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 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 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 , 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 , 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 (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 , 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 causes of curable hypertension. Use of sympathomimetics, nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, cocaine, or licorice commonly contributes to worsening of blood pressure control.

Although hypertension is common in patients with diabetes, diabetes is not considered a cause.

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 (2 Etiology 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 ).

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 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:

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 , 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. 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.

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— 1 Pathophysiology reference 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 ).

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.

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 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 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.

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 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 (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 ).

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.

Anxiety is by far the most common cause of hypertensive urgency Hypertensive urgencies A hypertensive emergency is severe hypertension with signs of damage to target organs (primarily the brain, cardiovascular system, and kidneys). Diagnosis is by blood pressure (BP) measurement... read more as well as pain. Moreover, referral to a psychologist or use of an anxiety alleviating medication to aid in managing the anxiety has proven helpful in many cases to reduce the frequency of hypertensive urgency (2 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 ).

The history includes the known duration of hypertension and previously recorded BP levels; any history or symptoms of coronary artery disease Overview of Coronary Artery Disease Coronary artery disease (CAD) involves impairment of blood flow through the coronary arteries, most commonly by atheromas. Clinical presentations include silent ischemia, angina pectoris, acute... read more , heart failure Heart Failure (HF) Heart failure (HF) is a syndrome of ventricular dysfunction. Left ventricular (LV) failure causes shortness of breath and fatigue, and right ventricular (RV) failure causes peripheral and abdominal... read more , sleep apnea or loud snoring; history or symptoms of other relevant coexisting disorders (eg, stroke Overview of Stroke Strokes are a heterogeneous group of disorders involving sudden, focal interruption of cerebral blood flow that causes neurologic deficit. Strokes can be Ischemic (80%), typically resulting... read more , renal dysfunction, peripheral arterial disease Peripheral Arterial Disease Peripheral arterial disease (PAD) is atherosclerosis of the extremities (virtually always lower) causing ischemia. Mild PAD may be asymptomatic or cause intermittent claudication; severe PAD... read more , dyslipidemia Dyslipidemia Dyslipidemia is elevation of plasma cholesterol, triglycerides (TGs), or both, or a low high-density lipoprotein cholesterol (HDL-C) level that contributes to the development of atherosclerosis... read more , diabetes Diabetes Mellitus (DM) Diabetes mellitus is impaired insulin secretion and variable degrees of peripheral insulin resistance leading to hyperglycemia. Early symptoms are related to hyperglycemia and include polydipsia... read more , gout Gout Gout is a disorder caused by hyperuricemia (serum urate > 6.8 mg/dL [> 0.4 mmol/L]) that results in the precipitation of monosodium urate crystals in and around joints, most often causing recurrent... read more ); 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 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 ; 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 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 .

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

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

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), cylindruria, or microhematuria, or if serum creatinine is elevated (≥ 1.4 mg/dL [≥ 124 micromole/L] in men; ≥ 1.2 mg/dL [≥ 106 micromole/L] in women).

Patients with hypokalemia unrelated to diuretic use are evaluated for primary aldosteronism Primary Aldosteronism Primary aldosteronism is aldosteronism caused by autonomous production of aldosterone by the adrenal cortex (due to hyperplasia, adenoma, or carcinoma). Symptoms and signs include episodic weakness... read more and high salt intake by measuring plasma aldosterone levels and plasma renin activity. Primary aldosteronism was previously thought to be present in only about 1% of patients with resistant hypertension. Studies have shown that about 10 to 20% of patients with resistant hypertension have primary aldosteronism as the cause (3–5 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 ).

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.

If 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 is suspected 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 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. A sleep study should also be strongly considered in these patients and 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 , a connective tissue disorder, 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 , 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 , 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 , or central nervous system (CNS) disorders are evaluated.

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:

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 Medications for Hypertension Drugs for Hypertension A number of drug classes are effective for initial and subsequent management of hypertension: Adrenergic modifiers Angiotensin-converting enzyme (ACE) inhibitors Angiotensin II receptor blockers... read more .)

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 Initial Approach to Management of High Blood Pressure 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 medications.

Medication selection is based on several factors. When one medication is given initially, for patients who do not have African ancestry, including those with diabetes, initial treatment may be with either an ACE inhibitor, angiotensin II receptor blocker, calcium channel blocker, or a thiazide-type diuretic (chlorthalidone or indapamide). For patients with African ancestry, including those with diabetes, a calcium channel blocker or a thiazide-type diuretic is recommended initially unless patients also have stage 3 or higher chronic kidney disease. In patients with African ancestry and stage 3 chronic kidney disease, an ACE inhibitor or angiotensin II receptor blocker is appropriate.

When 2 medications 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 Hypertensive Emergencies A hypertensive emergency is severe hypertension with signs of damage to target organs (primarily the brain, cardiovascular system, and kidneys). Diagnosis is by blood pressure (BP) measurement... read more require immediate blood pressure reduction with parenteral antihypertensives.

Some antihypertensives are contraindicated in certain disorders (eg, beta-blockers in asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more ) or are indicated particularly for hypertensive patients with certain disorders (eg, calcium channel blockers for angina pectoris Angina Pectoris Angina pectoris is a clinical syndrome of precordial discomfort or pressure due to transient myocardial ischemia without infarction. It is typically precipitated by exertion or psychologic stress... read more , ACE inhibitors or angiotensin II receptor blockers for diabetes with proteinuria Diabetic Nephropathy In patients with diabetes mellitus, years of poorly controlled hyperglycemia lead to multiple, primarily vascular, complications that affect small vessels (microvascular), large vessels (macrovascular)... read more —see tables Initial Choice of Antihypertensive Drug Class Initial Choice of Antihypertensive Drug Class and Antihypertensives for Patients With Co-existing Conditions Antihypertensives for Patients With Co-existing Conditions ).

If the target 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 angiotensin II receptor blocker 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 available (eg, for patients with African ancestry) or tolerated, a medication 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.

If initial systolic BP is > 160 mm Hg, 2 medications should be initiated regardless of lifestyle. An appropriate combination and dose are determined; many combinations are available as single tablets, which make adherence easier and are preferred. 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 drug therapy. Reluctance to titrate or add medications to control BP 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.

Percutaneous catheter-based radiofrequency ablation of the sympathetic nerves in the renal artery is used in Europe and Australia for resistant hypertension. Although initial studies appeared promising, studies that incorporated a sham ablation procedure in the control arm failed to show a benefit from radiofrequency ablation (1, 2 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 ). Thus, sympathetic ablation should be considered experimental and is done only in centers with extensive experience.

A 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 blood pressure. A long-term analysis of a statistically powered study showed that baroreflex activation therapy maintained its efficacy for persistent reduction of office BP in patients with resistant hypertension without major safety issues (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 ). 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 (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 ).