Browse the corpus

Hypertension Primary Hypertension e Nonpharmacologic and drug treatment is recommended for those with BP 2130/80 mm Hg and clinical cardiovas- Pathogenesis cular disease or a 10-year cardiovascular risk =10% to a BP Ninety percent of patients with hypertension are identified as goal of <130/80 mm Hg. having primary (essential) hypertension, in which no second- ¢ Nonpharmacologic and drug treatment is recommended for ary underlying etiology can be found. The pathogenesis is still those with no cardiovascular disease and a 10-year cardiovas- not completely understood, but potential mechanisms include cular risk of <10% for stage 2 hypertension (140/90 mm Hg). abnormal kidney sodium handling, increased activity of the renin-angiotensin system, and elevated sympathetic tone. e Adults with stage 2 hypertension and an average BP that is In general, hypertension is a complex polygenic disorder 20/10 mm Hg above their BP target should be treated with in which many genes or combinations may influence BP. a combination of two first-line antihypertensive drugs of Many genetic variants affect the distal tubular sodium trans- different classes.

In general, hypertension is a complex polygenic disorder 20/10 mm Hg above their BP target should be treated with in which many genes or combinations may influence BP. a combination of two first-line antihypertensive drugs of Many genetic variants affect the distal tubular sodium trans- different classes. port and may result in excess sodium retention, leading to e The target systolic BP goal for noninstitutionalized, ambu- hypertension. Genetic polymorphisms involving oxidative latory community-dwelling patients who are 265 years of stress, mediators of vascular smooth muscle tone, and vaso- age is <130 mm Hg. active mechanisms have also been implicated. However, e The target BP for patients with hypertension and diabetes associated genetic variants have only small effects, such that and/or CKD is <130/80 mm Hg. the collective effect of all identified BP loci account for only In 2020, the Department of Veterans Affairs (VA) and about 3.5% of BP variability. Monogenic forms, in which sin- Department of Defense (DOD) published guidelines for the gle gene mutations explain the underlying pathophysiology diagnosis and management of hypertension in the primary of hypertension, are less common and include such diseases care setting. Although most goals are analogous with those of as glucocorticoid-remediable aldosteronism, Liddle disease, ACC/AHA, there are some differences: and Gordon syndrome. Dietary factors have been implicated as contributors to e The VA/DOD recommend treating patients >60 years of hypertension development. Populations with low sodium age to a systolic BP goal <150 mm Hg, with the added ben- intake have lower BP than those with high intake. Habitual efit to lowering BP further for patients whose systolic BP

port and may result in excess sodium retention, leading to e The target systolic BP goal for noninstitutionalized, ambu- hypertension. Genetic polymorphisms involving oxidative latory community-dwelling patients who are 265 years of stress, mediators of vascular smooth muscle tone, and vaso- age is <130 mm Hg. active mechanisms have also been implicated. However, e The target BP for patients with hypertension and diabetes associated genetic variants have only small effects, such that and/or CKD is <130/80 mm Hg. the collective effect of all identified BP loci account for only In 2020, the Department of Veterans Affairs (VA) and about 3.5% of BP variability. Monogenic forms, in which sin- Department of Defense (DOD) published guidelines for the gle gene mutations explain the underlying pathophysiology diagnosis and management of hypertension in the primary of hypertension, are less common and include such diseases care setting. Although most goals are analogous with those of as glucocorticoid-remediable aldosteronism, Liddle disease, ACC/AHA, there are some differences: and Gordon syndrome. Dietary factors have been implicated as contributors to e The VA/DOD recommend treating patients >60 years of hypertension development. Populations with low sodium age to a systolic BP goal <150 mm Hg, with the added ben- intake have lower BP than those with high intake. Habitual efit to lowering BP further for patients whose systolic BP high sodium intake along with low potassium intake is a criti- is 130 to 140 mm Hg.

