Hypertension: Larochelle P

Khan NA, Hemmelgarn B, Herman RJ, Bell CM, Mahon JL, Leiter LA, Rabkin SW, Hill MD, Padwal R, Touyz RM, Larochelle P, Feldman RD, Schiffrin EL, Campbell NR, Moe G, Prasad R, Arnold MO, Campbell TS, Milot A, Stone JA, Jones C, Ogilvie RI, Hamet P, Fodor G, Carruthers G, Burns KD, Ruzicka M, DeChamplain J, Pylypchuk G, Petrella R, Boulanger JM, Trudeau L, Hegele RA, Woo V, McFarlane P, Vallée M, Howlett J, Bacon SL, Lindsay P, Gilbert RE, Lewanczuk RZ, Tobe S, Anonymous00150. · Division of General Internal Medicine, University of British Columbia, Vancouver, Canada. · Can J Cardiol. · Pubmed #19417859 No free full text.

Abstract: 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 patient's 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.

Khan NA, Hemmelgarn B, Padwal R, Larochelle P, Mahon JL, Lewanczuk RZ, McAlister FA, Rabkin SW, Hill MD, Feldman RD, Schiffrin EL, Campbell NR, Logan AG, Arnold M, Moe G, Campbell TS, Milot A, Stone JA, Jones C, Leiter LA, Ogilvie RI, Herman RJ, Hamet P, Fodor G, Carruthers G, Culleton B, Burns KD, Ruzicka M, deChamplain J, Pylypchuk G, Gledhill N, Petrella R, Boulanger JM, Trudeau L, Hegele RA, Woo V, McFarlane P, Touyz RM, Tobe SW, Anonymous00039. · Division of General Internal Medicine, University of British Columbia, Vancouver, British Columbia. · Can J Cardiol. · Pubmed #17534460 links to  free full text

Abstract: 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 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. 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.

Khan NA, McAlister FA, Rabkin SW, Padwal R, Feldman RD, Campbell NR, Leiter LA, Lewanczuk RZ, Schiffrin EL, Hill MD, Arnold M, Moe G, Campbell TS, Herbert C, Milot A, Stone JA, Burgess E, Hemmelgarn B, Jones C, Larochelle P, Ogilvie RI, Houlden R, Herman RJ, Hamet P, Fodor G, Carruthers G, Culleton B, Dechamplain J, Pylypchuk G, Logan AG, Gledhill N, Petrella R, Tobe S, Touyz RM, Anonymous00012. · Division of General Internal Medicine, University of British Columbia, Vancouver, BC, Canada. · Can J Cardiol. · Pubmed #16755313 links to  free full text

Abstract: 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 individual's 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.

Khan NA, McAlister FA, Lewanczuk RZ, Touyz RM, Padwal R, Rabkin SW, Leiter LA, Lebel M, Herbert C, Schiffrin EL, Herman RJ, Hamet P, Fodor G, Carruthers G, Culleton B, DeChamplain J, Pylypchuk G, Logan AG, Gledhill N, Petrella R, Campbell NR, Arnold M, Moe G, Hill MD, Jones C, Larochelle P, Ogilvie RI, Tobe S, Houlden R, Burgess E, Feldman RD, Anonymous00237. · Division of General Internal Medicine, University of British Columbia, Vancouver, Canada. · Can J Cardiol. · Pubmed #16003449 links to  free full text

Abstract: 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. While changes in cardiovascular morbidity and mortality were the primary outcomes of interest, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity/mortality data in this field, and for certain comorbid conditions, other relevant outcomes, such as development of proteinuria or worsening of kidney function, were considered. EVIDENCE: MEDLINE searches were conducted from November 2003 to October 2004 to update the 2004 recommendations. Reference lists were scanned, experts were contacted, and the personal files of the subgroup members and authors were used to identify additional published studies. All relevant articles were reviewed and appraised independently, using prespecified levels of evidence, by content and methodology experts. As per previous years, only studies that had been published in the peer-reviewed literature were included; evidence from abstracts, conference presentations and unpublished personal communications was not included. RECOMMENDATIONS: Lifestyle modifications to prevent and/or treat hypertension include the following: perform 30 min to 60 min of aerobic exercise on four to seven days of the 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 units per week in men or nine units per week in women; follow a reduced fat, low cholesterol diet with an adequate intake of potassium, magnesium and calcium; restrict salt intake; and consider stress management (in selected individuals). 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 140/90 mmHg or less in all patients, and to 130/80 mmHg or less in those with diabetes mellitus or chronic kidney disease. Most adults with hypertension require more than one agent to achieve target blood pressures. 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 (except in black patients), long-acting calcium channel blockers and angiotensin receptor antagonists. Other agents appropriate for first-line therapy for isolated systolic hypertension include long-acting dihydropyridine calcium channel blockers and 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 thiazides in patients with diabetes mellitus without albuminuria) 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 the strength of the evidence and voted on by the 43 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.

