Unmet Needs in Hypertension A Toolkit for Health Care Professionals American Heart Association, Inc. acknowledges Medtronic and its support.
Publisher’s Note Unmet Needs in Hypertension: A Toolkit for Health Care Professionals is published by Ascend Media. 401 SW Ward Road, Suite 210, Lee’s Summit, MO 64081 © 2024 American Heart Association, Inc., a 501(c)(3) not-for-profit. All rights reserved. Unauthorized use prohibited. All references and data are as of August 2024.
3 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Contents 6 Understanding Hypertension 8 Initial Management of Hypertension 9 Nonpharmacologic Interventions 10 Pharmacologic Interventions 12 What Is Resistant Hypertension (RH)? 14 Diagnosing Resistant Hypertension Is a Multistep Process 19 Managing Resistant Hypertension 20 Disparities in Resistant Hypertension 21 Shared Decision-Making Plus! List of common drugs and substances that can elevate BP Page 8 Top five barriers to medication adherence and screening approaches Page 15
4 Contributing Authors George Bakris, MD Joseph A. Diamond, MD, FACC, FASN, FAHA Erika R. Drury, MD Mulubrhan F. Mogos, PhD, MSc, FAHA Mary L. Velasquez, RN, MS, ACNP-BC George Bakris, MD, was a professor of medicine and director of the American Heart Association’s Comprehensive Hypertension Center at the University of Chicago. Over his career, Dr. Bakris authored more than 800 peer-reviewed manuscripts and book chapters on diabetic kidney disease, hypertension and nephropathy progression. Additionally, he was editor-in-chief of the American Journal of Nephrology, an ad hoc editor of Diabetes Care and an international consulting editor of Hypertension Research. Disclosures: Professional Services and Activities – Employment: University of Chicago Medicine Professional Services and Activities – Other Professional Activities: Alnylam Pharmaceuticals, Bayer, Novo Nordisk Joseph A. Diamond, MD, FACC, FASN, FAHA, is board certified in cardiology and is certified by the American Heart Association as Specialist in Clinical Hypertension. Dr. Diamond is director of Nuclear Cardiology at the Long Island Jewish Medical Center. He is a fellow of the American College of Cardiology, the American Society of Nuclear Cardiology and the American Heart Association Hypertension Section. Disclosures: Professional Services and Activities – Employment: Long Island Jewish Medical Center
5 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Erika R. Drury, MD, is an assistant professor of medicine in the Division of Nephrology at the University of Rochester in Rochester, New York. She is the assistant director of the hypertension program at the University of Rochester, an American Heart Association Comprehensive Hypertension Center. Her practice focuses on difficult-to-treat hypertension, including resistant hypertension and management of blood pressure in chronic kidney disease and end-stage renal disease. Disclosures: Professional Services and Activities – Employment: University of Rochester Medicine Mulubrhan F. Mogos, PhD, MSc, FAHA, is an assistant professor at Vanderbilt University School of Nursing. His research focuses on pregnancy-related cardiovascular health, with particular emphasis on hypertensive disorders of pregnancy. He investigates the health effects of behavioral, biological and environmental factors on maternal cardiovascular health, and he explores potential interventions that reduce cardiovascular disease, including hypertension risk among women. Disclosures: Professional Services and Activities – Employment: Vanderbilt School of Nursing Mary L. Velasquez, RN, MS, ACNP-BC, is a CPC/STEMI/ PSC program manager and coordinator for Teleneurology Services and Cardiovascular Data Registries at Sutter Health. As a cardiovascular clinician, Velasquez is a cardiovascular team member of the American College of Cardiology and the American Heart Association and Western States: Quality, Outcomes Research and Analytics Task Force. She has managed cardiac clinical research and is an expert in program development. Disclosures: Professional Services and Activities – Employment: Sutter Health Relationship disclosures within the past 24 months: The American Heart Association is committed to ensuring balance, independence, objectivity and scientific rigor in its certified educational activities. All faculty, planners and contributors in a position to control the content for an AHA-sponsored activity are required to disclose to the activity audience any financial relationships regardless of the amount during the prior 24 months with (1) the manufacturer(s) of any ineligible company product(s) and/or interest(s) of ineligible companies regardless of relation to the content of the activity and (2) any ineligible company supporters of the activity. When an unlabeled use of a commercial product or an investigational use not yet approved for any purpose is discussed during an educational activity, the faculty must disclose that the product is not labeled for the use under discussion or that the product is still investigational.
