Thus, if diuretic and ACE inhibitor or ARB treatment do not achieve BP target, other agents, such as CCB and/or mineralocorticoid receptor antagonist, may be added. 5. An overview of RCTs showed that larger reductions in SBP tended to be associated with greater reduction in risk of recurrent stroke. However, a separate overview of RCTs in patients who experienced a stroke noted that achieving an SBP level <130 mm Hg was not associ- ated with a lower stroke risk, and several observational Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e57 studies did not show benefit with achieved SBP levels 6. Patients with a lacunar stroke treated to an SBP target of <130 mm Hg versus 130 to 140 mm Hg may be less likely to experience a future ICH. 7. No published RCTs have specifically addressed this question, but a post hoc analysis of an RCT suggests that the effectiveness of antihypertensive treatment for sec- ondary stroke prevention diminishes as initial baseline 9.5. Peripheral Artery Disease Recommendation for Treatment of Hypertension in Patients With PAD References that support the recommendation are summarized in Online Data Supplement 45. COR LOE Recommendation I B-NR 1. Adults with hypertension and PAD should be treated similarly to patients with hypertension without PAD.S9.5-1 S9.5-4 Synopsis Patients with PAD are at increased risk of CVD and stroke. Hypertension is a major risk factor for PAD, so these patients are commonly enrolled in trials of antihypertensive drug therapy. However, patients with PAD typically comprise a small fraction of participants, so in the few trials that report results in patients with PAD, subgroup analyses are generally underpowered. Recommendation-Specific Supportive Text 1. There is no major difference in the relative risk re- duction in CVD from BP-lowering therapy between patients with hypertension and PAD and patients There is also no evidence that any one class of antihypertensive medication or strategy In the INVEST (International Verapamil-Trandolapril) study, the beta blocker at- enolol (with or without hydrochlorothiazide) was compared with the CCB verapamil (with or with- out perindopril). The study showed no significant difference in CVD outcomes between the 2 drug regimens in patients with and without PAD.S9.5-3 No trials have reported the effects of a higher ver- sus a lower BP goal in patients with PAD. In the 1 trial (ALLHAT) that reported the effects of different classes of BP medications on PAD as an outcome, there was no significant difference by medication Figure 9. Management of hypertension in patients with a previous history of stroke (secondary stroke prevention). Colors correspond to Class of Recommendation in Table 1. DBP indicates diastolic blood pressure; SBP, systolic blood pressure; and TIA, transient ischemic attack. 9.6. Diabetes Mellitus Recommendations for Treatment of Hypertension in Patients With DM References that support recommendations are summarized in Online Data Supplements 46 and 47 and Systematic Review Report. COR LOE Recommendations I SBP: B-RSR 1. In adults with DM and hypertension, antihypertensive drug treatment should be initiated at a BP of 130/80 mm Hg or higher with a treatment goal of less than 130/80 DBP: C-EO I ASR 2. In adults with DM and hypertension, all first- line classes of antihypertensive agents (ie, diuretics, ACE inhibitors, ARBs, and CCBs) are useful and effective.S9.6-1,S9.6-9,S9.6-10 IIb B-NR 3. In adults with DM and hypertension, ACE inhibitors or ARBs may be considered in the presence of albuminuria.S9.6-11,S9.6-12 SR indicates systematic review. Synopsis ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults for the complete system- atic evidence review for additional data and analyses.S9.6-13 The prevalence of hypertension among adults with DM is approxi- mately 80%, and hypertension is at least twice as common in persons with type 2 DM than in age-matched individuals with- The coexistence of hypertension and DM markedly increases the risk of developing CVD damage, result- ing in a higher incidence of CHD, HF, PAD, stroke, and CVD and may increase risk of microvascular disease, such as nephropathy or retinopathy.S9.6-16,S9.6-18 There is limited quality evidence to determine a precise BP target in adults with DM. No RCTs have explicitly 1) docu- mented whether treatment to an SBP goal <140 mm Hg versus a higher goal improves clinical outcomes in adults with hyper- tension and DM or 2) directly evaluated clinical outcomes associated with SBP <130 mm Hg.S9.6-2 However, 2 high-qual- ity systematic reviews of RCTs support an SBP target of <140 There is little or no available RCT evidence supporting a specific DBP threshold for initiation of pharmacological ther- apy. Several RCTs, including the HOT (Hypertension Optimal Treatment) trial, UKPDS (United Kingdom Prospective Diabetes Study), and ABCD (Appropriate Blood Pressure Control in Diabetes) trial,S9.6-19 S9.6-22 are often cited to support a lower DBP target (eg, 85 or 80 mm Hg) for adults with hypertension and DM. However, these trials were conducted when the diagnostic criteria for DM were more conservative than they are currently (2 fasting glucose levels >140 mg/dL as opposed to 126 mm/dL today). Recommendation-Specific Supportive Text 1. We recommend ASCVD risk assessment in all adults with hypertension, including adults with DM. As a matter of convenience, however, it can be assumed that the vast majority of adults with DM have a 10- year ASCVD risk 10%, placing them in the high risk category that requires initiation of antihypertensive drug therapy at BP 130/80 mm Hg (see Section 8.1.2, Figure 4 and Table 23 for BP thresholds for initiating an- tihypertensive drug treatment). The ACCORD trial,S9.6-5 which compared CVD outcomes in adults with DM and hypertension who were randomized to an SBP target of <140 mm Hg (standard therapy) or <120 mm Hg (intensive therapy), did not document a significant re- duction in the primary outcome (CVD composite) with the lower BP goal, but the trial was underpowered to detect a statistically significant difference between the 2 treatment arms. The ACCORD trial demonstrated a small reduction in absolute risk (1.1%) for stroke, but there were few such events. More adverse events (2% increase in absolute risk) were identified in the lower BP group, especially self-reported hypotension and a reduction in estimated GFR, but these did not result in an excess of stroke or ESRD. The ACCORD trial was a factorial study; secondary analysis demonstrat- ed a significant outcome benefit in the intensive BP/ standard glycemic group,S9.6-3 but benefit in the inten- sive BP/intensive glycemic control group was no bet- ter than in the intensive BP/standard glycemic control group, which suggests a floor benefit beyond which the combined intensive interventions were ineffective.S9.6-5 An ACCORD secondary analysis suggested that an SBP <120 mm Hg is superior to standard BP control in A meta-analysis of 73 913 patients with DM reported that an SBP <130 mm Hg reduced stroke by 39%. However, there was no significant risk reduction for MI.S9.6-23 Two meta-analyses addressing target BP in adults with DM restricted the analysis to RCTs that randomized patients to different BP levels.S9.6-4,S9.6-7 Target BP of 133/76 mm Hg provided significant benefit compared with that of 140/81 mm Hg for major cardiovascular events, MI, stroke, albu- minuria, and retinopathy progression.S9.6-4 Several meta- analyses of RCTs included all trials with a difference in but 2 restricted their analyses to trials in which participants were randomized to different BP target SPRINT demonstrated cardiovascular benefit from inten- sive treatment of BP to a goal of <120 mm Hg as compared with <140 mm Hg but did not include patients with DM. However, the results of ACCORD and SPRINT were generally In addition, a SPRINT substudy demonstrated that patients with prediabetes derived a benefit similar to that of patients with normoglycemia.S9.6-8 Previous trials have shown similar quantitative benefits from lowering BP in persons with and without DM.S9.6-9 2. BP control is more difficult to achieve in patients with DM than in those without DM, necessitating use of combination therapy in the majority of patients.S9.6-27 All major antihypertensive drug classes (ie, ACE inhibitors, ARBs, CCBs, and diuretics) are useful in the treatment of hypertension in DM.S9.6-1,S9.6-9 