Pierre Larochelle

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapy

OBJECTIVE To update the evidence-based recommendations for the prevention and management of hypertension in adults for 2009. OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions, evidence from randomized controlled trials and systematic reviews of trials was 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 lack of long-term morbidity and mortality data in this field. Progression of kidney dysfunction 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 from 2007 to August 2008 to update the 2008 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to less than 2300 mg (100 mmol)/day (and 1500 mg to 2300 mg [65 mmol to 100 mmol]/day in hypertensive patients); perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index 18.5 kg/m(2) to 24.9 kg/m(2)) and waist circumference (smaller than 102 cm for men and smaller than 88 cm for women); limit alcohol consumption to no more than 14 units per week in men or nine units per week in women; follow a diet that is reduced in saturated fat and cholesterol, and that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on by the patients global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to lower than 140/90 mmHg in all patients, and to lower than 130/80 mmHg in those 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, 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 (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor antagonists (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as the initial treatment of hypertension if the systolic blood pressure is 20 mmHg above the target or if the diastolic blood pressure is 10 mmHg above the target. The combination of ACE inhibitors and ARBs should not be used. Other agents appropriate for first-line therapy for isolated systolic hypertension include long- acting dihydropyridine CCBs or ARBs. 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/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. 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. VALIDATION 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.

The 2013 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

We updated the evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in adults for 2013. This years update includes 2 new recommendations. First, among nonhypertensive or stage 1 hypertensive individuals, the use of resistance or weight training exercise does not adversely influence blood pressure (BP) (Grade D). Thus, such patients need not avoid this type of exercise for fear of increasing BP. Second, and separately, for very elderly patients with isolated systolic hypertension (age 80 years or older), the target for systolic BP should be < 150 mm Hg (Grade C) rather than < 140 mm Hg as recommended for younger patients. We also discuss 2 additional topics at length (the pharmacological treatment of mild hypertension and the possibility of a diastolic J curve in hypertensive patients with coronary artery disease). In light of several methodological limitations, a recent systematic review of 4 trials in patients with stage 1 uncomplicated hypertension did not lead to changes in management recommendations. In addition, because of a lack of prospective randomized data assessing diastolic BP thresholds in patients with coronary artery disease and hypertension, no recommendation to set a selective diastolic cut point for such patients could be affirmed. However, both of these issues will be examined on an ongoing basis, in particular as new evidence emerges.

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

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 patients 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.

Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study

BACKGROUND The Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk, and it has been found that, despite intensive blood pressure lowering in all risk strata, morbid event rates increased with increasing risk stratum. OBJECTIVES Previously analysed global risk strata were based on combinations of risk factors. The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk, despite good BP control. METHODS Risk ratios (RR) for patients with and those without a risk factor were calculated with 95% confidence intervals (CI) using a Cox proportional hazard model, and adjusted for all variables except the one under examination. RESULTS For all risk factors considered and for all types of event, RR were always greater than 1, indicating a greater risk in the presence, compared with that in the absence of each factor. The male gender was a statistically significant risk for cardiovascular (CV) events, CV and total mortality and particularly for myocardial infarction (MI); age > or = 65 years for CV events, stroke, CV and particularly total mortality; smoking for all events analysed, but particularly for total mortality (twice higher in smokers than in non-smokers); high serum cholesterol (> 6.8 mmol/l) for CV events, MI and CV mortality; high serum creatinine (> 155 micromol/l) for CV events, stroke, CV and total mortality; diabetes for CV events, stroke, total mortality and particularly CV mortality; and ischaemic heart disease for all events analysed. Adjusted RR were often close to or greater than 2. CONCLUSIONS Each of the risk factors considered was found to be an important cause of residual risk, despite good BP control. These findings emphasize the importance of addressing other correctable risk factors, e.g. smoking, hypercholesterolaemia and diabetes, as well as rigorous control of blood pressure, and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest.

