Hypertension is a significant cause of morbidity and mortality and a major modifiable risk factor for cardiovascular disease (CVD), as well as stroke, end-stage renal failure, and peripheral vascular disease. Most adults (about 75%) with CVD comorbidities have hypertension, and poor control of hypertension further exacerbates CVD risk. Hypertension is also associated with shorter overall life expectancy. The goals of hypertensive management are to reduce elevated blood pressure, reduce overall cardiovascular risk, and prevent end-organ damage. These goals can be effectively accomplished through lifestyle interventions, diet, exercise and appropriate pharmacologic treatment. However, disparities in the treatment of hypertension still exist. As new clinical practice guidelines for hypertension will be issued in the near future, healthcare professionals should take the opportunity to incorporate the latest evidence-based medicine into clinical practice and improve outcomes in patients with hypertension.
This course is designed for all physicians, osteopaths, physician assistants, and nurses involved in the care of patients with hypertension.
NetCE is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. NetCE is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. NetCE is approved to offer continuing education through the Florida Board of Nursing Home Administrators, Provider #50-2405. NetCE is approved by the California Nursing Home Administrator Program as a provider of continuing education. Provider number 1622. NetCE is accredited by the International Association for Continuing Education and Training (IACET). NetCE complies with the ANSI/IACET Standard, which is recognized internationally as a standard of excellence in instructional practices. As a result of this accreditation, NetCE is authorized to issue the IACET CEU.
NetCE designates this enduring material for a maximum of 5 AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity. NetCE designates this continuing education activity for 5 ANCC contact hour(s). NetCE designates this continuing education activity for 5 pharmacotherapeutic/pharmacology contact hour(s). NetCE designates this continuing education activity for 6 hours for Alabama nurses. Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 5 MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program. Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit. Completion of this course constitutes permission to share the completion data with ACCME. This home study course is approved by the Florida Board of Nursing Home Administrators for 5 credit hour(s). This course is approved by the California Nursing Home Administrator Program for 5 hour(s) of continuing education credit - NHAP#1622005-5389/P. California NHAs may only obtain a maximum of 10 hours per course. AACN Synergy CERP Category A. NetCE is authorized by IACET to offer 0.5 CEU(s) for this program.
In addition to states that accept ANCC, NetCE is approved as a provider of continuing education in nursing by: Alabama, Provider #ABNP0353, (valid through December 12, 2017); California, BRN Provider #CEP9784; California, LVN Provider #V10662; California, PT Provider #V10842; Florida, Provider #50-2405; Iowa, Provider #295; Kentucky, Provider #7-0054 through 12/31/2017.
This activity is designed to comply with the requirements of California Assembly Bill 1195, Cultural and Linguistic Competency.
The purpose of this course is to provide healthcare professionals with the information necessary to develop treatment regimens associated with optimal adherence and provide adequate patient education, counseling, and support to patients with hypertension.
Upon completion of this course, you should be able to:
- Apply epidemiologic trends in hypertension to current practice so at-risk patient populations can be more easily identified, assessed, and treated.
- Utilize knowledge of the pathophysiology of hypertension to create comprehensive treatment strategies that target critical pathways in disease development and progression.
- Identify the nonpharmacologic interventions for hypertension that are supported by contemporary evidence and are in adherence with guideline recommendations.
- Discuss the risks and benefits of pharmacologic approaches to hypertension management.
- Describe strategies to improve patient adherence to hypertension medication by developing treatment regimens associated with optimal adherence and providing adequate patient education, counseling, and support.
- Analyze necessary modifications in treatment for special populations.
John J. Whyte, MD, MPH, is currently the Director of Professional Affairs and Stakeholder Engagement at the FDA's Center for Drug Evaluation and Research. Previously, Dr. Whyte served as the Chief Medical Expert and Vice President, Health and Medical Education at Discovery Channel, part of the media conglomerate Discovery Communications. In this role, Dr. Whyte developed, designed, and delivered educational programming that appeals to both a medical and lay audience.
Prior to this, Dr. Whyte was in the Immediate Office of the Director at the Agency for Healthcare Research Quality. He served as Medical Advisor/Director of the Council on Private Sector Initiatives to Improve the Safety, Security, and Quality of Healthcare. Prior to this assignment, Dr. Whyte was the Acting Director, Division of Medical Items and Devices in the Coverage and Analysis Group in the Centers for Medicare & Medicaid Services (CMS). CMS is the federal agency responsible for administering the Medicare and Medicaid programs. In his role at CMS, Dr.Whyte made recommendations as to whether or not the Medicare program should pay for certain procedures, equipment, or services. His division was responsible for durable medical equipment, orthotics/prosthetics, drugs/biologics/therapeutics, medical items, laboratory tests, and non-implantable devices. As Division Director as well as Medical Officer/Senior Advisor, Dr. Whyte was responsible for more national coverage decisions than any other CMS staff.
Dr. Whyte is a board-certified internist. He completed an internal medicine residency at Duke University Medical Center as well as earned a Master’s of Public Health (MPH) in Health Policy and Management at Harvard University School of Public Health. Prior to arriving in Washington, Dr. Whyte was a health services research fellow at Stanford and attending physician in the Department of Medicine. He has written extensively in the medical and lay press on health policy issues.
Contributing faculty, John J. Whyte, MD, MPH, has disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
John V. Jurica, MD, MPH
Jane C. Norman, RN, MSN, CNE, PhD
The division planners have disclosed no relevant financial relationship with any product manufacturer or service provider mentioned.
The purpose of NetCE is to provide challenging curricula to assist healthcare professionals to raise their levels of expertise while fulfilling their continuing education requirements, thereby improving the quality of healthcare.
Our contributing faculty members have taken care to ensure that the information and recommendations are accurate and compatible with the standards generally accepted at the time of publication. The publisher disclaims any liability, loss or damage incurred as a consequence, directly or indirectly, of the use and application of any of the contents. Participants are cautioned about the potential risk of using limited knowledge when integrating new techniques into practice.
It is the policy of NetCE not to accept commercial support. Furthermore, commercial interests are prohibited from distributing or providing access to this activity to learners.
- EPIDEMIOLOGY OF HYPERTENSION
- UNDERSTANDING THE PATHOPHYSIOLOGY OF HYPERTENSION
- SCREENING FOR HYPERTENSION
- NONPHARMACOLOGIC INTERVENTIONS FOR HYPERTENSION
- PHARMACOLOGIC INTERVENTIONS FOR HYPERTENSION
- ADHERENCE ISSUES
- TREATMENT CONSIDERATIONS IN SPECIAL POPULATIONS
- Works Cited
- Evidence-Based Practice Recommendations Citations
Supported browsers for Windows include Microsoft Internet Explorer 9.0 and up, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Supported browsers for Macintosh include Safari, Mozilla Firefox 3.0 and up, Opera 9.0 and up, and Google Chrome. Other operating systems and browsers that include complete implementations of ECMAScript edition 3 and CSS 2.0 may work, but are not supported.
#94221: Hypertension: Strategies to Improve Outcomes
Hypertension is a significant cause of morbidity and mortality and a major modifiable risk factor for cardiovascular disease (CVD) as well as stroke, end-stage renal failure, and peripheral vascular disease [1,2,3,4]. The majority (approximately 75%) of adults with CVD comorbidities have hypertension, and poor control of hypertension further exacerbates CVD risk [4,5]. Hypertension is also associated with shorter overall life expectancy . The goals of hypertensive management are to reduce elevated blood pressure, reduce overall cardiovascular risk, and prevent end-organ damage . These goals can be effectively accomplished through lifestyle interventions, diet, exercise, and appropriate pharmacologic treatment.
While the rates of blood pressure control in hypertensive patients have improved, the management of hypertension remains far from optimal. As of 2012, only 54% of all adults with hypertension had adequately controlled blood pressure . One reason for this is poor adherence to antihypertensive medications. About half of patients being treated discontinue their antihypertensive medications within one year . A study of older adults found that 14.1% had low medication adherence and 27.0% had a non-persistent medication possession ratio, reflecting an extended amount of time between prescription fills; 33.7% of the patients studied had uncontrolled blood pressure . Moreover, although certain patient populations (e.g., older adults, non-Hispanic blacks, patients with diabetes and/or chronic kidney disease [CKD]) are experiencing higher rates of antihypertensive treatment, they continue to experience high rates of inadequately controlled blood pressure . Importantly, continued efforts are needed to close treatment gaps and establish the benefits of antihypertensive therapy in all patients with hypertension.
Approximately 80 million Americans, or about one in three adults, have hypertension (defined as systolic blood pressure [SBP] ≥140 mm Hg and/or diastolic blood pressure [DBP] ≥90 mm Hg), while another 29.7% have prehypertension [4; 10; 11]. Prehypertension is defined as blood pressures ranging from 120–139 mm Hg systolic and/or 80–89 mm Hg diastolic in those individuals identified at high risk for developing hypertension and as potentially receiving benefit from early intervention with antihypertensive therapy . However, this data does not reflect how many patients suffer from hypertension but remain undiagnosed. Analysis of electronic medical records reveals that the diagnosis rate of prevalent hypertension is 62.9% while the diagnosis rate of incident hypertension is 19.9%, leaving many patients underdiagnosed [4,13]. Underdiagnosis is particularly common among survivors of transient ischemic attack (TIA) or minor stroke, due largely to medium-term variability in blood pressure measurements .
For individuals with hypertension, the majority (roughly 83%) are aware of their hypertension, with nearly 77% receiving antihypertensive treatment . However, as noted, only 54% have their hypertension adequately controlled . Of those with uncontrolled hypertension, 45.9% are not aware of their hypertension and 15.8% are aware but are not receiving pharmacologic treatment . Furthermore, 11.8% of U.S. adults with hypertension meet the criteria for resistant hypertension . Resistant hypertension is defined as blood pressure remaining above goal despite antihypertensive therapy consisting of at least three different classes of antihypertensive agents . Data further estimate that approximately 8% of U.S. adults have undiagnosed hypertension . By 2030, it is projected that 41.4% of all U.S. adults will have hypertension, an 8% increase from 2013 .
Risk factors for the development of hypertension include, but are not limited to, age, ethnicity, familial history of hypertension and genetic factors, lower levels of physical activity, weight gain, use of tobacco, and dietary factors such as inadequate intake of fruits and vegetables . Importantly, controlling dietary and lifestyle risk factors has the potential to significantly lower or prevent many cases of hypertension .
