5 Similar to self-BP measurements, ABPM values are typically lower
than office-based measurements. As a comparison, the normal upper limit for BP in
most patients is 140/90 mm Hg for office-based measurement, 130/80 mm Hg for
ABPM (135/85 mm Hg while awake and 120/75 mm Hg while asleep), and 135/85
mm Hg for self-BP measurements.
5 Therefore, the threshold for normal versus
abnormal is lower than that obtained during office-based measurements.
Evidence indicates that ABPM recordings can predict clinical outcomes more
strongly than office-based BP measurements, most likely because the device factors
in BP throughout nighttime hours, which provides a more accurate reflection of the
overall average pressure load.
9 However, in clinical practice ABPM is not
recommended for routine evaluation of responses to treatment for a number of
reasons, including lack of widespread availability, cost, and intrusiveness of
performing multiple ABPM sessions in the same patient.
BP values measured outside the office should be considered in the overall
treatment of patients with hypertension. However, it is important to acknowledge that
office-based BP measurements have been the source used in the major clinical trials
establishing that treatment of hypertension reduces morbidity and mortality rates.
Therefore, they are still considered the standard values that should guide evaluation
of response to antihypertensive drug therapy in most patients.
The reliability and accuracy of automated BP monitors, whether they are used in
the office or out of the office, can vary significantly. For a summary of commercially
available automatic monitors and whether they have passed validation protocols,
please refer to the dabl Educational Trust website
(http://www.dableducational.org). The use of BP measurements from automated
machines commonly found in grocery stores and pharmacies may have questionable
reliability. Measurements using these publically available machines should not be
Most patients with hypertension have essential hypertension (also known as primary
hypertension), in which there is no identifiable cause for their chronically elevated
Patients with secondary hypertension have a specific identified cause for elevated
BP (Table 9-2). Although only 5% to 10% of those among the hypertensive
population have causes that are purely secondary, further diagnostic evaluation
should occur if physical or laboratory findings suggest the possibility of a secondary
3,10,11 Some secondary causes are potentially reversible and may
normalize BP (e.g., coarctation of the aorta), whereas others are more often
superimposed on and worsen an already elevated BP (e.g., obstructive sleep apnea).
The distinction is important because treatment of an underlying cause may not always
be expected to completely normalize BP and allow discontinuation of
antihypertensive therapies. In patients who have resistant hypertension (requiring
three or more drugs for BP control) or who have a sudden and significant increase in
BP, further diagnostic workup for secondary causes should be considered.
White-coat hypertension describes patients who have consistently elevated BP
values measured in a clinical environment in the presence of a health care
professional (e.g., physician’s office), yet when measured elsewhere or with 24-hour
ambulatory monitoring, BP is not elevated.
5,6 Home BP monitoring or 24-hour ABPM
is warranted in patients suspected of having white-coat hypertension to differentiate
5 The commonly used definition is a persistently elevated
average office BP of greater than 140/90 mm Hg and an average awake ambulatory
reading of less than 135/85 mm Hg.
8 The label white-coat hypertension applies only
to patients without target-organ disease who are not on antihypertensive therapy.
Secondary Causes of Hypertension
Chronic steroid therapy and Cushing syndrome
Amphetamines (amphetamine, dexmethylphenidate, dextroamphetamine, lisdexamfetamine, methylphenidate,
phendimetrazine, and phentermine)
Antidepressants (bupropion, desvenlafaxine, and venlafaxine)
Antihypertensive agents that are abruptly stopped (only β-blockers and central a2
Anabolic steroids (e.g., testosterone)
Calcineurin inhibitors (cyclosporine and tacrolimus)
Cocaine and other illicit drugs
prednisone, and triamcinolone)
Erythropoiesis-stimulating agents (darbepoetin-alfa and erythropoietin)
Ergot alkaloids (ergonovine and methysergide)
Estrogen-containing oral contraceptives (ethinyl estradiol)
Licorice (including some chewing tobacco)
Nonsteroidal antiinflammatory drugs (all types)
Oral decongestants (e.g., pseudoephedrine)
Phenylephrine (ocular administration)
Vascular endothelial growth factor inhibitor (bevacizumab)
Vascular endothelial growth factor receptor tyrosine kinase inhibitor (sorafenib and sunitinib)
Thyroid or parathyroid disease
Significant controversies surround white-coat hypertension. Although this does not
represent a clinical diagnosis, patients with white-coat hypertension are at risk for
eventually developing essential hypertension. Moreover, patients with white-coat
hypertension are at a higher risk for CV disease than normotensive patients.