6 People with any degree of hypertension should be treated with nonpharmacologic interventions plus pharmacotherapy as needed to reach their BP goal.1-3.1 Understanding Hypertension What Is Hypertension? A direct relationship between increasing levels of blood pressure (BP) and increasing clinical morbidity and mortality has been recognized at least since the 1920s. Rigorously tested and effective BP treatments began to emerge in the 1960s and 1970s.1-Introduction Meta analysis of more than 60 prospective studies revealed a log-linear relationship between risk of cardiovascular disease (CVD) and both increasing levels of systolic blood pressure (SBP) and increasing levels of diastolic blood pressure (DBP). There is no “safe” level of uncontrolled hypertension.1-2.1 An elevated BP increases one’s risk of death from stroke, heart disease or other vascular disease.1-2.1 Heightened SBP and DBP are independently associated with increased risk of CVD incidence, angina, myocardial infarction (MI), heart failure (HF), stroke, peripheral artery disease (PAD) and abdominal aortic aneurysm (AAA). There are similar associations across broad age ranges less than 80 years, in both men and women, in multiple racial and ethnic categories and with a wide variety of comorbid conditions. The higher one’s BP, the higher one’s risk of CVD, ischemic disease and premature death.1-2.1 The current 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults replaced prior Joint National Committee (JNC) reports and has been updated by research in certain areas. The target BP for most adults who have been diagnosed with high blood pressure is <130/80 mm Hg regardless of age, sex, comorbidities, medications, race, ethnicity or other factors. A lower BP is better for reducing one’s risk of cardiovascular and other events.1-3.1 All BP measurements are based on an average of two careful readings obtained on at least two occasions.1-4.1.1 BP can be categorized into four levels.1-3 Table 6 BP CATEGORY BP (MM HG) SBP DBP NORMAL <120 and <80 ELEVATED 120-129 and <80 STAGE 1 HYPERTENSION 130-139 or 80-89 STAGE 2 HYPERTENSION ≥140 or ≥90
7 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Causes and Risk Factors Many of the common risk factors associated with high BP can be modified, including: Cigarette smoking/tobacco smoke exposure1-2.4 synopsis Diabetes Excessive alcohol consumption1-5.2.5 Hyperlipidemia Obstructive sleep apnea1-5.4.4 Overweight/obesity1-5.2.1 Physical inactivity/poor physical fitness1-5.2.4 Unhealthy diet1-2.4, 5.2 People with high BP may also have diabetes mellitus and dyslipidemia, including high levels of low-density lipoprotein (LDL) cholesterol or hypercholesterolemia, elevated triglycerides and low levels of high-density lipoprotein (HDL) cholesterol.1-2.4 There are complex and interdependent relationships between hypertension and other modifiable risk factors for CVD. Multiple risk factors share mechanisms of action and pathophysiology. Treating some risk factors may reduce BP through shared pathology, and reducing the global risk factor burden may reduce CVD risk. Common hypertension comorbidities include stroke, HF and chronic kidney diseases (CKD), which may both contribute to and be caused by elevated BP.1.9 Measurement and Diagnosis Obtaining accurate BP readings is a critical step in identifying hypertension. The AHA suggests following a checklist of straightforward practices prior to and during all in-office BP measurements.1-Table 8 • Instruct the patient to avoid smoking, caffeine and exercise at least 30 minutes before measurement. The patient should also have an empty bladder. • Confirm that the instrument is validated and properly calibrated. • Advise the patient to sit and relax, with feet on the floor and back supported for at least five minutes before the reading and to remain still and silent during the reading. • Support the patient’s limb that is used to measure BP and confirm that the BP cuff is positioned at heart level. Be sure to use the correct cuff size and do not take measurements over clothes. • At the patient’s initial visit, measure BP in both arms and use the higher reading. To minimize error, obtain two to three measurements taken on two to three separate occasions, one to two minutes apart, to get an accurate BP estimate. • Provide the patient with their SBP and DBP reading(s) both verbally and in writing.
8 Initial Management of Hypertension About 10% of adults with hypertension have a specific and remediable cause of elevated BP.1-5.4 Genetic predisposition for hypertension cannot be altered, but many risk factors that contribute to elevated BP can be modified. Diet, overweight/obesity, physical activity and alcohol consumption can all be monitored and modified.1-6 Introduction Lifestyle modifications alone can help to reverse contributing factors, prevent future hypertension, including in those with elevated BP, and manage existing cases of hypertension.1-6 Introduction Screening for secondary causes of hypertension should be considered in all patients with hypertension, and in adults with resistant hypertension, if history and physical examination findings suggest a specific cause. Appropriate confirmatory testing should be completed before initiating treatment.1-5.4 Synopsis If a cause of secondary hypertension is identified and treated, these people can improve BP control and reduce CVD risk. A long list of common drugs and other substances can elevate BP, including: • Alcohol • Amphetamines • Angiogenesis inhibitors • Antidepressants • Atypical antipsychotics • Caffeine • Cocaine and multiple recreational drugs • Decongestants • Glucocorticoids • Immunosuppressive agents, such as cyclosporine and tacrolimus • Mineralocorticoids • NSAIDs • Oral contraceptives • Recombinant human erythropoietin • Sympathomimetic amines • Systemic corticosteroids • Tyrosine kinase inhibitors • Vascular endothelial growth factor (VEGF) inhibitors1-5.4.1, Table 14, 5-Table 2 The effects of these agents can be highly heterogeneous with most people showing little to no BP effect while others demonstrate severe BP elevations.5-Table 2
