Etiology & Classification
A. Primary Essential Hypertension
“Essential hypertension” is the term applied to the 95% of hypertensive patients in which elevated blood pressure results from complex interactions between multiple genetic and environmental factors. The proportion regarded as “essential” will diminish with improved detection of clearly defined secondary causes and with better understanding of pathophysiology. Essential hypertension occurs in 10–15% of white adults and 20–30% of black adults in the United States. The onset is usually between ages 25 and 50 years; it is uncommon before age 20 years. The best understood endogenous and environmental determinants of blood pressure include overactivation of the sympathetic nervous and renin–angiotensin–aldosterone systems, blunting of the pressure-natriuresis relationship, variation in cardiovascular and renal development, and elevated intracellular sodium and calcium levels.
1. Sympathetic nervous system hyperactivity
This is most apparent in younger persons with hypertension, who may exhibit tachycardia and an elevated cardiac output. However, correlations between plasma catecholamines and blood pressure are poor. Insensitivity of the baroreflexes may play a role in the genesis of adrenergic hyperactivity, and polymorphisms in the phosducin gene have been linked to increased blood pressure responses to stress.
2. Abnormal cardiovascular or kidney development
The normal cardiovascular system develops so that elasticity of the great arteries is matched to the resistance in the periphery to optimize large vessel pressure waves. In this way, myocardial oxygen consumption is minimized and coronary flow maximized. Elevated blood pressure later in life could arise from abnormal development of aortic elasticity or reduced development of the microvascular network. This has been postulated as the sequence of events in low birth weight infants, who have an increased risk of hypertension developing in adulthood. Another hypothesis proposes that the association between low birth weight and hypertension arises from reduced nephron number.
3. Renin–angiotensin system activity
Renin, a proteolytic enzyme, is secreted by cells surrounding glomerular afferent arterioles in response to a number of stimuli, including reduced renal perfusion pressure, diminished intravascular volume, circulating catecholamines, increased sympathetic nervous system activity, increased arteriolar stretch, and hypokalemia. Renin acts on angiotensinogen to cleave off the ten-amino-acid peptide angiotensin I. This peptide is then acted upon by angiotensin-converting enzyme (ACE) to create the eight-amino-acid peptide angiotensin II, a potent vasoconstrictor and stimulant of aldosterone secretion. Despite the role of renin in the regulation of blood pressure, it probably does not play a central role in the pathogenesis of most primary (essential) hypertension; only 10% of patients have high renin activity, whereas 60% have normal levels, and 30% have low levels. Black persons with hypertension and older patients tend to have lower plasma renin activity, which may be associated with expanded intravascular volume.
According to the classic Guyton hypothesis, increased salt intake triggers an increase in blood pressure that in turn promotes increased natriuresis, thereby bringing blood pressure back toward basal levels. Salt has long been implicated in the genesis of hypertension, and so-called salt-sensitive hypertension probably arises from a defect in this self-regulating pressure-natriuresis feedback loop.
5. Intracellular sodium and calcium
Intracellular Na+ is elevated in primary (essential) hypertension. An increase in intracellular Na+ may lead to increased intracellular Ca2+ concentration as a result of facilitated exchange and might explain the increase in vascular smooth muscle tone that is characteristic of established hypertension.
Exacerbating factors include obesity, sleep apnea, increased salt intake, excessive alcohol use, cigarette smoking, polycythemia, nonsteroidal anti-inflammatory (NSAID) therapy, and low potassium intake. Obesity is associated with an increase in intravascular volume, elevated cardiac output, activation of the renin-angiotensin system, and, probably, increased sympathetic outflow. Lifestyle-driven weight reduction lowers blood pressure modestly, but the dramatic weight reduction following bariatric surgery results in improved blood pressure in most patients, and actual remission of hypertension in 20–40% of cases. In patients with sleep apnea, treatment with continuous positive airway pressure (CPAP) has been associated with improvements in blood pressure. Increased salt intake probably elevates blood pressure in some individuals so dietary salt restriction is recommended in patients with hypertension. Excessive use of alcohol also raises blood pressure, perhaps by increasing plasma catecholamines. Hypertension can be difficult to control in patients who consume more than 40 g of ethanol (two drinks) daily or drink in “binges.” Cigarette smoking raises blood pressure by increasing plasma norepinephrine. Although the long-term effect of smoking on blood pressure is less clear, the synergistic effects of smoking and high blood pressure on cardiovascular risk are well documented. The relationship of exercise to hypertension is variable. Aerobic exercise lowers blood pressure in previously sedentary individuals, but increasingly strenuous exercise in already active subjects has less effect. The relationship between stress and hypertension is not established. Polycythemia, whether primary, drug-induced, or due to diminished plasma volume, increases blood viscosity and may raise blood pressure. NSAIDs produce increases in blood pressure averaging 5 mm Hg and are best avoided in patients with borderline or elevated blood pressures. Low potassium intake is associated with higher blood pressure in some patients; an intake of 90 mmol/day is recommended.
