Hypertension Canada's 2018 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults and Children.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension in adults and children. This year, the adult and pediatric guidelines are combined in one document. The new 2018 pregnancy-specific hypertension guidelines are published separately. For 2018, 5 new guidelines are introduced, and 1 existing guideline on the blood pressure thresholds and targets in the setting of thrombolysis for acute ischemic stroke is revised. The use of validated wrist devices for the estimation of blood pressure in individuals with large arm circumference is now included. Guidance is provided for the follow-up measurements of blood pressure, with the use of standardized methods and electronic (oscillometric) upper arm devices in individuals with hypertension, and either ambulatory blood pressure monitoring or home blood pressure monitoring in individuals with white coat effect. We specify that all individuals with hypertension should have an assessment of global cardiovascular risk to promote health behaviours that lower blood pressure. Finally, an angiotensin receptor-neprilysin inhibitor combination should be used in place of either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in individuals with heart failure (with ejection fraction < 40%) who are symptomatic despite appropriate doses of guideline-directed heart failure therapies. The specific evidence and rationale underlying each of these guidelines are discussed.

Regulating the UAS/GAL4 system in adult Drosophila with Tet-off GAL80 transgenes.

The UAS/GAL4 system is the most used method in Drosophila melanogaster for directing the expression of a gene of interest to a specific tissue. However, the ability to control the temporal activity of GAL4 with this system is very limited. This study constructed and characterized Tet-off GAL80 transgenes designed to allow temporal control of GAL4 activity in aging adult muscles. By placing GAL80 under the control of a Tet-off promoter, GAL4 activity is regulated by the presence or absence of tetracycline in the diet. Almost complete inhibition of the expression of UAS transgenes during the pre-adult stages of the life cycle is obtained by using four copies and two types of Tet-off GAL80 transgenes. Upon treatment of newly emerged adults with tetracycline, induction of GAL4 activity is observed but the level of induction is influenced by the concentration of the inducer, the age, the sex and the anatomical location of the expression. The inhibition of GAL4 activity and the maintenance of induced expression are altered in old animals. This study reveals that the repressive ability of GAL80 is affected by the age and sex of the animal which is a major limitation to regulate gene expression with GAL80 in aged Drosophila.

Hypertension Canada's 2017 Guidelines for the Diagnosis, Assessment, Prevention, and Treatment of Pediatric Hypertension.

After the 2016 guidelines for blood pressure measurement, diagnosis, and investigation of pediatric hypertension, we now present evidence-based guidelines for the prevention and treatment of hypertension in children. These guidelines were developed by Hypertension Canada's Guideline Committee pediatric subgroup after thorough evaluation of the available literature. Included are 10 guidelines specifically addressing health behaviour management, indications for drug therapy in children with hypertension, choice of therapy for children with primary hypertension, and goals of therapy for children with hypertension. Although the pediatric literature is inherently limited by small numbers of participants, fewer trials, and a prolonged latency to the development of vascular outcomes, this report reflects the current and highest level of evidence and provides guidance for primary care practitioners on the management of pediatric hypertension. Studies of therapeutic lifestyle modifications in children are available to guide current management and more antihypertensive drugs have been studied in children since the Food and Drug Administration Modernization Act. Consistent with Hypertension Canada's guideline policy, diagnostic and therapeutic algorithm tools will be developed and the guidelines will be reviewed annually and updated according to new evidence.

Impact of dairy consumption on essential hypertension: a clinical study.

BACKGROUND: Several studies have presented evidence suggesting that dairy consumption has beneficial effects on blood pressure (BP) in healthy subjects; however, only a few studies have examined this possibility in patients with established essential hypertension using ambulatory blood pressure monitoring. The objective of this study was to investigate how consuming dairy products impacts mean daytime systolic and diastolic BP in men and women with mild to moderate essential hypertension. METHODS: Eighty-nine men and women with systolic BP ≥ 135 mm Hg and ≤ 160 mm Hg and diastolic BP ≤ 110 mm Hg were enrolled in this single-blind, randomized, cross-over, controlled study. Participants had to incorporate three daily servings of dairy products or control products equivalent in macronutrients and sodium during four-week treatment phases. Twenty-four hour ambulatory BP and endothelial function were assessed at screening and at the end of each dietary phase. RESULTS: The consumption of three daily servings of dairy products led to a significant reduction in mean daytime ambulatory systolic BP (-2 mm Hg; P = 0.05) in men compared with readings after the control phase. In women, dairy consumption had no effect on ambulatory systolic BP. Moreover, endothelial function was significantly improved by dairy consumption in the whole cohort. CONCLUSION: These data indicate that the consumption of three daily servings of dairy products have beneficial effects on daytime systolic ambulatory BP compared to a heart-healthy, dairy-free, diet in men with mild to moderate essential hypertension. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov as NCT01776216.