McAlister FA, Zarnke KB, Campbell NR, Feldman RD, Levine M, Mahon J, Grover SA, Lewanczuk R, Leenen F, Tobe S, Lebel M, Stone J, Schiffrin EL, Rabkin SW, Ogilvie RI, Larochelle P, Jones C, Honos G, Fodor G, Burgess E, Hamet P, Herman R, Irvine J, Culleton B, Wright JM, Anonymous00074. · University of Alberta Hospital, Edmonton, Canada. · Can J Cardiol. · Pubmed #12107420 links to  free full text

Abstract: OBJECTIVE: To provide updated, evidence-based recommendations for the therapy of hypertension in adults. OPTIONS: For patients with hypertension, a number of antihypertensive agents may control blood pressure. Randomized trials evaluating first-line therapy with thiazides, beta-adrenergic antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, alpha-blockers, centrally acting agents or angiotensin II receptor antagonists were reviewed. OUTCOMES: The health outcomes that were considered were changes in blood pressure, cardiovascular morbidity, and cardiovascular and/or all-cause mortality rates. Economic outcomes were not considered due to insufficient evidence. EVIDENCE: MEDLINE was searched for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension. Reference lists were scanned, experts were polled, and the personal files of the subgroup members and authors were used to identify other published studies. All relevant articles were reviewed and appraised, using prespecified levels of evidence, by content experts and methodological experts. VALUES: A high value was placed on the avoidance of cardiovascular morbidity and mortality. BENEFITS, HARMS AND COSTS: Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension. In certain settings, and for specific classes of drugs, blood-pressure lowering has been associated with reduced cardiovascular morbidity and/or mortality. RECOMMENDATIONS: The present document contains detailed recommendations pertaining to treatment thresholds, target blood pressures, and choice of agents in various settings in patients with hypertension. The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus, the amalgamation of the previous sections on treatment of hypertension in the young and old into one section, increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke. Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk, the presence and/or absence of target organ damage, and comorbidities. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group. Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation. Only those recommendations achieving high levels of consensus are reported here. These guidelines will continue to be updated annually.

Campbell NR, Leiter LA, Larochelle P, Tobe S, Chockalingam A, Ward R, Morris D, Tsuyuki R. · Department of Medicine, University of Calgary, Calgary, Canada. · Can J Cardiol. · Pubmed #19417860 No free full text.

Abstract: The Canadian Hypertension Education Program, Blood Pressure Canada, Canadian Hypertension Society, Heart and Stroke Foundation of Canada, Canadian Diabetes Association, College of Family Physicians of Canada, Canadian Pharmacists Association and the Canadian Council of Cardiovascular Nurses call on Canadian health care professionals to redouble efforts to help patients achieve treatment targets (blood pressure less than 130 mmHg systolic and less than 80 mmHg diastolic) in people with diabetes. Treatment of high blood pressure in people with diabetes results in large reductions in death and disability within a short period of time and needs to be a therapeutic priority. Achieving blood pressure targets requires sustained lifestyle modification, and three or more drugs including a diuretic are often required. Antihypertensive treatment in people with diabetes is one of the few medical treatments estimated to reduce overall health costs. The cost of treatment is less than the cost of complications prevented. Blood pressure needs to be assessed at all visits and home blood pressure assessment is encouraged. Management strategies need to include assessment and management of cardiovascular risks including smoking, unhealthy eating, physical inactivity, abdominal obesity, dyslipidemia as well as dysglycemia. The risks and benefits of acetylsalicylic acid in primary prevention of cardiovascular disease are uncertain in people with hypertension and diabetes. Intensive individualized lifestyle modification is recommended to prevent and treat hypertension, dyslipidemia, dysglycemia and other vascular risks in people with diabetes.

