Luc Poirier

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.

Captopril or conventional therapy in hypertensive type II diabetics. Three-year analysis.

The effects of long-term treatment with captopril and conventional therapy on albuminuria and metabolic parameters were compared in 74 hypertensive type II diabetics with normal serum creatinine. Patients were treated double-blind with either captopril monotherapy or combined with hydrochlorothiazide or therapy with metoprolol, hydrochlorothiazide, or both for 36 months. The treatment was titrated to achieve goal diastolic blood pressure of < or = 85 mm Hg. The reductions in blood pressures during treatment were similar in patients with (n = 21) and without (n = 53) microalbuminuria treated with either captopril or conventional therapy. No significant changes in albuminuria occurred in normoalbuminuric patients with either therapy. Although albuminuria fell in nearly all patients with microalbuminuria treated with captopril, it rose in eight of 12 patients on conventional therapy, with macroalbuminuria developing in two of them. Renal function was preserved by both types of treatment in both patient groups. Long-term treatment with either conventional therapy or captopril did not alter metabolic variables. We conclude that captopril alone or in combination decreases albuminuria and prevents the development of macroalbuminuria in hypertensive type II diabetics with persistent microalbuminuria. The renoprotective effect of this agent, however, remains to be demonstrated with longer term data on renal function. Aggressive antihypertensive treatment with either captopril or conventional therapy appears to be effective in preventing the onset of microalbuminuria in most normoalbuminuric patients. In contrast, with previous short-term studies, the use of converting enzyme inhibitors or conventional therapy did not cause adverse metabolic effects.

Effects of nebivolol and atenolol on insulin sensitivity and haemodynamics in hypertensive patients.

Objectives To compare the effects of nebivolol and atenolol in 25 ambulatory hypertensive patients with impaired glucose tolerance. Design Clinic and ambulatory blood pressure, insulin sensitivity (euglycemic-hyperinsulinemic clamp), glucose tolerance (intravenous glucose tolerance test), systemic and regional haemodynamics were measured after 4 weeks of placebo and after each 16-week treatment period in a double-blind, crossover fashion. Results Nebivolol and atenolol similarly reduced (P < 0.001) clinic and ambulatory blood pressure by approximately 15/10 mmHg, systolic and diastolic. Clinic and ambulatory heart rate was reduced to a greater extent (P < 0.01) by atenolol than nebivolol. Atenolol was associated with an approximately 20% reduction in insulin sensitivity (insulin-induced glucose disposal rate/mean insulin concentration ratio, P < 0.01) and an approximately 10% reduction in glucose disappearance rate (K- value, P < 0.05), whereas these variables were not significantly modified with nebivolol. Cardiac output was reduced similarly (P < 0.05) by both drugs at rest but forearm blood flow, forearm vascular resistance or total peripheral resistance were unaffected. A significant inverse correlation coefficient between cardiac output and insulin sensitivity was found at baseline, suggesting that a compensatory increase in systemic blood flow occurs in hypertensive patients with progressively more marked insulin resistance. This relationship was unaffected by nebivolol but was lost with atenolol. Conclusions These results indicate that insulin sensitivity was not modified significantly by nebivolol, whereas it was reduced by atenolol, although blood pressure was decreased to the same extent by both drugs. Neither drug induced systemic or forearm vasodilatation but the inverse relationship between cardiac output and insulin sensitivity was preserved with nebivolol but not with atenolol.

Effect of the renin-angiotensin system or calcium channel blockade on the circadian variation of heart rate variability, blood pressure and circulating catecholamines in hypertensive patients.

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.

Comparative Effects of a New Cardioselective Beta‐Blocker Nebivolol and Nifedipine Sustained‐Release on 24‐Hour Ambulatory Blood Pressure and Plasma Lipoproteins

This double‐blind, parallel‐group study compared the effects of Nebivolol, a novel cardioselective β‐blocker, with those of nifedipine sustained‐release on 24‐hour ambulatory blood pressure and plasma lipoprotein levels. After a washout period of 8 weeks, 51 patients with mild to moderate essential hypertension were randomized to double‐blind treatment with either nebivolol 5 mg once a day (n = 26) or nifedipine sustained‐release 20 mg bid (n = 25) over a period of 12 weeks. Both treatments produced similar and significant (P = .0001) reduction in office blood pressure as well as in 24‐hour, work, awake, and sleep ambulatory blood pressure. The clinical response (diastolic blood pressure < 90 mmHg or decreased by ≥10 mmHg) rate was 69% for nebivolol and 59% for nifedipine, respectively. Moreover, the nebivolol and nifedipine treatment‐induced decreases in mean 24‐hour ambulatory blood pressure were similar to the decreases in clinic blood pressure. Furthermore, the percentages of “blood pressure loads” (awake > 140/90 mmHg and asleep > 120/80 mmHg) were lowered significantly (P = .0001), from 60% to 29% with nebivolol and from 60% to 39% with nifedipine. Mean ambulatory heart rate was reduced (P = .0001) from 79 ± 7 to 68 ± 7 beats/minute during nebivolol therapy and from 80 ± 9 to 79 ± 7 (not significant) with nifedipine. Total plasma cholesterol and low‐density lipoprotein levels decreased significantly (P < .05) by 5 and 8%, respectively, after nebivolol treatment, and each decreased by 3% after nifedipine treatment. The results showed that both drugs controlled blood pressure during the 24‐hour period and seemed devoid of untoward effects on lipid profile.

