hypertension itc6 1.full 1

8/3/2019 Hypertension ITC6 1.Full 1

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in the clinic

Hypertension

Screening and Prevention page ITC6-2

Diagnosis page ITC6-3

Treatment page ITC6-6

Practice Improvement page ITC6-14

CME Questions page ITC6-16

Section EditorsChristine Laine, MD, MPHDavid Goldman, MDHarold C. Sox, MD

Physician WritersDebbie L. Cohen, MDRaymond R. Townsend, MD

The content ofIn the Clinic is drawn from the clinical information and

education resources of the American College of Physicians (ACP), including

PIER (Physicians Information and Education Resource) and MKSAP (Medical

Knowledge and Self-Assessment Program). Annals of Internal Medicine

editors develop In the Clinic from these primary sources in collaboration with

the ACPs Medical Education and Publishing Division and with the assistance

of science writers and physician writers. Editorial consultants from PIER and

MKSAP provide expert review of the content. Readers who are interested in these

primary resources for more detail can consult http://pier.acponline.org and otherresources referenced in each issue ofIn the Clinic.

The information contained herein should never be used as a substitute for clinical

judgment.

2008 American College of Physicians


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What long-term health risks areassociated with hypertension?The relationship between bloodpressure level and cardiovasculardisease is linear, continuous, andindependent of and additive toother risk factors. For persons age40 to 70 years, each increment of

either 20 mm Hg in systolic bloodpressure level or 10 mm Hg in dias-tolic blood pressure level doublesthe risk for cardiovascular disease(CVD) across the range of bloodpressure levels from 115/75 mm Hgto 185/115 mm Hg (2). Whenother cardiovascular risk factors,such as diabetes or chronic kidneydisease, are present, the CVD riskassociated with hypertension is evenhigher. Complications of hyperten-

sion include retinopathy, cerebrovas-cular disease, ischemic heart disease,atrial fibrillation, heart failure,chronic kidney disease, and periph-eral vascular disease.

Should clinicians screen forhypertension?The U.S. Preventive Services TaskForce recommends screening theadult general population for hyper-tension. It does not recommend aspecific screening interval because

of lack of evidence to support one(3). The Joint National Committeeon Prevention, Detection, Evalua-tion, and Treatment of High BloodPressure ( JNC 7) recommendsscreening every 2 years if bloodpressure level is less than 120/80mm Hg and annually if blood

pressure level is 120/80 to 139/89mm Hg (2).

What is prehypertension and what

is its proper management?

Prehypertension is a category thatfirst appeared in the seventh JNCreport. Prehypertension is defined

as a blood pressure level of 120/80to 139/89 mm Hg (2). Patientswith prehypertension are atincreased risk for developing overthypertension and CVD. Thesepatients should restrict dietarysodium, lose weight, reduce alcoholintake, and increase aerobic exer-cise. Several trials have evaluateddrug treatment for prehypertension.At present, drug therapy is not rec-ommended for prehypertension.

The Trial of Preventing Hypertension ran-

domly assigned participants with prehy-

pertension to active treatment with can-

desartan (an angiotensin-receptor blocker

[ARB]) or placebo for 2 years and followed

them for 4 years. Active treatment delayed

onset of hypertension but did not prevent

it (4).

Trials of Hypertension Prevention (TOHP) 1

and 2 examined the benefits of reductions

in weight, sodium intake, and stress and

supplementation with potassium, magne-sium, fish oil, and calcium in persons with

diastolic blood pressure levels of 80 to 90

mm Hg. TOHP 1 suggested that weight loss

(3/2mm Hg reduction) and sodiumrestriction (2/1mm Hg reduction) wereeffective. TOHP 2 confirmed that weight

loss and sodium restriction delay hyperten-

sion (5, 6).

2008 American College of Physicians ITC6-2 In the Clinic Annals of Internal Medicine 2 December 2008

Hypertension affects more than 65 million people in the UnitedStates, with about 2 million new cases diagnosed annually (1, 2).Most patients have primary or essential hypertension and are likely

to remain hypertensive for life. Risk factors for hypertension include a familyhistory of hypertension, African-American ethnicity, obesity, a high sodiumor alcohol intake, and a sedentary lifestyle. Treatment to control blood pres-sure level reduces the risk for cardiovascular, cerebrovascular, and renal out-comes of hypertension. Unfortunately, many people with hypertension do notreceive optimal therapy.

Screening and

Prevention

1. Ong KL, Cheung BM,Man YB, et al. Preva-lence, awareness,treatment, and con-trol of hypertensionamong United Statesadults 1999-2004.Hypertension.2007;49:69-75.[PMID: 17159087]

2. Chobanian AV, BakrisGL, Black HR, et al.National Heart, Lung,and Blood Institute.Seventh report of theJoint National Com-mittee on Prevention,Detection, Evaluation,and Treatment ofHigh Blood Pressure.

Hypertension.2003;42:1206-52.[PMID: 14656957]

3. U.S. Preventive Ser-vices Task Force.Screening for highblood pressure: U.S.Preventive Services

Task Force reaffirma-tion recommenda-tion statement. AnnIntern Med.2007;147:783-6.[PMID: 18056662]

4. Julius S, Nesbitt SD,Egan BM, et al. Feasi-bility of treating pre-hypertension with anangiotensin-receptorblocker. N Engl J

Med. 2006;354:1685-97. [PMID: 16537662]

5. Cook NR, Cutler JA,Obarzanek E, et al.Long term effects ofdietary sodiumreduction on cardio-vascular disease out-comes: observationalfollow-up of the trialsof hypertension pre-vention (TOHP). BMJ.2007;334(7599):885.


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6. Batey DM, KaufmannPG, Raczynski JM, etal. Stress manage-ment intervention forprimary preventionof hypertension:detailed results fromPhase I of Trials ofHypertension Preven-tion (TOHP-I). AnnEpidemiol.2000;10(1):45-58.