9 A Toolkit for Health Care Professionals Unmet Needs in Hypertension For most people who do not have secondary hypertension, nonpharmacologic interventions — or lifestyle modifications — are the first step in treatment. Nonpharmacologic interventions may be sufficient to prevent progression of hypertension in people with elevated BP and to meet BP goal for patients with stage 1 hypertension. Nonpharmacologic management is also integral to the treatment of stage 2 hypertension.1-6.2 The most effective proven nonpharmacologic interventions are: • Weight loss • Heart-healthy diets, such as DASH or Mediterranean diets • Reduced intake of dietary sodium • Enhanced intake of dietary potassium • Increased physical activity • Moderation or abstinence of alcohol consumption • Improved sleep hygiene • Stress management techniques • Smoking cessation1-6.2, Table 15 These interventions can be accomplished by behavioral strategies that change lifestyle, prescription of dietary supplements or kitchen-based changes that directly modify diet and eating patterns.1-6.1 Weight loss is the core recommendation to reduce BP in people with any degree of overweight or obesity. There is an apparent dose-response relationship of about 1 mm Hg reduction per one kilogram of weight loss. A patient can achieve weight loss with a combination of reduced calorie intake and increased physical activity. Other alternatives, such as pharmacotherapy or bariatric surgery, may be necessary.1-6.2.1 The DASH (Dietary Approaches to Stop Hypertension) eating plan is the dietary plan best shown to lower BP. DASH is high in fruits, vegetables and low-fat dairy products. It helps to reduce sodium intake while increasing intake of potassium, calcium, magnesium and fiber. This eating plan also limits sweets and foods that are high in saturated fats. Nonpharmacologic Interventions The Mediterranean diet, which is similar to DASH with increased allowances of fish, poultry, unprocessed red meats and small amounts of alcohol, has reduced BP — as have other dietary patterns that are low in calories from carbohydrates, high in protein or plant-based.1-6.2.2 Interventions to reduce sodium intake can help lower BP and prevent hypertension in adults. Reduction in dietary sodium by 1000 mg/d can lower SBP by 1-3 mm Hg in people who are nonhypertensive. BP reductions can be more than double in people who are salt sensitive, have hypertension or are on a DASH diet or other weight loss interventions. Optimal goal sodium intake is <1500 mg/d. Most dietary sodium in the U.S. comes from salt added during food processing or in fast-food and other restaurant kitchens. People can reduce dietary sodium intake by increasing their consumption of fresh, unprocessed foods, selecting processed foods with “no added sodium,” ordering carefully when eating out, using herbs and spices in place of salt while cooking and not adding salt at the table.1-6.2.3 Dietary potassium is inversely associated with BP and hypertension. Potassium intervention can lower BP, particularly in adults who are Black or consume high levels of sodium. Expect similar BP-lowering effects from potassium pills or from increased consumption of fruits, vegetables, low-fat dairy products, selected fish and meats, nuts and soy products.1-6.2.4 Potassium supplement pills should be used under supervision of medical professional to prevent hyperkalemia. Dynamic aerobic exercise and weight training can both help lower BP. Aerobic exercise can reduce SBP by 5-8 mm Hg in adults with hypertension. Isometric exercise may also result in substantial BP reductions.1-6.2.5 There is a strong, predictable and direct relationship between alcohol consumption and BP, especially above an intake of three standard drinks per day, approximately 36 ounces of standard beer, 15 ounces of wine or 4.5 ounces of distilled spirits. The data on significant BP or CVD consequences from consuming more than two drinks daily are not conclusive.1-6.2.6
10 Pharmacologic Interventions BP-lowering medications are recommended for: • Patients with existing CVD and stage 1 hypertension (BP ≥130/80 mm Hg1-8.1.2) • Patients with stage 1 hypertension and 10-year risk of atherosclerotic cardiovascular disease (ASCVD) greater than 10% • Patients with stage 2 hypertension (BP ≥140/90 mm Hg) There are multiple tools for CVD risk assessment. The AHA recommends use of the ACC/AHA Pooled Cohort Equations to estimate 10-year ASCVD risk.1-8.1.2 The Pooled Cohort Equations tool has been validated for U.S. adults 40–79 years old in the absence of concurrent statin therapy. Because people who are older than 79 generally have a 10-year ASCVD risk greater than 10%, the BP threshold for beginning antihypertensive drug treatment is 130/80 mm Hg.1-8.1.2 Initial Pharmacotherapy Recommendations Pharmacotherapy plus lifestyle modification remains the primary treatment for high BP. Multiple classes of oral and topical antihypertensive agents are available. 