The complex of abnormalities termed the “metabolic syndrome” (upper body obesity, insulin resistance, and hypertriglyceridemia) is associated with both the development of hypertension and an increased risk of adverse cardiovascular outcomes. Affected patients usually also have low high-density lipoprotein (HDL) cholesterol levels and elevated catecholamines and inflammatory markers such as C-reactive protein.
B. Secondary Hypertension
Approximately 5% of patients have hypertension secondary to identifiable specific causes (Table 11–1). Secondary hypertension should be suspected in patients in whom hypertension develops at an early age or after the age of 50 years, and in those previously well controlled who become refractory to treatment. Hypertension resistant to three medications is another clue, although multiple medications are usually required to control hypertension in persons with diabetes. Secondary causes include genetic syndromes; kidney disease; renal vascular disease; primary hyperaldosteronism; Cushing syndrome; pheochromocytoma; coarctation of the aorta and hypertension associated with pregnancy, estrogen use, hypercalcemia, and medications.
Table 11–1.Identifiable causes of hypertension. |Favorite Table|Download (.pdf) Table 11–1. Identifiable causes of hypertension.
Drug-induced or drug-related
Chronic kidney disease
Long-term corticosteroid therapy and Cushing syndrome
Coarctation of the aorta
Thyroid or parathyroid disease
Hypertension can be caused by mutations in single genes, inherited on a Mendelian basis. Although rare, these conditions provide important insight into blood pressure regulation and possibly the genetic basis of essential hypertension. Glucocorticoid remediable aldosteronism is an autosomal dominant cause of early-onset hypertension with normal or high aldosterone and low renin levels. It is caused by the formation of a chimeric gene encoding both the enzyme responsible for the synthesis of aldosterone (transcriptionally regulated by angiotensin II) and an enzyme responsible for synthesis of cortisol (transcriptionally regulated by ACTH). As a consequence, aldosterone synthesis becomes driven by ACTH, which can be suppressed by exogenous cortisol. In the syndrome of apparent mineralocorticoid excess, early-onset hypertension with hypokalemic metabolic alkalosis is inherited on an autosomal recessive basis. Although plasma renin is low and plasma aldosterone level is very low in these patients, aldosterone antagonists are effective in controlling hypertension. This disease is caused by loss of the enzyme 11beta-hydroxysteroid dehydrogenase, which normally metabolizes cortisol and thus protects the otherwise “promiscuous” mineralocorticoid receptor in the distal nephron from inappropriate glucocorticoid activation. Similarly, glycyrrhetinic acid, found in licorice, causes increased blood pressure through inhibition of 11beta-hydroxysteroid dehydrogenase. The syndrome of hypertension exacerbated in pregnancy is inherited as an autosomal dominant trait. In these patients, a mutation in the mineralocorticoid receptor makes it abnormally responsive to progesterone and, paradoxically, to spironolactone. Liddle syndrome is an autosomal dominant condition characterized by early-onset hypertension, hypokalemic alkalosis, low renin, and low aldosterone levels. This is caused by a mutation that results in constitutive activation of the epithelial sodium channel of the distal nephron, with resultant unregulated sodium reabsorption and volume expansion.
Renal parenchymal disease is the most common cause of secondary hypertension and is related to increased intravascular volume and increased activity of the renin–angiotensin–aldosterone system. Increased sympathetic nerve activity may also contribute.
3. Renal vascular hypertension
Renal artery stenosis is present in 1–2% of hypertensive patients. The most common cause is atherosclerosis, but fibromuscular dysplasia should be suspected in women under 50 years of age. The mechanisms of hypertension relate to excessive renin release due to reduction in renal perfusion pressure, while attenuation of pressure natriuresis contributes to hypertension in patients with a single kidney or bilateral lesions. Activation of the renal sympathetic nerves may also be important.