2008 American College of PhysiciansITC6-3In the ClinicAnnals of Internal Medicine2 December 2008

DiagnosisHow should clinicians diagnose

and stage hypertension?

The steps in diagnosing hyperten-sion are simple but often not fol-lowed. The most common errors(failure to have the patient sit qui-etly for 5 minutes before a readingis taken, failure to support the limbused to measure blood pressure, use

of a too-small cuff, and too-rapidcuff deflation) lead to falselyincreased readings. The best posi-tion for patients is sitting, becausethe studies that established thevalue of treating hypertension usedthis position to measure the bloodpressures that diagnosed hyper-tension and guided dose adjust-ment (7). See Table 1 and the Boxfor instructions on blood pressuremeasurement.

A persons blood pressure can varywidely. A single accurate measure-ment is a good start but notenough: Measure blood pressuretwice and take the average. Therunning average is more importantthan individual readings. Hyper-tension is diagnosed if the averageof at least 2 readings per visitobtained at 3 separate visits each 2

to 4 weeks apart is 140 mm Hg orgreater systolic and 90 mm Hg orgreater diastolic. According to theJNC 7, a normal blood pressurelevel is 120/80 mm Hg or less (2).Prehypertension is a blood pressurelevel of 120/80 to 139/89 mm Hg.Stage 1 hypertension is a systolicblood pressure level of 140 to 159

mm Hg or a diastolic blood pressurelevel of 90 to 99 mm Hg. Stage 2hypertension is a systolic blood pres-sure level greater than or equal to160 mm Hg or a diastolic bloodpressure level greater than or equalto 100 mm Hg. The JNC 7 classifi-cation combines the stage 2 and 3categories of older classifications (2).In persons older than 50 years, sys-tolic blood pressure levels greaterthan 140 mm Hg are a more impor-

tant CVD risk factor than diastolichypertension.

Pseudohypertension can occur inpatients with stiff, incompressiblearteries. To detect it, inflate theblood pressure cuff to at least 30mm Hg above the palpable systolicpressure and then try to rollthe brachial or radial artery under-neath your fingertips (Oslers

Screening and Prevention... Cardiovascular risk increases as blood pressureincreases, starting at a blood pressure level of 115/75 mm Hg. Guidelines recom-mend screening all adults for hypertension. Although evidence supporting a specificscreening interval is thin, consensus advocates intervals of 1 to 2 years. Prehyper-tension (a blood pressure level of 120/80 to 139/89 mm Hg) increases the risk forsustained hypertension and CVD. Lifestyle modification can delay onset of hyper-tension and CVD.

CLINICAL BOTTOM LINE

Instructions for Taking Blood

Pressure

Have patient relax, sitting (feeton floor, back supported) for >5min before taking the bloodpressure.

Support patients arm (for

example, resting on a desk) forthe measurement.

Use the stethoscope bell, notthe diaphragm, for auscultation.

Check blood pressure first inboth arms with the patient sit-ting. Note which arm gives thehigher reading and use this armfor all other (standing, lyingdown) and future readings.

Measure blood pressure in sit-ting, standing, and lying posi-tions. All measurements shouldbe separated by 2 min.

Use the correct cuff size andnote if a larger- or smaller-than-normal cuff size is needed(Table 1).

Record systolic (onset of firstsound) and diastolic (disappear-ance of sound) pressures.

Record exact results to nearesteven number.

Table 1. Blood Pressure Cuff Size Criteria

Arm Circumference Weight Cuff Size to Use Female Male

2432 cm 200 Large

3850 cm* Thigh

* Either cuff is acceptable for the overlap circumferences.


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7. Pickering TG, Hall JE,Appel LJ, et al. Rec-ommendations forblood pressure meas-

urement in humansand experimental ani-mals: part 1. Circula-tion. 2005;111:697-716. [PMID: 15699287]

8. Messerli FH. Oslersmaneuver, pseudohy-pertension, and truehypertension in theelderly. Am J Med.1986;80:906-10.[PMID: 2939716]

9. Pickering TG, ShimboD, Haas D. Ambula-tory blood-pressuremonitoring. N Engl JMed. 2006;354:2368-74. [PMID: 16738273]

10. Angeli F, Verdecchia P,Gattobigio R, et al.

White-coat hyperten-sion in adults. BloodPress Monit.2005;10:301-5.[PMID: 16496443]

11. Eguchi K, Hoshide S,Ishikawa J, et al. Car-diovascular prognosisof sustained andwhite-coat hyperten-sion in patients withtype 2 diabetes melli-tus. Blood PressMonit. 2008;13:15-20.[PMID: 18199919]


maneuver) (8). Healthy arteriesshould not be palpable when empty.If you feel a stiff, tube-like structure,the patient may have pseudohyper-tension.

What is white coat hypertension?White coat hypertension is definedas an elevated office blood pressurewith lower blood pressure readings

measured at home or with a 24-hour ambulatory blood pressuremonitor (9). The prevalence ofwhite coat hypertension is 10% to20% (10). These patients are at ele-vated risk for overt hypertensionand CVD (11). Current guidelinesdo not recommend pharmacologictreatment for these patients but dorecommend lifestyle modificationsand regular follow-up.

When is ambulatory bloodpressure monitoring indicated?The ambulatory blood pressuremonitor is a 24-hour portabledevice that the patient wears duringtheir regular activities. It measuresblood pressure every 15 to 20 min-utes during the day and every 30 to60 minutes at night. Ambulatoryblood pressure monitoring providesthe most accurate assessment ofblood pressure (10). Most patientswith hypertension do not need it,

and the Center for Medicare &Medicaid Services pays for only 1

indication: diagnosing white coathypertension.The Box lists the otherpotential situations in which ambu-latory monitoring may be helpful.