hypertension development. Populations with low sodium age to a systolic BP goal <150 mm Hg, with the added ben- intake have lower BP than those with high intake. Habitual efit to lowering BP further for patients whose systolic BP high sodium intake along with low potassium intake is a criti- is 130 to 140 mm Hg. cal factor contributing to the worldwide high prevalence of e For patients >60 years of age with type 2 diabetes mellitus, hypertension. This is especially true for those with salt sensi- the systolic BP goal is 140 mm Hg, with added benefit from tivity, common in Black patients, older adults, and those with lowering BP to 130 mm Hg. CKD or diabetes, in whom an increase in sodium intake leads e The diastolic BP target for all adults >30 years of age is to a disproportionate increase in BP. <90 mm Hg. Positive correlations also exist between BP and physical e The VA/DOD found insufficient evidence to recommend inactivity, overweight or obesity, excess alcohol intake, hyper- initiating combination therapy over monotherapy with uricemia, and insulin resistance. the sequential addition of a second medication.

cal factor contributing to the worldwide high prevalence of e For patients >60 years of age with type 2 diabetes mellitus, hypertension. This is especially true for those with salt sensi- the systolic BP goal is 140 mm Hg, with added benefit from tivity, common in Black patients, older adults, and those with lowering BP to 130 mm Hg. CKD or diabetes, in whom an increase in sodium intake leads e The diastolic BP target for all adults >30 years of age is to a disproportionate increase in BP. <90 mm Hg. Positive correlations also exist between BP and physical e The VA/DOD found insufficient evidence to recommend inactivity, overweight or obesity, excess alcohol intake, hyper- initiating combination therapy over monotherapy with uricemia, and insulin resistance. the sequential addition of a second medication. e Habitual high sodium intake along with low potassium Lifestyle Modifications intake is a critical factor contributing to the worldwide Lifestyle modifications and cardiovascular risk factors should high prevalence of hypertension. be addressed in all patients with elevated BP or hypertension. Several nonpharmacologic interventions have been shown to Management have efficacy in reducing BP (Table 15). Evidence shows that General Approach the most efficacious interventions for BP-lowering effects are Treatment recommendations for specific populations are out- weight loss, the Dietary Approaches to Stop Hypertension lined in respective sections. Importantly, consideration must (DASH) diet, and dietary sodium reduction. Weight reduction be given to individual patient characteristics and circum- is the most efficacious, followed by sodium reduction. stances to tailor management. Although difficult to achieve, a combination of lifestyle modi- The 2017 ACC/AHA BP guideline provides treatment rec- fications (e.g., DASH combined with a low-sodium diet alone ommendations, including the following: or in combination with weight loss) has BP-lowering effects e Nonpharmacologic therapy is recommended for those greater than or equal to those of single-drug therapy in with elevated BP (systolic BP between 120-129 mm Hg patients with hypertension. The VA/DOD conclude that data and diastolic BP <80 mm Hg) or stage 1 hypertension are inadequate to recommend weight loss medication or bari- (systolic BP between 130-139 mm Hg or diastolic BP atric surgery for the purposes of managing obesity and hyper- between 80-89 mm Hg) and a 10-year cardiovascular risk tension. Other effective nonpharmacologic interventions of <10%. include potassium supplementation (preferably in dietary

e Habitual high sodium intake along with low potassium Lifestyle Modifications intake is a critical factor contributing to the worldwide Lifestyle modifications and cardiovascular risk factors should high prevalence of hypertension. be addressed in all patients with elevated BP or hypertension. Several nonpharmacologic interventions have been shown to Management have efficacy in reducing BP (Table 15). Evidence shows that General Approach the most efficacious interventions for BP-lowering effects are Treatment recommendations for specific populations are out- weight loss, the Dietary Approaches to Stop Hypertension lined in respective sections. Importantly, consideration must (DASH) diet, and dietary sodium reduction. Weight reduction be given to individual patient characteristics and circum- is the most efficacious, followed by sodium reduction. stances to tailor management. Although difficult to achieve, a combination of lifestyle modi- The 2017 ACC/AHA BP guideline provides treatment rec- fications (e.g., DASH combined with a low-sodium diet alone ommendations, including the following: or in combination with weight loss) has BP-lowering effects e Nonpharmacologic therapy is recommended for those greater than or equal to those of single-drug therapy in with elevated BP (systolic BP between 120-129 mm Hg patients with hypertension. The VA/DOD conclude that data and diastolic BP <80 mm Hg) or stage 1 hypertension are inadequate to recommend weight loss medication or bari- (systolic BP between 130-139 mm Hg or diastolic BP atric surgery for the purposes of managing obesity and hyper- between 80-89 mm Hg) and a 10-year cardiovascular risk tension. Other effective nonpharmacologic interventions of <10%. include potassium supplementation (preferably in dietary 32

