The 2011 Canadian Hypertension Education Program Recommendations for the Management of Hypertension: Blood Pressure Measurement, Diagnosis, Assessment of Risk, and Therapy

Canadian Journal of Cardiology 27 (2011) 415– 433

Guidelines

The 2011 Canadian Hypertension Education Program Recommendations for the Management of Hypertension: Blood Pressure Measurement, Diagnosis, Assessment of Risk, and Therapy Doreen M. Rabi, MD, MSc,a Stella S. Daskalopoulou, MD, PhD,b Raj S. Padwal, MD, MSc,c Nadia A. Khan, MD, MSc,d Steven A. Grover, MD, MPA,e Daniel G. Hackam, MD, PhD,f Martin G. Myers, MD,g Donald W. McKay, PhD,h Robert R. Quinn, MD, PhD,i Brenda R. Hemmelgarn, MD, PhD,i Lyne Cloutier, RN, PhD,j Peter Bolli, MD,k Michael D. Hill, MD, MSc,l Thomas Wilson, MD,m Brian Penner, MD,n Ellen Burgess, MD,i Maxime Lamarre-Cliché, MD,o Donna McLean, RN, MN, NP, PhD(c),p Ernesto L. Schiffrin, MD, PhD,q George Honos, MD,r Karen Mann, MSc, PhD,s Guy Tremblay, MD,t Alain Milot, MD, MSc,u Arun Chockalingam, MS, PhD,v Simon W. Rabkin, MD,w Martin Dawes, MBBS, MD(Lond),x Rhian M. Touyz, MD, PhD,y Kevin D. Burns, MD,z Marcel Ruzicka, MD, PhD,cc Norman R. C. Campbell, MD,aa Michel Vallée, MD, PhD,bb G. V. Ramesh Prasad, MBBS, MSc,cc Marcel Lebel, MD,dd Tavis S. Campbell, PhD,ee M. Patrice Lindsay, BScN, PhD,ff Robert J. Herman, MD,gg Pierre Larochelle, MD,hh Ross D. Feldman, MD,ii J. Malcolm O. Arnold, MD,jj Gordon W. Moe, MD, MSc,kk Jonathan G. Howlett, MD,ll Luc Trudeau, MD,mm Simon L. Bacon, PhD,nn Robert J. Petrella, MD, PhD,oo Richard Lewanczuk, MD,pp James A. Stone, MD, PhD,qq Denis Drouin, MD,rr Jean-Martin Boulanger, MD,ss Mukul Sharma, MD, MSc,tt Pavel Hamet, MD, PhD,uu George Fodor, MD, PhD,vv George K. Dresser, MD, PhD,ww S. George Carruthers, MD,xx George Pylypchuk, MD,yy Richard E. Gilbert, MD, PhD,zz Lawrence A. Leiter, MD,aaa Charlotte Jones, MD, PhD,bbb Richard I. Ogilvie, MD,ccc Vincent Woo, MD,ddd Philip A. McFarlane, MD, PhD,eee Robert A. Hegele, MD,fff Luc Poirier, BPharm, MSc,ggg and Sheldon W. Tobe, MD;hhh for the Canadian Hypertension Education Program

Received for publication March 2, 2011. Accepted March 23, 2011. Corresponding author: Dr Doreen M. Rabi, Teaching, Research and Wellness Building, 3280 Hospital Dr NW, Room 3E33, Calgary, Alberta T2N 4N1, Canada. Tel.: ⫹1-403-220-8867; fax: ⫹1-403-270-0979. E-mail: [email protected]

See page 432 for disclosure information. A version of the hypertension recommendations designed for patient and public education has been developed to assist health care practitioners managing hypertension. The summary is available electronically (go to http:// www.hypertension.ca or http://www.heartandstroke.ca).

0828-282X/$ – see front matter © 2011 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved. doi:10.1016/j.cjca.2011.03.015

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Canadian Journal of Cardiology Volume 27 2011

a Departments of Medicine, Community Health, and Cardiac Sciences, University of Calgary, Calgary, Alberta, Canada; b Division of General Internal Medicine, McGill University, Montreal, Québec, Canada; c Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada; d Division of General Internal Medicine, University of British Columbia, Vancouver, British Columbia, Canada; e Division of Clinical Epidemiology, Montreal General Hospital, Montreal, Québec, Canada; f Department of Medicine and Endocrinology, University of Western Ontario, London, Ontario, Canada; g Division of Cardiology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; h Faculty of Medicine, Memorial University of Newfoundland, St John’s, Newfoundland, Canada; i Division of Nephrology, University of Calgary, Calgary, Alberta, Canada; j Department of Nursing, Université du Québec à Trois-Rivières, Québec, Canadak Ambulatory Internal Medicine Teaching Clinic, St Catharines, Ontario, Canada; l Departments of Clinical Neurosciences, Medicine, and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; m Department of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada; n Department of Pharmacology and Therapeutics, University of Manitoba, Winnipeg, Manitoba, Canada; o Institut de Recherché Clinique de Montréal, Montréal, Québec, Canada; p Faculty of Nursing, University of Alberta, Edmonton, Alberta, Canada; q Department of Medicine, Sir Mortimer B. Davis-Jewish General Hospital, McGill University, Montreal, Québec, Canada; r Division of Cardiology, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Québec, Canada; s Division of Medical Education, Dalhousie University, Halifax, Nova Scotia, Canada; t Service de Cardiologie, Centre Hospitalier Affilié Universitaire de Québec, Hopital St Sacrement, Québec, Québec, Canada; u Department of Medicine, Universite Laval, Québec, Québec, Canada; v Faculty of Health Sciences, Simon Fraser University, Burnaby, British Columbia, Canada; w Division of Cardiology, University of British Columbia, Vancouver, British Columbia, Canada; x Department of Family Medicine, University of British Columbia, Vancouver, British Columbia, Canada; y Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; z Division of Nephrology, University of Ottawa, Ottawa, Ontario, Canada; aa Departments of Medicine, Community Health Sciences, and Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada; bb Division of Nephrology, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montreal, Québec, Canada; cc Division of Nephrology, University of Toronto, Toronto, Ontario, Canada; dd Centre Hospitalier Affilié Universitaire de Québec,L’Hôtel-Dieu de Québec, Department of Medicine, l’Université Laval, Québec, Québec, Canada; ee Department of Psychology, University of Calgary, Calgary, Alberta; ff Canadian Stroke Network, Toronto, Ontario; gg Department of Medicine, University of Calgary, Calgary, Alberta; hh Institut de Recherché Clinique de Montréal, Montréal, Québec, Canada; ii Department of Medicine, University of Western Ontario, London, Ontario, Canada; jj London Health Sciences Centre, University of Western Ontario, London, Ontario, Canada; kk University Health Network, University of Toronto, Toronto, Ontario, Canada; ll Queen Elizabeth II Health Sciences Centre, Halifax, Nova Scotia, Canada; mm Department of Medicine, McGill University, Montréal, Québec, Canada; nn Department of Exercise Science, Concordia University, Montréal, Québec, Canada; oo Lawson Health Research Institute, University of Western Ontario, London, Ontario, Canada; pp University of Alberta, Edmonton, Alberta, Canada; qq Division of Cardiology, Department of Medicine, University of Calgary, Calgary, Alberta, Canada; rr Department of Family Medicine, Université Laval, Québec, Québec, Canada; ss Charles LeMoyne Hospital Research Centre, University of Sherbrooke, Sherbrooke, Québec, Canada; tt The Canadian Stroke Network, The Ottawa Hospital, Ottawa, Ontario, Canada; uu Faculté de Médicine, Université de Montréal, Montréal, Québec, Canada; vv Prevention and Rehabilitation Centre, University of Ottawa Heart Institute, Ottawa, Ontario, Canada; ww Department of Medicine, University of Western Ontario, London, Ontario, Canada; xx Five Hills Health Region, Moose Jaw, Saskatchewan, Canada; yy Division of Nephrology, St Paul’s Hospital, University of Saskatoon, Saskatoon, Saskatchewan, Canada; zz St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada; aaa Division of Endocrinology and Metabolism and Keenan Research Centre at the Li Ka Shing Knowledge Institute, St Michael’s Hospital, Toronto, Ontario, Canada; bbb Division of Endocrinology, Department of Medicine, University of Calgary, Calgary, Alberta; ccc University Health Network, University of Toronto, Toronto, Ontario, Canada; ddd Division of Endocrinology and Metabolism, University of Manitoba, Winnipeg, Manitoba, Canada; eee Division of Nephrology, St Michael’s Hospital, University of Toronto, Toronto, Ontario, Canada; fff Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada; ggg Hypertension Unit and Pharmacy Department, CHUQ, Québec, Québec, Canada; hhh Division of Nephrology, University of Toronto, Toronto, Ontario, Canada

ABSTRACT

RÉSUMÉ

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2011. The major guideline changes this year are: (1) a recommendation was made for using comparative risk analogies when communicating a patient’s cardiovascular risk; (2) diagnostic testing issues for renal artery stenosis were discussed; (3) recommendations were added for the management of hypertension during the acute phase of stroke; (4) people with hypertension and diabetes are now considered high risk for cardiovascular events if they have elevated urinary albumin excretion, overt kidney disease, cardiovascular disease, or the presence of other cardiovascular risk factors; (5) the combination of an angiotensin-converting enzyme (ACE) inhibitor and a dihydropyridine calcium channel blocker (CCB) is preferred over the combination of an ACE inhibitor and a thiazide diuretic in persons with diabetes and hypertension; and (6) a recommendation was made to coordinate with pharmacists to improve antihypertensive medication adherence. We also discussed the recent analyses that examined the association between angiotensin II receptor blockers (ARBs) and cancer.

Nous avons mis à jour les recommandations factuelles pour le diagnostic, l’évaluation, la prévention et le traitement de l’hypertension chez les adultes en 2011. Cette année, les changements majeurs aux lignes directrices sont les suivants : (1) une recommandation a été faite pour l’utilisation d’analogies comparatives de risque lors de la communication d’un risque cardiovasculaire au patient; (2) les enjeux reliés aux tests diagnostiques de la sténose de l’artère rénale ont été discutés; (3) des recommandations ont été ajoutées pour la gestion de l’hypertension durant la phase aiguë de l’accident vasculaire cérébral; (4) les personnes souffrant d’hypertension et de diabète sont maintenant considérées à haut risque d’événements cardiovasculaires s’ils ont des excrétions urinaires d’albumine élevées, une maladie rénale manifeste, une maladie cardiovasculaire ou la présence d’autres facteurs de risque cardiovasculaire; (5) la combinaison d’un inhibiteur de l’enzyme de conversion de l’angiotensine (ECA) et d’un bloqueur des canaux calciques (BCC) de la classe des dihydropyridines est préférable à la combinaison d’un inhibiteur de l’ECA et d’un diurétique thiazidique chez les personnes souffrant de diabète et d’hypertension; et (6) une recommandation a été faite pour convenir avec les pharmaciens d’améliorer l’adhésion à la médication antihypertensive. Nous avons aussi discuté de récentes analyses qui examinaient le lien entre les antagonistes des récepteurs de l’angiotensine II (ARA II) et le cancer.

