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Hypertension

By

George L. Bakris

, MD, University of Chicago School of Medicine

Reviewed/Revised Sep 2023
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Topic Resources

Hypertension is sustained elevation of resting systolic blood pressure ( 130 mm Hg), diastolic blood pressure ( 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 primary aldosteronism. Sleep apnea, chronic kidney disease, obesity, or renal artery stenosis are other causes of secondary hypertension. Usually, no symptoms develop unless hypertension is severe or long-standing. Diagnosis is by sphygmomanometry. Tests may be done to determine cause, assess organ damage, and identify other cardiovascular risk factors. Treatment involves lifestyle changes and medications, including diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers, and calcium channel blockers.

Hypertension is defined as a systolic blood pressure (BP) 130 mm Hg or a diastolic blood pressure 80 mm Hg or taking medication for hypertension. Nearly half of adults in the United States have hypertension. Many of these people are not aware that they have hypertension. About 80% of adults with hypertension have been recommended treatment with medication and lifestyle modification, but only about 50% with hypertension receive treatment (1 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ).

Even with medication and lifestyle modification only 26% of patients have their BP at goal (under control), and of treated adults whose BP is not at goal, almost 60% have a BP 140/90 mm Hg (1 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ).

High blood pressure is more common in non-Hispanic Black adults (58%) than in non-Hispanic White adults (49%), non-Hispanic Asian adults (45%), or Hispanic adults (39%— 1 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ). Among those recommended to take blood pressure medication and make lifestyle modifications, blood pressure control is higher among non-Hispanic White adults (31%) than in non-Hispanic Black adults (20%), non-Hispanic Asian adults (24%), or Hispanic adults (23%— 1 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ).

Blood pressure increases with age. About two thirds of people > 65 years have hypertension, and people with a normal BP at age 55 have a 90% lifetime risk of developing hypertension (2 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ). 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 is defined as resistant when BP remains above goal despite use of 3 different antihypertensive medications at maximally tolerated doses. Patients with resistant hypertension have higher cardiovascular morbidity and mortality (5 General references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more General references ).

Table

General references

  • 1. Million Hearts: Estimated Hypertension Prevalence, Treatment, and Control Among U.S. Adults. https://millionhearts.hhs.gov/data-reports/hypertension-prevalence.html March 21, 2021. Accessed September 5, 2023. https://millionhearts.hhs.gov/data-reports/hypertension-prevalence.html

  • 2. Vasan RS, Beiser A, Seshadri S, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: The Framingham Heart Study. JAMA 287(8):1003-1010, 2002. doi:10.1001/jama.287.8.1003

  • 3. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension. 2018 Jun;71(6):e136-e139] [published correction appears in Hypertension. 2018 Sep;72(3):e33]. Hypertension 71(6):1269-1324, 2018. doi:10.1161/HYP.000000000000006

  • 4. 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.

  • 5. Carey RM, Calhoun DA, Bakris GL, et al: Resistant hypertension: Detection, evaluation, and management: A Scientific Statement From the American Heart Association. Hypertension 72:e53–e90, 2018. doi: 10.1161/HYP.0000000000000084

Etiology of Hypertension

Hypertension may be

  • Primary (no specific cause—85% of cases)

  • Secondary (an identified cause)

Primary hypertension

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, stress) seem to affect only people who are genetically susceptible at younger ages; however, in patients > 65 years, high sodium intake is more likely to precipitate hypertension.