In the United States, the prevalence of hypertension in blacks is among the highest in the world and continues to increase . The overall prevalence of hypertension in black Americans is slightly more than 41%, with greater prevalence in black women (46%) [4,17]. Black Americans develop hypertension earlier in life, with much higher average blood pressures compared to whites . Thus, they face greater morbidity and mortality due to hypertension, with greater rates of fatal and nonfatal stroke, death due to heart disease, and end-stage kidney disease . The highest rates of hypertension within the black community tend to be among individuals who are middle-aged or older, physically inactive, typically overweight or obese, and have type 2 diabetes .
In Hispanic Americans, data indicate that rates of hypertension may be similar or lower than non-Hispanic whites . Black Hispanics are at greater risk of hypertension than white Hispanics, as data shows higher income, better-educated black Hispanics have higher rates of hypertension than lower-income, less-educated white Hispanics . In Mexican Americans, 29.6% of men and 29.9% of women have hypertension . Among Hispanic subpopulations, Puerto Rican Americans experience the highest mortality rate associated with hypertension (154.0 per 100,000) and Cuban Americans report the lowest (82.5 per 100,000) .
While efforts to raise awareness about hypertension and the importance of receiving antihypertensive treatment have been successful, substantial ethnic disparities remain in adequately controlling hypertension. Non-Hispanic blacks, for example, have 90% higher odds of poorly controlled blood pressure than that of whites . Similarly, Mexican Americans have 40% higher odds of uncontrolled blood pressure than non-Hispanic whites .
Treatment disparities associated with hypertension are not limited to a particular race or ethnicity; the elderly are also affected. While awareness, treatment, and control of hypertension in individuals 65 years of age and older have improved, 64% have blood pressures greater than 140/90 mm Hg . Indeed, among those 80 years of age and older, only 38% of men and 23% of women meet blood pressure targets advocated in clinical guidelines . Hypertension control is extremely poor in women 50 to 79 years of age, with only 36.1% of hypertensive women in this age-group having adequately controlled blood pressure . In postmenopausal women receiving hormonal therapy, hypertension is the most common comorbidity, with a prevalence of 34%, and is associated with significantly higher medical expenditures .
In addition to being a significant risk factor for CVD, hypertension is also a significant risk factor for stroke. For every 20/10 mm Hg increase in blood pressure, the mortality from ischemic heart disease and stroke doubles. Therefore, effectively reducing blood pressure will significantly reduce cardiovascular risk . More specifically, antihypertensive therapy can reduce the incidence of myocardial infarction (20% to 25%), stroke (35% to 40%), and heart failure (>50%) . Thus, effective antihypertensive treatment is critical in reducing the morbidity and mortality associated with hypertension. Hypertension is frequently comorbid with adverse cardiovascular outcomes and contributes to significant healthcare utilization; 69% of patients with a first myocardial infarction, 77% with a first stroke, and 74% with congestive heart failure have blood pressure >140/90 mm Hg . Furthermore, essential hypertension contributes to more than 11 million hospitalizations, nearly 40 million office visits, 940,000 emergency department visits, and 3.5 million outpatient visits annually .
In 2013, there were 71,942 deaths attributable to hypertension and 405,541 any-mention deaths attributable to hypertension . The death rate for blacks was significantly higher than for whites: 51.6 and 36.5 (per 100,000 population) for black men and women, respectively, compared with 18.9 and 15.8 for white men and women, respectively . As noted, hypertension is associated with significant healthcare expenditures, with estimated annual costs of $48.6 billion .
These prevalence and epidemiology data indicate that the prevention and management of hypertension is far from optimal. Addressing missed opportunities for adequate control of hypertension would lead to reduced associated morbidity and mortality .
The underlying pathophysiology of hypertension and coronary heart disease follow two pathways: atherogenesis and increased cardiac afterload . Endothelial injury induced by hypertension impairs the synthesis and release of nitric oxide and promotes inflammatory markers, an inflammatory process that figures prominently in the pathogenesis of both hypertension and atherosclerosis [24,25]. While hypertension accelerates the development of atherosclerosis, sustained periods of elevated blood pressure have a deleterious effect by destabilizing atherosclerotic lesions (i.e., plaque rupture) in the vasculature and contributing to acute coronary events through thrombogenesis . Similarly, mechanisms responsible for blood pressure maintenance (e.g., the renin-angiotensin-aldosterone system [RAS]) also promote atherosclerosis .
Increased cardiac afterload due to sustained periods of uncontrolled hypertension contributes to the development of left ventricular hypertrophy [26,27]. While left ventricular hypertrophy reduces coronary blood flow, it also serves as an independent predictor of adverse cardiovascular outcomes (e.g., heart failure, cardiac death) . Importantly, even in the absence of coronary heart disease, hypertension can induce myocardial ischemia .
Newer hypotheses regarding the pathogenesis of hypertension include sympathetic overactivity, which may result from obesity . For instance, animal studies show that rabbits fed a high-fat diet experienced elevated mean arterial pressure and renal sympathetic nerve activity after one week. When the rabbits resumed a normal diet, mean arterial pressure remained elevated, as did renal sympathetic nerve activity . Additionally, a study of obese hypertensive rats demonstrated that sensory denervation of white adipose tissue decreased renal sympathetic activity and mean arterial pressure, likely through inhibition of the adipose afferent reflex. Lidocaine inhibition of neurons in the paraventricular nucleus produced a similar result, suggesting a central pathway for renal sympathetic overactivity . More research is needed in this area.
It is also proposed that hypertension has an immunologic basis. Studies have revealed that hypertension is associated with renal infiltration of immune cells and that immunosuppression (either pharmacologically or pathologically induced) results in reduced blood pressure. Additionally, T lymphocytes and T-cell derived cytokines (e.g., interleukin 17) may play an important role. One hypothesis is that prehypertension results in oxidation and altered mechanical forces that lead to the formation of neoantigens. The neoantigens are presented to T cells, which leads to T-cell activation and infiltration of critical organs (e.g., the kidneys), resulting in persistent or severe hypertension and end organ damage. Activation of the sympathetic nervous system and noradrenergic stimuli has also been shown to promote T-lymphocyte activation and infiltration and contribute to the pathophysiology of hypertension [31,32,33,34,35,36].
In the elderly, alterations in arterial structure and function promote age-associated increases in hypertension . Large blood vessels become less flexible, which initiates a complex cardiovascular cascade that ultimately results in increased myocardial oxygen demand and limited organ perfusion . These effects are further enhanced by coronary stenosis . Progressive renal dysfunction further promotes hypertension through increased sodium, reduced sodium-calcium exchange, and decreased potassium excretion, which may lead to hyperkalemia .
While the effects of age and vascular risk factors have been well studied in the elderly, more recent data indicate that subtle effects from hypertension develop insidiously earlier in life, with observed effects in young adults . These data emphasize and support the need for early intervention and optimal control of hypertension.
Historically, clinicians have focused on reducing DBP vis-à-vis SBP in terms of controlling hypertension, and the issue of elevated SBP went largely unaddressed in most patients with hypertension, particularly the elderly. Indeed, survey data show that the majority of physicians (75%) fail to treat elevated SBP (140–159 mm Hg) in older patients . However, evidence continues to accumulate that indicates SBP is a major risk factor for CVD and thus warrants intervention .
Changes occur in blood pressure with increasing age. SBP rises continuously throughout life, whereas DBP rises until about 50 years of age and then plateaus [41,42]. Thus, diastolic hypertension (with or without elevated SBP) is a prominent cardiovascular risk factor before 50 years of age, and systolic hypertension is after 50 years of age. Importantly, studies show that controlling isolated systolic hypertension reduces total and cardiovascular mortality, stroke, and heart failure [43,44,45]. As the population ages, greater emphasis should be placed on treating systolic hypertension, because unattended SBP will lead to increased cardiovascular and renal disease .
White-coat hypertension is defined as situational elevated blood pressure observed in the presence of a healthcare professional in a clinical setting in contrast to normal blood pressure measurements (in the same patient) obtained through ambulatory or home blood pressure monitoring . Although its criteria may vary, as many as 20% of patients diagnosed with hypertension may be subject to this effect . Antihypertensive therapy for white-coat hypertension is of limited benefit and typically not indicated . Once diagnosed, the patient can be instructed on the importance of judiciously monitoring his or her blood pressure at home. If home monitoring is used, careful calibration of the blood pressure monitor and thorough patient education are essential . Ambulatory blood pressure monitoring may provide a more accurate depiction of variations in day and nighttime blood pressure and be helpful for further assessment of cardiovascular risk. Evidence supports serial blood pressure monitoring at three months after initial diagnosis, then every six months thereafter .
Despite little urgency to treat, white-coat hypertension is not an entirely benign condition, as it has been associated with an elevated stroke risk and cardiovascular risk compared to normotensive controls . Patients also have a 1.5 to 2 times increased risk of developing new-onset diabetes mellitus or sustained hypertension compared to normotensive patients . Firm guidelines for the treatment of white-coat hypertension are lacking, but some experts believe that cardiovascular risk factors and documented end-organ damage should be considerations for beginning treatment .
As previously stated, resistant hypertension is defined as blood pressure that remains above target goal despite the use of at least three different classes of antihypertensive therapies at optimal doses, with one being a diuretic . Approximately 13% of patients being treated for hypertension meet this criterion . Making the diagnosis, however, requires that all causes of pseudoresistance be ruled out, namely improper blood pressure measurement, inadequately prescribed medications, poor adherence to an adequate medication regimen, and white-coat hypertension . In resistant hypertension, blood pressure remains uncontrolled due to persistently elevated SBP . Patients with resistant hypertension typically have a high cardiovascular risk factor burden and systemic comorbidities (e.g., obesity, diabetes, CKD) . As the population ages and the incidence of obesity, diabetes, and CKD continues to rise, the number of patients with resistant hypertension will increase as well. Due to the need for multiple antihypertensive therapies, clinical practice guidelines for resistant hypertension indicate that treatment is largely empiric .
