Hypertension

Downloaded From: http://annals.org/ by aMcGill University User on08/26/2016 This article Sankey Williams,MD Darren Taichman, MD,PhD Jaya K.Rao,MD,MHS Deborah Cotton,MD,MPH Section Editors Matthew R.Weir, MD Physician Writer has been corrected, as © 2014 American CollegeofPhysicians judgment. The informationcontainedhereinshould neverbeusedasasubstituteforclinical diagnosis, treatment,andpracticeimprovement forhypertension. CME Objective: and otherresourcesreferencedineachissueofIntheClinic. smartmedicine.acponline.org, ww.acponline.org/products_services/mksap/15/?pr31, who areinterestedintheseprimaryresourcesformoredetailcanconsult http:// ACP SmartMedicineandMKSAPprovideexpertreviewofthecontent.Readers the assistanceofsciencewritersandphysicianwriters.Editorialconsultants from collaboration withtheACP’s MedicalEducationandPublishingdivisionswith of InternalMedicine resources oftheAmericanCollegePhysicians(ACP) The contentofIntheClinicisdrawnfromclinicalinformationandeducation Hypertension In theClinic Medicine CME Questions Patient Information Tool Kit Practice Improvement Treatment Diagnosis Screening andPrevention detailed and on MKSAP the To reviewcurrentevidenceforthe screening andprevention, last editors developIntheClinicfromtheseprimarysourcesin (Medical KnowledgeandSelf-AssessmentProgram).Annals page. The original version , includingACPSmart is appended page ITC16 page ITC15 page ITC14 page ITC14 page ITC2 page ITC6 page ITC3 to this article as a supplement at Inwww.annals.org. the Clinic ypertension affects more than 65 million persons in the United States, and about 2 million new cases are diagnosed annually (1, 2). HMost patients have primary or essential hypertension. It is a life- long, progressive, largely asymptomatic disease process. Risk factors include a family history of the condition, African American race, obesity, high sodium or alcohol intake, a low-potassium diet, and a sedentary lifestyle. Treatment to control blood pressure reduces the risk for cardiovascular, cerebrovascular, and renal outcomes of hypertension. Many persons with hypertension do not receive optimal therapy.

Screening and Prevention What long-term health risks are What is prehypertension, and associated with hypertension? what is its proper management? The relationship between blood Prehypertension is a category that pressure and cardiovascular disease first appeared in the JNC 7. It was (CVD) is linear, continuous, and in- defined as a blood pressure of dependent of and additive to other 120/80 to 139/89 mm Hg (1). This risk factors. For persons aged 40 to term is not included in the 2014 1. Chobanian AV, Bakris evidence-based guideline for the GL, Black HR, Cush- 70 years, each increment of 20 mm man WC, Green LA, management of high blood pressure Izzo JL Jr, et al; Joint Hg in systolic blood pressure or National Committee 10 mm Hg in diastolic blood pres- in adults (4). A clinically relevant on Prevention, Detec- question is whether patients with tion, Evaluation, and sure doubles the risk for CVD across Treatment of High the range of blood pressures from age-related increases in blood pres- Blood Pressure. Na- sure would derive benefit from ear- tional Heart, Lung, 115/75 to 185/115 mm Hg (1). and Blood Institute. ly interventions to alter the slope of When other cardiovascular risk fac- Seventh report of the their change in blood pressure. A Joint National Com- tors, such as diabetes or chronic kid- mittee on Prevention, cohort of 4681 young adults in the Detection, Evaluation, ney disease, are present, the CVD and Treatment of CARDIA (Coronary Artery Risk High Blood Pressure. risk associated with hypertension is Development in Young Adults) Hypertension. even higher. Complications of hy- 2003;42:1206-52. study was prospectively studied for [PMID: 14656957] pertension include retinopathy, cere- 2. Ong KL, Cheung BM, 25 years. Those with higher blood Man YB, Lau CP, Lam brovascular disease, ischemic heart pressure trajectories had higher risk KS. Prevalence, disease, left ventricular hypertrophy, awareness, treatment, for coronary artery calcification and control of hyper- atrial fibrillation, heart failure, than those with flatter trajectories tension among Unit- ed States adults chronic kidney disease, and periph- (5). Similarly, pharmacologic treat- 1999–2004. Hyper- eral vascular disease. tension. 2007;49:69- ment of blood pressure for 2 years 75. [PMID: 17159087] was shown to delay progression 3. U.S. Preventive Servic- Should clinicians screen for es Task Force. Screen- to a pressure of 140/90 mm Hg ing for high blood hypertension? even after patients stopped their pressure: U.S. Preven- tive Services Task The U.S. Preventive Services Task medications (6). Other studies have Force reaffirmation Force recommends screening the recommendation examined the utility of lifestyle statement. Ann In- general adult population for hy- modification to prevent an increase tern Med. 2007;147:783-6. pertension (3). It does not recom- in blood pressure to 140/90 mm [PMID: 18056662] mend a specific screening interval 4. James PA, Oparil S, Hg (7, 8). At present, drug therapy Carter BL, Cushman because of lack of evidence to sup- is not recommended for prehyper- WC, Dennison-Him- melfarb C, Handler J, port one. The Seventh Report of tension because of lack of evidence et al. 2014 evidence- the Joint National Committee that it decreases risk for cardiovas- based guideline for the management of [ JNC 7] on Prevention, Detec- cular events or prevents these high blood pressure in adults: report from tion, Evaluation, and Treatment of events. the panel members High Blood Pressure recommends appointed to the TROPHY (Trial of Preventing Hypertension) Eighth Joint National screening every 2 years if blood Committee (JNC 8). randomly assigned participants with prehy- JAMA. 2014;311:507- pressure is less than 120/80 mm pertension to active treatment with can- 20. [PMID: 24352797] Hg and annually if it exceeds desartan (an angiotensin-receptor blocker doi:10.1001/jama.201 3.284427 139/89 mm Hg (1). [ARB]) or placebo for 2 years and followed