Rabi et al. 2011 Canadian Recommendations for High BP

Executive Summary Objective: To update the evidence-based recommendations for the prevention, diagnosis, assessment, and treatment of hypertension in adults for 2011. Options and Outcomes: For lifestyle and pharmacologic interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. Evidence: A Cochrane Collaboration librarian conducted an independent MEDLINE search to August 2010 to update the 2010 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodologic experts using prespecified levels of evidence.

Recommendations Diagnosis and assessment Recommendations are outlined for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals. Automated office blood pressure measurements can be used in the assessment of office blood pressure. When used under proper conditions, automated office systolic blood pressure (SBP) of ⱖ 135 mm Hg or diastolic blood pressure (DBP) values of ⱖ 85 mm Hg should be considered analogous to mean awake ambulatory SBP of ⱖ 135 mm Hg and DBP of ⱖ 85 mm Hg, respectively. Changes to the recommendations for 2011 relate to using comparative risk analogies when communicating a patient’s cardiovascular risk and we discuss diagnostic testing for renal artery stenosis. Prevention and treatment For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults aged 50 years or less, to 1300 mg (57 mmol) per day in adults aged 51 to 70 years, and to 1200 mg (52 mmol) per day in adults older than 70 years; perform 30 to 60 minutes of moderate aerobic exercise 4 to 7 days per week; maintain a healthy body weight (body mass index 18.5 to 24.9 kg/m2) and waist circumference (⬍ 102 cm for men and ⬍ 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week in men or 9 standard drinks per week in women; follow a diet that emphasizes fruits, vegetables, low-fat dairy products, dietary and soluble fibre, whole grains, and protein from plant sources and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension.

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For the pharmacologic management of hypertension, treatment thresholds and targets should be predicated on the patient’s global atherosclerotic risk, target organ damage, and comorbid conditions. Blood pressure should be decreased to ⬍ 140/90 mm Hg in all patients and to ⬍130/80 mm Hg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin-converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin II receptor blockers (ARBs), or ␤-blockers (in those younger than 60 years). A combination of 2 first-line agents may also be considered as initial treatment of hypertension if SBP is 20 mm Hg above target or if DBP is 10 mm Hg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest the consideration of dual therapy. Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs, or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or ␤-blockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets, and agents outlined in the Canadian lipid treatment guidelines.1 Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered. Validation All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually.

Introduction Hypertension affects 27% of the Canadian adult population aged 35-64 years2 and remains one of the most common modifiable risk factors for cardiovascular disease in Canada and

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globally.3,4 This document summarizes the 2011 CHEP recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults, focusing on those recommendations that are new or updated. This year, the recommendations underwent significant revision with respect to the management of hypertension in those with diabetes mellitus and stroke. Two landmark trials—the Action to Control Cardiovascular Risk in Diabetes Blood Pressure Intervention Trial (ACCORD-BP)5 and the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial diabetes subgroup analyses6—were published and prompted a significant evaluation of the 2010 guidelines with respect to treatment targets and therapeutic decision making. Recognizing the significant role hypertension plays in stroke, CHEP worked in partnership with the Canadian Stroke Network to develop recommendations for the management in elevated blood pressure (BP) in the setting of acute stroke. Also new this year are recommendations for using comparative risk analogies when communicating a patient’s cardiovascular risk, incorporating pharmacists to aid antihypertensive therapy adherence, and we discuss diagnostic testing for renal artery stenosis. We also discuss the recent analyses that examined the association between ARBs and cancer. For issues related to the diagnosis and evaluation of high BP in children and adolescents, the reader is referred to separate guidelines.7 More detailed discussion of previous changes to the Canadian recommendations is available in prior publications.8-15 Summary documents of all recommendations, including downloadable slide kits, are available free of charge on the Canadian Hypertension Society Web site (www.hypertension.ca). Although we mention individual antihypertensive agents when discussing hypertension trials, the reader may assume that all drug-specific recommendations are applicable to the entire drug class in question, unless otherwise stated. Finally, while these recommendations are based on best evidence, health care providers must also use their own clinical judgement and consider patient preferences when applying these recommendations for their patients. Methods A Cochrane Collaboration librarian conducted a MEDLINE search using a highly sensitive search strategy for randomized trials and systematic reviews published through August 2010. To ensure that all relevant studies were included, bibliographies of identified articles were manually searched (Details of search strategies and retrieved articles are available on request.) Each subgroup, consisting of national and international hypertension experts, reviewed all identified articles relevant to their topic area. Members of the Canadian Stroke Network, Canadian Diabetes Association Guidelines Committee, and Canadian Society of Nephrology collaborated with CHEP subgroup members for the 2011 recommendations process. The subgroups appraised the quality of relevant studies using a standardized algorithm developed by CHEP. In brief, Grade A recommendations are based on studies with high levels of internal validity, statistical precision, generalizability, and clinical relevance. Grade B and C recommendations are derived from studies characterized by

Canadian Journal of Cardiology Volume 27 2011 Table 1. Grading scheme for recommendations Grade A

Grade B

Grade C

Grade D

Recommendations are based on randomized trials (or systematic reviews of trials) with high levels of internal validity and statistical precision, and for which the study results can be directly applied to patients because of similar clinical characteristics and the clinical relevance of the study outcomes Recommendations are based on randomized trials, systematic reviews or prespecified subgroup analyses of randomized trials that have lower precision, or if there is a need to extrapolate from studies because of differing populations or reporting of validated intermediate/surrogate outcomes rather than clinically important outcomes Recommendations from trials that have lower levels of internal validity and/or precision, or report unvalidated surrogate outcomes, or results from nonrandomized observational studies Recommendations are based on expert opinion alone

lower internal validity, precision, or generalizability or from studies reporting intermediate/surrogate outcomes instead of more clinically relevant ones. Grade D recommendations are based on expert opinion or studies with lower levels of internal validity or precision than Grade C recommendations. (See Table 1.) Subsequently, the central review committee, composed of clinical epidemiologists, reviewed draft recommendations from each subgroup and, in an iterative process, helped to refine and standardize all recommendations and their grading across subgroups (Table 1). The draft recommendations from each subgroup were then formally vetted by task force committee members at the 2011 consensus conference held in Vancouver, British Columbia. Based on the deliberations at the consensus conference, the 2011 recommendations were finalized and then submitted to all 63 voting members of the CHEP Evidence-Based Recommendations Task Force for approval. Members with conflicts of interest for certain recommendations were recused from voting. As in previous years, only those recommendations approved by ⬎ 70% of the Task Force were included in the final recommendations; in the actual vote, all recommendations received at least 80% approval. The 2011 CHEP Diagnosis and Assessment Recommendations I. Accurate measurement of blood pressure Recommendations 1. Health care professionals who have been specifically trained to measure BP accurately should assess BP in all adult patients at all appropriate visits to determine cardiovascular risk and monitor antihypertensive treatment (Grade D). 2. Use of standardized measurement techniques (see Table 2) is recommended when assessing BP (Grade D). 3. Automated office BP (AOBP) measurements can be used in the assessment of office BP (Grade D). 4. When used under proper conditions, automated office SBP of ⱖ 135 mm Hg or DBP of ⱖ 85 mm Hg should be considered analogous to mean awake ambulatory SBP of ⱖ 135 mm Hg and DBP of ⱖ 85 mm Hg, respectively (Grade D).

Rabi et al. 2011 Canadian Recommendations for High BP Table 2. Recommended technique for measuring blood pressure in the office* 1. Measurements should be taken with a sphygmomanometer known to be accurate. A recently calibrated aneroid or a validated electronic device can be used. Aneroid devices or mercury columns need to be clearly visible at eye level. 2. Choose a cuff with an appropriate bladder size matched to the size of the arm. For measurements taken by auscultation, bladder width should be close to 40% of arm circumference and bladder length should cover 80%-100% of arm circumference. When using an automated device, select the cuff size as recommended by its manufacturer. 3. Place the cuff so that the lower edge is 3 cm above the elbow crease and the bladder is centred over the brachial artery. The patient should be resting comfortably for 5 minutes in the seated position with back support. The arm should be bare and supported with the BP cuff at heart level, as a lower position will result in an erroneously higher SBP and DBP. There should be no talking, and patients’ legs should not be crossed. At least 3 measurements should be taken in the same arm with the patient in the same position. The first reading should be discarded and the latter 2 averaged. Blood pressure also should be assessed after 2 minutes standing (with arm supported) and at times when patients report symptoms suggestive of postural hypotension. Supine BP measurements may also be helpful in the assessment of elderly and diabetic patients. For auscultation, at least 3 measurements should be taken in the same arm with the patient in the same position. The first reading should be discarded and the latter 2 averaged. When using automated office oscillometric devices such as the BpTRU (BpTRU Medical Devices, Coquitlam, BC, Canada), the patient should be seated in a quiet room (no specified period of rest). With the device set to take measures at 1- or 2-minute intervals, the first measurement is taken by a health professional to verify cuff position and validity of the measurement. The patient is left alone after the first measurement while the device automatically takes subsequent readings. The BpTRU automatically discards the first measure and averages the next 5 measures. Steps 4-7 are specific to auscultation. 4. Increase the pressure rapidly to 30 mm Hg above the level at which the radial pulse is extinguished (to exclude the possibility of a systolic auscultatory gap). 5. Place the bell or diaphragm of the stethoscope gently and steadily over the brachial artery. 6. Open the control valve so that the rate of deflation of the cuff is approximately 2 mm Hg per heartbeat. A cuff deflation rate of 2 mm Hg per beat is necessary for accurate systolic and diastolic estimation. 7. Read the systolic level—the first appearance of a clear tapping sound (phase I Korotkoff)—and the diastolic level (the point at which the sounds disappear: phase V Korotkoff). If Korotkoff sounds persist as the level approaches 0 mm Hg, then the point of muffling of the sound is used (phase IV) to indicate the diastolic pressure. Leaving the cuff partially inflated for too long will fill the venous system and make the sounds difficult to hear. To avoid venous congestion, it is recommended that at least 1 minute should elapse between readings. 8. Record the blood pressure to the closest 2 mm Hg on the manometer (or 1 mm Hg on electronic devices) as well as the arm used and whether the patient was supine, sitting or standing. Avoid digit preference by not rounding up or down. Record the heart rate. The seated blood pressure is used to determine and monitor treatment decisions. The standing blood pressure is used to examine for postural hypotension, if present, which may modify the treatment. 9. In the case of arrhythmia, additional readings with auscultation may be required to estimate the average systolic and diastolic pressure. Isolated extra beats should be ignored. Note the rhythm and pulse rate. 10. Leaving the cuff partially inflated for too long will fill the venous system and make the sounds difficult to hear. To avoid venous congestion, it is recommended that at least 1 minute should elapse between readings. 11. Blood pressure should be taken in both arms on at least one visit, and if one arm has a consistently higher pressure, that arm should be subsequently used for blood pressure measurement and interpretation. BP, blood pressure; DBP, diastolic BP; SBP, systolic BP. * Unless specifically mentioned, steps apply to measurement by auscultation and oscillometry using an upper arm cuff. Reprinted with permission of the Canadian Hypertension Education Program.