Ambulatory blood pressure moni-toring may also be useful in identi-fying high-risk blood pressure pat-terns that are associated withincreased cardiovascular events in

patients with hypertension. One isloss of dipping status, which isassociated with worse cardiovascu-lar outcomes of hypertension.Blood pressure of patients with lossof dipping status falls less than 10%at night relative to daytime bloodpressure, in contrast to the bloodpressure of patients with dipper sta-tus, which falls at least 10% at night(12). The other high-risk pattern isblood pressure surges in the early

morning hours (13), which is associ-ated with increased cerebrovasculardisease risk. A surge is generallydefined as a greater than 55mm Hgdifference in systolic pressure levelbetween sleeping and early hourwaking. In these patients, physiciansmay wish to target treatment at thehigh morning systolic values.

What are the key elements of thehistory for patients withhypertension?

Assess the duration, rapidity ofonset, and severity of the hyperten-sion. Ask about cardiovascular riskfactors, concomitant medical condi-tions, symptoms of target organdamage, past treatment and itseffects, and lifestyle (dietary habits,alcohol consumption, tobacco use,and level of physical activity). Noteany family history of hypertension,renal disease, cardiovascular prob-lems, stroke, and diabetes mellitus.

Ask about increased stress, physicalinactivity, and dietary salt intake.

Sudden onset of severe hyperten-sion with previously normalblood pressure levels suggests asecondary form of hypertension.Ask about symptoms that suggestsecondary hypertension. Palpita-tions, tachycardia, paroxysmal

Potential Indications for Use of

Ambulatory Blood Pressure

Monitoring

Unusual variability of blood pressurelevel

Possible white coat hypertension

Evaluation of nocturnal hypertension

Evaluation of drug-resistanthypertension

Determining the efficacy of drugtreatment over 24 hours

Diagnosis and treatment of hyperten-sion in pregnancy

Evaluation of symptomatic hypoten-sion on various medications, suggest-ing that the patient may benormotensive

Evaluation of episodic hypertension orautonomic dysfunction


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15. Cordain L, Eaton SB,Sebastian A, et al.Origins and evolu-tion of the Westerndiet: health implica-tions for the 21stcentury. Am J ClinNutr. 2005;81:341-54.[PMID: 15699220]

pressure is less than 130/80 mm

Hg. Key diseases include diabetes;chronic kidney disease; establishedCVD or CAD equivalents, suchas acute coronary syndrome, STelevation myocardial infarction,stroke, and stable angina (2). Inpatients with more than 1 g pro-teinuria, the recommended goalblood pressure target is 125/75 mmHg or less.

What are treatment goals for

patients with hypertension?See Box for blood pressure goalsfrom different guidelines. Goalblood pressure level is less than140/90 mm Hg in a patient withhypertension without CVD-relatedcomorbid conditions. In patientswith comorbid illness or more thana 10% 10-year Framingham risk forcardiovascular events, goal blood

Treatment

Diagnosis... Diagnosis of hypertension requires careful measurement of bloodpressure levels on several occasions. Systolic blood pressure levels 140 mm Hg orgreater or diastolic blood pressure levels 90 mm Hg or greater, based on the aver-age of 3 sets of 2 or more readings obtained 2 to 4 weeks apart establishes thediagnosis of hypertension. The goals of the diagnostic evaluation are to search fora secondary cause, to detect other CVD risk factors, and to detect damage to tar-get organs. In addition, the history should focus on past treatment, current med-ications, and contributing lifestyle factors. The focal points of the physical exami-nation are eyegrounds, cardiovascular system, and nervous system. Levels ofhemoglobin, urinalysis, serum creatinine, glucose, lipids, electrolytes, and an ECGare routine laboratory tests for patients with newly diagnosed hypertension.


Table 3. Work-Up to Pursue Possible Secondary Hypertension

Secondary cause Evaluation (findings)

Coarctation of aorta Chest film (rib notching; reverse 3 sign), 2-dimensional echocardio-gram, aortogram (coarctation directly seen), MRI

The Cushing syndrome Dexamethasone suppression test (failure to suppress cortisol), 24-hurinary-free cortisol (elevated), CT (adrenomegaly)

Primary aldosteronism Plasma aldosterone-renin ratio (increased), aldosterone excretion rateduring salt loading (increased), adrenal CT (adenoma with lowHounsfield units)

Pheochromocytoma Plasma catecholamines or metanephrines (increased), urine cate-

cholamines or metanephrines (increased), clonidine suppression test(failure to suppress plasma norepinephrine after clonidine administra-tion), adrenal CT, MRI (adrenal tumor; T2-weighted MRI has charac-teristic appearance), iodine131-metaiodobenzylguanidine scan (signifi-cant adrenal or extra-adrenal tumor uptake)

Renal vascular disease Captopril renography (some limitations), renal duplex sonography(requires good operators; increased renal artery compared with aortavelocities suggests stenosis), MRA (renal vessel narrowing), CTA (renalvessel narrowing), angiography (gold standard; renal vessel narrow-ing), renal vein renin ratio (not commonly done)

Renal parenchymal disease 24-h urine protein and creatinine levels, renal ultrasound (small kid-ney size, unusual architecture), glomerular filtration rate (low), renalbiopsy (usually done to determine type of glomerular disease)

Parathyroid disorders Calcium and phosphorus levels (increased and decreased, respectively),serum parathyroid hormone level (increased), serum calcitonin level

(when MEN is suspected)Thyroid disease Serum thyroid hormone level (increased in hyperthyroidism), thyro-

tropin level (suppressed in hyperthyroidism)

CT = computed tomography; CTA = computed tomographic angiography; MEN = multiple endocrineneoplasia; MRA = magnetic resonance angiography; MRI = magnetic resonance imaging


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16. Mattes RD, DonnellyD. Relative contribu-tions of dietarysodium sources. JAm Coll Nutr.1991;10:383-93.[PMID: 1910064]

encourage patients to maintainlifestyle changes when drug therapybecomes necessary. Table 4 showsthe expected effects of lifestylemodification.