Hypertension TABLE 15. Efficacy of Lifestyle Modifications for Reducing Blood Pressure Approach Recommendation Effect on Systolic Blood Pressure Reduce weight BMI <25 5 to 10 mm Hg reduction per 10-kg (22-lb) weight loss Reduce dietary sodium 1500 to 2400 mg/d 2 to 8mm Hg reduction Follow DASH (Dietary Approaches to Fruits; vegetables; low-fat dairy; whole grains; 8to 14mm Hg reduction | Stop Hypertension) diet legumes; low saturated fat and sodium; high potassium, magnesium, and calcium Increase potassium intake 4700 mg/d Variable reductions Abstinence of or moderation in Men: <2 drinks per day; women: <1 drink per day 2to 4mm Hg reduction alcohol consumption | Exercise 30 min/d, most days (not consistently independent 4to9 mmHg reduction of weight loss) | Alternative approaches Device-guided breathing?; yoga; meditation; Variable reductions | | biofeedback; acupuncture | | |

biofeedback; acupuncture | | | Slow breathing exercises, which can be initiated by means of specific devices. L — a

biofeedback; acupuncture | | | Slow breathing exercises, which can be initiated by means of specific devices. L — a modification), increased physical activity, and abstinence of or effects on cardiovascular outcomes, with one exception: For moderation in alcohol consumption. Regardless of effects on the prevention of heart failure, initial therapy with a thiazide BP, tobacco cessation should be encouraged given that smok- diuretic was more effective than a calcium channel blocker ing is a significant risk factor for cardiovascular disease. (CCB) or an ACE inhibitor, and an ACE inhibitor was more Studies evaluating transcendental meditation, yoga, and effective than a CCB. The primary agents recommended are biofeedback had modest, mixed, or no consistent BP-lowering those that were shown to reduce clinical events and include a effects. More data support efficacy of device-guided breathing thiazide diuretic, CCB, ACE inhibitor, or angiotensin receptor than acupuncture among the noninvasive procedures and blocker (ARB) for hypertension in the general non-Black pop- devices that were evaluated. ulation, including those with diabetes. In Black patients, ini- It is imperative to tailor lifestyle modifications to the indi- tial antihypertensive therapy should include a thiazide diuretic vidual patient while considering a patient’s needs, support or a CCB (see Specific Populations, Black Patients). systems and resources, and readiness for behavioral change. There are not enough trials comparing B-blockers, central- or peripheral-acting o-blockers, vasodilators, aldos- terone receptor antagonists, or loop diuretics to the four drug e The 2017 American College of Cardiology/American classes mentioned. Therefore, these drug classes are not rec- Heart Association blood pressure (BP) guideline recom- ommended as first-line therapy but can be used in specific mends a BP goal of <130/80 mm Hg in most adult populations (B-blockers for post-myocardial infarction or patient populations. heart failure; aldosterone receptor blockers for heart failure; e In addition to lifestyle modification, pharmacologic loop diuretics for advanced CKD) or as add-on therapy for therapy should be initiated in patients with stage 1 resistant hypertension. hypertension and clinical cardiovascular disease or a Table 16 lists frequently used antihypertensive medica- 10-year cardiovascular risk >10% and in all patients tions. with stage 2 hypertension.