Khan NA, Hemmelgarn B, Herman RJ, Rabkin SW, McAlister FA, Bell CM, Touyz RM, Padwal R, Leiter LA, Mahon JL, Hill MD, Larochelle P, Feldman RD, Schiffrin EL, Campbell NR, Arnold MO, Moe G, Campbell TS, Milot A, Stone JA, Jones C, Ogilvie RI, Hamet P, Fodor G, Carruthers G, Burns KD, Ruzicka M, dechamplain J, Pylypchuk G, Petrella R, Boulanger JM, Trudeau L, Hegele RA, Woo V, McFarlane P, Vallée M, Howlett J, Katzmarzyk P, Tobe S, Lewanczuk RZ, Anonymous00046. · Division of General Internal Medicine, University of British Columbia, Vancouver, Canada. · Can J Cardiol. · Pubmed #18548143 links to  free full text

Abstract: OBJECTIVE: To update the evidence-based recommendations for the prevention and management of hypertension in adults. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, evidence was preferentially 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. 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 2006 to August 2007 to update the 2007 recommendations. To identify additional published studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium intake to less than 100 mmol/day (and 65 mmol/day 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 one 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 patient's 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. 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 nonblack patients), 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 for initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. 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 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 but 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.

Karas M, Lacourcière Y, LeBlanc AR, Nadeau R, Dubé B, Florescu M, Lamarre-Cliche M, Poirier L, Larochelle P, de Champlain J. · Institut de Recherches Cliniques de Montréal, Canada. · J Hypertens. · Pubmed #15894902 No free full text.

Abstract: OBJECTIVE: To determine the effects of 8 weeks of therapy with amlodipine, ramipril or telmisartan on the autonomic system over 24 h in hypertensives. METHODS: After a placebo run-in, 57 patients were included in a prospective randomized open-label design protocol for therapy with amlodipine (5 mg for 4 weeks followed by 10 mg for 4 weeks, n = 22), or ramipril (2.5 mg for 1 week, 5.0 mg for 3 weeks and 10 mg for 4 weeks, n = 17) or telmisartan (80 mg for 8 weeks, n = 18). Autonomic functions were assessed by norepinephrine (NE) and epinephrine (E), as well as by the spectral analysis of heart rate variability (HRV). RESULTS: The 24-h ambulatory blood pressure, plasma NE and HRV demonstrated the characteristic day-night circadian rhythm in hypertensives. Higher values for SBP and DBP and for NE levels, as well as for spectral analysis components - low frequency band (LF) and low frequency/high frequency (LF/HF) ratio - were found during the day, whereas the HF was higher during the night. In patients treated with amlodipine, the HF decreased significantly during the night, while the LF and the LF/HF ratio increased during the day in association with the rise in NE. The therapy with telmisartan did increase the HF during the night and the day, while ramipril did not influence all HRV components during the night but significantly increased the HF, and decreased the LF/HF ratio during the day. No changes were observed in plasma NE with telmisartan or ramipril, but a 50% increase in NE levels throughout the 24-h period was found in amlodipine-treated patients. CONCLUSION: These data suggest a sympathetic activation during the day and a decrease in parasympathetic activity during the night after therapy with amlodipine, correlated with increases in plasma NE. In contrast, the therapy with telmisartan significantly increased parasympathetic activity without changes in NE during the night and day. The therapy with ramipril increased the parasympathetic activity only during the day.

Poirier L, de Champlain J, Larochelle P, Lamarre-Cliche M, Lacourcière Y. · Unité d'hypertension, Centre Hospitalier de l'Université Laval, Université Laval, 2705 Boulevard Laurier S-120-A, Sainte-Foy, Quebec, Canada G1V 4G2. · Blood Press Monit. · Pubmed #15472494 No free full text.