However, in ALLHAT, doxazosin was clearly inferior to chlorthalidone, which Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e59 also reduced some events more than amlodipine or 3. ACE inhibitors and ARBs have the best efficacy among the drug classes on urinary albumin excretionS9.6-12 (see Section 9.3). Therefore, an ACE inhibitor or ARB may be considered as part of the combination. A meta- analysis of RCTs of primary prevention of albumin- uria in patients with DM demonstrated a significant reduction in progression of moderately to severely in- creased albuminuria with the use of ACE inhibitors or 9.7. Metabolic Syndrome Metabolic syndrome is a state of metabolic dysregulation characterized by visceral fat accumulation, insulin resis- tance, hyperinsulinemia, and hyperlipidemia, as well as pre- disposition to type 2 DM, hypertension, and atherosclerotic According to data from the NHANES III and the prevalence of metabolic syndrome in the United States was 34.2% in 2006 and has likely increased substantially since that time. The metabolic syndrome is linked to several other disorders, including non- alcoholic steatohepatitis, polycystic ovary syndrome, certain cancers, CKD, Alzheimer s disease, Cushing s syndrome, lipodystrophy, and hyperalimentation.S9.7-5,S9.7-6 Lifestyle modification, with an emphasis on improv- ing insulin sensitivity by means of dietary modification, weight reduction, and exercise, is the foundation of treat- ment of the metabolic syndrome. The optimal antihyper- tensive drug therapy for patients with hypertension in the setting of the metabolic syndrome has not been clearly Although caution exists with regard to the use of thiazide diuretics in this population because of their abil- ity to increase insulin resistance, dyslipidemia, and hyper- uricemia and to accelerate conversion to overt DM, no data are currently available demonstrating deterioration in car- diovascular or renal outcomes in patients treated with these Indeed, as shown in follow-up of ALLHAT, chlorthalidone use was associated with only a small increase in fasting glucose levels (1.5 4.0 mg/dL), and this increase did not translate into increased CVD risk at a later date.S9.7-7 In addition, in post hoc analysis of the nearly two thirds of participants in ALLHAT that met criteria for the meta- bolic syndrome, chlorthalidone was unsurpassed in reducing CVD and renal outcomes compared with lisinopril, amlo- dipine, or doxazosin.S9.7-9,S9.7-11 Similarly, high-dose ARB therapy reduces arterial stiffness in patients with hyperten- sion with the metabolic syndrome, but no outcomes data are available from patients in which this form of treatment was Use of traditional beta blockers may lead to dys- lipidemia or deterioration of glucose tolerance, and ability to lose weight.S9.7-2 In several large clinical trials, the risk of developing DM as a result of traditional beta-blocker therapy However, the newer vasodilating beta blockers (eg, labetalol, carvedilol, nebivolol) have shown neutral or favorable effects on metabolic profiles compared with the traditional beta blockers.S9.7-13 Trials using vasodila- tor beta blockers have not been performed to demonstrate effects on CVD outcomes. 9.8. Atrial Fibrillation Recommendation for Treatment of Hypertension in Patients With AF References that support the recommendation are summarized in Online Data Supplement 48. COR LOE Recommendation IIa B-R 1. Treatment of hypertension with an ARB can be useful for prevention of recurrence Synopsis AF and hypertension are common and often coexistent con- ditions, both of which increase in frequency with age. AF occurs in 3% to 4% of the population >65 years of age.S9.8-3 Hypertension is present in >80% of patients with AF and is by far the most common comorbid condition, regardless of AF is associated with systemic thromboembolism, as recognized in the CHADS2 and CHA2DS2-VASc scoring systems for stroke risk.S9.8-5 It is also associated with gradual worsening of ventricular function, the subsequent development of HF, and increased mortality. Hypertension has long been recognized as a risk factor for AF because it is associated with LVH, decreased diastolic function with impaired LV filling, rising left atrial pressures with left atrial hypertrophy and enlargement, increased atrial fibrosis, and slowing of intra-atrial and interatrial electrical conduction velocities. Such a distortion of atrial anatomy and physiology increases the incidence of AF.S9.8-6 Left atrial pres- sure also increases with ischemic or valvular heart disease and myopathies that are often associated with systemic hyperten- sion, potentially leading to AF. Although management of AF will continue to revolve around restoration of sinus rhythm when appropriate, rate con- trol when it is not, and anticoagulation, control of hypertension is a key component of therapy.S9.8-1,S9.8-2 Treatment of hypertension may prevent new-onsetAF, espe- cially in patients with LVH or LV dysfunction.S9.8-1 Five RCTs have compared the value of antihypertensive agents for reduc- tion of new-onset AF.S9.8-7 S9.8-11 One study suggested superiority of RAS blockade over a CCB,S9.8-8 and another reported supe- riority of RAS blockade over a beta blocker that is no longer recommended for treatment of hypertension.S9.8-9 In the largest trial, there was no difference in incident AF among adults with hypertension assigned to first-step therapy with a diuretic, ACE inhibitor, or CCB.S9.8-10 In ALLHAT, the incidence of AF was 23% higher during first-step antihypertensive therapy with the alpha-receptor blocker doxazosin than with chlorthalidone. Furthermore, the occurrence of AF or atrial flutter during the study, either new onset or recurrent, was associated with an increase in mortality of nearly 2.5-fold.S9.8-10 Recommendation-Specific Supportive Text 1. Although RAS blockade in theory is the treatment of choice for hypertension in patients with prior AF, relative to other classes of agents, all of the trials that have shown clinical superiority of ARBs over other agents were comparisons with CCBs or beta blockers that are no longer recommended as first-line agents for treatment of hypertension.S9.8-2 There are no available trials comparing ACE inhibitors with other drugs or any RAS-blocking agents with diuretics. 9.9. Valvular Heart Disease Recommendations for Treatment of Hypertension in Patients With Valvular Heart Disease References that support recommendations are summarized in Online Data Supplements 49 and 50. COR LOE Recommendations I B-NR 1. In adults with asymptomatic aortic stenosis, hypertension should be treated with pharmacotherapy, starting at a low dose and gradually titrating upward as IIa C-LD 2. In patients with chronic aortic insufficiency, treatment of systolic hypertension with agents that do not slow the heart rate (ie, avoid beta blockers) is reasonable.S9.9-5,S9.9-6 Recommendation-Specific Supportive Text 1. Hypertension is a risk factor for the development of aortic stenosis (stage A [eg, aortic sclerosis or bicuspid aortic valve]) and asymptomatic aortic stenosis (stage B [progressive asymptomatic aortic stenosis]). The combi- nation of hypertension and aortic stenosis, 2 resistors in series, increases the rate of complications. In patients with asymptomatic mild-to-moderate aortic stenosis, hypertension has been associated with more abnormal LV structure and increased cardiovascular morbidity and There is no evidence that antihypertensive medications will produce an inordinate degree of hypo- tension in patients with aortic stenosis. Nitroprusside infusion in hypertensive patients with severe aortic ste- nosis lowers pulmonary and systemic resistance, with improvements in stroke volume and LV end-diastolic Thus, careful use of antihypertensive agents to achieve BP control in patients with hypertension and aortic stenosis is beneficial. Although there are no spe- cific trials comparing various classes of antihypertensive agents, RAS blockade may be advantageous because of the potentially beneficial effects on LV fibrosis,S9.9-3 con- trol of hypertension, reduction of dyspnea, and improved Diuretics should be used sparingly in patients with small LV chamber dimensions. Beta blockers may be appropriate for patients with aortic stenosis who have reduced ejection fraction, prior MI, arrhythmias, or angina pectoris. In patients with mod- erate or severe aortic stenosis, consultation or co-man- agement with a cardiologist is preferred for hypertension management. 