Secondary hypertension

Common causes include

Other, much rarer, causes include pheochromocytoma Pheochromocytoma A pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. It causes persistent or paroxysmal hypertension. Diagnosis is by measuring catecholamine... read more , Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more Cushing Syndrome , congenital adrenal hyperplasia Overview of Congenital Adrenal Hyperplasia Congenital adrenal hyperplasia is a group of genetic disorders, each characterized by inadequate synthesis of cortisol, aldosterone, or both. In the most common forms, accumulated hormone precursors... read more , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism , hypothyroidism Hypothyroidism Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more Hypothyroidism (myxedema), primary hyperparathyroidism Hyperparathyroidism Hyperparathyroidism occurs when one or more of the parathyroid glands become overactive, causing elevated serum levels of parathyroid hormone and leading to hypercalcemia. Patients may be asymptomatic... read more , acromegaly Gigantism and Acromegaly Gigantism and acromegaly are syndromes of excessive secretion of growth hormone (hypersomatotropism) that are nearly always due to a pituitary adenoma. Before closure of the epiphyses, the result... read more Gigantism and Acromegaly , coarctation of the aorta Coarctation of the Aorta Coarctation of the aorta is a localized narrowing of the aortic lumen that results in upper-extremity hypertension, left ventricular hypertrophy, and, if severe, malperfusion of the abdominal... read more , and mineralocorticoid excess syndromes other than primary aldosteronism.

Excessive alcohol intake and use of oral contraceptives are common reversible causes of hypertension.

Also, use of sympathomimetics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cocaine, or licorice may contribute to worsening of blood pressure control.

Etiology reference

Pathophysiology of Hypertension

Because blood pressure equals cardiac output (CO) × total peripheral vascular resistance (TPR), pathogenic mechanisms involve

  • Increased CO

  • Increased TPR

  • Both

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 (eg, thyrotoxicosis Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism , arteriovenous fistula Arteriovenous Fistula An arteriovenous fistula is an abnormal communication between an artery and a vein. An arteriovenous fistula may be congenital (usually affecting smaller vessels) or acquired as a result of... read more , aortic regurgitation Aortic Regurgitation Aortic regurgitation (AR) is incompetency of the aortic valve causing backflow from the aorta into the left ventricle during diastole. Causes include valvular degeneration and aortic root dilation... read more Aortic Regurgitation ), particularly when stroke volume is increased, cause isolated systolic hypertension. Some older 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. Glomerular filtration rate (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.

Abnormal sodium transport

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 children who are normotensive but have a parent with hypertension.

Sympathetic nervous system

Sympathetic stimulation increases blood pressure, usually more in patients with elevated BP and hypertension than in patients who are normotensive. 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 patients with hypertension, circulating plasma catecholamine levels during rest are higher than normal.

Renin-angiotensin-aldosterone system

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 angiotensin-converting enzyme (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 [< 3.5 mmol/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, medications 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 Renovascular Hypertension Renovascular hypertension is blood pressure elevation due to partial or complete occlusion of one or more renal arteries or their branches. It is usually asymptomatic unless long-standing. A... read more 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 patients with African ancestry and older patients with hypertension, renin levels tend to be low (1 Pathophysiology references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Pathophysiology references ). Older patients 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.

Vasodilator deficiency

Deficiency of a vasodilator (eg, bradykinin, nitric oxide) rather than excess of a vasoconstrictor (eg, angiotensin, norepinephrine) may cause hypertension. Reductions in nitric oxide occur with aging, and this reduction contributes to salt sensitivity (ie, lesser amounts of salt ingestion will raise BP higher compared to younger people— 2 Pathophysiology references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Pathophysiology references ).

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 salty meal).

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 blood pressure.

Pathology and complications

No pathologic changes occur early in hypertension. Severe or prolonged hypertension damages target organs (primarily the cardiovascular system, brain, and kidneys), increasing risk of

The mechanism involves development of generalized arteriolosclerosis Atherosclerosis Atherosclerosis is characterized by patchy intimal plaques (atheromas) that encroach on the lumen of medium-sized and large arteries. The plaques contain lipids, inflammatory cells, smooth muscle... read more Atherosclerosis 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.

Pathophysiology references

  • 1. Williams SF, Nicholas SB, Vaziri ND, Norris KC. African Americans, hypertension and the renin angiotensin system. World J Cardiol 6(9):878-889, 2014. doi:10.4330/wjc.v6.i9.878

  • 2. Fujiwara N, Osanai T, Kamada T, et al: Study on the relationship between plasma nitrite and nitrate level and salt sensitivity in human hypertension: modulation of nitric oxide synthesis by salt intake. Circulation 101:856–861, 2000.