1-8.1.5, Table 18. See 1-Table 18 for agent-specific comments. Pharmacologic agents with complementary activity (synergy) can lower BP even more. Thiazide diuretics, for example, may stimulate the renin-angiotensin-aldosterone system (RAS), so adding an ACE inhibitor or ARB to a thiazide diuretic can produce additional BP lowering. Patients can begin with a single primary agent, but increasing evidence supports a two-drug approach. Initial combination Fixed-dose combination therapy, which is multiple medications combined into a single oral dose, is the preferred first-line strategy and recommendation for patients with stage 2 hypertension. Single-pill combinations give greater BP-lowering effects than multiple pills.1-12.1.1 Single-pill combinations also improve adherence to reduce CV events and all-cause mortality compared to multiple pills.3-Abstract, Conclusions Once-daily dosing improves adherence, and adherence falls as dosing frequency increases.1- 8.6.1 therapy has been shown to be more effective for BP control and CVD risk reduction than single-drug therapy. Combination therapy also demonstrates benefits earlier and promotes longer-term adherence.2-Combination Treatment as the First Step Drug combinations that have similar mechanisms of action or clinical effects should be avoided. Do not prescribe more than one drug from the same class, e.g. two different ACE inhibitors, beta blockers or nondihydropyradine CCBs.1-8.1.4 Multiple drugs from classes that target the same BP pathway, such as ACE inhibitors and ARBs, are less effective in combination and may be harmful. Avoid simultaneous use of RAS blockers, including ACE inhibitors with ARBs, ACE inhibitor or ARB with renin inhibitors, which increase cardiovascular and renal risk.1-8.1.4.1 The effects of incretin mimetics on blood pressure have not been well studied, but the class has documented benefits in CVD, weight loss and other metabolic conditions.33-Efficacy End Points People with stage 2 hypertension (BP ≥140/90 mm Hg) should begin BP-lowering medications regardless of preexisting CVD and regardless of their calculated ASCVD risk.1-8.1.2
11 A Toolkit for Health Care Professionals Unmet Needs in Hypertension First-line agents include:1-8.1.4, Table 18 Thiazide diuretics Chlorthalidone, 12.5-25 mg/dose, 1 daily Hydrochlorothiazide 25-50m mg/dose, 1 daily Indapamide 1.25-2.5 mg/dose, 1 daily Metolazone 2.5-5 mg/dose, 1 daily ACE (angiotensin converting enzyme) inhibitors Benazepril 10-40 mg/dose, 1-2 daily Captopril 12.5-150 mg/dose,2-3 daily Enalapril 5-40 mg/dose, 1-2 daily Fosinopril 10-40 mg/dose, 1 daily Lisinopril 10-40 mg/dose, 1 daily Moexipril 7.5-30 mg/dose, 1-2 daily Perindopril 4-16 mg/dose, 1 daily Quinapril 10-80 mg/dose, 1-2 daily Ramipril 2.5-20 mg/dose, 1-2 daily Trandolapril 1-4 mg/dose, 1 daily ARBs (angiotensin II receptor blockers) Azilsartan 40-80 mg/dose, 1 daily Candesartan 8-32 mg/dose, 1 daily Eprosartan 600-800 mg/dose, 1-2 daily Irbesartan 150-300 mg/dose, 1 daily Losartan 50-100 mg/dose, 1-2 daily Olmesartan 20-40 mg/dose, 1 daily Telmisartan 20-80 mg/dose, 1 daily Valsartan 80-320 mg/dose, 1 daily CCB (calcium channel blocker) dihydropyridines Amlodipine 2.5-10 mg/dose, 1 daily Felodipine 2.5-10 mg/dose, 1 daily Isradipine 5-10 mg/dose, 2 daily Nicardipine SR 60-120 mg/dose, 2 daily Nifedipine LA 30-90 mg/dose, 1 daily Nisoldipine 17-34 mg/dose, 1 daily CCBnondihydropryidines Diltiazem ER 120-360 mg/dose, 1 daily Verapamil IR 120-360 mg/dose, 3 daily Verapamil SR 120-360 mg/dose, 1-2 daily Verapamil-delayed onset ET, 100-300 mg/ dose, 1 in the evening Secondary agents include:1-8.1.4, Table 18 Diuretics—loop Bumetanide 0.5-2 mg/dose, 2 daily Furosemide 20-80 mg/dose, 2 daily Torsemide 5-10 mg/dose, 1 daily Diuretics— potassium-sparing Amiloride 5-10 mg/dose, 1-2 daily Triamterene 50-100, 1-2 daily Diuretics— aldosterone antagonists Eplerenone 50-100 mg/dose, 1-2 daily Spironolactone 25-100 mg/dose, 1 daily Beta blockers— cardioselective Atenolol 25-100 mg/dose, 2 daily Betaxolol 5-20 mg/dose, 1 daily Bisoprolol 2.5-10 mg/dose, 1 daily Metoprolol tartrate 100-200 mg/dose, 2 daily Metropole succinate 50-200 mg/dose, 1 daily Beta blockers— cardioselective and vasodilator Nebivolol 5-40 mg/dose, 1 daily Beta blockers— noncardioselective Nadolol 40-120 mg/dose, 1 daily Propranolol IR 80-160 mg/dose, 2 daily Propranolol LA 80-160 mg/dose, 1 daily Beta blockers— intrinsic sympathomimetic activity Acebutolol 200-800 mg/dose, 2 daily Penbutolol 10-40 mg/dose, 1 daily Pindolol 10-60 mg/dose, 2 daily Beta blockers— combined alpha and beta receptor Carvedilol 12.5-50 mg/dose, 2 daily Carvedilol phosphate, 20-80 mg/dose, 1 daily Labetalol 200-800 mg/dose, 2 daily Direct renin inhibitors Aliskiren 150-300 mg/dose, 1 daily Alpha-1 blockers Doxazosin 1-16 mg/dose, 1 daily Prazosin 2-20 mg/dose, 2-3 daily Terazosin 1-20 mg/dose, 1-2 daily Central alpha2agonist and other centrally active drugs Clonidine oral 0.1-0.8 mg/dose, 2 daily Clonidine patch 0.1-0.3 mg/dose, 1 weekly Methyldopa 250-1000 mg/dose, 2 daily Guanfacine 0.5-2 mg/dose, 1 daily Direct vasodilators Hydralazine 100-200 mg/dose, 2-3 daily Minoxidil 5-100 mg/dose, 1-3 daily Pharmacotherapy plus lifestyle modification remains the primary treatment for high BP.
12 1 2 What Is Resistant Hypertension (RH)? Resistant hypertension (RH) is defined as: • Above-goal BP despite the concurrent use of three antihypertensive drug classes at maximally tolerated doses, including a diuretic. or • Hypertension with four or more concurrent medications to achieve target BP. People with resistant hypertension remain at increased risk for target organ damage, morbidity and mortality despite ongoing antihypertensive drug therapy. 5-Introduction Most patients with hypertension respond to pharmacotherapy, but not all. Some people have treatment-resistant hypertension despite conscientious clinical management. The most common classes of antihypertensive agents used for individuals with difficult-totreat hypertension include: • A long-acting CCB • An RAS blocker (either an ACE inhibitor or an ARB) • A diuretic Apparent RH or True RH? True treatment-resistant hypertension requires three elements: 1. Appropriate antihypertensive drug regimen 2. Medication adherence 3. Elevated BP both in and out of office There are two types of aTRH: Uncontrolled aTRH BP ≥130/80 mm Hg on ≥3 BP medications Controlled aTRH BP ≤130/80 mmHg on ≥4 medications, unless otherwise specified5-Prevalence of RH If one or more elements is missing, then the patient has apparent treatmentresistant hypertension (aTRH). The conditions on the next page must be excluded before diagnosing true resistant hypertension.