Despite the resistance to respond to treatment in these patients, there is some evidence that this form of hypertension could be more effectively treated. A 2012 randomized controlled trial demonstrated a significant reduction in SBP and DBP when subjects exercised on a treadmill three times per week for 8 to 12 weeks. By the end of the study, SBP was reduced by 6±12 mm Hg, while DBP was reduced by 3±7 mm Hg . Another way to approach treatment for resistant hypertension is with the addition of spironolactone into the medication regimen. As an add-on to three-drug therapy, spironolactone resulted in significant decreases in SBP as measured by ambulatory monitoring. Significant decreases in DBP were not observed .
Newer therapies on the rise for resistant hypertension include denervation of renal arteries and aldosterone synthase inhibition. Sympathetic hyperactivity in the renal arteries is thought to contribute to hypertension via vasoconstriction and renin release; removal of this stimulus by denervation should therefore decrease blood pressure. The procedure can be done as a minimally invasive surgery with the use of a catheter and radiofrequency ablation. Clinical trials show that this procedure can result in reductions in blood pressure of 20/10 mm Hg one month after treatment and 31/14 mm Hg 24 months after treatment. Trials are underway to further explore these findings . The newer drug class of aldosterone synthase inhibitors is also being evaluated. The rationale behind this treatment is to reduce the amount of aldosterone produced in the body, thus modifying one stimulus for blood pressure elevation. Though this approach has been shown to significantly decrease blood pressure in patients with primary hypertension, it is only modestly effective in patients with resistant hypertension [56,57].
Although data support that lowering blood pressure improves outcomes in patients with hypertension, this does not apply universally; lower-than-desired DBP can promote adverse cardiovascular outcomes . This inverse relationship between low DBP and adverse cardiovascular outcomes has been known for decades and is referred to as the J-curve effect. The J-curve effect is most pronounced in patients with pre-existing hypertension, coronary heart disease, or left ventricular hypertrophy . Ideally, the DBP should be maintained between 80 and 85 mm Hg in patients with pre-existing cardiac disease . In addition to those with pre-existing CVD, other patient populations who may be impacted by the J-curve effect include the elderly and blacks . The effect may be intensified by the natural nocturnal decrease in blood pressure; thus, patients should avoid late-night doses of antihypertensives. Orthostatic hypotension can also intensify the J-curve effect .
Causes for the J-curve effect are unknown, though some explanations have been offered. One explanation is that a low DBP is the result of greater comorbidity, not necessarily the other way around. Another explanation holds that lower DBP signifies a sicker heart. Third, lower DBP may be associated with the widened pulse pressure that accompanies aortic disease. A fourth explanation points to reduced coronary perfusion as being responsible for the J-curve .
In high-risk elderly with cardiovascular complications, lowering blood pressure should be done slowly and carefully, avoiding lowering of DBP below 60 mm Hg to minimize decreases in coronary perfusion [58,61]. Because there is limited additional benefit for cardiovascular risk reduction to intensive blood pressure lowering, guidelines are more likely to ease target goals to <140/90 mm Hg, as advocated by the American Diabetes Association [61,62,63].
Accurate measurement and assessment are critical in identifying those patients with or at-risk for hypertension. Patients should be actively encouraged to also monitor their blood pressures outside the clinical setting. The Report of the 7th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) screening recommendations for patients without acute end-organ damage are listed inTable 1. The report of members of the 8th Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 8) was published in 2014, but this new guideline is limited to the pharmacologic management of hypertension; much of the guidance addressing screening, diagnosis, and lifestyle modification has been removed . As such, the screening recommendations from the JNC 7 remain the standard for now. The U.S. Preventive Services Task Force recommends screening for hypertension in adults 18 years of age and older . A Veterans' Affairs/Department of Defense task force recommends that screening occur periodically (preferably annually) .
HYPERTENSION SCREENING RECOMMENDATIONS
|Classification||Systolic/Diastolic Blood Pressure (mm Hg)||Follow-Up|
|Stage 1||140–159/90–99||Within two monthsa|
|Stage 2||≥160/≥100||Within one monthb|
Lifestyle modifications are critical as first-line therapy for both preventing and managing hypertension . In terms of lifestyle changes to manage blood pressure, the JNC 8 endorses the joint guideline from the American Heart Association (AHA) and the American College of Cardiology (ACC) on lifestyle management to reduce cardiovascular risk . This guideline recommends major lifestyle modifications recommended by JNC 7 known to lower blood pressure, including weight loss, increased physical activity, and adoption of the Dietary Approaches to Stop Hypertension (DASH) eating plan . For patients with hypertension who may be overweight or obese, even modest weight loss can reduce blood pressure [68,69]. Regular aerobic physical activity can further facilitate weight loss, decrease blood pressure, and reduce the overall risk of CVD [70,71,72]. Other modes of exercise can provide benefit to patients with hypertension. In addition to aerobic endurance training, dynamic resistance training, combined endurance and resistance training, and isometric resistance training can significantly lower DBP; all of these modes except combined training can lower SBP as well, but this may warrant further study. Additionally, moderate-to-high intensity bouts of aerobic endurance activity, cumulating in less than 210 minutes of exercise per week, demonstrated the largest reduction in blood pressure, suggesting that shorter bouts of more intense exercise are more effective for blood pressure reduction than longer bouts at a lower intensity . The American College of Sports Medicine recommends ≥30 minutes of moderate intensity exercise on most, preferably all, days of the week for patients with hypertension and that this training should be supplemented with resistance exercise as well . Though aerobic activity has been shown to have the greatest blood pressure-lowering effect in hypertensives, the effects of the other modes of training discussed are similar. Clinicians should consider the patient's preference of exercise mode when counseling, as patient choice may improve adherence to an exercise program. Examples of lifestyle modifications and their antihypertensive effects are provided in Table 2.
LIFESTYLE MODIFICATIONS TO PREVENT AND MANAGE HYPERTENSION
|Lifestyle Modification||Recommendation||Approximate Systolic Reduction (mm Hg)|
|Physical activity||↑aerobic physical activity to at least 30 min/day, most days||4–9|
|DASH eating plan||↑fruits, vegetables, and low-fat dairy products; ↓saturated and total fat||8–14|
|Restrict sodium intake||↓daily dietary sodium intake to 2.4 g sodium||2–8|
|Moderate alcoholic intake||Limit daily intake to 1 drink for women and 2 for men||2–4|
|Weight loss||Maintain normal body weight (body mass index 18.5–24.9 kg/m2)||5–20 per 10 kg weight loss|
|Stress reduction||Practice stress reduction measures||5|
|Smoking cessation||Any smoking cessation program||3–4|
Nutrition is a key component for the prevention and management of hypertension. Adoption of the DASH eating plan can be very beneficial in reducing blood pressure in hypertensive and normotensive patients and in reducing overall CVD [65,76,81]. The DASH eating plan reinforces reductions in saturated fat, cholesterol, and total fat while emphasizing fruits, vegetables, fat-free or low-fat milk, whole-grain products, fish, poultry, and nuts, and reducing lean red meat, sweets, added sugars, and sugar-containing beverages . DASH also focuses on increasing intake of potassium, calcium, and magnesium. Importantly, the DASH diet is highly endorsed by the AHA/ACC as an effective treatment option for patients with elevated blood pressure . Key nutritional provisions of the DASH eating plan are listed inTable 3. When combined with exercise and weight loss in overweight or obese patients with high blood pressure, the DASH diet results in even greater reductions of blood pressure (−11.2/−7.5 mm Hg [DASH alone] vs. −3.4/−3.8 mm Hg [usual diet controls]) and provides physiologic benefits, including improvements in vascular function and reduction in left ventricular mass .
DASH EATING PLAN RECOMMENDATIONS: DAILY NUTRIENT GOALS
|Food Group||Daily Servings||Examples||Significance Source|
|Whole grains||6||6 to 8||10 to 11||12 to 13||Bread, pasta, cereals, oatmeal, brown rice, popcorn||Energy, fiber|
|Vegetables||3 to 4||4 to 5||5 to 6||6||Broccoli, carrots, potatoes, spinach, tomatoes, green beans||Potassium, magnesium, fiber|
|Fruits||4||4 to 5||5 to 6||6||Apples, bananas, dates, grapes, oranges, melons, peaches, strawberries||Potassium, magnesium, fiber|
|Fat-free/low-fat dairy||2 to 3||2 to 3||3||3 to 4||Reduced-fat cheese/milk/yogurt||Calcium, protein|
|Lean meats, poultry, fish||3 to 6||≤6||6||6 to 9||Lean, trim visible fat, remove poultry skin, broil or roast||Magnesium, protein|
|Nuts, seeds, legumes||3 per week||4 to 5 per week||1||1||Almonds, peanuts, kidney beans, lentils, walnuts||Energy, magnesium, protein, fiber|
|Fats and oils||2||2 to 3||3||4||Soft margarine, vegetable oil, low-fat mayonnaise||—|
|Sweets/added sugars||0||≤5 per week||≤2||≤2||Fruit punch, hard candy, jelly, maple syrup, sorbet and ices, sugar||Low in fat|
Importantly, dietary sodium restriction, alcohol moderation, stress reduction, and smoking cessation can also lower blood pressure. A higher sodium intake is an independent risk factor for developing hypertension . Using multiple lifestyle modifications concurrently can have a synergistic effect on lowering blood pressure and is actively encouraged to reduce cardiovascular risk. For example, in patients with hypertension, simultaneous use of multiple lifestyle changes, such as weight loss, sodium reduction, increased physical activity, limited alcohol intake, and the DASH diet, not only significantly reduces blood pressure but cardiovascular risk as well .
The Academy of Nutrition and Dietetics strongly recommends medical nutrition therapy provided by a registered dietitian nutritionist to reduce blood pressure in adults with hypertension . The Academy recommends that the dietitian nutritionist provide medical nutrition therapy at least once per month for the first year, with follow-up sessions at least two to three times per year thereafter to maintain reductions in blood pressure. Their recommendations are based on research indicating significant reductions in SBP (up to 10 mm Hg) and in DBP (up to 6 mm Hg) at 3 months when therapy was provided every other week for a minimum of three sessions; at 6 to 12 months when therapy was provided at least monthly or with follow-up after five or more sessions; and up to four years when therapy was provided at least two to three times per year .
