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To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults.
For lifestyle and pharmacological interventions, evidence was reviewed from randomized controlled trials and systematic reviews of trials. 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 lack of long-term morbidity and mortality data in this field. For treatment of patients with kidney disease, the progression of kidney dysfunction was also accepted as a clinically relevant primary outcome.
A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to update the 2006 Canadian Hypertension Education Program recommendations. In addition, reference lists were scanned and experts were contacted to identify additional published studies. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence.
Dietary lifestyle modifications for prevention of hypertension, in addition to a well-balanced diet, include a dietary sodium intake of less than 100 mmol/day. In hypertensive patients, the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day. Other lifestyle modifications for both normotensive and hypertensive patients include: performing 30 min to 60 min of aerobic exercise four to seven days per week; maintaining a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm in men and less than 88 cm in women); limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women; following a diet reduced in saturated fat and cholesterol, and one that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and considering stress management in selected individuals with hypertension.
For the pharmacological management of hypertension, treatment thresholds and targets should take into account each individual’s global atherosclerotic risk, target organ damage and any comorbid conditions: blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease. Most patients require more than one agent to achieve these blood pressure targets. In adults without compelling indications for other agents, initial therapy should include thiazide diuretics; other agents appropriate for first-line therapy for diastolic and/or systolic hypertension include angiotensin-converting enzyme (ACE) inhibitors (except in black patients), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs. Certain comorbid conditions provide compelling indications for first-line use of other agents: in patients with angina, recent myocardial infarction, or heart failure, beta-blockers and ACE inhibitors are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor plus diuretic combination is preferred; in patients with nondiabetic chronic kidney disease, 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. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian Cardiovascular Society position statement (recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease). Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy. Once blood pressure is controlled, acetylsalicylic acid therapy should be considered.
All recommendations were graded according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 95% consensus. These guidelines will continue to be updated annually.
Le Programme a pour but de fournir des recommandations fondées sur des données probantes et mises à jour pour la prévention et la prise en charge de l’hypertension artérielle chez les adultes.
En ce qui a trait au mode de vie et aux interventions pharmacologiques, nous avons procédé à un examen des données provenant d’essais comparatifs hasardisés et d’examens méthodiques d’essais. Les principaux critères d’évaluation étaient les changements de morbidité et de mortalité d’origine cardiovasculaire. Cependant, l’abaissement de la pression artérielle (PA) a été accepté comme principal critère d’évaluation relativement aux interventions touchant au mode de vie compte tenu de l’insuffisance de données sur la morbidité et la mortalité à long terme dans le domaine. Pour ce qui est des patients atteints de néphropathie, l’évolution du dysfonctionnement rénal a aussi été acceptée comme critère d’évaluation clinique pertinent.
Un bibliothécaire de Collaboration Cochrane a effectué une recherche indépendante dans la base de données MEDLINE, de 2005 à août 2006, afin de mettre à jour les recommandations 2006 du Programme d’éducation canadien sur l’hypertension. On a également dépouillé des listes de références et communiqué avec des experts pour trouver d’autres études publiées. Tous les articles pertinents ont été examinés, puis évalués séparément par des experts en contenu et en méthodologie à l’aide d’une grille prédéterminée d’évaluation des données.
Outre un régime alimentaire équilibré, les modifications relatives aux habitudes alimentaires visant à prévenir l’hypertension artérielle (HTA) comprennent un apport de sodium d’origine alimentaire inférieur à 100 mmol/jour. Chez les personnes hypertendues, la prise de sodium alimentaire devrait se limiter à une consommation de 65 à 100 mmol/jour. À cela s’ajoutent des modifications du mode de vie qui s’appliquent autant aux personnes normotendues qu’aux personnes hypertendues : la pratique d’activités aérobiques, de 30 à 60 min, de 4 à 7 jours par semaine; le maintien d’un poids santé (indice de masse corporelle : 18,5 kg/m2 – 24,9 kg/m2) et du tour de taille (< 102 cm pour les hommes; < 88 cm pour les femmes); la limitation de la consommation d’alcool à 14 unités par semaine pour les hommes et à 9 unités par semaine pour les femmes; un régime alimentaire pauvre en graisses saturées et en cholestérol, et riche en fruits et légumes, en produits laitiers à faible teneur en matières grasses, en fibres alimentaires et en fibres solubles, en grains entiers et en protéines d’origine végétale; la maîtrise du stress chez certaines personnes hypertendues.
