14.1 Staging of hypertension (HTN) according to ACC/AHA
| BP Value | Stage | Treatment |
|---|---|---|
| <120/80 | Normal | |
| 120–129/<80 | Elevated blood pressure | Does not require drugs, but early interventions of lifestyle modifications (weight loss, low salt, and/or DASH diet, increased physical activity, and limiting alcohol) could reduce BP |
| 130–139/80–89 | HTN stage 1 | Pharmacological therapy is indicated if ≥135/85 or ≥130/80 + at least one risk factor (established cardiovascular disease or at high risk, type 2 diabetes, CKD, age ≥65) |
| ≥140/≥90 | HTN stage 2 | May start with two drugs if baseline SBP is ≥15 mmHg above goal |
14.2 Resistant, refractory, and accelerated HTN and HTN in pregnancy
| Classification | Definition | Treatment |
|---|---|---|
| Resistant HTN | BP above goal despite three agents of different classes, including a diuretic | Evaluate for causes and adherence to therapy (see below) and lifestyle modifications as listed above; consider ambulatory BP monitoring |
| Refractory HTN | BP uncontrolled despite ≥5 agents, including chlorthalidone and a mineralocorticoid receptor antagonist | Refer to a specialized HTN clinic; same as resistant HTN plus sympatholytic Rx may be effective in this group; renal sympathetic denervation and carotid sinus stimulation are investigational treatments |
| HTN urgency | Asymptomatic BP ≥180/120 |
|
| HTN emergency (accelerated or malignant HTN) | Symptomatic with retinal hemorrhages, papilledema, neurological symptoms, encephalopathy, and/or malignant nephrosclerosis; BP ≥180/120 (usually but not required) | Hospitalization, target BP <180/120 for the first hour and <160/110 for the first day (MAP reduction 10%–20% for the first hour and 5%–15% for the first day); overly aggressive reduction in BP may cause coronary, cerebral, or renal ischemia; evaluate for secondary causes of HTN |
| HTN in pregnancy |
| Treatment is indicated if BP ≥160/110, but others suggest treatment if BP ≥140/90, , end organ damage, or preeclampsia (see Rx below and Chapter 10 ) |
14.3 Which blood pressure reading should be followed?
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Systolic blood pressure (BP) has a better association with cardiovascular disease (CVD) events than diastolic BP in older adults; in younger patients (age <60 years), diastolic BP is significantly associated with CVD risk.
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Twenty-four-hour BP monitoring is the gold standard; otherwise, office-based BP measurement may be used. Home BP could be used to complement office measurement.
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If there is a discrepancy between office and home BP, 24-hour BP monitoring should be obtained (to rule out white coat or masked HTN).
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Consider ambulatory BP monitoring to evaluate the circadian rhythm of BP readings (e.g., higher values while awake and lower values at nighttime = BP “dipping”); control of nighttime rather than daytime BP seems most associated with better outcomes.
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Goal BP in patients with established CVD is 125 to 130/80 (office measurement) or 120 to 125/80 (other measurements).