Renal vascular hypertension should be suspected in the following circumstances: (1) if the documented onset is before age 20 or after age 50 years, (2) hypertension is resistant to three or more drugs, (3) if there are epigastric or renal artery bruits, (4) if there is atherosclerotic disease of the aorta or peripheral arteries (15–25% of patients with symptomatic lower limb atherosclerotic vascular disease have renal artery stenosis), (5) if there is an abrupt increase (more than 25%) in the level of serum creatinine after administration of angiotensin-converting enzyme (ACE) inhibitors, or (6) if episodes of pulmonary edema are associated with abrupt surges in blood pressure. (See Renal Artery Stenosis, Chapter 22.) There is no ideal screening test for renal vascular hypertension. If suspicion is sufficiently high and endovascular intervention is a viable option, renal arteriography, the definitive diagnostic test, is the best approach. Renal arteriography is not recommended as a routine adjunct to coronary studies. Where suspicion is moderate to low, noninvasive angiography using magnetic resonance (MR) or CT are reasonable approaches. Doppler sonography has good specificity but lacks sensitivity and is operator dependent. Gadolinium, a contrast agent used in MR angiography, is contraindicated in patients with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min because it might precipitate nephrogenic systemic fibrosis in patients with advanced kidney disease. In young patients with fibromuscular disease, angioplasty is very effective, but there is controversy regarding the best approach to the treatment of atheromatous renal artery stenosis. Correction of the stenosis in selected patients might reduce the number of medications required to control blood pressure and could protect kidney function, but the extent of preexisting parenchymal damage to the affected and contralateral kidney has a significant influence on both blood pressure and kidney function outcomes following revascularization. Angioplasty and stenting may prove to be superior to medical therapy in a subset of patients, but identifying this group remains a challenge. A reasonable approach advocates medical therapy as long as hypertension can be well controlled and there is no progression of kidney disease. The addition of a statin should be considered. Endovascular intervention might be considered in patients with uncontrollable hypertension, progressive kidney disease, or episodic pulmonary edema attributable to the lesion. Angioplasty might also be warranted when progression of stenosis is either demonstrated or is predicted by a constellation of risk factors, including systolic blood pressure greater than 160 mm Hg, advanced age, diabetes mellitus, or high-grade stenosis (more than 60%) at the time of diagnosis. However, multiple studies have failed to identify an overall advantage of stenting over medical management in patients with atherosclerotic renal artery stenosis. The CORAL study utilized a distal capture device to prevent embolization into the kidney, but the conclusion was once again that stenting is not superior to medical therapy (incorporating a statin) in the management of atherosclerotic renal artery stenosis. Although drugs modulating the renin-angiotensin system have improved the success rate of medical therapy of hypertension due to renal artery stenosis, they may trigger hypotension and (usually reversible) kidney dysfunction in individuals with bilateral disease.
4. Primary hyperaldosteronism
Hyperaldosteronism should be considered in people with resistant hypertension, blood pressures consistently greater than 150/100 mm Hg, hypokalemia (irrespective of diuretic exposure), adrenal incidentaloma, and in those with a family history of hyperaldosteronism. The initial screening step is the simultaneous measurement of aldosterone and renin in blood in a morning sample collected after 30 minutes quietly seated. Hyperaldosteronism is suggested when the plasma aldosterone concentration is elevated (normal: 1–16 ng/dL) in association with suppression of plasma renin activity (normal: 1–2.5 ng/mL/h). However, the plasma aldosterone/renin ratio (normal less than 30) is not highly specific as a screening test. This is because “bottoming out” of renin assays leads to exponential increases in the plasma aldosterone/renin ratio even when aldosterone levels are normal. Hence, an elevated plasma aldosterone/renin ratio should probably not be taken as evidence of hyperaldosteronism unless the aldosterone level is actually supranormal.
During the workup for hyperaldosteronism, an initial plasma aldosterone/renin ratio can be measured while the patient continues taking usual medications. If under these circumstances the ratio proves negative or equivocal, medications that alter renin and aldosterone levels, including ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, beta-blockers, and clonidine, should be discontinued for 2 weeks before repeating the plasma aldosterone/renin ratio; spironolactone and eplerenone should be held for 4 weeks. Slow-release verapamil and alpha-receptor blockers can be used to control blood pressure during this drug washout period. Patients with a plasma aldosterone level greater than 16 ng/dL and an aldosterone/renin ratio of 30 or more might require further evaluation for primary hyperaldosteronism.
The lesion responsible for hyperaldosteronism is an adrenal adenoma or bilateral adrenal hyperplasia. Approximately 50% of aldosterone-secreting adenomas arise as a consequence of somatic mutations in genes encoding glomerulosa cell membrane ion transporters, with resultant elevation of intracellular calcium concentration.
Hypertension occurs in about 80% of patients with spontaneous Cushing syndrome. Excess glucocorticoid may act through salt and water retention (via mineralocorticoid effects), increased angiotensinogen levels, or permissive effects in the regulation of vascular tone.
Diagnosis and treatment of Cushing syndrome are discussed in Chapter 26.
Pheochromocytomas are uncommon; they are probably found in less than 0.1% of all patients with hypertension and in approximately two individuals per million population. However, autopsy studies indicate that pheochromocytomas are very often undiagnosed in life. The blood pressure elevation caused by the catecholamine excess results mainly from alpha-receptor–mediated vasoconstriction of arterioles, with a contribution from beta-1-receptor-mediated increases in cardiac output and renin release. Chronic vasoconstriction of the arterial and venous beds leads to a reduction in plasma volume and predisposes to postural hypotension. Glucose intolerance develops in some patients. Hypertensive crisis in pheochromocytoma may be precipitated by a variety of drugs, including tricyclic antidepressants, antidopaminergic agents, metoclopramide, and naloxone. The diagnosis and treatment of pheochromocytoma are discussed in Chapter 26.