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Background. Some fully automated BP measuring devices available for use in the clinic are capable of taking repeated BP measurements when a patient is alone in the examining room. Using repeat-measure devices in this manner has been referred to as AOBP measurement. The 2011 CHEP recommendations include the use of AOBP as a device for assessment of office BP. The therapeutic thresholds for interpreting automated readings remain undetermined and at present, there are no studies that directly relate automated office readings to the occurrence of cardiovascular events. Some studies have shown that an automated office reading of 135/85 mm Hg is approximately equivalent to an ambulatory BP reading of 135/85 mm Hg.16,17 One small study in a selected population has related repeated automated office readings to repeated manual office readings (on which the current therapeutic thresholds are based).18 In a representative group of Ontario adults, the automated readings were 3/3 mm Hg lower than manual readings at a single visit.19 In a small selected group of firefighters, the difference between automated and manual office readings disappeared over 3-5 visits.18 Other studies have reported higher differences between automated office readings and manual office readings.20 Research studies to date have often used populations that are likely to have had a high prevalence of white coat hypertension (ie, patients referred for ambulatory BP monitoring), used readings taken in a specialist office, used office readings that were taken on a single occasion, or used manual office readings that were not performed by a trained technician using standardized technique.20,21 These limitations could increase the difference between automated and manual BP readings, limiting the ability to define the exact threshold for treating hypertension based on automated office readings in an unselected population of patients in a primary health care setting. Further, it may be more appropriate to compare bands, or ranges, of BP values when comparing the different techniques rather than considering an automated office reading of 135/85 equivalent to a manual office reading of 140/90. Further research is required to determine whether automated office measures can predict target organ damage and cardiovascular events better than manual office readings. Several AOBP devices have been independently validated for clinical accuracy, including the BpTRU automatic BP monitor (the most commonly used device in Canada), the BPM-100 electronic oscillometric office BP monitor (Omron Canada Inc, Canada), and the Omron office digital BP HEM907 monitor (Omron Canada Inc).16,23 However, most of the available research in this area has been based on results from use of the BpTRU device. When used under proper conditions (see Table 2), the available evidence suggests that repeat automated office SBP values of ⱖ 135 mm Hg, or DBP values of ⱖ 85 mm Hg, should be considered analogous to mean awake ambulatory SBP reading of ⱖ 135 mm Hg and DBP of ⱖ 85 mm Hg, respectively.16,17 Furthermore, it appears that the white coat effect may be reduced or even eliminated when the BpTRU is used properly.24 It is important to note that to date, only one paper has reported an association between AOBP readings and target organ damage;25 no data are available that relate AOBP readings to prognosis.

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Elevated Out of the Office BP measurement

Elevated Random Office BP measurement

Hypertension Visit 1

Hypertensive Urgency / Emergency

BP Measurement, History, and Physical Diagnostic tests ordered at visit 1 or 2

Hypertension Visit 2 within 1 month BP ≥ 180/110 OR BP 140-179/90-109 with Target Organ Damage, Diabetes, or Chronic Kidney Disease

Yes

Diagnosis of HTN

No

BP: 140-179 / 90-109

Office BPM

ABPM (If available)

Home BPM (If available)

Hypertension Visit 3* Diagnosis of HTN

>160 SBP or >100 DBP

≥ <160/100

or

ABPM or Home BPM if available

Awake BP < 135/85 or 24-hour < 130/80

Awake BP ≥ 135 SBP or ≥85 DBP or 24-hour ≥ 130 SBP or ≥ 80 DBP

< 135/85

or

≥ 135 SBP or > 85 DBP

≥

Hypertension Visit 4-5* >140 SBP or >90 DBP

<140/90

Diagnosis of HTN

Continue to follow-up

Diagnosis of HTN

Continue to follow-up

Diagnosis of HTN

Continue to follow-up

Figure 1. The expedited assessment and diagnosis of patients with hypertension (HTN): Focus on validated technologies for blood pressure (BP) assessment. ABPM, ambulatory BP monitoring; BPM, BP monitoring; DBP, diastolic BP; SBP, systolic BP. *Thresholds refer to BP values averaged across the corresponding number of visits and not just the most recent office visit. Reprinted with permission from the Canadian Hypertension Education Program.

II. Criteria for diagnosis of hypertension and recommendations for follow-up (Fig. 1) Recommendations 1. At initial presentation, patients demonstrating features of a hypertensive urgency or emergency (Table 3) should be diagnosed as hypertensive and require immediate management (Grade D). 2. If SBP is ⱖ 140 mm Hg and/or DBP is ⱖ 90 mm Hg, a specific visit should be scheduled for the assessment of hy-

pertension (Grade D). If BP is high-normal (SBP 130-139 mm Hg and/or DBP 85-89 mm Hg), annual follow-up is recommended (Grade C). 3. At the initial visit for the assessment of hypertension, if SBP is ⱖ 140 and/or DBP is ⱖ 90 mm Hg, ⬎ 2 additional readings should be taken during the same visit using a validated device and according to the recommended procedure for accurate BP determination (see Table 2). The first reading should be discarded and the latter 2 readings averaged. A history and physical exam-

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Table 3. Examples of hypertensive urgencies and emergencies

Table 5. Examples of key cardiovascular risk factors for atherosclerosis

Asymptomatic diastolic BP ⱖ 130 mm Hg Hypertensive encephalopathy Acute aortic dissection Acute left ventricular failure Acute myocardial ischemia

Nonmodifiable Age ⱖ 55 years Male Family history of premature cardiovascular disease (age ⬍ 55 in menand ⬍ 65 in women) Modifiable Sedentary lifestyle Poor dietary habits Abdominal obesity Dysglycemia Smoking Dyslipidemia Stress Nonadherence

BP, blood pressure. Reprinted with permission of the Canadian Hypertension Education Program.

ination should be performed and, if clinically indicated, diagnostic tests to search for target organ damage (Table 4) and associated cardiovascular risk factors (Table 5) should be arranged within 2 visits. Exogenous factors that can induce or aggravate hypertension should be assessed and removed if possible (Table 6). Schedule visit 2 within 1 month (Grade D). 4. At visit 2 for the assessment of hypertension, patients with macrovascular target organ damage, diabetes mellitus, or chronic kidney disease (CKD) (glomerular filtration rate [GFR] ⬍ 60 mL/min/1.73 m2) can be diagnosed as hypertensive if SBP is ⱖ 140 mm Hg and/or DBP is ⱖ 90 mm Hg (Grade D). 5. At visit 2 for the assessment of hypertension, patients without macrovascular target organ damage, diabetes mellitus, or CKD can be diagnosed as hypertensive if the SBP is ⱖ 180 mm Hg and/or the DBP is ⱖ 110 mm Hg (Grade D). Patients without macrovascular target organ damage, diabetes mellitus, or CKD but with lower BP levels should undergo further evaluation using any of the 3 approaches outlined next: i. Office manual BP measurements: Using office manual BP measurements, patients can be diagnosed as hypertensive if the SBP is ⱖ 160 mm Hg or the DBP is ⱖ 100 mm Hg averaged across the first 3 visits, or if the SBP averages ⱖ 140 mm Hg or the DBP averages ⱖ 90 mm Hg averaged across 5 visits (Grade D). ii. Ambulatory BP monitoring (ABPM): Using ABPM (see recommendation Ambulatory BP Measurement),

Table 4. Examples of target organ damage Cerebrovascular disease Stroke Ischemic stroke and transient ischemic attack Intracerebral hemorrhage Aneurysmal subarachnoid hemorrhage Dementia Vascular dementia Mixed vascular dementia and dementia of the Alzheimer’s type Hypertensive retinopathy Left ventricular dysfunction Left ventricular hypertrophy Coronary artery disease Myocardial infarction Angina pectoris Congestive heart failure Renal disease Chronic kidney disease (GFR ⬍ 60 mL/min/1.73 m2) Albuminuria Peripheral artery disease Intermittent claudication GFR, glomerular filtration rate. Reprinted with permission of the Canadian Hypertension Education Program.

Prior history of clinically overt atherosclerotic disease indicates a very high risk for a recurrent atherosclerotic event (eg, peripheral arterial disease, previous stroke, or transient ischemic attack). Reprinted with permission of the Canadian Hypertension Education Program.

patients can be diagnosed as hypertensive if the mean awake SBP is ⱖ 135 mm Hg or the DBP is ⱖ 85 mm Hg or if the mean 24-hour SBP is ⱖ 130 mm Hg or the DBP is ⱖ 80 mm Hg (Grade C). iii. Home BP measurement: Using home BP measurements (see recommendation Home Measurement of BP), patients can be diagnosed as hypertensive if the average SBP is ⱖ 135 mm Hg or the DBP is ⱖ 85 mm Hg (Grade C). If the average home BP is ⬍ 135/85 mm Hg, it is advisable to perform 24-hour ABPM to confirm that the mean 24-hour ABPM is ⬍ 130/80 mm Hg and the mean awake ABPM is ⬍ 135/85 mm Hg before diagnosing white coat hypertension (Grade D). 6. Investigations for secondary causes of hypertension should be initiated in patients with suggestive clinical and/or laboratory features (outlined later) (Grade D). 7. If at the last diagnostic visit the patient is not diagnosed as hypertensive and has no evidence of macrovascular target organ damage, the patient’s BP should be assessed at yearly intervals (Grade D). 8. Hypertensive patients receiving lifestyle modification advice alone (nonpharmacologic treatment) should be fol-

Table 6. Examples of exogenous factors that can induce/aggravate hypertension Prescription Drugs NSAIDs, including coxibs Corticosteroids and anabolic steroids Oral contraceptive and sex hormones Vasoconstricting/sympathomimetic decongestants Calcineurin inhibitors (cyclosporin, tacrolimus) Erythropoietin and analogues Antidepressants: Monoamine oxidase inhibitors (MAOIs), serotoninnorepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs) Midodrine Other Substances Licorice root Stimulants including cocaine Salt Excessive alcohol use Reprinted with permission of the Canadian Hypertension Education Program.

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Table 7. Dietary Approaches to Stop Hypertension (DASH) diet Food group

Daily serving

Examples and notes

Grains

7-8

Vegetables

4-5

Fruits

4-5

Low-fat or fat-free dairy foods

2-3

Meats, poultry, fish

ⱕ2

Nuts, seeds, dry beans

4-5/week

Whole wheat bread, oatmeal, popcorn Tomatoes, potatoes, carrots, beans, peas, squash, spinach Apricots, bananas, grapes, oranges, grapefruit, melons Fat-free (skim)/low-fat (1%) milk, fat-free/low-fat yogurt, fat-free/low-fat cheese Select only lean meats. Trim away fats. Broil, roast, or boil. No frying. Remove skin from poultry. Almonds, peanuts, walnuts, sunflower seeds, soybeans, lentils Soft margarines, low-fat mayonnaise, vegetable oil (olive, corn, canola, or safflower) Maple syrup, sugar, jelly, jam, hard candy, sorbet

Fats and oils

Sweets

2-3

5/week

Background. Cardiovascular risk, when explained as a percentage over a 10-year risk timeframe, is a difficult concept for many patients. To help patients reduce risk by lifestyle change or active treatment, a more effective presentation of risk is needed.27 Randomized clinical trials among individuals with dyslipidemia and/or hypertension demonstrated that explicitly calculating a patient’s cardiovascular risk compared to age- and sexmatched individuals and then communicating the risk as comparative risk analogy can significantly increase the likelihood of achieving treatment targets.28-31 Programs that compare risk use terms such as “cardiovascular age,” “vascular age,” or “heart age” were shown to improve risk perception by patients and risk factor management by physicians and can be accessed at the Web sites www.myhealthcheckup.com and www.monbilansante.com. The SCORE risk calculation was updated using Canadian data and is now available at the Web site http://www.scorecanada.ca. IV. Routine and optional laboratory tests for the investigation of patients with hypertension Recommendations

Background. The criteria for the diagnosis of hypertension have been previously discussed in detail.26 It should be emphasized that, when using manual office BPs to diagnose hypertension, the thresholds given earlier refer to readings averaged over the specified number of visits and not just on the last visit.