decision to treat or not treat white-coat hypertension is controversial. Many patients
enrolled in the landmark clinical trials that demonstrated reductions in CV morbidity
and mortality with antihypertensive therapy likely had white-coat hypertension
because only office BP measurements were used for inclusion. At minimum, patients
with white-coat hypertension should be treated with lifestyle modifications and need
to be closely monitored with a device that can measure BP outside the clinic
environment if they are not treated with antihypertensive drug therapy.
Hypertensive crises are situations in which measured BP values are markedly
elevated (>180/110 mm Hg). They are classified as either a hypertensive emergency
(with acute or progressive target-organ damage) or urgency (without acute or
progressive target-organ damage). Hypertensive emergencies require hospitalization
for immediate BP lowering. Hypertensive urgencies do not require immediate BP
lowering; instead, BP should be slowly reduced within 24 hours (but not generally to
goal BP so quickly) (see Chapter 16, Hypertensive Crises).
Hypertension is treated with both lifestyle modifications and pharmacotherapy. The
JNC-8 is considered the “gold standard” consensus guidelines for the management of
hypertension in the United States.
2 The overall principle of the guideline is to
implement lifestyle modifications in addition to pharmacotherapy to control BP in
patients with hypertension. The presence of specific comorbidities in any given
patient should be considered when selecting specific pharmacotherapy to treat
hypertension. These issues are discussed later in this chapter.
The overarching goal of treating patients with hypertension is to reduce associated
disease and other forms of CV disease.
Achieving goal BP is an important step in the overall treatment of patients with
hypertension. According to the JNC-8 guidelines, patients with hypertension of age
greater than 18 and less than 60 should have a BP goal of less than 140/90 mm Hg
In contrary to previous editions of the JNC guidelines, where the BP goal for
patients with diabetes or chronic kidney disease (CKD) is lower, JNC-8
recommends the same treatment goal for these patients (<140/90 mm Hg).
The change in recommendations is based on some more recent evidence failing to
show that more aggressive BP lowering to goal of less than 140/90 mm Hg further
improves clinical outcome. There is moderate-quality evidence from three trials
(Systolic Hypertension in the Elderly Program [SHEP], Syst-Eur, and UKPDS) that
treatment to an SBP goal of lower than 150 mm Hg improves CV and
cerebrovascular health outcomes and lowers mortality in adults with diabetes and
13–15 However, there are no randomized controlled trials addressing
whether treatment to an SBP goal of lower than 140 mm Hg compared with a higher
goal (e.g., <150 mm Hg) improves health outcomes in adults with diabetes and
hypertension. In the absence of such evidence, the panel recommends a BP goal
consistent with the BP goals in the general population younger than 60 years with
hypertension. Use of a consistent BP goal in the general population in adults with
diabetes of any age may facilitate guideline implementation. This recommendation
for an SBP goal of lower than 140 mm Hg in patients with diabetes is also supported
by the ACCORD-BP trial, demonstrating
16 no difference in the primary end point of
major CV events when patients with type 2 diabetes were treated to an SBP goal of
less than 120 mm Hg compared with an SBP goal of less than 120 mm Hg after a
mean of 4.7 years. There were also no differences in any of the secondary outcomes
except for a reduction in stroke. However, the incidence of stroke in the group treated
to lower than 140 mm Hg was much lower than expected, so the absolute difference
in fatal and nonfatal stroke between the two groups was only 0.21% per year.
Clinical Findings Suggestive of Secondary Hypertension
Sleep apnea Daytime fatigue and
Renovascular disease Moderate or severe high
Renoparenchymal disease Dysuria, polyuria, nocturia;
Coarctation of the aorta Intermittent claudication Diminished or absent
Pheochromocytoma Paroxysmal headaches,
Primary aldosteronism Weakness, polyuria,
Orthostatic hypotension Hypokalemia
Cushing syndrome Menstrual irregularity Moon face; truncal
BP, blood pressure; IVP, intravenous pyelogram; SBP, systolic blood pressure
Committee on Detection, Evaluation, and Treatment of High Blood Pressure.