2. Vasodilator therapy can reduce the LV volume and mass and improve LV performance in patients with aortic but improvement of long-term clinical outcomes, such as time to valve replacement, have been Beta blockers may result in increased diastolic filling period because of bradycardia, poten- tially causing increased aortic insufficiency. Marked reduction in DBP may lower coronary perfusion pres- sure in patients with chronic severe aortic regurgitation (stage B [progressive asymptomatic aortic regurgita- tion] and stage C [asymptomatic severe AR]). However, there are no outcomes data to support these theoretical concerns. 9.10. Aortic Disease Recommendation for Management of Hypertension in Patients With Aortic Disease COR LOE Recommendation I C-EO 1. Beta blockers are recommended as the preferred antihypertensive agents in patients with hypertension and thoracic aortic Synopsis Thoracic aortic aneurysms are generally asymptomatic until a person presents with a sudden catastrophic event, such as an aortic dissection or rupture, which is rapidly fatal in the majority of patients.S9.10-3,S9.10-4 The rationale for antihyperten- sive therapy is based largely on animal and observational stud- ies associating hypertension with aortic dissection.S9.10-5,S9.10-6 RCTs specifically addressing hypertension and aortic dis- ease are not available, and trials in patients with primary hypertension do not provide insight on either the optimal BP target or choice of antihypertensive drug therapy in patients with thoracic aortic aneurysm, aortic dissection, or aortic A study in 20 humans with hypertension suggested that hypertension is associated with significant changes in the mechanical properties of the aortic wall, with more strain-induced stiffening in hypertension than in normo- tension, which may reflect destruction of elastin and predispo- sition to aortic dissection in the presence of hypertension.S9.10-9 In a retrospective observational study, high BP variability was an independent risk factor for the prognosis of aortic Recommendations for treatment of acute aor- tic dissection are provided in Section 11.2. Recommendation-Specific Supportive Text 1. In patients with chronic aortic dissection, observational studies suggest lower risk for operative repair with beta- In a series of patients with type A and type B aortic dissections, beta blockers were asso- ciated with improved survival in both groups, whereas ACE inhibitors did not improve survival.S9.10-2 10. Special Patient Groups Special attention is needed for specific patient subgroups. 10.1. Race and Ethnicity In the United States, at any decade of life, blacks have a higher prevalence of hypertension than that of Hispanic Americans, whites, Native Americans, and other subgroups defined by race and ethnicity (see Section 3.3). Hypertension control rates are lower for blacks, Hispanic Americans, and Asian Americans than for whites.S10.1-1 Among men with hyperten- sion, non-Hispanic white (53.8%) adults had a higher preva- lence of controlled high blood pressure than did non-Hispanic black (43.8%), non-Hispanic Asian (39.9%), and Hispanic (43.5%) adults. For women with hypertension, the percentage Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e61 of non-Hispanic white (59.1%) adults with controlled high blood pressure was higher than among non-Hispanic black In Hispanic Americans, the lower control rates result primar- ily from lack of awareness and treatment,S10.1-2,S10.1-3 whereas in blacks, awareness and treatment are at least as high as in whites, but hypertension is more severe and some agents are less effective at BP control.S10.1-4 Morbidity and mortality attributed to hypertension are also more common in blacks and Hispanic Americans than in whites. Blacks have a 1.3- times greater risk of nonfatal stroke, 1.8-times greater risk of fatal strokes, 1.5-times greater risk of HF, and 4.2-times greater risk of ESRD.S10.1-4 Hispanic Americans have lower rates of hypertension awareness and treatment than those of whites and blacks, as well as a high prevalence of comorbid CVD risk factors (eg, obesity, DM). In 2014, age-adjusted hypertension-attributable mortality rates per 1000 persons for non-Hispanic white, non-Hispanic black, and Hispanic- American men and women were 19.3 and 15.8, 50.1 and 35.6, However, Hispanics in the United States are a heterogeneous subgroup, and rates of both hypertension and its consequences vary according to whether their ancestry is from the Caribbean, Mexico, Central or South America, or Europe.S10.1-6 S10.1-8 Hispanics from Mexico and Central America have lower CVD rates than US whites, whereas those of Caribbean origin have higher rates. Thus, pooling of data for Hispanics may not accurately reflect risk in a given patient. Finally, the excess risk of CKD out- comes in at least some blacks with hypertension may be due to the presence of high-risk APOL1 (apolipoprotein L1) genetic The rate of renal decline associated with this genotype appears to be largely unresponsive to either BP lowering or RAS inhibition.S10.1-9 S10.1-12 10.1.1. Racial and Ethnic Differences in Treatment Recommendations for Race and Ethnicity References that support recommendations are summarized in Online Data Supplement 51. COR LOE Recommendations I B-R 1. In black adults with hypertension but without HF or CKD, including those with DM, initial antihypertensive treatment should include a thiazide-type diuretic or I C-LD 2. Two or more antihypertensive medications are recommended to achieve a BP target of less than 130/80 mm Hg in most adults with hypertension, especially in black adults with Synopsis Lifestyle modification (ie, weight reduction, dietary modifica- tion, and increased physical activity) is particularly important in blacks and Hispanic Americans for prevention and first-line or adjunctive therapy of hypertension (see Sections 12.1.2 and 12.1.3). However, the adoption of lifestyle recommendations is often challenging in ethnic minority patients because of poor social support, limited access to exercise opportunities and healthy foods, and financial considerations. The greater prev- alence of lower socioeconomic status may impede access to basic living necessities,S10.1.1-8 including medical care and medi- cations. Consideration must also be given to learning styles and preference, personal beliefs, values, and culture.S10.1.1-9,S10.1.1-10 The principles of antihypertensive drug selection discussed in Sections 8.1.4 through 8.1.6 apply to ethnic minorities with a few caveats. In blacks, thiazide-type diuretics and CCBs are more effective in lowering BP when given as monother- apy or as initial agents in multidrug regimens.S10.1.1-11 S10.1.1-13 In addition, thiazide-type agents are superior to drugs that inhibit the RAS (ie, ACE inhibitors, ARBs, renin inhibitors, and beta blockers) for prevention of selected clinical out- comes in blacks.S10.1.1-2,S10.1.1-14 S10.1.1-16 For optimum endpoint protection, the thiazide chlorthalidone should be administered at a dose of 12.5 to 25 mg/day (or 25 50 mg/d for hydro- chlorothiazide) because lower doses are either unproven or less effective in clinical outcome trials.S10.1.1-2,S10.1.1-16 The CCB amlodipine is as effective as chlorthalidone and more effective than the ACE inhibitor lisinopril in reducing BP, CVD, and stroke events but less effective in preventing HF. Blacks have a greater risk of angioedema with ACE inhibitors,S10.1.1-2,S10.1.1-3 and Asian Americans have a higher incidence of ACE inhibi- ACE inhibitors and ARBs are recommended more generally as components of multidrug antihypertensive regimens in blacks with CKD (see Section 9.3), with the addition of beta blockers in those with HF (see Section 9.2). Beta blockers are recommended for treatment of patients with CHD who have had a MI. Most patients with hypertension, especially blacks, require 2 antihypertensive medications to achieve adequate BP control. A single-tablet combination that includes either a diuretic or a CCB may be particularly effective in achieving BP control in blacks. Racial and ethnic differences should not be the basis for excluding any class of antihypertensive agent in combination therapy. Recommendation-Specific Supportive Text 1. In blacks, thiazide diuretics or CCBs are more effective in lowering BP than are RAS inhibitors or beta block- ers and more effective in reducing CVD events than are RAS inhibitors or alpha blockers. RAS inhibitors are recommended in black patients with hypertension, DM, and nephropathy, but they offer no advantage over diuret- ics or CCBs in hypertensive patients with DM without nephropathy or HF. 2. Four drug classes (thiazide diuretic, CCB, ACE inhibi- tor, or ARB) lower BP and reduce cardiovascular or re- Thus, except for the combi- nation of ACE inhibitors and ARBs, regimens containing a combination of these classes are reasonable to achieve the BP target.S10.1.1-16,S10.1.1-21 Furthermore, the combina- tion of an ACE inhibitor or ARB with a CCB or thia- zide diuretic produces similar BP lowering in blacks as in other racial or ethnic groups. For blacks who do not achieve control with 3 drugs, see resistant hypertension (see Section 11.1). 