7. Coarctation of the aorta
This uncommon cause of hypertension is discussed in Chapter 10. Evidence of radial-femoral delay should be sought in all younger patients with hypertension.
8. Hypertension associated with pregnancy
Hypertension occurring de novo or worsening during pregnancy, including preeclampsia and eclampsia, is one of the most common causes of maternal and fetal morbidity and mortality (see Chapter 19). Autoantibodies with the potential to activate the angiotensin II type 1 receptor have been causally implicated in preeclampsia, in resistant hypertension, and in progressive systemic sclerosis.
A small increase in blood pressure occurs in most women taking oral contraceptives. A more significant increase above 140/90 mm Hg is noted in about 5% of women, mostly in obese individuals older than age 35 who have been treated for more than 5 years. This is caused by increased hepatic synthesis of angiotensinogen. Postmenopausal estrogen does not generally cause hypertension but rather maintains endothelium-mediated vasodilation.
10. Other causes of secondary hypertension
Hypertension has been associated with hypercalcemia, acromegaly, hyperthyroidism, hypothyroidism, baroreceptor denervation, compression of the rostral ventrolateral medulla, and increased intracranial pressure. A number of medications may cause or exacerbate hypertension—most importantly cyclosporine, tacrolimus, angiogenesis inhibitors, and erythrocyte-stimulating agents (such as erythropoietin. Decongestants, NSAIDs, cocaine and alcohol should also be considered. Over-the-counter products should not be overlooked, eg, a dietary supplement marketed to enhance libido was found to contain yohimbine, an alpha-2–antagonist, which can produce severe rebound hypertension in patients taking clonidine.
Referral to a hypertension specialist should be considered in cases of severe, resistant or early-/late-onset hypertension or when secondary hypertension is suggested by screening.
et al. Cardiovascular effects of bariatric surgery. Nat Rev Cardiol. 2016 Dec;13(12):730–43.
RM. Diagnosing and managing primary aldosteronism in hypertensive patients: a case-based approach. Curr Cardiol Rep. 2016 Oct;18(10):97.
et al. Primary aldosteronism: diagnosis and management. Am J Med Sci. 2016 Oct;352(4):391–8.
et al. Paradigm shifts in atherosclerotic renovascular disease: where are we now? J Am Soc Nephrol. 2015 Sep;26(9):2074–80.
et al. An update on novel mechanisms of primary aldosteronism. J Endocrinol. 2015 Feb;224(2):R63–77.
Complications of Untreated Hypertension
Elevated blood pressure results in structural and functional changes in the vasculature and heart. Most of the adverse outcomes in hypertension are associated with thrombosis rather than bleeding, possibly because increased vascular shear stress converts the normally anticoagulant endothelium to a prothrombotic state. The excess morbidity and mortality related to hypertension approximately doubles for each 6 mm Hg increase in diastolic blood pressure. However, target-organ damage varies markedly between individuals with similar levels of office hypertension; home and ambulatory pressures are superior to office readings in the prediction of end-organ damage.
A. Hypertensive Cardiovascular Disease
Cardiac complications are the major causes of morbidity and mortality in primary (essential) hypertension. For any level of blood pressure, left ventricular hypertrophy is associated with incremental cardiovascular risk in association with heart failure (through systolic or diastolic dysfunction), ventricular arrhythmias, myocardial ischemia, and sudden death (eFigure 11–1).
Left ventricular hypertrophy with left (superior) axis deviation. The mean frontal plane QRS axis is –45 degrees, suggesting the possibility of coexisting left anterior fascicular block. The R wave of 24 mm in aVL, however, strongly suggests (but does not prove) the presence of left ventricular hypertrophy. ST-segment depression and T wave inversion are present in aVL, and T wave inversion is present in V5–6. Precordial lead voltage criteria for left ventricular hypertrophy are not met. This may be due to the superior axis, as a result of which the lead axes of V5–6 are far removed from the mean QRS vector. Left ventricular hypertrophy was confirmed at autopsy examination. (Reproduced, with permission, from Goldschlager N, Goldman MJ. Principles of Clinical Electrocardiography, 13th ed. Originally published by Appleton & Lange. Copyright © 1989 by The McGraw-Hill Companies, Inc.)
The occurrence of heart failure is reduced by 50% with antihypertensive therapy. Hypertensive left ventricular hypertrophy regresses with therapy and is most closely related to the degree of systolic blood pressure reduction. Diuretics have produced equal or greater reductions of left ventricular mass when compared with other drug classes. Conventional beta-blockers are less effective in reducing left ventricular hypertrophy but play a specific role in patients with established coronary artery disease or impaired left ventricular function.