Data indicate that stress contributes to hypertension and cardiovascular mortality [79,86]. A meta-analysis examining stress reduction approaches (e.g., biofeedback, relaxation-assisted biofeedback, progressive muscle relaxation, stress management training, transcendental meditation) found that transcendental meditation was effective in significantly lowering blood pressure (−5.0/−2.8 mm Hg) and resulted in improvements in other CVD risk factors . Yoga is an exercise modality that not only reduces high blood pressure in prehypertensive and hypertensive individuals, but can also reduce blood glucose and cholesterol levels, with positive effects on body weight [87,88]. Data show that acupuncture not only improves the circadian rhythm of blood pressure in patients with hypertension but may be superior to pharmacologic therapy in relieving hypertension [89,90].
Despite known risks, almost 17% of U.S. adults (one in six) use tobacco . Tobacco use is associated with higher rates of CVD (e.g., hypertension, atherosclerosis), pulmonary diseases such as chronic obstructive pulmonary disease and emphysema, and cancer . Thus, hypertensive smokers experience greater rates of morbidity and significantly increased risk of cardiovascular and all-cause mortality than nonsmokers with hypertension [92,93]. Smoking cessation provides immediate benefits, with significant lowering of blood pressure (−3.5/−1.9 mm Hg) and heart rate (−7.3 beats per minute) seen as early as one week after cessation .
Another nonpharmacologic approach to reducing blood pressure is flaxseed supplementation. Adding flaxseed to the diet of patients with peripheral arterial disease significantly reduced SBP by 10 mm Hg and DBP by 7 mm Hg after six months . Clinical investigators hypothesized that such a drop in blood pressure would equate to a 30% and 50% reduction in the incidence of myocardial infarctions and strokes, respectively .
Coenzyme Q-10 is another dietary supplement with blood pressure control capabilities. When it is added to conventional medications, patients may experience significant reductions in SBP and DBP after eight weeks. Further reductions remain significant after one year .
Fish oil is a popular supplement used by patients suffering from CVD. Meta-analyses reveal that fish oil supplementation can result in statistically significant reductions in SBP and DBP of 2.56 mm Hg and 1.47 mm Hg, respectively. This effect was only observed in patients with hypertension, as normotensive patients experienced only nonsignificant reductions of blood pressure .
In 2013, the American Heart Association issued a scientific statement on alternative approaches to lowering blood pressure . It concludes that it is reasonable for clinicians to consider and recommend alternative approaches (such as exercise, yoga, medication, breathing exercises, and acupuncture) as long as they are used under appropriate circumstances and physician supervision. It is important for clinicians to remember that many of these alternative therapies have benefits beyond lowering of blood pressure.
The major change in the JNC 8 was an adjustment in the blood pressure levels at which pharmacotherapy should be initiated. In the general population of adults younger than 60 years of age, the Committee recommends pharmacologic treatment to lower BP be initiated at SBP ≥140 mm Hg and/or DBP ≥90 mm Hg [40,47]. The threshold levels are slightly higher for adults 60 years of age or older (i.e., ≥150/90 mm Hg) .
As discussed, the goals of hypertensive management are to reduce blood pressure, reduce overall cardiovascular risk, and prevent end-organ damage without adversely affecting quality of life, and effectively treating hypertension significantly reduces the incidence of fatal stroke, myocardial infarction, and heart failure and prolongs life expectancy [23,40,98,99]. While lifestyle modifications and nonpharmacologic treatment options are beneficial in reducing blood pressure, approximately 75% of patients with hypertension will require at least two antihypertensive agents to reduce blood pressure to within acceptable ranges [3,40,47,98] To reduce cardiovascular risk in patients with hypertension, antihypertensive agents should ideally provide effective and sustained blood pressure reduction throughout the 24-hour dosing period while attenuating early morning surges in blood pressure and reducing blood pressure variability . After antihypertensive therapy is initiated, patients should be monitored and treatment adjustments made monthly until the desired blood pressure goal is reached . The JNC 7 recommended that serum potassium and creatinine should be monitored every 6 to 12 months for patients receiving antihypertensive therapy; however, monitoring these levels is not addressed by the JNC 8 [3,40]
Pharmacologic treatment options for hypertension include, but are not limited to, thiazide diuretics, aldosterone receptor antagonists, α-adrenergic antagonists, β-blockers, angiotensin converting enzyme (ACE)-inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and direct renin inhibitors (Table 4). The management of hypertension can be challenging given the number of possible combinations of antihypertensive agents that may be needed to effectively reduce blood pressure to target goals.
SELECTED ANTIHYPERTENSIVE TREATMENT OPTIONS
|Thiazide diuretics||Bendroflumethiazide, hydrochlorothiazide, chlorthalidone, indapamide|
|Loop diuretics||Bumetanide, furosemide, torsemide|
|Potassium-sparing diureticsa||Amiloride, triamterene|
|Aldosterone receptor antagonistsa||Eplerenone, spironolactone|
|α1-adrenergic antagonistsb||Doxazosin, prazosin, terazosin|
|β-blockers||Acebutolol, atenolol, bisoprolol, metoprolol, nadolol, nebivolol, propranolol|
|α- and β-blockers||Carvedilol, labetalol|
|ACE inhibitors||Benazepril, captopril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril|
|Angiotensin II receptor blockers||Azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, valsartan|
|Calcium channel blockers||Amlodipine, diltiazem, felodipine, isradipine, nifedipine, nitrendipine, verapamil|
|Direct renin inhibitors||Aliskiren|
|Central α2 agonistsa||Clonidine, methyldopa, reserpine, guanfacine|
|Direct vasodilatorsa||Hydralazine, minoxidil|
An extensive review of all antihypertensive agents is beyond the scope of this course. However, an overview of the most commonly used and recommended approaches will be provided.
For uncomplicated hypertension in the general nonblack population, the JNC 8 recommends the use of a thiazide-type diuretic, CCB, ACE inhibitor, or ARB as initial antihypertensive therapy due to their propensity to prevent cardiovascular complications associated with hypertension . In the black population, the preferred first-line agents are thiazide diuretics or CCBs. The panel noted that heart failure outcomes were improved with initial treatment with a thiazide diuretic compared to a CCB or ACE inhibitor; all other outcomes measures were similar among the four drug classes . Thiazide-type diuretics are generally well-tolerated and effective at low doses; higher doses may be associated with hypokalemia and adverse effects such as increased uric acid and sexual dysfunction, with little added benefit . At particularly high doses, thiazide-induced hypokalemia may contribute to ventricular ectopy . Other medication (e.g., statins) classes may be considered if the patient does not respond to initial treatment or combination therapy with these agents .
Blood pressure elevation is typically the result of multiple physiologic factors, so it is very difficult to treat and manage through singular mechanisms of action [3,98]. The majority of patients with hypertension will require two or more antihypertensive agents to achieve target blood pressure goals, making combination therapy necessary [3,40,98]. Using combinations of antihypertensive agents that have complementary mechanisms of action allows for synergistic lowering of blood pressure, and such a strategy is far more effective in reducing blood pressure than increasing doses of any single antihypertensive agent [106,107]. Not only is combination therapy effective in reducing blood pressure, but it also offers the opportunity to use lower doses of each component, which may potentially lead to decreased side effects and improved adherence . It is important to note that ACE inhibitors and ARBs should not be prescribed together for combination therapy .
Combination antihypertensive therapy also reduces blood pressure variability, which is associated with an increased risk of myocardial infarction and stroke . For example, data show that reducing SBP variability with combination therapy consisting of a diuretic, a CCB, and an ACE inhibitor improves outcomes . Importantly, combination antihypertensive therapy should be approached cautiously in older patients and individuals who are at risk for orthostatic hypotension . However, despite demonstrated benefits, combination therapy for hypertension remains considerably underutilized .
The American Society of Hypertension has reviewed treatment combinations and classified them as preferred, acceptable, and less effective based on efficacy, tolerability, and adherence (Table 5) .
AMERICAN SOCIETY OF HYPERTENSION RECOMMENDATIONS FOR DRUG SELECTION IN HYPERTENSIVE PATIENTS WITH OR WITHOUT OTHER MAJOR CONDITION
|Patient Type||First Drug||Add Second Drug If Needed to Achieve a BP <140/90 mm Hg||If Third Drug is Needed to Achieve a BP <140/90 mm Hg|
|When hypertension is the only or main condition|
|Black patients (African ancestry): All ages||CCBa or thiazide diuretic||
|Combination of CCB + ACE inhibitor or ARB + thiazide diuretic|
|White and other non-black patients: Younger than 60 years of age||ARBb or ACE inhibitor||CCBa or thiazide diuretic||Combination of CCB + ACE inhibitor or ARB + thiazide diuretic|
|White and other non-black patients: 60 years of age and older||CCBa or thiazide diuretic (although ACE inhibitors or ARBs are also usually effective)||ARBb or ACE inhibitor (or CCB or thiazide if ACE inhibitor or ARB used first)||Combination of CCB + ACE inhibitor or ARB + thiazide diuretic|
|When hypertension is associated with other conditions|
|Hypertension and diabetes||
|The alternative second drug (thiazide or CCB)|
|Hypertension and chronic kidney disease||
|CCB or thiazide diureticc||The alternative second drug (thiazide or CCB)|
|Hypertension and clinical coronary artery diseased||β-blocker plus ARB or ACE inhibitor||CCB or thiazide diuretic||The alternative second step drug (thiazide or CCB)|
|Hypertension and stroke historye||ACE inhibitor or ARB||Thiazide diuretic or CCB||The alternative second drug (CCB or thiazide)|
|Hypertension and heart failure||Patients with symptomatic heart failure should usually receive an ARB or ACE inhibitor + β-blocker + diuretic + spironolactone regardless of BP. A dihydropyridine CCB can be added if needed for BP control.|
Blockade of the RAS system has become the cornerstone of antihypertensive management because ACE inhibitors and ARBs have additional benefits for comorbidities (e.g., CKD) . Indeed, ACE inhibitors or ARBs are recommended as foundation therapy for patients with comorbid diabetes . As a result, ACE inhibitors or ARBs are frequently used in combination with a thiazide diuretic (e.g., hydrochlorothiazide, chlorthalidone) to synergistically provide effective reductions in blood pressure . An ACE inhibitor or ARB may attenuate thiazide-induced hypokalemia but can alternatively cause hyperkalemia in susceptible patients [98,108]. Although hydrochlorothiazide is used most often as the diuretic in fixed-dose combination antihypertensive products, a fixed-dose combination of azilsartan and chlorthalidone was approved by the U.S. Food and Drug Administration in 2011 . Expert consensus and clinical trial data indicate that chlorthalidone may be more effective in reducing blood pressure and cardiovascular risk than hydrochlorothiazide [108,111,112].