10.2. Sex-Related Issues The prevalence of hypertension is lower in women than in men until about the fifth decade but is higher later in life.S10.2-1 Other than special recommendations for management of hyperten- sion during pregnancy, there is no evidence that the BP thresh- old for initiating drug treatment, the treatment target, the choice of initial antihypertensive medication, or the combina- tion of medications for lowering BP differs for women versus A potential limitation of RCTs, including SPRINT, is that they are not specifically powered to determine the value of inten- sive SBP reduction in subgroups, including women in the case of SPRINT. However, in prespecified analyses, there was no evidence of an interaction between sex and treatment effect. Furthermore, no significant differences in CVD outcomes were observed between men and women in a large meta- analysis that included 31 RCTs with about 100000 men and Some have called for a SPRINT-like trial with sufficient power to assess the effects of intensive SBP reduction in women.S10.2.1-2 In meta-analyses, there was no convincing evidence that different antihyperten- sive drug classes exerted sex-related differences in BP low- ering or provided distinct CVD protection.S10.2.1-1 Calcium antagonists offered slightly greater benefits for stroke preven- tion than did ACE inhibitors for women than for men, whereas calcium antagonists reduced all-cause deaths compared with placebo in men but not in women. However, these sex-related differences might have been due to chance because of the large number of statistical comparisons that were performed. The Heart Attack Trial and Hypertension Care Computing Project reported that beta blockers were associated with reduced mor- tality in men but not in women, but this finding was likely due to the low event rates in women.S10.2.1-3 Similarly, in the open-label Second Australian National BP study, a significant reduction in CVD events was demonstrated in men but not in women with ACE inhibitors versus diuretics.S10.2.1-4 Adverse effects of antihypertensive therapy were noted twice as often in women as in men in the TOMHS study.S10.2.1-5 A higher incidence of ACE inhibitor induced cough and of edema with calcium antagonists was observed in women than Women were more likely to experience hypoka- lemia and hyponatremia and less likely to experience gout with Hypertension in pregnancy has special require- ments (see Section 10.2.2). Recommendations for Treatment of Hypertension in Pregnancy References that support recommendations are summarized in Online Data Supplement 53. COR LOE Recommendations I C-LD 1. Women with hypertension who become pregnant, or are planning to become pregnant, should be transitioned to methyldopa, nifedipine, and/or labetalolS10.2.2-1 III: Harm C-LD 2. Women with hypertension who become pregnant should not be treated with ACE inhibitors, ARBs, or direct renin Synopsis BP usually declines during the first trimester of pregnancy and then slowly rises. Hypertension management during pregnancy includes 4 general areas: 1) the newly pregnant mother with existing hypertension; 2) incident hyperten- sion; 3) preeclampsia (a dangerous form of hypertension with proteinuria that has the potential to result in serious adverse consequences for the mother [stroke, HF] and fetus [small for gestational age, premature birth]); and 4) severe hypertension, often in the setting of preeclampsia, requir- ing urgent treatment to prevent HF, stroke, and adverse fetal outcomes. Hypertension during pregnancy and preeclamp- sia are recognized as risk factors for future hypertension BP management during pregnancy is complicated by the fact that many commonly used antihy- pertensive agents, including ACE inhibitors and ARBs, are contraindicated during pregnancy because of potential harm to the fetus.S10.2.2-2,S10.2.2-3 The goal of antihypertensive treat- ment during pregnancy includes prevention of severe hyper- tension and the possibility of prolonging gestation to allow the fetus more time to mature before delivery. There are 3 Cochrane database reviews of treatment for mild-to-moderate hypertension during pregnancy.S10.2.2-10 S10.2.2-12 With regard to the treatment of mild-to-moderate hyperten- sion (SBP of 140 169 or DBP of 90 109 mm Hg), anti- hypertensive treatment reduces the risk of progression to severe hypertension by 50% compared with placebo but has not been shown to prevent preeclampsia, preterm birth, small for gestational age, or infant mortality. Beta blockers and CCBs appear superior to alpha-methyldopa in prevent- An earlier review of 2 small trials did not show improved outcomes with more comprehen- sive treatment of BP to a target of <130/80 mm Hg.S10.2.2-11 Consistent with the results of the Cochrane reviews, a large multinational RCT of treatment in pregnant women with mild-to-moderate hypertension also reported that treat- ment prevented progression to severe hypertension, but other maternal and infant outcomes were unaffected by the intensity of treatment.S10.2.2-13 An earlier review confined to assessing the effect of beta blockers found them generally safe and effective but of no benefit for newborn outcomes, either in placebo-controlled studies or when compared with other antihypertensive agents. There was a suggestion that beta-blocker therapy might be associated with small for gestational age and neonatal bradycardia.S10.2.2-12 The larg- est experience for beta blockers is with labetalol; the larg- est experience for CCBs is with nifedipine. Methyldopa and hydralazine may also be used. A review of treatment for pregnancy-associated severe hypertension found insufficient evidence to recommend specific agents; rather, clinician experience was recommended in this setting.S10.2.2-14 Preeclampsia is a potentially dangerous condition for the pregnant woman and fetus, occurring in 3.8% of pregnancies, and preeclampsia and eclampsia account for 9% of maternal deaths in the United States.S10.2.2-15 Preeclampsia is associ- ated with an increased risk of preterm delivery, intrauterine growth restriction, placental abruption, and perinatal mortality and is twice as likely to occur in the first pregnancy. The US Preventive Services Task Force has recommended screening Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e63 all pregnant women for preeclampsia by measuring BP at every prenatal visit.S10.2.2-16 It is beyond the scope of the present guideline to address the management of hypertension during pregnancy in detail. Several international guidelines provide guidance on manage- ment of hypertension during pregnancy.S10.2.2-2,S10.2.2-3,S10.2.2-17 The American College of Obstetricians and Gynecologists has issued a task force report that includes recommenda- tions for prevention (aspirin in selected cases) and treatment (magnesium for severe hypertension) of hypertension in A report detailing treatment of hypertensive emergencies during pregnancy and postpartum has also been Recommendation-Specific Supportive Text 1. ACE inhibitors andARBs are not approved for use during pregnancy; they are fetotoxic. Among the agents recom- mended, no specific agent is first choice because there are no data supporting one over another. Therapeutic classes are not recommended because potential toxicity differs among agents within classes. 