1. Routine laboratory tests that should be performed for the investigation of all patients with hypertension include the following: i. Urinalysis (Grade D) ii. Blood chemistry (potassium, sodium, and creatinine) (Grade D) iii. Fasting blood glucose (Grade D) iv. Fasting serum total cholesterol and high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and triglycerides (Grade D) v. Standard 12-lead electrocardiography (Grade C) 2. Assess urinary albumin excretion in patients with diabetes (Grade D). 3. All treated hypertensive patients should be monitored according to the current Canadian Diabetes Association (CDA) guidelines for the new appearance of diabetes (Grade B). 4. During the maintenance phase of hypertension management, tests (including those for electrolytes, creatinine, and fasting lipids) should be repeated with a frequency reflecting the clinical situation (Grade D).

III. Assessment of overall cardiovascular risk in hypertensive patients

Background. There are no changes to these recommendations for 2011.

Recommendations

V. Assessment for renovascular hypertension

1. Global cardiovascular risk should be assessed. Multifactorial risk assessment models can be used to predict more accurately an individual’s global cardiovascular risk (Grade A) and to use antihypertensive therapy more efficiently (Grade D). In the absence of Canadian data to determine the accuracy of risk calculations, avoid using absolute levels of risk to support treatment decisions (Grade C). 2. Consider informing patients of their global risk to improve the effectiveness of risk factor modification (Grade B). Consider also using analogies that describe comparative risk such as “cardiovascular age,” “vascular age,” or “heart age” to inform patients of their risk status (Grade B).

Recommendations

DASH eating plan available at Web site http://www.nhlbi.nih.gov/health/ public/heart/hbp/dash/new_dash.pdf.

lowed up at 3- to 6-month intervals. Shorter intervals (every 1 or 2 months) are needed for patients with higher BPs (Grade D). 9. Patients on antihypertensive drug treatment should be seen monthly or every 2 months, depending on the level of BP, until readings on 2 consecutive visits are below their target (Grade D). Shorter intervals between visits will be needed for symptomatic patients and those with severe hypertension, intolerance to antihypertensive drugs, or target organ damage (Grade D). Once the target BP has been reached, patients should be seen at 3- to 6-month intervals (Grade D).

1. Patients presenting with ⱖ 2 of the clinical clues listed next, suggesting renovascular hypertension, should be investigated (Grade D): i. Sudden onset or worsening of hypertension and age ⬎ 55 or ⬍ 30 years ii. Presence of an abdominal bruit iii. Hypertension resistant to ⱖ 3 drugs iv. Rise in serum creatinine level ⱖ30% associated with use of an ACE inhibitor or angiotensin II receptor antagonist

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v. Other atherosclerotic vascular disease, particularly in patients who smoke or have dyslipidemia vi. Recurrent pulmonary edema associated with hypertensive surges When available, the following tests are recommended to aid in the usual screening for renal vascular disease: captopril-enhanced radioisotope renal scan, Doppler sonography, magnetic resonance angiography, and computed tomography (CT) angiography (for those with normal renal function) (Grade B). Captopril-enhanced radioisotope renal scan is not recommended for those with CKD (GFR ⬍ 60 mL/min/1.73 m2) (Grade D). Background. When evaluating individuals for the presence of renal artery stenosis due to fibromuscular dysplasia, magnetic resonance angiography and CT angiography appear to be less sensitive for detection of mid and distal renal artery lesions. Hence, selective angiography may be considered.31-33 In patients with advanced CKD (GFR ⬍ 30 mL/min/1.73 m2) and in patients with acute kidney injury, imaging tests other than magnetic resonance angiography should be considered because of the increased risk of nephrogenic systemic fibrosis associated with gadolinium.31-36 Finally, in individuals with documented renal artery stenosis, a hyperemic systolic pressure gradient over the stenosis of ⱖ 21 mm Hg prior to angioplasty appears to predict significant BP-lowering response and hence represents an indirect assessment of the functional significance of the stenosis.37 VI. Endocrine hypertension Recommendations A. Hyperaldosteronism: Screening and diagnosis 1. Screening for hyperaldosteronism should be considered for the following patients (Grade D): i. Hypertensive patients with spontaneous hypokalemia (K⫹ ⬍ 3.5 mmol/L) ii. Hypertensive patients with marked diuretic-induced hypokalemia (K⫹ ⬍ 3.0 mmol/L) iii. Patients with hypertension refractory to treatment with ⱖ 3 drugs iv. Hypertensive patients found to have an incidental adrenal adenoma 2. Screening for hyperaldosteronism should include assessment of plasma aldosterone and plasma renin activity (see Online Table S1). 3. For patients with suspected hyperaldosteronism [on the basis of the screening test, Online Table S1, Item 3], a diagnosis of primary aldosteronism should be established by demonstrating inappropriate autonomous hypersecretion of aldosterone using at least one of the manoeuvres listed in Online Table S1, Item 4). When the diagnosis is established, the abnormality should be localized using any of the tests described in Online Table S1, Item 5. B. Pheochromocytoma: Screening and diagnosis 1. If pheochromocytoma is strongly suspected, the patient should be referred to a specialized hypertension centre, particularly if

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biochemical screening tests (see Online Table S2) have already been found to be positive (Grade D). 2. The following patients should be considered for screening for pheochromocytoma (Grade D): i. Patients with paroxysmal and/or severe (BP ⱖ 180/110 mm Hg) sustained hypertension refractory to usual antihypertensive therapy ii. Patients with hypertension and multiple symptoms suggestive of catecholamine excess (eg, headaches, palpitations, sweating, panic attacks, and pallor) iii. Patients with hypertension triggered by ␤-blockers, monoamine oxidase inhibitors, micturition, or changes in abdominal pressure iv. Patients with incidentally discovered adrenal mass and patients with hypertension and multiple endocrine neoplasia (MEN) 2A or 2B, von Recklinghausen’s neurofibromatosis, or von Hippel-Lindau disease v. For patients with positive biochemical screening tests, localization of pheochromocytomas should involve the use of magnetic resonance imaging (MRI) (preferable), CT (if MRI is unavailable), and/or iodine I-131 metaiodobenzylguanidine (MIBG) scintigraphy (Grade C for each modality). Background. There are no changes to these recommendations for 2011. VII. Home measurement of BP Recommendations 1. Home BP readings can be used in the diagnosis of hypertension (Grade C). 2. The use of home BP monitoring on a regular basis should be considered for patients with hypertension, particularly those with: i. Diabetes mellitus (Grade D) ii. CKD (Grade C) iii. Suspected nonadherence (Grade D) iv. Demonstrated white coat effect (Grade C) v. BP controlled in the office but not at home (masked hypertension) (Grade C) 3. When white coat hypertension is suggested by home monitoring, its presence should be confirmed with ABPM before making treatment decisions are made (Grade D). 4. Patients should be advised to purchase and use only home BP monitoring devices that are appropriate for the individual and have met standards of the Association for the Advancement of Medical Instrumentation, the most recent requirements of the British Hypertension Society protocol, or the international protocol for validation of automated BP measuring devices. Patients should be encouraged to use devices with data recording capabilities or automatic data transmission to increase the reliability of reported home BP values (Grade D). 5. Home SBP values ⱖ 135 mm Hg or DBP values ⱖ 85 mm Hg should be considered elevated and associated with an increased overall mortality risk analogous to office SBP readings of ⱖ 140 mm Hg or DBP readings ⱖ 90 mm Hg (Grade C). 6. Health care professionals should ensure that patients who measure their BP at home have adequate training

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and, if necessary, repeat training in measuring their BP. Patients should be observed to determine that they measure BP correctly and should be given adequate information about interpreting these readings (Grade D). 7. The accuracy of all individual patients’ validated devices (including electronic devices) must be regularly checked against a device of known calibration (Grade D). 8. Home BP values for assessing white coat hypertension or sustained hypertension should be based on duplicate measures, morning and evening, for an initial 7-day period. First-day home BP values should not be considered (Grade D).

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Background. There are no changes to these recommendations for 2011. The CHEP 2011 Prevention and Treatment Recommendations I. Lifestyle management Recommendations A. Physical exercise

VIII. Ambulatory BP measurement

1. For nonhypertensive individuals (to reduce the possibility of becoming hypertensive) or for hypertensive patients (to reduce their BP), prescribe the accumulation of 30-60 minutes of moderate intensity dynamic exercise (eg, walking, jogging, cycling, or swimming) 4-7 days per week in addition to the routine activities of daily living (Grade D). Higher intensities of exercise are not more effective (Grade D).

Recommendations

B. Weight reduction

1. Ambulatory BP readings can be used in the diagnosis of hypertension (Grade C). ABPM should be considered when an office-induced increase in BP is suspected in treated patients with: i. BP that is not below target despite receiving appropriate chronic antihypertensive therapy (Grade C) ii. Symptoms suggestive of hypotension (Grade C) iii. Fluctuating office BP readings (Grade D) 2. Physicians should use only ABPM devices that have been validated independently using established protocols (Grade D). 3. Therapy adjustment should be considered in patients with a mean 24-hour ambulatory SBP of ⱖ 130 mm Hg or DBP of ⱖ 80 mm Hg or a mean awake SBP of ⱖ 135 mm Hg or DBP of ⱖ 85 mm Hg (Grade D). 4. The magnitude of changes in nocturnal BP should be taken into account in any decision to prescribe or withhold drug therapy based on ambulatory BP (Grade C) because a decrease in nocturnal BP of ⬍ 10% is associated with increased risk of cardiovascular events.

1. Height, weight, and waist circumference should be measured and body mass index calculated for all adults (Grade D). 2. Maintenance of a healthy body weight (body mass index 18.5 to 24.9 kg/m2, and waist circumference ⬍ 102 cm for men and ⬍ 88 cm for women) is recommended for nonhypertensive individuals to prevent hypertension (Grade C) and for hypertensive patients to reduce BP (Grade B). All overweight hypertensive individuals should be advised to lose weight (Grade B). 3. Weight loss strategies should employ a multidisciplinary approach that includes dietary education, increased physical activity, and behavioural intervention (Grade B).

Background. Information on validated BP monitors can be found at Web site http://hypertension.ca/chep/approvedhome-bp-devices. There are no changes to these recommendations for 2011.

