HYPERTENSION

Definition: HTN is a persistent, nonphysiologic elevation of BP; it is

defined as an SBP of 130 mm Hg or greater and/or a DBP of 80 mm
Hg or greater
A. Background
1. Prevalence
a. Most common chronic disease in the United States
b. Affects 46% of the population
c. Prevalence increases with age
d. Major modifiable risk factor for CV disease and stroke
2. Etiology
a. Essential HTN: 90% (no identifiable cause)
i. Obesity is a contributor
ii. Evaluate Na intake
b. Secondary HTN
i. Primary aldosteronism
ii. Renal parenchymal disease
iii. Renal artery stenosis
iv. Obstructive sleep apnea
v. Cushing syndrome
vi. Thyroid or parathyroid disease
vii. Medications (e.g., cyclosporine, NSAIDs, sympathomimetics)
viii. Pheochromocytoma
3. Diagnosis
a. Periodic screening for all people older than 21 years
b. Patient should be seated quietly in chair for at least 5 minutes.
c. Use appropriate cuff size (bladder length at least 80% the
circumference of the arm).
d. Take BP at least twice, separated by at least 2 minutes.
e. The average BP on two separate visits is required to diagnose HTN
accurately.
f. Home blood pressure monitoring (HBPM) and ambulatory blood
pressure monitoring (ABPM) are recommended to confirm diagnosis,
screen for white-coat HTN, and screen for masked HTN
i. White-coat HTN: Office blood pressure is 130/80-160/100 mm Hg
after a 3-month trial of lifestyle modification but with daytime ABPM
or HBPM blood pressure less than 130/80 mm Hg
ii. Masked HTN: Office blood pressure is 120-129/less than 80 mm Hg
after a 3-month trial of lifestyle modification; daytime ABPM or
HBPM blood pressure of 130/80 or greater
4. Benefits of lowering BP
a. 40% decrease in stroke
b. 25% decrease in MI
c. 50% decrease in HF
 5. Effects of lifestyle modifications on BP
Approximate Systolic BP Recommendation Modification
Reduction
5–20 mm Hg per Maintain a normal body weight (BMI 18.5–24.9 kg/m2) Weight reduction

10-kg weight loss

8–14 mm Hg Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of Adopt DASH eating plan
saturated and total fat
(includes substantial

potassium intake)
2–8 mm Hg Reduce sodium intake to ≤2400 mg/day (NaCl < 6000mg) Reduce sodium intake

Reducing sodium intake further to ≤1500 mg/day is associated with greater BP reduction

Reducing sodium intake by at least 1000 mg/day will lower BP if desired daily sodium intake
goal is not achieved
4–9 mm Hg Engage in regular aerobic physical activity such as brisk walking (at least 30 minutes/day most Physical activity
days of the week)
2–4 mm Hg Limit consumption to: Moderation of alcohol

Men: 2 drinks/day (24 ounces of beer, 10 ounces of wine, or 3 ounces of 80 proof whiskey) consumption
Women and those of lower body weight: 1 drink/day
New classification according to AHA
Classification of Blood Pressure in Adults*
Classification Blood Pressure
Normal blood pressure < 120/80 mm Hg
Elevated blood pressure 120–129/< 80 mm Hg
Stage 1 hypertension 130–139 mm Hg (systolic)
OR
80–89 mm Hg (diastolic)
Stage 2 hypertension ≥ 140 mm Hg (systolic)
OR
≥ 90 mm Hg (diastolic)
Hypertensive urgency/ emergency >180 (systolic)
or
>120 (diastolic)
2. Select treatment goal.
a. Initiating therapy with a single antihypertensive drug is
reasonable in adults with stage 1 HTN and a BP goal of less than
130/80 mm Hg
b. Initiating antihypertensive drug therapy with two first-line
agents of different classes is recommended in adults with stage 2
HTN and an average BP greater than 20/10 mm Hg above their BP
target
c. First-line agents include thiazide diuretics, CCBs, and ACEIs or
ARBs
Table. BP Thresholds for Goals of Pharmacologic Therapy in Patients with HTN According to Clinical Condition (AHA guidelines)