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 them for 4 years. Active treatment delayed persons with diastolic blood pressure 5. Allen NB, Siddique J, Wilkins JT, Shay C, but did not prevent onset of hypertension (6). 80 to 90 mm Hg. TOHP I suggested that Lewis CE, Goff DC, et weight loss (3/2–mm Hg reduction) and al. Blood pressure tra- TOHP (Trials of Hypertension Prevention) jectories in early sodium restriction (2/1–mm Hg reduction) adulthood and sub- phases I and II examined the benefits re- were effective in decreasing systolic and di- clinical atherosclerosis in middle age. duced weight, sodium intake, and stress astolic blood pressure, respectively. TOHP II JAMA. 2014;311:490- and supplementation with potassium, confirmed that weight loss and sodium re- 7. [PMID: 24496536] doi:10.1001/jama.201 magnesium, fish oil, and calcium in striction delay hypertension (7, 8). 3.285122 6. Julius S, Nesbitt SD, Egan BM, Weber MA, Michelson EL, Kaciroti N, et al; Trial of Pre- Screening and Prevention... Cardiovascular risk increases as blood pressure in- venting Hypertension creases, starting at 115/75 mm Hg. Guidelines recommend screening all adults for (TROPHY) Study In- vestigators. Feasibility hypertension. Although evidence supporting a specific screening interval is scarce, of treating prehyper- consensus advocates intervals of 1 to 2 years. Patients with a steeper blood pres- tension with an an- sure trajectory will probably reach a blood pressure of 140/90 mm Hg sooner, giotensin-receptor blocker. N Engl J which may increase risk for CVD. Lifestyle modification can delay the onset of hy- Med. 2006;354:1685- pertension and CVD, andhere is no evidence that pharmacotherapy should be 97. [PMID: 16537662] 7. Batey DM, Kaufmann added to lifestyle modifications to alter blood pressure trajectory or risk for car- PG, Raczynski JM, diovascular events. Hollis JF, Murphy JK, Rosner B, et al. Stress management intervention for primary CLINICAL BOTTOM LINE prevention of hypertension: detailed results from Phase I of Trials of Hypertension Prevention (TOHP-I). Ann Epidemiol. 2000;10:45-58. Diagnosis [PMID: 10658688] How should clinicians diagnose A person’s blood pressure can vary and stage hypertension? widely. A single accurate measure- The steps in diagnosing hyperten- ment is inadequate to diagnose sion are simple but are often not blood pressure–it should be meas- followed. The most common errors ured twice and averaged. The run- (failure to have the patient sit qui- ning average is more important than etly for 5 minutes before a reading individual readings. Hypertension is is taken, failure to support the limb diagnosed if the average of at least 2 Instructions for Taking Blood Pressure used to measure blood pressure, us- readings obtained at 3 visits 2 to 4 • Have patient relax, sitting (feet ing a cuff that is too small, and de- weeks apart is at least 140 mm Hg on floor, back supported) for >5 flating the cuff too rapidly) lead to (systolic) or at least 90 mm Hg (di- min. falsely increased readings. The best astolic). In the JNC 7 guidelines, • Support patient’s arm (for ex- position for patients is sitting be- blood pressure was staged as normal ample, resting on a desk). cause the studies that established (≤120/80 mm Hg), prehypertensive • Use the stethoscope bell, not the value of treating hypertension (120/80 to 139/89 mm Hg), stage 1 the diaphragm, for auscultation. • Check blood pressure first in used this position to measure the (140/90 to 159/99 mm Hg), or both arms. Note which arm blood pressures that diagnosed stage 2 (≥160/100 mm Hg). The gives the higher reading and hypertension and guided dose ad- 2014 guidelines avoid classification use this arm for all other justment (9). Table 1 and the Box definitions and focus on evidence- (standing, lying down) and fu- ture readings. provide instructions on blood pres- based blood pressure goals (4). In • Measure blood pressure in sit- sure measurement persons older than 50 years, systolic ting, standing, and lying posi- tions. All measurements should be separated by 2 min. • Use the correct cuff size and Table 1. Blood Pressure Cuff Size Criteria note if a larger- or smaller- Arm Circumference Weight Cuff Size to Use than-normal cuff size is needed Female Male (Table 1). 24–32 cm <150 <200 Regular • Record systolic (onset of first 33–42 cm* >150 >200 Large sound) and diastolic (disappear- 38–50 cm* – – Thigh ance of sound) pressures. • Record exact results to nearest * Either cuff is acceptable for the overlap circumferences. even number.

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 blood pressure greater than 140 mm minutes at night. Ambulatory Hg is a more important CVD risk blood pressure monitoring provides factor than diastolic hypertension. the most accurate assessment of 8. Cook NR, Cutler JA, blood pressure (12). Most patients Obarzanek E, Buring Pseudophypertension can occur in JE, Rexrode KM, Ku- with hypertension do not need it, manyika SK, et al. patients with stiff, incompressible and the Centers for Medicare & Long term effects of dietary sodium re- arteries. To detect it, clinicians Medicaid Services pays for only 1 duction on cardiovas- should inflate the blood pressure cular disease out- indication: diagnosing white coat comes: observational cuff to at least 30 mm Hg above the hypertension. The Box lists the follow-up of the trials palpable systolic pressure and then of hypertension pre- other situations in which ambulato- vention (TOHP). BMJ. try to “roll” the brachial or radial ry monitoring may be helpful. 2007;334:885-8. [PMID: 17449506] artery underneath their fingertips 9. Pickering TG, Hall JE, (“Osler’s maneuver”) (10). Healthy Ambulatory blood pressure moni- Appel LJ, Falkner BE, Graves J, Hill MN, et arteries should not be palpable when toring may also be useful in identi- al. Recommendations fying high-risk blood pressure for blood pressure empty. The patient may have measurement in hu- pseudohypertension if the clinician patterns that are associated with mans and experi- mental animals: part feels a stiff, tube-like structure. increased cardiovascular events in 1: blood pressure patients with hypertension. One is measurement in hu- mans: a statement for What is white coat hypertension? loss of “dipping status,” which is as- professionals from White coat hypertension is de- sociated with worse cardiovascular the Subcommittee of Professional and Pub- fined as an elevated blood pressure outcomes of hypertension. Blood lic Education of the at the office with lower blood American Heart Asso- pressure of patients with loss of ciation Council on pressure measured at home or with dipping status decreases less than High Blood Pressure Research. Circulation. a 24-hour ambulatory blood pres- 10% at night relative to daytime 2005;111:697-716. sure monitor (11). The prevalence blood pressure (16). The other [PMID: 15699287] 10. Messerli FH. Osler’s of white coat hypertension is 10% high-risk pattern is blood pressure maneuver, pseudohypertension, and to 20% (12). These patients are at surges in the early morning hours true hypertension in elevated risk for overt hyperten- (17), which are associated with in- the elderly. Am J Med. 1986;80:906- sion and CVD (13). Current creased cerebrovascular disease risk. 10. [PMID: 2939716] 11. Pickering TG, Shim- guidelines do not recommend A surge is generally defined as a bo D, Haas D. Ambu- pharmacologic treatment for these difference in systolic pressure latory blood-pressure monitoring. N patients but do recommend greater than 55 mm Hg between Engl J Med. sleeping and early-hour waking. In 2006;354:2368-74. lifestyle modifications and regular [PMID: 16738273] follow-up. these patients, physicians may wish to target treatment at the high sys- What is masked hypertension? tolic values in the morning. As many as 10% to 40% of patients who are normotensive in the office What are the key elements of the history? Potential Indications for Use of have masked hypertension (14). Ambulatory Blood Pressure Masked hypertension has been The duration, rapidity of onset, Monitoring associated with increased risk for and severity of the hypertension • Unusual variability of blood pressure sustained hypertension and cardio- should be assessed. Clinicians • Possible white coat hypertension vascular death (15). Because of this should ask about cardiovascular • Evaluation of nocturnal hypertension risk, home readings and ambulatory risk factors, concomitant medical • Evaluation of drug-resistant blood pressure monitoring are valu- conditions, symptoms of target hypertension able in screening patients with sus- organ damage, past treatment and • Determining the efficacy of drug pected masked hypertension. its effects, and lifestyle (dietary treatment over 24 hours habits, alcohol consumption, to- • Diagnosis and treatment of hyper- When is ambulatory blood tension in pregnancy bacco use, and level of physical ac- • Evaluation of symptomatic hy- pressure monitoring indicated? tivity). They should also note any potension on various medications, The ambulatory blood pressure family history of hypertension, re- suggesting that the patient may monitor is a 24-hour portable de- nal disease, cardiovascular prob- be normotensive vice that the patient wears during lems, stroke, and diabetes mellitus • Evaluation of episodic hypertension or autonomic dysfunction regular activities. It measures blood and should ask about increased • Possible masked hypertension pressure every 15 to 20 minutes stress, physical inactivity, and di- during the day and every 30 to 60 etary salt intake.