Progressive improvement in the structure of resistance arteries of hypertensive patients after 2 years of treatment with an angiotensin i-converting enzyme inhibitor Comparison with effects of a β-blocker

To investigate the effects of antihypertensive drugs on resistance artery structure, 17 essential hypertensive patients were randomly assigned to be treated with an angiotensin I-converting enzyme inhibitor, cilazapril, or a beta-blocker, atenolol, for 2 years. Blood pressure was well controlled throughout the 2 years. Before starting treatment, at the end of the first year and at the end of the second year, patients were subjected to gluteal subcutaneous fat biopsies, from which resistance-size arteries were dissected to be studied. The media width to lumen diameter ratio of arteries from patients in the cilazapril group was 7.5 +/- 0.3% before starting treatment, and decreased significantly (P < .05) to 6.3 +/- 0.2% at the end of the first year, and to 5.8 +/- 0.2% at the end of the second year, at which time it was not different from that of arteries from normotensive subjects (5.2 +/- 0.2%). In patients treated with atenolol, resistance arteries exhibited a media-to-lumen ratio of 8.0 +/- 0.6% before treatment, 8.1 +/- 0.5% after 1 year of treatment, and 7.9 +/- 0.3% at the end of the second year of treatment, all significantly higher (P < .01) than that of arteries from normotensive subjects. Thus, treatment for 2 years with the angiotensin I-converting enzyme inhibitor cilazapril resulted in progressive normalization of the structure (media-to-lumen ratio) of gluteal subcutaneous fat resistance arteries of essential hypertensive patients, whereas there was no change in patients treated with the beta-blocker atenolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of valsartan compared to amlodipine on preventing type 2 diabetes in high-risk hypertensive patients: The VALUE trial

Context Type 2 diabetes is emerging as a major health problem, which tends to cluster with hypertension in individuals at high risk of cardiovascular disease. Objective To test for the first time the hypothesis that treatment of hypertensive patients at high cardiovascular risk with the angiotensin-receptor blocker (ARB) valsartan prevents new-onset type 2 diabetes compared with the metabolically neutral calcium-channel antagonist (CCA) amlodipine. Design Pre-specified analysis in the VALUE trial. Follow-up averaged 4.2 years. The risk of developing new diabetes was calculated as an odds ratio (OR) with 95% confidence intervals (CI) for different definitions of diabetes. Patients A sample of 9995 high-risk, non-diabetic hypertensive patients. Interventions Valsartan or amlodipine with or without add-on medication [hydrochlorothiazide (HCTZ) and other add-ons, excluding other ARBs, angiotensin-converting enzyme (ACE) inhibitors, CCAs]. Main outcome measure New diabetes defined as an adverse event, new blood-glucose-lowering drugs and/or fasting glucose > 7.0 mmol/l. Results New diabetes was reported in 580 (11.5%) patients on valsartan and in 718 (14.5%) patients on amlodipine (OR 0.77, 95% CI 0.69–0.87, P < 0.0001). Using stricter criteria (without adverse event reports) new diabetes was detected in 495 (9.8%) patients on valsartan and in 586 (11.8%) on amlodipine (OR 0.82, 95% CI 0.72–0.93, P = 0.0015). Conclusion Compared with amlodipine, valsartan reduces the risk of developing diabetes mellitus in high-risk hypertensive patients.

The 2006 Canadian Hypertension Education Program recommendations for the management of hypertension: Part II - Therapy

OBJECTIVE To provide updated, evidence-based recommendations for the management of hypertension in adults. OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions, evidence from randomized, controlled trials and systematic reviews of trials was preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. For lifestyle interventions, blood pressure (BP) lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field. For treatment of patients with kidney disease, the development of proteinuria or worsening of kidney function was also accepted as a clinically relevant primary outcome. EVIDENCE MEDLINE searches were conducted from November 2004 to October 2005 to update the 2005 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 content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise four to seven days per week; maintain a healthy body weight (body mass index of 18.5 kg/m2 to 24.9 kg/m2) and waist circumference (less than 102 cm for men and less than 88 cm for women); limit alcohol consumption to no more than 14 standard drinks per week in men or nine standard drinks per week in women; follow a diet that is reduced in saturated fat and cholesterol and that emphasizes fruits, vegetables and low-fat dairy products; restrict salt intake; and consider stress management in selected individuals. Treatment thresholds and targets should take into account each individuals global atherosclerotic risk, target organ damage and comorbid conditions. BP should be lowered to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease (regardless of the degree of proteinuria). Most adults with hypertension require more than one agent to achieve these target BPs. For adults without compelling indications for other agents, initial therapy should include thiazide diuretics. Other agents appropriate for first-line therapy for diastolic hypertension with or without systolic hypertension include beta-blockers (in those younger than 60 years), angiotensin-converting enzyme (ACE) inhibitors (in nonblack patients), long-acting calcium channel blockers or angiotensin receptor antagonists. Other agents for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers or angiotensin receptor antagonists. 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 diabetes mellitus, ACE inhibitors or angiotensin receptor antagonists (or in patients without albuminuria, thiazides or dihydropyridine calcium channel blockers) are appropriate first-line therapies; and in patients with nondiabetic chronic kidney disease, ACE inhibitors are recommended. All hypertensive patients should have their fasting lipids screened, and those with dyslipidemia should be treated using the thresholds, targets and agents recommended by the Canadian Hypertension Education Program Working Group on the management of dyslipidemia and the prevention of cardiovascular disease. Selected patients with hypertension, but without dyslipidemia, should also receive statin therapy and/or acetylsalicylic acid therapy. VALIDATION All recommendations were graded according to strength of the evidence and voted on by the 45 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.