Abstract: OBJECTIVES: The aim of the study was to compare the antihypertensive effects and the duration of action of telmisartan, amlodipine and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure (ABP) monitoring. METHODS: After a 2-4-week single-blind, placebo run-in period, qualifying patients were randomized to receive telmisartan 80 mg (n=18); amlodipine 5 mg (n=22); titrated to 10 mg after 4 weeks; or ramipril 2.5 mg (n=17); titrated to 5 mg and 10 mg after 1 and 3 weeks, respectively, administered once daily in the morning (0700 h). Ambulatory blood pressure monitoring was performed at baseline and at the end of the 8-week treatment period. Plasma renin activity was measured over 24 h at the same time points. RESULTS: Telmisartan and amlodipine provided significant reductions from baseline (P<0.0001) and not statistically different reductions between treatments in ABP during daytime (9.3/6.0 and 14.7/9.4 mmHg, respectively) and night-time (12.4/7.7 and 13.3/8.6 mmHg, respectively) at the end of 8 weeks' treatment. In contrast, although ramipril provided significant reductions in ambulatory systolic and diastolic BP from 2-6 h post dose (peak effect), it failed to induce significant reductions in mean daytime (4.5/1.6 mmHg) and night-time (1.8/0.1 mmHg) ambulatory BP. In addition, the greater reductions in ABP with telmisartan and amlodipine were associated with a significant rise in plasma renin activity whereas ramipril only increased renin during the first 4 h of the administration interval. CONCLUSION: The results of the present study confirm the efficacy of both telmisartan and amlodipine in reducing ABP during each period of the 24-h interval. Because ABP reduction with ramipril was restricted to its peak effect, the present data do not support the use of this agent when administered once daily in the morning.

Kostis JB, Cobbe S, Johnston C, Ford I, Murphy M, Weber MA, Black HR, Plouin PF, Levy D, Mancia G, Larochelle P, Kolloch RE, Alderman M, Ruilope LM, Dahlöf B, Flack JM, Wolf R, Anonymous00007. · University of Medicine and Dentistry of New Jersey--Robert Wood Johnson Medical School, New Brunswick 08903-0019, USA. · Am J Hypertens. · Pubmed #11863257 No free full text.

Abstract: The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.

Zanchetti A, Hansson L, Dahlöf B, Elmfeldt D, Kjeldsen S, Kolloch R, Larochelle P, McInnes GT, Mallion JM, Ruilope L, Wedel H. · Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Ospedale Maggiore and Istituto Auxologico Italiano. · J Hypertens. · Pubmed #11403365 No free full text.

Abstract: 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.

Kjeldsen SE, McInnes GT, Mancia G, Hua TA, Julius S, Weber MA, Coca A, Girerd X, Jamerson K, Larochelle P, Macdonald T, Schmieder RE, Anthony Schork M, Viskoper R, Widimsky J, Zanchetti A. · Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA. · Blood Press. · Pubmed #18608200 No free full text.

Abstract: We have previously shown that the angiotensin receptor blocker valsartan is associated with a lower incidence of new-onset type 2 diabetes than that with the calcium-channel antagonist amlodipine in the treatment of hypertensive patients at high cardiovascular risk. We have now investigated the benefits of valsartan vs amlodipine in patients of different categories of diabetogenic risk. Some 9995 patients without diabetes at onset participated in VALUE, with average follow-up of 4.2 years. Predictors of new diabetes were analyzed by stepwise logistic regression. A diabetes risk score for each patient was calculated based on a multivariate model. The risk of developing new diabetes in quartiles of risk for the disease was calculated as an odds ratio (OR) with 95% confidence intervals (CI). New diabetes was reported in 580 (11.5%) patients on valsartan and in 718 (14.5%) patients on amlodipine (p<0.0001). There was a more than sevenfold rise in the development of new diabetes from the lowest to the highest quartile of risk. When study treatment was included in the risk model, the odds in favor of valsartan in preventing new diabetes progressively increased with higher risk. Fifty-two (4.03%) patients developed diabetes on valsartan and 50 (4.14%) patients on amlodipine in the lowest quartile of risk, 73 (5.70%) patients on valsartan and 83 (6.81%) patients on amlodipine in the second quartile, and 126 (10.27%) patients on valsartan and 160 (12.58%) patients on amlodipine in the third quartile. The difference between treatments was highly significant in quartile 4 with 329 (26.68%) patients developing new diabetes on valsartan vs 425 (33.57%) patients on amlodipine (OR = 0.72, 95% CI 0.61-0.86, p = 0.0002). The number of patients needed for treatment for the duration of the trial in order to gain the benefit of valsartan over amlodipine in preventing one new case of diabetes was 43 in the third quartile and 15 in the fourth quartile of risk categories. We conclude that valsartan compared with amlodipine reduces the risk of developing diabetes mellitus, particularly in hypertensive patients with the highest susceptibility for development of diabetes.