Clinical Condition BP Threshold, BP Goal,

mm Hg mm Hg
Clinical CVD or 10-year ASCVD risk ≥10% ≥130/80 < 130/80
No clinical CVD and 10-year ASCVD risk <10% ≥140/90 for all
Diabetes mellitusa 130/80≥
Chronic kidney disease 130/80≥
Chronic kidney disease after renal transplantation 130/80≥
Heart failure 130/80≥
Stable ischemic heart disease 130/80≥
Secondary stroke prevention ≥140/90
Secondary stroke prevention (lacunar) 130/80≥
Peripheral arterial disease 130/80≥
Older persons (≥65 years; noninstitutionalized, ≥130 (SBP) <130
ambulatory, community-living) (SBP)
 Initial Approach to Management of High Blood Pressure
BP ASCVD Risk < 10% ASCVD Risk ≥ 10% Clinical ASCVD*
Elevated: 120–129/< Lifestyle changes, Lifestyle changes, Lifestyle changes,
80 reassess in 3 to 6 mo reassess in 3 to 6 mo reassess in 3 to 6 mo
Stage 1 Hypertension: Lifestyle changes, Drug monotherapy, Drug monotherapy,
130–139/80–89 reassess in 3 to 6 mo reassess in 1 mo† reassess in 1 mo†
Stage 2 hypertension‡: Two-drug therapy, Two-drug therapy, Two-drug therapy,
Systolic ≥ 140 reassess in 1 mo reassess in 1 mo reassess in 1 mo
OR
Diastolic ≥ 90

*Coronary artery disease, heart failure, or stroke

†
Lifestyle changes also are recommended for all patients receiving drug therapy.
‡
For BP 140–159/90–100, consider starting with 2 drugs (of different classes). For BP ≥ 160/100, definitely use
2 drugs and reassess frequently.
ASCVD = atherosclerotic cardiovascular disease; BP = blood pressure.
• If the target BP is not achieved in 1 mo, assess adherence and reinforce the
importance of following treatment.
• If patients are adherent, the dose of the initial drug can be increased or a second
drug added (selected from the drugs recommended for initial treatment).
• Note that an ACE inhibitor and an angiotensin receptor blocker should not be used
together.
• Therapy is titrated frequently.
• If target BP cannot be achieved with 2 drugs, a third drug from the initial group is
added.
• If such a third drug is not available (eg, for black patients) or tolerated, a drug from
another class (eg, beta-blocker, aldosterone antagonist) can be used. Patients with
such difficult to control BP may benefit from consultation with a hypertension
specialist.
• Now we use Thiazide-like diuretics* (chlorthalidone or indapamide)
5. Considerations with specific antihypertensive agents
a. β-Blockers
i. Caution with asthma, severe chronic obstructive pulmonary disease (especially higher doses)
because of pulmonary β-receptor blockade
ii. Increased risk of developing diabetes (impair insulin release); use caution in patients at high risk
of diabetes mellitus (e.g., family history, obese)
iii. May mask some signs of hypoglycemia in patients with diabetes mellitus
iv. May cause depression
b. Thiazides
i. May worsen gout by increasing serum uric acid
ii. Increased risk of developing diabetes (hypokalemia, impair glucose tolerance); use caution in
patients at high risk of diabetes mellitus (e.g., family history, obese)
iii. May assist in the management of osteoporosis by preventing urine calcium loss
c. Angiotensin-converting enzyme inhibitors and ARBs
i. Contraindicated in pregnancy
ii. Contraindicated with bilateral renal artery stenosis
iii. Monitor K closely, especially if renal insufficiency exists or another K-sparing
drug is in use.
d. Aliskiren
i. A direct rennin antagonist
ii. Contraindicated in pregnancy
iii. Contraindicated in patients with diabetes when used in combination with ACE
inhibitors or ARBs because of increased risk of renal impairment, hyperkalemia,
and hypotension
e. Calcium channel blockers
i. Dihydropyridine CCBs
(a) Amlodipine, felodipine, nifedipine
(b) Monitor for peripheral edema, reflex tachycardia, and orthostatic hypotension
(c) Useful for isolated systolic hypertension or use in African American patients
ii. Nondihydropyridine CCBs
(a) Diltiazem, verapamil
(b) Indicated in hypertensive patients with comorbid conditions which would benefit
from HR reduction (e.g., atrial fibrillation, stable angina)
(c) Contraindicated in HFrEF, heart block and sick sinus syndrome
(d) Potential drug interactions due to CYP450 inhibition
6. Considerations within specific patient populations
a. Patients with ischemic heart disease: Potent
vasodilators may cause reflex tachycardia, thereby
increasing myocardial oxygen demand (hydralazine,
minoxidil, and dihydropyridine calcium channel
blockers); can attenuate this by also using an
atrioventricular nodal depressant (non-dihydropyridine
calcium channel blocker or β-blocker)
b. Elderly patients:
i. Caution with antihypertensive agents and orthostatic hypotension
ii. Initiate with low dose and titrate slowly.
iii. Treatment of HTN with an SBP treatment goal of less than 130 mm Hg is
recommended for noninstitutionalized ambulatory community-dwelling adults
with an average SBP of 130 mmHg or greater
iv. The SPRINT trial showed that targeting an SBP of less than 120 mmHg,
compared with less than 140 mm Hg, resulted in lower rates of fatal and nonfatal
major CV events and death from any cause among patients at high risk of CV
events but without DM.
Twenty-five percent of the study population was older than 75 years.
c. Black patients: β-Blockers and ACE inhibitors are generally less effective as
monotherapy than in non–black patients. In black adults with HTN but without HF
or CKD, including those with diabetes mellitus, initial antihypertensive treatment
should include a thiazide-type diuretic or CCB.
β-blockers and ACE inhibitors should still be used if comorbid conditions dictate.