Blunted effects of endothelin upon small subcutaneous resistance arteries of mild essential hypertensive patients.

OBJECTIVE In experimental models of hypertension in the rat, resistance arteries present a blunted response to endothelin, a potent vasoconstrictor peptide. The primary objective of this study was to investigate whether, as in hypertensive rat blood vessels, the response of human resistance arteries to endothelin was altered in essential hypertensive patients, in order to further understand the possible physiopathological involvement of this peptide in human hypertension. DESIGN Normotensive male subjects and sex- and age-matched mild essential hypertensive patients who had not received antihypertensive drugs for more than 6 months were investigated. METHODS Small arteries were dissected from gluteal subcutaneous biopsies and mounted on a wire-myograph. Blood vessels were measured and dose-response curves to different agents tested. RESULTS The external diameter of blood vessels of the hypertensive patients tended to be smaller and the width of their media tended to be thicker, but the cross-sectional area of the wall was similar in both groups. Lumen diameters were significantly smaller in hypertensives and the media:lumen ratio was significantly increased in hypertensive patients. Active tension responses and sensitivity to norepinephrine, arginine vasopressin and angiotensin II were similar in both groups, but calculated active pressure responses were enhanced in hypertensives due to the smaller blood vessel lumen. Tension responses to endothelin-1 at increasing concentrations of 0.1 to 100 nmol/l were lower in hypertensive patients, but the calculated transmural active pressure developed was not significantly different at or above 10 nmol/l. CONCLUSION These results suggest that gluteal subcutaneous small resistance arteries of male essential hypertensive patients exhibit a decrement in responsiveness to endothelin-1. The altered design of the hypertensive blood vessels enhanced calculated pressure responses, which may contribute to the maintenance of elevated blood pressure.

Role of Tumor Necrosis Factor-α Gene Locus in Obesity and Obesity-Associated Hypertension in French Canadians

Obesity represents a serious risk factor for the development of cardiovascular diseases, including hypertension. Segregation studies suggest that obesity and obesity-associated hypertension may share some genetic determinants. The results of the present candidate gene investigation suggest that in hypertensive pedigrees of French-Canadian origin, one such determinant is the tumor necrosis factor (TNF)-alpha gene locus. Gender-pooled quantitative sib-pair analysis demonstrated a significant effect of the gene locus on 3 global and 7 regional measures of obesity (P=0.05 to 0.0004). Gender-separate quantitative sib-pair analyses showed that the impact of the locus on obesity is most significant in the abdominal region in men and in the thigh region in women. Furthermore, the haplotype relative-risk test demonstrated a significant association between the TNF-alpha gene locus and both obesity (P=0.006) and obesity-associated hypertension (P=0.02). These effects were most significant in individuals with nonmorbid obesity. In conclusion, the results of linkage and association analyses suggest that in hypertensive pedigrees of French-Canadian origin, the TNF-alpha gene locus contributes to the determination of obesity and obesity-associated hypertension. In addition, the data indicate that gender modifies the effect of the locus on the regional distribution of body fat.

HypertensionThe 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 2 – therapyLes recommandations de 2009 du Programme d’éducation canadien sur l’hypertension pour la prise en charge de l’hypertension : 2e partie – le traitement

OBJECTIVE To provide updated, evidence-based recommendations for the prevention and management of hypertension in adults. OPTIONS AND OUTCOMES 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. EVIDENCE 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. RECOMMENDATIONS 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 individuals 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. VALIDATION 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.