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 Sudden onset of severe hypertension Table 2. Physical Examination and Key Findings in Patients With Hypertension with previously normal blood pres- Item Routine Evaluation sure potentially indicates a secondary General appearance, height, Look for signs of metabolic syndrome (overweight, form of hypertension. Clinicians weight, body mass index, waist abdominal obesity), skin changes can indicate rare should ask about symptoms that circumference, skin lesions causes of secondary hypertension (striae in the Cushing suggest this. Palpitations, tachycar- syndrome, mucosal fibromas can indicate MEN II) dia, paroxysmal headache, and Funduscopy Retinal changes reflect severity of hypertension: arteriolar narrowing (grade 1), arteriovenous com- sweating suggest pheochromocy- pression (grade 2), hemorrhages or exudates (grade 3), toma. Muscle weakness and polyuria and papilledema (grade 4) suggest hypokalemia from excess Examination of neck Assess for thyroid enlargement, carotid bruits aldosterone. Snoring and daytime Cardiopulmonary examination Rales and gallops may indicate heart failure, inter- sleepiness can indicate sleep apnea, scapular murmur during auscultation of the back can and heat intolerance and weight loss indicate coarctation of the aorta suggest hyperthyroidism. Abdominal examination Palpable kidneys suggest polycystic kidney disease; midepigastric bruits can indicate renal arterial disease Current medications (including Neurologic examination Look for evidence of previous stroke, evaluate cognition (hypertension is a risk factor for cognitive decline). over-the-counter drugs), which Peripheral pulses Reduced leg pulses can indicate coarctation of the may affect blood pressure, should aorta or systemic atherosclerosis be reviewed. Clinicians should ask about oral contraceptives, cortico- MEN = multiple endocrine neoplasia. steroids, licorice, sympathomimetics, and antimigraine drugs. Nonsteroidal anti-inflammatory drugs other than Table 3. Work-up for Possible Secondary Hypertension aspirin can decrease the efficacy of Secondary Cause Evaluation (Findings) antihypertensive drugs (18). Coarctation of aorta Chest film (rib notching; reverse “3” sign), 2-dimensional echocar- diogram, aortogram (coarctation directly seen), MRI What are the essential elements The Cushing syndrome Dexamethasone suppression test (failure to suppress cortisol), 24-h of the physical examination? urinary-free cortisol (elevated), CT (adrenomegaly) The physical examination should Primary aldosteronism Plasma aldosterone-renin ratio (increased), aldosterone excretion look for signs of secondary causes rate during salt loading (increased), adrenal CT (adenoma with low Hounsfield units) of hypertension and end-organ Pheochromocytoma Plasma catecholamines or metanephrines (increased); most would damage related to hypertension. recommend 24-hour fractionated catecholamines and meta- Table 2 outlines key components nephrines by HPLC with electrochemical detection or tandem mass of the examination of patients with spectroscopy, clonidine-suppression test (failure to suppress plasma norepinephrine after clonidine administration), adrenal CT, MRI hypertension. (adrenal tumor; T2-weighted MRI has characteristic appearance), iodine131-metaiodobenzylguanidine scan (significant adrenal or Which laboratory tests should be extra-adrenal tumor uptake) done in newly diagnosed cases? Renal vascular disease Renal duplex sonography (requires good operators; increased renal Patients with newly diagnosed hy- artery compared with aorta velocities suggests stenosis), MRA (re- pertension should have measure- nal vessel narrowing), CTA (renal vessel narrowing), angiography (gold standard; renal vessel narrowing), renal vein—renin ratio (of ment of hemoglobin or hematocrit, limited value) serum electrolyte, serum creatinine, Renal parenchymal disease Spot urine protein—creatinine ratio or 24-h urine protein and crea- serum glucose, and fasting lipid tinine levels, renal ultrasonography (small kidney size, unusual ar- levels; urinalysis with microscopic chitecture), glomerular filtration rate (low), renal biopsy (usually done to determine type of glomerular disease) examination; and 12-lead electro- Parathyroid disorders Calcium and phosphorus levels (increased and decreased, respec- cardiography. Additional testing tively), serum parathyroid hormone level (increased), serum calci- may be indicated by clinical factors, tonin level (when MEN is suspected) suspicion of secondary causes, and Thyroid disease Serum thyroid hormone level (increased in hyperthyroidism), thyro- anticipated treatment. tropin level (suppressed in hyperthyroidism) CT = computed tomography; CTA = computed tomographic angiography; HPLC = high-performance Table 3 summarizes tests that may liquid chromatograpy; MEN = multiple endocrine neoplasia; MRA = magnetic resonance angiography; be useful in evaluation of possible MRI = magnetic resonance imaging secondary hypertension. Echocar- diography is more sensitive than electrocardiography for left ventricular hypertrophy, which would tip the scales toward drug treatment

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 rather than only a trial of lifestyle to guide selection of therapy in Symptoms and Signs That changes or toward true hyperten- patients with diabetes and indicates Suggest Secondary Hypertension sion rather than white coat hyper- greater risk for CVD. • New-onset hypertension at age tension. However, the cost of <25 or >55 years Which patients should be evaluated • Drug-resistant hypertension (re- echocardiography does not justify quires 3 or more drugs at maximal its use as a screening tool in pa- for secondary hypertension, and doses) tients with hypertension. If a pa- how should they be evaluated? • Spontaneous hypokalemia tient has gout, serum uric acid The Box lists symptoms and signs •Palpitations, headaches, and levels should be checked before that suggest secondary hyperten- sweating diuretics are prescribed. The pression. Table 3 outlines suggested • Severe vascular disease, including coronary artery disease, carotid ence of microalbuminuria may help tests for secondary hypertension. disease, and peripheral vascular disease • Epigastric bruit Diagnosis... Diagnosis of hypertension requires careful measurement of blood • Radial-femoral pulse delay, especially with an interscapular murmur. pressure on several occasions. Systolic blood pressure of 140 mm Hg or greater or diastolic blood pressure of 90 mm Hg or greater, based on the average of 3 sets of 2 or more readings obtained 2 to 4 weeks apart, establishes a diagnosis of hypertension. The goals of the diagnostic evaluation are to search for a secondary cause, detect other CVD risk factors, and detect damage to target organs. In addition, the history should focus on past treatment, current medications, and contributing lifestyle factors. The focal points of the physical examination are eyegrounds, the cardiovascular system, and the nervous system. Measurement of hemoglobin, serum creatinine, glucose, lipid, and electrolyte levels; urinalysis; and electrocardiography are routine laboratory tests for patients with newly diagnosed hypertension.

CLINICAL BOTTOM LINE

Treatment What are treatment goals for What are the recommended patients with hypertension? lifestyle modifications for treating The Box provides blood pressure hypertension? goals from different guidelines. The Practice guidelines recommend non- goal is less than 140/90 mm Hg in pharmacologic treatment of hyper- 12. Angeli F, Verdecchia P, Gattobigio R, Sar- a patient with hypertension. tension with lifestyle modification done M, Reboldi G. White-coat hyper- for all patients with hypertension tension in adults. and prehypertension (4, 20). Al- Blood Press Monit. Guidelines for Blood Pressure Goals 2005;10:301-5. though adherence to lifestyle [PMID: 16496443] Joint National Commission (JNC): JNC changes can substantially decrease 13. Eguchi K, Hoshide S, 8 recommends treatment to a goal Ishikawa J, Ishikawa blood pressure, these changes and S, Pickering TG, Gerin blood pressure of <140/90 mm Hg for W, et al. Cardiovas- patients younger than 60 years. For their benefits can be difficult to sus- cular prognosis of those older than 60 years, a goal of tain. Physicians must encourage pa- sustained and white-coat hyper- less than 150/90 mm Hg is recom- tients to maintain lifestyle changes mended (4). tension in patients when drug therapy becomes neces- with type 2 diabetes Kidney Disease Improving Global Out- mellitus. Blood Press sary. Table 4 shows the expected ef- Monit. 2008;13:15- comes (KDIGO): KDIGO recommends 20. [PMID: 18199919] a blood pressure of 130/80 mm Hg for fects of lifestyle modification. doi:10.1097/MBP.0b0 patients with chronic kidney disease 13e3282f13f4a 14. Mallion JM, Clerson and below 130/80 mm Hg for patients Salt restriction P, Bobrie G, Genes N, excreting >30 mg urine albumin/d Vaisse B, Chatellier G. (19). The effect of salt intake on blood Predictive factors for pressure is well-established. Dietary masked hyperten- The American Heart Association (AHA) sion within a popu- and the American College of Cardi- sodium restriction can reduce systolic lation of controlled ology (ACC): AHA/ACC recommends a blood pressure by 1 to 4 mm Hg. hypertensives. target blood pressure below 140/90 J Hypertens. Dietary sodium restriction to less than 2006;24:2365-70. mm Hg (20). [PMID: 17082717] 2300 mg/d is often the first lifestyle