Symptoms and Signs of 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 (typically defined as systolic blood pressure 180 mm Hg and/or diastolic blood pressure 120 mm Hg) can be asymptomatic (hypertensive urgency). When severe hypertension causes severe cardiovascular, neurologic, renal, and retinal symptoms (eg, symptomatic coronary atherosclerosis, heart failure, hypertensive encephalopathy, renal failure), it is referred to as a hypertensive emergency Hypertensive Emergencies A hypertensive emergency is severe hypertension (often defined as systolic blood pressure (BP) ≥ 180 mm Hg and/or diastolic blood pressure ≥ 120 mm Hg) with signs of damage to target organs... read more .

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 Hypertensive Retinopathy Hypertensive retinopathy is retinal vascular damage caused by hypertension. Signs usually develop late in the disease. Funduscopic examination shows arteriolar constriction, arteriovenous nicking... read more Hypertensive Retinopathy ). Changes are classified (according to the Keith, Wagener, and Barker classification) into 4 groups with increasingly worse prognosis:

  • Grade 1: Constriction of arterioles only

  • Grade 2: Constriction and sclerosis of arterioles

  • Grade 3: Hemorrhages and exudates in addition to vascular changes

  • Grade 4: Papilledema

Diagnosis of Hypertension

  • Multiple measurements of BP to confirm

  • Testing to diagnose causes and complications

Hypertension is diagnosed by sphygmomanometry. History, physical examination, and other tests help identify etiology and determine whether target organs are damaged.

Blood pressure measurement

The blood pressure used for formal diagnosis should be an average of 2 or 3 measurements taken at different times with the patient:

  • Seated in a chair (not examination table) for > 5 minutes, feet on floor, back supported

  • With their limb supported at heart level with no clothing covering the area of cuff placement

  • Having had no exercise, caffeine, or smoking for at least 30 minutes

At the first visit, measure BP in both arms; subsequent measurements should use the arm that gave the higher reading.

A properly sized BP cuff 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, patients with obesity usually require large cuffs. The clinician 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 (1 Diagnosis references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Diagnosis references ).

BP is measured in both arms because BP that is > 15 mm Hg higher in one arm than the other requires evaluation of the upper vasculature.

BP is measured in a thigh (with a much larger cuff) to rule out coarctation of the aorta Coarctation of the Aorta Coarctation of the aorta is a localized narrowing of the aortic lumen that results in upper-extremity hypertension, left ventricular hypertrophy, and, if severe, malperfusion of the abdominal... read more , 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.

Home or ambulatory BP monitoring Holter monitor The standard electrocardiogram (ECG) provides 12 different vector views of the heart’s electrical activity as reflected by electrical potential differences between positive and negative electrodes... read more 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.

History

The history includes the

Social history includes exercise levels and use of tobacco, alcohol, and stimulants (including medications and illicit drugs).

A dietary history focuses on intake of salt and stimulants (eg, tea, coffee, caffeine-containing sodas, energy drinks).

Physical examination

The physical examination includes measurement of height, weight, and waist circumference; funduscopic examination for retinopathy Symptoms and Signs Hypertensive retinopathy is retinal vascular damage caused by hypertension. Signs usually develop late in the disease. Funduscopic examination shows arteriolar constriction, arteriovenous nicking... read more Symptoms and Signs ; 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 years. A unilateral renal artery bruit may be heard in thin patients with renovascular hypertension Renovascular Hypertension Renovascular hypertension is blood pressure elevation due to partial or complete occlusion of one or more renal arteries or their branches. It is usually asymptomatic unless long-standing. A... read more Renovascular Hypertension .

