Secondary Hypertension
Secondary hypertension affects a small but significant number of the hypertensive population and, unlike primary hypertension, is a potentially curable condition. The determinant for workup is dependent on the index of suspicion elicited during patient examination and treatment. Specific testing is available and must be balanced depending on the risk and cost of the workup and treatment with the benefits obtained if the secondary cause is eliminated.
A thorough search for secondary causes (Table) is not cost-effective in most patients with hypertension but becomes critically important in two circumstances: (1) when there is a compelling finding on the initial evaluation and (2) when the hypertensive process is so severe that it either is refractory to intensive multiple-drug therapy or requires hospitalization.
GUIDE TO EVALUATION OF SECONDARY HYPERTENSION
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Suspected Diagnosis |
Clinical Clues |
Diagnostic Testing |
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Renal parenchymal hypertension |
Estimated GFR <60 mL/min/1.73 m2 |
Renal ultrasonography |
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Urine albumin-to-creatinine ratio ≥30 mg/g |
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Renovascular disease |
New elevation in serum creatinine, marked elevation in serum creatinine with initiation of ACEI or ARB, refractory hypertension, flash pulmonary edema, abdominal bruit |
Magnetic resonance or CT angiography, invasive angiography |
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Coarctation of the aorta |
Arm pulses > leg pulses, arm BP > leg BP, chest bruits, rib notching on chest radiography |
Magnetic resonance imaging, aortography |
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Primary aldosteronism |
Hypokalemia, refractory hypertension |
Plasma renin and aldosterone, 24-hour urine potassium, 24-hour urine aldosterone and potassium after salt loading, adrenal CT, adrenal vein sampling |
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Cushing’s syndrome |
Truncal obesity, wide and blanching purple striae, muscle weakness |
Plasma cortisol, urine cortisol after dexamethasone, adrenal CT |
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Pheochromocytoma |
Headaches, paroxysmal hypertension, palpitations, perspiration, and pallor; diabetes |
Plasma metanephrine and normetanephrine, 24-hour urine catechols, adrenal CT |
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Obstructive sleep apnea |
Loud snoring, daytime somnolence, obesity, large neck |
Sleep study |
Modified from
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ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; BP = blood pressure; CT = computed tomography; GFR = glomerular filtra-tion rate. |
Renal Parenchymal Hypertension
Chronic kidney disease is the most common cause of secondary hypertension. Hypertension is present in more than 85% of patients with chronic kidney disease and is a major factor causing their increased cardiovascular morbidity and mortality. The mechanisms causing the hypertension include an expanded plasma volume and peripheral vasoconstriction; the peripheral vasoconstriction is caused by both activation of vasoconstrictor pathways (renin-angiotensin and sympathetic nervous systems) and inhibition of vasodilator pathways (nitric oxide).
Most forms of renal disease are associated with hypertension. The prevalence of hypertension in chronic renal parenchymal disease varies with each. Hypertension is most evident with glomerular diseases, in which 70% to 80% of patients are affected, including diabetic nephropathy (DN), membranous glomerulonephritis (MGN), membranoproliferative glomerulonephritis (MPGN) and focal segmental glomerulonephritis (FSGN). Minimal change nephropathy (MCN) is a notable exception. Tubulointerstitial disorders such as analgesic nephropathy, chronic interstitial nephritis (CIN), medullary cystic diseases, and chronic reflux nephropathies are less commonly associated with hypertension.
Renal insufficiency should be considered when there is proteinuria by dipstick or when the serum creatinine level is greater than 1.2 mg/dL in hypertensive women or greater than 1.4 mg/dL in hypertensive men. The diagnosis and staging of chronic kidney disease are done by a simple spot urine collection and standard blood chemistries revealing an estimated glomerular filtration rate below 60 mL/min/1.73 m2 or albuminuria, defined as a urine albumin–to–urine creatinine ratio of 30 mg/g (equivalent to excretion of 30 mg of albumin per 24 hours) or higher. Several calculators of glomerular filtration rate are readily available on the Internet (www.nephron.com; www.newtech.kidney.org).
In patients with mild (stage 2: glomerular filtration rate of 60 to 90 mL/min/1.73 m2) or moderate (stage 3: glomerular filtration rate of 30 to 60 mL/min/1.73 m2) chronic kidney disease, stringent blood pressure control is imperative both to slow the progression to end-stage renal disease and to reduce the excessive cardiovascular risk. In patients with severe chronic kidney disease, hypertension often becomes difficult to treat and may require either (1) intensive medical treatment with loop diuretics, potent vasodilators (e.g., minoxidil), high-dose β-adrenergic blockers, and central sympatholytics or (2) initiation of chronic hemodialysis as the only effective way to reduce plasma volume. In chronic hemodialysis patients, the challenge is to control interdialytic hypertension without exacerbating dialysis-induced hypotension. The gross annual mortality rate in the hemodialysis population is 25%; half of this excessive mortality is caused by cardiovascular events that are related, at least in part, to hypertension.
Renovascular Hypertension
Unilateral or bilateral renal artery stenosis is present in less than 2% of hypertensive patients in a general medical practice but up to 30% of patients referred to a hypertension specialist for refractory hypertension.
The main causes of renal artery stenosis are atherosclerosis (85% of cases), typically in older persons with other clinical manifestations of systemic atherosclerosis, and fibromuscular dysplasia (15% of cases), typically in women between the ages of 15 and 50 years. Unilateral renal artery stenosis leads to underperfusion of the juxtaglomerular cells, thereby producing renin-dependent hypertension even though the contralateral kidney is able to maintaiormal blood volume. In contrast, bilateral renal artery stenosis (or unilateral stenosis with a solitary kidney) constitutes a potentially reversible cause of progressive renal failure and volume-dependent hypertension.
The following clinical clues increase the suspicion of renovascular hypertension: any hospitalization for urgent or emergent hypertension; recurrent “flash” pulmonary edema; recent worsening of long-standing, previously well controlled hypertension; severe hypertension in a young adult or after the age of 50 years; precipitous and progressive worsening of renal function in response to angiotensin-converting enzyme (ACE) inhibition or angiotensin II receptor blockade; unilateral small kidney by any radiographic study; extensive peripheral arteriosclerosis; and a flank bruit.
The diagnosis of fibromuscular dysplasia in a young woman with recent-onset hypertension is readily supported by noninvasive testing with magnetic resonance or spiral computed tomographic angiography showing the classic “string of beads” appearance of a renal artery (Figure). Once the diagnosis is confirmed with invasive angiography, balloon angioplasty is the treatment of choice, with complete cure of hypertension in 40% of patients, improved blood pressure control in almost all patients, and a restenosis rate of only 10%. Medical therapy with an ACE inhibitor also may be effective, but the risks of teratogenicity must be considered in women of childbearing age.
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The classic “string of beads” lesion of fibromuscular dysplasia before (A) and after PTRA (B) |
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In contrast, the approach to the older patient with generalized atherosclerosis and renal artery stenosis is not straightforward and must be highly individualized.
Primary hypertension and renovascular hypertension frequently coexist in older persons, and angiographic documentation of renal artery stenosis does not prove that the lesion is an important and reversible cause of the hypertension. For this reason, angioplasty improves hypertension in less than 30% of patients, and complete cures are rare; surgical revascularization is often reserved for patients undergoing simultaneous aortic reconstruction.
In the absence of definitive data from randomized trials, revascularization should be considered for medically refractory hypertension, progressive renal failure with medical therapy, and bilateral renal artery stenosis or stenosis of a solitary functioning kidney.
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Atherosclerotic RAS before and after stenting |
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Hypertension due to obstruction of a renal artery, renovascular hypertension, is a potentially curable form of hypertension. The mechanism of hypertension is generally related to activation of the renin-angiotensin system. Two groups of patients are at risk for this disorder: older arteriosclerotic patients who have a plaque obstructing the renal artery, frequently at its origin, and patients with fibromuscular dysplasia. Although fibromuscular dysplasia may occur at any age, it has a strong predilection for young Caucasian women. The prevalence in females is eightfold that in males. There are several histologic variants of fibromuscular dysplasia, including medial fibroplasia, perimedial fibroplasia, medial hyperplasia, and intimal fibroplasia. Medial fibroplasia is the most common variant and accounts for approximately two-thirds of patients. The lesions of fibromuscular dysplasia are frequently bilateral, and in contrast to atherosclerotic renovascular disease, tend to affect more distal portions of the renal artery.
In addition to the age and gender of the patient, several clues from the history and physical examination suggest a diagnosis of renovascularhypertension. Patients should first be evaluated for evidence of atherosclerotic vascular disease. Although response to antihypertensive therapy does not exclude the diagnosis, severe or refractory hypertension, recent loss of hypertension control or recent onset of moderately severe hypertension, and unexplained deterioration of renal function or deterioration of renal function associated with an ACE inhibitor should raise the possibility of renovascular hypertension. Approximately 50% of patients with renovascular hypertension have an abdominal or flank bruit, and the bruit is more likely to be hemodynamically significant if it lateralizes or extends throughout systole into diastole.
If blood pressure is adequately controlled with a simple antihypertensive regimen and renal function remains stable, there may be little impetus to pursue an evaluation for renal artery stenosis, particularly in an older patient with atherosclerotic disease and comorbid conditions. Patients with long-standing hypertension, advanced renal insufficiency, or diabetes mellitus are less likely to benefit from renal vascular repair. The most effective medical therapies include an ACE inhibitor or an angiotensin II receptor blocker; however, these agents decrease glomerular filtration rate in the stenotic kidney owing to efferent renal arteriolar dilation. In the presence of bilateral renal artery stenosis or renal artery stenosis to a solitary kidney, progressive renal insufficiency may result from the use of these agents. Importantly, the renal insufficiency is generally reversible following discontinuation of the offending drug.