13 A Toolkit for Health Care Professionals Unmet Needs in Hypertension White Coat and Masked Hypertension Inaccurate BP measurements can masquerade as RH. How the patient is prepared, environmental conditions, cuff size and BP measurement technique can all contribute to significant variability in BP results.1-4.1, Table 8 White coat hypertension (white coat effect) occurs when a person’s in-office BP is above goal while out-of-office BP readings are below goal. In contrast, masked hypertension (and masked uncontrolled hypertension) occurs when a person’s in-office BP is below goal while out-of-office BP readings are above goal. Both effects can be misleading and lead to misdiagnosis for the patient and underestimation of BP control rates in the office.1-4.4 AHA guidelines call for at least two readings on two or more separate occasions due to the inherent irregularity in BP measurements.1-4.1.1 Between 28% and 39% of people diagnosed with RH may be misdiagnosed due to the white coat effect.5-White-Coat Effect According to population-based studies, masked hypertension occurs in 10% to 26% of people.1-4.4 Masked hypertension is more common (up to 30%) in patients with CKD.1-9.3 Out-of-office BP readings are essential to confirm a diagnosis of RH and prevent misdiagnosis. The gold standard for out-of-office BP measurement is 24-hour ambulatory BP monitoring (ABPM), but ABPM may be unavailable due to cost, lack of insurance reimbursement, equipment shortage and other factors. Home BP monitoring generally correlates with daytime ABPM values and is an acceptable alternative if ABPM is not available. Clinicians should instruct the patient on how to perform home BP monitoring using a validated, calibrated device to accurately confirm or exclude white coat or masked hypertension.5-White-Coat Effect See page 8 for a full list of substances and common drugs that can elevate BP. How Common Is aTRH? The overall prevalence of aTRH is about 19.7% in the U.S., but it varies by population.4-Results The National Health and Nutrition Examination Survey (NHANES; n=2586) 2005-2008 showed a total aTRH, controlled plus uncontrolled, of 14.5% of adults with treated hypertension. REGARDS (n=14,731) 2003-2007 reported 14.1% while the subset of REGARDS CKD (n-3134) reported 28.1%. The ALLHAT clinical trial (n-14,684) 1994-2002 reported 12.7% and INVEST (n=17,190) 1997-2003 reported 37.8%.5-Table 1 Common RH Comorbidities Resistant hypertension is characterized by a variety of distinct demographics, comorbidities, physiological aberrations and metabolic abnormalities that can be significantly interdependent. Factors such as being male, older age and/or Black people could increase the probability of developing RH.5-Patient Characteristics Patients with RH are at higher risk for poor outcomes compared to patients with hypertension that is responsive to treatment.5-Prognosis In a retrospective study, those with RH were found to be nearly twice as likely to suffer from CVD events, myocardial infraction (MI), heart failure (HF), stroke, chronic kidney disease (CKD) and/or death, across an average of four years of monitoring. Most people with RH have sleep apnea and/or other sleep abnormalities. Vascular disease/dysfunction including elevated rates of atherosclerosis, impaired endothelial function, reduced arterial compliance and elevated systemic vascular resistance are also common. 5-Patient Characteristics
14 Diagnosing Resistant Hypertension Is a Multistep Process Correctly diagnosing resistant hypertension, whether controlled or uncontrolled, requires the patient to meet all four elements.5-Prevalence of RH To exclude aTRH, confirm that the patient is: 1 On an appropriate antihypertensive drug regimen 2 Truly adherent to the appropriate antihypertensive medications at maximum tolerated dose 3 Measuring BP accurately without white coat effect, with no medications or substances that may increase BP to masquerade as RH 4 Not suffering from an identifiable secondary cause of hypertension or other condition that is not adequately controlled Confirm Adherence Once a clinician has prescribed the appropriate medication regimen at maximum tolerated doses, the first step in diagnosing RH is to confirm medication adherence. Failure to identify and remedy nonadherence contributes to the overestimation of genuine RH. Rates of nonadherence vary widely, from 7% by pharmacy refill records to more than 60% by serum drug levels trials.5-Identifying and Correcting Medication Nonadherence The 2018 AHA Scientific Statement on RH recommends thiazide-like diuretics and mineralocorticoid receptor blockers as part of antihypertensive therapy.5-Specific Therapeutic Regimens and Figure 3 NHANES data suggest that a minority of patients who are taking these two agents and the majority of patients with aTRH are missing one or both medications in their treatment regimen.4-Perspectives A quarter of patients newly started on hypertensive therapy fail to fill their initial prescription. During the first year of treatment, the typical patient has their prescribed antihypertensive medication(s) only 50% of the time, and only 20% of patients have sufficiently high adherence to achieve the antihypertensive results reported in clinical trials.5-Identifying and Correcting Medication Nonadherence
15 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Adherence barriers fall into five areas: Sociodemographic factors such as age, ethnicity, income and health literacy levels, housing stability, copayments, transportation, rural residency, social status and support, war and disasters. Health care factors such as patientclinician relationship, patient-centeredness, clinician’s communication style and ability, teambased care, qualitybased payment, access to care, cost of care and therapeutic inertia. Therapy factors such as complex treatment regimens, treatment changes, time to benefit, adverse effects, refill frequency and refill consolidation. Conditional factors particularly comorbidities such as depression, psychoses, drug or alcohol abuse, dementia, major disability, symptom severity and quality of life. Patient factors such as lack of knowledge/ misunderstanding, poor perception of hypertension and treatment effects, diagnosis denial, fear of dependence or adverse effects, forgotten doses, limited follow-up, low self-efficacy and use of alternative therapies.7-Table 2 1 2 3 4 5 Two general approaches can be used to screen for adherence: The 4Ps use patient questionnaires and self-reports, patient interviews, pill counting and prescription refill data. They are simple and inexpensive but are not necessarily reliable and cannot confirm ingestion of medication.6-Screening Methods The 4Ms use medication ingestion under observation, medication event monitoring systems (MEMS), medication level measurement in body fluids and a digital medicine. They are more reliable than the 4Ps but are more expensive and difficult to conduct in real-world clinical practice.6-Screening Methods Nonadherence is more prevalent among newly diagnosed patients with hypertension and is generally higher among young males of underrepresented race/ethnicity and in older people. However, sex race/ethnicity and age alone do not predict adherence. Population-level data show that racial/ethnic people who have lower income, less education and are publicly insured have similar BP control compared to those who are affluent, better educated and privately insured people.6-Contributing Factors of Medication Non-Adherance A practical approach to adherence addresses as many of the potential barriers to adherence as possible across all five areas. Adherence improves with better patient knowledge and appropriate perception of hypertension, especially if combined with satisfaction with clinic visits. Patient-centered strategies and nonjudgmental clinician communication are vital to adherence success. Tailoring interventions to individual patient needs is also important.6-Practical Approaches to Improve Medication Adherence