14.4 Causes of resistant or refractory hypertension to consider
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Secondary HTN (see below)
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Improper BP measurements (e.g., inappropriate cuff size) or “white coat” HTN
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Calcification or sclerosis of brachial arteries (falsely high by arm sphygmomanometer)
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Nonadherence to anti-HTN medications
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Use of other drugs (over-the-counter meds, such as nonsteroidal antiinflammatory drugs [NSAIDs] and decongestants)
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Dietary indiscretion of salt or alcohol
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Volume overload with inadequate diuretic therapy
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Comorbidities (e.g., obesity, obstructive sleep apnea)
14.5 Evaluation of secondary causes of hypertension (especially in young onset, resistant, or accelerated HTN)
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Patient studies:
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History—HTN related to drugs: hormonal contraceptives, NSAIDs, cocaine, amphetamines, sympathomimetics, corticosteroids, licorice, epoetin, excessive alcohol
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Endocrinopathies—hyperthyroidism, Cushing syndrome, pheochromocytoma
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Sleep study if obstructive sleep apnea is considered
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Ambulatory 24-hour BP monitoring (“white coat” labile HTN, nighttime dipping)
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Laboratory tests:
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All patients:
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Creatinine (renal function)
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Urinalysis (detect proteinuria, kidney disease)
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Electrolytes/glucose (hypokalemia, metabolic alkalosis, or diabetes may suggest hypermineralocorticoid state)
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Specific studies (based on findings):
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Aldosterone, renin levels (primary hyperaldosteronism or secondary hyperreninemic state; for example, renal artery stenosis, kidney tumor)
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Thyroid stimulating hormone (TSH; hyperthyroidism)
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Cortisol (Cushing syndrome)
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Plasma or urine catecholamines (pheochromocytoma)
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Drug screening (e.g., cocaine)
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Radiological imaging:
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Renal ultrasound (US) with Doppler (cystic/anatomic diseases, obstructive uropathy, signs of renal artery stenosis)
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CT or MR angiogram (detect/confirm renal artery stenosis, fibromuscular dysplasia, coarctation of the aorta)
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Radiocontrast angiography (confirm main or segmental renal artery stenosis)
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Adrenal vein aldosterone and cortisol levels for laterality of adrenal adenomas
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14.6 Selection of initial therapy in patients with no specific indications
Stage 1
Thiazide diuretic, or angiotensin converting enzyme inhibitor (ACEi), or angiotensin receptor blocker (ARB), or calcium channel blocker (CCB)
Stage 2
Long-acting CCB and ACEi or ARB
ACEi/ARB and a thiazide diuretic (chlorthalidone preferred)
Selection of initial therapy based on demographics:
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In Blacks, ACEi may be less effective in lowering BP than either a thiazide-type diuretic or a CCB.
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Blacks and Asians have greater rates of angioedema and cough as side effects with ACEi.
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In older adults, HTN and isolated systolic HTN should be treated; lower initial doses should be used; could start initial therapy with a long-acting CCB and adding an ACEi/ARB if needed; in the absence of a specific indication (e.g., heart failure), beta blockers should not be used as the primary therapy for HTN; avoid orthostatic hypotension; alpha blockers should generally be avoided unless indicated for symptoms of prostatic hypertrophy.
14.7 Treatment based on specific indications or comorbid conditions
14.7.1 Patients with kidney disease
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Target SBP: <120
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In patients with proteinuric renal disease: ACEi or ARB slows progression of chronic kidney disease (CKD); ACEi or ARB should be administered using the highest approved dose that is tolerated.
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Combination therapy with an ACEi and an ARB is associated with an increased risk of adverse events among patients with diabetic nephropathy. Aliskiren has been shown to decrease proteinuria, but the long-term effect on CKD needs elucidation.
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Thiazide diuretics become less effective when the glomerular filtration rate (GFR) is less than 30 mL/min/1.73m 2 . In such patients, loop diuretics are preferred as initial therapy to achieve BP control by relieving hypervolemia.
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A mineralocorticoid receptor antagonist (spironolactone or eplerenone) is an effective agent for the treatment of resistant HTN in patients with CKD.
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In CKD patients: ≥3 drugs including a diuretic are commonly needed to achieve a goal SBP ≤120.
14.7.2 Patients with diabetes mellitus
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With proteinuria: ACEi or ARB first to slow progression of CKD.
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Sodium-glucose co-transporter-2 inhibitors (SGLT-2i), such as canagliflozin, empagliflozin, and dapagliflozin, have been shown to decrease proteinuria, slow the progression of CKD, and lower the risk of end-stage kidney disease (ESKD) and death from renal causes in patients with or without type 2 diabetes.
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In patients with CKD and type 2 diabetes, treatment with finerenone (a nonsteroidal selective mineralocorticoid receptor antagonist) resulted in lower risks of CKD progression and cardiovascular events though systolic blood pressures decreased by only about 2-3 mm Hg. ,
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Thiazide diuretics may be needed but may worsen glucose tolerance: potassium depletion may impair pancreatic islet beta-cell insulin release and thiazides may increase insulin resistance of target tissues (avoid hypokalemia by potassium repletion and use low-dose diuretic with co-administration of ACEi or ARB).