Background. There are no changes to these recommendations for 2011. IX. Role of echocardiography Recommendations 1. Routine echocardiographic evaluation of all hypertensive patients is not recommended (Grade D). 2. An echocardiogram for assessment of left ventricular hypertrophy is useful in selected cases to help define the future risk of cardiovascular events (Grade C). 3. Echocardiographic assessment of left ventricular mass as well as of systolic and diastolic left ventricular function is recommended for hypertensive patients suspected to have left ventricular dysfunction or coronary artery disease (Grade D). 4. Patients with hypertension and evidence of heart failure should have an objective assessment of left ventricular ejection fraction, by either echocardiogram or nuclear imaging (Grade D).

C. Alcohol consumption 1. To reduce BP, alcohol consumption should be in accordance with Canadian low-risk drinking guidelines in both normotensive and hypertensive individuals. Healthy adults should limit alcohol consumption to ⱕ 2 drinks per day, and consumption should not exceed 14 standard drinks per week for men and 9 standard drinks per week for women (Grade B). (Note: One standard drink is considered to be the equivalent of 13.6 g or 17.2 mL of ethanol or approximately 44 mL [1.5 oz] of 80 proof [40%] spirits, 355 mL [12 oz] of 5% beer, or 148 mL [5 oz] of 12% wine.) D. Dietary recommendations 1. It is recommended that hypertensive patients and normotensive individuals at increased risk of developing hypertension consume a diet that emphasizes fruits, vegetables, low-fat dairy products, dietary and soluble fibre, whole grains, and protein from plant sources that is reduced in saturated fat and cholesterol (Dietary Approaches to Stop Hypertension [DASH] diet; Table 7) (Grade B). E. Sodium intake 1. For the prevention and treatment of hypertension, a dietary sodium intake of 1500 mg (65 mmol) per day is recom-

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mended for adults aged ⱕ 50 years; 1300 mg (57 mmol) per day for age 51-70 years; and 1200 mg (52 mmol) per day for age ⬎ 70 years (Grade B). F. Potassium, calcium, and magnesium intake 1. Supplementation of potassium, calcium, and magnesium is not recommended for the prevention or treatment of hypertension (Grade B). G. Stress management 1. In hypertensive patients in whom stress may be contributing to BP elevation, stress management should be considered as an intervention (Grade D). Individualized cognitive-behavioural interventions are more likely to be effective when relaxation techniques are used (Grade B). Background. There are no changes to these recommendations for 2011. II. Indications for drug therapy for adults with hypertension without compelling indications for specific agents Recommendations 1. Antihypertensive therapy should be prescribed for average DBP measurements of ⱖ 100 mm Hg (Grade A) or average SBP measurements of ⱖ 160 mm Hg (Grade A) in patients without macrovascular target organ damage or other cardiovascular risk factors. 2. Antihypertensive therapy should be strongly considered if DBP readings average ⱖ 90 mm Hg in the presence of macrovascular target organ damage or other independent cardiovascular risk factors (Grade A). 3. Antihypertensive therapy should be strongly considered if SBP readings average ⱖ 140 mm Hg in the presence of macrovascular target organ damage (Grade C for 140-160 mm Hg; Grade A for ⬎ 160 mm Hg). 4. Antihypertensive therapy should be considered in all patients meeting the above indications regardless of age (Grade B). Caution should be exercised in elderly patients who are frail.

425 Table 8. Possible reasons for poor response to antihypertensive therapy Noncompliance Dietary Medication Associated Conditions Obesity Cigarette smoking Excessive alcohol consumption Sleep apnea Chronic pain Drug Interactions Nonsteroidal anti-inflammatory drugs (including cyclo-oxygenase-2 inhibitors) Oral contraceptives Corticosteroids and anabolic steroids Sympathomimetics and decongestants Cocaine Amphetamines Erythropoietin Cyclosporine, tacrolimus Licorice Over-the-counter dietary supplements (e.g. ephedra, ma huang, bitter orange) Monoamine oxidase inhibitors, certain selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors Suboptimal Treatment Regimens Dosage too low Inappropriate combinations of antihypertensive agents Volume Overload Excessive salt intake Renal sodium retention (pseudotolerance) Secondary Hypertension Renal insufficiency Renovascular disease Primary hyperaldosteronism Thyroid disease Pheochromocytoma and other rare endocrine causes Obstructive sleep apnea Adapted from McAlister et al.38

Background. There are no changes to these recommendations for 2011. III. Choice of therapy for adults with hypertension without compelling indications for specific agents Recommendations

3.

A. Recommendations for individuals with diastolic and/or systolic hypertension 1. Initial therapy should be monotherapy with a thiazide diuretic (Grade A); a ␤-blocker (in patients younger than 60 years, Grade B); an ACE inhibitor (in nonblack patients, Grade B); a longacting CCB (Grade B); or an ARB (Grade B). If there are adverse effects, another drug from this group should be substituted. Hypokalemia should be avoided in patients treated with thiazide diuretic monotherapy (Grade C). 2. Additional antihypertensive drugs should be used if target BP levels are not achieved with standard-dose monotherapy

4. 5. 6.

(Grade B). Add-on drugs should be chosen from first-line choices. Useful choices include a thiazide diuretic or CCB with either an ACE inhibitor, ARB, or ␤-blocker (Grade B for the combination of thiazide diuretic and a dihydropyridine CCB; Grade C for the combination of dihydropyridine CCB and ACE inhibitor; and Grade D for all other combinations). Caution should be exercised in combining a nondihydropyridine CCB and a ␤-blocker (Grade D). The combination of an ACE inhibitor and an ARB is not recommended (Grade A). Combination therapy using 2 first-line agents may also be considered as initial treatment of hypertension (Grade C) if SBP is 20 mm Hg above target or if DBP is 10 mm Hg above target. However, caution should be exercised in patients in whom a substantial fall in BP from initial combination therapy is more likely to occur or in whom it would be poorly tolerated (eg, elderly patients). If BP is still not controlled with a combination of ⱖ 2 first-line agents, or there are adverse effects, other antihypertensive drugs may be added (Grade D). Possible reasons for poor response to therapy (Table 8) should be considered (Grade D). ␣-Blockers are not recommended as first-line agents for uncomplicated hypertension (Grade A); ␤-blockers are not recommended as first-line therapy for uncomplicated hypertension in patients 60 years of age or older (Grade A); and ACE

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inhibitors are not recommended as first-line therapy for uncomplicated hypertension in black patients (Grade A). However, these agents may be used in patients with certain comorbid conditions or in combination therapy. B. Recommendations for individuals with isolated systolic hypertension 1. Initial therapy should be monotherapy with a thiazide diuretic (Grade A), a long-acting dihydropyridine CCB (Grade A), or an ARB (Grade B). If there are adverse effects, another drug from this group should be substituted. Hypokalemia should be avoided in patients treated with thiazide diuretic monotherapy (Grade C). 2. Additional antihypertensive drugs should be used if target BP levels are not achieved with standard-dose monotherapy (Grade B). Add-on drugs should be chosen from first-line options (Grade D). 3. If BP is still not controlled with a combination of ⱖ 2 first-line agents, or there are adverse effects, other classes of drugs (such as ␣-blockers, ACE inhibitors, centrally acting agents, or nondihydropyridine CCBs) may be added or substituted (Grade D). 4. Possible reasons for poor response to therapy (see Table 8) should be considered (Grade D). 5. ␣-Blockers are not recommended as first-line agents for uncomplicated isolated systolic hypertension (Grade A); ␤-blockers are not recommended as first-line therapy for isolated systolic hypertension in patients aged ⱖ 60 years (Grade A). However, both agents may be used in patients with certain comorbid conditions or in combination therapy. Background. The 2011 guidelines continue to recommend the use of ARBs in appropriate clinical situations. A recently published post-hoc meta-analysis of 8 randomized controlled trials (RCTs) examining the association between ARBs and cancer was reviewed.39 This analysis was prompted by an unexpected finding that candesartan was associated with a significantly higher risk of fatal malignancy (2%-3% vs 1%-6%; P ⫽ 0.038) compared to placebo in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity (CHARM)-Overall program.40 Included studies had a minimum follow-up period of 1 year and a minimum sample size of 100 patients. ARBs were compared to placebo in 4 studies and to active treatment in 4 studies. Telmisartan was the study drug used in 30,014 of the subjects (85.7%) receiving ARBs. Pooled analysis of 5 trials (N ⫽ 61,590) demonstrated an increased risk of incident cancer (7.2% vs 6.0%; pooled relative risk [RR] 1.08 [95% confidence interval (CI), 1.01-1.15]). Lung cancer incidence was significantly higher among patients receiving ARBs (0.9% vs 0.7%; RR 1.25 [95% CI, 1.05-1.49]). The risk of other solid tumours was not significantly increased. Pooled analysis from 8 trials (N ⫽ 93,515) found no significantly increased risk of cancer death (1.8% vs 1.6%; RR 1.07 [95% CI, 0.97-1.18]). This analysis provides associative but not causal evidence for an increased risk of malignancy with ARB therapy. Ascertainment bias is a potential concern, particularly in the 5 trials in which cancer was not a prespecified endpoint. Furthermore, only trials in which cancer endpoint data were available could be analyzed and publication bias is a potential concern. Also

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arguing against a causal relationship is the lack of compelling data demonstrating a biological link between ARB treatment and carcinogenesis, including the absence of a signal in preclinical carcinogenicity studies. The task force noted that the U.S. Food and Drug Administration (FDA) has recommended against discontinuation of ARB treatment pending the results of their safety review.41 Given the potential that increased cardiovascular events may result from the sudden discontinuation of antihypertensive therapy, the task force viewed the stance of the FDA as prudent and plans to revisit this issue as forthcoming data become available. Notably, a follow-up systematic review including the VALUE study (which had not been included in the initial review) published following the CHEP annual review failed to substantiate the findings related to the increased cancer risk of ARB therapy alone but did continue to show a small but significant increased risk of cancer with combination of ARBs and ACE inhibitors.42 IV. Global vascular protection therapy for adults with hypertension without compelling indications for specific agents Recommendations 1. Statin therapy is recommended in hypertensive patients with ⱖ 3 cardiovascular risk factors as defined in Table 9 (Grade A in patients ⬎ 40 years) or with established atherosclerotic disease (Grade A regardless of age). 2. Strong consideration should be given to the addition of low-dose acetylsalicylic acid therapy in hypertensive patients (Grade A in patients ⬎ 50 years). Caution should be exercised if BP is not controlled (Grade C). Background. There has been increasing concern regarding the use of acetylsalicylic acid in primary prevention. A number of recent meta-analyses, in the absence of new data, have questioned its utility in a general population at moderate risk.44-46 However, CHEP noted that for patients at moderate risk, the number needed to treat (NNT)10s for benefit (the net of events saved-adverse events) reported are fairly comparable to the NNT10s associated with reducing BPs of ⬎ 100 mm Hg DBP in mild/moderate risk patients (ie, 20-80) as was reported in HOT.47 Further, the HOT study

Table 9. Cardiovascular risk factors for consideration of statin therapy in nondyslipidemic patients with hypertension Male sex Age ⱖ 55 years Left ventricular hypertrophy Other electrocardiogram abnormalities: left bundle branch block, left ventricular strain pattern, abnormal Q waves or ST-T changes compatible with ischemic heart disease Peripheral arterial disease Previous stroke or transient ischemic attack Microalbuminuria or proteinuria Diabetes mellitus Smoking Family history of premature cardiovascular disease Total cholesterol to high-density lipoprotein ratio ⱖ 6 If hypertensive patients have ⱖ 3 of these risk factors, statins should be considered. Data from Sever et al.43