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 Table 4. Lifestyle Modifications to Reduce Blood Pressure Lifestyle Modification Recommendation Potential Decrease in SBP Dietary sodium Restrict dietary sodium to no more 2–8 mm Hg restriction than 2400 mg/d or 100 meq/d Weight loss Maintain normal body weight 5–20 mm Hg/10 kg 15. Bobrie G, Chatellier (BMI, 18.5–24.9 kg/m2) of weight lost G, Genes N, Clerson P, Vaur L, Vaisse B, et Aerobic exercise Engage in regular aerobic exercise, 4–9 mm Hg al. Cardiovascular aiming to do 30 min of aerobic prognosis of “masked hyperten- exercise on most days of the week. It sion” detected by is suggested that patients walk about blood pressure self- 1 mile per day above current activity level measurement in elderly treated hyper- DASH diet Consume a diet rich in fruits, vegetables, 4–14 mm Hg tensive patients. and low-fat dairy, with reduced saturated JAMA. and total fat 2004;291:1342-9. [PMID: 15026401] Limit alcohol intake Consume no more than 2 mixed drinks, 2–4 mm Hg 16. Cicconetti P, Morelli two 12-ounce cans of beer, or two S, De Serra C, Ciotti 4-ounce glasses of wine daily for men V, Chiarotti F, de Marle MG, et al. Left and one half of this quantity for women ventricular mass in dippers and nondip- BMI = body mass index; DASH = Dietary Approaches to Stop Hypertension; SBP = systolic blood pressure pers with newly diagnosed hypertension. Angiology. 2003;54:661-9. [PMID: 14666954] change, although a recent Institute of adults with systolic blood pressure less than 17. Kario K, Pickering TG, 160 mm Hg and diastolic blood pressure of 80 Umeda Y, Hoshide S, Medicine report suggests that studies Hoshide Y, Morinari on health outcomes are inconsistent in to 95 mm Hg to 8 weeks of a control diet (25); M, et al. Morning quality and insufficient in quantity to a diet rich in fruits and vegetables; or a “com- surge in blood pres- bination” diet rich in fruits, vegetables, and sure as a predictor of determine whether sodium intake less silent and clinical low-fat dairy products. The combination diet cerebrovascular dis- than 2300 mg/d increases or decreases ease in elderly hy- reduced systolic and diastolic blood pressure pertensives: a the risk for heart disease, stroke, or all- by 5.5 and 3.0 mm Hg more, respectively, prospective study. cause mortality (21). A recent study Circulation. than the control diet (P < 0.001); the fruits- 2003;107:1401-6. examining fasting urine samples for and-vegetables diet reduced systolic blood [PMID: 12642361] P 18. Fierro-Carrion GA, sodium excretion as a measure of in- pressure by 2.8 mm Hg more ( < 0.001) and Ram CV. Nons- take in more than 100 000 persons diastolic blood pressure by 1.1 mm Hg more teroidal anti-inflam- than the control diet (P= 0.07). Blood pressure matory drugs from 17 countries noted that estimat- (NSAIDs) and blood ed sodium intake between 3 and 6 g/d reductions were larger in 133 patients with pressure [Editorial]. hypertension than in normotensive patients. Am J Cardiol. was associated with a lower risk for 1997;80:775-6. A diet rich in fruits, vegetables, and low-fat [PMID: 9315588] cardiovascular death (22). The average dairy foods decreases blood pressure (26). 19. (KDIGO) Blood Pres- sure Work Group. Western diet contains 3400 mg of Kidney Disease: Im- sodium per day, and patients are often Other lifestyle interventions proving Global Out- comes (KDIGO) unaware of the high sodium content Weight loss (to <20% above the ideal Blood Pressure Work of many foods (23, 24). Patients Group. KDIGO Clini- body weight for the patient’s height) cal Practice Guide- should especially avoid processed should be encouraged. Systolic blood line for the Manage- ment of Blood foods, lunchmeats, soups, bread, pressure decreases by approximately Pressure in Chronic cheese, Chinese food, and canned Kidney Disease. Kid- 1 mm Hg for every kilogram of ney Int [Suppl]. processed food and should preferen- weight loss (27). Clinicians should 2012;2:414. 20. Go AS, Bauman MA, tially eat fresh fruit and vegetables. also encourage at least 30 minutes of Coleman King SM, aerobic exercise on most days of the Fonarow GC, In TOHP I, adults with diastolic blood pres- Lawrence W, week. Smoking cessation should be Williams KA, et al; sure of 80 to 89 mm Hg and systolic blood strongly encouraged; it does not di- American Heart As- pressure less than 160 mm Hg were random- sociation. An effec- rectly decrease blood pressure but does tive approach to ly assigned to 18-month interventions to lose high blood pressure weight or reduce dietary sodium intake or to decrease cardiovascular risk. Alcohol control: a science intake should be reduced to no more advisory from the 1 of 2 control groups. After 7 years, the inci- American Heart As- dence of hypertension was 18.9% in the than two mixed drinks, two 12-ounce sociation, the Ameri- can College of Cardi- weight-loss group and 40.5% in its control cans of beer, or two 4-ounce glasses of ology, and the group and 22.4% in the sodium reduction wine daily for men and to one half of Centers for Disease Control and Preven- group and 32.9% in its control group (8). these quantities for women (28, 29). tion. Hypertension. 2014;63:878-85. The DASH (Dietary Approaches to Stop Hy- [PMID: 24243703] The PREMIER trial randomly assigned 810 doi:10.1161/HYP.000 pertension) trial randomly assigned 459 participants to behavioral intervention 0000000000003

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 (weight loss, exercise, and limited sodium results for the other 3 drugs supported di- and alcohol intake), the DASH diet plus be- uretics as first-choice therapy because of havioral intervention, or one-time advice their efficacy in reducing cardiovascular only. Compared with the advice-only inter- death and nonfatal myocardial infarction, vention, systolic blood pressure at 6 months superiority in secondary outcomes (heart decreased by 3.7 mm Hg (behavioral change failure and stroke), and low cost (33). only) and 4.3 mm Hg (behavioral change plus DASH diet) (30). Clinicians should strongly consider

21. Committee on the treating hypertension in very elder- Consequences of Several lifestyle changes are of dubi- ly patients. Sodium Reduction in Populations; Food ous value. Fish oil, magnesium, and and Nutrition Board; calcium supplementation do not HYVET (Hypertension in the Very Elderly Tri- Board on Population al) randomly assigned 3845 patients older Health and Public reduce blood pressure. Although pa- Health Practice; Insti- tients may consider relaxation thera- than 80 years with systolic blood pressure tute of Medicine; of 160 to 199 mm Hg to either placebo or a Strom BL, Yaktine AL, pies, such as meditation and yoga, Oria M, eds. Sodium diuretic (indapamide, 1.5 mg/d) with the intake in popula- their effect is short-term (31). Caf- addition of an ACE inhibitor (perindopril, tions: assessment of feine may transiently increase blood evidence. Washing- 4 to 8 mg/d) as needed. The trial was ton, DC: National pressure but has little sustained effect stopped early because of the large benefit Academy of Sci- ences; 2013:1-4. on blood pressure in patients with of active treatment, with an expected 30% [PMID: 24851297] hypertension (32). reduction in fatal and nonfatal stroke and 22. O’Donnell M, Mente A, Rangarajan S, Mc- an unexpected 21% reduction in all-cause Queen MJ, Wang X, When is antihypertensive drug mortality. This study confirmed the value Liu L, et al; PURE In- vestigators. Urinary therapy indicated, and which of drug treatment for patients aged 80 sodium and potassi- drugs should clinicians prescribe years or older who have systolic blood um excretion, mortality, and cardiovas- as initial therapy? pressure of at least 150 mm Hg (34). cular events. N Engl J Med. 2014;371:612- Many patients with hypertension re- 23. [PMID: 25119607] quire drug therapy to control blood How should clinicians modify the doi:10.1056/NEJ- choice of antihypertensive Moa1311889 pressure despite lifestyle modifica- 23. Cordain L, Eaton SB, treatment on the basis of patient Sebastian A, Mann tion. The JNC 8 recommends start- N, Lindeberg S, ing all patients on a thiazide-type characteristics and comorbid Watkins BA, et al. conditions? Origins and evolu- diuretic unless they have diabetes or tion of the Western Although thiazide-type diuretics are diet: health implica- chronic kidney disease, in which case tions for the 21st an angiotensin-converting enzyme generally the recommended first- century. Am J Clin Nutr. 2005;81:341-54. (ACE) inhibitor or ARB alone or choice agent, clinicians should mod- [PMID: 15699220] ify drug selection on the basis of 24. Mattes RD, Donnelly combined with a drug from another D. Relative contribu- class is recommended first. Table 5 patient characteristics and comorbid tions of dietary sodi- conditions. Older and African um sources. J Am shows the doses, mechanisms, and Coll Nutr. American patients tend to be salt- 1991;10:383-93. advantages and disadvantages of [PMID: 1910064] some commonly used antihyperten- sensitive and respond well to diuret- 25. Appel LJ, Moore TJ, ics or calcium-channel blockers. Obarzanek E, sive drugs. The Figure provides an Vollmer WM, Svetkey algorithm for treatment of hyperten- LP, Sacks FM, et al. A Younger patients with hypertension clinical trial of the ef- sion, and Table 6 elaborates on com- fects of dietary pat- often respond well to suppression of terns on blood pres- pelling drug indications. sure. DASH the renin–angiotensin system, and an Collaborative Re- ALLHAT (Antihypertensive and Lipid- ACE inhibitor or ARB may be a search Group. N Engl J Med. Lowering Treatment to Prevent Heart At- good initial choice for these patients. 1997;336:1117-24. tack Trial) randomly assigned 44 000 [PMID: 9099655] These drugs are helpful in patients 26. Bray GA, Vollmer patients older than 55 years with hyperten- with diabetes, particularly if microal- WM, Sacks FM, sion and 1 additional cardiovascular risk Obarzanek E, buminuria is present. Patients with Svetkey LP, Appel LJ; factor to initial treatment with a diuretic heart failure can benefit from ACE DASH Collaborative (chlorthalidone), an α-blocker (doxazosin), Research Group. A inhibitors, diuretics, cardioselective further subgroup an ACE inhibitor (lisinopril), or a calcium- β β analysis of the ef- channel blocker (amlodipine). Addition of a -blockers, and ARBs. -Blockers fects of the DASH and ACE inhibitors are good anti- diet and three di- second drug was permitted as needed. The etary sodium levels doxazosin group was discontinued when hypertensive agents for patients who on blood pressure: results of the DASH- interim results showed that the drug was have had a myocardial infarction. Sodium Trial. Am J not superior to a diuretic and that heart Patients with reduced glomerular fil- Cardiol. 2004;94:222- 7. [PMID: 15246908] failure was higher with doxazosin. The tration rate can benefit from ACE