d. Women
i. Oral estrogen-containing contraceptives can increase BP, and the risk can
increase with the duration of use.
ii. HTN increases the risk to mother and fetus in women who are pregnant.
Preferred medications include methyldopa, nifedipine, and labetalol. ACE
inhibitors, ARBs, and aliskiren should not be used because of the potential for
fetal defects.
7. Monitoring
a. Have the patient return in 4 weeks to assess
efficacy.
b. If there is an inadequate response from the first
agent (and adherence verified) and no compelling
indication exists, initiate therapy with a drug from a
different class.
8. Resistant HTN
a. Confirm diagnosis
i. Office BP of 130/80 mm Hg or greater and patient taking at least three
antihypertensive medications at optimal doses, including a diuretic (confirmed
adherence) OR
ii. Office BP of < 130/80 mm Hg but patient requires at least four
antihypertensive medications
b. Exclude pseudoresistance
i. Ensure accurate office BP readings
ii. Exclude white-coat HTN
iii. Ensure adherence
c. Identify and reverse contributing factors
i. Lifestyle factors
(a) Obesity
(b) High-salt, low-fiber diet
(c) Physical inactivity
(d) Excessive alcohol use
ii. Interfering medications
(a) NSAIDs
(b) Sympathomimetics
(c) Stimulants
(d) Oral contraceptives
d. Screen and treat for secondary causes of HTN (described earlier)
e. Assess for target organ damage
f. Pharmacological treatment
i. Maximize diuretic therapy
(a) Use thiazide or thiazide-like diuretics if eGFR>25-30 mL/min/m2
(1) Chlorthalidone and indapamide have the most evidence for reducing
cardiovascular outcomes
(2) Chlorthalidone is more effective at inducing predictable natriuresis in
patients with an eGFR 30-45 mL/min/m2
(b) Use loop diuretics if eGFR<30 mL/min/m2
ii. Add Mineralocorticoid Receptor Antagonists (MRA) (spironolactone or
eplerenone)
iii. Alter dosing times to include a nocturnal dose or divide doses of drugs with
short half-lives
iv. Add other agents from different drug classes
v. Addition of hydralazine or minoxidil requires concomitant use of a ß-blocker
and diuretic
g. Follow-up
i. Ensure attainment of target BP after six months of therapy
ii. If patient not at goal, refer to appropriate specialists
 Hypertensive crisis (Urgency and
Emergency )
A. Definitions
1. Hypertensive urgency – Acutely elevated BP, greater than 180/110
mm Hg, in the absence of symptoms or target organ damage (may be
mild degree of retinopathy)
2. Hypertensive emergency – HTN with evidence of target organ
damage to brain, heart, kidneys, eyes (e.g., hypertensive
encephalopathy, intracranial hemorrhage, acute neurologic deficit; UA
or acute MI; acute HF; pulmonary edema (shortness of breath); aortic
dissection)
B. Goals
1. Hypertensive urgency
a. Treated by reinstitution ‫اعادة‬or intensification of antihypertensive drug therapy
b. No indication for referral to the ED, immediate reduction in blood pressure in
the ED, or hospitalization
c. No proven benefit exists from rapid reductions in blood pressure.
d. Choice of agent used in this setting varies, and in many cases, adjusting
chronic oral therapy (increasing doses), reinitiating therapy in the non-adherent,
or adding a new agent (i.e., diuretic) to long-term therapy is appropriate.
e. All patients with hypertensive urgency should be reevaluated within 7 days
(preferably after 1–3 days).
2. Hypertensive emergency – Lower mean arterial pressure (MAP) by no more than
25% in the first hour then SBP to 160 and diastolic blood pressure to 100–110 mm Hg
over next 2–6 hours, then to normal over next 24–48 hours.
Exceptions:
i. Do not lower blood pressure in acute ischemic stroke unless greater than 220/120
mm Hg or greater than 185/110 mm Hg in tissue plasminogen activator candidates.
ii. Rapidly lower blood pressure to less than 140 mm Hg in the first hour of treatment
in severe preeclampsia or eclampsia and in pheochromocytoma with hypertensive
crisis.
iii. Rapidly lower blood pressure to less than 120 mm Hg and HR less than 60
beats/minute in the first hour of treatment in aortic dissection.
Intravenous medications used commonly
 C. Treatment Options
Commonly Used Intravenous Drugs for Hypertensive Emergencies
Drug (onset, duration) Intravenous Dose Adverse Effects
Vasodilators
Sodium nitroprusside 0.25–0.5 mcg/kg/minute, Cyanide/thiocyanate toxicity, nausea, vomiting,
methemoglobinemia
(Nipriss) (immediate, 2–3 minutes) maximum 3 mcg/kg/minute
CIs: Renal, hepatic failure