Contemporary use of ß-blockers: clinical relevance of subclassification.

ß-Adrenergic receptor blockers or ß-blockers represent one of the oldest classes of cardiovascular agents and have been considered a cornerstone therapy for hypertension and heart disease for the past 5 decades. They are advocated as a first-line treatment for uncomplicated essential hypertension in patients younger than 60 years of age as recommended by the Canadian Hypertension Education Program. However, despite the well-established antihypertensive and cardiovascular benefits of ß-blockers, a number of studies argue that they might not have the same clinical advantages of other classes of agents in terms of morbidity/mortality outcomes. This review will focus on the heterogeneity of the pharmacologic characteristics of ß-blockers, and we will discuss the metabolic and hemodynamic differences within the ß-blocker class and try to assess the potential implications of these differences for optimal selection in hypertension.

Nutrient-dependent requirement for SOD1 in lifespan extension by protein restriction in Drosophila melanogaster.

Reactive oxygen species (ROS) modulate aging and aging-related diseases. Dietary composition is critical in modulating lifespan. However, how ROS modulate dietary effects on lifespan remains poorly understood. Superoxide dismutase 1 (SOD1) is a major cytosolic enzyme responsible for scavenging superoxides. Here we investigated the role of SOD1 in lifespan modulation by diet in Drosophila. We found that a high sugar-low protein (HS-LP) diet or low-calorie diet with low-sugar content, representing protein restriction, increased lifespan but not resistance to acute oxidative stress in wild-type flies, relative to a standard base diet. A low sugar-high protein diet had an opposite effect. Our genetic analysis indicated that SOD1 overexpression or dfoxo deletion did not alter lifespan patterns of flies responding to diets. However, sod1 reduction blunted lifespan extension by the HS-LP diet but not the low-calorie diet. HS-LP and low-calorie diets both reduced target of rapamycin (TOR) signaling and only the HS-LP diet increased oxidative damage. sod1 knockdown did not affect phosphorylation of S6 kinase, suggesting that SOD1 acts in parallel with or downstream of TOR signaling. Surprisingly, rapamycin decreased lifespan in sod1 mutant but not wild-type males fed the standard, HS-LP, and low-calorie diets, whereas antioxidant N-acetylcysteine only increased lifespan in sod1 mutant males fed the HS-LP diet, when compared to diet-matched controls. Our findings suggest that SOD1 is required for lifespan extension by protein restriction only when dietary sugar is high and support the context-dependent role of ROS in aging and caution the use of rapamycin and antioxidants in aging interventions.

The evolving role of ß-adrenergic receptor blockers in managing hypertension.

ß-Adrenergic blocking agents (or ß-blockers) have been widely used for the treatment of hypertension for the past 50 years, and continue to be recommended as a mainstay of therapy in many national guidelines. They have also been used in a variety of cardiovascular conditions commonly complicating hypertension, including angina pectoris, myocardial infarction (MI), acute and chronic heart failure, as well as conditions like essential tremor and migraine. Moreover, they have played a primary role in controlling blood pressure in patients with these specific comorbidities and in reducing cardiovascular risk with regard to the composite outcome of death, stroke, and MI among patients younger than 60 years of age. However, in patients 60 years of age or older, ß-blockers were not associated with significantly lower rates of MI, heart failure or death, and demonstrated higher rates of stroke compared with other first-line therapies. Consequently, the Canadian Hypertension Education Program recommends the use of ß-blockers as first-line therapy in hypertensive patients younger than 60 years of age but not for those age 60 and older, with the exception of patients with concomitant ß-blocker-requiring cardiac diseases. Several reports suggest that the lack of consistent outcome data may relate to the use of traditional ß-blockers such as atenolol and their ability only to reduce cardiac output, without beneficial effect on peripheral vascular resistance. The present report will describe the clinically relevant mechanisms of action of ß-blockers, their pharmacological differences, their metabolic effects, and their usefulness in patients with hypertension.

Challenges and scientific considerations in hypertension management reflected in the 2012 recommendations of the Canadian Hypertension Education Program.

