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Overview of Hypertension
Hypertension is sustained elevation of resting systolic BP (≥ 130 mm Hg), diastolic BP (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential hypertension) is most common. Hypertension with an identified cause (secondary hypertension) is usually due to sleep apnea, chronic kidney disease, or primary aldosteronism. Usually, no symptoms develop unless hypertension is severe or long-standing. Diagnosis is by sphygmomanometry. Tests may be done to determine cause, assess damage, and identify other cardiovascular risk factors. Treatment involves lifestyle changes and drugs, including diuretics, beta- blockers, ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers.
(See also 2017 ACC/AHA Hypertension Guidelines)
In the US, about 75 million people have hypertension. About 81% of these people are aware that they have hypertension, only 75% are being treated, and only 51% have adequately controlled BP. In adults, hypertension occurs more often in blacks (41%) than in whites (28%) or Mexican Americans (28%), and morbidity and mortality are greater in blacks.
Blood pressure increases with age. About two thirds of people > 65 have hypertension, and people with a normal BP at age 55 have a 90% lifetime risk of developing hypertension. Because hypertension becomes so common with age, the age-related increase in BP may seem innocuous, but higher BP increases morbidity and mortality risk. Hypertension may develop during pregnancy (see Hypertension in Pregnancy and see Preeclampsia and Eclampsia).
BP in adults is classified as normal, elevated BP, stage 1 (mild) or stage 2 hypertension (see Table: Classification of Blood Pressure in Adults*). Normal blood pressure in infants and adolescents is much lower (1).
Classification of Blood Pressure in Adults*
Hypertension may be
Hemodynamics and physiologic components (eg, plasma volume, activity of the renin-angiotensin system) vary, indicating that primary hypertension is unlikely to have a single cause. Even if one factor is initially responsible, multiple factors are probably involved in sustaining elevated blood pressure (the mosaic theory). In afferent systemic arterioles, malfunction of ion pumps on sarcolemmal membranes of smooth muscle cells may lead to chronically increased vascular tone. Heredity is a predisposing factor, but the exact mechanism is unclear. Environmental factors (eg, dietary sodium, obesity, stress) seem to affect only genetically susceptible people at younger ages; however, in patients > 65, high sodium intake is more likely to precipitate hypertension.
Common causes include
Other much rarer causes include pheochromocytoma, Cushing syndrome, congenital adrenal hyperplasia, hyperthyroidism,hypothyroidism (myxedema), primary hyperparathyroidism, acromegaly, coarctation of the aorta, and mineralocorticoid excess syndromes other than primary aldosteronism. Excessive alcohol intake and use of oral contraceptives are common causes of curable hypertension. Use of sympathomimetics, NSAIDs, corticosteroids, cocaine, or licorice commonly contributes to worsening of blood pressure control.
Because blood pressure equals cardiac output (CO) × total peripheral vascular resistance (TPR), pathogenic mechanisms must involve
In most patients, CO is normal or slightly increased, and TPR is increased. This pattern is typical of primary hypertension and hypertension due to primary aldosteronism, pheochromocytoma, renovascular disease, and renal parenchymal disease.
In other patients, CO is increased (possibly because of venoconstriction in large veins), and TPR is inappropriately normal for the level of CO. Later in the disorder, TPR increases and CO returns to normal, probably because of autoregulation. Some disorders that increase CO (thyrotoxicosis, arteriovenous fistula, aortic regurgitation), particularly when stroke volume is increased, cause isolated systolic hypertension. Some elderly patients have isolated systolic hypertension with normal or low CO, probably due to inelasticity of the aorta and its major branches. Patients with high, fixed diastolic pressures often have decreased CO.
Plasma volume tends to decrease as BP increases; rarely, plasma volume remains normal or increases. Plasma volume tends to be high in hypertension due to primary aldosteronism or renal parenchymal disease and may be quite low in hypertension due to pheochromocytoma. Renal blood flow gradually decreases as diastolic BP increases and arteriolar sclerosis begins. GFR remains normal until late in the disorder; as a result, the filtration fraction is increased. Coronary, cerebral, and muscle blood flow is maintained unless severe atherosclerosis coexists in these vascular beds.
In many cases of hypertension, sodium transport across the cell wall is abnormal, because the sodium-potassium pump (Na+, K+-ATPase) is defective or inhibited or because permeability to sodium ions is increased. The result is increased intracellular sodium, which makes the cell more sensitive to sympathetic stimulation. Calcium follows sodium, so accumulation of intracellular calcium may be responsible for the increased sensitivity. Because Na+, K+-ATPase may pump norepinephrine back into sympathetic neurons (thus inactivating this neurotransmitter), inhibition of this mechanism could also enhance the effect of norepinephrine, increasing BP. Defects in sodium transport may occur in normotensive children of hypertensive parents.