2. ACE inhibitors and ARBs are fetotoxic in the second and third trimesters of pregnancy. Adverse effects in the first trimester of pregnancy may be secondary to hypertension or the medication.S10.2.2-4,S10.2.2-5 Adverse events in the later trimesters have been suggested by observational data and For ARBs, case reports with effects similar to ACE inhibitors have been published.S10.2.2-19 10.3. Age-Related Issues 10.3.1. Older Persons Recommendations for Treatment of Hypertension in Older Persons References that support recommendations are summarized in Online Data Supplement 54. COR LOE Recommendations I A 1. Treatment of hypertension with a SBP treatment goal of less than 130 mm Hg is recommended for noninstitutionalized ambulatory community-dwelling adults ( 65 years of age) with an average SBP of 130 mm Hg or higher.S10.3.1-1 IIa C-EO 2. For older adults ( 65 years of age) with hypertension and a high burden of comorbidity and limited life expectancy, clinical judgment, patient preference, and a team-based approach to assess risk/ benefit is reasonable for decisions regarding intensity of BP lowering and choice of antihypertensive drugs. Synopsis Because of its extremely high prevalence in older adults, hyper- tension is not only a leading cause of preventable morbidity and mortality but, perhaps more importantly, is under-recognized as a major contributor to premature disability and institution Both SBP and DBP increase linearly up to the fifth or sixth decade of life, after which DBP gradually decreases while SBP continues to rise.S10.3.1-6 Thus, isolated systolic hypertension is the predominant form of hyperten- sion in older persons.S10.3.1-7,S10.3.1-8 RCTs have clearly dem- onstrated that BP lowering in isolated systolic hypertension (defined as SBP 160 mm Hg with variable DBP 90, 95, or 110 mm Hg) is effective in reducing the risk of fatal and nonfatal stroke (primary outcome), cardiovascular events, and Cross-sectional and longitudinal epidemiologic studies in older adults have raised questions about the benefits of more intensive antihypertensive treatment and the relation- ship between BP lowering and risk of falls.S10.3.1-13 Treatment of elevated BP in older persons is challenging because of a high degree of heterogeneity in comorbidity, as well as poly-pharmacy, frailty, cognitive impairment, and variable life expectancy. However, over the past 3 decades, RCTs of antihypertensive therapy have included large numbers of older persons, and in every instance, including when the SBP treatment goal was <120 mm Hg, more intensive treat- ment has safely reduced the risk of CVD for persons over Both HYVET (Hypertension in the Very Elderly Trial) and SPRINT included those who were frail but still living independently in the community,S10.3.1-1,S10.3.1-14 and both were stopped early for benefit (HYVET after 1.8 years and SPRINT after 3.26 years). In fact, BP-lowering therapy is one of the few inter- ventions shown to reduce mortality risk in frail older indi- viduals. RCTs in noninstitutionalized community-dwelling older persons have also demonstrated that improved BP con- trol does not exacerbate orthostatic hypotension and has no adverse impact on risk of injurious falls.S10.3.1-1,S10.3.1-15,S10.3.1-16 It should be noted, however, that SPRINT excluded those with low (<110 mm Hg) standing BP on study entry. Older persons need to be carefully monitored for orthostatic hypotension during treatment. Intensive BP control increases the risk of acute kidney injury, but this is no different from the risk seen in younger adults.S10.3.1-1 In summary, despite the complexity of management in caring for older persons with hypertension, RCTs have demonstrated that in many community-dwelling older adults, even adults >80 years of age, BP-lowering goals during antihypertensive treatment need not differ from those selected for persons <65 years of age.S10.3.1-17 Importantly, no randomized trial of BP lowering in persons >65 years of age has ever shown harm or less benefit for older versus younger adults. However, clinicians should implement careful titra- tion of BP lowering and monitoring in persons with high comorbidity burden; large RCTs have excluded older persons at any age who live in nursing homes, as well as those with prevalent dementia and advanced HF. Recommendation-Specific Supportive Text 1. We recommend ASCVD risk assessment in all adults with hypertension, including older persons. As a mat- ter of convenience, however, it can be assumed that the vast majority of older adults have a 10-year ASCVD risk 10%, placing them in the high risk category that requires initiation of antihypertensive drug therapy at BP 130/80 mm Hg (see Section 8.1.2, Figure 4 and Table 23 for BP thresholds for initiating antihypertensive drug treatment). Large RCTs using medications to re- duce hypertension-related CVD risk with a mean fol- low-up of 2 years have now included a large number of adults 65 years of age. These trials have enrolled a broad range of ages 65 years, including persons in their 90s and even 100s, as well as those with mild-to-mod- erate frailty but who were ambulatory and able to travel to a treatment clinic. In these patients, RCTs have shown that BP lowering decreased CVD morbidity and mortali- ty but did not increase the risk of orthostatic hypotension Analysis of the NHANES (2011 2014) data set indicates that 88% of US adults (98% men and 80% women) 65 years old have a 10- year predicted ASCVD risk 10% or have a history of CVD (CHD, stroke, or HF). For persons 75 years of age, 100% have an ASCVD risk score 10% or a history of CVD. Therefore, the BP target of 130/80 mm Hg would be appropriate (see Section 8.1.2). Initiation of antihypertensive therapy with 2 agents should be un- dertaken cautiously in older persons, and they need to be monitored carefully for orthostatic hypotension and history of falls. In SPRINT, the benefit was for an SBP goal of <120 mm Hg. Older persons may pres- ent with neurogenic orthostatic hypotension associated with supine hypertension. This is particularly common in Parkinson s disease and other neurodegenerative dis- orders. For management of this problem, the reader is referred to the recommendations of a 2017 consensus 2. Patients with prevalent and frequent falls, advanced cog- nitive impairment, and multiple comorbidities may be at risk of adverse outcomes with intensive BP lowering, especially when they require multiple BP-lowering medi- cations. Older persons in this category typically reside in nursing homes and assisting living facilities, are unable to live independently in the community, and have not been represented in RCTs. 10.3.2. Children and Adolescents Pediatric guidelines are available from other The 2011 report updates the 2004 report for publications through 2008 (antihypertensive medi- cation trials, normative data on pediatric BP) but is otherwise unchanged. In the 2011 guideline,S10.3.2-3 BP was stratified into normal, prehypertension (90th percentile to 95th percentile), stage 1 hypertension (95th percentile to >99th percentile), and stage 2 hypertension (above stage 1) by using age-, sex-, and height-based tables beginning at 1 year of age, which were based on the distribution of BP in >60000 healthy children in various population-based studies.S10.3.2-1 These definitions were designed to be analogous to definitions in the extant JNC 7 report; for older adolescents ( 14 years), the JNC 7 thresh- olds generally apply.S10.3.2-4 Treatment recommendations are based on hypertension severity, published short-term clinical trials of antihypertensive treatment, age, coexisting CVD risk factors, and risk stratification by presence of LVH on echo- cardiogram. The treatment goal is to achieve BP <90th per- centile. New tables for ambulatory BP distribution in children have been developed. A classification of BP that is based on these ambulatory BP results has been proposed.S10.3.2-5,S10.3.2-6 A new pediatric BP guideline was published in late 2017.S10.3.2-7 11. Other Considerations 11.1. Resistant Hypertension The diagnosis of resistant hypertension is made when a patient takes 3 antihypertensive medications with complementary mechanisms of action (a diuretic should be 1 component) but does not achieve control or when BP control is achieved but On the basis of the previous cutoff of 140/90 mm Hg, the prevalence of resistant hyperten- sion is approximately 13% in the adult population.S11.1-2,S11.1-3 Multiple single-cohort studies have indicated that common risk factors for resistant hypertension include older age, obesity, CKD, black race, and DM. Estimates suggest