En ce qui concerne la prise en charge pharmacologique de l’hypertension, la détermination des seuils et des valeurs cibles devrait reposer sur le risque global d’athérosclérose et sur la présence de lésions des organes cibles et de toute autre maladie concomitante chez chaque patient; la PA devrait être abaissée à moins de 140/90 mm Hg chez tous les patients et à moins de 130/80 mm Hg chez les patients atteints de diabète sucré ou d’une néphropathie chronique. L’atteinte de ces valeurs cibles nécessitera, dans la plupart des cas, une association de médicaments antihypertenseurs. Chez les adultes qui ne présentent pas d’indications impératives d’emploi de médicaments particuliers, le traitement de départ devrait comprendre les diurétiques thiazidiques; d’autres médicaments conviennent également au traitement de première intention de l’HTA diastolique ou systolique : les inhibiteurs de l’enzyme de conversion de l’angiotensine (IECA), sauf chez les Noirs; les inhibiteurs calciques (IC) à action prolongée; les antagonistes des récepteurs de l’angiotensine (ARA); et les bêta-bloquants (chez les patients de moins de 60 ans). Le traitement de première intention de l’hypertension systolique isolée comprend les IC dihydropyridiniques à action prolongée ou les ARA. Toutefois, certaines maladies concomitantes constituent des indications impératives d’emploi d’autres médicaments : chez les patients souffrant d’angine de poitrine ou d’insuffisance cardiaque ou ayant subi depuis peu un infarctus du myocarde, les bêta-bloquants et les IECA sont recommandés en première intention; chez les patients présentant une atteinte cérébrale vasculaire, l’association d’un IECA et d’un diurétique est à privilégier; chez les patients atteints d’une néphropathie chronique non diabétique, les IECA sont recommandés; et chez les diabétiques, les IECA ou les ARA (ou, chez les patients ne présentant pas d’albuminurie, les diurétiques thiazidiques ou les IC dihydropyridiniques) conviennent en première intention. Tous les patients hypertendus à la fois dyslipidémiques devraient être traités selon les seuils, les valeurs cibles et les médicaments proposés dans la déclaration de la Société canadienne de cardiologie (recommandations sur le diagnostic et le traitement de la dyslipidémie et la prévention des maladies cardiovasculaires). Un traitement aux statines devrait néanmoins être prescrit à certains patients hypertendus, à risque élevé, qui ne parviennent pas à atteindre les seuils établis pour ce type de traitement, dans la déclaration. L’emploi d’acide acétylsalicylique pourra être envisagé une fois la PA stabilisée.
Toutes les recommandations ont été cotées en fonction de la fiabilité des données et soumises au vote des 57 membres du groupe de travail sur les recommandations fondées des données probantes du Programme d’éducation canadien sur l’hypertension. Les recommandations présentées dans l’article ont toutes recueilli un consensus d'au moins 95 %. Les présentes lignes directrices continueront à faire l’objet d’une mise à jour annuelle.
Hypertension accounts for up to 66% of stroke (1) and 35% of myocardial infarction in women and 20% of hypertension is one of the major strategies for reducing the global burden of cardiovascular disease and death (3). The Canadian Hypertension Education Program (CHEP) is a national knowledge translation strategy that aims to improve hypertension prevention and control in Canada. The CHEP Recommendations Task Force systematically reviews and translates the growing body of hypertension studies annually to give health care providers practical, updated, evidence-based recommendations on the management of hypertension. In this document, we report the 2007 recommendations for lifestyle and pharmacological management of hypertension, as well as the evidence and rationale supporting all new recommendations. Summary documents of these recommendations, along with a freely downloadable slide kit, are available on The Canadian Hypertension Society Web site (www.hypertension.ca).
This year, there were several important developments in the recommendations and recommendations processes. First, the CHEP collaborated with the Canadian Diabetes Association (CDA) and the Canadian Society of Nephrology (CSN) to harmonize blood pressure recommendations across these national guideline bodies. The CDA and the CSN joined the CHEP subgroups to appraise the evidence and draft unified hypertension recommendations.
Another area of focus was promoting dietary changes and reducing dietary salt intake in normotensive individuals to prevent or delay the onset of hypertension. Preventing hypertension is a critical part of overall hypertension control, and even small reductions in blood pressure on a population level are estimated to substantially reduce cardiovascular disease (4,5). The new recommendations were based on the recent publications of three randomized trials on dietary interventions (6–8) and a large meta-analysis (9) of sodium restriction among normotensive individuals.