Sympathetic stimulation increases blood pressure, usually more in patients with elevated BP and hypertension than in normotensive patients. Whether this hyperresponsiveness resides in the sympathetic nervous system or in the myocardium and vascular smooth muscle is unknown. A high resting pulse rate, which may result from increased sympathetic nervous activity, is a well-known predictor of hypertension. In some hypertensive patients, circulating plasma catecholamine levels during rest are higher than normal.
The renin-angiotensin-aldosterone system helps regulate blood volume and therefore blood pressure. Renin, an enzyme formed in the juxtaglomerular apparatus, catalyzes conversion of angiotensinogen to angiotensin I. This inactive product is cleaved by ACE, mainly in the lungs but also in the kidneys and brain, to angiotensin II, a potent vasoconstrictor that also stimulates autonomic centers in the brain to increase sympathetic discharge and stimulates release of aldosterone and vasopressin. Aldosterone and vasopressin cause sodium and water retention, elevating BP. Aldosterone also enhances potassium excretion; low plasma potassium (< 3.5 mEq/L) increases vasoconstriction through closure of potassium channels. Angiotensin III, present in the circulation, stimulates aldosterone release as actively as angiotensin II but has much less pressor activity. Because chymase enzymes also convert angiotensin I to angiotensin II, drugs that inhibit ACE do not fully suppress angiotensin II production.
Renin secretion is controlled by at least 4 mechanisms, which are not mutually exclusive:
A renal vascular receptor responds to changes in tension in the afferent arteriolar wall
A macula densa receptor detects changes in the delivery rate or concentration of sodium chloride in the distal tubule
Circulating angiotensin has a negative feedback effect on renin secretion
Sympathetic nervous system stimulates renin secretion mediated by beta-receptors (via the renal nerve)
Angiotensin is generally acknowledged to be responsible for renovascular hypertension, at least in the early phase, but the role of the renin-angiotensin-aldosterone system in primary hypertension is not established. However, in black and elderly patients with hypertension, renin levels tend to be low. The elderly also tend to have low angiotensin II levels.
Hypertension due to chronic renal parenchymal disease (renoprival hypertension) results from the combination of a renin-dependent mechanism and a volume-dependent mechanism. In most cases, increased renin activity is not evident in peripheral blood. Hypertension is typically moderate and sensitive to sodium and water balance.
Deficiency of a vasodilator (eg, bradykinin, nitric oxide) rather than excess of a vasoconstrictor (eg, angiotensin, norepinephrine) may cause hypertension.
Reduction in nitric oxide due to stiff arteries is linked to salt-sensitive hypertension, an inordinate increase of > 10 to 20 mm Hg systolic BP after a large sodium load (eg, a meal of Chinese food).
If the kidneys do not produce adequate amounts of vasodilators (because of renal parenchymal disease or bilateral nephrectomy), blood pressure can increase.
Vasodilators and vasoconstrictors (mainly endothelin) are also produced in endothelial cells. Therefore, endothelial dysfunction greatly affects BP.
No pathologic changes occur early in hypertension. Severe or prolonged hypertension damages target organs (primarily the cardiovascular system, brain, and kidneys), increasing risk of
Stroke (particularly hemorrhagic)
The mechanism involves development of generalized arteriolosclerosis and acceleration of atherogenesis. Arteriolosclerosis is characterized by medial hypertrophy, hyperplasia, and hyalinization; it is particularly apparent in small arterioles, notably in the eyes and the kidneys. In the kidneys, the changes narrow the arteriolar lumen, increasing TPR; thus, hypertension leads to more hypertension. Furthermore, once arteries are narrowed, any slight additional shortening of already hypertrophied smooth muscle reduces the lumen to a greater extent than in normal-diameter arteries. These effects may explain why the longer hypertension has existed, the less likely specific treatment (eg, renovascular surgery) for secondary causes is to restore blood pressure to normal.
Because of increased afterload, the left ventricle gradually hypertrophies, causing diastolic dysfunction. The ventricle eventually dilates, causing dilated cardiomyopathy and heart failure (HF) due to systolic dysfunction often worsened by arteriosclerotic coronary artery disease. Thoracic aortic dissection is typically a consequence of hypertension; almost all patients with abdominal aortic aneurysms have hypertension.