modification), increased physical activity, and abstinence of or effects on cardiovascular outcomes, with one exception: For moderation in alcohol consumption. Regardless of effects on the prevention of heart failure, initial therapy with a thiazide BP, tobacco cessation should be encouraged given that smok- diuretic was more effective than a calcium channel blocker ing is a significant risk factor for cardiovascular disease. (CCB) or an ACE inhibitor, and an ACE inhibitor was more Studies evaluating transcendental meditation, yoga, and effective than a CCB. The primary agents recommended are biofeedback had modest, mixed, or no consistent BP-lowering those that were shown to reduce clinical events and include a effects. More data support efficacy of device-guided breathing thiazide diuretic, CCB, ACE inhibitor, or angiotensin receptor than acupuncture among the noninvasive procedures and blocker (ARB) for hypertension in the general non-Black pop- devices that were evaluated. ulation, including those with diabetes. In Black patients, ini- It is imperative to tailor lifestyle modifications to the indi- tial antihypertensive therapy should include a thiazide diuretic vidual patient while considering a patient’s needs, support or a CCB (see Specific Populations, Black Patients). systems and resources, and readiness for behavioral change. There are not enough trials comparing B-blockers, central- or peripheral-acting o-blockers, vasodilators, aldos- terone receptor antagonists, or loop diuretics to the four drug e The 2017 American College of Cardiology/American classes mentioned. Therefore, these drug classes are not rec- Heart Association blood pressure (BP) guideline recom- ommended as first-line therapy but can be used in specific mends a BP goal of <130/80 mm Hg in most adult populations (B-blockers for post-myocardial infarction or patient populations. heart failure; aldosterone receptor blockers for heart failure; e In addition to lifestyle modification, pharmacologic loop diuretics for advanced CKD) or as add-on therapy for therapy should be initiated in patients with stage 1 resistant hypertension. hypertension and clinical cardiovascular disease or a Table 16 lists frequently used antihypertensive medica- 10-year cardiovascular risk >10% and in all patients tions. with stage 2 hypertension. ° Lifestyle modifications (weight loss, diet, dietary Diuretics sodium reduction) and cardiovascular risk factors Initial antihypertensive treatment may include thiazide diuret- should be addressed in all patients with elevated blood ics, which act by inhibiting the sodium-chloride-cotransporter pressure and hypertension. in the distal renal tubule. Although hydrochlorothiazide is the most commonly used thiazide, at times chlorthalidone may be Pharmacologic Therapy preferred because of a prolonged half-life, which allows once- Clinical trials suggest that antihypertensive medication ther- daily dosing. Loop diuretics are preferred in patients with apy can be associated with up to a 40% reduction in stroke, symptomatic heart failure or CKD with an eGFR <30 mL/min/ 25% reduction in myocardial infarction, and 50% reduction in 1.73 m2? (see Kidney Disease, Management). heart failure. Suboptimal BP therapy in patients with difficult-to- Clinical trials revealed that lowering BP is more important control hypertension is frequently the result of not including a than the agent class used to achieve control. Head-to-head diuretic, which ensures that extracellular volume expansion trials of antihypertensive medications revealed comparable is prevented or treated. This is particularly important in

° Lifestyle modifications (weight loss, diet, dietary Diuretics sodium reduction) and cardiovascular risk factors Initial antihypertensive treatment may include thiazide diuret- should be addressed in all patients with elevated blood ics, which act by inhibiting the sodium-chloride-cotransporter pressure and hypertension. in the distal renal tubule. Although hydrochlorothiazide is the most commonly used thiazide, at times chlorthalidone may be Pharmacologic Therapy preferred because of a prolonged half-life, which allows once- Clinical trials suggest that antihypertensive medication ther- daily dosing. Loop diuretics are preferred in patients with apy can be associated with up to a 40% reduction in stroke, symptomatic heart failure or CKD with an eGFR <30 mL/min/ 25% reduction in myocardial infarction, and 50% reduction in 1.73 m2? (see Kidney Disease, Management). heart failure. Suboptimal BP therapy in patients with difficult-to- Clinical trials revealed that lowering BP is more important control hypertension is frequently the result of not including a than the agent class used to achieve control. Head-to-head diuretic, which ensures that extracellular volume expansion trials of antihypertensive medications revealed comparable is prevented or treated. This is particularly important in 33