Karas M, Larochelle P, LeBlanc RA, Dubé B, Nadeau R, Champlain J. · Institut de Recherches Cliniques de Montréal, Research Laboratory on the Autonomic Nervous System, Faculty of Medicine, Université de Montréal, Montréal, Canada. · J Clin Hypertens (Greenwich). · Pubmed #18256574 No free full text.

Abstract: The effect of age on autonomic nervous system was assessed at rest and while standing using systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate, and power spectral analysis of the time duration between 2 consecutive R waves of an electrocardiogram (RR) interval variability, as well as on plasma norepinephrine and epinephrine levels in mild to moderate hypertensive patients (DBP, 90-110 mm Hg). Patients younger than 60 years (n=57) and older than 60 years (n=32), were evaluated after a 3- to 4-week placebo period. Plasma catecholamines were measured in the supine position at rest and after 10 minutes of standing. Power spectral analysis of the RR interval variability was performed in each condition using the high-frequency (HF) band (0.15-0.4 Hz) as an index of parasympathetic activity and the low-frequency (LF) band (0.05-0.15 Hz) and LF-HF ratio to estimate sympathetic activity. The total power was calculated as the sum of LF and HF power. supine SBP was significantly higher in older patients (P<.05). SBP and DBP increased significantly only in younger patients during standing (P<.05), while the changes were smaller and nonsignificantly lower in older patients. HR was similar in both groups at rest and increased similarly during standing. Norepinephrine and epinephrine levels were similar at rest and increased similarly in both groups of patients during standing. At rest, lower LF and HF components were observed in older patients. The LF component increased less and the HF component decreased less in older patients during standing. A lower sympathetic and parasympathetic basal cardiac tone was observed at rest in older hypertensive patients. Moreover, reduced hemodynamic and sympathetic responses to standing as assessed by SBP, DBP, and the LF component of HR variability were observed in older hypertensives in the presence of a normal catecholamine response. These observations could reflect a decreased sensitivity of cardiac beta-adrenoceptors with aging.

de Champlain J, Karas M, Assouline L, Nadeau R, LeBlanc AR, Dubé B, Larochelle P. · Institut de Recherches Cliniques de Montréal, Faculty of Medicine, Université de Montréal, Sacré-Coeur Hospital, Québec, Canada. · J Clin Hypertens (Greenwich). · Pubmed #17341993 No free full text.

Abstract: To compare the effects of valsartan and amlodipine alone or in combination on plasma norepinephrine (NE) at rest and standing for 10 minutes in patients with hypertension, 47 patients with a sitting diastolic blood pressure (BP) (DBP)>95 mm Hg and<110 mm Hg were randomized in a double-blind fashion to either valsartan or amlodipine. During the first 4 weeks of treatment, patients received a low dose of either valsartan (80 mg) or amlodipine (5 mg). The patients were force-titrated to the high dose of either drug (160 or 10 mg) for 4 weeks. After 8 weeks of therapy, those who still had a DBP>90 mm Hg (nonresponders) received combination therapy with the other drug, whereas patients with a DBP<90 mm Hg (responders) continued on monotherapy. Decreases in ambulatory BP and clinic systolic BP and DBP were significant (P<.05) after 8 weeks' therapy with no difference between the 2 groups. Amlodipine but not valsartan as monotherapy consistently increased NE levels at rest and enhanced NE levels during standing. Valsartan decreased basal NE in responders. Combination therapy with valsartan and amlodipine did not attenuate the rise in NE levels induced by amlodipine. This study indicates that therapy with amlodipine increases peripheral sympathetic basal tone and reactivity to standing in patients with hypertension, whereas valsartan does not. Combined therapy with amlodipine/valsartan did not attenuate the sympathetic activation induced by amlodipine. The hypotensive action of valsartan may be mediated in part by an inhibition of the sympathetic baroreflex in patients with hypertension.