If renal artery stenosis is suspected, and if the clinical condition warrants an intervention such as percutaneous transluminal renal angioplasty (PTRA), placement of a vascular endoprosthesis (stent), or surgical renal revascularization, imaging studies should be the next step in the evaluation. As a screening test, renal blood flow may be evaluated with a radionuclide [131I]-orthoiodohippurate (OIH) scan or glomerular filtration rate may be evaluated with [99mTc]-diethylenetriamine pentaacetic acid (DTPA) scan, before and after a single dose of captopril (or other ACE inhibitor). The following are consistent with a positive study: (1) decreased relative uptake by the involved kidney, which contributes <40% of total renal function; (2) delayed uptake on the affected side; or (3) delayed washout on the affected side. In patients with normal, or near-normal, renal function, a normal captopril renogram essentially excludes functionally significant renal artery stenosis; however its usefulness is limited in patients with renal insufficiency (creatinine clearance < 20 mL/min) or bilateral renal artery stenosis. Additional imaging studies are indicated if the scan is positive. Doppler ultrasound of the renal arteries produces reliable estimates of renal blood flow velocity and offers the opportunity to track a lesion over time. Positive studies are usually confirmed at angiography, whereas false-negative results occur frequently, particularly in obese patients. Gadolinium-contrast magnetic resonance angiography offers clear images of the proximal renal artery but may miss distal lesions. An advantage is the opportunity to image the renal arteries with an agent that is not nephrotoxic. Contrast arteriography remains the “gold standard” for evaluation and identification of renal artery lesions. Potential risks include nephrotoxicity, particularly in patients with diabetes mellitus or preexisting renal insufficiency.
Some degree of renal artery obstruction may be observed in almost 50% of patients with atherosclerotic disease, and there are several approaches for evaluating the functional significance of such a lesion to predict the effect of vascular repair on blood pressure control and renal function. Each approach has varying degrees of sensitivity and specificity, and no single test is sufficiently reliable to determine a causal relationship between a renal artery lesion and hypertension. On angiography, the presence of collateral vessels to the ischemic kidney suggests a functionally significant lesion. A lateralizing renal vein renin ratio (ratio > 1.5 of affected side/contralateral side) has a 90% predictive value for a lesion that would respond to vascular repair; however, the false-negative rate for blood pressure control is 50–60%. Measurement of the pressure gradient across a renal artery lesion does not reliably predict the response to vascular repair.
In the final analysis, a decision concerning vascular repair vs. medical therapy and the type of repair procedure should be individualized for each patient. Patients with fibromuscular disease have more favorable outcomes than patients with atherosclerotic lesions, presumably owing to their younger age, shorter duration of hypertension, and less systemic disease. Because of its low risk-versus-benefit ratio and high success rate (improvement or cure of hypertension in 90% of patients and restenosis rate of 10%), PTRA is the initial treatment of choice for these patients. Surgical revascularization may be undertaken if PTRA is unsuccessful or if a branch lesion is present. In atherosclerotic patients, vascular repair should be considered if blood pressure cannot be adequately controlled with medical therapy or if renal function deteriorates. Surgery may be the preferred initial approach for younger atherosclerotic patients without comorbid conditions; however, for most atherosclerotic patients, depending on the location of the lesion, the initial approach may be PTRA and/or stenting. Surgical revascularization may be indicated if these approaches are unsuccessful, if the vascular lesion is not amenable to PTRA or stenting, or if concomitant aortic surgery is required, e.g., to repair an aneurysm.
Young W. N Engl J Med 2007;356:601-610
Mineralocorticoid-Induced Hypertension Due to Primary Aldosteronism
The most common causes of primary aldosteronism are a unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia.
Aldosteroma
Young W. N Engl J Med 2007;356:601-610
Young W. N Engl J Med 2007;356:601-610
Young W. N Engl J Med 2007;356:601-610
Pheochromocytoma (Panel A), Benign Cortical Adenoma (Panel B), and Adrenocortical Carcinoma (Panel C)
Because aldosterone is the principal ligand for the mineralocorticoid receptor in the distal nephron, excessive aldosterone production causes excessive renal Na+-K+ exchange, often resulting in hypokalemia. The diagnosis should always be suspected when hypertension is accompanied by either unprovoked hypokalemia (serum potassium concentration below 3.5 mmol/L in the absence of diuretic therapy) or a tendency to develop excessive hypokalemia during diuretic therapy (serum potassium concentration below 3.0 mmol/L). However, more than one third of patients do not have hypokalemia on initial presentation, and the diagnosis should also be considered in any patient with resistant hypertension. Laparoscopic surgery and mineralocorticoid receptor blockade with eplerenone constitute highly effective therapeutic options that target the disease-causing mechanism with a favorable risk-to-benefit ratio.
Excess aldosterone production due to primary aldosteronism is a potentially curable form of hypertension. In patients with primary aldosteronism, increased aldosterone production is independent of the renin-angiotensin system, and the consequences are sodium retention, hypertension, hypokalemia, and low PRA. The reported prevalence of this disorder varies from <2% to ~15% of hypertensive individuals. In part, this variation is related to the intensity of screening and to the criteria for establishing the diagnosis.
History and physical examination provide little information about the diagnosis. The age at the time of diagnosis is generally in the third through fifth decades. Hypertension is usually mild to moderate but occasionally may be severe; primary aldosteronism should be considered in all patients with refractory hypertension. Hypertension in these patients may be associated with glucose intolerance. Most patients are asymptomatic, although, infrequently, polyuria, polydypsia, paresthesias, or muscle weakness may be present as a consequence of hypokalemic alkalosis. The simplest screening test is measurement of serum potassium concentration. In a hypertensive patient with unprovoked hypokalemia (i.e., unrelated to diuretics, vomiting, or diarrhea), the prevalence of primary aldosteronism approaches 40–50%. In patients on diuretics, serum potassium <3.1 mmol/L (<3.1 meq/L) also raises the possibility of primary aldosteronism; however, serum potassium is an insensitive and nonspecific screening test. On initial presentation, serum potassium is normal in ~25% of patients subsequently found to have an aldosterone-producing adenoma, and higher percentages of patients with other etiologies of primary aldosteronism are not hypokalemic. Additionally, hypokalemic hypertension may be a consequence of secondary aldosteronism, other mineralocorticoid- and glucocorticoid-induced hypertensive disorders, and pheochromocytoma.
The ratio of plasma aldosterone to plasma renin activity (PA/PRA) is a useful screening test. These measurements are preferably obtained in ambulatory patients in the morning. A ratio >30:1 in conjunction with a plasma aldosterone concentration > 555 pmol/L (>20 ng/dL) reportedly has a sensitivity of 90% and a specificity of 91% for an aldosterone-producing adenoma. In a Mayo Clinic series, an aldosterone-producing adenoma was subsequently surgically confirmed in >90% of hypertensive patients with a PA/PRA ratio 20 and a plasma aldosterone concentration 415 pmol/L (15 ng/dL). There are, however, several caveats to interpreting the ratio. The cutoff for a “high” ratio is laboratory- and assay-dependent. Although some antihypertensive agents may affect the ratio (e.g., aldosterone antagonists, angiotensin receptor antagonists, and ACE inhibitors may increase renin; aldosterone antagonists may increase aldosterone), the ratio has been reported to be useful as a screening test in measurements obtained with patients taking their usual antihypertensive medications. A high ratio in the absence of an elevated plasma aldosterone level is considerably less specific for primary aldosteronism since many patients with essential hypertension have low renin levels in this setting, particularly African Americans and elderly patients. In patients with renal insufficiency, the ratio may also be elevated because of decreased aldosterone clearance. In patients with an elevated PA/PRA ratio, the diagnosis of primary aldosteronism can be confirmed by demonstrating failure to suppress plasma aldosterone to <277 pmol/L (<10 ng/dL) after IV infusion of
Several adrenal abnormalities may culminate in the syndrome of primary aldosteronism, and appropriate therapy depends on the specific etiology. Some 60–70% of patients have an aldosterone-producing adrenal adenoma. The tumor is almost always unilateral, and most measure <
Adrenal CT or MRI should be carried out in all patients diagnosed with primary aldosteronism. High-resolution CT may identify tumors as small as -[I131]iodomethyl-19-norcholesterol after dexamethasone suppression (0.5 mg every 6 h for 7 days); however, this technique has decreased sensitivity for adenomas <
Hypertension is generally responsive to surgery in patients with adenoma but not in patients with bilateral adrenal hyperplasia. Unilateral adrenalectomy, often done via a laparoscopic approach, is curative in 40–70% of patients with an adenoma. Surgery should be undertaken after blood pressure has been controlled and hypokalemia corrected. Transient hypoaldosteronism may occur for up to 3 months postoperatively, resulting in hyperkalemia. Potassium should be monitored during this time, and hyperkalemia should be treated with potassium-wasting diuretics and with fludrocortisone, if needed. Patients with bilateral hyperplasia should be treated medically. The drug regimen for these patients, as well as for patients with an adenoma who are poor surgical candidates, should include an aldosterone antagonist and, if necessary, other potassium-sparing diuretics.
Glucocorticoid-remediable hyperaldosteronism is a rare, monogenic autosomal dominant disorder characterized by moderate to severe hypertension, often at an early age. Hypokalemia is usually mild or absent. Normally, angiotensin II stimulates aldosterone production by the adrenal zona glomerulosa, whereas ACTH stimulates cortisol production in the zona fasciculata. Owing to a chimeric gene on chromosome 8, ACTH also regulates aldosterone secretion by the zona fasciculata in patients with glucocorticoid-remediable hyperaldosteronism. The consequence is overproduction in the zona fasciculata of both aldosterone and hybrid steroids (18-hydroxycortisol and 18-oxocortisol) due to oxidation of cortisol. The diagnosis may be established by urine excretion rates of these hybrid steroids that are twenty to thirty times normal or by direct genetic testing. Therapeutically, suppression of ACTH with low-dose glucocorticoids corrects the hyperaldosteronism, hypertension, and hypokalemia. Spironolactone is also a therapeutic option.