Hypertension TABLE 16. Frequently Used Antihypertensive Medications Class/Agent Common Side Effects/Contraindications Thiazide diuretics (e.g., hydrochlorothiazide; chlorthalidone) Hypokalemia; hyponatremia; hyperlipidemia; hyperuricemia; hyperglycemia. Avoid in gout unless patient is on urate-lowering therapy. | ACE inhibitors (e.g., captopril; lisinopril; enalapril; benazepril) Hyperkalemia; cough. Avoid use with angiotensin receptor blockers or direct renin inhibitors. Contraindicated in pregnancy. Angiotensin receptor blockers (e.g., candesartan; losartan; Hyperkalemia. Avoid use with ACE inhibitors or direct renin valsartan; irbesartan) inhibitors. Contraindicated in pregnancy. Calcium channel blockers Dihydropyridines (e.g., amlodipine; felodipine; nifedipine) Pedal edema; headache; flushing. Nondihydropyridines (e.g., diltiazem; verapamil) Constipation. Avoid in HFrEF. Avoid routine use with B-blockers (heart block, bradycardia). Drug interactions (CYP3A4 major substrate and moderate inhibitor). B-Blockers (e.g., atenolol; metoprolol tartrate; metoprolol Fatigue; bronchospasm; sexual dysfunction; hyperglycemia. | succinate; labetalol) | Potassium channel openers (vasodilators) (e.g., hydralazine; Edema. Hydralazine: lupus-like syndrome. Minoxidil: hypertrichosis. | / minoxidil) a-Blockers (e.g., prazosin) Orthostatic hypotension; dizziness. | Central o-agonists (e.g., clonidine, oral or patch) Fatigue; depression; rebound hypertension.

| Potassium channel openers (vasodilators) (e.g., hydralazine; Edema. Hydralazine: lupus-like syndrome. Minoxidil: hypertrichosis. | / minoxidil) a-Blockers (e.g., prazosin) Orthostatic hypotension; dizziness. | Central o-agonists (e.g., clonidine, oral or patch) Fatigue; depression; rebound hypertension. | Potassium-sparing diuretics (e.g., spironolactone; amiloride; Hyperkalemia. Caution if GFR <45 mL/min/1.73 m2. Spironolactone: | eplerenone) gynecomastia. GFR = glomerular filtration rate; HFrEF = heart failure with reduced ejection fraction.

| Potassium-sparing diuretics (e.g., spironolactone; amiloride; Hyperkalemia. Caution if GFR <45 mL/min/1.73 m2. Spironolactone: | eplerenone) gynecomastia. GFR = glomerular filtration rate; HFrEF = heart failure with reduced ejection fraction. sodium-retentive, edematous conditions (heart failure, liver medications concomitantly with B-blockers or in patients cirrhosis, or CKD). Even in the absence of edematous condi- with heart failure with severely reduced ejection fraction, sick tions, persistent intravascular volume expansion without sinus syndrome, or second- or third-degree atrioventricular apparent edema can still contribute to hypertension that block. Additionally, short-acting nifedipine can be associated appears resistant to treatment. In addition, diuretic medica- with increased mortality if used immediately after acute myo- tion should be prescribed in adequate doses, with dosing fre- cardial infarction because of profound hypotension and sym- quency tailored appropriately to the diuretic half-life. For pathetic activation. Finally, there may be an increased risk for example, loop diuretics such as furosemide should be dosed at myopathy if a CCB (especially a nondihydropyridine) is used least twice to three times daily, and higher doses should be concomitantly with a high-dose statin. used in patients with low GFR. Potassium-sparing diuretics, such as aldosterone receptor Renin-Angiotensin System Agents antagonists (spironolactone or eplerenone) or epithelial Renin-angiotensin system (RAS) agents are ACE inhibitors, sodium channel blockers (amiloride), are weaker diuretics. ARBs, and direct renin inhibitors (such as aliskiren). Clinical These are often used in patients with liver cirrhosis, heart trials reported similar efficacy of ACE inhibitors and ARBs on failure (where evidence suggests reduced mortality), or resist- reducing BP, progression of albuminuria and CKD, and risk for ant hypertension. Caution and close monitoring are advised cardiovascular events. Therefore, neither class is preferred when these medications are prescribed concomitantly with over the other. There are less outcomes data on the effects of other drug classes that also raise the serum potassium, such as aliskiren, although similar BP-lowering effect is expected. ACE inhibitors, ARBs, or direct renin inhibitors, and in patients Dry cough is a side effect of ACE inhibitors but is generally with reduced GFR. not reported with ARBs. Angioedema, a life-threatening con- dition, is a complication of both ACE inhibitors and renin Calcium Channel Blockers inhibitors. Patients with a compelling indication for RAS inhi- There are two classes of CCBs: dihydropyridines (amlodipine, bition who develop angioedema can be treated with an ARB felodipine, nifedipine) and nondihydropyridines (diltiazem, with very careful monitoring, given a low but possible risk for verapamil). No data support the use of one class over the other occurrence. RAS agents should not be used in combination, for hypertension management, although long-acting dihydro- and they are contraindicated in pregnancy. pyridines are usually chosen. Nondihydropyridines have more pronounced cardiac effects, such as diminished cardiac con- Combination Therapy tractility (negative inotropy) and atrioventricular nodal block- Combination therapy with more than one drug class (sepa- ade, and caution should be taken in prescribing these rately or as a single-dose pill) may be necessary to control BP.