Testing

After hypertension is diagnosed based on blood pressure measurements, testing is needed to

  • Detect target-organ damage

  • Identify cardiovascular risk factors

The more severe the hypertension and the younger the patient, the more extensive is the evaluation. Tests may include

  • Urinalysis and urinary albumin:creatinine ratio; if abnormal, consider renal ultrasonography

  • Lipid panel, complete metabolic panel (including creatinine, potassium, and calcium), fasting plasma glucose

  • ECG

  • Sometimes measurement of thyroid-stimulating hormone levels

  • Sometimes measurement of plasma free metanephrines (to detect pheochromocytoma)

  • Sometimes a sleep study

Depending on results of the examination and initial tests, other tests may be needed.

Renal ultrasonography to evaluate kidney size may provide useful information if urinalysis detects albuminuria (proteinuria), casts, or microhematuria, or if serum creatinine or cystatin C is elevated.

On ECG, a broad, notched P-wave indicates atrial hypertrophy and, although nonspecific, may be one of the earliest signs of hypertensive heart disease. Elevated QRS voltage with or without evidence of ischemia, may occur later and indicates left ventricular hypertrophy (LVH). When LVH is seen on ECG, echocardiography is often done.

Patients with labile, significantly elevated BP and symptoms such as headache, palpitations, tachycardia, excessive perspiration, tremor, and pallor are screened for pheochromocytoma Diagnosis A pheochromocytoma is a catecholamine-secreting tumor of chromaffin cells typically located in the adrenals. It causes persistent or paroxysmal hypertension. Diagnosis is by measuring catecholamine... read more by measuring plasma free metanephrines and for hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism , first by measuring thyroid-stimulating hormone (TSH). A sleep study should also be strongly considered in those whose history suggests sleep apnea.

Patients with symptoms suggesting Cushing syndrome Cushing Syndrome Cushing syndrome is a constellation of clinical abnormalities caused by chronic high blood levels of cortisol or related corticosteroids. Cushing disease is Cushing syndrome that results from... read more Cushing Syndrome , systemic rheumatic diseases, eclampsia Preeclampsia and Eclampsia Preeclampsia is new-onset or worsening of existing hypertension with proteinuria after 20 weeks gestation. Eclampsia is unexplained generalized seizures in patients with preeclampsia. Diagnosis... read more , acute porphyria Acute Porphyrias Acute porphyrias result from deficiency of certain enzymes in the heme biosynthetic pathway, resulting in accumulation of heme precursors that cause intermittent attacks of abdominal pain and... read more , hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism , myxedema Hypothyroidism Hypothyroidism is thyroid hormone deficiency. Symptoms include cold intolerance, fatigue, and weight gain. Signs may include a typical facial appearance, hoarse slow speech, and dry skin. Diagnosis... read more Hypothyroidism , acromegaly Gigantism and Acromegaly Gigantism and acromegaly are syndromes of excessive secretion of growth hormone (hypersomatotropism) that are nearly always due to a pituitary adenoma. Before closure of the epiphyses, the result... read more Gigantism and Acromegaly , or central nervous system (CNS) disorders also require further evaluation.

Diagnosis references

  • 1. Muntner P, Shimbo D, Carey RM, et al: Measurement of blood pressure in humans: A scientific statement from the American Heart Association. Hypertension 73:e35–e66, 2019.

  • 2. Burrello J, Monticone S, Losano I, et al: Prevalence of Hypokalemia and Primary Aldosteronism in 5100 Patients Referred to a Tertiary Hypertension Unit. Hypertension 2020;75(4):1025-1033. doi:10.1161/HYPERTENSIONAHA.119.14063

  • 3. Mulatero P, Stowasser M, Loh KC, et al: Increased diagnosis of primary aldosteronism, including surgically correctable forms, in centers from five continents. J Clin Endocrinol Metab 2004;89(3):1045-1050. doi:10.1210/jc.2003-031337

Treatment of Hypertension

  • Weight loss and exercise

  • Smoking cessation

  • Adequate sleep duration (> 6 hours/night)

  • Diet: Increased fruits and vegetables, decreased salt, limited alcohol

  • Medications: Depending on BP and presence of cardiovascular disease or risk factors

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.