The addition of an ACE inhibitor or ARB to a CCB not only provides effective reduction in blood pressure, but in the case of dihydropyridine-type CCBs (e.g., nifedipine) also improves their tolerability by attenuating the reflex tachycardia and peripheral edema that may be associated with their use [98,108,113,114]. Although providing comparable reduction in blood pressure in high-risk diabetic patients with ischemic heart disease, the combination of ACE inhibitor plus CCB provides greater reductions in cardiovascular risk factors (e.g., myocardial infarction, stroke) than ACE inhibitor plus diuretic .
While effective antihypertensive agents when used as monotherapy, data show that dual inhibition with both an ACE inhibitor and ARB may not only ineffectively reduce blood pressure but may cause significant adverse effects as well. In patients with vascular disease or high-risk diabetes, the combination of telmisartan and ramipril was associated with significantly increased risk of syncope, hypotension, and renal dysfunction . Similarly, when combined with an ACE inhibitor or ARB, the renin inhibitor aliskiren led to an increase in nonfatal stroke, renal dysfunction, hyperkalemia, and hypotension, which led to a premature study termination .
Data show that the combination of the CCB amlodipine plus hydrochlorothiazide is well-tolerated and has similar mortality reduction to valsartan [108,118]. The combination of a dihydropyridine CCB plus a β-blocker (e.g., felodipine and metoprolol) may effectively reduce blood pressure, although β-blockers should be used cautiously with the CCBs diltiazem and verapamil due to their synergistic effects on heart rate and atrioventricular conduction potentially leading to bradycardia or heart block [98,108]. Although β-blockers reduce cardiovascular end points, meta-analyses indicate less effectiveness in treating hypertension than diuretics, ACE inhibitors, ARBs, and CCBs [119,120,121]. β-blockers in combination with thiazide diuretics effectively lower blood pressure, but they may be associated with an increased risk of glucose intolerance, fatigue, and sexual dysfunction .
In addition to the American Society of Hypertension clinical practice guidelines on hypertension, clinical practice guidelines are also available on the management of hypertension in the elderly (65 years of age or older), in patients with diabetes, and in patients with CKD [37,110,122,123].
Guidelines for the elderly recommend identifying reversible and/or treatable causes of hypertension, evaluating for end-organ damage, assessing for other CVD risk factors/comorbid conditions, and identifying barriers to treatment adherence . In addition to history, physical exam, and lab testing, there is particular emphasis on accurate assessments of blood pressure, kidney function, and CVD . Recommended lab tests include urinalysis, blood chemistries, lipids, fasting blood glucose, and electrocardiogram. Care should be taken to address pseudohypertension due to noncompressible arteries and white-coat hypertension . Recommended target blood pressure goals in the elderly are <150/90 mm Hg for uncomplicated hypertension and <140/90 mm Hg for those with coronary artery disease or CKD if they are able to tolerate antihypertensive therapy . However, treatment need not be adjusted for older patients who have achieved a lower blood pressure without adverse effects on health or quality of life . After lifestyle modifications, thiazide diuretics should be the initial pharmacotherapy. However, in elderly patients with coronary artery disease and stable angina or prior myocardial infarction, β-blockers should be the initial pharmacotherapy. Clinicians should pay particular attention to polypharmacy in these patients, and quality of life should be always considered when making therapeutic decisions [1,124]. Management of hypertension in the elderly is made more difficult by limited clinical trial data upon which to base clinical decision-making.
The American Diabetes Association (ADA) has issued guidelines for the management of hypertension in diabetic patients . Blood pressure should be measured at every routine visit and, if elevated, measured again on a separate day. The ADA and the JNC 8 agree that the goal for people with diabetes and hypertension is SBP <140 mm Hg, though the ADA states a goal of 130 mm Hg is appropriate in younger patients, if tolerated. Both the JNC 8 and the ADA recommend DBP should be treated to <90 mm Hg; the ADA has set a lower threshold of <80mm Hg in younger patients when appropriate [40,63]. Patients who have blood pressure >120/80 mm Hg should initially be advised to undertake lifestyle changes without further pharmacotherapy. Patients who have blood pressure >140/80 mm Hg, however, should promptly begin pharmacotherapy in addition to lifestyle modifications . Pharmacotherapy for this patient population centers on either an ACE inhibitor or an ARB but not both, and multi-drug therapy is generally required to achieve target blood pressure. These medications should be managed by monitoring of serum creatinine/estimated glomerular filtration rate and serum potassium levels .
The National Kidney Foundation published guidelines on the management of hypertension in CKD in 2004 and revised them in 2012 [122,123]. Because hypertension is a risk factor for faster progression of kidney disease, antihypertensive therapy not only helps to control blood pressure but also slows this progression. Lifestyle modifications should be initiated, and sodium intake should be limited to <2 grams per day. In patients with CKD with or without hypertension, antihypertensive treatment with ACE inhibitors or ARBs is recommended to lower blood pressure (<130/80 mm Hg), reduce CVD, and slow the rate of kidney decline, with adjustments based on proteinuria . Most patients should also receive diuretics. Long-acting agents should be used when possible, and patients who have SBP >20 mm Hg above goal should begin initial therapy with two agents. A multidisciplinary approach is highly recommended to optimize outcomes in patients with CKD .
Since the publication of the National Kidney Foundation guidelines in 2004, the JNC 8 published its own recommendations for blood pressure management in patients with CKD. The JNC 8 recommends initiating pharmacologic treatment at ≥140/90 mm Hg for adults with CKD .
Successful management of hypertension can only be accomplished through appropriate selection of antihypertensive therapy to effectively lower blood pressure and maintenance of adherence to such therapy by both the patient and clinician. Indeed, successful antihypertensive treatment must be carried out continuously for many years . However, patient nonadherence to antihypertensive therapy is a major barrier to effective control of blood pressure [126,127]. Research indicates that as many as 70% of hypertensive patients do not take their antihypertensive medications as prescribed . Long-term data indicate that less than 60% of patients are still on their antihypertensive treatment 2 years after starting and only 39% of patients with hypertension remain adherent after 10 years of therapy . Thus, the ultimate challenge is to individualize antihypertensive therapy to achieve optimal levels of blood pressure control while ensuring patient adherence to and continuation of prescribed therapy . The increasing prevalence of uncontrolled or suboptimally controlled blood pressure in the face of significant advances in antihypertensive management has been characterized as the "hypertension paradox" .
Factors that contribute to suboptimal patient adherence to antihypertensive therapy are multifactorial, complex, and involve both the patient and his or her healthcare providers. Data from the World Health Organization have categorized factors associated with long-term adherence as social and economic, disease-related, therapy-related, patient-related, and healthcare system/healthcare team-related . Clearly, a number of issues can potentially adversely influence patient adherence. Interestingly, simply forgetting is the most common reason patients give for not taking antihypertensive medication . Other barriers that contribute to nonadherence include cost of care and medication, lack of insurance, transportation issues, and comorbidities .
Increasingly complex antihypertensive treatment regimens and unfavorable tolerability profiles are associated with poorer adherence [127,133,134]. Simply switching from twice-daily to once-daily antihypertensive agents can improve adherence up to 20% . Moreover, use of single-pill, fixed-dose combination therapy can improve adherence by 26% . Commercially available fixed-dose product formulations may incorporate two or three separate antihypertensive agents.
Clinicians often overestimate levels of adherence to antihypertensive therapy . Furthermore, therapeutic or clinical inertia by clinicians contributes to suboptimal control of blood pressure [137,138,139]. Data indicate that in patients with cardiovascular risk factors or established CVD, physicians are frequently less likely to intensify antihypertensive treatment when blood pressure goals have not been met . The quality of the patient-clinician relationship for communicating and building trust can favorably impact adherence; the risk for patient nonadherence increases by 19% in patients whose clinician communicates poorly [129,140]. Communication skills training programs targeting healthcare professionals' behaviors are promising strategies to reduce disparities and build trust in ethnic minority patients with hypertension . Encouragement and continual reinforcement of patients' active participation in their own care improves adherence to antihypertensive therapy as well as improves self-monitoring of their blood pressure .
In a study of older Mexican American patients, those who reported using Spanish more often than English in mass media were more likely to have undiagnosed hypertension . Language barriers can be a serious consideration when engaging in patient education and elucidating possible causes of non-adherence to the established treatment regimen. When a patient does not speak the same language as the clinician, a professional interpreter should be consulted to ensure accurate communication. Use of professional interpreters has been associated with improvements in communication (errors and comprehension), utilization, clinical outcomes, and satisfaction with care .
Studies show that suboptimal control of blood pressure is not limited to the primary care setting. For example, one study found that 30.3% of patients with hypertension being seen in a cardiology clinic had suboptimal control of blood pressure (≥140/90 mm Hg) . Moreover, clinic physicians failed to document a treatment plan to address hypertension in 38% of patients with elevated blood pressure . Thus, there are many cases where blood pressure is not only suboptimally controlled but elevated blood pressure is not acted upon when observed. Such data demonstrate a potential opportunity for improvement in hypertension management.
Suboptimal adherence to antihypertensive therapy adversely affects clinical outcomes in patients with hypertension and increases the risk of cardiovascular morbidity and mortality. Acknowledging the need to improve outcomes, the American Society of Hypertension has proposed several strategies to improve patient adherence and persistence to antihypertensive therapy that will result in more effective control of blood pressure (Table 6).
RECOMMENDATIONS FOR IMPROVING ADHERENCE IN HYPERTENSION
|Focus on clinical outcomes||
|Empower patients and encourage self-care||
|Implement a team approach||
As noted, the prevalence and control of hypertension differ across racial subgroups. In blacks, hypertension is more common, more severe, develops at an earlier age, and is associated with greater sequelae (e.g., higher rates of stroke, heart disease, end-stage renal disease, and mortality) than in non-Hispanic whites [4,145]. Blacks have a greater prevalence of other cardiovascular risk factors, especially obesity . In fact, hypertension is the single most common contributor to the mortality gap between blacks and whites . For every 10-mm Hg increase in SBP, the risk of stroke in blacks is triple that of whites (24% vs. 8%, respectively) . Non-Hispanic blacks and Mexican Americans have poorer blood pressure control rates than non-Hispanic whites . Differences in outcomes may be attributable to differences in socioeconomic conditions, access to healthcare services, attitudes regarding health care, and cultural beliefs .