Mendelian Forms of Mineralocorticoid-Induced Hypertension
A number of rare forms of monogenic hypertension have been identified (Table).
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These disorders may be recognized by their characteristic phenotypes, and in many instances the diagnosis may be confirmed by genetic analysis. Several inherited defects in adrenal steroid biosynthesis and metabolism result in mineralocorticoid-induced hypertension and hypokalemia. In patients with a 17-hydroxylase deficiency, synthesis of sex hormones and cortisol is decreased (Fig. 241-3). Consequently, these individuals do not mature sexually; males may present with pseudohermaphroditism and females with primary amenorrhea and absent secondary sexual characteristics. Because cortisol-induced negative feedback on pituitary ACTH production is diminished, ACTH-stimulated adrenal steroid synthesis proximal to the enzymatic block is increased. Hypertension and hypokalemia are consequences of increased synthesis of mineralocorticoids proximal to the enzymatic block, particularly desoxycorticosterone. Increased steroid production and, hence, hypertension may be treated with low-dose glucocorticoids. An 11-hydroxylase deficiency results in a salt-retaining adrenogenital syndrome, occurring in -hydroxysteroid dehydrogenase deficiency have an impaired capacity to metabolize cortisol to its inactive metabolite, cortisone, and hypertension is related to activation of mineralocorticoid receptors by cortisol. This defect may be inherited or acquired, due to licorice-containing glyccherizic acid. This same substance is present in the paste of several brands of chewing tobacco. The defect in Liddle’s syndrome results from constitutive activation of amiloride-sensitive epithelial sodium channels (ENaC) on the distal renal tubule, resulting in excess sodium reabsorption; the syndrome is ameliorated by amiloride. Hypertension exacerbated in pregnancy is due to activation of the mineralocorticoid receptor by progesterone. Approximately 20% of pheochromocytomas are familial and may be associated with distinctive phenotypes.
Adrenal enzymatic defects
Almost all the rare mendelian forms of hypertension are mineralocorticoid induced and involve excessive activation of the epithelial Na+ channel (ENaC), the final common pathway for reabsorption of sodium from the distal nephron (Fig. 66-9). Thus, salt-dependent hypertension can be caused both by gain-of-function mutations of ENaC or the mineralocorticoid receptor and by increased production or decreased clearance of mineralocorticoid receptor ligands, which are aldosterone, deoxycorticosterone, and cortisol.
Glucocorticoid-Remediable Aldosteronism
Fewer than 100 cases of glucocorticoid-remediable aldosteronism have been reported, but many additional cases probably go unreported or are undetected or misdiagnosed as bilateral adrenal hyperplasia. Inherited as an autosomal dominant mutation, glucocorticoid-remediable aldosteronism mimics an aldosterone-producing adenoma by causing severe mineralocorticoid-induced hypertension with hypokalemia, elevated plasma aldosterone, and suppressed plasma renin activity.
In the normal adrenal gland, angiotensin II acts on the enzyme aldosterone synthase in the zona glomerulosa to drive production of aldosterone; adrenocorticotropic hormone (ACTH) causes transcriptional activation of the enzyme 11β-hydroxylase in the zona fasciculata to drive production of cortisol. Glucocorticoid-remediable aldosteronism is caused by a gene duplication arising by unequal crossing over between the genes encoding aldosterone synthase and 11β-hydroxylase. The resulting chimeric gene encodes a hybrid protein that has aldosterone synthase activity, is expressed “ectopically” in the zona fasciculata, and is regulated entirely by ACTH rather than by angiotensin II. Thus, aldosterone production becomes inappropriately linked to cortisol production. In the attempt to maintain the appropriate production of normal levels of cortisol, aldosterone is constantly produced, resulting in volume-dependent hypertension. Although the expanded plasma volume suppresses plasma renin activity and thus angiotensin II, the reduced angiotensin II cannot downregulate aldosterone production.
The clinical clue to the diagnosis is that the hypertension is familial and discovered before the age of 20 years. In contrast, primary aldosteronism is sporadic and usually discovered between the ages of 30 and 60 years. The diagnosis of glucocorticoid-remediable aldosteronism is confirmed by Southern blot analysis for the chimeric gene, a test available at no cost through the International Registry for Glucocorticoid-Remediable Aldosteronism (www.bwh.partners.org/gra). By suppressing ACTH and thus aldosterone secretion from the zona fasciculata, low-dose dexamethasone completely reverses the biochemical abnormalities in glucocorticoid-remediable aldosteronism and is the recommended therapy.
Hypertension Caused by Deoxycorticosterone
The rare but distinctive hypertensive syndromes caused by deoxycorticosterone include those due to congenital deficiency of either 11β-hydroxylase or 17α-hydroxylase. In both cases, decreased production of cortisol reduces feedback inhibition on ACTH, which drives overproduction of deoxycorticosterone (a potent mineralocorticoid). These patients typically present to the pediatrician with hypertension plus abnormal sexual development.
Hypertension Caused by Cortisol
Cortisol is a mineralocorticoid as well as a glucocorticoid, so both excessive production of cortisol and defective cortisol metabolism cause hypertension plus hypokalemia. Normally, the enzyme 11β-hydroxysteroid dehydrogenase type 2 converts cortisol to cortisone, which cannot bind the mineralocorticoid receptor. The syndrome of apparent mineralocorticoid excess, which is an autosomal recessive disease due to a loss-of-function mutation of this protective enzyme, results in early-onset hypertension with hypokalemia accompanied by suppressed plasma renin activity and undetectable plasma aldosterone. Glycerrhetinic acid, a metabolite found in licorice (and often used as a flavoring in chewing tobacco and an increasing number of herbal supplements) is a potent inhibitor of 11β-hydroxysteroid dehydrogenase type 2. Thus, habitual ingestion of these substances causes a phenocopy of apparent mineralocorticoid excess. Biochemical confirmation consists of elevations in urinary free cortisol. The congenital syndrome is treated with spironolactone, whereas the phenocopy is treated with diet.
Hypertension occurs in 75–80% of patients with Cushing’s syndrome.
Cushing’s syndrome
The mechanism of hypertension may be related to stimulation of mineralocorticoid receptors by cortisol and increased secretion of other adrenal steroids. If clinically suspected, in patients not taking exogenous glucocorticoids, laboratory screening may be carried out with measurement of 24-h excretion rates of urine free cortisol or an overnight dexamethasone-suppression test. Recent evidence suggests that late night salivary cortisol is a sensitive and convenient screening test. Further evaluation is required to confirm the diagnosis and to identify the specific etiology of Cushing’s syndrome. Appropriate therapy depends on the etiology.
Pheochromocytoma
Pheochromocytomas are rare catecholamine-producing tumors of the adrenal (or sometimes extra-adrenal) chromaffin cells.
The diagnosis should be suspected when hypertension is accompanied by frequent or refractory headaches or by paroxysms of headache, palpitations, pallor, or diaphoresis. In some patients, pheochromocytoma is misdiagnosed as panic disorder. A family history of early-onset hypertension may suggest pheochromocytoma as part of the multiple endocrine neoplasia syndromes. If the diagnosis is missed, outpouring of catecholamines from the tumor can cause unsuspected hypertensive crisis during unrelated surgical or diagnostic procedures, such as the intravenous administration of contrast material; in such cases, mortality exceeds 80%.
Catecholamine-secreting tumors are located in the adrenal medulla (pheochromocytoma) or in extra-adrenal paraganglion tissue (paraganglioma) and account for hypertension in ~0.05% of patients. Approximately 20% of pheochromocytomas are familial with an autosomal dominant inheritance. Inherited pheochromocytomas may be associated with multiple endocrine neoplasia (MEN) type 2A and type 2B. If unrecognized, pheochromocytoma may result in lethal cardiovascular consequences. Clinical manifestations, including hypertension, are primarily related to increased circulating catecholamines, although some of these tumors may secrete a number of other vasoactive substances. In a small percent of patients, epinephrine is the predominant catecholamine secreted by the tumor, and these patients may present with hypotension rather than hypertension. The initial suspicion of the diagnosis is based on symptoms and/or the association of pheochromocytoma with other disorders. Laboratory testing consists of measuring catecholamines in either urine or plasma. Genetic screening is also available for evaluating patients and relatives suspected of harboring a pheochromocytoma associated with a familial syndrome. Surgical excision is the definitive treatment of pheochromocytoma and results in cure in ~90% of patients.
Hypertension Caused by Progesterone
A gain-in-function mutation in the mineralocorticoid receptor is a rare cause of autosomal dominant, early-onset hypertension that is markedly accelerated during pregnancy. Whereas mineralocorticoid receptor activity normally is unaffected by progesterone and blocked by spironolactone, the mutant receptor is activated by either of these compounds, producing severe salt-sensitive hypertension with secondary suppression of renin and aldosterone. Because progesterone increases 100-fold during pregnancy, this mutation constitutes a rare but dramatic cause of accelerated hypertension during pregnancy. In one family, all the affected males developed hypertension before 20 years of age. Amiloride is the suggested treatment of choice, and spironolactone is contraindicated.
Liddle’s Syndrome
Liddle’s syndrome is a rare monogenic form of salt-dependent hypertension due to gain-in-function mutations in ENaC, resulting in an excessive number of Na+ channels on the epithelial surface of the distal renal tubule. Mutations that truncate large segments of the cytoplasmic carboxyl terminus of the β or γ ENaC subunits disrupt the neural precursor cell expressed, developmentally down-regulated gene 4 (NEDD4) ubiquitin ligase–binding site so that the channels cannot be internalized within the cell. Inherited as an autosomal dominant trait, these mutations cause severe salt-dependent hypertension beginning in young adulthood. Plasma renin activity and plasma aldosterone levels are suppressed. The diagnosis is confirmed by genetic testing for the mutant gene. Because the defect is downstream from the mineralocorticoid receptor, the hypertension is unresponsive to spironolactone but is best treated with thiazides plus amiloride or triamterene, diuretics that are potent inhibitors of ENaC.