16 Strategies to Improve Adherence Multiple factors on multiple levels contribute to poor adherence. No single solution is likely to be effective, but a sustained approach using several supporting strategies can make a significant difference in adherence. Strategies should address the barriers as well as the importance and advantages of adhering to treatment. 7-Table 5, 7-Clinical Management/Mitigation of Suboptimal Adherence 1x Convenience and simplicity are key for treatment adherence. Polypharmacy may be unavoidable, but fewer pills are better than more pills. Mounting evidence supports improved adherence and improved clinical outcomes using once daily dosing over multiple daily doses as well as fixed-dose combination agents over multiple pills.3-Conclusion, 7-Clinical Management/Mitigation of Suboptimal Adherence Whenever possible, recommend that multiple medications be taken at the same time of day, consolidate refills for multiple medications and use 90-day prescriptions to reduce pharmacy visits. Easing treatment burden can improve adherence.6-Screening Methods, 7-Table 5, 8-Practice Pointers Treatment cost is also frequently a concern. Low-cost and generic agents are almost always preferred, even if not mandated by insurance coverage or other factors. Hypertension is a silent disease with no obvious signs and symptoms and taking hypertension medications brings little or no immediately obvious improvement for patients. However, hypertension education is crucial for patients, their families and caregivers — from the potentially dire consequences of hypertension to the potentially adverse effects of hypertension medications. Better informed patients are more engaged and involved in the decisionmaking process and more adherent. Telehealth and/or digital solutions including SMS, electronic monitoring and smartphone apps can help maintain contact and engagement between visits.9-Patient Factors Individual patient education and training on tools such as home BP monitoring can also boost engagement and adherence. Monitoring BP at home gives patients insight into their health and improves their sense of involvement in managing their own care and health.5-Multisystem Intervention to Improve Adherence Patient-centered motivational counseling can identify barriers to adherence and better include patients in treatment decisions. Successfu motivational approaches l include: • Daily reminder charts • Training in self-determination • Simplified treatment regimens • Combination of multiple medications that are meant to be taken together • Social and family support • Reminder texts and calls • Electronic aids • Virtual counseling7-Table 5, 8-Evidence-Based Answer, Practice Pointers Clinicians may also benefit from training to enhance their communication skills, boost their cultural competence and improve their interactions with patients. And all health care professionals can improve the care they provide if allowed more time with patients.5, Assessment of Adherence, Multisystem Intervention to Improve Adherence Patients may not have the health literacy skills needed to successfully navigate and manage the complex health care system. The Health Literacy Universal Precautions Toolkit recommends assuming that patients may have difficulty understanding. Create a supportive environment where all patients receive both written and oral communications in plain, non-medical terms in their preferred language to support empowerment and self-management. Key elements include visual, interactive education, a medication list and/or a pictorial medication schedule. The familiar teach-back method offers clinicians a nonthreatening way to confirm that patients understand what has been explained to them.5-Multisystem Intervention to Improve Adherence
A Toolkit for Health Care Professionals Unmet Needs in Hypertension 17 Assess Medication/Substance Use Multiple classes of medications and nonprescription substances can increase BP and contribute to RH. When diagnosing RH, it is essential to assess for and, if possible, mitigate medications or other substances that may be a factor of elevated BP. See page 8 for a full list of substances and common drugs that can elevate BP. Recognize Secondary Hypertension About 10% of adults with hypertension have a specific, remediable cause related to an existing health condition. All new patients with hypertension should be screened for secondary hypertension with a history, exam and labs prior to initiating treatment.1-5.4 Secondary Forms of Hypertension Once secondary hypertension is properly diagnosed and treated, patients can attain marked improvements in BP control and CVD risk. The following conditions are often associated with secondary hypertension. Primary aldosteronism is a group of disorders characterized by excessive or inappropriate secretion of aldosterone. This includes hypertension caused by volume expansion and sympathetic nervous system activation, metabolic alkalosis, advanced cardiovascular disease, renal disease and, in severe cases of potassium excretion, hypokalemia. Other adverse effects include left ventricular hypertrophy (LVH), diastolic dysfunction and heart failure, large artery stiffness, oxidative stress, widespread tissue inflammation and fibrosis and increased resistance vessel remodeling.5-Primary Aldosteronism Primary aldosteronism occurs in about 20% of patients with confirmed RH. This high prevalence means all patients with RH should be screened for primary aldosteronism. Patients who test positive are usually referred to an endocrinologist or hypertension specialist for further evaluation and management.5-Primary Aldosteronism Renal parenchymal disease, usually referred to as CKD, is both a cause and a complication of poorly controlled hypertension. CKD prevalence will increase as the population ages, leading to an increase in RH. Patients with CKD and RH are at higher risk for CVD events and renal events, including end-stage kidney disease, compared to patients with CKD without RH declines.5-Renal Parenchymal Disease It is recommended that all patients with RH be screened for CKD, as well as other potential forms of secondary hypertension including renal artery stenosis, primary aldosteronism or other endocrine causes. Most people with CKD eventually require antihypertensive medications, but achievement of BP goals declines with higher CKD stages despite increasing use of BP medications. Because reduced salt intake may improve efficacy of hypertensive medications, special attention should be focused on dietary sodium reductions. Effective control generally requires a diuretic in the mix with evolution to more potent thiazide-type agents at higher doses or loop diuretics as renal function declines.5-Renal Parenchymal Disease Renal artery stenosis can exacerbate or worsen hypertension. It is among the most common causes of RH and may affect up to 24% of older people. Atherosclerotic disease is the usual culprit, but fibromuscular dysplasia, renal artery dissection or infarction, Takayasu arteritis, radiation fibrosis, endovascular stent grafts and other uncommon blockages can cause renovascular hypertension. Current practice focuses on optimizing antihypertensive drug therapy, most often using RAS blockade such as ACE inhibitors or ARBs.5-Renal Artery Stenosis Pheochromocytoma and paraganglioma, which are two types of chromaffin cell tumors, can be elevated in up to 4% of patients with RH. Symptoms include paroxysmal hypertension, which may be accompanied by headache, palpitations, pallor and piloerection or “cold sweat.” Clinicians should consider the diagnosis in anyone referred for RH. The screening test of choice is measurement of circulating catecholamine metabolites.5-Pheochromocytoma/ Paraganglioma