Before initiation of antihypertensive therapy, weight and sodium reduction are particularly effective in minorities . For example, the low-sodium DASH eating plan is associated with significant blood pressure reductions in blacks . However, monotherapy with ACE inhibitors, ARBs, or β-blockers is less effective in lowering blood pressure in blacks than whites [3,103]. Moreover, blacks and Asians have a three- to fourfold higher risk of angioedema and have more cough attributed to ACE inhibitors than whites [3,150]. The use of combination antihypertensive drug therapy, including a thiazide diuretic, will lower blood pressure and reduce the cardiovascular and renal burden in minorities [40,103,148]. Chlorthalidone is particularly beneficial in low-renin patients as well as the elderly and patients with diabetes . Importantly, identifying and addressing treatment barriers is critical to improving outcomes in minority populations .
Hypertension affects most elderly people, and these individuals are more likely to have organ damage or clinically relevant CVD. On average, elderly patients are taking more than six prescription drugs, so polypharmacy, nonadherence, and potential drug-drug interactions are all important concerns that should be monitored and addressed . Caution is advised when initiating antihypertensive agents in the elderly, and treatment must be individualized. For example, hypertensive elderly patients have a 43% increased risk of hip fracture during the first 45 days after starting antihypertensive treatment . Conducting a risk factor assessment for falls in older adults initiating antihypertensive therapy may improve the recognition of those at risk for serious fall injuries. Independent risk factors include older age; female sex; white race; history of stroke, syncope, osteoporosis, depression or dementia; use of more than 10 medications; and a serious fall injury in the 12 months prior to initiation of antihypertensive therapy .
In the elderly, thiazide diuretics are recommended for initiating therapy and are generally well tolerated . Thiazide diuretics reduce cardiovascular events in the elderly but may also exacerbate hyperuricemia, glucose abnormalities, and dyslipidemia, which are frequently seen in the elderly . A 2015 scientific statement from the AHA/ACC/ASH urges caution when using thiazide diuretics in the elderly to avoid decreases in DBP due to reduced coronary perfusion . β-blockers are best suited for patients with migraine and/or cardiovascular comorbidities such as heart failure and coronary artery disease . All β-blockers may result in a decreased response in the elderly as compared with younger adults. Dose reduction, initial lower dose, or dose titrated to the response should be considered . In the elderly, α-adrenergic antagonists are not recommended as first-line therapy due to a possible increase in cardiovascular events [37,40,153]. Similar to β-blockers, CCBs are considered safe and effective in elderly patients with cardiovascular comorbidities (e.g., angina, supraventricular arrhythmias) [37,104]. However, dosing should start at the lower end of dosing range and be titrated to response. Elderly patients have shown a decreased clearance of amlodipine . Immediate-release nifedipine should be avoided due to the potential for postural hypotension, which may precipitate dizziness and falls . Generic versions of verapamil that are bioequivalent in young adults may not be bioequivalent in the elderly . The CCBs verapamil and diltiazem may precipitate heart block in those with underlying defects in cardiac conduction . ACE inhibitors and ARBs are well tolerated, are renal protective, and reduce cardiovascular morbidity and mortality . As with younger patients, combination therapy in the elderly offers an opportunity for enhanced effectiveness, more convenience, and potentially more favorable tolerability in a simplified antihypertensive regimen.
Hypertension is a major risk factor for CVD and is associated with significant morbidity and mortality. Despite a multitude of treatment options, management of hypertension remains suboptimal. Patient adherence with antihypertensive therapy has historically been less than ideal, and the fact that the majority of patients with hypertension will require two or more antihypertensive agents further complicates its management. While the increased use of multiple antihypertensive agents has led to improvement in blood pressure control, disparities in the treatment of hypertension still exist. As new clinical practice guidelines for hypertension will be issued in the near future, clinicians should take the opportunity to incorporate the latest evidence-based medicine into clinical practice and improve outcomes in patients with hypertension.
1. Roger VL, Go AS, Lloyd-Jones DM, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125(1):e2-e220.
2. Centers for Disease Control and Prevention. Vital signs: awareness and treatment of uncontrolled hypertension among adults—United States, 2003–2010. MMWR. 2012;61(35):703-709.
3. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension. 2003;42(6):1206-1252.
4. Mozaffarian D, Benjamin EJ, Go AS, et al. Heart disease and stroke statistics––2016 update: a report from the American Heart Association. Circulation. 2016;133(4):e38-e360.
5. Wong ND, Lopez VA, L'Italien G, Chen R, Kline SE, Franklin SS. Inadequate control of hypertension in U.S. adults with cardiovascular disease comorbidities in 2003–2004. Arch Intern Med. 2007;167(22):2431-2436.
6. Franco OH, Peeters A, Bonneux L, de Laet C. Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. Hypertension. 2005;46(2):280-286.
7. Morgan SG, Yan L. Persistence with hypertension treatment among community-dwelling BC seniors. Can J Clin Pharmacol. 2004;12(2):e267-e273.
8. Krousel-Wood MA, Muntner P, Islam T, Morisky DE, Webber LS. Barriers to and determinants of medication adherence in hypertension management: perspective of the Cohort Study of Medication Adherence among Older Adults (CoSMO). Med Clin North Am. 2009;93(3):753-769.
9. Gu Q, Burt VL, Dillon CF, Yoon S. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health and Nutrition Examination Survey, 2001 to 2010. Circulation. 2012;126(17):2105-2114.
10. Fields LE, Burt LV, Vutler JA, Hughes J, Roccella EJ, Sorlie P. The burden of adult hypertension in the United States 1999 to 2000: a rising tide. Hypertension. 2004;44(4):398-404.
11. Ogunniyi MO, Croft JB, Greenlund KJ, Giles WH, Mensah GA. Racial/ethnic differences in microalbuminuria among adults with prehypertension and hypertension: National Health and Nutrition Examination Survey (NHANES), 1999–2006. Am J Hypertens. 2010;23(8):859-864.
12. Kuritzky L. White coat hypertension: addressing the 10 most important questions. Curr Cardiol Rep. 2012;14(6):678-683.
13. Banerjee D, Chung S, Wong EC, Wang EJ, Stafford RS, Palaniappan LP. Underdiagnosis of hypertension using electronic health records. Am J Hypertens. 2012;25(1):97-102.
14. Cuffe RL, Howard SC, Algra A, Warlow CP, Rothwell PM. Medium-term variability of blood pressure and potential underdiagnosis of hypertension in patients with previous transient ischemic attack or minor stroke. Stroke. 2006;37(11):2776-2783.
15. Calhoun DA, Jones D, Textor S, et al. Resistant hypertension: diagnosis, evaluation, and treatment. A scientific statement from the American Heart Association Professional Education Committee of the Council for High Blood Pressure Research. Circulation. 2008;117(25):e510-e526.
16. Forman JP, Stampfer MJ, Curhan GC. Diet and lifestyle risk factors associated with incident hypertension in women. JAMA. 2009;302(4):401-411.
17. Hertz RP, Unger AN, Cornell JA, Saunders E. Racial disparities in hypertension prevalence, awareness, and management. ArchIntern Med. 2005;165(18):2098-2104.
18. Centers of Disease Control and Prevention. Hypertension-related mortality among Hispanic subpopulations—United States, 1995–2002. MMWR. 2006;55(7):177-180.
19. Lloyd-Jones DM, Evans JC, Levy D. Hypertension in adults across the age spectrum: current outcomes and control in the community. JAMA. 2005;294(4):466-472.
20. Wassertheil-Smoller S, Anderson G, Psaty BM, et al. Hypertension and its treatment in postmenopausal women: baseline data from the Women's Health Initiative. Hypertension. 2000;36(5):780-789.
21. Hawkins K, Mittapally R, Chang J, Nahum GG, Gricar J. Burden of illness of hypertension among women using menopausal hormone therapy: a U.S. perspective. Curr Med Res Opin. 2010;26(12):2823-2832.
22. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet. 2002;360(9349):1903-1913.
23. Neal B, MacMahon S, Chapman N. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomized trials. Lancet. 2000;356(9246):1955-1964.
24. Olafiranye O, Zizi F, Brimah P, et al. Management of hypertension among patients with coronary heart disease. Int J Hypertens. 2011;2011:653903.
25. Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003;139(9):761-776.
26. Levy D, Anderson KM, Savage DD, Kannel WB, Christiansen JC, Castelli WP. Echocardiographically detected left ventricular hypertrophy: prevalence and risk factors. Ann Intern Med. 1988;108(1):7-13.
27. Rheeder P, Stolk RP, Mosterd A, Pols HA, Hofman A, Grobbee DE. Insulin resistance syndrome and left ventricular mass in an elderly population (the Rotterdam study). Am J Cardiol. 1999;84(2):233-236.
29. Armitage JA, Burke SL, Prior LJ, et al. Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension. 2012;60(1):163-171.
30. Xiong XQ, Chen WW, Han Y, et al. Enhanced adipose afferent reflex contributes to sympathetic activation in diet-induced obesity hypertension. Hypertension. 2012;60(5):1280-1286.
31. Harrison DG, Guzik TJ, Lob HE, et al. Inflammation, immunity, and hypertension. Hypertension. 2011;57(2):132-140.
32. Guzik TJ, Hoch NE, Brown KA, et al. Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med. 2007;204(10);2449-2460.
33. Madhur MS, Lob HE, McCann LA, et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55(2):500-507.
34. Madhur MS. Hypertension. Available at http://emedicine.medscape.com/article/241381-overview#a3. Last accessed September 26, 2016.
35. Caillon A, Schiffrin EL. Role of inflammation and immunity in hypertension? Recent epidemiological, laboratory, and clinical evidence. Curr Hypertens Rep. 2016;18(3):21.
36. Rodríguez-IB, Pons H, Quiroz Y, Johnson RJ. The immunological basis of hypertension. Am J Hypertens. 2014;27(11):1327-1337.
37. Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents. Circulation. 2011;123(21):2434-2506.
38. Maillard P, Seshadri S, Beiser A, et al. Effects of systolic blood pressure on white-matter integrity in young adults in the Framingham Heart Study: a cross-sectional study. Lancet Neurol. 2012;11(12):1039-1047.