Antihypertensive effect of isradipine administered once or twice daily on ambulatory blood pressure

The antihypertensive efficacy of sustained-release isradipine administered once daily compared to the immediate-release formulation administered twice daily was assessed by ambulatory blood pressure (BP) monitoring in a double-blind randomized crossover study in 76 mild-to-moderate hypertensive patients. Conventional BP and heart rate parameters were evaluated after a 4-week placebo period and patients qualified for entry if sitting diastolic BP was between 95 and 114 mm Hg. Ambulatory BP monitoring was measured at baseline and after active treatment with both formulations. The 2 regimens induced a significant and almost identical reduction (p less than 0.001) in the mean 24-hour BP without affecting heart rate. Isradipine was more effective in patients whose clinical hypertension was confirmed by ambulatory BP monitoring (35) than in patients who remained normotensive by ambulatory BP monitoring criteria (41). The isradipine-treated ambulatory hypertensive group experienced significantly greater decreases in BP during 24-hour, work, awake and sleep periods than did the ambulatory normotensive group. These data suggest that sustained-release isradipine has a sustained antihypertensive effect throughout 24 hours comparable to that of isradipine given twice daily and may improve compliance with long-term treatment. In addition, the results confirm the usefulness of ambulatory BP monitoring in determining truly hypertensive patients likely to respond to drug administration.

2010 Canadian Hypertension Education Program (CHEP) recommendations: The scientific summary – an update of the 2010 theme and the science behind new CHEP recommendations

The present article is a summary of the theme, the key recommendations for management of hypertension and the supporting clinical evidence of the 2010 Canadian Hypertension Education Program (CHEP). In 2010, CHEP emphasizes the need for health care professionals to stay informed about hypertension through automated updates at www.htnupdate.ca. A new interactive Internet-based lecture series will be available in 2010 and a program to train community hypertension leaders will be expanded. Patients can also sign up to receive regular updates in a pilot program at www.myBPsite.ca. In 2010, the new recommendations include consideration for using automated office blood pressure monitors, new targets for dietary sodium for the prevention and treatment of hypertension that are aligned with the national adequate intake values, and recommendations for considering treatment of selected hypertensive patients at high risk with calcium channel blocker/angiotensin-converting enzyme inhibitor combinations and the use of angiotensin receptor blockers.

Antihypertensive effects of amlodipine and hydrochlorothiazide in elderly patients with ambulatory hypertension

Recent studies and authorities have advocated the use of low-dose thiazide diuretics as first-line treatment agents in elderly hypertensives. However, these recommendations were based solely on blood pressure (BP) measured in the clinic. The objective of the present 32-week double-blind study was to compare the effects of hydrochlorothiazide (HCTZ) and amlodipine (AML) in elderly patients with confirmed ambulatory hypertension. After a 4-week placebo washout period, 42 (25 men, 17 women) patients (mean age, 69 years) with clinic sitting diastolic BP of 95 to 114 mm Hg and daytime ambulatory diastolic BP of > or = 90 mm Hg were randomized double-blind to receive AML 5 to 10 mg (n = 21) or HCTZ 12.5 to 25 mg (n = 21) once daily. After 8 weeks of monotherapy, patients in whom clinic diastolic BP remained > or = 90 mm Hg were given combination therapy with the other agent. Amlodipine monotherapy induced significant reductions in clinic, mean 24-h, daytime and sleep systolic/diastolic BPs whereas only clinic BP decreased significantly in patients treated with HCTZ monotherapy. Moreover, 19/21 versus 8/21 patients on AML and HCTZ monotherapies achieved adequate BP control. At the end of the 32-week treatment period, combination therapy in the HCTZ group resulted in statistically significant reductions in clinic as well as in 24-h, daytime and sleep ambulatory BPs that were similar to those observed in the AML monotherapy group. In conclusion, the administration of AML monotherapy induced significant reductions in both clinic and ambulatory BPs in elderly patients whereas only clinic BP was significantly decreased by HCTZ monotherapy. Moreover, the addition of AML to HCTZ in patients inadequately controlled by monotherapy has permitted statistically significant decrements in clinic as well as in ambulatory BP. Consequently, the results of the present study suggest that the use of HCTZ in doses of up to 25 mg daily is inadequate for ambulatory BP control in the elderly despite official recommendations.