Kjeldsen SE, Julius S, Mancia G, McInnes GT, Hua T, Weber MA, Coca A, Ekman S, Girerd X, Jamerson K, Larochelle P, MacDonald TM, Schmieder RE, Schork MA, Stolt P, Viskoper R, Widimský J, Zanchetti A, Anonymous00204. · Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, Michigan, USA. · J Hypertens. · Pubmed #16794491 No free full text.

Abstract: 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.

Lamarre-Cliche M, de Champlain J, Lacourcière Y, Poirier L, Karas M, Larochelle P. · Institut de Recherches Cliniques de Montréal (IRCM), Canada. · Am J Hypertens. · Pubmed #15691618 No free full text.

Abstract: BACKGROUND: The aldosterone-to-renin ratio (ARR) is frequently used to screen primary hyperaldosteronism. This study, part of a clinical trial, was designed to measure the influence of circadian rhythms, antihypertensive drugs, and body posture on plasma renin, on aldosterone, and on their interrelation. METHODS: In a prospective, randomized, open-label, parallel-designed protocol, 57 essential hypertensives (41 men, 16 women) were randomized to a morning dose of telmisartan (80 mg), ramipril (10 mg), or amlodipine (10 mg) for 8 weeks. At baseline and after 8 weeks of therapy, blood pressure (BP), plasma renin (in nanograms per liter), and plasma aldosterone (in picomoles per liter) concentrations were assessed in the supine position every 4 h for 24 h and after 10 min of standing at 9 am. RESULTS: There was no significant association between renin, aldosterone, the ARR and demographic factors, or BP. Circadian variations of plasma renin and aldosterone were clearly present. Aldosterone variations were of greater relative amplitude with earlier-occurring peaks than renin. The ARR exhibited statistically and clinically significant circadian variations with the low and peak values averaging 55.9 +/- 32.3 and 161.84 +/- 85.4 pmol/L/ng/dL, respectively. Telmisartan, ramipril, and amlodipine significantly decreased the ARR. Telmisartan had the greatest influence on the ARR. Posture had a clinically significant but statistically nonsignificant effect on the ARR. CONCLUSIONS: Renin, aldosterone, and their interrelation are influenced by circadian rhythms, telmisartan, ramipril, and amlodipine in patients with essential hypertension. Telmisartan has a greater impact on these parameters than ramipril and amlodipine. Measurement of the ARR in treated hypertensive patients should take these influences into account.

Lamarre-Cliche M, Lacourcière Y, de Champlain J, Poirier L, Larochelle P. · Department of Clinical Pharmacology, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Montréal, Qc, Canada. · Heart Dis. · Pubmed #12877758 No free full text.

Abstract: The QT interval corrected for heart rate (QTc) is believed to reflect sympathovagal balance. It has also been established that beta-blockers and dihydropyridine-type calcium channel blockers (DHPCCB) influence the autonomic nervous system. This study tested the hypothesis that QTc interval length is a predictor of the blood pressure reduction induced by beta1-selective beta-blockers or DHPCCB. The predictive values of pretreatment heart rate and of the heart rate change with therapy were also evaluated. The authors conducted an historical reanalysis of 5 clinical trials that looked at the antihypertensive effects of beta-blockers (nebivolol) or DHPCCB (amlodipine, felodipine, isradipine, nifedipine). Correlation and quintile analyses were performed to measure the association between QTc interval, heart rate, or heart rate change and therapeutic blood pressure response. Separate analyses were undertaken for beta-blockers and DHPCCB. Seventy-three and 98 hypertensive subjects respectively were included in the beta-blocker and DHPCCB analyses. QTc interval, pretreatment heart rate, and heart rate change with therapy were not associated with therapeutic blood pressure response. In this study, QTc interval length, pretreatment heart rate, and heart rate change with therapy were not good predictors of the blood pressure response to beta1-selective beta-blockers or DHPCCB in hypertensive subjects.