39. Hyman DJ, Pavlik VN, Vallbona C. Physician role in lack of awareness and control of hypertension. J Clin Hypertens (Greenwich). 2000;2(5):324-330.
40. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.
41. Burt VL, Whelton P, Roccella EJ, et al. Prevalence of hypertension in the U.S. adult population. Results from the Third National Health and examination Survey, 1988–1991. Hypertension. 1995;25(3):305-313.
42. Franklin SS, Gustin W, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. Circulation. 1997;96(1):308-315.
43. Kostis JB, Davis BR, Cutler J, et al. Prevention of heart failure by antihypertensive drug treatment in older persons with isolated systolic hypertension. JAMA. 1997;278(3):212-216.
44. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265(24):3255-3264.
45. Staessen JA, Thijs L, Fagard R, et al. Predicting cardiovascular risk using conventional vs. ambulatory blood pressure in older patients with systolic hypertension. JAMA. 1999;282(6):539-546.
46. Pickering TG, Coats A, Mallion JM, Mancia G, Verdecchia P. Blood pressure monitoring: task force V: white-coat hypertension. Blood Press Monit. 1999;4(6):333-341.
47. National Guideline Clearinghouse. University of Michigan Health System. Guideline Summary: Essential Hypertension. Available at https://www.guideline.gov/summaries/summary/48196/essential-hypertension. Last accessed September 26, 2016.
48. Muxfeldt ES, Fiszman R, de Souza F, Viegas B, Oliveira FC, Salles GF. Appropriate time interval to repeat ambulatory blood pressure monitoring in patients with white-coat resistant hypertension. Hypertension. 2012;59(2):384-389.
49. Bombelli M, Grassi G, Mancia G, Seravalle G. Diagnosis and management of patients with white-coat and masked hypertension. Nat Rev Cardiol. 2011;8(12):686-693.
50. Celis H, Fagard RH. White-coat hypertension: a clinical review. Eur J Intern Med. 2004;15(6):348-357.
51. Persell SD. Prevalence of resistant hypertension in the United States, 2003–2008. Hypertension. 2011;57(6):1076-1080.
53. Dimeo F, Pagonas N, Seibert F, Arndt R, Zidek W, Westhoff TH. Aerobic exercise reduces blood pressure in resistant hypertension. Hypertension. 2012;60(3):653-658.
54. Václavík J, Sedláck R, Plachý, et al. Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial. Hypertension. 2011;57(6):1069-1075.
55. Polimeni A, Curcio A, Indolfi C. Renal sympathetic denervation for treating resistant hypertension. Circ J. 2013;77(4):857-863.
56. Calhoun DA, White WB, Krum H, et al. Effects of a novel aldosterone synthase inhibitor for treatment of primary hypertension: results of a randomized, double-blind, placebo- and active-controlled phase 2 trial. Circulation. 2011;124(18):1945-1955.
57. Karns AD, Bral JM, Hartman D, Peppard T, Schumacher C. Study of aldosterone synthase inhibition as an add-on therapy in resistant hypertension. J Clin Hypertension. 2013;15(3):186-192.
58. Park CG, Lee JY. The significance of the J-curve in hypertension and coronary artery diseases. Korean Circ J. 2011;41(7):349-353.
60. Filippone EJ , Foy A. The J-curve revisited: a therapeutic dilemma. Cardiol Rev. 2012;20(5):253-258.
61. Cunnane RT, Bakris GL. Hypertensive goals in patients with coronary artery disease. Curr Cardiol Rep. 2012;14(6):667-672.
62. Arguedas JA, Perez MI, Wright JM. Treatment blood pressure targets for hypertension. Cochrane Database Syst Rev. 2009;(3):CD004349.
63. American Diabetes Association. Standards of medical care in diabetes––2016. Diabetes Care. 2016;39(Supp 1):S1-S112.
64. National Guideline Clearinghouse. U.S. Preventive Services Task Force. Guideline Summary: Screening for High Blood Pressure in Adults: U.S. Preventive Services Task Force Recommendation Statement. Available at https://www.guideline.gov/summaries/summary/49877/screening-for-high-blood-pressure-in-adults-us-preventive-services-task-force-recommendation-statement. Last accessed September 26, 2016.
65. National Guideline Clearinghouse. Department of Defense, Department of Veterans Affairs. Guideline summary: VA/DoD Clinical Practice Guideline for the Diagnosis and Management of Hypertension in the Primary Care Setting. Available at https://www.guideline.gov/summaries/summary/48858/vadod-clinical-practice-guideline-for-the-diagnosis-and-management-of-hypertension-in-the-primary-care-setting. Last accessed September 26, 2016.
66. Whelton PK, He J, Appel LJ, et al. Primary prevention of hypertension: clinical and public health advisory from the National High Blood Pressure Education Program. JAMA. 2002;288(15):1882-1888.
67. Eckel RH, Jakicic JM, Ard JD, et al. AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. 2014;129(25 Suppl 2):S76-S99.
68. The Trials of Hypertension Prevention Collaborative Research Group. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high normal blood pressure. Arch Intern Med. 1997;157(6):657-667.
69. He J, Whelton PK, Appel LJ, Charleston J, Klag MJ. Long-term effects of weight loss and dietary sodium reduction on incidence of hypertension. Hypertension. 2000;35(2):544-549.
70. Kelley GA, Kelley KS. Progressive resistance exercise and resting blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2000;35(3):838-843.
71. Whelton SP, Chin A, Xin X, He J. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials.Ann Intern Med. 2002;136(7):493-503.
72. Hagberg JM, Park JJ, Brown MD. The role of exercise training in the treatment of hypertension: an update. Sports Med. 2000;30(3):193-206.
73. Cornelissen VA, Smart NA. Exercise training for blood pressure: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2(1):e004473.
74. Pescatello LS, Franklin BA, Fagard R, et al. Exercise and hypertension. Med Sci Sport Exer. 2004;36(3):533-553.
75. Xin X, He J, Frontini MG, Ogden LG, Motsamai OI, Whelton PK. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38(5):1112-1117.
76. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pressure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. N Engl J Med. 2001;344(1):3-10.
77. Vollmer WM, Sacks FM, Ard J, et al. Effects of diet and sodium intake on blood pressure: subgroup analysis of the DASH-sodium trial. Ann Intern Med. 2001;135(12):1019-1028.
78. Chobanian AV, Hill M. National Heart, Lung, and Blood Institute Workshop on Sodium and Blood Pressure: a critical review of current scientific evidence. Hypertension. 2000;35(4):858-863.
79. Rainforth MV, Schneider RH, Nidich SI, Gaylord-King C, Salerno JW, Anderson JW. Stress reduction programs in patients with elevated blood pressure: a systematic review and meta-analysis. Curr Hypertens Rep. 2007;9(6):520-528.
80. Minami J, Ishimitsu T, Matsuoka H. Effects of smoking cessation on blood pressure and heart rate variability in habitual smokers. Hypertension. 1999;33(1 Opt 2):586-590.
81. National Guideline Clearinghouse. Academy of Nutrition and Dietetics. Guideline summary: Hypertension Evidence-Based Nutrition Practice Guidelines. Available at https://www.guideline.gov/summaries/summary/50137/hypertension-evidencebased-nutrition-practice-guideline. Last accessed September 26, 2016.
82. National Heart, Lung, and Blood Institute. Your Guide to Lowering Your Blood Pressure with DASH. DASH Eating Plan: Lower Your Blood Pressure. Available at http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/new_dash.pdf. Last accessed September 26, 2016.
83. Blumenthal JA, Babyak MA, Hinderliter A, et al. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med. 2010;170(2):126-135.
84. Forman JP, Scheven L de Jong PE, Bakker SJ, Curhan GC, Gansevoort RT. Association between sodium intake and change in uric acid, urine albumin excretion, and the risk of developing hypertension. Circulation. 2012;125(25):3108-3116.
85. Appel LJ, Champagne CM, Harsha DW, et al. Effects of comprehensive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289(16):2083-2093.
86. Rozanski A, Blumenthal JA, Davidson KW, Saab PG, Kubzansky L. The epidemiology, pathophysiology, and management of psychosocial risk factors in cardiac practice: the emerging field of behavioral cardiology. J Am Coll Cardiol. 2005;45(5):637-651.
87. Okonta NR. Does yoga therapy reduce blood pressure in patients with hypertension? An integrative review. Holist Nurs Pract. 2012;26(3):137-141.
88. Subramanian H, Soudarssanane MB, Jayalakshmy R, et al. Non-pharmacological interventions in hypertension: a community-based cross-over randomized controlled trial. Indian J Community Med. 2011;36(3):191-196.
89. Kim HM, Cho SY, Park SU, et al. Can acupuncture affect the circadian rhythm of blood pressure? A randomized, double-blind, controlled trial. J Altern Complement Med. 2012;18(10):918-923.
90. Chen NY, Zhou Y, Dong Q, Zhou CX. Observation on therapeutic effect of acupuncture in the treatment of German hypertension patients. Zhen Ci Yan Liu. 2010;35(6):462-466.
91. Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults in the United States. Available at https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/. Last accessed September 26, 2016.
92. Bailey AM, Macaulay T. Pharmacologic approaches to smoking cessation. Orthopedics. 2012;35(6):505-511.
93. Ge Z, Hao Y, Cao J, et al. Does cigarette smoking exacerbate the effect of blood pressure on the risk of cardiovascular and all-cause mortality among hypertensive patients? J Hypertens. 2012;30(12):2307-2013.
94. Rodriguez D, Weighell W, Edel A, et al. Potent anti-hypertensive actions of dietary flaxseed in patients with peripheral arterial disease in the Flaxpad Trial. Circulation. 2012;126:A12080.
95. Rasmussen CB, Glisson JK, Minor DS. Dietary supplements and hypertension: potential benefits and precautions. J Clin Hypertens(Greenwich). 2012;14(7):467-471.
96. Campbell F, Dickinson HO, Critchley JA, Ford GA, Bradburn M. A systematic review of fish-oil supplements for the prevention and treatment of hypertension. Eur J Prev Cardiol. 2013;20(1):107-120.
97. Brook RD, Appel LJ, Rubenfire M, et al. Beyond medications and diet: alternative approaches to lowering blood pressure: a scientific statement from the American Heart Association. Hypertension. 2013;61(6):1360-1383.