Hypertension is usually asymptomatic until complications develop in target organs. Dizziness, facial flushing, headache, fatigue, epistaxis, and nervousness are not caused by uncomplicated hypertension. Severe hypertension (hypertensive emergencies) can cause severe cardiovascular, neurologic, renal, and retinal symptoms (eg, symptomatic coronary atherosclerosis, HF, hypertensive encephalopathy, renal failure).
A 4th heart sound is one of the earliest signs of hypertensive heart disease.
Retinal changes may include arteriolar narrowing, hemorrhages, exudates, and, in patients with encephalopathy, papilledema (hypertensive retinopathy). Changes are classified (according to the Keith, Wagener, and Barker classification) into 4 groups with increasingly worse prognosis:.
Multiple measurements of BP to confirm
Urinalysis and urinary albumin:creatinine ratio; if abnormal, consider renal ultrasonography
Blood tests: Fasting lipids, creatinine, potassium
Renal ultrasonography if creatinine increased
Evaluate for aldosteronism if potassium decreased
ECG: If left ventricular hypertrophy, consider echocardiography
Sometimes thyroid-stimulating hormone measurement
Evaluate for pheochromocytoma or a sleep disorder if BP elevation sudden and labile or severe
Hypertension is diagnosed and classified by sphygmomanometry. History, physical examination, and other tests help identify etiology and determine whether target organs are damaged.
The blood pressure used for formal diagnosis should be an average of 2 or 3 measurements taken at 2 or 3 different times with the patient:
At the first visit, measure BP in both arms and subsequent measurements should use the arm that gave the higher reading.
A properly sized BP cuff (see Table 9 BP Cuff Size in Adults in the 2017 Hypertension Guidelines) is applied to the upper arm. An appropriately sized cuff covers two thirds of the biceps; the bladder is long enough to encircle > 80% of the arm, and bladder width equals at least 40% of the arm’s circumference. Thus, obese patients require large cuffs. The health care practitioner inflates the cuff above the expected systolic pressure and gradually releases the air while listening over the brachial artery. The pressure at which the first heartbeat is heard as the pressure falls is systolic BP. Total disappearance of the sound marks diastolic BP. The same principles are followed to measure BP in a forearm (radial artery) and thigh (popliteal artery). Mechanical devices should be calibrated periodically; automated readers are often inaccurate.
BP is measured in both arms because BP > 15 mm Hg higher in one arm than the other is associated with higher mortality, and requires evaluation of the upper vasculature when this pattern of measurement is found.
BP is measured in a thigh (with a much larger cuff) to rule out coarctation of the aorta, particularly in patients with diminished or delayed femoral pulses; with coarctation, BP is significantly lower in the legs.
If BP is in the stage 1 hypertensive range or is markedly labile, more BP measurements are desirable. BP measurements may be sporadically high before hypertension becomes sustained; this phenomenon probably accounts for “white coat hypertension,” in which BP is elevated when measured in the physician’s office but normal when measured at home or by ambulatory BP monitoring. However, extreme BP elevation alternating with normal readings is unusual and possibly suggests pheochromocytoma, a sleep disorder such as sleep apnea, or unacknowledged drug use.
The history includes the known duration of hypertension and previously recorded BP levels; any history or symptoms of coronary artery disease, heart failure, sleep apnea or loud snoring; history or symptoms of other relevant coexisting disorders (eg, stroke, renal dysfunction, peripheral arterial disease, dyslipidemia, diabetes, gout); and a family history of any of these disorders.
Social history includes exercise levels and use of tobacco, alcohol, and stimulant drugs (prescribed and illicit). A dietary history focuses on intake of salt and stimulants (eg, tea, coffee, caffeine-containing sodas, energy drinks).
The physical examination includes measurement of height, weight, and waist circumference; funduscopic examination for retinopathy; auscultation for bruits in the neck and abdomen; and a full cardiac, respiratory, and neurologic examination. The abdomen is palpated for kidney enlargement and abdominal masses. Peripheral arterial pulses are evaluated; diminished or delayed femoral pulses suggest aortic coarctation, particularly in patients < 30. A unilateral renal artery bruit may be heard in slim patients with renovascular hypertension.
The more severe the hypertension and the younger the patient, the more extensive is the evaluation. Generally, when hypertension is newly diagnosed, routine testing is done to
Ambulatory blood pressure monitoring, renal radionuclide imaging, chest x-ray, screening tests for pheochromocytoma, and renin-sodium profiling are not routinely necessary.
However, home or ambulatory BP monitoring is indicated when "white coat hypertension" is suspected. In addition, ambulatory BP monitoring also may be indicated when "masked hypertension" (a condition in which BP measured at home is higher than values obtained in the clinician's office) is suspected, typically in patients who demonstrate sequelae of hypertension without evidence of hypertension according to in-office measurements.
