
The overactive sympathetic drive results in activation of the renin-angiotensin-aldosterone system (RAAS).10-12 Stimulation of the RAAS promotes synthesis of angiotensin II contributing to vasoconstriction, vascular wall thickening, and adrenal production of aldosterone. Both angiotensin II and aldosterone increase renal tubular sodium reabsorption, water retention, intravascular volume expansion, and vascular remodeling-all of which can elevate BP.12 In addition, accumulation of visceral fat around the kidneys leads to renal tissue and renal arterial flow compression, which also stimulates RAAS, giving rise to a further increase in BP.12
Diagnosis of obesity and HTN
Calculating BMI based on an individual's weight and height is the most common way to diagnose overweight and obesity. Measures are defined as follows: overweight, BMI of 25-29.9 kg/m2; obesity class I, BMI of 30-34.9 kg/m2; obesity class II, BMI of 35-39.9 kg/m2; and obesity class III, BMI greater than or equal to 40 kg/m2.2 However, BMI measurements may overestimate the degree of adiposity in individuals who are very muscular and underestimate it in frail older adults in whom significant muscle mass loss has occurred.2 Measurement of waist circumference in combination with calculation of BMI can provide additional information on obesity-associated risks. A waist circumference of greater than or equal to 40 inches for males or greater than or equal to 35 inches for females indicates the presence of visceral obesity and a higher cardiovascular risk.2
Diagnosis of HTN (stage I, SBP of 130-139 mm Hg or DBP of 80-89 mm Hg; stage II, SBP >=140 mm Hg or DBP >=90 mm Hg) requires multiple BP readings taken with an appropriate technique and confirmed by out-of-office measurements when possible.5 Proper positioning (sitting with feet flat on floor and back supported); choice of correct cuff size (with a length covering 80%-100% of the upper arm circumference and with a width of at least 40% of the arm circumference); and taking a 5-minute rest, emptying the bladder, and avoiding the influences of caffeine and tobacco prior to measurement are crucial to obtaining reliable data.5,13
Twenty-four-hour ambulatory BP monitoring (ABPM) is the preferred method of confirming the diagnosis of HTN but has limited availability in routine practice.5,14 Home BP monitoring (HBPM), when performed by a patient utilizing a proper technique and a validated BP device, is an acceptable alternative to ABPM.5,14 HBPM provides more accurate assessment of BP than office-based readings and may also be more predictive of adverse outcomes than BP measurements obtained in the clinic.5,14 Using the average of several readings over the specified time period, most experts agree that home SBP greater than or equal to 130 mm Hg or DBP greater than or equal to 80 mm Hg confirms the diagnosis of HTN.5,14
Treatment of obesity-related HTN
Lifestyle modifications
Weight loss in patients with HTN and obesity is the cornerstone treatment of HTN and other related conditions. The BP-lowering effects of weight loss appear to be linear, with a BP reduction of around 1 mm Hg per 1 kg of weight loss.12 Weight reduction can be achieved through lifestyle intervention, behavioral approaches, pharmacologic therapy, and surgical procedures.