JNC-8 similarly recommends the same goal DBP in adults with diabetes and
hypertension as in the general population (<90 mm Hg). There is no sufficient
evidence to support such a lower goal.
Similarly, in patients with CKD, JNC-8 has recommended individuals younger
than 70 years with an estimated glomerular filtration rate (GFR) or measured GFR
less than 60 mL/minute/1.73 m2 and people of any age with albuminuria defined as
greater than 30 mg of albumin/g of creatinine at any level of GFR to have a BP goal
for <140/90 mm Hg. This recommendation is less aggressive than previous JNC
The new panel also felt that in adults younger than 70 years with CKD, the
evidence is insufficient to determine if there is a benefit in mortality or CV or
cerebrovascular health outcomes with antihypertensive drug therapy to a lower BP
goal (e.g., <130/80 mm Hg) compared with a goal of lower than 140/90 mm Hg.
There is evidence of moderate quality demonstrating no benefit in slowing the
progression of kidney disease from treatment with antihypertensive drug therapy to a
lower BP goal (e.g., <130/80 mm Hg) compared with a goal of lower than 140/90
It is important to note that the recommendation of BP goal for patients with CKD
applies only to those younger than 70 years. Based on current available evidence,
JNC-8 cannot make similar recommendation for a BP goal in people aged 70 years
or older with GFR less than 60 mL/minute/1.73 m2
. The commonly used estimating
equations for GFR were not developed in populations with significant numbers of
people older than 70 years and have not been validated in older adults. No outcome
trials included large numbers of adults older than 70 years with CKD.
Hypertension-Associated Complications and Major Cardiovascular Risk Factors
Hypertension-Associated Complications
Atherosclerotic vascular disease
Coronary artery disease (sometimes called coronary heart disease)
Left ventricular dysfunction (systolic heart failure)
Advanced age (>55 years for men, >65 years for women)
Kidney disease (microalbuminuria or estimated GFR <60 mL/minute/1.73 m
BMI, body mass index; CV, cardiovascular; GFR, glomerular infiltration rate.
The issue of whether more aggressive BP goals (i.e., <130/80 or <120/80 mm Hg)
result in better reductions in risk of CV events than the standard goal of less than
140/90 mm Hg remains an ongoing clinical controversy. Until newer clinical data
and newer consensus guidelines are published, it is reasonable for clinicians to
follow the BP goals recommended in the JNC-8. The Systolic Blood Pressure
Intervention Trial (SPRINT) is a randomized, multicenter clinical trial that is
comparing intensive hypertension treatment (SBP goal <120 mm Hg) with standard
treatment (SBP goal <140 mm Hg) in approximately 7,500 patients with hypertension
and at least one other CV risk factor (patients with a history of diabetes or stroke are
excluded). The SPRINT will not be completed until the year 2018 or later, but when
completed it will provide further evidence regarding goal BP values.
Another area of controversy is the BP goal value in the very elderly, commonly
defined as those 80 years of age or older. JNC-8 recommends that, in the general
population aged 60 years or older, hypertension should be treated to a goal of
2 However, within this population, the only clear prospective data
supporting antihypertensive therapy is from the Hypertension in the Very Elderly
Trial (HYVET), which used a BP goal of less than 150/80 mm Hg.
note that BP goals among the elderly are based primarily on expert consensus. BP
treatment goal for individual elderly patients to a certain extent should be determined
by their frailty and their ability in tolerating side effects of antihypertensive agents
(such as orthostatic hypotension).
Lifestyle modifications are the cornerstone of management for preventing and treating
hypertension. AHA guidelines for lifestyle modifications recommend both diet and
21,22 These recommendations are summarized in Table 9-5. Engaging in these
modifications is encouraged for all persons to prevent the development of
hypertension; however, they are recommended as a component of first-line therapy in
all patients with prehypertension and in all patients with a diagnosis of hypertension
regardless of whether their BP values are at goal or not.
lowering, CV risk may also be reduced.