Pseudohypoaldosteronism Type II (Gordon’s Syndrome)
This rare syndrome is characterized by familial (autosomal dominant) salt-dependent low-renin hypertension with hyperkalemia, mild hyperchloremic metabolic acidosis, and otherwise normal renal function. The disease-causing genes encode WNK1 and WNK4, members of a novel family of serine-threonine kinases that normally regulate the thiazide-sensitive Na+-Cl− cotransporter, which is overactive in affected individuals. Both the hypertension and all its associated metabolic abnormalities are exquisitely sensitive to treatment with thiazide diuretics.
Familial Brachydactyly and Hypertension
Severe autosomal dominant hypertension can be associated with brachydactyly and short stature. The gene has been mapped to the short arm of chromosome 12, but the mechanism of the hypertension is unknown.
Hand roentgenogram of a 6 year-old Turkish boy with autosomal dominant hypertension (blood pressure 150/90 mm Hg) and brachydactyly type E is shown. The white arrow indicates the shortened metacarpal bones, which define this form of brachydactyly. The phalanges are also shortened. Additionally, cone shaped epiphyses are present
Unlike the other mendelian forms of hypertension, plasma renin and aldosterone levels are normal, and the hypertension is not salt sensitive.
Other Neurogenic Causes
Other causes of neurogenic hypertension that can be confused with pheochromocytoma include sympathomimetic agents (cocaine, methamphetamine; Chapter 32), baroreflex failure, and obstructive sleep apnea. A history of surgery and radiation therapy for head and neck tumors (Chapter 200) raises suspicion of baroreceptor damage. Snoring and somnolence suggest sleep apnea; continuous positive airway pressure or corrective surgery can improve blood pressure control in some patients with sleep apnea.
Other Causes of Secondary Hypertension
Coarctation of the aorta typically occurs just distal to the origin of the left subclavian artery, so the blood pressure is lower in the legs than in the arms (opposite of the normal situation). The clue is that the pulses are weaker in the lower than in the upper extremities, indicating the need to measure blood pressure in the legs as well as in both arms. Intercostal collaterals can produce bruits on examination and rib notching on the chest radiograph. Coarctations can be cured with surgery or angioplasty.
Coarctation of the aorta
Coarctation of the aorta is the most common congenital cardiovascular cause of hypertension. The incidence is 1–8 per 1000 live births. It is usually sporadic but occurs in 35% of children with Turner’s syndrome. Even when the anatomic lesion is surgically corrected in infancy, up to 30% of patients develop subsequent hypertension and are at risk of accelerated coronary artery disease and cerebrovascular events.
Patients with less severe lesions may not be diagnosed until young adulthood. The physical findings are diagnostic, and include diminished and delayed femoral pulses and a systolic pressure gradient between the right arm and the legs, and, depending on the location of the coarctation, between the right and left arms. A blowing systolic murmur may be heard in the posterior left interscapular areas. The diagnosis may be confirmed by chest x-ray and transesophageal echocardiogram. Therapeutic options include surgical repair or balloon angioplasty, with or without placement of an intravascular stent. Subsequently, many patients do not have a normal life expectancy but may have persistent hypertension with death due to ischemic heart disease, cerebral hemorrhage, or aortic aneurysm.
Hyperthyroidism tends to cause systolic hypertension with a wide pulse pressure, whereas hypothyroidism tends to cause mainly diastolic hypertension. Treatment is for the underlying disease.
Hypertension due to obstructive sleep apnea is being recognized with increasing frequency. Independent of obesity, hypertension occurs in >50% of individuals with obstructive sleep apnea, the severe end of the sleep-disordered breathing syndrome. The severity of hypertension correlates with the severity of sleep apnea. Approximately 70% of patients with obstructive sleep apnea are obese. Hypertension related to obstructive sleep apnea should also be considered in patients with drug-resistant hypertension and in patients with a history of snoring. The diagnosis can be confirmed by polysomnography. In obese patients, weight loss may alleviate or cure sleep apnea and related hypertension. Continuous positive airway pressure (CPAP) administered during sleep is an effective therapy for obstructive sleep apnea. With CPAP, patients with apparently drug-resistant hypertension may be more responsive to antihypertensive agents.
Cyclosporine and tacrolimus are important causes of secondary hypertension in the population of transplant recipients, apparently by inhibition of calcineurin, the calcium-dependent phosphatase that is expressed not only in lymphoid tissue but also ieural, vascular, and renal tissue. In the absence of outcomes data, non-dihydropyridine calcium-channel blockers (CCBs) have become the drugs of first choice, but they increase cyclosporine blood levels. Combination therapy with diuretics, CCBs, and central sympatholytics often is required.
Overview of keypoints
Definition
Hypertensive is defined as an abnormal elevation in diastolic pressure and/or systolic pressure. In past years, the diastolic value was emphasized in assessing hypertension. However, elevations in systolic pressure (“systolic hypertension”) are also associated with increased incidence of coronary and cerebrovascular disease (e.g., stroke). Therefore, we now recognize that both systolic and diastolic pressure values are important to note.
According to the latest
Table 1. Classification and management of blood pressure for adults*
|
BP classification |
SBP, mmHg |
DBP, mmHg |
Lifestyle modification |
Initial drug therapy |
|
|
Without Compelling Indication |
Without Compelling Indication |
||||
|
Normal |
<120 |
And <80 |
Encourage |
No antihypertensive drug indicated |
Drug(s) for compelling indications.* |
|
Prehypertension |
120-139 |
or 80-89 |
yes |
||
|
Stage 1 Hypertension |
140-159 |
or 90-99 |
yes |
Thiazide-type diuretics for most. May consider ACEI, ARB, BB, CCB, or combination. |
Drug(s) for the com-pelling indications.* Other antihypertensive drugs (diuretics, ACEI, ARB, BB, CCB) as needed. |
|
Stage 2 Hypertension |
>160 |
or >100 |
yes |
Two-drug combination for most1″ (usually thiazide-type diuretic and ACEI or ARB or BB or CCB). |
|
DBP, diastolic blood pressure; SBP, systolic blood pressure.
Drug abbreviations: ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BB, beta-blocker; CCB, calcium channel blocker.
* Treatment determined by highest BP category. Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension. Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg. [JNC 7 Report The Seventh Report of the Joint National Committee on Prevention, Detection , Evaluation, and Treatment of High Blood Pressure]
African-Americans are more likely to develop hypertension and to develop it at a younger age. Genetic research suggests that African-Americans seem to be more sensitive to salt. In people who have a gene that makes them salt-sensitive, just a half-teaspoon of salt can raise blood pressure by
Two Classes of Hypertension
In 90-95% of patients presenting with hypertension, the cause is unknown. This condition is called primary (or essential) hypertension. Hypertension that results secondarily from renal disease, endocrine disorders, or other identifiable causes is called secondary hypertension.
Hypertension and Sodium
Sodium, a major component of salt, can raise blood pressure by causing the body to retain fluid, which leads to a greater burden on the heart. The American Heart Association recommends eating less than 1,500 milligrams of sodium per day. Processed foods contribute up to 75% of our sodium intake. Canned soups and lunch meats are prime suspects.
Hypertension and Stress
Stress can make the blood pressure spike, but there’s no evidence that it causes high blood pressure as an ongoing condition. However, stress may affect risk factors for heart disease, so it may have an indirect connection to hypertension. Stress may lead to other unhealthy habits, such as a poor diet, alcohol use, or smoking, which can contribute to high blood pressure and heart disease.
Hypertension and Weight
Being overweight places a strain on the heart and increases a risk of high blood pressure. That is why diets to lower blood pressure are often also designed to control calories. They typically call for cutting fatty foods and added sugars, while increasing fruits, vegetables, lean protein, and fiber. Even losing
Hypertension and Alcohol
Guidelines from the American Heart Association state for limitation the amount to no more than two drinks a day for men, or one a day for women. They define a drink as one 12-ounce beer, four ounces of wine,
Hypertension and Caffeine
It might have a temporary effect, but studies haven’t shown any link between caffeine and the development of hypertension. According to the American Heart Association is safely to drink one or two cups a day.
Hypertension and Pregnancy
Gestational hypertension is a kind of high blood pressure that occurs in the second half of pregnancy. Without treatment, it may lead to a serious condition called preeclampsia that endangers both the mother and baby. The condition can limit blood and oxygen flow to the baby and can affect the mother’s kidneys and brain. After the baby is born, the mother’s blood pressure usually returns to its normal level.
Hypertension and Medicine
Cold and flu medicines that contain decongestants are one of several classes of medicine that can cause your blood pressure to rise. Others include NSAID pain relievers, steroids, diet pills, birth control pills, and some antidepressants.
‘White Coat’ Hypertension
The initial visit to the physician’s office is often the cause of an artificially high blood pressure that may disappear with repeated testing after rest and with follow-up visits and blood pressure checks. One out of four people that are thought to have mild hypertension actually may have normal blood pressure when they are outside the physician’s office. An increase in blood pressure noted only in the doctor’s office is called ‘white coat hypertension.’ A diagnosis of white coat hypertension might imply that it is not a clinically important or dangerous finding.
Etiology
· Kidney disease
1. Diabetes complications (diabetic nephropathy).
2. Polycystic kidney disease. In this inherited condition, cysts in the kidneys prevent the kidneys from working normally, and can raise blood pressure.
3. Glomerular disease.
4. Renovascular hypertension. This is a type of secondary hypertension caused by stenosis of one or both arteries leading to the kidneys. Renovascular hypertension can cause severe hypertension and irreversible kidney damage. It’s often caused by the same type of fatty plaques that can damage also coronary arteries (atherosclerosis) or a condition in which the muscle and fibrous tissues of the renal artery wall thicken and harden into rings (fibromuscular dysplasia).