This article provides the scientific rationale and background information for the Canadian Hypertension Education Program's 2012 recommendations for the management of hypertension. It also summarizes the key new recommendations and the theme for 2012, which is the prevention of hypertension. The full recommendations are available at www.hypertension.ca.

Canadian Hypertension Education Program: the science supporting New 2011 CHEP recommendations with an emphasis on health advocacy and knowledge translation.

This is a summary of the theme, key new recommendations, and supporting science of the 2011 Canadian Hypertension Education Program (CHEP). In 2011, the ACCORD trial challenged current blood pressure treatment targets for people with diabetes. After consideration of multiple factors relating to the ACCORD trial design and its reporting, the current treatment target of <130/80 mm Hg was not changed. A meta-analysis implicated angiotensin receptor blockers in causing cancer; however, weaknesses in the meta-analysis and ongoing close scrutiny of the issue by the U.S. Food and Drug Administration precluded any changes in current CHEP recommendations. New expert opinion-based recommendations were added to assist the management of hypertension in the setting of acute stroke. To promote healthier blood pressure in Canadians, CHEP emphasizes the need for all Canadians-in particular, health care professionals and their organizations-to more actively work with different levels of government to implement healthy public policies. These should build community capacity to promote healthy behaviours with the goal of the prevention of hypertension and its consequences. To aid a substantive knowledge translation gap, health care professionals and people with hypertension can now receive regular CHEP updates by signing up at the Web sites htnupdate.ca and www.myBPsite.ca.

Increasing the doses of both diuretics and angiotensin receptor blockers is beneficial in subjects with uncontrolled systolic hypertension.

BACKGROUND: Blood pressure (BP) control is frequently difficult to achieve in patients with predominantly elevated systolic BP. Consequently, these patients frequently require combination therapy including a thiazide diuretic such as hydrochlorothiazide (HCTZ) and an agent blocking the renin-angiotensin-aldosterone system. Current clinical practice usually limits the daily dose of HCTZ to 25 mg. This often leads to the necessity of using additional antihypertensive agents to control BP in a high proportion of patients. OBJECTIVES: To compare the efficacy of two doses of losartan (LOS)/HCTZ combinations in patients with uncontrolled ambulatory systolic hypertension after six weeks of treatment with LOS 100 mg/HCTZ 25 mg (LOS100/HCTZ25). METHODS: Following a two- to four-week washout period, subjects with a mean clinic sitting systolic BP of 160 mmHg or higher and a mean ambulatory daytime systolic BP (MDSBP) of 135 mmHg or higher on LOS100/HCTZ25 (n=105; 33 women and 72 men) were randomly assigned to receive LOS 150 mg/HCTZ 25 mg (group 1; n=53) or LOS 150 mg/HCTZ 37.5 mg (LOS150/HCTZ37.5, group 2; n=52). The primary end point was the difference in MDSBP reductions. RESULTS: At the end of the six-week treatment period, the respective additional decreases in MDSBP were 1.2 mmHg (P=0.335) on LOS 150 mg/HCTZ 25 mg and 5.6 mmHg (P<0.0001) on LOS150/HCTZ37.5 (difference of 4.4 mmHg; P=0.011). Daytime systolic ambulatory BP goal (lower than 130 mmHg) achievement tended to be higher (25% versus 17%; P=0.313) with LOS150/HCTZ37.5, while it was significantly higher (65% versus 43%; P=0.024) for mean daytime diastolic BP (lower than 80 mmHg). No deleterious metabolic changes were observed. CONCLUSIONS: In patients with uncontrolled systolic ambulatory hypertension receiving LOS100/HCTZ25, increasing both HCTZ and LOS dosages simultaneously to LOS150/HCTZ37.5 may be an effective strategy that does not affect metabolic parameters.

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.

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy.