Peripheral plasma renin activity is not helpful in diagnosis or drug selection.
Depending on results of initial tests and examination, other tests may be needed. If urinalysis detects albuminuria (proteinuria), cylindruria, or microhematuria, or if serum creatinine is elevated (≥ 1.4 mg/dL [124 μmol/L] in men; ≥ 1.2 mg/dL [106 μmol/L] in women), renal ultrasonography to evaluate kidney size may provide useful information. Patients with hypokalemia unrelated to diuretic use are evaluated for primary aldosteronism and high salt intake.
On ECG, a broad, notched P-wave indicates atrial hypertrophy and, although nonspecific, may be one of the earliest signs of hypertensive heart disease. Left ventricular hypertrophy, indicated by a sustained apical thrust and elevated QRS voltage with or without evidence of ischemia, may occur later. If either of these findings is present, echocardiography is often done. In patients with an abnormal lipid profile or symptoms of coronary artery disease, tests for other cardiovascular risk factors (eg, C-reactive protein) may be useful.
If coarctation of the aorta is suspected, chest x-ray, echocardiography, CT, or MRI helps confirm the diagnosis.
Patients with labile, significantly elevated BP and symptoms such as headache, palpitations, tachycardia, excessive perspiration, tremor, and pallor are screened for pheochromocytoma (eg, by measuring plasma free metanephrines). A sleep study should also be strongly considered in these patients and those whose history suggests sleep apnea.
1.Flynn J.T, Kaelber DC, Baker-Smith CM, et al; Subcommittee on Screening and Management of High Blood Pressure in Children: Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140(3):e20171904, 2017.
The higher the blood pressure and the more severe the retinal changes and other evidence of target-organ involvement, the worse is the prognosis. Systolic BP predicts fatal and nonfatal cardiovascular events better than diastolic BP. Without treatment, 1-yr survival is < 10% in patients with retinal sclerosis, cotton-wool exudates, arteriolar narrowing, and hemorrhage (grade 3 retinopathy), and < 5% in patients with the same changes plus papilledema (grade 4 retinopathy). CAD is the most common cause of death among treated hypertensive patients. Ischemic or hemorrhagic stroke is a common consequence of inadequately treated hypertension. However, effective control of hypertension prevents most complications and prolongs life.
Primary hypertension has no cure, but some causes of secondary hypertension can be corrected. In all cases, control of blood pressure can significantly limit adverse consequences. Despite the theoretical efficacy of treatment, BP is lowered to the desired level in only one third of hypertensive patients in the US.
Treatment targets for the general population, including all those with a kidney disorder or diabetes:
Lowering BP below 130/80 mm Hg appears to continue to reduce the risk of vascular complications. However, it also increases the risk of adverse drug effects. Thus, the benefits of lowering BP to levels approaching 120 mm Hg systolic should be weighed against the higher risk of dizziness and light-headedness and possible worsening of kidney function. This is a particular concern among patients with diabetes, in whom BP < 120 mm Hg systolic or a diastolic BP approaching 60 mm Hg increases risk of these adverse events.
Even the elderly and frail elderly can tolerate a diastolic BP as low as 60 to 65 mm Hg well and without an increase in cardiovascular events. Ideally, patients or family members measure BP at home, provided they have been trained to do so, they are closely monitored, and the sphygmomanometer is regularly calibrated.
Treatment of hypertension during pregnancy requires special considerations because some antihypertensive drugs can harm the fetus.
Lifestyle modifications are recommended for all patients with elevated BP or any stage hypertension (see also Table 15. Nonpharmacological Interventions in 2017 Hypertension Guidelines ). The best proven nonpharmacological interventions for prevention and treatment of hypertension include the following:
Increased physical activity with a structured exercise program
Weight loss if overweight or obese
Healthy diet rich in fruits, vegetables, whole grains, and low-fat dairy products, with reduced saturated and total fat content
Reduced dietary sodium to < 1500 mg/day (< 3.75 g sodium chloride) optimally, but at least a 1000 mg/day reduction
Enhanced dietary potassium intake, unless contraindicated due to chronic kidney disease or use of drugs that reduce potassium excretion
Moderation in alcohol intake in those who drink alcohol to ≤ 2 drinks daily for men and ≤ 1 drink daily for women (one drink is about 12 oz of beer, 5 oz of wine, or 1.5 oz distilled spirits)
Dietary modifications can also help control diabetes, obesity, and dyslipidemia. Patients with uncomplicated hypertension do not need to restrict their activities as long as blood pressure is controlled.