18 Pseudopheochromocytoma is a paroxysmal hypertension syndrome that often presents with panic at the onset and abrupt elevation of BP. This is due to anxiety and panic disorders as underlying conditions associated with the disease. Chronic poor sleep quality can produce similar symptoms and be a result of restless leg syndrome, insomnia and obstructive sleep apnea (OSA).5-Sleep Disorders and Pseudophoechromocytoma Cushing syndrome is an uncommon endocrine disorder caused by chronic excessive glucocorticoid exposure from endogenous or exogenous sources. Chronic exposure leads to a collection of symptoms, including mood disorders, menstrual irregularities, muscle weakness, weight gain, abdominal striae, hirsutism, dorsal and supraclavicular fat and fragile skin. Glucose disorders and hypertension are also common, mimicking severe metabolic syndrome. Cushing syndrome does not appear to be a common cause of RH.5-Cushing Syndrome Obstructive sleep apnea (OSA) is common in patients with RH and is possibly linked to increased fluid retention and accompanying upper airway edema. Clinicians should refer patients with OSA symptoms, such as loud snoring, frequent nocturnal arousal, witnessed apnea or excessive daytime sleepiness, for polysomnography at a sleep laboratory or athome sleep apnea monitoring.5-Obstructive Sleep Apnea Coarctation of the aorta surgery can increase a patient’s risk of hypertension or premature CVD, including MI, aortic aneurysm, stroke and HF. All patients with a history of coarctation repair and hypertension should be evaluated for residual aortic arch obstruction with computed tomography angiography. If hypertension is resistant to treatment, consider surgical or catheter-based intervention depending on the risk/benefit ratio.5-Coarctation of the Aorta Less common causes of secondary hypertension include acromegaly and hyperthyroid/parathyroidism, among others.5-Table 3 Evaluate Target Organ Damage Elevated BP can damage multiple organs, including eyes and kidneys, as well as the cardiovascular system and circulation. Health care professionals should evaluate possible organ damage by administering the following tests: physical exam, basic labs, fundoscopic eye exam of retina and eye grounds, cardiac exam and listening for carotid bruits. The risk of target organ damage increases with duration and severity of hypertension. Reducing BP to target goal is highly recommended to prevent or limit further damage. Elevated BP can lead to hypertensive retinopathy and worsening visual acuity. Changes to the retina may be better assessed with funduscopic examination and retinal imaging using multiple forms of optical coherence tomography than with funduscopic examination.10-Background, Diagnostics of Hypertensive Retinopathy Kidney disease is common in people with hypertension and prevalence increases as kidney function declines. Hypertension can be both a cause and an effect of CKD. Hypertension masked by CKD predicts elevated risk of CKD progression. Clinicians should screen for proteinuria and reduced glomerular filtration rate (GRF) to assess the extent of kidney disease.1-9.3 Chronic Kidney Disease Common cardiovascular damage includes LVH and coronary artery disease. LVH is commonly assessed using electrocardiography, echocardiography or MRI. Atherosclerosis and other coronary artery diseases can be assessed using pulse-wave velocity, carotid intimamedia thickness and coronary artery calcium score. 1-7.2 Cardiovascular Target Organ Damage Hypertension is a major risk factor for peripheral arterial disease (PAD), a manifestation of systemic atherosclerosis. PAD, in turn, is a risk factor for cardiovascular and ischemic limb events. Adequate BP control is critical in PAD; no data show significant differences in clinical outcome by antihypertensive drug class.1-9.5, Peripheral Artery Disease
19 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Managing Resistant Hypertension Step 1: Assess Current Management The first step begins with excluding other causes of hypertension, including white coat effect, medication nonadherence and secondary hypertension. Next, ensure the patient is keeping to a low-sodium diet (<1500mg/day) and maximizing lifestyle interventions with more than six hours of uninterrupted sleep, following a DASH-style diet, meeting weight goals, getting adequate physical exercise and stopping tobacco use. Finally, optimize a three-drug regimen and confirm adherence with three antihypertensive medications in different classes, i.e., RAS blocker, CCB and diuretic, at maximum or maximally tolerated doses. The diuretic selected must be appropriate for kidney function.5-Fig3, Management of RH, Pharmacological Treatment of RH After assessing the patient’s existing management plan, continue to follow the steps below to customize and adjust strategies if the patient’s BP remains above target. Step 2 Substitute an optimally dosed thiazide-like diuretic such as chlorthalidone or indapamide for the prior diuretic.5-Fig3, Pharmacological Treatment of RH, Specific Therapeutic Regimens RH Step 3 Add a mineralocorticoid receptor antagonist (MRA), i.e., spironolactone or epelerone.5-Fig 3, Specific Therapeutic Regimens, 11-Abstract, Research in Context, Table 2, Discussion Step 4 If the patient’s heart rate is above 70, consider adding a beta blocker (metoprolol or bisoprolol), a combined alpha-beta blocker (labetalol or carvedilol) or a central alpha antagonist (clonidine or guanfacine). Step 5 Add hydralazine, starting at 25 mg three times daily and up titrate to the maximum tolerated dose. For patients with HF with reduced ejection fraction, consider hydralazine with background isosorbide mononitrate 30-90 mg daily. 5-Fig3, Specific Therapeutic Regimens Step 6 Substitute minoxidil for hydralazine. Begin patients at 2.5 mg two or three times daily and up titrate to the maximum tolerated dose. Step 7 The final step is to refer the patient to a hypertension specialist12-10.2 or a certified hypertension center13 and consider referral for renal denervation (RDN), an emerging treatment option for patients with resistant hypertension.14 The FDA has approved two devices for RDN using either ultrasound or radiofrequency.14 RDN can reduce BP whether or not patients are taking antihypertensive medication, and individual responses vary.15,16 It is important for patients and health care professionals to engage in a thorough discussion to critically evaluate the benefits and potential risks associated with RDN and decide if RDN is the best treatment strategy for them. Further research is needed to identify those who may benefit most.34 Patients with RH are at higher risk for poor cardiovascular, kidney and other outcomes compared to patients without. Similarly, RH is associated with worse outcomes for comorbid conditions including cardiovascular and kidney disease.5-Prognosis of RH The AHA suggests a phased approach to managing RH.5-Fig3