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If beta blockers are indicated, they may have deleterious metabolic consequences: increased severity and duration of hypoglycemic episodes in type 1 diabetes mellitus (DM) by impairing the hepatic glycogenolytic response to adrenal epinephrine release in hypoglycemia (decrease this effect by using cardioselective beta blockers at low doses). Beta blockers may elevate plasma triglycerides (though beta blockers with intrinsic sympathomimetic [partial agonist] activity [e.g., pindolol or acebutolol] are less likely to cause this effect).
14.7.3 Patients with resistant or refractory HTN
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Low-sodium diet should be stressed (test for 24-hour urinary Na excretion).
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Diuretics (counter the volume expansion caused by other anti-HTN agents and potentiate their effect). Start with thiazides, use loop diuretics in those with low GFR, and consider adding aldosterone blockade with spironolactone or eplerenone or potassium-sparing collecting-duct sodium channel blockade with amiloride or triamterene.
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Combine effects of different anti-HTN medication classes: renin-angiotensin-aldosterone antagonism with ACEi, ARB, or beta blocker (e.g., labetalol or carvedilol); long-acting CCB; CNS acting agent (e.g., clonidine); or direct vasodilator (e.g., hydralazine or minoxidil).
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Consider investigational use of endovascular radiofrequency renal sympathetic denervation or electrical stimulation of carotid sinus baroreceptors in severe cases. Neither is approved for treatment of HTN in the United States.
14.7.4 Patients with HTN emergency (accelerated or malignant HTN)
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Start with parenteral IV administration: commonly a direct vasodilator (nitroprusside), an alpha and beta sympatholytic (labetalol), a CCB with vasodilator activity (nicardipine or clevidipine), or a postsynaptic dopamine receptor agonist (fenoldopam).
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Other IV medications that can be used include esmolol, enalaprilat, hydralazine, and urapidil.
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Use a loop diuretic for volume overload.
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Follow with oral agents as for resistant HTN, combining effects of different classes (e.g., labetalol, amiloride, clonidine, prazosin, hydralazine).
14.7.5 Patients with heart failure
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In heart failure with a reduced ejection fraction (HFrEF), HTN should be treated with a renin-angiotensin system inhibitor (e.g., neprilysin inhibitor [sacubitril], ACEi, or ARB), a beta blocker (e.g., carvedilol), and a mineralocorticoid receptor antagonist (spironolactone or eplerenone).
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The combination of hydralazine and isosorbide dinitrate might be effective in Black patients on standard therapies.
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Use diuretics for peripheral or pulmonary edema.
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Use a long acting CCB (e.g., amlodipine, felodipine) if needed.
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In heart failure with a preserved ejection fraction (HFpEF), optimal therapy of HTN is uncertain but usually includes diuretics and a mineralocorticoid receptor antagonist.
14.7.6 Patients with sleep apnea
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Nasal continuous positive airway pressure may be effective treatment of HTN.
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Prescribe weight reduction for obesity.
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Otherwise, conventional antihypertensive treatment should be undertaken.
14.7.7 Patients with obstructive airways disease (COPD or asthma)
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Beta-adrenergic antagonists can increase airway reactivity and should be considered second-line therapy unless there is another indication (e.g., coronary artery disease), in which case a selective beta-1-blocker should be preferred.
14.7.8 Patients with dyslipidemia
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Thiazides may increase serum cholesterol levels, especially LDL, however the effect is generally dose dependent; co-administration of an ACEi blunts or abolishes thiazide-induced metabolic abnormalities.
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Beta blockers cause an elevation in serum triglyceride levels (beta blockers with intrinsic sympathomimetic [partial agonist] activity [e.g., pindolol or acebutolol] are less likely to cause this effect).
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ACEi and calcium channel antagonists have little effect on lipids.
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Alpha-1-antagonists may elevate HDL.
14.7.9 Pregnant patients
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BP ≥160/110 should be pharmacologically treated with consideration when BP is ≥140/90.
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Methyldopa: centrally alpha agonist, may cause sedation
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Hydralazine: long-term safety data
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Long-acting CCB: for example, amlodipine or extended-release nifedipine
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Labetalol: combined alpha and beta blocker, can cause bronchoconstriction
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Diuretics controversial; okay for volume overload
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Acute treatment: parenteral labetalol, hydralazine, or nicardipine
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ACEi, nitroprusside: contraindicated in pregnancy
14.7.10 Patients with pheochromocytoma
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Preoperative management: alpha-adrenergic blockade (e.g., oral phenoxybenzamine for control of BP and tachyarrhythmias)
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If alpha-blockade alone does not normalize BP and HR, beta blockers may be added (e.g., propranolol, nadolol). Beta-blockade may be used only after effective alpha-blockade is in place to prevent unopposed alpha-adrenergic mediated vasoconstriction by elevated circulating catecholamines.