OBJECTIVE: To update the evidence-based recommendations for the prevention and treatment of hypertension in adults for 2010. OPTIONS AND OUTCOMES: For lifestyle and pharmacological interventions, randomized trials and systematic reviews of trials were preferentially reviewed. Changes in cardiovascular morbidity and mortality were the primary outcomes of interest. However, for lifestyle interventions, blood pressure lowering was accepted as a primary outcome given the general lack of long-term morbidity and mortality data in this field. Progressive renal impairment was also accepted as a clinically relevant primary outcome among patients with chronic kidney disease. EVIDENCE: A Cochrane Collaboration librarian conducted an independent MEDLINE search from 2008 to August 2009 to update the 2009 recommendations. To identify additional studies, reference lists were reviewed and experts were contacted. All relevant articles were reviewed and appraised independently by both content and methodological experts using prespecified levels of evidence. RECOMMENDATIONS: For lifestyle modifications to prevent and treat hypertension, restrict dietary sodium to 1500 mg (65 mmol) per day in adults 50 years of age or younger, to 1300 mg (57 mmol) per day in adults 51 to 70 years of age, and to 1200 mg (52 mmol) per day in adults older than 70 years of age; perform 30 min to 60 min of moderate 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 (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 for men or nine standard drinks per week for women; follow a diet that emphasizes fruits, vegetables and low-fat dairy products, dietary and soluble fibre, whole grains and protein from plant sources, and that is low in saturated fat and cholesterol; and consider stress management in selected individuals with hypertension. For the pharmacological management of hypertension, treatment thresholds and targets should be predicated on the patient's global atherosclerotic risk, target organ damage and comorbid conditions. Blood pressure should be decreased to less than 140/90 mmHg in all patients, and to less than 130/80 mmHg in patients with diabetes mellitus or chronic kidney disease. Most patients will require more than one agent to achieve these target blood pressures. Antihypertensive therapy should be considered in all adult patients regardless of age (caution should be exercised in elderly patients who are frail). For adults without compelling indications for other agents, considerations for initial therapy should include thiazide diuretics, angiotensin- converting enzyme (ACE) inhibitors (in patients who are not black), long-acting calcium channel blockers (CCBs), angiotensin receptor blockers (ARBs) or beta-blockers (in those younger than 60 years of age). A combination of two first-line agents may also be considered as initial treatment of hypertension if systolic blood pressure is 20 mmHg above target or if diastolic blood pressure is 10 mmHg above target. The combination of ACE inhibitors and ARBs should not be used, unless compelling indications are present to suggest consideration of dual therapy. Agents appropriate for first-line therapy for isolated systolic hypertension include thiazide diuretics, long-acting dihydropyridine CCBs or ARBs. In patients with coronary artery disease, ACE inhibitors, ARBs or betablockers are recommended as first-line therapy; in patients with cerebrovascular disease, an ACE inhibitor/diuretic combination is preferred; in patients with proteinuric nondiabetic chronic kidney disease, ACE inhibitors or ARBs (if intolerant to ACE inhibitors) are recommended; and in patients with diabetes mellitus, ACE inhibitors or ARBs (or, in patients without albuminuria, thiazides or dihydropyridine CCBs) are appropriate first-line therapies. In selected high-risk patients in whom combination therapy is being considered, an ACE inhibitor plus a long-acting dihydropyridine CCB is preferable to an ACE inhibitor plus a thiazide diuretic. All hypertensive patients with dyslipidemia should be treated using the thresholds, targets and agents outlined in the Canadian lipid treatment guidelines. Selected patients with hypertension who do not achieve thresholds for statin therapy, but who are otherwise at high risk for cardiovascular events, should nonetheless receive statin therapy. Once blood pressure is controlled, low-dose acetylsalicylic acid therapy should be considered. VALIDATION: All recommendations were graded according to the strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. All recommendations reported here achieved at least 80% consensus. These guidelines will continue to be updated annually. SPONSORS: The Canadian Hypertension Education Program process is sponsored by the Canadian Hypertension Society, Blood Pressure Canada, the Public Health Agency of Canada, the College of Family Physicians of Canada, the Canadian Pharmacists Association, the Canadian Council of Cardiovascular Nurses, and the Heart and Stroke Foundation of Canada.

Valsartan plus hydrochlorothiazide for first-line therapy in hypertension.

Goal blood pressure levels are only being achieved in approximately a third of hypertensive patients, which suggests that there is a need for new and/or improved approaches to the treatment of hypertension. The majority of patients with hypertension require combination therapy to control their blood pressure. The use of a combination of drugs with complementary mechanisms of action may provide greater efficacy and tolerability compared with monotherapy, and may allow more rapid achievement of target blood pressure. Moreover, the use of single-pill combinations has the potential to increase adherence and persistence, and reduce costs. The single-pill combination of valsartan plus hydrochlorothiazide was recently approved by the US FDA for first-line use in hypertensive patients who are likely to need multiple drugs to achieve their blood pressure goals. The focus of this article is on those randomized, double-blind trials in which this combination was administered as first-line therapy in patients with essential hypertension.