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 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 (12.5–50) systolic hypertension, diabetics, and African hypokalemia; photosensitivity Chlorothiazide (250–500) Americans, who are likely to be salt-sensitive; Chlorothalidone (12.5–50) inexpensive ACE inhibitors Preferred for chronic kidney disease, heart failure, Cough in 15% (switch to an ARB). Can accept up to 30% Enalapril (5–40) and diabetes. Work well with diuretics. Generic increase in serum creatinine with ACE inhibitors. Angio- Fosinopril (10–40) ACE inhibitors are inexpensive edema in 0.1%–0.7%. Contraindicated in pregnancy Lisinopril (5–40) Perindopril (4–16) Quinapril (5–80) Ramipril (1.25–20) ARBs Usually well-tolerated. Angiedema uncommon. Dizziness. Relatively expensive. Contraindicated in pregnancy Losartan (25–100) Work well with a diuretic. Do not cause cough Candesartan (16–32)

Irbesartan (150–300) Potassium-sparing diuretics Most useful when a thiazide causes hypokalemia Hyperkalemia (rare with triamterene); gynecomastia (spirono- Spironolactone (25–100) lactone); weak antihypertensives Triamterene (25–100) ß-blockers Carvedilol is an a- and ß-blocker. Nebivolol is Bronchospasm, bradycardia, heart failure; masks Atenolol (25–100) also a vasodilator. Note: Don’t use ß-blockers insulin-induced hypoglycemia; impairs peripheral circulation; Metoprolol (50–300) as initial therapy except in heart failure insomnia; fatigue; decreased exercise tolerance; Propranolol (40–480) hypertriglyceridemia (unless ISA present); several trials show Nebivolol (2.5–10) worse outcomes with atenolol than ACE inhibitors, ARBs, Carvedilol (12.5–50) and CCBs CCBs Well-tolerated and effective. Dihydropyridines, Diuretic-resistant edema (lesser problem if ACE inhibitor or Amlodipine (2.5–10) like amlodipine, are quite potent. Relatively ARB added), headache, cardiac conduction defects, constipa- Diltiazem (120–360) inexpensive tion, gingival hypertrophy Verapamil (120–480) Nifedipine (30–120) Reserpine (0.05–0.25) Inexpensive Nasal congestion, depression, peptic ulcer Central ß-agonists Inexpensive Sedation, dry mouth, bradycardia, withdrawal (rebound) Methyldopa (500–3000) hypertension Clonidine (0.2–1.2) Guanethidine (10–50) Very potent; inexpensive Postural hypotension; diarrhea; heart failure increased with a-blockers doxasin in ALLHAT Prazosin (2–30) Doxasosin (1–16) Terazosin (1–20) Hydralazine (50–300) Inexpensive Lupus reaction; headache; edema Direct renin inhibitor Newly approved. Reduced plasma renin could be Diarrhea Aliskiren (150–300) therapeutic per se; effective in combination

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

inhibitors or ARBs, particularly if of the patients also had hypertension, the needed) or to a combination of a calcium- proteinuria is present. authors concluded that an ACE inhibitor is channel blocker (amlodipine) and an ACE reasonable initial hypertension therapy in inhibitor (perindopril) if needed and, in a fac- The HOPE (Heart Outcomes Prevention patients with vascular disease (35). torial design, to either a statin or placebo. Evaluation) trial randomly assigned more After median follow-up of 5.5 years, the trial than 9000 patients older than 55 years In ASCOT (Anglo-Scandinavian Cardiac was stopped because cardiovascular events with CVD to ramipril, 10 mg at night, or Outcomes Trial), more than 19 000 adults and total mortality were significantly lower placebo and found that those receiving with hypertension and 3 or more CVD risk in the group that received the amlodipine- ramipril had less morbidity and mortality factors were randomly assigned to either a based regimen. Although blood pressure than those receiving placebo. Because half β-blocker plus a thiazide-type diuretic (if was well-controlled in both groups, it was

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 Table 6. Compelling Indications for Individual Drug Classes* Compelling Indication† Recommended Drugs Heart failure Diuretic, ß-blocker, ACE inhibitor, ARB, aldosterone antagonist

27. Whelton PK, Appel Postmyocardial infarction ß-blocker, ACE inhibitor, aldosterone antagonist LJ, Espeland MA, Ap- High coronary disease risk Diuretic, ß-blocker, ACE inhibitor, ARB + CCB plegate WB, Ettinger WH Jr, Kostis JB, et al. Diabetes Diuretic, ß-blocker, ACE inhibitor, ARB, CCB Sodium reduction Chronic kidney disease ACE inhibitor, ARB and weight loss in the treatment of hy- Recurrent stroke prevention Diuretic, ACE inhibitor pertension in older persons: a random- ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channel ized controlled trial blocker. of nonpharmacolog- ic interventions in * Adapted from JNC 7 Hypertension Clinical Practice Guidelines (www.nhlbi.nih.gov/guidelines/ the elderly (TONE). hypertension/express.pdf). TONE Collaborative Research Group. † Compelling indications for antihypertensive drugs are based on benefits from outcome studies or ex- JAMA. 1998;279:839- isting clinical guidelines; the compelling indication is managed in parallel with the blood pressure. 46. [PMID: 9515998]

Figure. Algorithm for treatment of hypertension. From reference 4. ACE = angiotensin-converting enzyme; ARB = angiotensin-receptor blocker; CCB = calcium-channel blocker; CKD = chronic kidney disease; DBP = diastolic blood pressure; SBP = systolic blood pressure.