B. Hypertensive Cerebrovascular Disease and Dementia
Hypertension is the major predisposing cause of hemorrhagic and ischemic stroke. Cerebrovascular complications are more closely correlated with systolic than diastolic blood pressure. The incidence of these complications is markedly reduced by antihypertensive therapy. Preceding hypertension is associated with a higher incidence of subsequent dementia of both vascular and Alzheimer types. Home and ambulatory blood pressure may be a better predictor of cognitive decline than office readings in older people. Effective blood pressure control may reduce the risk of development of cognitive dysfunction later in life, but once cerebral small-vessel disease is established, low blood pressure might exacerbate this problem.
C. Hypertensive Kidney Disease
Chronic hypertension is associated with injury to vascular, glomerular, and tubulointerstitial compartments within the kidney, accounting for about 25% of end-stage kidney disease. Nephrosclerosis is particularly prevalent in blacks, in whom susceptibility is linked to APOL1 mutations and hypertension results from kidney disease rather than causing it.
Hypertension is a contributing factor in many patients with dissection of the aorta. Its diagnosis and treatment are discussed in Chapter 12.
E. Atherosclerotic Complications
Most Americans with hypertension die of complications of atherosclerosis, but antihypertensive therapy seems to have a lesser impact on atherosclerotic complications compared with the other effects of treatment outlined above. Prevention of cardiovascular outcomes related to atherosclerosis probably requires control of multiple risk factors, of which hypertension is only one.
et al. Can the treatment of hypertension in the middle-aged prevent dementia in the elderly? High Blood Press Cardiovasc Prev. 2016 Jun;23(2):97–104.
et al. Hypertension-attributed nephropathy: what’s in a name? Nat Rev Nephrol. 2016 Jan;12(1):27–36.
et al. Hypertensive nephropathy. Moving from classic to emerging pathogenetic mechanisms. J Hypertens. 2017 Feb;35(2):205–12.
The clinical and laboratory findings are mainly referable to involvement of the target organs: heart, brain, kidneys, eyes, and peripheral arteries.
Mild to moderate primary (essential) hypertension is largely asymptomatic for many years. The most frequent symptom, headache, is also very nonspecific. Accelerated hypertension is associated with somnolence, confusion, visual disturbances, and nausea and vomiting (hypertensive encephalopathy).
Hypertension in patients with pheochromocytomas that secrete predominantly norepinephrine is usually sustained but may be episodic. The typical attack lasts from minutes to hours and is associated with headache, anxiety, palpitation, profuse perspiration, pallor, tremor, and nausea and vomiting. Blood pressure is markedly elevated, and angina or acute pulmonary edema may occur. In primary aldosteronism, patients may have muscular weakness, polyuria, and nocturia due to hypokalemia; malignant hypertension is rare. Chronic hypertension often leads to left ventricular hypertrophy and diastolic dysfunction, which can present with exertional and paroxysmal nocturnal dyspnea. Cerebral involvement causes stroke due to thrombosis or hemorrhage from microaneurysms of small penetrating intracranial arteries. Hypertensive encephalopathy is probably caused by acute capillary congestion and exudation with cerebral edema, which is reversible.
Like symptoms, physical findings depend on the cause of hypertension, its duration and severity, and the degree of effect on target organs.
Blood pressure is taken in both arms and, if lower extremity pulses are diminished or delayed, in the legs to exclude coarctation of the aorta. An orthostatic drop of at least 20/10 mm Hg is often present in pheochromocytoma. Older patients may have falsely elevated readings by sphygmomanometry because of noncompressible vessels. This may be suspected in the presence of Osler sign—a palpable brachial or radial artery when the cuff is inflated above systolic pressure. Occasionally, it may be necessary to make direct measurements of intra-arterial pressure, especially in patients with apparent severe hypertension who do not tolerate therapy.
Narrowing of arterial diameter to less than 50% of venous diameter, copper or silver wire appearance, exudates, hemorrhages, or hypertensive retinopathy (eFigure 11–2) are associated with a worse prognosis. The typical changes of hypertensive retinopathy are shown in Figure 11–2.
Keith-Wagener retinopathy stage IV. This may include the same retinal changes as stage III, but in addition there is disk swelling. (Reproduced, with permission, from Vaughan DG, Asbury T, Riordan-Eva P [editors]. General Ophthalmology, 15th ed. Originally published by Appleton & Lange. Copyright © 1999 by The McGraw-Hill Companies, Inc.)
Mild papilledema. The disk margins are blurred superiorly and inferiorly by the thickened layer of nerve fibers entering the disk. (Reproduced, with permission, from Vaughan D, Asbury T, Riordan-Eva P. General Ophthalmology, 15th ed. Originally published by Appleton & Lange. Copyright © 1999 by The McGraw-Hill Companies, Inc.)