Lifestyle Modifications to Prevent and Treat Hypertension
Weight management Lose weight if overweight or obese, ideally attaining a BMI <25 kg/m
Maintain a desirable BMI (18.5–24.9 kg/m
Consume a diet that is rich in fruits and vegetables (8–10 servings/day), rich in
low-fat dairy products (2–3 servings/day), but has reduced amounts of
Reduced sodium intake Reduce daily dietary sodium intake as much as possible, ideally to <65
mmol/day (equal to 1.5 g/day sodium or 3.8 g/day sodium chloride)
Increase daily dietary potassium intake to 120 mmol/day (4.7 g/day), which is
the amount provided in a DASH-type diet
For patients who drink alcohol, limit consumption to no more than two drinks
per day in men and no more than one drink per day in women and lighterweight people.
a Do not recommend alcohol consumption in patients who do
continuous or intermittent 5 day/week, but preferably daily
BMI, body mass index; DASH, Dietary Approaches to Stop Hypertension.
Weight loss as small as 5% to 10% of body weight in overweight individuals may
significantly lower CV risk. For most patients, an average weight loss of 10 kg can
reduce SBP by 5 to 20 mm Hg, a reduction comparable to that achieved from the
addition of an antihypertensive drug used as monotherapy.
The DASH (Dietary Approaches to Stop Hypertension) diet is rich in fruits,
vegetables, and low-fat dairy foods, coupled with reduced saturated and total fat.
The patient education publication entitled “Your Guide to Lowering Your Blood
Pressure with DASH” can be found at
http://www.nhlbi.nih.gov/health/public/heart/hbp/dash/index.htm. The DASH diet
can substantially reduce BP (8–14 mm Hg in SBP for most patients) and yield similar
results to single-drug therapy. The low-fat component of this diet is important
because weight loss is more readily achieved by a reduced-calorie diet (fats
contribute more calories per gram than
do either carbohydrates or protein) and lowered fat intake also reduces the risk of
CV disease by lowering cholesterol.
The average American intake of sodium is more than 6 g/day. Restricting sodium
should be encouraged for patients with prehypertension or hypertension, and the
current recommendation to restrict daily sodium intake to no more than 1.5 g is lower
than what has traditionally been suggested. Some clinicians may argue that the
efficacy of implementing sodium restriction in patients with hypertension may vary.
Evidence from clinical trials has shown, however, that sodium restriction provides
mean reductions in BP of 5/2.7 mm Hg in patients with hypertension.
sodium to less than 1.5 g daily has been shown to decrease SBP by more than 20 mm
Hg in patients with resistant hypertension.
24 Some populations (diabetic patients,
blacks, and elderly persons) respond better to sodium restriction than the general
population, but all patients with hypertension should be instructed to reduce their
sodium intake. They should be counseled not to add salt to foods and to avoid or
minimize ingestion of processed or packaged foods, foods with high sodium content,
and nonprescription drugs containing sodium.
Increasing dietary potassium intake is recommended, although it is not commonly
identified by most patients as a dietary modification that will lower BP. Adhering to
a DASH eating plan will usually assure an intake of the recommended 4.7 g daily.
Dietary supplementation should be the primary strategy to increase potassium.
Implementing potassium supplementation outside of dietary sources for the sole
purpose of lowering BP should be avoided because of the potential harm from
hyperkalemia. Moreover, potassium supplementation in patients with hypertension
who are treated with a potassium-sparing diuretic, aldosterone antagonist, ACEI, or
an ARB may cause hyperkalemia. This can also occur in patients with hypertension
and CKD who are treated with potassium supplementation.
Explaining the need to limit alcohol consumption is complicated. Whereas data
suggest that small daily doses of alcohol (e.g., one glass of red wine with dinner) are
associated with lower CV risk, excessive alcohol intake can elevate BP, decrease
the effectiveness of antihypertensive medications, and increase the risk of stroke.
Patients who consume three to four drinks per day experience a 3- to 4-mm Hg
increase in SBP and a 1- to 2-mm Hg increase in DBP compared with those who do
not drink. These increases are even higher in patients who consume more alcohol.
Moderate alcohol consumption of two or fewer drinks daily in men and one or fewer
drinks daily in women or lighter-weight individuals can decrease SBP approximately
2 to 4 mm Hg. Patients should be instructed that one drink is equal to 1.5 ounces of
80-proof whiskey, 5 ounces of wine, or 12 ounces of beer.