Because the majority of hypertensive patients require more than a single agent to reach target blood pressure levels, the CHEP also expanded the recommendations for combination therapy in the treatment of hypertension in patients without compelling indications for other agents based on results from the Felodipine EVEnt Reduction (FEVER) trial (10) and the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) study (11).
Although we discuss specific antihypertensive agents in reviewing hypertension trials, all recommendations specify drug classes unless there is compelling evidence that any trial-proven benefits are not a class effect. 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.
The methods for the 2007 recommendations are outlined in detail in the current issue of the Journal (pages 529–538). In brief, a Cochrane collaboration librarian conducted a MEDLINE search using a highly sensitive search strategy for randomized trials and systematic reviews published in 2005 to August 2006. To ensure that all relevant studies were included, bibliographies of identified articles were hand-searched. (Details of search strategies and retrieved articles are available on request.)
Each subgroup, consisting of national and international hypertension experts (Table 2 in pages 551–555 in the current issue of the Journal), reviewed all identified articles relevant to their topic area. Members of the CDA Guidelines Committee and the CSN collaborated with the CHEP subgroup members for the 2007 recommendations process. The subgroups appraised the quality of any recommendations arising from relevant articles using a standardized scheme (Figures 2 to 5 in pages 551–555 of the current issue of the Journal ). Subsequently, the central review committee, composed of epidemiologists (Table 2 on page 552 of the current issue of the Journal), reviewed the draft recommendations from each subgroup and, in an iterative process, helped to refine and standardize all recommendations and their grading across subgroups (Table 1).
A consensus conference was held in Toronto, Ontario, in September 2006 to review and debate the draft recommendations from each subgroup. Based on discussions at the consensus conference, the 2007 recommendations were finalized and submitted to all 57 voting members of the CHEP Evidence-Based Recommendations Task Force for approval. As in previous years, only those recommendations approved by more than 70% of the task force members were included in the final recommendations presented here.
Lifestyle modifications can lower blood pressure from 2 mmHg to 11 mmHg (13), which is comparable with the blood pressure-lowering effect of a single antihypertensive agent (14,15). Lifestyle therapy also reduces the incidence of type 2 diabetes mellitus (16), and improves lipid levels (17) and overall quality of life (18). Given these benefits, lifestyle modification is a key strategy for the prevention and treatment of hypertension (3).
Feeding studies have demonstrated that DASH-type diets lower blood pressure (19). Such diets are low in sodium and saturated fat and are rich in potassium, calcium, magnesium and fibre, all of which are factors that likely contribute to blood pressure reduction (20). Several recent randomized controlled feeding studies (6–8) found that diets rich in plant proteins or monounsaturated fats also appear to be beneficial in lowering blood pressure. The OmniHeart trial (6) compared blood pressure changes in 164 individuals fed carbohydrate-rich, protein-rich (mainly derived from plant sources such as soybean) or monounsaturated fat-rich diets in a randomized, three-period crossover study. Despite having a similar caloric intake, individuals consuming a diet rich in protein or monounsaturated fat demonstrated greater mean blood pressure reductions from baseline compared with those consuming a diet rich in carbohydrates (protein-rich diet: –8.0/4.4 mmHg, monounsaturated fat diet: –7.7/3.9 mmHg, versus carbohydrate-rich diet: –7.0/3.6 mmHg among normotensive patients). Blood pressure reductions were more pronounced in hypertensive individuals.
In 2007, the recommendation for reduced salt intake to prevent hypertension has been broadened to apply to all individuals, not just those most likely to be salt-sensitive (black Canadians, patients with renal disease or diabetes, obese individuals and those older than 45 years of age). This was done after careful consideration of the pros and cons of population-wide sodium restriction. The task force recognizes the potential drawbacks of salt deficiency such as fatigue, hyponatremia and iodine deficiency. However, these harmful effects are unlikely with a salt restriction threshold of 100 mmol/day (2300 mg of sodium or 5750 mg of sodium chloride per day) (6). Although the benefits of reducing sodium are attenuated in patients who are already consuming diets rich in potassium or similar to DASH-type diets (20), most individuals do not consume diets that are similar to the DASH eating plan (21). The task force concluded that the preponderance of higher-quality evidence favoured population-wide salt-restriction (9,22,23). He and MacGregor (9) recently conducted a systematic review of 11 randomized controlled trials with 2220 normotensive patients randomly assigned to modest salt reduction for at least four weeks. Although there was heterogeneity across trials, modest salt reduction lowered blood pressure by 2/1 mmHg among normotensive patients. On a population-wide level, even this small reduction is estimated to reduce the risk of stroke deaths by 6% and ischemic heart disease deaths by 4% (4,5).