(See also Drugs for Hypertension.)
The decision to use drug treatment is based on the BP level and the presence of atherosclerotic cardiovascular disease (ASCVD) or its risk factors (see Table: Initial Approach to Management of High Blood Pressure). The presence of diabetes or kidney disease is not factored in separately because these diseases are part of ASCVD risk assessment.
An important part of management is continued reassessment. If patients are not at target BP, clinicians should strive to optimize adherence before switching or adding drugs.
Initial Approach to Management of High Blood Pressure
Drug selection is based on several factors. When one drug is given initially, for non-black patients, including those with diabetes, initial treatment may be with either an ACE inhibitor, angiotensin II receptor blocker, calcium channel blocker, or a thiazide-like diuretic (chlorthalidone or indapamide). For black patients, including those with diabetes, a calcium channel blocker or a thiazide-like diuretic is recommended initially unless patients also have stage 3 or higher chronic kidney disease. In black patients with stage 3 chronic kidney disease, an ACE inhibitor or angiotensin II receptor blocker is appropriate.
When 2 drugs are given initially, a single-pill combination with either an ACE inhibitor or angiotensin II receptor blocker and either a diuretic or a calcium channel blocker.
Signs of hypertensive emergencies require immediate blood pressure reduction with parenteral antihypertensives.
Some antihypertensives are contraindicated in certain disorders (eg, beta-blockers in asthma) or are indicated particularly for hypertensive patients with certain disorders (eg, calcium channel blockers for angina pectoris, ACE inhibitors or angiotensin II receptor blockers for diabetes with proteinuria—see Table: Initial Choice of Antihypertensive Drug Class and Antihypertensives for High-Risk Patients).
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.
Initial Choice of Antihypertensive Drug Class
If initial systolic BP is > 160 mm Hg, 2 drugs should be initiated regardless of lifestyle. An appropriate combination and dose are determined; many are available as single tablets, which improve compliance and are preferred. For resistant hypertension, 3 or 4 drugs are commonly needed.
Achieving adequate control often requires several evaluations and changes in drug therapy. Reluctance to titrate or add drugs to control must be overcome. Lack of patient adherence, particularly because lifelong treatment is required, can interfere with adequate BP control. Education, with empathy and support, is essential for success.
Antihypertensives for High-Risk Patients
Percutaneous catheter-based radiofrequency ablation of the sympathetic nerves in the renal artery is approved in Europe and Australia for resistant hypertension. Hypertension is defined as resistant when BP remains > 160/100 mm Hg despite use of 3 different antihypertensive drugs with complementary mechanisms of action (one of which being a diuretic). Although initial studies appeared promising, a recent large, double-blind study was done (1). This study for the first time incorporated a sham ablation procedure in the control arm and failed to show a benefit from radiofrequency ablation. Thus, sympathetic ablation should still be considered experimental and done only in European or Australian centers with extensive experience.
A second physical intervention involves stimulating the carotid baroreceptor with a device surgically implanted around the carotid body. A battery attached to the device, much like a pacemaker, is used to stimulate the baroreceptor and, in a dose-dependent manner, lower BP. This procedure has so far proven safe and effective, although experience is limited and trials are ongoing. This device is not yet approved in the US for treatment of hypertension.
1. Bhatt DL, Kandzari DE, O'Neill WW, et al, for the SYMPLICITY HTN-3 Investigators: A controlled trial of renal denervation for resistant hypertension. N Engl J Med 370:1393–1401, 2014. DOI: 10.1056/NEJMoa1402670.
Only about three quarters of patients in the US with hypertension are being treated and only half have adequate BP control.
Most hypertension is primary; only 5 to 15% is secondary to another disorder (eg, renal parenchymal or vascular disease, sleep apnea, pheochromocytoma, Cushing syndrome, congenital adrenal hyperplasia, hyperthyroidism).
Severe or prolonged hypertension damages the cardiovascular system, brain, and kidneys, increasing risk of MI, stroke, and renal failure.
Hypertension is usually asymptomatic until complications develop in target organs.
When hypertension is newly diagnosed, do urinalysis, spot urine albumin:creatinine ratio, blood tests (creatinine, potassium, sodium, fasting plasma glucose, lipid profile, and often TSH), and ECG.
Reduce BP to < 130/80 mm Hg for everyone up to age 80, including those with a kidney disorder or diabetes.
Treatment involves lifestyle changes, especially a low-sodium and higher potassium diet, management of secondary causes of hypertension, and drugs (including diuretics, ACE inhibitors, angiotensin II receptor blockers, and calcium channel blockers).
Drug NameSelect Trade
indapamideNo US brand name