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 lower in the amlodipine group by an aver- (Ongoing Telmisartan Alone and in age of 2.7/1.9 mm Hg. The amlodipine and Combination with Ramipril Global ACE inhibitor drug combination reduced the Endpoint Trial) confirmed that ACE 28. Fagrell B, De Faire U, risk for stroke by about 25%, for coronary inhibitors and ARBs are not additive Bondy S, Criqui M, events and procedures by 15%, and for car- Gaziano M, Gron- in combination therapy for hyperten- baek M, et al. The ef- diovascular deaths by 25% (36). fects of light to sion and have more adverse effects, moderate drinking such as hyperkalemia and a slight de- on cardiovascular What is the role of combination diseases. J Intern therapies? crease in glomerular filtration rate Med. 1999;246:331- 40. [PMID: 10583704] Combination therapies are gaining (39). An ACE inhibitor, an ARB, or 29. Xin X, He J, Frontini a combination of the 2 drugs had the MG, Ogden LG, Mot- popularity. They have several advan- samai OI, Whelton tages, including better adherence. same effect on cardiovascular events. PK. Effects of alcohol Moreover, in the recently completed reduction on blood Whether they ultimately cost less for pressure: a meta- ALTITUDE (Aliskiren Trial in Type analysis of random- patients than individual prescriptions ized controlled trials. for each of the drugs depends on the 2 Diabetes Using Cardiovascular and Hypertension. Renal Disease Endpoints) (40) and 2001;38:1112-7. patients’ insurance programs. [PMID: 11711507] VA Nephron-D (Veterans Affairs 30. McGuire HL, Svetkey LP, Harsha DW, Elmer ACE inhibitors or ARBs combined with Nephropathy in Diabetes Study) PJ, Appel LJ, Ard JD. hydrochlorothiazide (41), it was evident that using a renin Comprehensive lifestyle modification Many ACE inhibitors and ARBs inhibitor with an ACE inhibitor or and blood pressure control: a review of are available in combination with a an ARB, or using an ACE inhibitor the PREMIER trial. J thiazide. This combination is well- and an ARB did not relieve the risk Clin Hypertens (Greenwich). tolerated and is often good initial for cardiovascular and renal end 2004;6:383-90. [PMID: 15249794] therapy for patients with a blood pres- points in patients with diabetes and 31. Alexander CN, sure greater than 160/100 mm Hg. kidney disease compared with a Schneider RH, Stag- gers F, Sheppard W, renin–angiotensin system blocker Clayborne BM, Rain- ACE inhibitors and ARBs combined with alone and was associated with more forth M, et al. Trial of nonhydropyridine calcium-channel stress reduction for adverse events. hypertension in old- blockers er African Ameri- cans. II. Sex and risk An ACE inhibitor or ARB with When blood pressure is poorly subgroup analysis. amlodipine is available in various controlled, how should clinicians Hypertension. 1996;28:228-37. doses and in generic versions. decide among increasing dose, [PMID: 8707387] 32. Taubert D, Roesen R, Adding an ACE inhibitor or ARB adding an additional agent, or Schömig E. Effect of avoids the edema of amlodipine switching to another drug class? cocoa and tea intake on blood pressure: a monotherapy (37). When blood pressure is poorly meta-analysis. Arch controlled, it is important to avoid Intern Med. In the ACCOMPLISH (Avoiding Cardiovascu- 2007;167:626-34. clinical inertia (42). The following [PMID: 17420419] lar events through Combination therapy in 33. Major cardiovascular principles were formulated to deal events in hyperten- Patients Living with Systolic Hypertension) sive patients ran- trial, 11 506 patients with hypertension re- with a particular form of poorly con- domized to doxa- trolled blood pressure called “resistant zosin vs ceived benazepril, 40 mg, with either am- chlorthalidone: the lodipine or hydrochlorothiazide plus other hypertension,” but they are useful antihypertensive when blood pressure is above the tar- and lipid-lowering medications as needed to control blood treatment to pre- pressure. The primary end point was a com- get. Resistant hypertension is when vent heart attack trial (ALLHAT). ALLHAT posite of cardiovascular outcomes and blood pressure is above the target Collaborative Re- death. Blood pressure was controlled effec- despite use of a rational, full-dose, search Group. JAMA. 2000;283:1967-75. tively in each group (131.6/73.3 mm Hg in triple-drug regimen that includes a [PMID: 10789664] the benazepril–amlodipine group and diuretic (43, 44). If the patient has no 34. Beckett NS, Peters R, 132.5/74.4 mm Hg in the benazepril– Fletcher AE, Staessen target organ damage, the clinician JA, Liu L, Dumitrascu hydrochlorothiazide group). After a mean D, et al; HYVET Study should consider ambulatory blood follow-up of 36 months, the study was termi- Group. N Engl J Med. pressure monitoring to see whether 2008;358: 1887-98. nated early because of a 19.6% relative risk [PMID: 18378519] the white coat effect is a contributing doi:10.1056/NEJ- reduction in the primary end point in pa- Moa0801369 tients receiving benazepril–amlodipine (38). factor. The clinician should ask about 35. Yusuf S, Sleight P, comedication with blood pressure– Pogue J, Bosch J, Davies R, Dagenais ACE inhibitor–ARB combination therapy increasing drugs and excessive alco- G. The Heart Out- comes Prevention ACE inhibitor–ARB combinations hol or salt intake. Secondary causes Evaluation Study In- do not seem to have clinical advan- of hypertension should be reconsid- vestigators. N Engl J Med. 2000;342:145- tages. The recent ONTARGET ered because they are much more 53. [PMID: 10639539]

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 common in resistant hypertension. How often should patients with Poor adherence is also common, so hypertension be seen? adherence should be carefully evalu- Blood pressure and clinical judg- ated before treatment is changed. ment should guide decisions about the frequency of monitoring blood Because clinically apparent volume pressure. Suggested recheck intervals 36. Dahlöf B1, Sever PS, overload is common, clinicians are 2 months for blood pressure of Poulter NR, Wedel H, Beevers DG, should start treating uncontrolled 140/90 to 159/99 mm Hg and Caulfield M, et al; AS- hypertension by adding or increas- COT Investigators. within 1 month for higher blood Lancet. 2005; ing diuretic therapy with a thiazide pressure. If the systolic and diastolic 366:895-906.[PMID: or thiazide-like diuretic in patients 16154016] blood pressures fall into different 37. Weir MR, Rosenberg- with reasonable renal function categories, recommendations for the er C, Fink JC. Am J Hypertens. (estimated glomerular filtration shorter follow-up time should be 2001;14:963-8. rate >45 mL/min) or a loop diuret- [PMID: 11587165] followed. After adjusting medica- 38. Jamerson K, Weber ic in those with abnormal renal tions, clinicians should allow 2 to 4 MA, Bakris GL, Dahlöf B, Pitt B, Shi V, function (estimated glomerular fil- weeks for the blood pressure to sta- et al; ACCOMPLISH tration rate ≤45 mL/min). A key to Trial Investigators. bilize before modifying therapy. N Engl J Med. success is using several drugs, each Clinical opinion rather than evi- 2008;359:2417-28. targeting a different disease mecha- [PMID: 19052124] dence determines the interval for doi:10.1056/NEJ- nism. Table 7 shows physiologic seeing patients with stable, well- Moa0806182 39. Yusuf S, Teo KK, mechanisms and the drug class that controlled hypertension; 6- to Pogue J, Dyal L, counteracts each. If the patient is Copland I, Schu- 12-month intervals are typical. De- macher H, et al; taking 2 drugs that attack the same cisions about appropriate intervals ONTARGET Investi- gators. N Engl J Med. disease mechanism, 1 should be re- for laboratory testing depend on the 2008;358:1547-59. placed with a drug from a different [PMID: 18378520] number and type of medications doi:10.1056/NEJ- class. If the patient is taking 3 and medical comorbidity. Moa0801317 drugs and blood pressure remains 40. Parving HH, Brenner BM, McMurray JJ, de uncontrolled, the clinician should What is the value of home blood Zeeuw D, Haffner pressure monitoring? SM, Solomon SD, et ensure that the patient is taking al; ALTITUDE Investi- drugs from different classes. Clini- Home blood pressure monitoring gators. N Engl J Med. 2012;367:2204- cians should consider adding a is a relatively inexpensive way to 13. [PMID: 23121378] potassium-sparing diuretic, such as monitor blood pressure, especially doi:10.1056/NEJ- Moa1208799 spironolactone or amiloride, for pa- before and after changing therapy. 41. Fried LF, Emanuele N, Zhang JH, Brophy tients taking 3 or 4 drugs if blood Measurements of home blood pres- M, Conner TA, Duck- pressure is still uncontrolled. A sure more accurately represent what worth W, et al; VA NEPHRON-D Investi- combined α- and β-blocker, a cen- is seen with 24-hour ambulatory gators. N Engl J Med. 2013;369: trally acting agent, or reserpine (in blood pressure monitoring than 1892-903. [PMID: low doses) should be considered. If blood pressure measured in the of- 24206457] doi:10.1056/NEJ control remains elusive, a specialist fice (45). Some patients become Moa1303154 in hypertension management obsessed with their blood pressure, 42. Phillips LS, Branch WT, Cook CB, Doyle should be consulted. and the physician may have to set JP, El-Kebbi IM, Galli- na DL, et al. Ann Intern Med. 2001;135:825-34. [PMID: 11694107] Table 7. Drug Therapy for Specific Disease Mechanisms of Hypertension* 43. Calhoun DA, Jones D, Textor S, Goff DC, Disease Mechanism Drug Class Comment Murphy TP, Toto RD, et al; American Heart Volume overload Thiazide; loop diuretic; Association Profes- aldosterone antagonist sional Education Sympathetic overactivity ß-blocker Use to counteract reflex tachycardia Committee. Circula- tion. 2008;117:e510- from vasodilators or in heart failure 26. [PMID: 18574054] Increased vascular resistance Angiotensin-converting Use in heart failure doi:10.1161/CIRCU- LATIONAHA.108. enzyme inhibitor or 189141 angiotensin-receptor 44. Moser M, Setaro JF. blocker Clinical practice. N Engl J Med. Smooth-muscle contraction Dihydropyridine calcium- 2006;355:385-92. channel blockers; [PMID: 16870917] ß-blockers; hydralazine 45. Pickering T. Am J Hy- pertens. 1996;9:1-11. * Adapted from reference 33. [PMID: 8834700]