the prevalence would be about 4% higher with the newly recommended con- trol target of <130/80 mm Hg (subject to validation in future study). The prognosis of resistant hypertension (by the previ- compared with the prognosis of those who more readily achieve control, has not been fully ascertained; however, risk of MI, stroke, ESRD, and death in adults with resistant hypertension and CHD may be 2- to 6-fold higher than in hypertensive adults without resistant hypertension.S11.1-4 S11.1-6 The evaluation of resistant hypertension involves consideration of many patient characteristics, pseudoresistance (BP technique, white coat hypertension, and medication compliance), and screen- ing for secondary causes of hypertension (Figure 10; Section 5.4; Table 13). The term refractory hypertension has been used to refer to an extreme phenotype of antihypertensive treatment fail- ure, defined as failure to control BP despite use of at least 5 anti- hypertensive agents of different classes, including a long-acting thiazide-type diuretic, such as chlorthalidone, and a mineralocor- ticoid receptor antagonist, such as spironolactone.S11.1-7 The prevalence of refractory hypertension is low; patients with refractory hypertension experience high rates of CVD compli- cations, including LVH, HF, and stroke. Treatment of resistant hypertension involves improv- ing medication adherence, improving detection and correc- tion of secondary hypertension, and addressing other patient Pharmacological therapy with com- binations of medications with complementary mechanisms of action provides an empirical approach that enhances BP control while mitigating untoward effects of potent vasodilators (eg, fluid retention and reflex tachycardia). CCBs, inhibitors of RAS, and chlorthalidone comprise a common 3-drug regimen.S11.1-11 Considerable evidence indicates that the addition of spironolac- tone to multidrug regimens provides substantial BP reductionS11.1-12 when compared with placebo. Substantial data also demonstrate the advantage of spironolactone as compared with other active In particular, the recent PATHWAY-2 (Optimum Treatment for Drug-Resistant Hypertension) RCT demonstrated the superiority of spironolactone over alpha and beta There is also clinical trial evidence that the addition of hydralazine or minoxidil is effective in achieving BP control in patients resistant to usual combination therapy.S11.1-8,S11.1-12 S11.1-16 The dosing of multidrug regimens, occasionally including night- time dosing, may be best optimized by hypertension specialists. Several studies have investigated devices that interrupt sympathetic nerve activity (carotid baroreceptor pacing and catheter ablation of renal sympathetic nerves); how- ever, these studies have not provided sufficient evidence to Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e65 recommend the use of these device in managing resistant In particular, 2 RCTS of renal sympa- thetic nerve ablation have been negative.S11.1-8,S11.1-9 11.2. Hypertensive Crises Emergencies and Urgencies Recommendations for Hypertensive Crises and Emergencies References that support recommendations are summarized in Online Data Supplement 55. COR LOE Recommendations I B-NR 1. In adults with a hypertensive emergency, admission to an intensive care unit is recommended for continuous monitoring of BP and target organ damage and for parenteral administration of an appropriate agent (Tables 19 and 20).S11.2-1,S11.2-2 I C-EO 2. For adults with a compelling condition (ie, aortic dissection, severe preeclampsia or eclampsia, or pheochromocytoma crisis), SBP should be reduced to less than 140 mm Hg during the first hour and to less than 120 mm Hg in aortic dissection. I C-EO 3. For adults without a compelling condition, SBP should be reduced by no more than 25% within the first hour; then, if stable, to 160/100 mm Hg within the next 2 to 6 hours; and then cautiously to normal during the following 24 to 48 hours. Figure 10. Resistant hypertension: diagnosis, evaluation, and treatment. *See additional details in Section 6, Nonpharmacological Intervention. See Section 5.4.1 and Table 14 for complete list of drugs that elevate BP. See Section 5.4 and Table 13 for secondary hypertension. BP indicates blood pressure; CKD, chronic kidney disease; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; NSAIDs, nonsteroidal anti-inflammatory drugs; and SBP, systolic blood pressure. Adapted with permission from Calhoun et alS11.1-1 (American Heart Association, Inc.). Recommendations for Hypertensive Crises and Emergencies (Continued) COR LOE Recommendations Synopsis Hypertensive emergencies are defined as severe elevations in BP (>180/120 mm Hg) associated with evidence of new or worsening target organ damage.S11.2-3 S11.2-6 The 1-year death rate associated with hypertensive emergencies is >79%, and the median survival is 10.4 months if the emergency is left The actual BP level may not be as important as the rate of BP rise; patients with chronic hypertension can often tolerate higher BP levels than previously normotensive individuals. Hypertensive emergencies demand immediate reduction of BP (not necessarily to normal) to prevent or limit further target organ damage. Examples of target organ damage include hypertensive encephalopathy, ICH, acute ischemic stroke, acute MI, acute LV failure with pulmonary edema, unstable angina pectoris, dissecting aortic aneurysm, acute renal failure, and eclampsia. In general, use of oral therapy is discouraged for hypertensive emergencies. Hypertensive emergencies in patients with acute ICH and acute ischemic stroke are discussed in Section 9.4. In contrast, hypertensive urgencies are situations associ- ated with severe BP elevation in otherwise stable patients without acute or impending change in target organ damage or dysfunction. Many of these patients have withdrawn from or are noncompliant with antihypertensive therapy and do not have clinical or laboratory evidence of acute target organ damage. These patients should not be considered as having a hypertensive emergency and instead are treated by reinstitu- tion or intensification of antihypertensive drug therapy and treatment of anxiety as applicable. There is no indication for referral to the emergency department, immediate reduction in BP in the emergency department, or hospitalization for such patients. Figure 11 is an algorithm on diagnosis and management of a hypertensive crisis. Tables 19 and 20 summarize intra- venous antihypertensive drugs for treatment of hypertensive emergencies. Recommendation-Specific Supportive Text 1. There is no RCT evidence that antihypertensive drugs reduce morbidity or mortality in patients with hyper- However, from clinical expe- rience, it is highly likely that antihypertensive therapy is an overall benefit in a hypertensive emergency.S11.2-9 There is also no high-quality RCT evidence to inform clinicians as to which first-line antihypertensive drug class provides more benefit than harm in hypertensive This lack of evidence is related to the small size of trials, the lack of long-term follow-up, and failure to report outcomes. However, 2 trials have dem- onstrated that nicardipine may be better than labetalol in achieving the short-term BP target.S11.2-1,S11.2-10 S11.2-12 Several antihypertensive agents in various pharmacologi- cal classes are available for the treatment of hypertensive Figure 11. Diagnosis and management of a hypertensive crisis. Colors correspond to Class of Recommendation in Table 1. *Use drug(s) specified in Table 19. If other comorbidities are present, select a drug specified in Table 20. BP indicates blood pressure; DBP, diastolic blood pressure; ICU, intensive care unit; and SBP, systolic blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e67 emergencies (Table 19). Because autoregulation of tis- sue perfusion is disturbed in hypertensive emergencies, continuous infusion of short-acting titratable antihyper- tensive agents is often preferable to prevent further target The selection of an antihyper- tensive agent should be based on the drug s pharmacol- ogy, pathophysiological factors underlying the patient s hypertension (as well as they can be rapidly determined), degree of progression of target organ damage, the de- sirable rate of BP decline, and the presence of comor- bidities (Table 20). The therapeutic goal is to minimize target organ damage safely by rapid recognition of the problem and early initiation of appropriate antihyperten- sive treatment. 