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remains the most significant trial examining the impact of acetylsalicylic acid in a wholly hypertensive population. Our current perspective is unchanged (ie, for patients with hypertension, acetylsalicylic acid prescription is reasonable in moderate- to high-risk patients). For further guidance in the management of patients with dyslipidemia, readers are referred to the 2009 Canadian Cardiovascular Society/Canadian guidelines for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease in the adult.1 V. Goal of therapy for adults with hypertension without compelling indications for specific agents Recommendations 1. The SBP treatment goal is a pressure level of ⬍ 140 mm Hg (Grade C). The DBP treatment goal is a pressure level of ⬍ 90 mm Hg (Grade A). Background. There are no changes to these recommendations for 2011. VI. Treatment of hypertension in association with ischemic heart disease Recommendations A. Recommendations for hypertensive patients with coronary artery disease 1. An ACE inhibitor or ARB is recommended for most patients with hypertension and coronary artery disease (Grade A). 2. For patients with stable angina, ␤-blockers are preferred as initial therapy (Grade B). CCBs may also be used (Grade B). 3. Short-acting nifedipine should not be used (Grade D). 4. For patients with coronary artery disease, but without coexisting systolic heart failure, the combination of an ACE inhibitor and ARB is not recommended (Grade B). 5. In high-risk patients, when combination therapy is being used, choices should be individualized. The combination of an ACE inhibitor and a dihydropyridine CCB is preferable to an ACE inhibitor and a diuretic in selected patients (Grade A). B. Recommendations for patients with hypertension who have had a recent myocardial infarction 1. Initial therapy should include both a ␤-blocker and an ACE inhibitor (Grade A). 2. An ARB can be used if the patient is intolerant of an ACE inhibitor (Grade A in patients with left ventricular systolic dysfunction). 3. CCBs may be used in post–myocardial infarction patients when ␤-blockers are contraindicated or not effective. Nondihydropyridine CCBs should not be used when there is heart failure, as evidenced by pulmonary congestion on examination or radiography (Grade D). Background. There are no changes to these recommendations for 2011.

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VII. Treatment of hypertension in association with heart failure Recommendations 1. In patients with systolic dysfunction, ACE inhibitors (Grade A) and ␤-blockers (Grade A) are recommended for initial therapy. Aldosterone antagonists (Grade B) are also recommended for patients with NYHA class III or IV symptoms of heart failure or post myocardial infarction. Other diuretics are recommended as additional therapy if needed (Grade B for thiazide diuretics for BP control and Grade D for loop diuretics for volume control). Beyond considerations of BP control, doses of ACE inhibitors or ARBs should be titrated to those found to be effective in trials unless adverse effects become manifest (Grade B). 2. An ARB is recommended if ACE inhibitors are not tolerated (Grade A). 3. A combination of hydralazine and isosorbide dinitrate is recommended if ACE inhibitors and ARBs are contraindicated or not tolerated (Grade B). 4. For hypertensive patients whose BP is not controlled, an ARB may be added to an ACE inhibitor and other antihypertensive drug treatment (Grade A). Careful monitoring should be used if combining an ACE inhibitor and an ARB due to potential adverse effects such as hypotension, hyperkalemia, and worsening renal function (Grade C). Additional therapies may also include dihydropyridine CCBs (Grade C). Background. There are no changes to these recommendations for 2011. VIII. Treatment of hypertension in association with stroke Recommendations A. Blood pressure management in acute stroke (onset to 72 hours) 1. For patients with ischemic stroke not eligible for thrombolytic therapy, treatment of hypertension in the setting of acute ischemic stroke or transient ischemic attack should not be routinely undertaken (Grade D). Extreme BP elevation (eg, SBP ⬎ 220 mm Hg or DBP ⬎ 120 mm Hg) may be treated to reduce the BP by approximately 15% (Grade D), and not more than 25%, over the first 24 hours with gradual reduction thereafter (Grade D). Avoid excessive lowering of BP as this may exacerbate existing ischemia or may induce ischemia, particularly in the setting of intracranial arterial occlusion or extracranial carotid or vertebral artery occlusion (Grade D). Pharmacologic agents and routes of administration should be chosen to avoid precipitous falls in BP (Grade D). 2. For patients with ischemic stroke eligible for thrombolytic therapy, very high BP (⬎ 185/110 mm Hg) should be treated concurrently in patients receiving thrombolytic therapy for acute ischemic stroke to reduce the risk of secondary intracranial hemorrhage (Grade B). B. Blood pressure management after acute stroke 3. Strong consideration should be given to the initiation of antihypertensive therapy after the acute phase of a stroke or transient ischemic attack (Grade A).

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4. Following the acute phase of a stroke, BP-lowering treatment is recommended to a target of consistently ⬍ 140/90 mm Hg (Grade C). 5. Treatment with an ACE inhibitor/diuretic combination is preferred (Grade B). 6. For patients with stroke, the combination of an ACE inhibitor and ARB is not recommended (Grade B). Background. Hypertension following the acute phase of stroke is associated with increased risk of recurrent stroke and death. Antihypertensive use lowers this risk substantially. CHEP continues to recommend lowering BP consistently to ⬍ 140/90 mm Hg following stroke. This year, CHEP worked in conjunction with the Canadian Stroke Network to provide recommendations for elevated BP in patients with acute stroke (within 4 days of stroke symptom onset). In the setting of acute stroke, 75% of patients will experience elevated BPs, potentially due to preexisting hypertension, activation of the neuroendocrine response to acute stroke, neurogenic hypertension due to the stroke itself, disruption of normal cerebral autoregulation, or development of intracranial mass. Although BP tends to fall to prestroke baseline values within a few days following acute stroke in the majority of patients, observational studies demonstrate that very high BP immediately following acute stroke is associated with early neurologic deterioration, stroke progression or recurrence, and mortality. In an analysis of 17,398 acute ischemic stroke patients enrolled in the International Stroke Trial (IST), those with an SBP ⬎ 200 mm Hg had a ⬎ 50% greater risk of recurrence in the first 14 days than did those with a pressure of 130 mm Hg.48 Whether actively lowering BP in the acute phase of stroke will reduce this risk remains unclear. In the Intravenous Nimodipine West European Stroke Trial (INWEST) of 265 patients with acute ischemic stroke, lowering DBP with IV nimodipine ⬎ 20% was associated with increased risk of death or dependency.49 In the Acute Candesartan Cilexetil Therapy in Stroke Survivors (ACCESS) trial, lowering BP with candesartan (15% reduction in mean arterial pressure) was not associated with adverse outcomes, but this trial excluded patients with carotid stenosis defined by ultrasound and the candesartan arm did not have a significantly lower BP than the placebo arm in the early phase after stroke.49,50 These and other smaller studies collectively suggest that large falls in BP among patients with very high BP in acute stroke are associated with harm. However, it remains unclear whether more modest reductions in BP are beneficial. In intracerebral hemorhage, small studies, such as the pilot phase of Intensive Blood Pressure Lowering in Acute Cerebral Haemorrhage Trial (INTERACT), have suggested that BP lowering results in reduced enlargement of intraparenchemal hematoma. The full INTERACT trial is now under way in Australasia and Europe and will provide more definitive evidence on whether BP lowering is beneficial to clinical outcomes.51 CHEP recommends that antihypertensive agents should not generally be administered in the acute phase of both ischemic stroke and intracerebral hemorrhage. In those with extremely high BP (eg, ⬎ 220/110 mm Hg), pressures may be lowered approximately 15% but should not be lowered ⬎ 25% of the mean arterial pressure within

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the first 24 hours of stroke onset (Grade D). Pharmacologic agents and routes of administration should be chosen to avoid precipitous falls in BP (Grade D). Patients with ischemic stroke who will be receiving thrombolytic therapy and who have elevated BP should, however, have their prethrombolytic BP lowered to a target of ⬍ 185/110 mm Hg. Thrombolysis is contraindicated in patients with ischemic stroke with systolic BP levels ⬎ 185 mm Hg and/or diastolic BP ⬎ 110 mm Hg because of associated higher risks of intracranial hemorrhage.52 In the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study, identifying benefit of thrombolytic therapy in acute ischemic stroke, and in subsequent thrombolytic stroke trials, patients with SBP levels ⬎ 185 mm Hg and/or DBP ⬎ 110 mm Hg were excluded from the study and those who required aggressive (ie, intravenous) antihypertensive treatment to reach these targets were also excluded.53 Since the publication of this study, several stroke organizations, the Canadian Stroke Network, European Stroke, and American Stroke Association guidelines recommend nonaggressive antihypertensive treatment intervention if BP exceeds this threshold prior to and concurrent with thrombolytic treatment. IX. Treatment of hypertension in association with left ventricular hypertrophy Recommendations 1. Hypertensive patients with left ventricular hypertrophy should be treated with antihypertensive therapy to lower the rate of subsequent cardiovascular events (Grade C). 2. The choice of initial therapy can be influenced by the presence of left ventricular hypertrophy (Grade D). Initial therapy can be drug treatment using ACE inhibitors, ARBs, long-acting CCBs, or thiazide diuretics. Direct arterial vasodilators such as hydralazine or minoxidil should not be used. Background. There are no changes to these recommendations for 2011. X. Treatment of hypertension in association with nondiabetic chronic kidney disease Recommendations 1. For patients with nondiabetic chronic kidney disease, target BP is ⬍ 130/80 mm Hg (Grade C). 2. For patients with hypertension and proteinuric chronic kidney disease (urinary protein ⬎ 500 mg/24 hr or albuminto-creatinine ratio [ACR] ⬎ 30 mg/mmol), initial therapy should be an ACE inhibitor (Grade A) or an ARB if there is intolerance to ACE inhibitors (Grade B). 3. Thiazide diuretics are recommended as additive antihypertensive therapy (Grade D). For patients with chronic kidney disease and volume overload, loop diuretics are an alternative (Grade D). 4. In most cases, combination therapy with other antihypertensive agents may be needed to reach target BPs (Grade D). 5. The combination of an ACE inhibitor and ARB is not recommended for patients with nonproteinuric chronic kidney disease (Grade B).