Salt restrictionThe effect of salt intake on bloodpressure is well-established. Dietarysodium restriction can reduce sys-

tolic blood pressure level by 1 to 4mm Hg. Dietary sodium restrictionto less than 2400 mg per day isoften the first lifestyle change. Theaverage Western diet contains 3800mg of sodium per day (15), andpatients are often unaware of thehigh sodium content of many foods(16). Patients should especiallyavoid processed foods, lunchmeats,soups, Chinese food, and cannedprocessed food.

In TOHP I, adults with diastolic blood pres-

sure levels of 80 to 89 mm Hg and systolic

blood pressure levels


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How should clinicians modifychoice of antihypertensivetreatment based on patientcharacteristics and comorbidconditions?Although diuretics are generally therecommended first-choice agent,

treatment with an expected 30% reduc-

tion in fatal and nonfatal stroke and an

unexpected 21% reduction in all-cause

mortality. This study confirms the value of

drug treatment for patients age >80

years who have systolic blood pressure

levels >150 mm Hg (26 ).

25. Major cardiovascularevents in hyperten-sive patients ran-domized to doxa-zosin vs chlorthali-done. ALLHAT Col-laborative ResearchGroup. JAMA2000;283:1967-75. [PMID:10789664]

Table 5. Drug Treatments for Hypertension*

Drug Class (daily dose, mg) Advantages Disadvantages

Diuretics Most effective in the elderly, those with isolated May increase glucose, cholesterol, and uric acid levels;Hydrochlorothiazide (12.550) systolic hypertension, diabetics, and African hypokalemia; photosensitivityChlorothiazide (250500) Americans, who are likely to be salt-sensitive;Chlorothalidone (12.550) inexpensive

ACE inhibitors Preferred for chronic kidney disease, heart failure, Cough in 15% (switch to an ARB). Can accept up to 30%Enalapril (540) and diabetes. Work well with diuretics. Generic increase in serum creatinine with ACE inhibitors. Angio-Fosinopril (1040) ACE inhibitors are inexpensive edema in 0.1%0.7%. Contraindicated in pregnancy

Lisinopril (540)Perindopril (416)Quinapril (580)Ramipril (1.2520)

Angiotensin-receptor blocker Usually well-tolerated. Angiedema uncommon. Dizziness. Relatively expensive. Contraindicated in pregnancy(ARB) Work well with a diuretic; Do not cause coughLosartan (25100)Candesartan (1632)Irbesartan (150300)

Potassium-sparing diuretics Most useful when a thiazide causes hypokalemia Hyperkalemia (rare with triamterene); gynecomastia (spirono-Spironolactone (25100) lactone); weak antihypertensivesTriamterene (25100)

-blockers Carvedilol is an - and -blocker. Nebivolol is Bronchospasm, bradycardia, heart failure; masksAtenolol (25100) also a vasodilator. Note: Dont use -blockers insulin-induced hypoglycemia; impairs peripheral circulation;

Metoprolol (50300) as initial therapy except in heart failure insomnia; fatigue; decreased exercise tolerance;Propranolol (40480) hypertriglyceridemia (unless ISA present); several trials showNebivolol (2.510) worse outcomes with atenolol than ACE inhibitors, ARBs,Carvedilol (12.550) and CCBs

CCBs Well-tolerated and effective. Dihydropyridines, Diuretic-resistant edema (lesser problem if ACE inhibitor orAmlodipine (2.510) like amlodipine, are quite potent. Relatively ARB added), headache, cardiac conduction defects, constipa-Diltiazem (120360) inexpensive tion, gingival hypertrophyVerapamil (120480)Nifedipine (30120)

Reserpine (0.050.25) Inexpensive Nasal congestion, depression, peptic ulcer

Central -agonists Inexpensive Sedation, dry mouth, bradycardia, withdrawal (rebound)Methyldopa (5003000) hypertensionClonidine (0.21.2)

Guanethidine (1050) Very potent; inexpensive Postural hypotension; diarrhea-blockersPrazosin (230) in ALLHAT

Terazosin (120)

Hydralazine (50300) Inexpensive Lupus reaction; headache; edema

Direct renin inhibitor Newly approved. Reduced plasma renin could be DiarrheaAliskiren (150300) therapeutic per se; effective in combination

ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channel blocker; ISA = irregular spiking activity.

* For a full listing of drugs, see Oral Antihypertensive Drug Treatment table in PIER hypertension module.

Doxazosin (116)

Postural hypotension; heart failure increased with doxazosin


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clinicians should modify drug selec-tion on the basis of patient charac-teristics and comorbid conditions.

26. HYVET Study Group.Treatment of hyper-tension in patients80 years of age orolder. N Engl J Med.

2008;358:1887-98.[PMID: 18378519]

27. Yusuf S, Sleight P,Pogue J, et al. Effectsof an angiotensin-converting-enzymeinhibitor, ramipril, oncardiovascularevents in high-riskpatients. The HeartOutcomes Preven-tion EvaluationStudy Investigators.N Engl J Med.2000;342:145-53.[PMID: 10639539]

Elderly and African-Americanpatients tend to be salt-sensitiveand respond well to diuretics.