· Endocrinological disorders
1. Cushing’s syndrome. In this condition, corticosteroid medications, a pituitary tumor or other factors cause overproduction of adrenal glands hormones. This raises blood pressure.
2. Aldosteronism. A tumor in the adrenal gland cause releasing an excessive amount of the hormone aldosterone, which raises blood pressure.
3. Pheochromocytoma. This rare tumor, usually found in an adrenal gland, increases production of the hormones adrenaline and noradrenaline, which can lead to long-term high blood pressure or short-term spikes in blood pressure.
4. Thyroid problems (hypothyroidism or hyperthyroidism)
5. Hyperparathyroidism. The glands secrete too much parathyroid hormone, the amount of calcium in the blood rises — which triggers a rise in blood pressure.
· Coarctation of the aorta. This congenital disorder, in turn, raises blood pressure — particularly in the arms.
· Sleep apnea.
· Obesity. In overweight (obese) patients the amount of blood circulating through the body increases. This puts added pressure on the artery walls, increasing the blood pressure. In addition, excess weight often is associated with an increase in heart rate and a reduction in the capacity of the blood vessels to transport blood. All of these factors can increase blood pressure.
· Pregnancy. Pregnancy can make existing high blood pressure worse, or may cause high blood pressure to develop (pregnancy-induced hypertension or preeclampsia).
Medications and supplements. Drug-induced hypertension is among the most common causes of secondary hypertension and is frequently encountered in everyday clinical practice. The administration of offending drugs can result in excessive blood pressure elevation in some individuals, while most individuals will experience little or no increases of blood pressure. This variability represents a rule without exception. Therefore, it would be very important to identify predictors of blood pressure elevation, in order to individualize drug treatment.
Various prescription medications — from pain relievers to antidepressants can cause or aggravate high blood pressure in some people. Birth control pills, decongestants and certain herbal supplements may have the same effect.
|
Table 2: Drugs inducing or exacerbating hypertension. |
|
(i) Nonsteroidal anti-inflammatory drugs |
|
(ii) Oral contraceptives |
|
(iii) Sympathomimetics |
|
(iv) Illicit drugs |
|
(v) Glucocorticoids |
|
(vi)Mineralocorticoids |
|
(vii) Cyclosporine, tacrolimus |
|
(iix) Erythropoietin |
|
(ix) Herbal supplements |
|
(x) VEGF inhibitors |
NSAIDs-Induced Hypertension.
The most common cause of drug-induced hypertension is the use of NSAIDs. Osteoarthritis and hypertension often coexist, since both conditions are age related. It has been reported that approximately 50% of patients with osteoarthritis suffer from hypertension. NSAIDs affect blood pressure levels via different mechanisms: activation of the renin-angiotensin-aldosterone system, sodium and water retention, induction of vasoconstriction through endothelin-1 and arachidonic acid metabolites, and mainly inhibition of renal vasodilatory prostaglandins (E2 and I2)
Oral Contraceptives. Women using oral contraceptives had an 80% higher risk of developing hypertension compared to women that were not using such drugs.
Anti-VEGF Agents. Another class of agents that emerged as inducers of hypertension are the antineoplastic drugs
that target the VEGF pathway.
Renal artery stenosis (renovascular disease)
Renal artery disease can cause of narrowing of the vessel lumen. The reduced lumen diameter decreases the pressure at the afferent arteriole in the kidney and reduces renal perfusion. This stimulates renin release by the kidney, which increases circulating angiotensin II (AII) and aldosterone. These hormones increase blood volume by enhancing renal reabsorption of sodium and water. Increased AII also causes systemic vasoconstriction and enhances sympathetic activity. Chronic elevation of AII promotes cardiac and vascular hypertrophy. The net effect of these renal mechanisms is an increase in blood volume that augments cardiac output by the Frank-Starling mechanism. Therefore, hypertension caused by renal artery stenosis results from both an increase in systemic vascular resistance and an increase in cardiac output.
Chronic renal disease
· Any number of pathologic processes (e.g., diabetic nephropathy, glomerulonephritis) can damage nephrons in the kidney. When this occurs, the kidney cannot excrete normal amounts of sodium which leads to sodium and water retention, increased blood volume, and increased cardiac output by the Frank-Starling mechanism. Renal disease may also result in increased release of renin leading to a renin-dependent form of hypertension. The elevation in arterial pressure secondary to renal disease can be viewed as an attempt by the kidney to increase renal perfusion and restore glomerular filtration.
Primary hyperaldosteronism
Increased secretion of aldosterone generally results from adrenal adenoma or adrenal hyperplasia. Increased circulating aldosterone causes renal retention of sodium and water (see figure), so blood volume and arterial pressure increase. Plasma renin levels are generally decreased as the body attempts to suppress the renin-angiotensin system; there is also hypokalemia associated with the high levels of aldosterone.
|
Classification |
Systolic |
Diastolic |
|
Normal |
<120 |
<80 |
|
Prehypertension |
120-139 |
80-89 |
|
Stage 1 |
140-159 |
90-99 |
|
Stage 2 |
>160 |
>100 |
Diagnosing Secondary Hypertension
Secondary hypertension is elevated blood pressure that results from an underlying, identifiable, often correctable cause. Only about 5 to 10 percent of hypertension cases are thought to result from secondary causes. The ABCDE mnemonic can be used to help determine a secondary cause of hypertension:
· Accuracy of diagnosis, obstructive sleep Apnea, Aldosteronism
· presence of renal artery Bruits (suggesting renal artery stenosis), renal parenchymal disease (Bad kidneys)
· excess Catecholamines, Coarctation of the aorta, Cushing’s syndrome,
· Drugs, Diet,
· excess Erythropoietin, and Endocrine disorders.
An algorithm showing the general strategy to help screen for factors involved in secondary hypertension is presented. Routine urinalysis, complete blood cell count, blood chemistry profile (potassium, sodium, creati-nine, fasting glucose, fasting lipid levels), and a 12-lead electrocardiogram are recommended for all patients with hypertension.
Patients with hypertension have some underlying mechanism that elevates their blood pressure. Conceptually, it is useful to think of patients with hypertension as having either essential hypertension (systemic hypertension of unknown cause) or secondary hypertension (hypertension that results from an underlying, identifiable, often correctable cause).1
Although only about 5 to 10 percent of hypertension cases are thought to result from secondary causes, hypertension is so common that secondary hypertension probably will be encountered frequently by the primary care practitioner.2–4
The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI)5 defines four goals for the evaluation of the patient with elevated blood pressure: detection and confirmation of hypertension; detection of target organ disease (e.g., renal damage, congestive heart failure); identification of other risk factors for cardiovascular disorders (e.g., diabetes mellitus, hyperlipidemia); and detection of secondary causes of hypertension. Physicians can use the mnemonic ABCDE to help determine secondary causes in the patient with elevated blood pressure (Table 1).
TABLE 1
Findings That Suggest Secondary Hypertension
|
Findings |
Disorder suspected |
Further diagnostic studies |
|
Snoring, daytime somnolence, obesity |
Obstructive sleep apnea |
Sleep study |
|
Hypernatremia, hypokalemia |
Aldosteronism |
Ratio of plasma aldosterone to plasma renin activity, CT scan of adrenal glands |
|
Renal insufficiency, atherosclerotic cardiovascular disease, edema, elevated blood urea nitrogen and creatinine levels, proteinuria |
Renal parenchymal disease |
Creatinine clearance, renal ultrasonography |
|
Systolic/diastolic abdominal bruit |
Renovascular disease |
Magnetic resonance angiography, captopril (Capoten)-augmented radioisotopic renography, renal arteriography |
|
Use of sympathomimetics, perioperative setting, acute stress, tachycardia |
Excess catecholamines |
Confirm patient is normotensive in absence of high catecholamines. |
|
Decreased or delayed femoral pulses, abnormal chest radiograph |
Coarctation of aorta |
Doppler or CT imaging of aorta |
|
Weight gain, fatigue, weakness, hirsutism, amenorrhea, moon facies, dorsal hump, purple striae, truncal obesity, hypokalemia |
Cushing’s syndrome |
Dexamethasone-suppression test |
|
Use of drug in |
Drug side effect |
Trial off drug, if possible |
|
High salt intake, excessive alcohol intake, obesity |
Diet side effects |
Trial of dietary modification |
|
Erythropoietin use in renal disease, polycythemia in COPD |
Erythropoietin side effect |
Trial off drug, if possible |
|
Paroxysmal hypertension, headaches, diaphoresis, palpitations, tachycardia |
Pheochromocytoma |
Urinary catecholamine metabolites (vanillylmandelic acid, metanephrines, normetanephrines) |
|
|
|
Plasma free metanephrines |
|
Fatigue, weight loss, hair loss, diastolic hypertension, muscle weakness |
Hypothyroidism |
TSH levels |
|
Heat intolerance, weight loss, palpitations, systolic hypertension, exophthalmos tremor, tachycardia |
Hyperthyroidism |
TSH levels |
|
Kidney stones, osteoporosis, depression, lethargy, muscle weakness |
Hyperparathyroidism |
Serum calcium, parathyroid hormone levels |
|
Headaches, fatigue, visual problems, enlargement of hands, feet, tongue |
Acromegaly |
Growth hormone level |
CT = computed tomography; COPD = chronic obstructive pulmonary disease; TSH = thyroid-stimulating hormone.
Traditionally, the principal target organ for aldosterone was said to be the kidney; MR are found in high concentration in the renal distal nephron as well as other epithelial sites, such as the colon and ducts of sweat and salivary glands (10). However, MR have also been identified ionepithelial sites, such as heart, brain, vascular smooth muscle, liver, and peripheral blood leukocytes
Symptoms
Most of the time, there are no symptoms. For most patients, high blood pressure is found when they visit their health care provider or have it checked elsewhere.