sodium-retentive, edematous conditions (heart failure, liver medications concomitantly with B-blockers or in patients cirrhosis, or CKD). Even in the absence of edematous condi- with heart failure with severely reduced ejection fraction, sick tions, persistent intravascular volume expansion without sinus syndrome, or second- or third-degree atrioventricular apparent edema can still contribute to hypertension that block. Additionally, short-acting nifedipine can be associated appears resistant to treatment. In addition, diuretic medica- with increased mortality if used immediately after acute myo- tion should be prescribed in adequate doses, with dosing fre- cardial infarction because of profound hypotension and sym- quency tailored appropriately to the diuretic half-life. For pathetic activation. Finally, there may be an increased risk for example, loop diuretics such as furosemide should be dosed at myopathy if a CCB (especially a nondihydropyridine) is used least twice to three times daily, and higher doses should be concomitantly with a high-dose statin. used in patients with low GFR. Potassium-sparing diuretics, such as aldosterone receptor Renin-Angiotensin System Agents antagonists (spironolactone or eplerenone) or epithelial Renin-angiotensin system (RAS) agents are ACE inhibitors, sodium channel blockers (amiloride), are weaker diuretics. ARBs, and direct renin inhibitors (such as aliskiren). Clinical These are often used in patients with liver cirrhosis, heart trials reported similar efficacy of ACE inhibitors and ARBs on failure (where evidence suggests reduced mortality), or resist- reducing BP, progression of albuminuria and CKD, and risk for ant hypertension. Caution and close monitoring are advised cardiovascular events. Therefore, neither class is preferred when these medications are prescribed concomitantly with over the other. There are less outcomes data on the effects of other drug classes that also raise the serum potassium, such as aliskiren, although similar BP-lowering effect is expected. ACE inhibitors, ARBs, or direct renin inhibitors, and in patients Dry cough is a side effect of ACE inhibitors but is generally with reduced GFR. not reported with ARBs. Angioedema, a life-threatening con- dition, is a complication of both ACE inhibitors and renin Calcium Channel Blockers inhibitors. Patients with a compelling indication for RAS inhi- There are two classes of CCBs: dihydropyridines (amlodipine, bition who develop angioedema can be treated with an ARB felodipine, nifedipine) and nondihydropyridines (diltiazem, with very careful monitoring, given a low but possible risk for verapamil). No data support the use of one class over the other occurrence. RAS agents should not be used in combination, for hypertension management, although long-acting dihydro- and they are contraindicated in pregnancy. pyridines are usually chosen. Nondihydropyridines have more pronounced cardiac effects, such as diminished cardiac con- Combination Therapy tractility (negative inotropy) and atrioventricular nodal block- Combination therapy with more than one drug class (sepa- ade, and caution should be taken in prescribing these rately or as a single-dose pill) may be necessary to control BP. 34