Caution: Increased ICP

Nitroglycerin (2–5 minutes, 5–10 minutes) 5–10 mcg/minute, Headache, nausea, vomiting, tachyphylaxis,
methemoglobinemia
maximum 100 mcg/minute
Caution: Increased ICP
5–10 mg every 4–6 hours Reflex tachycardia, headache, flushing
Hydralazine (Apresoline)
(not to exceed 20 mg/dose) Caution: Angina/MI, increased ICP, aortic
10 minutes, 1–4 hours)
dissection

Enalaprilat 0.625–1.25 mg every 4–6 hours, maximum 5 mg Renal insufficiency/failure, hyperkalemia

every 6 hours
(Vasotec) (within 30 minutes, 12–24 hours) CIs: Pregnancy, renal artery stenosis

(Note: Long half-life)

 Commonly Used Intravenous Drugs for Hypertensive Emergencies

Drug (onset, duration) Intravenous Dose Adverse Effects

Fenoldopam (Corlopam) (< 5 0.1 mcg/kg/minute, Headache, flushing, tachycardia,

minutes, 30 minutes) maximum 1.6 mcg/kg/minute cerebral ischemia

Caution: Glaucoma
Nicardipine 5–15 mg/hour, maximum 15 mg/hour Reflex tachycardia, nausea, vomiting,

(Cardene) (1–5 minutes, 15–30 headache, flushing

minutes – Up to 4 hours if prolonged Caution: Angina/MI, acute HF,
infusion)
increased ICP
Clevidipine (Cleviprex) 1–2 mg/hour CIs: Soy/egg product allergy, severe