Severe acute hypertensive retinopathy with disk edema, intraretinal hemorrhages, nerve fiber layer infarcts (cotton-wool spots) and arteriovenous nicking. Retinal arteries show irregular narrowing. (Used, with permission, from Courtney Francis, MD, Department of Ophthalmology, University of Washington School of Medicine.)
A left ventricular heave indicates severe or long-standing hypertrophy. Aortic regurgitation may be auscultated in up to 5% of patients, and hemodynamically insignificant aortic regurgitation can be detected by Doppler echocardiography in 10–20%. A presystolic (S4) gallop due to decreased compliance of the left ventricle is quite common in patients in sinus rhythm (AUDIO 11–1).
Fourth heart sound. The fourth heart sound immediately precedes the first heart sound and is heard best over the left sternal border. (Reproduced, with permission, from Cardionics, Inc., Houston, Texas.)
Radial-femoral delay suggests coarctation of the aorta; loss of peripheral pulses occurs due to atherosclerosis, less commonly aortic dissection, and rarely Takayasu arteritis, all of which can involve the renal arteries.
Recommended testing includes the following: hemoglobin; urinalysis and serum creatinine; fasting blood sugar level (hypertension is a risk factor for the development of diabetes, and hyperglycemia can be a presenting feature of pheochromocytoma); plasma lipids (necessary to calculate cardiovascular risk and as a modifiable risk factor); serum uric acid (hyperuricemia is a relative contraindication to diuretic therapy); and serum electrolytes.
D. Electrocardiography and Chest Radiographs
Electrocardiographic criteria are highly specific but not very sensitive for left ventricular hypertrophy (see eFigure 11–1). The “strain” pattern of ST–T wave changes is a sign of more advanced disease and is associated with a poor prognosis. A chest radiograph is not necessary in the workup for uncomplicated hypertension.
The primary role of echocardiography should be to evaluate patients with clinical symptoms or signs of cardiac disease.
Additional diagnostic studies are indicated only if the clinical presentation or routine tests suggest secondary or complicated hypertension. These may include 24-hour urine free cortisol, urine or plasma metanephrines, and plasma aldosterone and renin concentrations to screen for endocrine causes of hypertension. Renal ultrasound will detect structural changes (such as polycystic kidneys, asymmetry, and hydronephrosis) as well as echogenicity and reduced cortical volume, which are reliable indicators of advanced chronic kidney disease. Evaluation for renal artery stenosis should be undertaken in concert with subspecialist consultation.
Since most hypertension is essential or primary, few studies are necessary beyond those listed above. If conventional therapy is unsuccessful or if secondary hypertension is suspected, further studies and perhaps referral to a hypertension specialist are indicated.
Lifestyle modification may have an impact on morbidity and mortality. A diet rich in fruits, vegetables, and low-fat dairy foods and low in saturated and total fats (DASH diet) has been shown to lower blood pressure. Additional measures, listed in Table 11–2, can prevent or mitigate hypertension or its cardiovascular consequences.
Table 11–2.Lifestyle modifications to manage hypertension.1 |Favorite Table|Download (.pdf) Table 11–2. Lifestyle modifications to manage hypertension.1
|Modification ||Recommendation ||Approximate Systolic BP Reduction, Range |
|Weight reduction ||Maintain normal body weight (BMI, 18.5–24.9) ||5–20 mm Hg/10 kg weight loss |
|Adopt DASH eating plan ||Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced content of saturated fat and total fat ||8–14 mm Hg |
|Dietary sodium reduction ||Reduce dietary sodium intake to no more than 100 mEq/day (2.4 g sodium or 6 g sodium chloride) ||2–8 mm Hg |
|Physical activity ||Engage in regular aerobic physical activity such as brisk walking (at least 30 minutes per day, most days of the week) ||4–9 mm Hg |
|Moderation of alcohol consumption ||Limit consumption to no more than two drinks per day (1 oz or 30 mL ethanol [eg, 24 oz beer, 10 oz wine, or 3 oz 80-proof whiskey]) in most men and no more than one drink per day in women and lighter-weight persons ||2–4 mm Hg |
All patients with high-normal or elevated blood pressures, those who have a family history of cardiovascular complications of hypertension, and those who have multiple coronary risk factors should be counseled about nonpharmacologic approaches to lowering blood pressure. Approaches of proved but modest value include weight reduction, reduced alcohol consumption, and, in some patients, reduced salt intake (less than 5 g salt or 2 g sodium). Gradually increasing activity levels should be encouraged in previously sedentary patients, but strenuous exercise training programs in already active individuals may have less benefit. Alternative approaches that may be modestly effective include relaxation techniques and biofeedback. Calcium and potassium supplements have been advocated, but their ability to lower blood pressure is limited. Smoking cessation will reduce cardiovascular risk. Overall, the effects of lifestyle modification on blood pressure are modest.
et al. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med. 2010 Jan 25;170(2):126–35.
et al; American Heart Association Professional Education Committee of the Council for High Blood Pressure Research, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Council on Nutrition, Physical Activity. Beyond medications and diet: alternative approaches to lowering blood pressure: a scientific statement from the American Heart Association. Hypertension. 2013 Jun;61(6):1360–83.
et al. JAMA patient page. Dietary guidelines for Americans—eat less salt. JAMA. 2016 Aug 16;316(7):782.
et al. Non-pharmacological aspects of blood pressure management: what are the data? Kidney Int. 2011 May;79(10):1061–70.