2. Compelling conditions requiring rapid lowering of SBP, usually to <140 mm Hg, in the first hour of treatment Table 19. Intravenous Antihypertensive Drugs for Treatment of Hypertensive Emergencies Class Drug(s) Usual Dose Range Comments CCB dihydropyridines Nicardipine Initial 5 mg/h, increasing every 5 min by 2.5 mg/h to maximum 15 mg/h. Contraindicated in advanced aortic stenosis; no dose adjustment needed for elderly. Clevidipine Initial 1 2 mg/h, doubling every 90 s until BP approaches target, then increasing by less than double every 5 10 min; maximum dose 32 mg/h; maximum duration 72 h. Contraindicated in patients with soybean, soy product, egg, and egg product allergy and in patients with defective lipid metabolism (eg, pathological hyperlipidemia, lipoid nephrosis or acute pancreatitis). Use low-end dose range for elderly patients. Vasodilators Nitric- oxide dependent Sodium nitroprusside Initial 0.3 0.5 mcg/kg/min; increase in increments of 0.5 mcg/kg/min to achieve BP target; maximum dose 10 mcg/kg/min; duration of treatment as short as possible. For infusion rates 4 10 mcg/kg/min or duration >30 min, thiosulfate can be coadministered to prevent cyanide toxicity. Intra-arterial BP monitoring recommended to prevent overshoot. Lower dosing adjustment required for elderly. Tachyphylaxis common with extended use. Cyanide toxicity with prolonged use can result in irreversible neurological changes and cardiac arrest. Nitroglycerin Initial 5 mcg/min; increase in increments of 5 mcg/min every 3 5 min to a maximum of 20 mcg/min. Use only in patients with acute coronary syndrome and/or acute pulmonary edema. Do not use in volume-depleted patients. Vasodilators direct Hydralazine Initial 10 mg via slow IV infusion (maximum initial dose 20 mg); repeat every 4 6 h as needed. BP begins to decrease within 10 30 min, and the fall lasts 2 4 h. Unpredictability of response and prolonged duration of action do not make hydralazine a desirable first-line agent for acute treatment in most patients. Adrenergic receptor selective antagonist Esmolol Loading dose 500 1000 mcg/kg/min over 1 min followed by a 50-mcg/kg/min infusion. For additional dosing, the bolus dose is repeated and the infusion increased in 50-mcg/kg/min increments as needed to a maximum of 200 mcg/kg/min. Contraindicated in patients with concurrent beta-blocker therapy, bradycardia, or decompensated HF. Monitor for bradycardia. May worsen HF. Higher doses may block beta2 receptors and impact lung function in reactive airway disease. Adrenergic blockers combined and nonselective beta receptor antagonist Labetalol Initial 0.3 1.0-mg/kg dose (maximum 20 mg) slow IV injection every 10 min or 0.4 1.0-mg/kg/h IV infusion up to 3 mg/kg/h. Adjust rate up to total cumulative dose of 300 mg. This dose can be repeated every 4 6 h. Contraindicated in reactive airways disease or chronic obstructive pulmonary disease. Especially useful in hyperadrenergic syndromes. May worsen HF and should not be given in patients with second- or third-degree heart block or bradycardia. Adrenergic blockers nonselective alpha receptor antagonist Phentolamine IV bolus dose 5 mg. Additional bolus doses every 10 min as needed to lower BP to target. Used in hypertensive emergencies induced by catecholamine excess (pheochromocytoma, interactions between monamine oxidase inhibitors and other drugs or food, cocaine toxicity, amphetamine overdose, or clonidine withdrawal). -receptor selective agonist Fenoldopam Initial 0.1 0.3 mcg/kg/min; may be increased in increments of 0.05 0.1 mcg/kg/min every 15 min until target BP is reached. Maximum infusion rate 1.6 mcg/ kg/min. Contraindicated in patients at risk of increased intraocular pressure (glaucoma) or intracranial pressure and those with sulfite allergy. ACE inhibitor Enalaprilat Initial 1.25 mg over a 5-min period. Doses can be increased up to 5 mg every 6 h as needed to achieve BP target. Contraindicated in pregnancy and should not be used in acute MI or bilateral renal artery stenosis. Mainly useful in hypertensive emergencies associated with high plasma renin activity. Dose not easily adjusted. Relatively slow onset of action (15 min) and unpredictability of BP response. BP indicates blood pressure; CCB, calcium channel blocker; HF, heart failure; IV, intravenous; and MI, myocardial infarction. include aortic dissection, severe preeclampsia or eclamp- sia, and pheochromocytoma with hypertensive crisis. 3. There is no RCT evidence comparing different strategies to reduce BP, except in patients with ICH.S11.2-9,S11.2-13 Neither is there RCT evidence to suggest how rapidly or how much BP should be lowered in a hypertensive emergency.S11.2-9 However, clinical experience indicates that excessive re- duction of BP may cause or contribute to renal, cerebral, or coronary ischemia and should be avoided. Thus, com- prehensive dosing of intravenous or even oral antihyper- tensive agents to rapidly lower BP is not without risk. Oral loading doses of antihypertensive agents can engender cumulative effects, causing hypotension after discharge from the emergency department or clinic. 11.3. Cognitive Decline and Dementia Recommendation for Prevention of Cognitive Decline and Dementia References that support the recommendation are summarized in Online Data Supplement 56. COR LOE Recommendation IIa B-R 1. In adults with hypertension, BP lowering is reasonable to prevent cognitive decline and Synopsis Dementia is a leading cause of mortality and placement into nursing homes and assisted living facilities, affecting >46 mil- lion individuals globally and 5 million persons in the United States, a number that is expected to double by 2050.S11.3-7 A 5-year delay in onset of dementia would likely decrease the number of cases of incident dementia by about 50% after Vascular disease and its risk factors are implicated in a large proportion of patients with demen- tia, including those with Alzheimer s dementia.S11.3-9 S11.3-11 Hypertension is also the primary risk factor for small-vessel Most observational studies have suggested that better control of SBP may reduce Alzheimer s disease and other dementias, and the evidence is stronger for BP lowering in middle age than in older adults.S11.3-9,S11.3-16 Clinical trials with dementia assessment have evaluated all-cause dementia but not Alzheimer s disease specifically. However, all of these trials have methodological issues, such as low power, insuf- ficient follow-up length, and inadequately designed dementia assessment batteries. Recommendation-Specific Supportive Text 1. Five clinical trials of BP lowering have included as- sessment for incident dementia. Of these 5 trials, 4 Table 20. Intravenous Antihypertensive Drugs for Treatment of Hypertensive Emergencies in Patients With Selected Comorbidities Comorbidity Preferred Drug(s)* Comments Acute aortic dissection Esmolol, labetalol Requires rapid lowering of SBP to 120 mm Hg.Beta blockade should precede vasodilator (eg, nicardipine or nitroprusside) administration, if needed for BP control or to prevent reflex tachycardia or inotropic effect; SBP 120 mm Hg should be achieved within 20 min. Acute pulmonary edema Clevidipine, nitroglycerin, nitroprusside Beta blockers contraindicated. Acute coronary syndromes Esmolol, labetalol, nicardipine, nitroglycerin Nitrates given in the presence of PDE-5 inhibitors may induce profound hypotension. Contraindications to beta blockers include moderate-to-severe LV failure with pulmonary edema, bradycardia (<60 bpm), hypotension (SBP <100 mm Hg), poor peripheral perfusion, second- or third-degree heart block, and reactive airways disease. Acute renal failure Clevidipine, fenoldopam, nicardipine N/A Eclampsia or preeclampsia Hydralazine, labetalol, nicardipine Requires rapid BP lowering.ACE inhibitors, ARBs, renin inhibitors, and nitroprusside contraindicated. Perioperative hypertension (BP 160/90 mm Hg or SBP elevation 20% of the preoperative value that persists for Clevidipine, esmolol, nicardipine, nitroglycerin Intraoperative hypertension is most frequently seen during anesthesia induction and airway manipulation. Acute sympathetic discharge or catecholamine excess states (eg, pheochromocytoma, post-carotid endarterectomy status) Clevidipine, nicardipine, phentolamine Requires rapid lowering of BP. Acute ICH Section 9.4.1 Section 