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 limits on how often the patient a hypertensive crisis (Box). Indica- Situations in Which Severe takes home blood pressure readings tions for referral to a hypertension Hypertension Constitutes a Crisis lest their anxiety over the results specialist include drug-resistant hy- Cardiovascular increase their blood pressure. Pa- pertension uncontrolled with 3 or • Left-ventricular failure tients should be instructed on the more drugs, uncertainty about how • Myocardial infarction correct technique for measurement to evaluate or manage suspected • Unstable angina and asked to keep a journal in secondary hypertension (especially • Aortic dissection which they chart their blood pres- pheochromocytoma or primary • After vascular surgery or coronary sure once or twice per day. Brachial hyperaldosteronism), or need for artery bypass grafting artery blood pressure cuff measure- assistance in assessing the extent of Neurologic ments are more likely to be accu- target organ damage. • Hypertensive encephalopathy rate than wrist cuff measurements. • Subarachnoid or intracranial When patients present with hemorrhage Home blood pressure monitoring markedly elevated blood pressure, • Thrombotic stroke can help to confirm a diagnosis of how should clinicians distinguish Other between a hypertensive emergency • Severe catecholamine excess, such as hypertension in an untreated pa- clonidine withdrwal, pheochromocy- tient (46, 47). Clinicians should and a pseudocrisis? toma, tyramine-MAOI interaction, or instruct the patient to take at least A sudden increase in blood pressure intoxication (cocaine, phenylcyclidine, 2 readings on at least 3 (preferably is classified as either hypertensive phenylpropanolamine) 7) consecutive days between 6:00 urgency or hypertensive emergency • Eclampsia in pregnancy and 10:00 a.m. and to repeat them (49). The former is defined as blood MAOI = monoamine oxidase inhibitors. between 6:00 and 10:00 p.m. each pressure greater than 180/110 mm day. If the average pressure is less Hg without target organ damage. than 125/75 mm Hg (disregarding Patients can usually be managed the first day’s values), hypertension with oral medications as outpa- is unlikely in an untreated person tients and sent home after a few (48). An average untreated home hours of observation. A hyperten- blood pressure of 135/85 mm Hg sive emergency is defined as an or higher suggests hypertension. elevated blood pressure with im- In-between values are an indication pending or acute progressive target for further evaluation by ambulatory organ damage. These patients 46. Pickering TG, Miller usually require admission to an in- NH, Ogedegbe G, blood pressure monitoring. Home Krakoff LR, Artinian readings can also assist in the di- tensive care unit and intravenous NT, Goff D; American Heart Association. agnosis of white coat or masked medication to decrease their blood Hypertension. pressure (50). Several drugs de- 2008;52:1-9. hypertension. [PMID: 18497371] crease blood pressure quickly; the doi:10.1161/HYPER- When should clinicians consider TENSIONA- choice depends on the physician’s HA.107.189011 hospitalization or referral to a level of comfort and experience 47. Wilson MD, Johnson KA. Hypertension hypertension specialist? with the drugs. The Box shows sit- management in The primary indication for hospital- uations in which severe hyperten- managed care: the role of home blood ization for elevated blood pressure is sion constitutes a crisis. pressure monitoring. Blood Press Monit. 1997;2:201-206. [PMID: 10234118] 48. Williams B, Poulter Treatment... The blood pressure goal should be less than 140/90 mm Hg unless NR, Brown MJ, Davis M, McInnes GT, Pot- the patient is older than 60 years, in which case the goal is less than 150/90 mm Hg. ter JF, et al; British Lifestyle modifications can decrease blood pressure, but most patients also need Hypertension Socie- at least 1 drug to reach the blood pressure goal, such as a thiazide-type diuretic, ty. Guidelines for management of hy- an ACE inhibitor, an ARB, a calcium-channel blocker, or a combination. If the pertension: report of patient has diabetes or chronic kidney disease, an ACE inhibitor or ARB is the pre- the fourth working party of the British ferred initial agent. Failure to reach the target blood pressure on a near-maximal Hypertension Socie- dose of 1 or more drugs is an indication to add a drug that attacks another mecha- ty, 2004-BHS IV. J Hum Hypertens. nism for hypertension. Severe hypertension requires urgent treatment, often in the 2004;18:139-85. hospital, if acute cardiovascular or neurologic events are present, if the patient is [PMID: 14973512] pregnant, or if severe catecholamine excess is present. 49. Townsend R. Hyper- tensive Crises. In Lankin PN, ed. The Intensive Care Unit Manual. Philadel- CLINICAL BOTTOM LINE phia: WB Saunders; 2000:602-14.

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 Downloaded From: http://annals.org/ by aMcGill University User on08/26/2016 © 2014 AmericanCollegeofPhysicians 50. LipGY, Beevers M, [PMID: 8557970 tens. 1995;13:915-24. JHyper- pertension. malignant-phase hy- of 315patientswith cations andsurvival Beevers DG.Compli- Hypertension Tool Kit In theClinic Improvement Practice ACP inpatientswithdiabetes. ofhypertension forthecare DiabetesMonthly www.acpinternist.org/diabetes/?dbp from theNationalGuidelines KidneyFoundation formanaginghypertension www.kidney.org/professionals/KDOQI/guidelines.cfm Associationformanaginghypertension Heart from theAmerican Guidelines circ.ahajournals.org/cgi/reprint/CIRCULATIONAHA.107.183885 oftheJointNational CommitteeonPrevention, Report The Seventh https://hyper.ahajournals.org/content/42/6/1206.full.pdf+html Clinical Guidelines From forPerformance Consortium thePhysician Improvement. Amongthetools www.ama-assn.org/ama/pub/physician-resources/physician-consortium-performance From Forum. the National Quality www.qualityforum.org Practice Measures Medicinemoduleonhypertension. Access theSmart http://smartmedicine.acponline.org/index.aspx Smart MedicineModules in patientswithrenal disease. disease. cardiovascular atherosclerotic to prevent Detection, Evaluation, and Treatment ofHighBloodPressure. is agoodflow sheetforrecording keydataover time. -improvement/pcpi-measures.page ITC14 well isitcontrolled? hypertension treatment,andhow How manyU.S.patientsreceive Among patientsaged60yearsor persons, Americans. andMexican both sexes, non-Hispanicblack in rates increased substantially in 2003to2004(2). The control 1999 to2000and36.8%±2.3% control ratewas29.2%±2.3%in are improving: The bloodpressure ment. control rates Hypertension 55%are receivingmately treat- thirds are aware ofitandapproxi- pertension; amongthese, two only One thirdofU.S. adultshavehy- In theClinic Annals ofInternal Medicine Physicians. (19), Collegeof andtheAmerican ease: Improving GlobalOutcomes (20),of Cardiology KidneyDis- College Association andAmerican the JNC8(4), Heart theAmerican represents therecommendations of generally The adviceinthisarticle organizations recommend? What doprofessional rates approach 65%. tients withhypertension, control (2).nificantly Amongtreated pa- control rateshaveallincreased sig- older, awareness, treatment, and