Regular physical activity can reduce SBP by 4 to 9 mm Hg in most patients.
include reducing the incidence of hypertension, assisting weight loss and weight loss
maintenance, and improving overall CV fitness. Most patients with hypertension can
safely increase their regular aerobic activity. Those with more severe forms of
target-organ damage (e.g., angina and previous MI) may, however, need a medical
evaluation before increasing their activity level. Physical activity should ideally
occur for at least 30 minutes, at least 5 days of the week, but preferably daily.
Walking, running, cycling, swimming, and cross-country skiing are examples of
aerobic exercise that are recommended for physical activity.
Numerous clinical trials have demonstrated that antihypertensive pharmacotherapy
reduces the risk of hypertension-associated complications (e.g., CV morbidity and
mortality). This evidence is the foundation for JNC-8 consensus guidelines, which
provide specific evidence-based pharmacotherapy recommendations based on
patient-specific medical history and CV risk.
JNC-8 guidelines recommend that in the general nonblack population, including
those with diabetes, initial antihypertensive treatment should include a thiazide-type
diuretic, calcium-channel blocker (CCB), ACEI, or ARB. In the general black
population, including those with diabetes, initial antihypertensive treatment should
include a thiazide-type diuretic or CCB. In the population aged ≥18 years with CKD,
initial (or add-on) antihypertensive treatment should include an ACEI or ARB to
improve kidney outcomes. This applies to all CKD patients with hypertension
regardless of race or diabetes status. Evidence obtained since the 2003 JNC-7
guidelines demonstrates that, for first-line treatment in primary prevention patients,
β-blocker therapy is not as effective in reducing CV events compared with ACEI,
ARB, CCB, or thiazide diuretic therapy.
25 Therefore, unlike previous versions of the
JNC guidelines, β-blocker is no longer recommended as one of the first-line
treatment option. Moreover, newer evidence also suggests that the reductions in CV
events with ACEI, ARB, CCB, or thiazide diuretic are comparable, so that one agent
is not automatically preferred over another.
26 Unlike previous versions of JNC
guidelines, JNC-8 guidelines also did not discuss selection of antihypertensive
agents in patients with specific other comorbidities (aside from diabetes and CKD).
Clinicians are to consult treatment guidelines of the specific comorbidities (e.g.,
heart failure and coronary artery disease) to help make treatment decisions.
Angiotensin-Converting Enzyme Inhibitors
The ACEIs directly inhibit ACE, blocking the conversion of angiotensin I to
angiotensin II. This action reduces angiotensin II-mediated vasoconstriction and
aldosterone secretion and ultimately lowers BP. Because additional pathways exist
for the formation of angiotensin II, ACEIs do not completely block the production of
angiotensin II. Aldosterone release is indirectly suppressed by ACEIs; thus,
hyperkalemia is possible and potassium concentrations should be monitored. Patients
with CKD or volume depletion may be more susceptible to hyperkalemia or to
further kidney dysfunction owing to a higher dependence on the vasoconstriction
provided by angiotensin II to support GFR among these patients.
Inhibiting ACE also prevents the breakdown and inactivation of bradykinin, which
may lead to additive vasodilation by enhancing NO. However, bradykinin
accumulation can also cause a nonproductive cough in some patients, which is the
most frequent, yet harmless, side effect of ACEI therapy. ACEI therapy has been
associated with angioedema, which is a rare, but serious, hypersensitivity reaction.
Angioedema typically presents as swelling of the tongue, lips, and mouth, but can
also involve the eyes and upper airway.
The development of angioedema requires discontinuation of the ACEI. These
agents are metabolically neutral and may have a positive effect on insulin resistance
and risk of progression to type 2 diabetes.
The ARBs modulate the RAAS by directly blocking the angiotensin II type 1 receptor
site, preventing angiotensin II-mediated vasoconstriction and aldosterone release.
Overall, ARBs are the best tolerated of the first-line agents.
and are therefore associated with less incidence of cough. Because aldosterone is
indirectly suppressed, monitoring of potassium is important to avoid hyperkalemia.
Similar to the ACEIs, patients with CKD or volume depletion may be more
susceptible to hyperkalemia or to further kidney dysfunction. These agents are
metabolically neutral and may have a positive effect on insulin resistance and risk of
progression to type 2 diabetes.