Because there are no symptoms, people can develop heart disease and kidney problems without knowing they have high blood pressure.
If a severe headache, nausea or vomiting, bad headache, confusion, changes in the vision, or nosebleeds you may have a severe and dangerous form of high blood pressure called malignant hypertension. A physical exam include checking signs of heart disease, damage to the eyes, and other changes in your body.
Diagnosis: ABCDE
A: ACCURACY, APNEA, ALDOSTERONISM
Accuracy
The first, most practical step in evaluating an elevated blood pressure reading is to investigate its accuracy. A blood pressure cuff that is too small, tight-fitting sleeves that are not removed, or a brachial artery that is noncompressible because of calcification (sometimes seen in the elderly) can cause falsely elevated readings. White-coat hypertension (blood pressure that is elevated in the physician’s office but normal at other times) accounts for about 20 percent of patients with elevated readings.3 JNC-VI recommends confirming high blood pressure readings outside of the office setting.
Apnea
Obstructive sleep apnea (OSA), a repetitive mechanical obstruction of the upper airway during sleep, is an independent risk factor for hypertension.6 At least one half of patients with OSA have hypertension.7 Treatment of OSA with surgery or nasal continuous positive air way pressure reduces hypertension in these patients.8 Daytime somnolence, obesity, snoring, lower-extremity edema (secondary to the right-sided congestive heart failure that occurs after repetitive anoxic insults to the myocardium during sleep), morning headaches, and nocturia suggest OSA.9 There is a high incidence of OSA in patients with chronic obstructive pulmonary disease (COPD). A formal sleep study usually is needed for diagnosis of OSA and determination of corrective interventions.
Aldosteronism
Primary hyperaldosteronism is defined as overproduction of aldosterone independent of its usual regulator, the renin-angiotensin system.10 The resulting retention of excess salt and water suppresses renin levels (as opposed to elevating renin levels, which causes secondary hyperaldosteronism). Increased urinary excretion of potassium signals hyperal-dosteronism, which should be suspected in all hypertensive patients with unprovoked (i.e., not diuretic-induced) hypokalemia.11 The next diagnostic test should be demonstration of an elevated ratio of plasma aldosterone levels to plasma renin activity.12
B: BRUITS, BAD KIDNEYS (RENAL PARENCHYMAL DISEASE)
Bruits
Renovascular hypertension is defined as hypertension resulting from compromised arterial supply to the kidneys. About 65 percent of renovascular disease is secondary to atherosclerosis in the renal arteries, usually seen after age
About one half of patients with renovascular hypertension will have an abdominal bruit identifiable on physical examination.13 Bruits heard in both systole and diastole are more suggestive of renovascular hypertension than systolic bruits alone.14 In unselected populations of hypertensive persons, the incidence of renovascular hypertension is less than 1 percent.14 However, identification of this relatively small population can be important because surgery or angioplasty can reverse the hypertension, especially if performed early enough to prevent permanent renal damage.
Magnetic resonance angiography (MRA) is a noninvasive imaging modality with a sensitivity of 100 percent and a specificity of 70 to 90 percent compared with renal arteriography for detection of renal artery stenosis.2,15 MRA best delineates the proximal renal vasculature and is therefore useful as an initial diagnostic tool for patients suspected of having atherosclerotic renal artery stenosis, which usually involves the proximal renal artery.16 Patients suspected of having FMD, which tends to involve the distal renal artery, should undergo conventional angiography or computed tomographic angiography.16
Captopril (Capoten)-augmented radioisotopic reno-gram.17 This test is based on the fact that a kidney that is receiving an inadequate blood supply will activate the renin-angiotensin system. Therefore, a single dose of the angiotensin-converting enzyme (ACE) inhibitor captopril will abruptly reduce renal function in the ischemic kidney. A scan is considered positive if there is delayed or decreased uptake of the radioisotope in the stenotic kidney compared with the non-stenotic one, so this test is not as useful if stenosis is present bilaterally.2
Duplex ultrasound scanning is another diagnostic option, but it can be limited by its dependence on operator skill and experience. Renal arteriography remains the gold standard for defining the vessel anatomy but does not always correlate with postprocedural outcomes (i.e., surgical correction of the renal artery stenosis often does not resolve the hypertension).13
Bad Kidneys
Renal parenchymal disease can be a cause or consequence of hypertension. Progressive renal damage is caused by the mechanical and humoral effects of glomerular hypertension. The renal damage decreases the kidneys’ ability to excrete salt and excess fluid (resulting in a low renin state, as opposed to the high renin state found in renovascular hypertension), and the hypertension worsens. As renal damage progresses, hyperparathyroidism develops and erythropoietin production increases, exacerbating the hypertension.5,18 Thus, a vicious cycle of worsening renal function and hypertension begins.
Aggressive treatment of hypertension (particularly with ACE inhibitors) in patients with renal parenchymal disease can lower the blood pressure and slow the disease’s progression, although it is difficult to effectively control hypertension in chronic renal disease. Early treatment of hypertension and diabetes, the two most common causes of end-stage renal disease, can lower the incidence of long-term renal complications.18
Diagnosis is based on loss of renal cortical function (demonstrated by elevated serum creatinine levels and decreased creatinine clearance), although it may be impossible to tell if the renal dysfunction is primary or secondary to the hypertension.2
C: CATECHOLAMINES, COARCTATION, CUSHING’S SYNDROME
Catecholamines
Excess catecholamine levels play a role in causing white-coat hypertension and hypertension in pheochromocytoma, OSA, and other diseases discussed in this article. Acute stress induces catecholamine release and often contributes to preoperative or postoperative hypertension. Over-the-counter or prescription decongestants can have sympathomimetic effects, as do nonprescription weight-loss preparations containing ephedra (ma huang).19,20 The hypertensive effects of cocaine and amphetamines also are sympathomimetic.
Coarctation of the Aorta
Coarctation of the aorta is a congenital narrowing of the aortic lumen, most often occurring just distal to the origin of the left subclavian artery. Patients with less severe forms of the disorder may not be diagnosed until young adulthood but have a high incidence of premature death.21 Diagnostic clues include decreased lower-extremity (femoral) pulses with upper-extremity hypertension, dyspnea on exertion, and chest radiographic findings of notched ribs (from dilated collateral vessels) and dilation of the aorta above and below the constriction (the “
Cushing’s Syndrome
Cushing’s syndrome can cause hypertension via the mineralocorticoid effects of excess glucocorticoids and is best screened for with a dexamethasone-suppression test.23
D: DRUGS, DIET
Drugs
Many prescription and nonprescription drugs can cause or exacerbate hypertension (Table 2). Immunosuppressive agents such as cyclosporine (Sandimmune), tacrolimus (Prograf), and corticosteroids increase blood pressure in up to 80 percent of solid-organ transplant recipients.5 Nonsteroidal anti-inflammatory drugs (NSAIDs) elevate blood pressure via their antiprostaglandin effects on the kidneys. Estrogen, in the dosages most often used in oral contraceptive pills (30 to 35 mcg), appears to have only a mild hypertensive effect and no increased risk for overall mortality or myocardial infarction (if smokers over age 35 are excluded).24 Nicotine in cigarettes, smokeless tobacco, and cigars causes transient (30 minutes or less) increases in blood pressure, although trans-dermal nicotine preparations do not appear to have this effect.26 Because patients who smoke often have a cigarette just before coming into the physician’s office, blood pressure should be rechecked after 30 minutes if initial readings are elevated. Although caffeine can raise blood pressure acutely, tolerance develops rapidly, and there appears to be no direct relationship between caffeine intake and chronic hypertension.27 Chronic overuse of alcohol is a potentially reversible cause of hypertension.4
TABLE 2
Drugs That Can Raise Blood Pressure
|
Drug class |
Drug examples |
|
Immunosuppressive agents |
Cyclosporine (Sandimmune), tacrolimus (Prograf), corticosteroids |
|
Nonsteroidal anti-inflammatory drugs |
Ibuprofen (Motrin), naproxen (Naprosyn), piroxicam (Feldene) |
|
COX-2 inhibitors |
Celecoxib (Celebrex), rofecoxib (Vioxx), valdecoxib (Bextra) |
|
Estrogens |
30- to 35-mcg estrogen oral contraceptives |
|
Weight-loss agents |
Sibutramine (Meridia), phentermine (Adipex), ma huang (ephedra) |
|
Stimulants |
Nicotine, amphetamines |
|
Mineralocorticoids |
Fludrocortisone (Florinef) |
|
Antiparkinsonian |
Bromocriptine (Parlodel) |
|
Monoamine oxidase inhibitors |
Phenelzine (Nardil) |
|
Anabolic steroids |
Testosterone |
|
Sympathomimetics |
Pseudoephedrine (Novafed) |
COX-2 = cyclooxygenase-2.
Diet
Excess consumption of dietary sodium is linked to chronic hypertension, although the lower limit of “excess” can be difficult to define. Blacks, the elderly, patients with diabetes, and patients with essential hypertension appear to be particularly sensitive to dietary sodium intake.5 Low intake of potassium, calcium, and magnesium can have a similar but less pronounced effect.5 Dietary patterns that cause obesity also can cause hypertension. Sustained weight reduction lowers blood pressure—often to normal levels—in at least one half of obese patients.28 A loss of 5 to 10 percent of body weight can significantly reduce blood pressure.