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Preoperative management should include intravascular volume expansion. Some patients with pheochromocytoma are volume contracted; encourage high-sodium diet.
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CCB could be used when BP is still uncontrolled.
14.7.11 Patients with other conditions
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Atrial fibrillation: beta blockers help control heart rate.
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Essential tremor: beta blockers have beneficial effect on tremor.
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Prostatic hypertrophy: alpha blockers help with voiding hesitancy.
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Obese patients: weight reduction is a primary goal of Rx.
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Scleroderma (progressive systemic sclerosis): ACEi is preferred therapy, with captopril used most commonly, or an ARB if ACEi isn’t tolerated; CCB or a direct vasodilator added if necessary; beta blockers may aggravate Raynaud phenomenon so should be avoided.
14.7.12 Renal artery stenosis (RAS): Causes, evaluation, and treatment
14.7.12.1 Causes of RAS
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Atherosclerosis (most common: 90% of cases)
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Fibromuscular dysplasia
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Other: vasculitis, neurofibromatosis, congenital bands, extrinsic compression, and radiation
14.7.12.2 Evaluation of patient for RAS
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Renal US with Doppler: detects RAS with ∼80% sensitivity
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US-resistive indices helpful to predict outcome of intervention (better when <0.8; poorer when >0.8)
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Radiocontrast CT angiography
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MR angiography
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Radiocontrast aortography and selective renal arteriography to confirm RAS, particularly for segmental or fibromuscular arterial disease
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Renal vein renin levels to assess lateralization when findings are indecisive (false positives and negatives have decreased this test’s usefulness)
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Radionuclide renography to assess differential renal blood flow and function (as a percentage of overall renal function)
14.7.12.3 Treatment of RAS
Medical therapy
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ACEi or ARB is effective in >85% of patients but has risk of a hemodynamic decrease in renal function, particularly with bilateral RAS
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Often need to combine Rx with a diuretic
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Should urge smoking cessation, lipid-lowering Rx, and aspirin or antiplatelet agents, if indicated
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Concerns: progression of disease, long-term ischemic damage
Interventional therapy.
Revascularization is not indicated in all patients since overall results are similar to medical Rx; should be considered in those with hemodynamically significant RAS with worsening renal function, HTN that is difficult to control, intolerance to optimal medical therapy, unexplained flash pulmonary edema, or refractory heart failure.
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Percutaneous intervention: balloon angioplasty, with or without stenting; stent placement for atherosclerotic RAS for a higher initial primary success rate and higher patency rate at 6 months
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Renal artery stenting did not confer a significant benefit with respect to the prevention of major renal and cardiovascular events when added to medical therapy in people with atherosclerotic RAS and HTN or CKD
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Surgical therapy might be equally or more effective than percutaneous intervention in the treatment of atherosclerotic disease
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Surgical revascularization may be indicated for certain cases not amenable to percutaneous angioplasty: unilateral aortorenal bypass surgery and extraanatomical bypass (bypass originates from the celiac or mesenteric branches)
14.7.13 Hypertensive nephropathy (hypertensive nephrosclerosis)
Hypertensive nephropathy is thought to be the second most common cause of ESKD after diabetic nephropathy. If HTN is poorly controlled, renal insufficiency may progress slowly over years with benign nephrosclerosis, the nephropathy associated with benign hypertension, whereas with malignant hypertension, malignant nephrosclerosis is a rapidly progressive renal disease with ESKD that may occur in weeks.
14.7.14 Predictors of kidney injury
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Severity of HTN
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Presence of comorbid conditions (e.g., diabetes)
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Male gender
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Black race (a coexisting condition of genetic focal segmental glomerular sclerosis may be a contributing cause of progressive nephropathy; see Chapter 8 )
14.7.15 Mechanism of kidney injury