The CCBs are pharmacologically complex. They reduce calcium entry into smooth
muscles, which causes coronary and peripheral vasodilation and lowers BP. All
decrease cardiac contractility (except amlodipine and felodipine). Dihydropyridine
CCBs are primarily vasodilators that can cause a reflex tachycardia. This is in
contrast to the nondihydropyridine CCBs (verapamil and diltiazem) that directly
block the atrioventricular (AV) node, decrease heart rate, and decrease cardiac
contraction, yet still have vasodilatory effects. Side effects depend on the type of
CCB, but can include flushing, peripheral edema, tachycardia, bradycardia or heart
Diuretics, particularly thiazide and thiazide-like (e.g., chlorthalidone) diuretics, have
been extensively studied in large landmark clinical trials for hypertension. When
initially started, they induce a natriuresis that causes diuresis and decreases plasma
volume and CO. With chronic use, diuresis usually dissipates, and CO gradually
returns to near-normal levels. The long-term BP-lowering effect in the face of these
changes suggests a sustained decrease in PVR as the primary mechanism responsible.
Dose-related electrolyte and metabolic alterations (e.g., hypokalemia,
hyperuricemia, hyperglycemia, and hypercholesterolemia) can occur with thiazide
diuretics. These effects were particularly problematic when high doses were used
many years ago (e.g., hydrochlorothiazide [HCTZ] 100–200 mg/day), but are
drastically minimized by using lower doses that are now considered the standard of
care (e.g., HCTZ 12.5–25 mg/day).
26 Thiazide diuretics can be used in combination
with a potassium- sparing diuretic (i.e., triamterene and amiloride) to minimize
potential potassium depletion. Other biochemical changes in glucose and cholesterol
are minimal and mostly transient with low-dose therapy.
JNC-8 consensus statement recommends that first-line agents should be used when
initiating antihypertensive therapy or when added on to existing antihypertensive
therapy unless patients have contraindications to them.
β-Blockers have several direct effects on the CV system. They can decrease cardiac
contractility and CO, lower heart rate, blunt sympathetic reflex with exercise, reduce
central release of adrenergic substances, inhibit norepinephrine release peripherally,
and decrease renin release from the kidney. All these contribute to their
antihypertensive effects. Adverse metabolic effects include altered lipids and
increased glucose concentrations. Similar to thiazide diuretics, these changes are
generally temporary and have minimal to no clinical significance. These agents were
considered first line for the treatment of most patients with hypertension in the JNC-7
guideline. However, evidence published after the 2003 JNC-7 has further defined
25 Unless patients have other indication for β-blockers (e.g., CAD or left
ventricular dysfunction), they should not be used as first-line agent for primary
prevention of CV events in patients with hypertension.
Spironolactone and eplerenone are aldosterone antagonists. Potent blockade of the
aldosterone receptor inhibits sodium and water retention and inhibits
vasoconstriction. These agents are also considered potassium-sparing diuretics.
Hyperkalemia is a known dose-dependent effect with aldosterone antagonists and is
more prominent in patients with CKD or in patients taking a concurrent RAAS
blocking agent (ACEI, ARB, or direct renin inhibitor). Gynecomastia is a side effect
of spironolactone, usually more common with higher doses, that does not occur with
There are other antihypertensive drug classes, many of which are older agents, which
should primarily be used to provide additional BP lowering only after first-line and
second-line agents have been implemented.
Loop diuretics (e.g., furosemide and torsemide) can be used in some patients for
26 When dosed appropriately, they can provide BP reductions similar to
those seen with a thiazide diuretic. Because they are short-acting and subject to a
significant postdose antinatriuretic effect, they should generally be reserved for
patients with heart failure or severe CKD in whom their diuretic action remains
prolonged. Significant edema usually accompanies these conditions, such that they
generally require a loop diuretic instead of a thiazide diuretic for adequate diuresis
and volume removal. Because they are more potent at inducing diuresis compared
with thiazide diuretics, they can cause more electrolyte disturbances (e.g.,
Aliskiren, approved in 2007, is the only direct renin inhibitor. Similar to an ACEI
or ARB, this agent is a RAAS blocker. It is approved for treatment of hypertension
and has been studied in combination with an ACEI, ARB, or thiazide diuretic. It is
the newest antihypertensive drug class; therefore, its exact role will continue to
evolve as additional clinical data are generated.
α-Blockers (e.g., doxazosin, prazosin, and terazosin) attach to peripheral α1
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