E: ERYTHROPOIETIN, ENDOCRINE DISORDERS
Erythropoietin
Elevated erythropoietin levels can be endogenous (as in response to the chronic hypoxia of COPD) or exogenous (administered to alleviate the anemia seen in chronic renal failure). High erythropoietin levels can elevate blood pressure either via a polycythemia/hyperviscosity mechanism or by direct pressor effects.7
Endocrine Disorders
Hypothyroidism can cause decreased cardiac output with a compensatory increase in vascular tone, resulting in a more prominent rise in diastolic blood pressure than in systolic blood pressure.7 Conversely, hyperthyroidism induces increased cardiac output and compensatory decreased vascular tone, causing a greater increase in systolic blood pressure.7 A thyroid-stimulating hormone level is the best diagnostic screening test for thyroid disorders.
Hyperparathyroidism (primary or secondary to chronic renal insufficiency) is a potentially reversible cause of hypertension. However, only 30 to 40 percent of patients with hyperparathyroidism have hypertension, and parathyroidectomy does not reliably resolve hypertension in patients with this disorder.29 It is unclear how hyperparathyroidism increases blood pressure, because there is no direct correlation with parathyroid hormone or calcium levels.
Pregnancy-induced hypertension has an incompletely understood neurohumoral mechanism (possibly initiated by inadequate establishment of blood supply to the developing placenta) and occasionally can develop in the immediate postpartum period.
Pheochromocytoma is another endocrine cause of hypertension. The classic symptoms include headache, diaphoresis, palpitations, and paroxysmal hypertension. The syndrome can vary depending on the types of catecholamines being produced, the amount and frequency of their release into the circulation, and other factors. The usual screening test has been urinary measurement of catecholamine metabolites (vanillylmandelic acid, metanephrines, normetanephrines).30 Determination of plasma free metanephrines might be the test of first choice for diagnosis of this tumor, although availability of this test at hospital and reference laboratories is limited.31 Pheochromocytoma is very rare, and routine screening in hypertensive patients is not recommended.
Acromegaly (elevated growth hormone) is a rare endocrine cause of hypertension.
DIAGNOSTIC
A medical history should include the following:
· family history of high blood pressure, premature CHD, stroke, CVD, diabetes mellitus, and dyslipidemia
· patient history or symptoms of cardiovascular, cerebrovascular, or renal disease; diabetes mellitus; dyslipidemia; or gout
· known duration and levels of elevated blood pressure
· history of weight gain, leisure-time physical activities, smoking, using of dietary assessment, including sodium intake, alcohol use, and intake of cholesterol and saturated fats
· results and side-effects of previous antihypertensive therapy
· symptoms suggesting secondary hypertension
· psychosocial and environmental factors (e.g., family situation, employment status and working conditions, educational level) that may influence blood pressure control
· use of drugs that may influence blood pressure (e.g., oral contraceptives, steroids, nonsteroidal anti-inflammatory drugs, nasal decongestants and other cold remedies, appetite suppressants, cyclosporine, erythropoietin, tricyclic antidepressants, and monoamine oxidase inhibitors).
Physical Examination
· two or more blood pressure measurements with patient supine or seated and standing
· verification of blood pressure in the contralateral arm
· height and weight
· funduscopic examination of eyes for hypertensive changes
· examination of neck for thyroid enlagement, bruits, distended veins
· examination of the lungs
· examination of the heart for increased rate, size, precordial heaves, rhythm, gallops, murmurs
· examination of abdomen for enlarged kidneys, masses, aortic dilitation, bruits
· examination of extremities for peripheral pulses, edema, etc.
· neurological assessment
The electrocardiogram is a useful but imperfect tool for detecting LVH. The utility of the ECG relates to its being relatively inexpensive and widely available. The limitations of the ECG relate to its moderate sensitivity or specificity depending upon which of the many proposed sets of criteria are applied
General electrocardiograpic findins
Left ventricular hypertrophy and related changes can produce five major ECG changes: increased QRS voltage; increased QRS duration; left axis deviation; repolarization (ST-T) changes; and left atrial abnormality. Echocardiography is the procedure of choice for diagnosing LVH. It can also permit quantitation of
Philip M Mottram, Thomas H Marwick/ Assessment of diastolic function: what the general cardiologist needs to know// Heart 2005;91:681-695 doi:10.1136/hrt.2003.029413
Laboratory testing is not diagnostic for hypertension, but tests are frequently ordered to detect conditions that may be causing and/or exacerbating high blood pressure and to evaluate and monitor organ function over time.
General tests that may be ordered include:
· Urinalysis – ordered to help assess kidney function
· Hematocrit – may be ordered as part of the Complete Blood Count (CBC) to evaluate the ratio of fluid to solids in the blood
· BUN (Blood Urea Nitrogen) and/or Creatinine – to detect and monitor kidney dysfunction or to monitor the effect of medications on the kidneys
· Potassium – may be ordered as part of the Electrolyte panel, which also includes sodium, chloride, and carbon dioxide (CO2); used to evaluate and monitor the balance of the body’s electrolytes; some high blood pressure medications can upset the balance by causing excessive sodium and potassium loss
· Fasting Glucose – ordered to determine if blood glucose levels are within healthy ranges
· Calcium – may be ordered to determine how much total calcium or ionized calcium is circulating in the blood; increased activity of the parathyroid glands, which produces an increase in serum calcium, is associated with hypertension
· TSH (Thyroid Stimulating Hormone) and T4 – may be ordered to detect and monitor thyroid dysfunction
· Lipid Profile – may be ordered to evaluate levels of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides
The Basic Metabolic Panel (BMP) includes several of the tests listed above, so it may be ordered instead of the individual tests.
Specific tests that may be ordered based on the patient’s medical history, physical findings, and routine laboratory test results to help detect, diagnose, and monitor conditions causing secondary hypertension include:
· Aldosterone and Renin – to help detect the overproduction of aldosterone by the adrenal glands (which may be due to a tumor)
· Cortisol – to detect an overproduction of cortisol that may be due to Cushing’s syndrome
· Catecholamines and Metanephrines – to measure epinephrine, norepinephrine, and their metabolites primarily to help detect the presence of a pheochromocytoma that can cause episodes of severe hypertension
Non-Laboratory Tests
Blood pressure measurement
This is the primary tool for detecting and monitoring hypertension. Although it caow be evaluated with a variety of electronic devices, blood pressure is traditionally and most accurately measured with a stethoscope and a blood pressure cuff
· ECG (Electrocardiography) – to evaluate the heart rate and rhythm and look for evidence of heart damage
· Eye Exam – to look at the retina for changes in the blood vessels (retinopathy)
· Physical Exam – to help evaluate the kidneys, to look for abdominal tenderness, to listen for bruits (the sound of blood flowing through a narrowed artery), to examine the thyroid gland in the throat for any enlargement or signs of dysfunction, and to detect any other clinical signs as they present
· Imaging scans, such as X-ray or ultrasound of the kidneys or X-ray of the chest
Recommendations
A more aggressive evaluation for secondary causes of hypertension should be considered in certain clinical situations (Table 3).5,32,33 A diagnostic algorithm for secondary hypertension is presented in Figure 1. However, there is little objective evidence that following these recommendations would significantly benefit patients. Despite this uncertainty, it would seem reasonable for the physician to follow the recommendations in the JNC-VI (Table 4) for routine medical history, physical examination, and laboratory testing. Although it is not one of the JNC-VI recommendations, obtaining fasting low-density lipoprotein cholesterol levels and triglyceride levels makes sense, because recent treatment recommendations by the National Cholesterol Education Program (NCEP-III) are based on these findings.
TABLE 3
Risk Factors for Secondary Hypertension
|
Poor response to therapy (resistant hypertension) |
|
Worsening of control in previously stable hypertensive patient |
|
Stage 3 hypertension (systolic blood pressure > |
|
Onset of hypertension in persons younger than age 20 or older than age 50 |
|
Significant hypertensive target organ damage |
|
Lack of family history of hypertension |
|
Findings on history, physical examination, or laboratory testing that suggest a secondary cause (Table 1) |
Information from references 5,32, and 33.
Evaluation for Secondary Causes of Hypertension
FIGURE 1.General strategy for diagnosing a secondary cause of hypertension.
TABLE 4
Routine Screening Laboratory Tests for Hypertension
|
Urinalysis |
|
Complete blood count |
|
Blood chemistries (potassium, sodium, creatinine, fasting glucose) |
|
Fasting lipid profile (LDL, HDL, triglycerides, total cholesterol) |
|
12-lead electrocardiogram |
LDL = low-density lipoprotein; HDL = high-density lipoprotein.
Information from Joint National Committee. The sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med 1997;157:2413–46.
For practical reasons the term hypertension is used in daily practice and patients are categorized as shown in Table 1(based on 2007 ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension). However the real threshold for defining hypertension must be considered as flexible, being high or low based on the total CV risk of each individual.
All patients should be classified not only in relation to the grades of hypertension but also in terms of the total CV risk resulting from the coexistence of different risk factors, organ damage and disease.
Decisions on treatment strategies (initiation of drug treatment, BP threshold and target for treatment, use of combination treatment, need of a statin and other non-antihypertensive drugs) all importantly depend on the initial level of risk.
There are several methods by which total CV risk can be assessed, all with advantages and limitations. Categorization of total risk as low, moderate, high, and very high added risk has the merit of simplicity and can therefore be recommended. The term ‘added risk’ refers to the risk additional to the average one. Total risk is usually expressed as the absolute risk of having a CV event within 10 years. Because of its heavy dependence on age, in young patients absolute total CV risk can be low even in the presence of high BP with additional risk factors. If insufficiently treated, however, this condition may lead to a partly irreversible high risk condition years later. In younger subjects treatment decisions should better be guided by quantification of relative risk, i.e. the increase in risk in relation to average risk in the population.
Using rigid cut-offs of absolute risk (e.g. > 20% within 10 years) in order to decide on treatment is discouraged.
3. Stratification of total CV risk
In the Figure 1 total CV risk is stratified in four categories. Low, moderate, high and very high risks refer to 10 year risk of a fatal or non-fatal CV event. The term added indicates that in all categories risk is greater than average. The dashed line indicates how the definition of hypertension (and thus the decision about the initiation of treatment) is flexible, i.e. may be variable depending on the level of total CV risk.