Goal blood pressure for the most patients, including patients with a kidney disorder or diabetes, is

  • BP < 130/80 mm Hg regardless of age up to age 80 years

Lowering BP below 130/80 mm Hg appears to continue to reduce the risk of vascular complications. However, decreasing systolic pressure further also increases the risk of adverse medication 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 (1 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ).

Even older patients, including frail older patients, can tolerate a diastolic BP as low as 60 to 65 mm Hg well and without an increase in cardiovascular events (2, 3 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ). 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 Treatment requires careful medication selection because some antihypertensive medications can harm the fetus.

Lifestyle modifications

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 nonpharmacologic interventions for prevention and treatment of hypertension include the following:

Adequate sleep duration (> 6 hours/night) is also recommended. Short sleep duration (typically defined as < 5 or 6 hours per night in adults, has been associated with hypertension (4 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ). For example, data suggest that optimizing sleep quality and duration (> 6 hours/night) improves blood pressure control in patients with chronic kidney disease (5 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ).

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.

Medications

The decision to treat with medication is based on the BP level and the presence of atherosclerotic cardiovascular disease (ASCVD) or its risk factors (see table ). 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 goal BP, clinicians should strive to optimize adherence before switching or adding medications.

Table

Medication selection is based on several factors, including comorbidities and contraindications. For most patients, when selecting an agent for monotherapy, initial treatment may be with any of the following medication classes:

  • Angiotensin-converting enzyme (ACE) inhibitor

  • Angiotensin II receptor blocker (ARB)

  • Dihydropyridine calcium channel blocker

  • Thiazide diuretic (preferably a thiazide-like diuretic such as chlorthalidone or indapamide)

In addition, some experts recommend that for patients of African ancestry who are candidates for monotherapy, a calcium channel blocker or a thiazide diuretic should be used initially (unless patients also have stage 3 or higher chronic kidney disease). The preference for a calcium channel blocker or a thiazide diuretic in patients of African ancestry is based on evidence from randomized trials showing that these classes of medications have superior efficacy in lowering blood pressure and rates of cardiovascular events than ACE inhibitors or ARBs (6, 7, 8, 9 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ). However, subsequent data suggest that despite the use of this race-based approach, control of hypertension and racial disparities in blood pressure control have not improved (10 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ). Thus, some experts favor an individualized approach to therapeutic selection rather than a race-based approach. In addition, there is substantial variability in blood pressure response within racial groups (11 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ).

When combination therapy with 2 antihypertensive agents is selected, options include either an ACE inhibitor or ARB combined with either a diuretic or a calcium channel blocker. Many combinations are available as single pills, which are preferable to improve patient adherence (12, 13 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ).

If the goal BP is not achieved within 1 month, assess adherence and reinforce the importance of following treatment. If patients are adherent, the dose of the initial medication can be increased or a second medication added (selected from among the medications recommended for initial treatment). Note that an ACE inhibitor and an ARB should not be used together. Therapy is titrated frequently. If target BP cannot be achieved with 2 medications, a third medication from the initial group is added. If such a third medication is not tolerated or is contraindicated, a medication from another class (eg, aldosterone antagonist) can be used. Patients with such difficult to control BP may benefit from consultation with a hypertension specialist.

Table

If initial systolic BP is > 160 mm Hg, 2 medications should be initiated regardless of cardiovascular disease risk. An appropriate combination and dose are determined. For resistant hypertension (BP remains above goal despite use of 3 different antihypertensive medications), 4 or more medications are commonly needed.

Achieving adequate blood pressure control often requires several evaluations and changes in pharmacotherapy. Reluctance to titrate or add medications to control BP must be overcome. Nonadherence to therapy, particularly because lifelong treatment is required, can interfere with adequate BP control. Education, with empathy and support, is essential for success.

Table

Devices and physical interventions

Percutaneous catheter-based radiofrequency ablation of the sympathetic nerves in the renal artery is used in Europe and Australia for resistant hypertension. Several industry-funded sham-controlled studies with different patient populations (eg, those with untreated hypertension [ 14 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ], treated hypertension [ 15 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ], or resistant hypertension [ 16 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ]) have demonstrated statistically and/or clinically significant reductions in systolic blood pressure. However, whether these devices reduce major cardiovascular events remains uncertain. Thus, sympathetic ablation should be considered experimental and used only in centers with extensive experience.