Table 6. Compelling Indications for Individual Drug Classes*

Compelling Indication

Recommended Drugs

Heart Failure Diuretic, -blocker, ACE inhibitor, ARB, aldosterone antagonist

Postmyocardial infarction -blocker, ACE inhibitor, aldosterone antagonist

High coronary disease risk Diuretic, -blocker, ACE inhibitor, ARB + CCB

Diabetes Diuretic, -blocker, ACE inhibitor, ARB, CCB

Chronic kidney disease ACE inhibitor, ARB

Recurrent stroke prevention Diuretic, ACE inhibitor

ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channelblocker.

* Adapted from JNC 7 Hypertension Clinical Practice Guidelines (http://www.nhlbi.nih.gov/guidelines/hypertension/express.pdf).

Compelling indications for antihypertensive drugs are based on benefits from outcome studies orexisting clinical guidelines; the compelling indication is managed in parallel with the blood pressure.

Figure. Algorithm for treatment of hypertension. Adapted from JNC 7 HypertensionClinical Practice Guidelines (http://www.nhlbi.nih.gov/guidelines/hypertension/

express.pdf). ACE = angiotensin-converting enzyme; ARB = angiotensin-receptorblocker; CCB = calcium-channel blocker; DBP = diastolic blood pressure; SBP= systolicblood pressure.

Lifestyle Modifications

Initial Drug Choices

Not at Goal Blood Pressure

Optimize dosages or add additional drugs until goal blood pressure is achieved.Consider consultation with hypertension specialist if control remains elusive.

Not at goal blood pressure (


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Younger patients with hypertensionoften respond well to suppressionof the renin-angiotensin systemand an ACE inhibitor or ARB maybe a good initial choice for thesepatients. ACE inhibitors are help-ful in patients with diabetes, partic-ularly if microalbuminuria is pres-ent. Patients with heart failure can

benefit from ACE inhibitors,diuretics, cardioselective -blockers,and ARBs. -blockers and ACEinhibitors are good antihyperten-sive agents for patients who havehad a myocardial infarction.Patients with renal insufficiencycan benefit from ACE inhibitors,particularly if proteinuria is present.

The HOPE trial randomly assigned more

than 9000 patients >55 years old with CVD

to ramipril 10 mg at night or placebo and

found that those on ramipril had less mor-bidity and mortality than those on

placebo. Because one half of the patients

also had hypertension, the authors con-

cluded that an ACE inhibitor is reasonable

initial hypertension therapy in patients

with vascular disease (27).

In the ASCOT trial, more than 19 000 adults

with hypertension and 3 or more CVD risk

factors were randomly assigned to either a

-blocker plus a thiazide-type diuretic (if

needed) or to a combination of a calcium-

channel blocker (amlodipine) and an ACE

inhibitor (perindopril) if needed and, in a

factorial design, to either a statin or

placebo. After median follow-up of 5.5

years, the trial was stopped because car-

diovascular events and total mortality were

significantly lower in the group that received

the amlodipine-based regimen. Although

blood pressure level was well-controlled in

28. ASCOT Investigators.Prevention of cardio-vascular events withan antihypertensive

regimen of amlodip-ine adding perindo-pril as required ver-sus atenolol addingbendroflumethiazideas required, in theAnglo-ScandinavianCardiac Outcomes

Trial-Blood PressureLowering Arm(ASCOT-BPLA): amulticentre ran-domised controlledtrial. Lancet.2005;366:895-906.[PMID: 16154016]

both groups, it was lower in the amlodipine

group by an average difference of 2.7/1.9

mm Hg. The amlodipine and ACE inhibitor

drug combination reduced the risk for

stroke by about 25%, for coronary events

and procedures by 15%, and for cardiovas-

cular deaths by 25% (28).

What is the role of combination

therapies for hypertension?

Combination therapies are gainingpopularity.They have severaladvantages, including better med-ication adherence. Whether theyultimately cost less for patients thanindividual prescriptions for each ofthe drugs depends on the patientsinsurance programs.

ACE inhibitors or ARBs combined withhydrochlorothiazide

Many different ACE inhibitors andARBs are available in combinationwith a thiazide. This combinationis well-tolerated and is oftengood initial therapy for stage 2hypertension.

ACE inhibitors and ARBs combined with

blockers

An ACE inhibitor with amlodipineis available in various doses, includ-ing generics. ARBs are not avail-able as generics. Adding an ACE

inhibitor or ARB avoids the edemaof amlodipine monotherapy.

ACEARB combination therapy

ACEARB combinations do notseem to have advantages. The recentONTARGET (Ongoing Telmisar-tan Alone and in Combination with

Table 7. Drug Therapy for Specific Disease Mechanisms of Hypertension*

Disease Mechanism Drug Class Comment

Volume overload Thiazide; loop diuretic;

aldosterone antagonistSympathetic overactivity -blocker Use to counteract reflex tachycardia

from vasodilators or in heart failure

Increased vascular resistance Angiotensin-converting Use in heart failureenzyme inhibitor orangiotensin-receptorblocker

Smooth-muscle contraction Dihydropyridine calcium-channel blockers;-blockers; hydralazine

* Adapted from reference 33.

dihydropyridine calcium-channel


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Ramipril Global Endpoint Trial)study confirms that ACE inhibitorsand ARBs are not additive in com-bination therapy for hypertensionand have more side effects, such ashyperkalemia and slight decline inglomerular filtration rate (29).ACE inhibitor, ARB, and ACEARB combination had the same

effect on cardiovascular events.When blood pressure is poorly

controlled, how should clinicians

decide between increasing dose,adding an additional agent, or

switching to another drug class?

When blood pressure is poorlycontrolled, it is important to avoidclinical inertia (30). The followingprinciples were formulated to dealwith a particular form of poorly con-trolled blood pressure called resist-

ant hypertension, but they are usefulwhenever the blood pressure is abovethe target level. Resistant hyperten-sion is when the blood pressure isabove the target level on a rational,full-dose, triple-drug regimen thatincludes a diuretic (31, 32). If thepatient has no target organ damage,consider ambulatory blood pressuremonitoring to see if the white coateffect is a contributing factor. Askabout co-medication with blood

pressureraising drugs and excessivealcohol or salt intake. Reconsidersecondary causes of hypertension asthey are much more common inresistant hypertension. Poor adher-ence is also common, so carefullyevaluate adherence before changingtreatment.