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Background. There are no changes to these recommendations for 2011. XI. Treatment of hypertension in association with renovascular disease Recommendations 1. Renovascular hypertension should be treated in the same manner as hypertension without compelling indications, except for caution in the use of ACE inhibitors or ARBs due to the risk of acute renal failure in bilateral disease or unilateral disease with a solitary kidney (Grade D). 2. Close follow-up and early intervention (angioplasty and stenting or surgery) should be considered for patients with uncontrolled hypertension despite therapy with ⱖ 3 drugs, deteriorating kidney function, bilateral atherosclerotic renal artery lesions (or tight atherosclerotic stenosis in a single kidney), or recurrent episodes of flash pulmonary edema (Grade D). Background. There are no changes to these recommendations for 2011. XII. Treatment of hypertension in association with diabetes mellitus Recommendations 1. Persons with diabetes mellitus should be treated to attain SBPs of ⬍ 130 mm Hg (Grade C) and DBPs of ⬍ 80 mm Hg (Grade A). (These target BP levels are the same as the BP treatment thresholds.) Combination therapy using 2 first-line agents may also be considered as initial treatment of hypertension (Grade B) if SBP is 20 mm Hg above target or if DBP is 10 mm Hg above target. However, caution should be exercised in patients in whom a substantial fall in BP is more likely or poorly tolerated (eg, elderly patients and patients with autonomic neuropathy). 2. For persons with cardiovascular or kidney disease, including microalbuminuria or with cardiovascular risk factors in addition to diabetes and hypertension, an ACE inhibitor or an ARB is recommended as initial therapy (Grade A). 3. For persons with diabetes and hypertension not included in the above recommendation, appropriate choices include (in alphabetical order): ACE inhibitors (Grade A), angiotensin receptor blockers (Grade B), dihydropyridine CCBs (Grade A), and thiazide/thiazide-like diuretics (Grade A). 4. If target BPs are not achieved with standard-dose monotherapy, additional antihypertensive therapy should be used. For persons in whom combination therapy with an ACE inhibitor is being considered, a dihydropyridine CCB is preferable to hydrochlorothiazide (Grade A). Background. This year, new data from the ACCORD-BP and the ACCOMPLISH trials were examined in detail.5,6 ACCORD-BP randomized 4733 patients with type 2 diabetes to either an intensive BP-lowering strategy to achieve a target SBP of ⬍ 120 mm Hg or a standard treatment strategy targeting an SBP of ⬍ 140 mm Hg. The trial also examined the effect of intensive vs standard glucose control using a 2 ⫻ 2 factorial design. Achieved BPs were 119 mm Hg in the intensive group and 133 mm Hg in the standard group. The primary composite endpoint was nonfa-

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tal myocardial infarction, nonfatal stroke, and death from cardiovascular causes. After a mean follow-up of 4.7 years, the use of an intensive strategy did not significantly reduce the annual rates of the primary outcome (1.87% vs 2.09%; hazard ratio [HR] 0.88; 95% CI, 0.73-1.06) but did reduce stroke, a prespecified secondary endpoint (0.32 vs 0.53%; HR 0.59; 95% CI, 0.39-0.89). Intensive therapy did increase the risk of major adverse events including symptomatic hypotension, bradycardia, arrhythmia, and hyperkalemia. Three major issues complicate interpretation of the ACCORD-BP trial. First, the study may have been underpowered, as event rates were nearly 50% lower than expected. Second, ACCORD did not explicitly examine the BP threshold of 130 mm Hg, and therefore, the trial does not directly inform whether current thresholds are most appropriate. The evidence for this threshold has been previously reviewed.38 Third, there was evidence for possible statistical interaction between the BP-lowering and glucose-lowering parts of the study (P ⫽ 0.08). The presence of interaction mandates that the study results be interpreted within the factorial subgroups rather than as a whole.54 Given these uncertainties, the Task Force voted to make no change to the current recommendation pending forthcoming data and new evidence will continue to be reviewed in detail on an annual basis. Previous iterations of these guidelines specifically identified those with diabetes and evidence of increased urinary albumin excretion as persons at high risk for cardiovascular events and recommended ACE or ARB as first-line therapeutic agents.8,9,15 The new recommendations now identify those with known cardiovascular disease, renal disease, or elevated urinary albumin excretion and those with additional cardiovascular risk factors to be highrisk patients who should receive and ACE or an ARB as first line therapy. This risk assessment strategy is consistent with that currently recommended by the Canadian Diabetes Association.55 Also new this year is a recommendation supporting ACE/ CCB combination therapy in patients with type 2 diabetes. This is based on the ACCOMPLISH trial, which compared Table 10. Strategies to improve patient adherence Assist your patient to adhere by: ● Tailoring pill-taking to fit patients’ daily habits (Grade D) ● Simplifying medication regimens to once-daily dosing (Grade D) ● Replacing multiple pill antihypertensive combinations with single pill combinations (Grade C) ● Utilizing unit-of-use packaging (of several medications to be taken together) (Grade D) ● Adherence to an antihypertensive prescription can be improved by a multidisciplinary team approach (Grade B). Assist your patient in getting more involved in their treatment by: ● Encouraging greater patient responsibility/autonomy in monitoring their blood pressure and adjusting their prescriptions (Grade C) ● Educating patients and patients’ families about their disease and treatment regimens (Grade C) Improve your management in the office and beyond by: ● Assessing adherence to pharmacologic and nonpharmacologic therapy at every visit (Grade D) ● Encouraging adherence with therapy by out-of-office contact (either by telephone or mail), particularly during the first 3 months of therapy (Grade D) ● Coordinating with pharmacists and worksite health care givers to improve monitoring of adherence with pharmacologic and lifestyle modification prescriptions (Grade D) ● Using electronic medication compliance aids (Grade D)

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Table 11. Considerations in the individualization of antihypertensive therapy Initial therapy Diastolic ⫾ systolic hypertension

Isolated systolic hypertension without other compelling indications

Diabetes mellitus with albuminuria,* cardiovascular disease, renal disease or additional cardiovascular risk factors Diabetes mellitus not included in the above category

Coronary artery disease

Prior myocardial infarction Heart failure

Left ventricular hypertrophy Past stroke or TIA

Second-line therapy

Hypertension without other compelling indications (target BP < 140/90 mm Hg) Thiazide diuretics, ␤-blockers, Combinations of first-line ACE inhibitors, ARBs, or drugs long-acting calcium channel blockers (consider ASA and statins in selected patients). Consider initiating therapy with a combination of first-line drugs if the blood pressure is ⱖ 20 mm Hg systolic or ⱖ 10 mm Hg diastolic above target

Thiazide diuretics, ARBs or Combinations of first-line long-acting drugs dihydropyridine calcium channel blockers Diabetes mellitus (target blood pressure < 130/80 mm Hg) ACE inhibitors or ARBs Addition of dihydropyridine CCB is preferred over thiazide ACE inhibitors, ARBs, dihydropyridine CCBs, or thiazide diuretics

Combination of first-line drugs or, if first-line agents are not tolerated, addition of cardioselective ␤-blockers and/or long-acting nondihydropyridine CCBs Cardiovascular disease (target blood pressure < 140/90 mm Hg) ACE inhibitors or ARBs Long-acting CCBs. When (except in low-risk combination therapy is patients); ␤-blockers for being used for high-risk patients with stable angina patients, an ACE inhibitor/dihydropyridine CCB is preferred ␤-Blockers, ACE inhibitors Long-acting CCBs (ARBs if ACE inhibitor intolerant) ACE inhibitors (ARBs if ACE ARB in addition to ACE inhibitor-intolerant) and inhibitor. Hydralazine/ ␤-blockers. Spironolactone isosorbide dinitrate in patients with NYHA combination Thiazide or class III or IV symptoms. loop diuretics are recommended as additive therapy Does not affect initial treatment recommendations ACE inhibitor/diuretic combinations

Combination of additional agents Combination of additional agents

Notes and/or cautions

␤-blockers are not recommended as initial therapy in those older than 60 years of age. Hypokalemia should be avoided by using potassiumsparing agents in those who are prescribed diuretics as monotherapy. ACE inhibitors are not recommended in blacks. ACE inhibitors, ARBs and direct renin inhibitors are potential teratogens, and caution is required if prescribing to women of child-bearing potential. Combination of an ACE inhibitor with an ARB is not recommended. Same as diastolic ⫾ systolic hypertension

A loop diuretic could be considered in hypertensive CKD patients with extracellular fluid volume overload Normal albumin-to-creatinine ratio [ACR] ⬍ 2.0 mg/mmol in men and ⬍ 2.8 mg/mmol in women Combination of an ACE inhibitor with an ARB is specifically not recommended. Avoid short-acting nifedipine. Combination of an ACE inhibitor with an ARB is specifically not recommended Combination of an ACE inhibitor with an ARB is specifically not recommended Titrate doses of ACE inhibitors and ARBs to those used in clinical trials. Avoid nondihydropyridine CCBs (diltiazem, verapamil). Monitor potassium and renal function if combining an ACE inhibitor with ARB Hydralazine and minoxidil can increase left ventriculare hypertrophy This does not apply to acute stroke. Blood pressure reduction reduces recurrent strokes in stable patients. Combination of an ACE inhibitor with an ARB is specifically not recommended.

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Table 11. Continued. Initial therapy

Second-line therapy

Nondiabetic chronic kidney disease (target blood pressure < 130/80 mm Hg) Nondiabetic chronic kidney disease with ACE inhibitors (ARBs if ACE Combinations of additional proteinuria† inhibitor-intolerant) if agents there is proteinuria Diuretics as additive therapy

Renovascular disease

Peripheral arterial disease Dyslipidemia Overall vascular protection

Does not affect initial treatment recommendations

Combinations of additional agents

Other conditions (target blood pressure < 140/90 mm Hg) Does not affect initial Combinations of additional treatment agents recommendations Does not affect initial Combinations of additional treatment agents recommendations Statin therapy for patients with – 3 or more cardiovascular risk factors or atherosclerotic disease Low-dose ASA in patients with controlled blood pressure

Notes and/or cautions Avoid ACE inhibitors or ARBs if bilateral renal artery stenosis or unilateral disease with solitary kidney. Patients placed on an ACE inhibitor or an ARB should have their serum creatinine and potassium carefully monitored. Combinations of an ACE inhibitor and ARB are specifically not recommended in patients with chronic kidney disease without proteinuria Avoid ACE inhibitors or ARB if bilateral renal artery stenosis or unilateral disease with solitary kidney Avoid ␤-blockers with severe disease – Caution should be exercised with the ASA recommendation if blood pressure is not controlled.

ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; ASA, acetylsalicylic acid; CCB, calcium channel blocker; CKD, chronic kidney disease; NYHA, New York Heart Association; TIA, transient ischemic attack. * Albuminuria is defined as persistent albumin to creatinine ratio (ACR) ⬎ 2.0 mg/mmol in men and ⬎ 2.8 mg/mmol in women. † Proteinuria is defined as urinary protein ⬎ 500 mg/24 hr or ACR ⬎ 30 mg/mmol.

benzapril/amlodipine combination treatment vs benzapril/thiazide therapy.6 The primary endpoint was a composite of myocardial infarction, stroke, cardiovascular death, hospitalization for angina, resuscitated cardiac arrest, and coronary revascularization. The trial enrolled 6946 high-risk subjects with type 2 diabetes; 2842 participants were deemed to be particularly “high risk” by virtue of a previous cardiac, cerebrovascular, or renal event. Benzapril/amlodipine reduced occurrence of the primary event compared to benzapril/thiazide in all subjects with diabetes (8.8% vs 11%; HR 0.79; 95% CI, 0.68-0.92) and the subgroups of subjects who were considered high risk (13.6% vs 17.3%; HR 0.77; 95% CI, 0.64-0.93).

growing literature supporting the effectiveness of pharmacists in improving BP control. XIV. Treatment of secondary hypertension due to endocrine causes Recommendations 1. Treatments of hyperaldosteronism and pheochromocytoma are outlined in Online Table S1 and Online Table S2. Background. There are no changes to these recommendations for 2011.