Who Should Be Treated With Medications?
Treatment should ideally be offered to all persons in whom blood pressure reduction, irrespective of initial blood pressure levels, will appreciably reduce overall cardiovascular risk with an acceptably low rate of medication-associated adverse effects. Outcomes data indicate that patients with office-based blood pressure measurements that consistently exceed 160/100 mm Hg (stage 2 hypertension) will benefit from antihypertensive therapy irrespective of cardiovascular risk. Several international guidelines suggest that treatment thresholds evaluated by home-based measurements should be lower, perhaps 150/95 mm Hg using home blood pressure or daytime ambulatory measurements. However, prospective outcomes data for treatment based on measurements taken outside the clinic are lacking. As outlined in Figure 11–3, treatment should be offered at lower thresholds in those with elevated cardiovascular risk or in the presence of existing end-organ damage. The corollary of this is that treatment thresholds might reasonably be set higher for young people with extremely low cardiovascular risk. The Canadian guidelines suggest a threshold of greater than 160/100 mm Hg in low-risk individuals, but specialist referral is advised in such cases to avoid underestimating risk (a real concern in younger people) and to exclude secondary causes. By contrast, the Eighth US Joint National Committee (JNC 8) document, which makes no reference to modes of blood pressure measurement or consideration of cardiovascular risk, recommends initiating antihypertensive therapy at blood pressures above 140/90 mm Hg in those younger than 60 years of age and above 150/90 mm Hg in people older than 60 years of age. Simple guidelines such as those offered by the JNC 8 report may be effective in population blood pressure control, but other experts have argued that a more nuanced approach will reduce the number of people receiving unnecessary treatment and allow for a more efficient use of limited health care resources.
British Hypertension Society algorithm for diagnosis and treatment of hypertension, incorporating total cardiovascular risk in deciding which “prehypertensive” patients to treat. Cardiovascular disease (CVD) risk chart available at qrisk.org. (Reproduced, with permission, from guidelines for management of hypertension: report of the Fourth Working Party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens. 2004 Mar;18(3):139–85.)
Some experts have suggested that early treatment, perhaps in the prehypertensive phase, might modify the natural history of hypertension, ultimately leading to diminished requirements for multiple antihypertensive agents and, perhaps, a much more dramatic effect on cardiovascular risk than can be attained with initiation of treatment once hypertension is established. However, outcomes-based studies addressing early treatment in prehypertension are lacking and the public health consequences of recommendations to treat prehypertension would be enormous. Forty-eight percent of all Americans have hypertension or prehypertension, and much higher proportions fit these categories in a typical family medicine population. The situation is a little clearer in nonhypertensive patients at elevated cardiovascular risk, in whom the HOPE and PROGRESS trials indicated improved outcomes with antihypertensive medication (ACE inhibitor and ACE inhibitor plus diuretic, respectively).
Since evaluation of total cardiovascular risk (Table 11–3) is important in deciding who to treat with antihypertensive medications, risk calculators are becoming essential clinical tools. QRisk2 is a reliable and regularly updated online calculator. Free smartphone applications are also available to estimate coronary heart disease risk. In general, a 20% total cardiovascular risk (which includes stroke) is equivalent to a 15% coronary heart disease risk.
Table 11–3.Cardiovascular risk factors. |Favorite Table|Download (.pdf) Table 11–3. Cardiovascular risk factors.
Major risk factors
Obesity (BMI ≥ 30)1
Microalbuminuria or estimated GFR < 60 mL/min
Age (> 55 years for men, > 65 years for women)
Family history of premature cardiovascular disease (men < 55 years or women < 65 years)
Left ventricular hypertrophy
Angina or prior myocardial infarction
Prior coronary revascularization
Stroke or transient ischemic attack
Chronic kidney disease
Peripheral arterial disease
The blood pressure target in most patients with hypertension is less than 140/90 mm Hg. Observational studies suggest that there does not seem to be a blood pressure level below which decrements in risk taper off. However, this may not be true with respect to pharmacologically modulated blood pressure. Overenthusiastic treatment may have adverse consequences in certain settings. There is an association between lower blood pressure and cognitive decline in elderly patients subjected to intensification of antihypertensive treatment later in life. Antihypertensive treatment in those who are both very elderly and frail may paradoxically increase mortality. Excessive lowering of diastolic pressure, perhaps below 70 mm Hg, should be avoided in patients with coronary artery disease.