General approach to pharmacologic therapy
For the pharmacological management of hypertension according to The 2010 Canadian Hypertension Education Program, treatment thresholds and targets should be predicated on the patient’s global atherosclerotic risk, target organ damage and comorbid conditions.
Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease.
Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy [DG Hackam, NA Khan, BR Hemmelgarn, et al. The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy. Can J Cardiol 2010;26(5):249-258].
Target blood pressure is less than 140/90. The decision as to which drug to use first can usually be made on the basis of age, race, the presence of other medical problems, side effects, long-term safety, and cost. If one drug is found to be well-tolerated but only partially effective, the addition of a second drug of another class is rational. Half or more of patients will probably require a second drug, and about 10% will require three.
I. Lifestyle management
Recommendations
A. Physical exercise
1. For nonhypertensive individuals (to reduce the possibility of becoming hypertensive) or for hypertensive patients (to reduce their blood pressure), prescribe the accumulation of 30 min to 60 min of moderate-intensity dynamic exercise (such as walking, jogging, cycling or swimming) four to seven days per week in addition to the routine activities of daily living (grade D). Higher
intensities of exercise are no more effective (grade D).
B. Weight reduction
1. Height, weight and waist circumference should be measured and body mass index calculated for all adults (grade D).
2. Maintenance of a healthy body weight (body mass index 18.5 kg/m2 to 24.9 kg/m2, and waist circumference less than
3. Weight loss strategies should employ a multidisciplinary approach that includes dietary education, increased physical activity and be havioural intervention (grade B).
|
Initial Drug Choices1 |
|
|
If the patient is young (≤55 years) and non-black, start with: · (A) Angiotensin-converting enzyme (ACE) inhibitor or low-cost Angiotensin-II receptor antagonist (AIIRA). · Beta-blocker may be appropriate in younger adults if ACE not tolerated, in women who may become pregnant or if evidence of increased sympathetic drive. |
If the patient is aged >55 years or a black person of African or · (C) Calcium-channel blocker (CCB). |
|
Stage 2 Drug Choices
· (A+C) ACE inhibitor or Angiotensin-II receptor antagonist with Calcium-channel blocker. · Use ACE/AIIRA and thiazide-like Diuretic (D) if CCB not tolerated (or if any evidence of heart failure). · If initially started on beta-blocker, add CCB rather than thiazide-like Diuretic second-line (reduce diabetic risk). · Consider AIIRA rather than ACE with CCB in black (African or |
|
|
Stage 3 Drug Choices
· (A+C+D) ACE inhibitor or Angiotensin-II receptor antagonist and Calcium-channel blocker and thiazide-like Diuretic (chlortalidone or indapamide). |
|
|
Stage 4 Drug Choices
· (A+C+D) ACE inhibitor or Angiotensin–II receptor antagonist and Calcium–channel blocker and thiazide–like Diuretic plus further diuretic (higher–dose thiazide–like diuretic or spironolactone, depending on potassium). |
|
1. The combination of angiotensin-converting enzyme (ACE) inhibitor with an angiotensin-II receptor antagonist (AIIRA) is not recommended for the treatment of hypertension.1 Hypertension: management of hypertension in adults in primary care, NICE Clinical
2.
Guide
line (August 2011))
– Base therapy on pre-existing comorbidities, diabetes, heart failure, CAD
– Begin with a low-dose diuretic in uncomplicated hypertension
– Begin therapy at half the usual dose and increase slowly, consider
– low-dose combination therapy if goal SBP is not met on single-agent therapy
– Focus on systolic blood pressure and patient comorbidities
– Avoid excessive lowering of diastolic blood pressure (70 mmHg)
– Adjust goals when adverse events (postural hypotension, postprandial hypotension) cannot be avoided
– Continue and emphasize nonpharmacologic therapies throughout treatment
Abbreviations: CAD, coronary artery disease; SBP, systolic blood pressure.
Antihypertensive treatment: Preferred drugs as per new European guidelines
|
Subclinical organ damage |
Treatment |
|
LVH |
ACE inhibitors, calcium antagonists, angiotensin receptor blockers |
|
Asymptomatic atherosclerosis |
Calcium antagonists, ACE inhibitors |
|
Microalbuminuria |
ACE inhibitors, angiotensin receptor blockers |
|
Renal dysfunction |
ACE inhibitors, angiotensin receptor blockers |
|
Clinical event |
|
|
Previous stroke |
Any BP-lowering agent |
|
Previous MI |
Beta blockers, ACE inhibitors, angiotensin receptor blockers |
|
Angina pectoris |
Beta blockers, calcium antagonists |
|
Heart failure |
Diuretics, beta blocker, ACE inhibitors, angiotensin receptor blockers, antialdosterone agents |
|
Atrial fibrillation |
|
|
—Recurrent |
Angiotensin receptor blockers, ACE inhibitors |
|
—Permanent |
Beta blockers, nonhydropyridine calcium antagonists |
|
ESRD/proteinuria |
ACE inhibitors, angiotensin receptor blockers, loop diuretics |
|
PAD |
Calcium antagonists |
|
Condition |
|
|
ISH (elderly) |
Diuretics, calcium antagonists |
|
Metabolic syndrome |
ACE inhibitors, angiotensin receptor blockers, calcium antagonists |
|
Diabetes mellitus |
ACE inhibitors, angiotensin receptor blockers |
|
Pregnancy |
Calcium antagonists, methyldopa, beta blockers |
|
Blacks |
Diuretics, calcium antagonists |
LVH=left ventricular hypertrophy; ESRD=end-stage renal disease; PAD=peripheral arterial disease; ISH=isolated systolic hypertension
Nonpharmacologic therapies in stage 1 hypertension
· W eight loss with a focus on reduction of central adiposity
· Aerobic exercise (goal 30 minutes/day, 5 days/week) combined with strength training
· Smoking cessation
· Moderation of alcohol intake (two drinks per day in men, one in women)
· Modification of diet to decrease sodium, cholesterol, and saturated fat intake while maintaining adequate potassium, magnesium, and calcium intake
In patients with a SBP >20 mmHg above their target, it is likely that 2 drugs will need to be initiated. Current recommendations suggest combinations of a low-dose thiazide diuretic with an angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB), or long-acting calcium channel
antagonist (CCA). Many preparations are available combined into a single tablet which would improve ease of administration and compliance. More recently, evidence is beginning to demonstrate that BP reductions may be greater and side effects lower with low-dose combinations of 2 or more antihypertensive agents than with a single agent increased to full dose. As there is no universal agreement on the approach to choosing alternative agents or combination therapy, these decisions should be based on a patient’s comorbidities, weighted with the advantages and disadvantages of a specific drug [Philip A Kithas. Mark A Supiano/Practical recommendations for treatment of hypertension in older patients//Vascular Health and Risk Management.2010:6.P. 561-569].
In general, centrally acting agents (eg, clonidine, methyldopa) and direct vasodilators (minoxidil), due to their CNS side effects (sedation) and propensity to cause significant orthostatic hypotension, should be avoided. Finally, beta-blockers are best avoided in the older hypertensive patient without a specific indication, such as CAD. In the older population, beta-blockers have been associated with no reduction in the risk of stroke or coronary events [Clement DL, De Buyzere ML, De Bacquer Da, et al. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003;348:2407–2415.]
Hypertensive emergencies
By definition, a hypertensive emergency involves an elevated BP (usually 180 mmHg systolic) in association with signs and/or symptoms of target organ damage. The resultant vascular compromise of the affected organ may include hypertensive encephalopathy, acute heart failure with pulmonary edema (flash pulmonary edema), dissecting aortic aneurysm, acute renal failure, and unstable angina. Management requires acute hospitalization for administration of parenteral antihypertensives, with continuous BP monitoring to lower BP rapidly yet not initially to a normal level. Normalization of BP immediately can lead to coronary and cerebral hypoperfusion syndromes. Therefore, BP should be lowered no more than 25% in the first 2 hours, with gradual lowering over the first
6 hours to a target of less than 160/100 mmHg. In comparison with emergencies, hypertensive urgencies are situations requiring BP lowering within 24 hours in order to avoid target organ damage. Again, gradual lowering of
BP is indicated, and can be obtained by administering oral agents in the setting of close follow-up.
Complications:
· Neurologic – Hypertensive encephalopathy, cerebral vascular accident/cerebral infarction. subarachnoid hemorrhage, intracranial hemorrhage
· Cardiovascular – Myocardial ischemia/infarction, acute left ventricular dysfunction, acute pulmonary edema, aortic dissection
· Other – Acute renal failure/insufficiency, retinopathy, eclampsia, microangiopathic hemolytic anemia
Age-associated trends in clinical hypertension
References.
A – Basic:
1. Davidson’s Principles and practice of medicine (21st revised ed.) / by Colledge N.R., Walker B.R., and Ralston S.H., eds. – Churchill Livingstone, 2010. – 1376 p.
2.
3. The Merck Manual of Diagnosis and Therapy (nineteenth Edition)/ Robert Berkow, Andrew J. Fletcher and others. – published by Merck Research Laboratories, 2011.
4. Web -sites:
B – Additional:
1. Braunwald’s Heart Disease: a textbook of cardiovascular medicine (9th ed.) / by Bonow R.O., Mann D.L., and Zipes D.P., and Libby P. eds. – Saunders, 2012. – 2048 p.
2. Braunwald’s Heart Disease: review and assessment (9th ed.) / Lilly L.S., editor. – Saunders, 2012. – 320 p.
3. Cardiology Intensive Board Review. Question Book (2nd ed.) / by Cho L.,
4.
5. Hurst’s the Heart (13th ed.) / by Fuster V., Walsh R.A., Harrington R., eds. – McGraw-Hill, 2010. – 2500 p.
5.