9.4.1 Acute ischemic stroke Section 9.4.2 Section 9.4.2 *Agents are listed in alphabetical order, not in order of preference. Agent of choice for acute coronary syndromes. ACE indicates angiotensin-converting enzyme; ARB, angiotensin receptor blocker; BP, blood pressure; bpm, beats per minute; ICH, intracerebral hemorrhage; LV, left ventricular; PDE-5, phosphodiesterase type-5; and SBP, systolic blood pressure. Whelton et al 2017 High Blood Pressure Clinical Practice Guideline e69 demonstrated a reduction in dementia incidence, with 2 of these 4 demonstrating statistical significance (746-751). SYST-EUR (Systolic Hypertension in and PROGRESS (Perindopril Protection Against Recurrent Stroke)S11.3-18 both showed statis- tically significant reductions in incident dementia. SYST-EUR achieved an SBP of 152 mm Hg in the treatment arm (8.3 mm Hg lower than placebo arm) during its blinded phase and an SBP of 149 mm Hg (7.0 mm Hg lower than comparison group) during its open-label follow-up phase.S11.3-2,S11.3-3 PROGRESS achieved an SBP of 138 mm Hg in the treatment group (9 mm Hg lower than the placebo group) and demon- strated dementia prevention in patients with a recent The trial showing no benefit in the direc- tion of dementia reduction achieved an SBP reduction of only 3.2 mm Hg, whereas the other 4 trials achieved SBP reductions of 7 to 15 mm Hg (746-751). When the rate of cognitive decline (not dementia) has been a trial outcome, 7 clinical trials of BP-lowering ther- apy have been completed, and 2 of these have shown No randomized trial of BP lowering has demonstrated an adverse impact on dementia incidence or cognitive function. However, the anticipated results from SPRINT, the first ad- equately powered RCT to test whether intensive BP control reduces dementia, may help clarify this issue in the near future. 11.4. Sexual Dysfunction and Hypertension An association among sexual dysfunction, atherosclerosis, and hypertension can be constructed from several epidemi- ology surveys, clinical trials, and cohort studies. Although these data converge to suggest that endothelial dysfunc- tion is a common denominator, the story is incomplete. Sexual dysfunction represents several domains in desire or interest, as well as physical limitations such as erectile dysfunction. In addition, beta blockers, mineralocorticoid receptor antagonists, and other antihypertensive drugs can have negative effects on libido and erectile function. There are emerging data on the association between erectile dys- function and CVD compared with other domains of sexual dysfunction. Experimental and clinical studies describe a role for angiotensin II, endothelin, and hydrogen sulfide on cavernous tissue function.S11.4-1 Many of the signaling path- ways for the increased production of oxidative stress and the subsequent deleterious effects of oxidative stress on vascular tissue have been described. Accordingly, it is rea- sonable to suggest that hypertension might lead to vascu- lar changes that cause erectile dysfunction but, conversely, erectile dysfunction may be part of the causal pathway to Although there is insufficient evidence to rec- ommend screening for CVD risk factors in all men with erectile dysfunction, it has been reported as a sole precur- sor for CVD in men.S11.4-2 S11.4-6 With the introduction of the phosphodiesterase-5 inhibi- tors, which can be coadministered with antihypertensive medications, there is now effective therapy for erectile dysfunction that has implications for systemic vascular These drugs have additive effects on lowering BP and are recommended as a primary therapy for pulmonary Although data are available to suggest that some antihypertensive medications affect erectile dysfunc- tion more than others, the use of phosphodiesterase-5 inhibi- tors make drug class distinctions for erectile dysfunction less The long-term safety and efficacy of chronic administration of phosphodiesterase-5 inhibitors for the mit- igation of CVD has yet to be determined and represents an important knowledge gap. 11.5. Patients Undergoing Surgical Procedures Recommendations for Treatment of Hypertension in Patients Undergoing Surgical Procedures References that support recommendations are summarized in Online Data Supplements 57 and 58. COR LOE Recommendations Preoperative I B-NR 1. In patients with hypertension undergoing major surgery who have been on beta blockers chronically, beta blockers should be IIa C-EO 2. In patients with hypertension undergoing planned elective major surgery, it is reasonable to continue medical therapy for hypertension until surgery. IIb B-NR 3. In patients with hypertension undergoing major surgery, discontinuation of ACE inhibitors or ARBs perioperatively may be IIb C-LD 4. In patients with planned elective major surgery and SBP of 180 mm Hg or higher or DBP of 110 mm Hg or higher, deferring surgery may be considered.S11.5-11,S11.5-12 III: Harm B-NR 5. For patients undergoing surgery, abrupt preoperative discontinuation of beta blockers or clonidine is potentially III: Harm B-NR 6. Beta blockers should not be started on the day of surgery in beta blocker na ve Intraoperative I C-EO 7. Patients with intraoperative hypertension should be managed with intravenous medications (Table 19) until such time as oral medications can be resumed. Synopsis Hypertension in the perioperative period increases the risk of CVD, cerebrovascular events, and bleeding.S11.5-15,S11.5-16 As many as 25% of patients who undergo major noncar- and 80% of patients who have cardiac surgery experience perioperative hypertension.S11.5-16,S11.5-18 In general, the level of risk is related to the severity of the hypertension. No high-quality RCTs were identified relating to the treatment of hypertension in patients undergoing major surgical procedures. One analysis evaluated data from 3 prospective, randomized, open-label, parallel-comparison studies in patients undergoing cardiac surgery and concluded that clevidipine is a safe and effective treatment for acute hypertension in patients undergoing cardiac surgery.S11.5-19 Another systematic review and meta-analysis, including 4 studies, concluded that clevidipine is more effective than other antihypertensive drugs in the management of periop- erative hypertension without adverse events.S11.5-20 Several general strategies and principles based on experience and observation are recommended for this section. In the man- agement of patients with perioperative hypertension, it is important to assess other potential contributing factors, such as volume status, pain control, oxygenation, and bladder distention, when the use of pharmacological therapy to con- trol BP is under consideration. Uncontrolled hypertension is associated with increased perioperative and postopera- tive complications. Certain medications (eg, beta blockers, clonidine) may be associated with rebound hypertension if Therefore, several general strat- egies and principles based on experience and observation are recommended for this section. These recommendations for beta blockers, ACE inhibi- tors, and ARBs are generally consistent with the 2014 ACC/AHA Guideline on Perioperative Cardiovascular Evaluation and Management of Patients Undergoing Noncardiac Surgery and are provided to assist in the man- agement of patients undergoing major noncardiac surgical Recommendation-Specific Supportive Text 1. If well tolerated, beta blockers should be continued in patients who are currently receiving them for longitu- dinal reasons, particularly when longitudinal treatment is provided according to GDMT, such as for MI.S11.5-22 Multiple observational studies support the benefits of continuing beta blockers in patients who are undergo- ing surgery and who are on these agents for longitudinal 2. In the absence of conclusive RCTs, the expert opinion of this writing committee is that control of BP to lev- els recommended by the present guideline (BP <130/80 mm Hg) or other target levels specified for a particular individual is reasonable before undertaking major elec- tive procedures in either the inpatient or outpatient set- ting. If the patient is unable to take oral medications, it is reasonable to use intravenous medications (Table 19) as necessary to control BP. Special consideration of paren- teral therapy usually occurs for patients taking clonidine or beta blockers because of the risk of stopping these medications acutely. 