Because volume overload is com-mon, start treating uncontrolledhypertension by adding or increas-

ing diuretic therapy with a thiazide(with normal renal function) or aloop diuretic (with abnormal renalfunction). A key to success is usingseveral different drugs, each ofwhich attacks a different diseasemechanism. Table 7 shows physio-logic mechanisms and the drug classthat counteracts each. If the patient

is taking 2 drugs that attack thesame disease mechanism, replace 1of them with a drug from a differentclass. If patient is taking 3 drugs andblood pressure remains uncontrolled,ensure that the patient is takingdrugs from different classes. Con-sider adding a potassium-sparingdiuretic, such as aldactone or

amiloride, in patients taking 3 to 4drugs if blood pressure is stilluncontrolled. Consider a combined- and -blocker, a centrally actingagent, or reserpine (in low doses). Ifcontrol remains elusive, considerconsulting a specialist in hyperten-sion management.

How often should patients with

hypertension be seen?

Blood pressure levels and clinicaljudgment should guide decisions

about the frequency of monitoringblood pressure. Suggested recheckintervals for blood pressure levels140/90 to 159/99 mm Hg are 2months, and within 1 month if lev-els are higher. If the systolic anddiastolic blood pressure levels fallinto different categories, follow rec-ommendations for the shorter fol-low-up time. After adjusting med-ications, allow 2 to 4 weeks for theblood pressure level to stabilize

before modifying therapy. Clinicalopinion rather than evidence deter-mines the interval for seeingpatients with stable, well-controlledhypertension; 6- to 12-monthintervals are typical practice.

What is the value of home blood

pressure level monitoring?

Home blood pressure monitoring isa relatively inexpensive way tomonitor blood pressure levels, espe-

cially before and after changingtherapy. Measurements of homeblood pressure levels are more accu-rate than office blood pressure lev-els (33). Some patients becomeobsessed with their blood pressurelevel, and the physician may haveto set limits on how often they takehome blood pressure readings, lest

29. ONTARGET Investi-gators. Telmisartan,ramipril, or both inpatients at high riskfor vascular events.

N Engl J Med.2008;358:1547-59.[PMID: 18378520]

30. Phillips LS, BranchWT, Cook CB, et al.Clinical inertia. AnnIntern Med.2001;135:825-34.[PMID: 11694107]

31. Moser M, Setaro JF.Clinical practice.Resistant or difficult-to-control hyperten-sion. N Engl J Med.2006;355:385-92.[PMID: 16870917]

32. American HeartAssociation Profes-sional EducationCommittee. Resis-

tant hypertension:diagnosis, evalua-tion, and treatment:a scientific state-ment from theAmerican HeartAssociation Profes-sional EducationCommittee of theCouncil for HighBlood PressureResearch. Circula-tion. 2008;117:e510-26. [PMID: 18574054]

33. Pickering T. Recom-mendations for theuse of home (self)and ambulatoryblood pressuremonitoring. Ameri-

can Society ofHypertension AdHoc Panel. Am JHypertens. 1996;9:1-11. [PMID: 8834700]

34. Wilson MD, JohnsonKA. Hypertensionmanagement inmanaged care: therole of home bloodpressure monitoring.Blood Press Monit.1997;2:201-206.[PMID: 10234118]



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their anxiety over the results raisetheir blood pressure level. Instructpatients on correct technique oftaking blood pressure level and askthem to keep a journal in whichthey chart their blood pressure levelonce to twice daily.

Home blood pressure level moni-toring can help to confirm a diag-nosis of hypertension in anuntreated patient (34, 35). Instructthe patient to check at least 2 read-ings on at least 3 (preferably 7)consecutive days in the morningbetween 6 and 10 a.m. and torepeat them in the evening between6 and 10 p.m. If the average homeblood pressure level is less than125/76 mm Hg (after dropping thefirst days values), hypertension isvery unlikely in an untreated per-

son (36). Average untreated homeblood pressure levels of 135/85 mmHg and higher suggest hyperten-sion. In-between values are anindication for further evaluationby ambulatory blood pressuremonitoring.

When should clinicians consider

hospitalization or referral to a

hypertension specialist?

The main indication for hospital-

ization because of elevated bloodpressure is a hypertensive crisis(see Box). Indications to refer toa hypertension specialist includethe following: drug-resistant

hypertension uncontrolled on 3 ormore drugs; uncertainty about howto evaluate or manage suspectedsecondary hypertensionespeciallypheochromocytoma or primaryhyperaldosteronismor assistanceneeded to assess the extent oftarget organ damage.

When patients present with

markedly elevated blood pressurelevels, how should cliniciansdistinguish between a

hypertensive emergency and apseudocrisis?

A sudden rise in blood pressure levelis classified as either hypertensiveurgency or a hypertensive emergency(37). Hypertensive urgency isdefined as an elevated blood pressurelevel greater than 180/110 mm Hgwithout target organ damage.

Patients can usually be managedwith oral medications as outpatientsand sent home after a few hours ofobservation. A hypertensive emer-gency is defined as an elevated bloodpressure level with impending oracute progressive target organ dam-age. These patients usually requireadmission to an intensive care unitand intravenous medication to lowerblood pressure level (38). Severaldrugs lower blood pressure quickly.

The choice depends on the physi-cians level of comfort and experiencewith the drugs. See the Box for situ-ations in which severe hypertensionconstitutes a crisis.