Hypertension The 2017 ACC/AHA BP guideline recommends combination White Coat Hypertension therapy with two first-line antihypertensive drugs of different White coat hypertension refers to elevated BP measured in classes for adults with stage 2 hypertension and an average BP the office, but out-of-office BP averages that are not elevated of 20/10 mm Hg above their BP target (typically >150/90 mm (see Table 12). Using automated office BP measurements Hg). There are no definitive recommendations for best drug without an observer may lessen the prevalence. In adults combinations, but some data suggest an ACE inhibitor/CCB with untreated systolic BP >130 mm Hg but <160 mm Hg or combination may be more efficacious than an ACE inhibitor/ diastolic BP >80 mm Hg but <100 mm Hg, it is reasonable to thiazide diuretic combination. Using a thiazide diuretic/CCB screen for white coat hypertension using either daytime combination is also an option. ABPM or home BP monitoring. Before white coat hyperten- Combined use of any RAS drug classes (ACE inhibitors, sion is diagnosed, the reliability of out-of-office measure- ARBs, and direct renin inhibitors) is not recommended; sev- ments must be confirmed; for example, the patient’s home eral clinical trials (ONTARGET, NEPHRON-D, ALTITUDE) have BP monitor should be calibrated against the office sphyg- revealed more adverse events with these combinations (hyper- momanometer or, preferably, BP should be measured by kalemia, hypotension, AKI), without additional cardiovascular ABPM. or renal benefits. The prevalence of white coat hypertension is approxi- mately 15% to 30% among patients with office BP in the Assessment of Adherence, Efficacy, and hypertensive range. Although these patients may have a Medication Titration slightly higher cardiovascular risk compared with normo- Adherence and response to treatment should be assessed tensive patients (but a lower risk than in those with masked 4 weeks after treatment initiation or sooner, based on the or sustained hypertension), it is unclear whether antihyper- urgency for BP lowering. Further assessments are necessitated tensive drug treatment lowers cardiovascular risk. Lifestyle until target is achieved. Three strategies are possible for dose modification is still recommended in patients with white titration: coat hypertension. However, there is a 1% to 5% per year risk 1. Maximize the first medication dose before adding a for conversion of white coat hypertension to sustained hyper- second. tension. This risk is higher with older age, obesity, or Black

The 2017 ACC/AHA BP guideline recommends combination White Coat Hypertension therapy with two first-line antihypertensive drugs of different White coat hypertension refers to elevated BP measured in classes for adults with stage 2 hypertension and an average BP the office, but out-of-office BP averages that are not elevated of 20/10 mm Hg above their BP target (typically >150/90 mm (see Table 12). Using automated office BP measurements Hg). There are no definitive recommendations for best drug without an observer may lessen the prevalence. In adults combinations, but some data suggest an ACE inhibitor/CCB with untreated systolic BP >130 mm Hg but <160 mm Hg or combination may be more efficacious than an ACE inhibitor/ diastolic BP >80 mm Hg but <100 mm Hg, it is reasonable to thiazide diuretic combination. Using a thiazide diuretic/CCB screen for white coat hypertension using either daytime combination is also an option. ABPM or home BP monitoring. Before white coat hyperten- Combined use of any RAS drug classes (ACE inhibitors, sion is diagnosed, the reliability of out-of-office measure- ARBs, and direct renin inhibitors) is not recommended; sev- ments must be confirmed; for example, the patient’s home eral clinical trials (ONTARGET, NEPHRON-D, ALTITUDE) have BP monitor should be calibrated against the office sphyg- revealed more adverse events with these combinations (hyper- momanometer or, preferably, BP should be measured by kalemia, hypotension, AKI), without additional cardiovascular ABPM. or renal benefits. The prevalence of white coat hypertension is approxi- mately 15% to 30% among patients with office BP in the Assessment of Adherence, Efficacy, and hypertensive range. Although these patients may have a Medication Titration slightly higher cardiovascular risk compared with normo- Adherence and response to treatment should be assessed tensive patients (but a lower risk than in those with masked 4 weeks after treatment initiation or sooner, based on the or sustained hypertension), it is unclear whether antihyper- urgency for BP lowering. Further assessments are necessitated tensive drug treatment lowers cardiovascular risk. Lifestyle until target is achieved. Three strategies are possible for dose modification is still recommended in patients with white titration: coat hypertension. However, there is a 1% to 5% per year risk 1. Maximize the first medication dose before adding a for conversion of white coat hypertension to sustained hyper- second. tension. This risk is higher with older age, obesity, or Black 2. Add a second medication before reaching the maximum race. Annual follow-up with ABPM or home BP measure- ments should be considered to determine if conversion to dose of the first. sustained hypertension has occurred, requiring the addition 3. Start with two medication classes separately or as fixed- of antihypertensive drug therapy. Screening echocardiogra- dose combinations. phy may also be considered to screen for left ventricular There are no randomized trials comparing these strate- hypertrophy, the presence of which necessitates treatment gies; therefore, the strategy should be tailored to the indi- with antihypertensives. vidual patient, dose-related side effects, and adherence. Generally, there is diminishing return in BP lowering if the dose is titrated up from 50% to 100% of maximum. Also, it is ¢ Lifestyle modifications and careful monitoring should unlikely that increasing the dose from 50% to 100% of maxi- be considered for patients with white coat hypertension mum will result in an additional >5-mm Hg BP reduction; because of increased risk for future development of an additional agent may therefore need to be added. Finally, hypertension and slightly higher cardiovascular risk titration to maximum doses may more commonly result in compared with normotensive patients.