98. Gradman AH, Basile JN, Carter BL, Bakris GL. Combination therapy in hypertension. J Am Soc Hypertens (Greenwich). 2011;13(3):146-154.
100. Baguet JP. Out-of-office blood pressure: from measurement to control. Int Blood Press Control. 2012;5:27-34.
101. Novartis. Tekturna Prescribing Information [Package Insert]. Available at http://www.pharma.us.novartis.com/product/pi/pdf/tekturna.pdf. Last accessed September 26, 2016.
102. Takedi Pharmaceuticals. Edarbi Prescribing Information [Package Insert]. Available at http://www.edarbi.com. Last accessed September 26, 2016.
103. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension. J Hypertens. 2014;32(1): 3-15.
104. LexiComp Online. Available at http://online.lexi.com. Last accessed September 26, 2016.
105. Siscovick DS, Raghunathan TE, Psaty BM, et al. Diuretic therapy for hypertension and the risk of primary cardiac arrest. N Engl J Med. 1994;330(26):1852-1857.
106. Sood N, Reinhart KM, Baker WL. Combination therapy for the management of hypertension: a review of the evidence. Am J Health-Syst Pharm. 2010;67(11):885-894.
107. Wald DS, Law M, Morris JK, Bestwick JP, Wald NJ. Combination therapy versus monotherapy in reducing blood pressure: meta-analysis on 11,000 participants from 42 trials. Am J Med. 2009;122(3):290-300.
108. Sever PS, Messerli FH. Hypertension management 2011: optimal combination therapy. Eur Heart J. 2011;32(20):2499-2506.
109. Neutel JM. Prescribing patterns in hypertension: the emerging role of fixed-dose combinations for attaining blood pressure goals in hypertensive patients. Curr Med Res Opin. 2008;24(8):2389-2401.
110. Bakris GL, Sowers JR; American Society of Hypertension Writing Group. ASH position paper: treatment of hypertension in patients with diabetes—an update. J Clin Hypertens. 2008;10(9):707-713.
111. Bakris GL, Sica D, White WB, et al. Antihypertensive efficacy of hydrochlorothiazide versus chlorthalidone combined with azilsartan medoxomil. Am J Med. 2012;125(12)1229:e1-1229.e10.
112. Germino FW. Which diuretic is the preferred agent for treating essential hypertension: hydrochlorothiazide or chlorthalidone?Curr Cardiol Rep. 2012;14(6):673-677.
113. Philipp T, Smith TR, Galzer R, et al. Two multicenter, 8-week, randomized, double-blind, placebo-controlled, parallel-group studies evaluating the efficacy and tolerability of amlodipine and valsartan in combination and as monotherapy in adult patients with mild to moderate essential hypertension. Clin Ther. 2007;29(4):563-580.
114. Chrysant SG, Melino M, Karki S, Lee J, Heyrman R. The combination of olmesartan medoxomil and amlodipine besylate in controlling high blood pressure: COACH, a randomized, double-blind, controlled, 8-week factorial efficacy and safety study.Clin Ther. 2008;30(4):587-604.
115. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med. 2008;359(23):2417-2428.
116. Yusuf S, Teo KK, Pogue J, et al. Telmisartan, ramipril or both in patients at high risk for vascular events. N Engl J Med. 2008;358(15):1547-1559.
117. Parving HH, Brenner BM, McMurray JJ, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med. 2012;367(23):2204-2213.
118. Julius S, Kjeldsen SE, Brunner H, et al. VALUE trial: long-term blood pressure trends in 13,449 patients with hypertension and high cardiovascular risk. Am J Hypertens. 2003;16(7):544-548.
119. Carlberg B, Samuelsson O, Lindholm LH. Atenolol in hypertension: is it a wise choice? Lancet. 2004;364(9446):1684-1689.
120. Lindholm LH, Carlberg B, Samuelsson O. Should beta-blockers remain first choice in the treatment of primary hypertension? A meta-analysis. Lancet. 2005;366(9496):1545-1553.
121. Bradley HA, Wiysonge CS, Volmnik JA, Mayosi BM, Opie LH. How strong is the evidence for use of beta-blockers as first-line therapy for hypertension? Systematic review and meta-analysis. J Hypertens. 2006;24(11):2131-2141.
122. Kidney Disease Outcomes Quality Initiative. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004;43(5 Suppl 1):S1-S290.
123. Kidney Disease: Improving Global Outcomes. Guideline Summary: KDIGO Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease. Available at https://www.guideline.gov/summaries/summary/39430/kdigo-clinical-practice-guideline-for-the-management-of-blood-pressure-in-chronic-kidney-disease. Last accessed September 26, 2016.
124. Aronow WS, Fleg JL, Pepine CJ, et al. ACCF/AHA 2011 expert consensus Document on hypertension in the elderly: a report of the American College of Cardiology Foundation Task Force on Clinical Expert Consensus Documents Developed in Collaboration With the American Academy of Neurology, American Geriatrics Society, American Society for Preventive Cardiology, American Society of Hypertension, American Society of Nephrology, Association of Black Cardiologists, and European Society of Hypertension. J Am Coll Cardiol. 2011;57(20):2037-2114.
125. Hoyer J. Non-pharmacological and pharmacological treatment of arterial hypertension: current situation. Herz. 2012;37(7):728-734.
126. Chobanian AV. Impact of nonadherence to antihypertensive therapy. Circulation. 2009;120(16):1558-1560.
127. Chapman RH, Benner JS, Petrilla AA, et al. Predictors of adherence with antihypertensive and lipid-lowering therapy. Arch Intern Med. 2005;165(10):1147-1152.
128. Van Wijk BL, Klungel OH, Heerdink ER, de Boer A. Rate and determinants of 10-year persistence with antihypertensive drugs.J Hypertens. 2005;23(11):2101-2107.
129. Hill MN, Miller NH, DeGeest S, et al. ASH position paper: adherence and persistence with taking medication to control high blood pressure. J Clin Hypertens (Greenwich). 2010;12(10):757-764.
130. Chobanian AV. The hypertension paradox—more uncontrolled disease despite improved therapy. N Engl J Med. 2009;361(9):878-887.
131. De Geest S, Sabate E. Adherence to long-term therapies: evidence for action. Eur J Cardiovasc Nurs. 2003;2(4):323.
132. Vawter L, Tong X, Gemilyan M, Yoon PW. Barriers to antihypertensive medication among adults—United States, 2005. J Clin Hypertens (Greenwich). 2008;10(12):922-929.
133. Burnier M. Medication adherence and persistence as the cornerstone of effective antihypertensive therapy. Am J Hypertens. 2006;19(11):1190-1196.
134. Erdine S. Compliance with the treatment of hypertension: the potential of combination therapy. J Clin Hypertens (Greenwich). 2010;12(1):40-46.
135. Schroeder K, Fahey T, Ebrahim S. How can we improve adherence to blood pressure-lowering medication in ambulatory care?Arch Intern Med. 2004;164(7):722-732.
136. Bangalore S, Kamalakkannan G, Parkar S, Messerli FH. Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med. 2007;120(8):713-719.
138. Okonofua EC, Simpson KN, Jesri A, Rehman SU, Durkalski VL, Egan BM. Therapeutic inertia is an impediment to achieving the Healthy People 2010 blood pressure control goals. Hypertension. 2006;47(3):345-351.
139. Rose AJ, Berlowitz DR, Orner MB, Kressin NR. Understanding uncontrolled hypertension: is it the patient or the provider? J Clin Hypertens. 2007;9(12):937-943.
140. Zolnierek KB, DiMatteo MR. Physician communication and patient adherence to treatment: a meta-analysis. Med Care. 2009;47(8):826-834.
141. Martin KD, Roter DL, Beach MC, Carson KA, Cooper LA. Physician communication behaviors and trust among black and white patients with hypertension. Med Care. 2013;51(2):151-157.
142. Eamranond PP, Patel KV, Legedza AT, Marcantonio ER, Leveille SG. The association of language with prevalence of undiagnosed hypertension among older Mexican Americans. Ethn Dis. 2007;17(4):699-706.
143. Karliner L, Jacobs EA, Chen AH, Mutha S. Do professional interpreters improve clinical care for patients with limited English proficiency? A systematic review of the literature. Health Serv Res. 2007;42(2):727-754.
144. Navar-Boggan AM, Boggan JC, Stafford JA, Muhbaier LH, McCarver C, Peterson ED. Hypertension control among patients followed by cardiologists. Circ Cardiovasc Qual Outcomes. 2012;5(3):352-357.
145. Odedosu T, Schoenthaler A, Vieira DL, Agyemang C, Ogedegbe G. Overcoming barriers to hypertension control in African Americans. Cleve Clin J Med. 2012;79(1):46-56.
146. Douglas JG, Bakris GL, Epstein M, et al. Management of high blood pressure in African Americans: consensus statement of the Hypertension in African Americans Working Group of the International Society on Hypertension in Blacks. Arch Intern Med. 2003;163(5):525-541.
147. Howard G, Lackland DT, Kleindorfer DO, et al. Racial differences in the impact of elevated systolic blood pressure on stroke risk. JAMA Intern Med. 2013;173(1):46-51.
148. Flack JM, Sica DA, Bakris G, et al. Management of high blood pressure in Blacks: an update of the International Society on Hypertension in Blacks consensus statement. Hypertension. 2010;56(5):780-800.
149. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336(16):1117-1124.
150. Ferdinand KC. A compendium of antihypertensive therapy. J Clin Hypertens (Greenwich). 2011;13(9):636-638.
151. Butt DA, Mamdani M, Austin PC, Tu K, Gomes T, Glazier RH. The risk of hip fracture after initiating antihypertensive drugs in the elderly. Arch Intern Med. 2012;172(22):1739-1744.
152. Reynolds K, Shimbo D, Bowling CB, et al. OS 16-06 risk factors for serious fall injuries following initiation of antihypertensive medication. J Hypertens. 2016;34(Suppl 1):e219-e220.
1. Diagnosis and Management of Hypertension Working Group. VA/DoD Clinical Practice Guideline for the Diagnosis and Management of Hypertension in the Primary Care Setting. Washington, DC: Department of Veterans Affairs, Department of Defense; 2014. Summary retrieved from National Guideline Clearinghouse at https://www.guideline.gov/summaries/summary/48858. Last accessed September 28, 2016.
Mention of commercial products does not indicate endorsement.