XIII. Adherence strategies for patients Recommendations 1. Adherence to an antihypertensive prescription can be improved by a multipronged approach (Table 10). Background. CHEP has included coordinating with pharmacists in addition to worksite health care givers to improve adherence in hypertension. A prospective cluster randomized trial of clinical pharmacists working with physicians was found to improve physician guideline adherence and also led to greater reductions in patient BP.56 The findings from this trial support the involvement of pharmacists in assisting physicians with BP management and are consistent with a

Future Directions The present paper (see Table 11 for summary) represents the 12th iteration of the annually updated CHEP recommendations for the management of hypertension, and we will continue to conduct yearly systematic reviews of the clinical trial evidence to annually update our recommendations for therapy. Funding Sources The CHEP process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacy Association, the Canadian Coun-

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cil of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.

Disclosures Disclosures can be found in Online Appendix I available online at www.onlinecjc.ca.

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Supplementary Material To access the supplementary material accompanying this article, visit the online version of the Canadian Journal of Cardiology and at www.onlinecjc.ca, doi:10.1016/j.cjca.2011.03.015.

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ONLINE APPENDIX I Author

Canadian Hypertension Education Program Faculty Summary: Declared Conflicts of Interest (2010)*

J. Malcolm O. Arnold

Paid consultant/advisory board: Novartis, Takeda Canada, Pfizer, Boehringer-Ingelheim, GlaxoSmithKline, Abbott/Solvay Pharma, Merck Frosst, Sanofi-Aventis, Schering-Plough Canada Research sponsored by: GlaxoSmithKline (asthma) Paid to speak CHE: Merck Frosst No conflicts of interest to disclose. No conflicts of interest to disclose. No conflicts of interest to disclose. Paid consultant/advisory board: Ortho Biotech Inc. Paid consultant/advisory board: Bristol-Myers Squibb, Sanofi Paid to speak CHE: Sanofi-Aventis, Bristol-Myers Squibb, Bayer, Biovail

Simon L. Bacon Peter Bolli Jean-Martin Boulanger Ellen Burgess Kevin D. Burns Norman R.C. Campbell Tavis S. Campbell S. George Carruthers Arun Chockalingam Lyne Cloutier Stella S. Daskalopoulou Martin Dawes George K. Dresser Denis Drouin Ross D. Feldman George Fodor Richard E. Gilbered

Steven A. Grover Daniel G. Hackam Pavel Hamet

Robert A. Hegele Brenda R. Hemmelgarn Robert J. Herman Michael D. Hill George Honos Jonathan G. Howlett Charlotte Jones Nadia A. Khan Maxime LamarreCliché Pierre Larochelle Marcel Lebel Lawrence A. Leiter

Richard Lewanczuk M. Patrice Lindsay Karen Mann Philip A. McFarlane

No conflicts of interest to disclose. No conflicts of interest to disclose. No conflicts of interest were disclosed. Paid to speak CHE: Pfizer, Novartis, Bristol-Myers Squibb, Schering-Plough, Sanofi, Servier, AstraZeneca, Merck No conflicts of interest to disclose. No conflicts of interest to disclose. Research sponsored by: Pfizer, AiCuris Paid consultant/advisory board: Boehringer-Ingleheim, Novartis, Biovail, Solvay Pharma Paid to speak CHE: Boehringer-Ingelheim, Novartis, AstraZeneca, Bristol-Myers Squibb, Merck, Pfizer, Sanofi-Aventis, Servier Paid consultant/advisory board: Novartis, AstraZeneca, Pfizer, Sanofi-Aventis, Unilever Canada, CIHR, Public Health Quebéc City Reviewer CIHR and Canadian Cardiovascular Journal, Heart and Stroke Foundation of Quebéc and Ontario Research sponsored by: Pfizer, Boehringer-Ingleheim Paid consultant/advisory board: Boehringer-Ingleheim, Merck, Novartis, Pfizer, Servier Paid to speak CHE: Bayer, Boehringer-Ingelheim, Novartis Research sponsored by: AstraZeneca, Solvay Research sponsored by: Novartis, Merck, Sanofi-Aventis, Bristol-Myers Squibb Paid consultant/ advisory board: Bristol-Myers Squibb, Novartis, Sanofi-Aventis Paid to speak CHE: Novartis, Sanofi-Aventis, Bristol-Myers Squibb Patent: Co-inventor on the use of Novartis compounds in cardiovascular and kidney disease Research sponsored by: Merck, Bayer, AstraZeneca Paid consultant/advisory board: Merck, AstraZeneca, Bristol-Myers Squibb Paid to speak CHE: Merck No conflicts of interest to disclose. Research sponsored by: Pfizer Paid consultant/advisory board: Servier, Bellos Health, Pfizer, Bristol-Myers Squibb, Eli Lilly, Cybiocare, BioK⫹ Paid to speak CHE: Merck, Bristol-Myers Squibb, Servier, Novartis, Sanofi-Aventis, Bayer, Solvay, Eli Lilly Patents: List available No conflicts of interest to disclose. Research sponsored by: Roche, Merck No conflicts of interest to disclose. Research sponsored by: Roche, Merck, Bayer Paid to speak CHE: Sanofi, Boehringer-Ingelheim, Hoffmann-La Roche, Bristol-Myers Squibb, GE Healthcare Paid consultant/advisory board: Bayer, Merck, Novartis, Pfizer, AstraZeneca, Boehringer-Ingelheim Paid to speak CHE: Merck, Schering-Plough, Abbott, Bayer, Merck, Novartis, Pfizer, AstraZeneca, Boehringer-Ingelheim Research sponsored by: Merck, AstraZeneca, Servier Paid consultant/advisory board: Merck, AstraZeneca, Novartis, Servier, Boehringer-Ingelheim Paid to speak CHE: AstraZeneca No conflicts of interest to disclose. Research sponsored by: Sanofi-Aventis, Boehringer-Ingelheim Paid consultant/advisory board: Novartis Research sponsored by: Pfizer Canada, Boehringer-Ingelheim Paid consultant/advisory board: Pfizer Canada Inc, Boehringer-Ingelheim, Novartis, Merck, AstraZeneca Paid to speak CHE: Servier, Novartis, Merck Frosst, Boehringer-Ingelheim No conflicts of interest to disclose. Research sponsored by: AstraZeneca, Eli Lilly, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Roche, Sanofi-Aventis Paid consultant/advisory board: AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck, Sanofi-Aventis, Novo Nordisk, Roche, Servier, Novartis Paid to speak CHE: AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Novartis, Novo Nordisk Research sponsored by: Afexa Life Sciences Paid to speak CHE: Merck, Novartis, Boehringer-Ingelheim No conflicts of interest to disclose. No conflicts of interest to disclose. Research sponsored by: Boehringer-Ingelheim, GlaxoSmithKline, Biovail, AstraZeneca, Amgen, Ortho-Biotech, Novartis, Novo Nordsik Paid consultant/advisory board: Boehringer-Ingelheim, GlaxoSmithKline, Biovail, Amgen, Ortho-Biotech, Novartis, Novo Nordsik, Sanofi Paid to speak CHE: Abbott/Solvay, Biovail, Novartis, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Boehringer-Ingelheim, Sanovi-Aventis

Rabi et al. / 27 (2011) 415– 433 ONLINE APPENDIX I Continued. Author Donald W. McKay Donna McLean Alain Milot Gordon W. Moe Martin G. Myers Richard I. Ogilvie Raj S. Padwal Brian Penner Robert J. Petrella Luc Poirier G.V. Ramesh Prasad George Pylypchuk Robert R. Quinn Doreen M. Rabi Simon W. Rabkin Marcel Ruzicka Ernesto L. Schiffrin Mukul Sharma James A. Stone Sheldon W. Tobe

Rhian M. Touyz Guy Tremblay Luc Trudeau Michel Vallée Thomas Wilson Vincent Woo

Canadian Hypertension Education Program Faculty Summary: Declared Conflicts of Interest (2010)* Research sponsored by: Solvay Pharma No conflicts of interest to disclose. Research sponsored by: Boehringer-Ingelheim, GlaxoSmithKline Paid to speak CHE: Merck, Boehringer-Ingelheim, Bristol-Myers Squibb, Sanofi-Aventis, Novartis, Schering-Plough Research sponsored by: Roche-Diagnostics, Novartis Research sponsored by: Novartis Paid consultant/advisory board: Servier, Palatin Technologies, Ideal life Devices Paid to speak CHE: Servier, Merck Paid consultant/advisory board: Schering-Plough, Merck, AstraZeneca, Bayer Paid to speak CHE: Biovail, Merck, Servier, Abbott No conflicts of interest to disclose. No conflicts of interest to disclose. No conflicts of interest to disclose. Research sponsored by: Novartis, Gead Paid consultant/advisory board: Novartis, Merck Paid to speak CHE: Pfizer, Novartis, Merck, Biovail, AtraZeneca No conflicts of interest to disclose. Research sponsored by: Merck Paid consultant/advisory board: Bristol-Myers Squibb, Sanofi No conflicts of interest to disclose. No conflicts of interest to disclose. No conflicts of interest were disclosed. Research sponsored by: Pfizer, Bayer Paid consultant/advisory board: Novartis, Boehringer, Abbott Paid consultant/advisory board: Bristol, Novartis Paid to Speak CHE: Daiichi-Sankyo Paid consultant/advisory board: Bayer, Lundbeck Paid to speak CHE: Board: Boehringer-Ingelheim, Bristol-Myers Squibb, Sanofi Paid to speak CHE: Bristol-Myers Squibb/Sanofi, Pfizer, Merck, Boehringer Paid consultant/advisory board: AstraZeneca, Merck, Novartis, Pfizer, Sanofi, Servier Paid to speak CHE: AstraZeneca, Sanofi-Aventis, Merck, Novartis, Servier Research sponsored by: Baxter, Janssen Ortho, Boehringer-Ingelheim, AtraZeneca, Hoffmann-La Roche, Amgen, Mercer Paid consultant/advisory board: Bristol-Myers Squibb/Sanofi-Aventis, Pfizer, Abbott, Merck Frosst Paid to speak CHE: Abbott, Bristol-Myers Squibb/Sanofi, AstraZeneca, Pfizer, Merck, Boehringer Patents: For dialysis solutions Research sponsored by: Pfizer, AstraZeneca Paid to speak CHE: Bristol-Myers Squibb/Sanofi Paid consultant/advisory board: AstraZeneca Paid to speak CHE: Université Laval Research sponsored by: Servier, Novartis Paid consultant/advisory board: Merck, Sanofi-Aventis, Bristol-Myers Squibb, Abbott, Novartis Paid to speak CHE: Biovail, Servier, Merck, Boehringer-Ingelheim, Sanofi-Aventis Paid consultant/advisory board: Shire, Abbott, Bristol-Myers Squibb Paid to speak CHE: Merck, Bristol-Myers Squibb, Sanofi, Novartis No conflicts of interest to disclose. Research sponsored by: Bristol-Myers Squibb, Merck, Boehringer-Ingelheim, AstraZeneca, Pfizer, GlaxoSmithKline Paid consultant/advisory board: Merck, GlaxoSmithKline, Bristol-Myers Squibb, Bayer, AstraZeneca Paid to speak CHE: Merck, GlaxoSmithKline, Bristol-Myers Squibb, AstraZeneca

CHE, Continuing Health Education; CIHR, Canadian Institute of Health Research. * Completed, signed conflict-of-interest forms are kept on file.

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