2. Add a second medication before reaching the maximum race. Annual follow-up with ABPM or home BP measure- ments should be considered to determine if conversion to dose of the first. sustained hypertension has occurred, requiring the addition 3. Start with two medication classes separately or as fixed- of antihypertensive drug therapy. Screening echocardiogra- dose combinations. phy may also be considered to screen for left ventricular There are no randomized trials comparing these strate- hypertrophy, the presence of which necessitates treatment gies; therefore, the strategy should be tailored to the indi- with antihypertensives. vidual patient, dose-related side effects, and adherence. Generally, there is diminishing return in BP lowering if the dose is titrated up from 50% to 100% of maximum. Also, it is ¢ Lifestyle modifications and careful monitoring should unlikely that increasing the dose from 50% to 100% of maxi- be considered for patients with white coat hypertension mum will result in an additional >5-mm Hg BP reduction; because of increased risk for future development of an additional agent may therefore need to be added. Finally, hypertension and slightly higher cardiovascular risk titration to maximum doses may more commonly result in compared with normotensive patients. side effects and reduce adherence. Other specific actionable steps to increase adherence include the use of longer-acting antihypertensive drugs that only require once-daily dosing Masked Hypertension and combination pills to reduce pill burden. Masked hypertension, defined as BP that is normal in the office but elevated in the ambulatory setting (see Table 12),

side effects and reduce adherence. Other specific actionable steps to increase adherence include the use of longer-acting antihypertensive drugs that only require once-daily dosing Masked Hypertension and combination pills to reduce pill burden. Masked hypertension, defined as BP that is normal in the office but elevated in the ambulatory setting (see Table 12), e A thiazide diuretic, calcium channel blocker, ACE inhib- is associated with an increased prevalence of target organ itor, or angiotensin receptor blocker is recommended as damage and risk for cardiovascular disease, stroke, and initial therapy for hypertension in the general non-Black mortality compared with normotension. In adults with population, including those with diabetes mellitus. elevated office BP (120-129/<80 mm Hg) but not meeting the criteria for hypertension or with end-organ damage, ¢ Combination therapy with two first-line antihyper- such as left ventricular hypertrophy, screening for tensive drugs of different classes is recommended for masked hypertension with daytime ABPM or home BP is adults with stage 2 hypertension and an average reasonable. blood pressure (BP) that is 20/10 mm Hg above their The prevalence of masked hypertension varies from 10% BP target. to 26% in population-based surveys and from 14% to 30% in 35