The SPRINT study suggests that outcomes may improve in nondiabetic patients with elevated cardiovascular risk when treatment lowers systolic pressures to less than 120 mm Hg compared to less than 140 mm Hg. In response to this study, Hypertension Canada’s guidelines for 2016 suggest a systolic blood pressure goal of less than 120 mm Hg in nondiabetic patients sharing the risk features of the SPRINT population, including cardiovascular disease, chronic kidney disease, and cardiovascular risk exceeding 15%. It is important to note that the SPRINT study was the first such study to use automated office blood pressure measurements, which have been shown to read 16/7 mm Hg lower than manual office readings. Hence, in generalizing the findings of the SPRINT study to the practice setting, blood pressure should be measured with the automated protocol and not by conventional manual measurements.
In the ACCORD study of diabetic patients, treatment of systolic pressures to below 130–135 mm Hg significantly increased the risk of serious adverse effects with no additional gain in terms of heart, kidney, or retinal disease. On the other hand, reducing systolic pressure below 130 mm Hg in this study seemed to further lower the risk of stroke, so lower targets might be justified in diabetic patients at high risk for cerebrovascular events.
Similarly, in the SPS3 trial in patients recovering from a lacunar stroke, treating the systolic blood pressure to less than 130 mm Hg (mean systolic blood pressure of 127 mm Hg among treated versus mean systolic blood pressure 138 mm Hg among untreated patients) probably reduced the risk of recurrent stroke (and with an acceptably low rate of adverse effects from treatment).
Large-scale trials in hypertension have focused on discrete end points occurring over relatively short intervals, thereby placing the emphasis on the prevention of catastrophic events in advanced disease. There is an ongoing shift in emphasis in viewing hypertension in the context of lifelong cardiovascular risk. Accordingly, treatment of persons with hypertension should focus on comprehensive risk reduction with more careful consideration of the possible long-term adverse effects of antihypertensive medications, which include the metabolic derangements linked to conventional beta-blockers and thiazide diuretics.
Statins should be more widely used. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) showed that statins can significantly improve outcomes in persons with hypertension (with modestly elevated background cardiovascular risk) whose total cholesterol is less than 250 mg/dL (6.5 mmol/L). Notably, the effect of statins appeared to be synergistic with calcium channel blocker/ACE inhibitor regimens but not beta-blocker/diuretic regimens. The British Hypertension Society guidelines recommend that statins be offered as secondary prevention to patients whose total cholesterol exceeds 135 mg/dL (3.5 mmol/L) if they have documented coronary artery disease or a history of ischemic stroke. In addition, statins should be considered as primary prevention in patients with longstanding type 2 diabetes or in those with type 2 diabetes who are older than age 50 years, and perhaps in all persons with type 2 diabetes. Low-dose aspirin (81 mg/day) is likely to be beneficial in patients older than age 50 with either target-organ damage or elevated total cardiovascular risk (greater than 20–30%). Care should be taken to ensure that blood pressure is controlled to the recommended levels before starting aspirin to minimize the risk of intracranial hemorrhage.
Table 11–4 summarizes the blood pressure treatment thresholds and targets published in national guidelines from the United States, Canada, and United Kingdom.
Table 11–4.Treatment thresholds and goals in hypertension management. |Favorite Table|Download (.pdf) Table 11–4. Treatment thresholds and goals in hypertension management.
|Population ||Age ||When to Treat ||Target Blood Pressure |
|General ||< 60 years || |
JNC 8: > 140/90 mm Hg
> 160/100 mm Hg
> 140/90 mm Hg, if high CV risk2
|< 140/90 mm Hg3 |
| ||> 60 years || |
JNC 8: > 150/90 mm Hg
> 160/100 mm Hg
> 140/90 mm Hg, if high CV risk2
JNC 8: < 150/90 mm Hg4
Others: < 140/90 mm Hg3
| ||> 80 years || |
JNC 8: > 150/90 mm Hg
Others:1 > 160/100 mm Hg
|< 150/90 mm Hg |
|Diabetes or chronic kidney disease ||All ages ||> 140/90 mm Hg || |
< 140/90 mm Hg
KDIGO: < 130/80 if proteinuria
ACCORD Study Group; Cushman
et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575–85.
et al; CHEP Guidelines Task Force. Hypertension Canada’s 2016 Canadian Hypertension Education Program guidelines for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. 2016 May;32(5):569–88.
et al; ASCOT Steering Committee Members. Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J. 2006 Dec;27(24):2982–8.
SPRINT Research Group; Wright
et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015 Nov 26;373(22):2103–16.