2 December2014 In theClinic WHAT YOU SHOULD KNOW In the Clinic Annals of Internal Medicine ABOUT HYPERTENSION

What is hypertension? Hypertension, or high blood pressure, is a common health problem. Blood pressure measures the force of blood pushing against the walls of your arteries as your heart pumps blood through your body. High blood pressure strains your blood vessels and your heart. Your heart has to work harder with every heartbeat. If you don’t get treated for your hypertension, there is a higher risk for heart attack, heart failure, stroke, or kidney failure.

What are the warning signs? Hypertension often has no symptoms. Some people can tell when their blood pressure may be high, but the only way to know for sure is to have it measured. For most people, there is no one cause. Your family history, diet, weight, and other lifestyle habits can affect your blood pressure. Certain medical problems, such as kidney or thyroid disease, may cause blood pressure to rise. Also, certain medicines, like those for arthritis or colds, can raise blood pressure. Some women develop a special type of high blood pressure during pregnancy. This usually goes away after the baby is born, but sometimes it can linger. How is it treated? There are many different medicines to help treat high How is it diagnosed? blood pressure. Your doctor may prescribe one Blood pressure is measured by placing a cuff around the medicine or a combination of medicines. Many arm and inflating the cuff, which is connected to a lifestyle changes can also help to lower your blood device that measures pressure. The test is easy and pressure. Almost everyone with high blood pressure painless. Your doctor may want to take several can bring down their numbers with lifestyle changes, readings at different times before diagnosing you with medicines, or both. Follow these healthy habits even hypertension. This is because blood pressure normally if you take blood pressure medicine: changes during the day. The reading is given as two numbers (example: 120/80). The top number is called • Eat less salt systolic pressure, and it measures the pressure while • Exercise your heart is beating. The bottom number is called • Eat more fruits and vegetables diastolic pressure, and measures the pressure while the • Lose weight heart is relaxed between beats. Normal blood pressure • Drink less alcohol is any pressure equal to or less than 120/80. • Quit smoking

For More Information

www.acponline.org/patients_families/pdfs/health/hypertension _report.pdf American College of Physicians: ACP Special Report: Living with Hypertension

www.acponline.org/patients_families/pdfs/health/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 Patient Information Patient

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 CME Questions

1. A 23-year-old woman is evaluated during A. Ambulatory blood pressure Using the patient’s home device, blood a follow-up visit. She was initially monitoring pressure measurements are 150/86 mm evaluated at a walk-in clinic for flu-like B. Echocardiography Hg and 147/83 mm Hg. BMI is 25. Other symptoms and was found to have a C. Hydralazine vital signs are normal. The remainder of blood pressure of 144/90 mm Hg. At her D. Urine metanephrine measurement the examination is unremarkable. first office visit 3 weeks ago, his blood Within the past year, she has had normal pressure was 136/83 mm Hg seated 3. A 42-year-old woman is evaluated during chemistry laboratory test results and a (average of three readings). Medical a follow-up visit for high blood pressure. normal electrocardiogram. history is unremarkable. She takes no Two weeks ago, her blood pressure was medications. 150/94 mm Hg. She says she has never Ambulatory blood pressure monitoring is been told she has high blood pressure ordered, and results show an average 24- On physical examination today, blood hour systolic blood pressure of 127 mm pressure is 133/79 mm Hg seated before but thinks her last BP reading was 4 years ago. She has no history of Hg and an average 24-hour diastolic (average of three readings); other vital blood pressure of 82 mm Hg; the average signs are normal. The remainder of the cardiovascular disease. She takes no prescription medications. daytime pressure is less than 130/80 mm examination is normal. Hg, and the average nighttime pressure is Which of the following is the most likely On physical examination, temperature is less than 120/70 mm Hg (all values ° ° diagnosis? 37.1 C (98.8 F), blood pressure is 148/96 normal). mm Hg seated and 156/100 mm Hg A. Masked hypertension standing, pulse rate is 82/min, and Which of the following is the most B. Normotension respiration rate is 18/min. BMI is 27. appropriate next step in management? C. Prehypertension Funduscopic examination shows A. Continue home blood pressure D. White coat hypertension arteriolar narrowing with two measurements arteriovenous crossing defects (“nicking”). B. Initiate chlorthalidone 2. An 83-year-old woman is evaluated The remainder of the examination is C. Order echocardiography during a follow-up visit for a 3-year unremarkable. D. Order a plasma aldosterone-plasma history of hypertension. She feels relatively well. She stopped smoking Initial laboratory studies, including serum renin activity ratio cigarettes 40 years ago. She appears to electrolyte levels, complete blood count, E. Order a spot urine be adherent to her medication regimen, lipid profile, and urinalysis, are normal. albumin–creatinine ratio which consists of maximum doses of Normal kidney function is noted. chlorthalidone, enalapril, amlodipine, and Which of the following is the most Disclosures: Dr. Weir, ACP Contributing carvedilol, and which her daughter appropriate next step in management? Author, has disclosed the following administers. A. Atenolol conflicts of interest: Consultancy: On physical examination, seated blood B. Electrocardiography Amgen, Relypsa, Keryx, Sanofi, pressure is 158/68 mm Hg, and pulse C. Home blood pressure monitoring Novartis, Janssen, BMS, Otsuka, rate is 68/min; other vital signs are D. Plasma aldosterone-plasma renin AbbVie, Sandoz. Disclosures can also normal. BMI is 26. A systolic crescendo- activity ratio be viewed at www.acponline.org/ decrescendo murmur is noted at the right authors/icmje/ConflictOfInterest upper sternal border. The carotid 4. A 53-year-old woman is evaluated during Forms.do?msNum=M14-1897. upstrokes are normal, and no bruits are a follow-up visit for hypertension. Her heard. Trace pedal edema is noted. office blood pressure measurements are Laboratory studies reveal normal high; however, her home readings range electrolytes, complete blood count, from 118 to 140 mm Hg systolic and 82 fasting glucose, and fasting lipid profile to 88 mm Hg diastolic, averaging 126/84 as well as normal kidney function. mm Hg. She has no known cardiovascular disease. She consumes a vegetarian diet, Which of the following is the most exercises almost daily, and does not appropriate next step in management? smoke cigarettes.

Questions are largely from the ACP’s Medical Knowledge Self-Assessment Program (MKSAP, accessed at http://mksap.acponline.org/). Go to www.annals.org/intheclinic.aspx to complete the quiz and earn up to 1.5 CME credits, or to purchase the complete MKSAP program.

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016 CORRECTION

Correction: In the Clinic: Hypertension A recent In the Clinic (1) contained errors. In the Guidelines for Blood Pressure Goals sidebar on page ITC6, the first recommendation is JNC 8, reference 4.

In the third row of boxes in the Figure on ITC 10, the first box should have a greater than/equal to sign and the second box should have a less than sign. The arrow to the next step is missing from the blood pressure goal boxes to the following step. The corrected figure appears below.

On page ITC11, amlodipine is a dihydropyridine calcium-channel blocker as opposed to a nonhydropine calcium-channel blocker, as implied by the heading.

Reference 1. Weir M. In the Clinic: hypertension. Ann Intern Med. 2014;161:ITC1-16

Downloaded From: http://annals.org/ by a McGill University User on 08/26/2016