35. Pickering TG, MillerNH, Ogedegbe G, etal. Call to action onuse and reimburse-ment for homeblood pressuremonitoring: execu-tive summary: a jointscientific statementfrom the AmericanHeart Association,American Society OfHypertension, and

Preventive Cardio-vascular NursesAssociation. Hyper-tension. 2008;52:1-9.[PMID: 18497371]

36. Williams B, PoulterNR, Brown MJ, et al.Guidelines for man-agement of hyper-tension: report ofthe fourth workingparty of the BritishHypertension Soci-ety, 2004-BHS IV. JHum Hypertens.2004;18:139-85.[PMID: 14973512]

37. Townsend R. H yper-tensive crisis. In:Lanken PN, ed. The

Intensive Care UnitManual. Vol. 2000.Philadelphia: WBSaunders; 2000:602-14.

38. Lip GY, Beevers M,Beevers DG. Compli-cations and survivalof 315 patients withmalignant-phasehypertension. JHypertens.1995;13:915-24.[PMID: 8557970]


Treatment... The goal blood pressure level should be less than 140/90 mm Hgunless the patient has other cardiovascular risk factors or diabetes, which lowersthe target to less than 130/80 mm Hg. Lifestyle modifications can lower the bloodpressure level, but most patients also need at least 1 drug to reach goal bloodpressure. A diuretic is a good choice for initial therapy absent a compelling indica-tion for another drug (for example, vascular disease is a strong indication to startwith an ACE inhibitor). Failure to reach target blood pressure level on a near-max-imal dose of one or more drugs is an indication to add a drug that attacks anothermechanism for hypertension. Severe hypertension requires urgent treatment, oftenin the hospital, if acute cardiovascular or neurologic events are present, if thepatient is pregnant, or if severe catecholamine excess is present.


Situations in which Severe

Hypertension Constitutes a Crisis

Cardiovascular

Left-ventricular failure

Myocardial infarction

Unstable angina

Aortic dissection

After vascular surgery or coronaryartery bypass grafting

Neurologic

Hypertensive encephalopathy

Subarachnoid or intracranial hem-orrhage

Thrombotic stroke

Other

Severe catecholamine excess, suchas clonidine withdrwal, pheochro-mocytoma, tyramine-MAOI*interaction, or intoxication(cocaine, phenylcyclidine,phenylpropanolamine)

Eclampsia in pregnancy

* MAOI = monoamine oxidase inhibitors.


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Practice

Improvement How many patients withhypertension receive treatment,and how well is hypertensioncontrolled in the United States?Of the one third of U.S. adults thathave hypertension, only two thirdsare aware of their hypertension, and

approximately 55% are on treat-ment. Hypertension control ratesare improving: The blood pressurelevel control rate was 29.2% 2.3%in 1999 to 2000 and 36.8% 2.3%in 2003 to 2004 (1). The controlrates increased substantially in bothsexes, non-Hispanic blacks, andMexican Americans. Among thegroup of patients age 60 years andolder, awareness, treatment, and

control rates have all increasedsignificantly (1). Among treatedpatients with hypertension, controlrates approach 65%.

What do professional

organizations recommend about

the management of patients with

hypertension?

The advice in this In The Clinicarticle generally represents the rec-ommendations of the JNC 7 (2),the American Heart Association,the National Kidney Foundation,and the American College ofPhysicians. Links to the guidelinesare listed in the Toolkit.

intheclinic

Tool Kitin the clinic

Hypertension

PIER Modulespier.acponline.org

Access the PIER module on hypertension, which provided the up-to-date evidencecited in this In the Clinic article. PIER modules provide evidence-based, currentinformation on prevention, diagnosis, and treatment in an easy-to-use electronicformat designed for rapid access at the point-of-care.

Patient Education Resourceswww.annals.org/intheclinic

Access the Patient Information material that appears on the following page forduplication and distribution to patients.

Practice Measures

pier.acponline.org/qualitym/index.htmlPIER has a list of practice measures, including those of the Physician Quality Report-ing Initiative (PQRI). Hypertension quality measures appear under Endocrinology,Diabetes, and Metabolism and under Nephrology.

www.qualityforum.org/pdf/ambulatory/tbAMBALLMeasuresendorsed%2012-10-07.pdf

The National Quality Forum: This influential groups practice measures appear underDiabetes and Hypertension.

www.ama-assn.org/ama1/pub/upload/mm/370/hypertension-8-05.pdf

Practice measures from the Physicians Consortium for Performance Improvement(PCPI). Among the tools is a good flow sheet for recording key data over time.

Guidelineshyper.ahajournals.org/cgi/content/full/42/6/1206

The Seventh Report of the Joint National Committee on Prevention, Detection,Evaluation, and Treatment of High Blood Pressure.

circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.183885Guidelines from the American Heart Association for managing hypertension toprevent atherosclerotic cardiovascular disease.

www.kidney.org/professionals/KDOQI/guidelines.cfm

Guidelines from the National Kidney Foundation for managing hypertension inpatients with renal disease.

diabetes.acponline.org/custom_resources/ACP_DiabetesCareGuide_Ch10.pdf?dbp

ACP Guidelines for the care of hypertension in patients with diabetes.


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THINGS PEOPLE SHOULDKNOW ABOUT HYPERTENSION

In the ClinicAnnals of Internal Medicine

annals.org

Hypertension, often called high blood

pressure, is a common health problem.

Most people do not know they have

high blood pressure. Some people get

headaches or swollen legs due to prob-

lems related to hypertension, such as

heart failure.

We dont know what causes hyperten-

sion. In a few people who have another

disease that causes hypertension, it

can be cured. But most people musttake medicines to control their blood

pressure.

If you dont get treated for your hyper-

tension, there is a better chance you

could have a heart attack, stroke, or

kidney failure.