Dietary modifications. There are several dietary patterns that have shown weight reduction benefits, which include carbohydrate-restricted diet, fat-restricted diet, very low-calorie diet, plant-based diet, and Mediterranean diet.2 Intermittent fasting or time-restricted eating are sometimes recommended for weight loss, though findings on their efficacy remain inconclusive.2
Most experts agree that the goal of dietary therapy is to reduce total caloric intake below caloric expenditure.2 Thus, choosing a dietary pattern of healthful low-calorie foods is more important than focusing on a specific macronutrient (carbohydrate, protein, or fat) composition.11 The DASH (Dietary Approaches to Stop Hypertension) eating plan and Mediterranean diet are two nutritional patterns that emphasize consumption of fruits, vegetables, legumes, and nuts, with moderate intake of fish and low-fat dairy as well as low consumption of processed meats and simple sugars.2,5,11 The Mediterranean diet is beneficial for modest weight (-1.8 kg), SBP (-3 mm Hg), and DBP (-2 mm Hg) reduction.11,15 The DASH has a stronger effect on BP reduction (-11 mm Hg of SBP and -7 mm Hg of DBP), especially when combined with exercise (-16 mm Hg of SBP and -10 mm Hg of DBP).11,15 Irrespective of dietary plans, a reduction in sodium consumption has also demonstrated a modest benefit in terms of lowering BP, particularly in older and Black individuals.5
The direct comparison of dietary patterns has yielded mixed evidence.2 However, the best predictor of weight loss is the degree of adherence to the chosen diet.2 Thus, a chosen dietary plan should incorporate the patient's preferences as well as any behavioral (for example, time of eating, frequency of takeout, cultural and religious practices) and social (for example, finances and family support) considerations that are pertinent to the patient's nutritional choices. A referral to a registered dietitian may be warranted. Return office visits to assess barriers, discuss next steps, and provide support are essential for therapy success.
Physical activity modifications. Regular physical activity (PA) is more beneficial for weight loss maintenance than for initial weight loss. However, the evidence is clear that achieving even a modest 5%-10% loss in total body weight can result in improvements in cardiometabolic health and BP reduction (-5 mm Hg of SBP and -4 mm Hg of DBP).11,16,17 In general, 150 to 225 minutes per week of moderate-intensity PA (like brisk walking or swimming) produces 5 to 7.5 kg weight loss.11 There is a dose-response relationship between PA and weight reduction, and those individuals who engage in more intense PA benefit from an additional decrease in weight and BP.18 Reducing periods of inactivity by interrupting sitting time can also lead to a reduction in SBP or DBP of between 1 and 16 mm Hg.11,19
Before prescribing a PA program, patients should be screened for PA habits, using, for example, the Physical Activity Vital Sign.20 The activity should be slowly increased over time as tolerated. Patients' medical comorbidities (cardiovascular, pulmonary, musculoskeletal), environmental (neighborhood) safety, and preferences for types of exercise should all be considered. To mitigate cardiovascular risk, an exercise preparticipation health screening algorithm should be utilized.21 Patients should be encouraged to monitor their PA using pedometers or smartphone applications and incorporate more activity into their daily routines to increase likelihood of adherence.
Behavioral modifications. Despite effectiveness of nonpharmacologic approaches, few patients succeed in maintaining long-term weight loss and BP reduction with lifestyle modifications alone.11 Behavioral therapy, which is an essential aspect of obesity management, is intended to help patients to make lasting changes.2 Important components of behavioral therapy are self-monitoring, controlling stimuli that trigger eating, and problem solving. Weekly weighing and monitoring of diet appear to be independent predictors of weight loss maintenance over time.2
The US Preventive Services Task Force recommends referring adults with obesity to intensive multicomponent behavioral interventions.22 Unfortunately, many patients are unable to access these interventions due to shortage of services or high out-of-pocket costs. Improving access and affordability of behavioral services is the key to addressing behavioral aspects of obesity.