A physical intervention to lower blood pressure 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 designed to stimulate the baroreceptor and, in a dose-dependent manner, lower blood pressure. Long-term follow-up of patients with resistant hypertension who were included in earlier pivotal trials suggests that baroreflex activation therapy maintained its efficacy for persistent reduction of office BP without major safety issues (17 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ). However, the 2017 American College of Cardiology/American Heart Association guidelines concluded that studies have not provided sufficient evidence to recommend the use of these devices in managing resistant hypertension (18 Treatment references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Treatment references ).

Treatment references

  • 1. Gomadam P, Shah A, Qureshi W, et al. Blood pressure indices and cardiovascular disease mortality in persons with or without diabetes mellitus. J Hypertens 36(1):85-92, 2018. doi:10.1097/HJH.0000000000001509

  • 2. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs Standard Blood Pressure Control and Cardiovascular Disease Outcomes in Adults Aged 75 Years: A Randomized Clinical Trial. JAMA 315(24):2673-2682, 2016. doi:10.1001/jama.2016.7050

  • 3. White WB, Wakefield DB, Moscufo N, et al. Effects of Intensive Versus Standard Ambulatory Blood Pressure Control on Cerebrovascular Outcomes in Older People (INFINITY). Circulation 140(20):1626-1635, 2019. doi:10.1161/CIRCULATIONAHA.119.041603

  • 4. Thomas SJ, Calhoun D. Sleep, insomnia, and hypertension: current findings and future directions. J Am Soc Hypertens 11(2):122-129, 2017. doi:10.1016/j.jash.2016.11.008

  • 5. Ali W, Gao G, Bakris GL. Improved Sleep Quality Improves Blood Pressure Control among Patients with Chronic Kidney Disease: A Pilot Study. Am J Nephrol 51(3):249-254, 2020. doi:10.1159/000505895

  • 6. Materson BJ, Reda DJ, Cushman WC, et al. Single-drug therapy for hypertension in men. A comparison of six antihypertensive agents with placebo. The Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents [published correction appears in N Engl J Med 1994 Jun 9;330(23):1689]. N Engl J Med 1993;328(13):914-921. doi:10.1056/NEJM199304013281303

  • 7. Yamal JM, Oparil S, Davis BR, et al. Stroke outcomes among participants randomized to chlorthalidone, amlodipine or lisinopril in ALLHAT. J Am Soc Hypertens 2014;8(11):808-819. doi:10.1016/j.jash.2014.08.003

  • 8. Wright JT Jr, Harris-Haywood S, Pressel S, et al. Clinical outcomes by race in hypertensive patients with and without the metabolic syndrome: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Arch Intern Med 2008;168(2):207-217. doi:10.1001/archinternmed.2007.66

  • 9. Hall WD, Reed JW, Flack JM, Yunis C, Preisser J. Comparison of the efficacy of dihydropyridine calcium channel blockers in African American patients with hypertension. ISHIB Investigators Group. International Society on Hypertension in Blacks. Arch Intern Med 158(18):2029-2034, 1998. doi: 10.1001/archinte.158.18.2029

  • 10. Egan BM, Li J, Sutherland SE, Rakotz MK, Wozniak GD. Hypertension Control in the United States 2009 to 2018: Factors Underlying Falling Control Rates During 2015 to 2018 Across Age- and Race-Ethnicity Groups. Hypertension 78(3):578-587, 2021. doi:10.1161/HYPERTENSIONAHA.120.16418

  • 11. Mokwe E, Ohmit SE, Nasser SA, et al. Determinants of blood pressure response to quinapril in black and white hypertensive patients: the Quinapril Titration Interval Management Evaluation trial. Hypertension 2004;43(6):1202-1207. doi:10.1161/01.HYP.0000127924.67353.86