Antihypertensive drug therapy is associated with a 20% to 25% reduction in cardiovascular events and a 10% reduction in mortality (27,28). To achieve these substantial cardiovascular benefits, patients often require multiple antihypertensive agents. In recognition of the need for multidrug therapy, combination and add-on therapy trials are emerging. This year, the task force added a new drug combination of a thiazide diuretic with a dihydropyridine CCB for patients who have not achieved target blood pressure with antihypertensive monotherapy based on the results of the FEVER trial (10). In this study, 9711 hypertensive patients from China, 50 to 79 years of age with either established cardiovascular disease or two cardiovascular risk factors, were initiated on low-dose hydrochlorothiazide after a washout of all previous agents. Patients were subsequently randomly assigned to additional low-dose felodipine or placebo, with the option of further open-label antihypertensive agents to maintain a blood pressure of lower than 160/95 mmHg. Those randomly assigned to felodipine plus hydrochlorothiazide had lower blood pressure (138.1/82.3 mmHg), compared with those assigned placebo plus hydrochlorothiazide (141.1/83.9 mmHg), and a significantly lower risk of fatal or nonfatal stroke (hazard ratio [HR] 0.73; 95% CI 0.60 to 0.89) after a mean follow-up period of 3.3 years. Although it was unclear whether imaging was used to ascertain the primary outcome of stroke, there was a consistent benefit favouring felodipine plus hydrochlorothiazide for secondary end points, including cardiovascular events (HR 0.73; 95% CI 0.61 to 0.86) and total mortality (HR 0.69; 95% CI 0.54 to 0.89). These results, demonstrating the efficacy of a dihydropyridine CCB and diuretic combination, are consistent with findings from the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial (11). In this trial, 15,245 patients older than 50 years of age with cardiovascular disease or cardiovascular risk factors were randomly assigned to a valsartan-or an amlodipine-based regimen. Amlodipine and valsartan treatment groups were given hydrochlorothiazide as the first step add-on drug to achieve target blood pressure (25% of the amlodipine group were receiving hydrochlorothiazide in combination). Overall, there was no difference in the primary outcome of cardiac morbidity and mortality (HR 1.03; 95% CI 0.94 to 1.14) between amlodipine- and valsartan-based regimens.
This year, the CHEP removed the specific drug combinations for patients with isolated systolic hypertension given the paucity of evidence for combination therapy in this population. We continue to endorse the general recommendation to choose add-on agents from first-line therapies.
Because there has not been a significant change in the evidence base, these recommendations are unchanged (29).
Because there has not been a substantive change in the evidence base, these recommendations are unchanged from our previous recommendations (26).
It is well established that antihypertensive medications reduce cardiovascular risk among patients with coronary artery disease, and the evidence supporting the choice of agents is unchanged from previous years (24,26). However, a recent analysis of the International Verapamil-Trandolapril Study (INVEST ) raises concern about excessive diastolic blood pressure lowering among patients with hypertension and coronary artery disease. In this post hoc analysis of 22,576 patients randomly assigned to either verapamil SR or atenolol, patients with a diastolic pressure below 70 mmHg to 80 mmHg had an associated increased risk of myocardial infarction and death. However, given significant methodological limitations of this analysis, the CHEP thought that a recommendation to avoid reducing diastolic blood pressure below this threshold was not warranted at this time.
Please also note that while ACE inhibitors reduce cardiovascular events among most patients with coronary artery disease, these benefits do not appear to extend to coronary artery disease patients with low cardiovascular risk (ie, those with normal ejection fraction, adequate coronary revascularization and well-controlled atherosclerotic risk factors).
These recommendations are unchanged from 2006 (29).