Weight-loss medications
Medical therapy with weight-reducing medication can be considered in patients who have limited treatment response to lifestyle modifications and have either a BMI greater than or equal to 30 kg/m2 or, in the presence of weight-related comorbidities such as HTN, a BMI greater than or equal to 27 kg/m2.2 As of today, five medications are approved by the FDA for long-term weight loss: orlistat, phentermine/topiramate extended release, naltrexone/bupropion, liraglutide, and semaglutide.2 Phentermine is approved only for short-term use (up to 12 weeks) for weight loss.2
Phentermine alone is the most prescribed drug for weight loss and belongs to the anorectic class.2 Phentermine, phentermine/topiramate ER, and naltrexone/bupropion help with weight loss by working on the brain appetite centers and reducing hunger and cravings.2 Glucagon-like peptide-1 (GLP-1) agonists (liraglutide and semaglutide) are incretin mimetics; they mimic actions of naturally produced intestinal hormones called incretins by increasing glucose-dependent insulin production and slowing gastric emptying.2 Orlistat, a lipase inhibitor, impairs digestion of dietary fat.2 Each weight-loss medication has a different adverse-reaction profile, but they are all proven to be effective in decreasing weight when compared with placebo (see Antiobesity medications for a summary of FDA-approved antiobesity medications and their effects on weight and BP).2 The choice of drug should be patient-centric, depending on the patient's comorbidities, preferences, adverse reactions, insurance coverage, and cost.2
Weight-loss drugs have a heterogeneous effect on BP that is primarily determined by magnitude of achieved weight loss. There is a slight decrease in BP with orlistat, phentermine/topiramate, and liraglutide compared with placebo.11 In contrast, there is a potential risk for increased BP with phentermine and a clinically insignificant elevation in BP associated with naltrexone/bupropion.11
A recent randomized controlled trial (RCT) demonstrated that, combined with lifestyle modifications, semaglutide 2.4 mg once weekly resulted in a 14.9% decrease in body weight and a 6.2 mm Hg drop in SBP compared with decreases of 2.4% and 1.1 mm Hg, respectively, with placebo at 68 weeks.23
Tirzepatide is a novel incretin mimetic, currently approved only for management of T2DM, that is a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonist. In addition to management of T2DM, this medication also shows promise for substantial reduction in weight and BP in patients with or without T2DM. Tirzepatide was found to be superior to semaglutide 1 mg with respect to weight loss (relative difference, -5.5 kg) in patients with T2DM and overweight or obesity.24 A new RCT that compared three different doses of tirzepatide with placebo among patients with obesity but without diabetes showed a weight loss at 72 weeks of an astounding 15% with the lowest dose (5 mg) and 21% with the highest dose (15 mg).25 Tirzepatide treatment also significantly reduced mean SBP by 7.2 mm Hg.25 The use of tirzepatide for treatment of obesity is currently off-label; however, it is highly anticipated that this novel drug will soon be approved for weight loss as well.
Despite proven benefits, weight-loss medications are underutilized. Only 1.3% of eligible patients receive a prescription for one of these medications.26 There are multiple barriers to prescribing: high cost, inconsistent insurance coverage, concerns about long-term safety, and perception that obesity is a personal fault rather than a legitimate medical condition.26 Future studies are warranted to establish long-term effects of weight-loss medications. Education of providers and more inclusive coverage are needed to expand the use of medical therapies.
Antihypertensive medications
Most patients with obesity-related HTN are treated with BP-lowering medications. First-line antihypertensive agents (angiotensin-converting enzyme inhibitors [ACEIs], angiotensin receptor blockers [ARBs], calcium channel blockers [CCBs], and thiazide diuretics) effectively reduce BP and HTN-associated risk.5,27 There is solid evidence that the extent of BP reduction and not the choice of a particular drug is the major determinant of cardiovascular protection.5,27
Nevertheless, most HTN trials do not address patients with obesity as a distinct group; thus, there is paucity of evidence on the optimal choice of antihypertensive medications for this subset of patients. Some experts advocate for ACEIs and ARBs as the best initial therapy considering the role of activated RAAS in the pathogenesis of obesity-related HTN.11,28 Most ACEIs and ARBs are weight neutral.29 Similar to ACEIs and ARBs, CCBs (amlodipine, felodipine) have a neutral effect on weight and are generally considered a good choice for patients with HTN and obesity.12