  • 12. Parati G, Kjeldsen S, Coca A, Cushman WC, Wang J. Adherence to Single-Pill Versus Free-Equivalent Combination Therapy in Hypertension: A Systematic Review and Meta-Analysis. Hypertension 77(2):692-705, 2021. doi:10.1161/HYPERTENSIONAHA.120.15781

  • 13. Williams B, Mancia G, Spiering W, et al. 2018 Practice Guidelines for the management of arterial hypertension of the European Society of Hypertension and the European Society of Cardiology: ESH/ESC Task Force for the Management of Arterial Hypertension [published correction appears in J Hypertens 2019 Feb;37(2):456]. J Hypertens 8;36(12):2284-2309, 2018. doi:10.1097/HJH.0000000000001961

  • 14. Böhm M, Kario K, Kandzari DE, et al. Efficacy of catheter-based renal denervation in the absence of antihypertensive medications (SPYRAL HTN-OFF MED Pivotal): a multicentre, randomised, sham-controlled trial. Lancet 395(10234):1444-1451, 2020. doi:10.1016/S0140-6736(20)30554-7

  • 15. Mahfoud F, Kandzari DE, Kario K, et al. Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial. Lancet 399(10333):1401-1410, 2022. doi:10.1016/S0140-6736(22)00455-X

  • 16. Bhatt DL, Vaduganathan M, Kandzari DE, et al. Long-term outcomes after catheter-based renal artery denervation for resistant hypertension: final follow-up of the randomised SYMPLICITY HTN-3 Trial. Lancet 400(10361):1405-1416, 2022. doi:10.1016/S0140-6736(22)01787-1

  • 17. de Leeuw PW, Bisognano JD, Bakris GL, Nadim MK, Haller H, Kroon AA, DEBuT-T and Rheos Trial Investigators: Sustained reduction of blood pressure with baroreceptor activation therapy: Results of the 6-year open follow-up. Hypertension 69:836–843, 2017.

  • 18. Whelton PK, Carey RM, Aronow WS, et al: 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 71(6):e13–e115, 2018. doi: 10.1161/HYP.0000000000000065

Prognosis for Hypertension

The higher the blood pressure and the more severe the retinal changes and other evidence of target-organ involvement, the worse the prognosis. Systolic BP predicts fatal and nonfatal cardiovascular events better than diastolic BP (1, 2 Prognosis references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Prognosis references ).

Without treatment, 1-year 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 [ 3 Prognosis references Hypertension is sustained elevation of resting systolic blood pressure (≥ 130 mm Hg), diastolic blood pressure (≥ 80 mm Hg), or both. Hypertension with no known cause (primary; formerly, essential... read more Prognosis references ]).

Coronary artery disease is the most common cause of death among treated patients. Ischemic or hemorrhagic stroke is a common consequence of inadequately treated hypertension. However, effective control of hypertension prevents most complications and prolongs life.

Prognosis references

Key Points

  • Only about 50% of patients in the United States with hypertension receive treatment, and about one quarter of those patients have adequate blood pressure (BP) control.

  • Most hypertension is primary; only 5 to 15% is secondary to another disorder (eg, primary aldosteronism , renal parenchymal disease).

  • Severe or prolonged hypertension damages the cardiovascular system, brain, and kidneys, increasing risk of myocardial infarction, stroke, and chronic kidney disease.

  • Hypertension is usually asymptomatic until complications develop in target organs.

  • When hypertension is newly diagnosed, do a urinalysis, spot urine albumin:creatinine ratio, blood tests (creatinine, potassium, sodium, calcium, fasting plasma glucose, lipid panel, and often thyroid-stimulating hormone), and ECG.

  • Reduce BP to < 130/80 mm Hg for everyone up to age 80 years, 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 medications (including thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and dihydropyridine calcium channel blockers).

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

Drugs Mentioned In This Article

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Thalitone
Lozol
Katerzia, Norliqva, Norvasc
Prinivil, QBRELIS, Zestril
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