This year, the Recommendations Task Force removed beta-blockers from the list of initial therapies for left ventricular hypertrophy based on the re-evaluation of the Losartan Intervention For Endpoint reduction (LIFE) trial (31). The LIFE trial compared the effect of losartan with atenolol in 9193 patients older than 55 years of age with electrocardiogram-diagnosed left ventricular hypertrophy and hypertension. This study found a significant reduction in the composite end point of death, myocardial infarction or stroke favouring losartan (RR 0.87; 95% CI 0.77 to 0.98), even after accounting for differences in trial blood pressures. Although the superiority of ARBs compared with antihypertensives other than beta-blockers could not be established (thus, the drug classes are not assigned evidence grades), the LIFE trial demonstrated the inferiority of beta-blockers in patients with left ventricular hypertrophy. The remaining recommendations are unchanged from 2006 (29).
It is well established that elevated levels of urinary protein are associated with progressive decline in renal function (32). This year, the CHEP-CSN collaboration recommended ACE inhibitors as initial therapy for patients with urinary protein excretion greater than 0.5 g/day (or an ACR greater than 30 mg/mmol) rather than for all individuals with nondiabetic chronic kidney disease. This distinction was made based on evidence demonstrating that the response to ACE inhibition is modified by baseline urinary protein excretion. Jafar et al (33) evaluated the response to ACE inhibitors according to baseline urinary protein excretion levels in an individual-level meta-analysis of 11 randomized controlled trials involving 1860 nondiabetic chronic kidney disease patients. ACE inhibitors conferred progressively greater benefits in reducing the risk of developing end stage renal disease with increasing levels of urinary protein excretion beginning at a threshold of approximately 0.5 g/day. Whether the benefits of ACE inhibition extend below this threshold is unknown given the paucity of ACE inhibitor studies evaluating patients with lower urinary protein excretion rates, and the imprecision of urinary protein measurements at these lower levels.
The evidence supporting ARBs as an alternative to ACE inhibitors is derived from patients with baseline urinary protein excretion greater than 0.5 g/day (34). Patients who are initiated on ACE inhibitor or ARB should have their serum creatinine and potassium levels monitored carefully, preferably within the first two weeks of therapy (35). These agents may be continued as long as serum creatinine levels do not rise by more than 30% from baseline, because acute increases generally plateau within two months (35).
For patients with nondiabetic chronic kidney disease but normal or low urinary protein excretion, physicians should select the initial therapy from first-line agents for patients with systolic and/or diastolic hypertension without compelling indications. The remaining recommendations are unchanged from 2006 (26,29,36).
Because there has not been a substantial change in the evidence base, these recommendations are unchanged this year (26).
The choice of antihypertensive agent among patients with diabetes is guided by urinary albumin excretion rates, because urinary albumin excretion is a powerful prognostic marker for the development of kidney and cardiovascular disease among diabetic patients. Microalbuminuria is associated with a two- to fourfold increase in cardiovascular disease (37,38). Thus, accurate measurement of albuminuria is essential for managing hypertension among patients with diabetes. In 2007, the CHEP, in partnership with the CDA, replaced urinary albumin measurement with sex-specific ACR, because the ACR is a more sensitive and specific measure of albumin excretion rate (39). Thus, a random urine ACR, based on a morning urine sample, is recommended as a screening procedure to determine the ACR.
From the prespecified subgroup analysis of the INVEST study (40), the CHEP has added nondihydropyridine CCBs to the list of alternative antihypertensive agents for patients with diabetes and normal urinary albumin excretion. In this analysis, 6400 patients with diabetes, coronary artery disease and hypertension were randomly assigned to verapamil SR or atenolol. After a mean follow-up of 2.7 years, there was no significant difference in the primary composite end point, total mortality, nonfatal myocardial infarction or nonfatal stroke in the verapamil SR and atenolol study groups (RR 1.05; 95% CI 0.92 to 1.19). Although urinary protein measurements were not available and this was a high-risk coronary artery disease population, the CHEP believed that it was reasonable to extrapolate the findings, given that patients with diabetes often have coexisting coronary artery disease (41). This year, the CHEP also adds the caution that patients who are initiated on an ACE inhibitor or an ARB should have their serum creatinine and potassium levels monitored carefully, preferably within the first two weeks of therapy (35). The remaining recommendations are unchanged from 2006 (29,36).
Because there has been no substantive change in the evidence base this past year, the recommendations for this section are unchanged (42).
Because there has been no substantive change in the evidence base this past year, the recommendations for this section are unchanged.
The present paper represents the eighth iteration of the annually updated CHEP recommendations for the management of hypertension. A summary of the considerations for selecting anihypertensive therapy is presented in Table 8. We will continue to conduct yearly systematic reviews of the clinical trial evidence to annually update our recommendations for therapy.
SPONSORS: 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 Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.