Thiazide diuretics (chlorthalidone, hydrochlorothiazide) are very effective in controlling BP and associated with modest weight loss.29 However, this class can worsen metabolic abnormalities (elevated cholesterol and hyperglycemia), which are common in patients with excess weight. The frequency and degree of these adverse reactions are much lower with low-dose therapy (12.5-25 mg/day).29
Beta-blockers are not routinely used to treat uncomplicated HTN due to suboptimal protection against stroke compared with other antihypertensives.5,30 Many traditional beta-blockers (metoprolol, atenolol, propranolol) can lead to a slight increase in serum triglycerides.30 Vasodilating beta-blockers (carvedilol) have a more favorable metabolic profile.30 Beta-blockers may be associated with minimal and not clinically important weight gain for the first few months of therapy, followed by a plateau period.30 Therefore, their use should not be restricted for specific compelling indications such as heart failure and postmyocardial infarction, for which beta-blockers improve outcomes beyond BP control.5,29
Metabolic surgery
Metabolic (bariatric) surgery has emerged as the most effective therapy for achieving substantial and sustained weight loss.12 Surgical procedures may be considered for patients with either a BMI greater than or equal to 40 kg/m2 or, with at least one obesity-related complication (including HTN), a BMI of 35 to 39.9 kg/m2.2
Metabolic procedures currently performed in the US include sleeve gastrectomy (58% of all procedures), Roux-en-Y gastric bypass (19%), adjustable gastric banding (3%), and biliopancreatic diversion with duodenal switch (0.6%).12 Adjustable gastric banding is a purely restrictive procedure that reduces the stomach's capacity.2 Sleeve gastrectomy, in addition to gastric restriction, diminishes production of hunger hormones.2 Other operations are both restrictive and malabsorptive, with reduced nutrient absorption resulting from shortening the length of the small intestine.2
Regardless of the specific bariatric procedure used, bariatric surgery results in greater long-term weight loss than the best available nonsurgical treatments.2,12 In a retrospective study of more than 65,000 patients, there was 14%-31% loss of total body weight 1 year after surgery, and the 5-year total weight loss was 12%-25%.31
Metabolic surgery may also improve HTN control.11 To date, only one RCT has been performed to evaluate the impact of metabolic surgery on HTN.32 Compared with patients receiving medical therapy alone, patients who underwent Roux-en-Y gastric bypass plus medical therapy were significantly more likely to achieve at least a 30% reduction in total number of BP medications while maintaining BPs of less than 140/90 mm Hg. Remission of HTN (defined in the study as BP <140/90 mm Hg with no medication use) was also more common after this procedure.32 At 3-year follow-up, 35% of patients who had Roux-en-Y gastric bypass maintained HTN remission compared with 2% of patients who were treated medically.33
Conclusions and implications for advanced nursing practice
Obesity increases risk of HTN and other cardiometabolic comorbidities. NPs and other advanced practice registered nurses (APRNs) are well positioned to mitigate these risks by focusing on management of obesity and HTN. APRNs should routinely assess patients' weight, BMI, waist circumference, and BP to address these problems in a timely way. Patients with obesity-related HTN should be counseled about lifestyle modifications. Allocating sufficient time for counseling should be a priority. Patients' preferences, dietary and exercise habits, environmental factors, and medical comorbidities should be considered. Regardless of which diet or exercise program is chosen, frequent follow-ups to address barriers and offer encouragement are essential for treatment success. Medications to treat obesity, especially incretin mimetics, reduce weight while improving BP control. NPs and other APRNs should be familiar with indications, mechanisms of action, and adverse reactions of weight-loss medications, as well as their respective authorization processes. Broader and more consistent insurance coverage of weight-management medications is needed to expand the use of these treatments to patients in need. Metabolic surgery offers the greatest reduction in weight and may cure HTN (induce HTN remission) in some patients. Fundamental to the success of the surgery is proper patient selection, counseling, and continuous follow-up care.
NPs and other APRNs are often at the forefront of these issues. Selecting antihypertensive drugs that promote weight loss or are at least weight neutral is the key to effective control of obesity-related HTN. Importantly, treating patients living with obesity and HTN with respect and dignity as well as actively involving them in their care and medical decision-making can enhance their adherence to therapies and ultimately improve their overall health and well-being.
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