20 Disparities in Resistant Hypertension Resistant hypertension is more common in people who are Black, male and/or older age.5-Patient Characteristics Non-Hispanic Black adults, compared to non-Hispanic white adults, have higher rates of hypertension and lower rates of hypertension control, as well as treatment intensification.19-Medication and Treatment Considerations Race is not a biological construct for disparities in hypertension and other CVD outcomes. Race and ethnicity are factors within the context of socioeconomic, environmental and systemic issues such as structural racism.17-Race and Ethnicity The hypertension burden in Black Americans is driven not by identifiable genetic factors but by social determinants of health (SDOH). Factors such as disparate rates of unemployment, family income, food insecurity, lower educational levels, lack of private health insurance and not living with a spouse or partner are significantly and independently associated with premature death. After adjusting for SDOH, the increased risk of early death for Black adults compared to white adults disappears, according to one study.20-Non-Pharmcologic Approaches A recent study identified three common health barriers (another term for SDOH) as key factors in hypertension outcomes: health literacy, patient activation and financial stress.21-Introduction Black patients made up one-third of the cohort but accounted for nearly half of patients with two or more health barriers.21-Results Patients who had no health barriers had greater BP control than those with one or more health barriers regardless of race. However, there was no difference in BP control between Black and white patients who had two or more health barriers.21-Results, Discussion Access to health care, socioeconomic status, limited access to healthy foods, acculturation, health literacy and language are important drivers of SDOH among underrepresented racial and ethnic groups.19-Conclusions Disparities in RH can and should be addressed. SDOH should always be considered in clinical assessments. Future efforts should focus on community outreach and tailored approaches that address barriers to hypertension control,7-Highlights including equitable access to care. 17-Conclusions Evidence-based medicine is the standard of care for all patients regardless of their race/ethnicity, sex/gender, socioeconomic status, geography or ability/disability. 20-Conclusion Patients with hypertension who track their own BP using ambulatory or home BP monitoring rather than in-office measurement are more engaged in their own care and may show increased adherence. Use of 24-hour ABPM or home BP monitoring in place of office BP monitoring can help with confirmation and management of hypertension.23-Discussion, Conclusion Simplify treatment regimens as much as possible to ease medication burden and improve adherence.23-Conclusion Encourage patients to build their social networks and expand their social contacts. For example, the Jackson Heart Study found that more diverse social networks are independently associated with lower prevalence of aTRH.24-Abstract, Results, Discussion The burden of hypertension does not fall evenly across all populations. Black adults in the U.S. have the highest prevalence of hypertension. 59% 47% White adults 45% Asian adults 44% Hispanic adults Black people are two to three times more likely to die of preventable CVD and strokes than white people.18-Abstract 17-Racial/Ethnic Disparities in Epidemiology of HTN, U.S. National Data
21 A Toolkit for Health Care Professionals Unmet Needs in Hypertension Shared Decision-Making Decision-making that is equally shared by patient and clinician(s) is an effective approach to improving outcomes in multiple diseases and is currently recommended in cardiovascular guidelines as well as a recent scientific statement from the AHA. The shift to shared decision-making (SDM) is part of a larger move to patient-centered care, which puts each patient’s individual health needs and preferences in outcomes at the center of all care decisions.25-Introduction SDM is a communication process by which patients and clinicians collaborate to choose tests, treatments and care plans that most align with the specific patient’s preferences and values. A growing body of evidence supports the use of SDM to improve cardiovascular outcomes. The “2019 ACC [American College of Cardiology]/AHA Clinical Performance and Quality Measures for Adults With High Blood Pressure” singled out SDM as a patient-centered approach to control BP.25-Introduction SDM is intended to ensure that the patient has the knowledge and tools to make good decisions about their health while minimizing later decisional regret or conflict and using their clinician’s assistance and clinical expertise.25-Models of SDM Shared decision-making requires three key components to be effective: 1. Clear communication of unbiased medical evidence on the risks and benefits of medical interventions and reasonable alternatives, including no intervention at all. 2. Clinical expertise provided in a way that tailors the evidence for the specific patient. 3. Explicit inclusion of the patient’s values, goals and preferences, as well as the potential treatment burdens in the decision-making process.25-Models of SDM SDM can involve multiple interactions and should facilitate the inclusion of the patient’s own support network, such as family, friends and other health care clinicians who have relevant information and/or clinical expertise.25-Models of SDM SDM is not limited to face-to-face interactions. It can happen during telemedicine and other virtual visits, web portals with patient decision aids or support tools and secure email or chat.25-Models of SDM It is proven that SDM can improve outcomes in hypertension care. “Medication Adherence and Blood Pressure Control: A Scientific Statement From the American Heart Association” cited multiple studies demonstrating that a therapeutic alliance between patient and clinician and the degree to which treatment decisions are patient-centered all affect treatment adherence and BP control. Patients who have participated in medication decisions are more adherent than patients who are not part of the decision-making process.26-Risk Factors and Predictors of Medication Adherence The effects of SDM have been studied in multiple populations, including adults who have or are at risk for developing CVD, athletes who have or are at risk for CVD and other groups.25-Effect of SDM Across the Cardiovascular Spectrum Shared decision-making can and should be incorporated into the continuum of hypertension treatment beginning with lifestyle modifications and the most appropriate first-line medications considered in primary care. SDM has been shown to reduce both smoking and BP in young males who already are diagnosed with hypertension and have been prescribed antihypertensive medications.27-Outcome changes of the whole group BP reduction and CVD risk reduction were more pronounced in patients with stage 2 hypertension.27-Outcome changes of patients with hypertension graded 2 Similarly, adults treated for hypertension in Federally Qualified Health Centers (FQHCs) — many of which are subject to adverse SDOH, such as low income and from underrepresented racial and ethnic groups — are nearly three times more likely to achieve BP control after six months of SDM compared to standard care.28-Introduction, Discussion, Table 2
RkJQdWJsaXNoZXIy MjI2NjI=