Approximately 122 million Americans (47%) have hypertension (defined as systolic blood pressure [SBP] ≥130 mm Hg and/or diastolic blood pressure [DBP] ≥80 mm Hg), while another 28.2% have prehypertension [1]. 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 [1,10]. However, these data do 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 [11]. Underdiagnosis is particularly common among survivors of transient ischemic attack (TIA) or minor stroke, due largely to medium-term variability in blood pressure measurements [12].

Approximately 122 million Americans (47%) have hypertension (defined as systolic blood pressure [SBP] ≥130 mm Hg and/or diastolic blood pressure [DBP] ≥80 mm Hg), while another 28.2% have prehypertension [1]. 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 [1,10]. However, these data do 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 [11]. Underdiagnosis is particularly common among survivors of transient ischemic attack (TIA) or minor stroke, due largely to medium-term variability in blood pressure measurements [12].

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 Black Americans, for example, have the poorest rates of blood pressure control, with 70% higher odds of poorly controlled blood pressure than that of White Americans [1].

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, 78% have blood pressures greater than 140/90 mm Hg [1]. 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 [18]. 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 [19]. 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 [20].

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 [21]. More specifically, antihypertensive therapy can reduce the incidence of myocardial infarction (20% to 25%), stroke (35% to 40%), and heart failure (>50%) [22]. 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 [3]. Furthermore, essential hypertension contributes to nearly 18 million hospitalizations, nearly 34 million office visits, 914,000 emergency department visits, and 3.7 million outpatient visits annually [1].

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 [36].

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 [40]. 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 [41]. Importantly, studies show that controlling isolated systolic hypertension reduces total and cardiovascular mortality, stroke, and heart failure [42,43,44]. As the population ages, greater emphasis should be placed on treating systolic hypertension, because unattended SBP will lead to increased cardiovascular and renal disease [39].

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 [82]. 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 [67]. 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 [83].

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 [22,39,99,100]. While lifestyle modifications and nonpharmacologic treatment options are beneficial in reducing blood pressure, approximately 70% of patients with hypertension will require at least two antihypertensive agents to reduce blood pressure to within acceptable ranges [3,39,46,99] 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 [101]. After antihypertensive therapy is initiated, patients should be monitored and treatment adjustments made monthly until the desired blood pressure goal is reached [39]. 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 [3,39,46]

For uncomplicated hypertension in the general non-Black 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 [39]. 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 [39]. 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 [3]. At particularly high doses, thiazide-induced hypokalemia may contribute to ventricular ectopy [106]. Other medication classes (e.g., statins) may be considered if the patient does not respond to initial treatment or combination therapy with these agents [39].

Data show that the combination of the CCB amlodipine plus hydrochlorothiazide is well-tolerated and has similar mortality reduction to valsartan [109,121]. 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 [99,109]. Although β-blockers reduce cardiovascular end points, meta-analyses indicate less effectiveness in treating hypertension than diuretics, ACE inhibitors, ARBs, and CCBs [122,123,124]. However, there is some evidence that β-blockers may be a reasonable first-line choice in younger-to-middle-aged (younger than 60 years of age) individuals [125,126]. 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 [99].

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 [136]. 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 [137]. Other barriers that contribute to nonadherence include cost of care and medication, lack of insurance, transportation issues, and comorbidities [134].

Increasingly complex antihypertensive treatment regimens and unfavorable tolerability profiles are associated with poorer adherence [132,138,139]. Simply switching from twice-daily to once-daily antihypertensive agents can improve adherence up to 20% [140]. Moreover, use of single-pill, fixed-dose combination therapy can improve adherence by 26% [141]. Commercially available fixed-dose product formulations may incorporate two or three separate antihypertensive agents.

As noted, the prevalence and control of hypertension differ across racial subgroups. In Black individuals, 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 White individuals [1,150]. Blacks have a greater prevalence of other cardiovascular risk factors, especially obesity [151]. In fact, hypertension is the single most common contributor to the mortality gap between Black and White Americans [3]. For every 10-mm Hg increase in SBP, the risk of stroke in Black Americans is triple that of White Americans (24% vs. 8%, respectively) [152]. Non-Hispanic Black and Mexican Americans have poorer blood pressure control rates than non-Hispanic White Americans [1]. Differences in outcomes may be attributable to differences in socioeconomic conditions, access to healthcare services, attitudes regarding health care, and cultural beliefs [3].

Before initiation of antihypertensive therapy, weight and sodium reduction are particularly effective in minorities [153]. For example, the low-sodium DASH eating plan is associated with significant blood pressure reductions in Black patients [154]. However, monotherapy with ACE inhibitors, ARBs, or β-blockers is less effective in lowering blood pressure in Black patients than White patients [3,104]. Moreover, Black and Asian patients have a three- to fourfold higher risk of angioedema and have more cough attributed to ACE inhibitors than White patients [3,155]. The use of combination antihypertensive drug therapy, including a thiazide diuretic, will lower blood pressure and reduce the cardiovascular and renal burden in minorities [39,104,153]. Chlorthalidone is particularly beneficial in low-renin patients as well as the elderly and patients with diabetes [155]. Importantly, identifying and addressing treatment barriers is critical to improving outcomes in minority populations [150].

In the elderly, thiazide diuretics are recommended for initiating therapy and are generally well tolerated [36]. Thiazide diuretics reduce cardiovascular events in the elderly but may also exacerbate hyperuricemia, glucose abnormalities, and dyslipidemia, which are frequently seen in the elderly [36]. 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 [158]. β-blockers are best suited for patients with migraine and/or cardiovascular comorbidities such as heart failure and coronary artery disease [36]. 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 [105]. In the elderly, α-adrenergic antagonists are not recommended as first-line therapy due to a possible increase in cardiovascular events [36,39,158]. Similar to β-blockers, CCBs are considered safe and effective in elderly patients with cardiovascular comorbidities (e.g., angina, supraventricular arrhythmias) [36,105]. However, dosing should start at the lower end of dosing range and be titrated to response [36]. Elderly patients have shown a decreased clearance of amlodipine [105]. Immediate-release nifedipine should be avoided due to the potential for postural hypotension, which may precipitate dizziness and falls [36]. Generic versions of verapamil that are bioequivalent in young adults may not be bioequivalent in the elderly [105]. The CCBs verapamil and diltiazem may precipitate heart block in those with underlying defects in cardiac conduction [36]. ACE inhibitors and ARBs are well tolerated, are renal protective, and reduce cardiovascular morbidity and mortality [36]. 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.