(2–4 minutes, 5–15 minutes) maximum 16 mg/hour aortic stenosis, defective lipid
metabolism
 Commonly Used Intravenous Drugs for Hypertensive Emergencies
Drug (onset, duration) Intravenous Dose Adverse Effects

Adrenergic Inhibitors
Esmolol (Brevibloc) 250–400 mcg/kg/minute IVB; Caution: Acute HF, asthma, heart block

(1–2 minutes, 10–30 minutes) then 50–100 mcg/kg/minute infusion,

maximum 300 mcg/kg/minute

Labetalol (Normodyne, Trandate) (5–10 20–80 mg every 15 minutes Same as esmolol

minutes, 3–6 hours)
OR 0.5–2 mg/minute maximum 300
mg/24 hours

Phentolamine (2 min, 15–30 min) IVB dose 5 mg; additional bolus Used in hypertensive emergencies
doses every 10 min as needed induced by catecholamine excess
Phentolamine is a reversible,
(pheochromocytoma, monamine oxidase
competitive antagonist at alpha-1 inhibitors interactions with food and/or
and alpha-2 adrenergic receptors drugs, cocaine toxicity, amphetamine
overdose, or clonidine withdrawal)
 Agents Preferred for Hypertensive Crises Based on Comorbidities
Comorbidity Preferred Agents Comments
Acute aortic dissection Labetalol, esmolol Requires rapid lowering of SBP to ≤ 120 mm Hg within
20 min; β-blocker should be given before vasodilator
(nicardipine or NTP) if needed for BP control or to
prevent reflex tachycardia or inotropic effect; SBP ≤ 120
mm Hg should be achieved within 20 min
Acute heart failure Nitroprusside, nitroglycerin, or ACE
inhibitors in combination with diuretics
if pulmonary edema (Note: Avoid β-
blockers)
Acute pulmonary edema Clevidipine, nitroglycerin, nitroprusside β-Blockers contraindicated; NTG preferred for ADHF
Perioperative HTN (BP ≥ Clevidipine, esmolol, nicardipine, Intraoperative HTN is most common during anesthesia
160/90 mm Hg or SBP induction and airway manipulation
NTG
elevation > 20% of the
preoperative value that
persists > 15 min)
Comorbidity Preferred Agents Comments

Acute coronary syndromes Esmolol or NTG (preferred), Nitrates given in the presence of PDE-5
labetalol, nicardipine inhibitors may induce profound hypotension
Acute renal failure Clevidipine, fenoldopam,
nicardipine
Eclampsia or preeclampsia Labetalol, nicardipine, Requires rapid BP lowering to < 140 mm Hg
hydralazine (second line) within first hour; ACE inhibitor, ARBs, renin
inhibitors, and NTP contraindicated
Acute sympathetic discharge or Clevidipine, nicardipine, Requires rapid lowering of BP
catecholamine excess states (e.g., phentolamine (Note: Avoid
pheochromocytoma, post-carotid unopposed β-blockade which
endarterectomy status) causes unopposed α-receptor
stimulation)
Comorbidity Preferred Agents Comments

Acute ischemic No preference of agent Early initiation or resumption of antihypertensive treatment indicated
stroke only in

(1) patients treated with tissue-type plasminogen activator to an SBP <

185/110 mm Hg and

(2) patients with SBP > 220 mm Hg or DBP > 120 mm Hg; cerebral
autoregulation in the ischemic penumbra of the stroke is grossly
abnormal and rapid reduction of BP can be harmful; reinitiate
antihypertensive therapies in those with preexisting HTN after
neurologic stability
Acute intracranial IV continuous infusion Lower BP in those who present with SBP > 220 mm Hg with continuous
hemorrhage IV infusion and close BP monitoring; immediate lowering of SBP < 140
mm Hg is not of benefit and may be harmful. Avoiding medications that
can increase ICP and worsen cerebral ischemia (hydralazine, NTG, and
NTP)