Just having healthy habits may lower

your blood pressure. Follow these

healthy habits even if you take blood

pressure medicine: Eat less salt, exer-

cise more, eat more fruits and vegeta-

bles, lose weight, drink less alcohol,

and stop smoking.

Work with your doctor to have better

health habits, measure your blood

pressure at home, and take your medi-

cine every day. Keep all of your doctor

appointments.

P

atientInformation

For More Information

American College of Physicians: ACP Special Report:

Living with Hypertension

www.doctorsforadults.com/images/healthpdfs/hypertension_report.pdf

American Heart Association: High Blood Pressure

www.americanheart.org/presenter.jhtml?identifier=2114

National Heart, Lung, and Blood Institute: Your Guide

to Lowering Blood Pressure

www.nhlbi.nih.gov/health/public/heart/hbp/hbp_low/hbp_low.pdf

National Kidney Foundation: High Blood Pressure

(Hypertension)

www.kidney.org/atoz/atozTopic.cfm?topic=1


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CME Questions

A 58-year-old black man has had hyper-tension for 5 years. He has maintained ablood pressure of 135/85 mm Hg withuse of hydrochlorothiazide, 25 mg/d.Laboratory assessment reveals a serum

sodium level of 141 meq/L, serum potas-sium level of 4.1 meq/L, and fastingplasma glucose level of 132 mg/dL.These values are confirmed onremeasurement several days later.

What is most appropriate managementof this patients hypertension?

A. Continue the current therapy, witha target blood pressure less than140/90 mm Hg

B. Discontinue hydrochlorothiazidetherapy and begin ramipriltherapy

C. Add amlodipine tohydrochlorothiazide therapy

D. Add ramipril tohydrochlorothiazide therapy

E. Increase the hydrochlorothiazidedosage to 50 mg/d

A 31-year-old man is referred for man-agement of multidrug-resistant hyper-tension. His hypertension was diagnosed2 years ago, and treatment with multi-ple blood pressure medications, bothalone and in combination, has beenineffective. His current medical regimen

includes oral hydrochlorothiazide, 25mg/d; oral amlodipine, 10 mg/d; andatenolol, 100 mg/d.

Blood pressure is 160/100 mm Hg, pulserate is 80 per min and regular, and res-piration rate is 18 per min. There is anS4 gallop and trace pretibial edema. Thepatient has been consistentlyhypokalemic in the past, with a serumpotassium level of 2.5 to 3.4 meq/L evenwith potassium supplementation.

His serum creatinine level is 1.1 mg/dL,blood urea nitrogen is 12 mg/dL, seriumsodium level is 136 meq/L, serum potas-sium level is 2.8 meq/L, serum chloridelevel is 108 meq/L, serum bicarbonate30 meq/L. Electrocardiography showsleft ventricular hypertrophy by voltagecriteria.

What is the most likely diagnosis?

A. Volume and potassium depletionsecondary to chronic overdiuresis

B. PheochromocytomaC. Primary aldosteronism

D. Severe essential hypertensionE. The Bartter syndrome

A 68-year-old woman is hospitalizedwith palpitations and shortness ofbreath. She has a history of hyperten-sion and chronic atrial fibrillation, andher medications include furosemide,candesartan, and warfarin. On physicalexamination, the heart rate is 120 bpmwith an irregularly irregular rhythm, andblood pressure is 130/80 mm Hg; shehas an elevated jugular venous pulse,crackles in both lungs, and markedlower extremity edema. Echocardiogra-phy shows left ventricular hypertrophy,an ejection fraction of 70%, and no sig-nificant valvular disease. She is treatedwith intravenous diuretics, withimprovement in her symptoms and reso-lution of peripheral edema and of crack-les on lung examination. Her heart rateis now 99 bpm and her blood pressure is120/75 mm Hg.

Which of the following would be themost appropriate medication to add?

A. LisinoprilB. SpironolactoneC. AmlodipineD. MetoprololE. Hydrochlorothiazide

A 58-year-old man who has longstand-ing diabetes mellitus and peripheral vas-cular disease involving the left legcomes to your office for a routine fol-low-up visit. He has intermittent claudi-cation when he plays golf. He is obese,with a body mass index of 40 kg/m2, andhis blood pressure is 160/95 mm Hg.

Physical examination shows normaljugular venous pressure. Cardiac exami-nation is normal. Examination of theextremities shows no edema and absentleft pedal pulses. The left leg anklebrachial index is 0.8. Electrocardiogram

obtained 1 year ago showed no signifi-cant findings. His last lipid profileshowed a total serum cholesterol levelof 260 mg/dL, high-density lipoproteincholesterol level of 25 mg/dL, low-

density lipoprotein cholesterol level of165 mg/dL, and triglyceride level of 250mg/dL. His hemoglobin A1c level was8%. Heart failure has not been sus-pected or diagnosed. The patient smokesand is sedentary. However, he works andis apparently compliant with his med-ication regimen. He was taking simvas-tatin, 40 mg/d, last year, but discontin-ued this medication because of diffusemuscle and joint aches that have sinceresolved. He takes rosiglitazone, 4 mg/d;atenolol, 50 mg/d; hydrochlorothiazide,50 mg/d; and aspirin, 80 mg/d. You

suggest smoking cessation, weight loss,and physical conditioning.

Which of the following interventionswould prevent the progression of com-plications of diabetes and athero-sclerosis in this patient?

A. Prescribe a nonstatin lipid-lowering agent

B. Recommend vitamin E, 500 IU/dC. Substitute insulin for rosiglitazoneD. Start treatment with amlodipineE. Start treatment with ramipril

Questions are largely from the ACPs Medical Knowledge Self-Assessment Program (MKSAP). Go to www.annals.org/intheclinic/

to obtain up to 1.5 CME credits, to view explanations for correct answers, or to purchase the complete MKSAP program.

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