Pharmacologic Therapies for Aortic Stiffness in End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Increased carotid-femoral pulse wave velocity (cf-PWV), a surrogate of increased aortic stiffness, is a risk factor for cardiovascular events and all-cause mortality in end-stage renal disease (ESRD). To minimize the deleterious effects of an increased aortic stiffness in ESRD patients, several interventions have been developed and cf-PWV has been used to monitor responses. OBJECTIVE: The aim of this study was to determine the effects of pharmacologic interventions that target aortic stiffness on cf-PWV and systolic blood pressure (SBP) in adults with ESRD. STUDY DESIGN: This study implements a systematic review and meta-analysis. DATA SOURCES: MEDLINE, EMBASE, Cochrane Central, Health Technology Assessment, and EBM databases were searched. STUDY ELIGIBILITY PARTICIPANTS AND INTERVENTIONS: Randomized and non-randomized studies involving adults (>18 years) with ESRD of any duration, receiving or not renal replacement therapy (hemodialysis, peritoneal dialysis) and exposed to a pharmacologic intervention whose effects were assessed by cf-PWV. METHODS: Study screening, selection, data extraction, and quality assessments were performed by 2 independent reviewers. Narrative synthesis and quantitative data analysis summarized the review. RESULTS: We included 1027 ESRD participants from 13 randomized and 5 non-randomized studies. Most pharmacologic interventions targeted bone mineral metabolism disorder or hypertension. Treatment with vitamin D analogues or cinacalcet did not decrease cf-PWV or SBP over placebo or matched controls (P > .05). Calcium-channel blockers (CCB) decreased cf-PWV and SBP compared with placebo or standard care (P < .05). Renin-angiotensin system inhibitors did not show any advantage over placebo in decreasing cf-PWV (P > .05). LIMITATIONS: Quality of evidence ranged from very low to moderate. Overall evidence was limited by the low number of studies, small sample sizes, and methodological inconsistencies. CONCLUSIONS: Pharmacologic interventions targeting aortic stiffness in ESRD have mixed effects on reducing cf-PWV, with some strategies suggesting potential benefit. The quality of evidence, however, is insufficient to draw definitive conclusions on their use to slow progression of aortic stiffness in ESRD. Further well-designed studies are needed to confirm these associations and their impact on cardiovascular outcomes in ESRD.Registered in PROSPERO (CRD42016033463).

CONTEXTE: L'accroissement de la vitesse de l'onde de pouls carotido-fémorale (VOPcf), un substitut à l'accroissement de la rigidité aortique, constitue un facteur de risque d'événements cardiovasculaires et de mortalité toutes causes confondues en contexte d'insuffisance rénale terminale (IRT). Plusieurs interventions pharmacologiques ont été développées pour minimiser les effets délétères de l'accroissement de la rigidité aortique chez les patients atteints d'IRT, et la VOPcf a été employée pour en mesurer la réponse. OBJECTIF: Mesurer les effets d'interventions pharmacologiques ciblant la rigidité aortique sur la VOPcf et la pression systolique (PS) d'adultes atteints d'IRT. TYPE D'ÉTUDE: Revue systématique et méta-analyse. SOURCES: Les bases de données MEDLINE, EMBASE, Cochrane Central, EMB et du Service d'évaluation des technologies de la santé ont été consultées. ADMISSIBILITÉ PARTICIPANTS ET INTERVENTIONS: Ont été sélectionnées les études réparties aléatoirement ou non, peu importe leur durée, qui portaient sur des adultes atteints d'IRT, recevant ou non une thérapie de remplacement rénal (hémodialyse, dialyse péritonéale), qui avaient été exposés à une intervention pharmacologique dont les effets avaient été mesurés avec la VOPcf. MÉTHODOLOGIE: Deux réviseurs indépendants ont procédé à la recherche et à la sélection des études, à l'extraction des données et à l'évaluation de leur qualité. Une synthèse narrative et une analyse quantitative des données ont synthétisé les résultats de la revue. RÉSULTATS: L'étude porte sur un total de 1 027 sujets atteints d'IRT issus de 13 études à répartition aléatoire et de 5 études non réparties aléatoirement. La plupart des interventions pharmacologiques ciblaient l'hypertension ou un trouble du métabolisme de la densité osseuse. Lorsque comparés à un placebo ou à un témoin, les traitements impliquant un analogue de la vitamine D ou le cinacalcet n'ont eu aucun effet réducteur sur la VOPcf ou la PS (p>0,05). Les bloqueurs des canaux calciques ont montré un effet réducteur sur la VOPcf et la PS en comparaison du placebo ou du traitement standard (p<0,05). Les inhibiteurs du système rénine-angiotensine n'ont présenté aucun avantage pour réduire la VOPcf par rapport au placebo (p>0,05). LIMITES: La qualité des données recueillies variait de très pauvre à modérée. L'ensemble des données recueillies est limité par le faible nombre d'études, la petite taille des échantillons et par des divergences méthodologiques. CONCLUSION: Les interventions pharmacologiques ciblant la rigidité aortique en contexte d'IRT ont eu des résultats mitigés sur la réduction de la VOPcf, quoique certaines stratégies suggèrent de potentiels avantages. La qualité des données recueillies est toutefois insuffisante pour conclure de façon définitive que ces interventions ralentissent la progression de la rigidité aortique chez les patients atteints d'IRT. Des études bien conçues sont nécessaires pour confirmer ces associations et leur incidence sur les issues cardiovasculaires en contexte d'IRT.

Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults.

Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg. For individuals with diastolic hypertension (with or without systolic hypertension), fixed-dose single-pill combinations are now recommended as an initial treatment option. Preference is given to pills containing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in combination with either a calcium channel blocker or diuretic. Whenever a diuretic is selected as monotherapy, longer-acting agents are preferred. In patients with established ischemic heart disease, caution should be exercised in lowering diastolic non-AOBP to ≤ 60 mm Hg, especially in the presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended. Finally, guidance is now provided for screening, initial diagnosis, assessment, and treatment of renovascular hypertension arising from fibromuscular dysplasia. The specific evidence and rationale underlying each of these guidelines are discussed.

Hypertension Canada's 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension.

Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force provides annually updated, evidence-based recommendations to guide the diagnosis, assessment, prevention, and treatment of hypertension. This year, we present 4 new recommendations, as well as revisions to 2 previous recommendations. In the diagnosis and assessment of hypertension, automated office blood pressure, taken without patient-health provider interaction, is now recommended as the preferred method of measuring in-office blood pressure. Also, although a serum lipid panel remains part of the routine laboratory testing for patients with hypertension, fasting and nonfasting collections are now considered acceptable. For individuals with secondary hypertension arising from primary hyperaldosteronism, adrenal vein sampling is recommended for those who are candidates for potential adrenalectomy. With respect to the treatment of hypertension, a new recommendation that has been added is for increasing dietary potassium to reduce blood pressure in those who are not at high risk for hyperkalemia. Furthermore, in selected high-risk patients, intensive blood pressure reduction to a target systolic blood pressure ≤ 120 mm Hg should be considered to decrease the risk of cardiovascular events. Finally, in hypertensive individuals with uncomplicated, stable angina pectoris, either a ß-blocker or calcium channel blocker may be considered for initial therapy. The specific evidence and rationale underlying each of these recommendations are discussed. Hypertension Canada's Canadian Hypertension Education Program Guidelines Task Force will continue to provide annual updates.

The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

The Canadian Hypertension Education Program reviews the hypertension literature annually and provides detailed recommendations regarding hypertension diagnosis, assessment, prevention, and treatment. This report provides the updated evidence-based recommendations for 2015. This year, 4 new recommendations were added and 2 existing recommendations were modified. A revised algorithm for the diagnosis of hypertension is presented. Two major changes are proposed: (1) measurement using validated electronic (oscillometric) upper arm devices is preferred over auscultation for accurate office blood pressure measurement; (2) if the visit 1 mean blood pressure is increased but < 180/110 mm Hg, out-of-office blood pressure measurements using ambulatory blood pressure monitoring (preferably) or home blood pressure monitoring should be performed before visit 2 to rule out white coat hypertension, for which pharmacologic treatment is not recommended. A standardized ambulatory blood pressure monitoring protocol and an update on automated office blood pressure are also presented. Several other recommendations on accurate measurement of blood pressure and criteria for diagnosis of hypertension have been reorganized. Two other new recommendations refer to smoking cessation: (1) tobacco use status should be updated regularly and advice to quit smoking should be provided; and (2) advice in combination with pharmacotherapy for smoking cessation should be offered to all smokers. The following recommendations were modified: (1) renal artery stenosis should be primarily managed medically; and (2) renal artery angioplasty and stenting could be considered for patients with renal artery stenosis and complicated, uncontrolled hypertension. The rationale for these recommendation changes is discussed.

The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension.

Herein, updated evidence-based recommendations for the diagnosis, assessment, prevention, and treatment of hypertension in Canadian adults are detailed. For 2014, 3 existing recommendations were modified and 2 new recommendations were added. The following recommendations were modified: (1) the recommended sodium intake threshold was changed from ≤ 1500 mg (3.75 g of salt) to approximately 2000 mg (5 g of salt) per day; (2) a pharmacotherapy treatment initiation systolic blood pressure threshold of ≥ 160 mm Hg was added in very elderly (age ≥ 80 years) patients who do not have diabetes or target organ damage (systolic blood pressure target in this population remains at < 150 mm Hg); and (3) the target population recommended to receive low-dose acetylsalicylic acid therapy for primary prevention was narrowed from all patients with controlled hypertension to only those ≥ 50 years of age. The 2 new recommendations are: (1) advice to be cautious when lowering systolic blood pressure to target levels in patients with established coronary artery disease if diastolic blood pressure is ≤ 60 mm Hg because of concerns that myocardial ischemia might be exacerbated; and (2) the addition of glycated hemoglobin (A1c) in the diagnostic work-up of patients with newly diagnosed hypertension. The rationale for these recommendation changes is discussed. In addition, emerging data on blood pressure targets in stroke patients are discussed; these data did not lead to recommendation changes at this time. The Canadian Hypertension Education Program recommendations 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 year's 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 2012 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 2012. The new recommendations are: (1) use of home blood pressure monitoring to confirm a diagnosis of white coat syndrome; (2) mineralocorticoid receptor antagonists may be used in selected patients with hypertension and systolic heart failure; (3) a history of atrial fibrillation in patients with hypertension should not be a factor in deciding to prescribe an angiotensin-receptor blocker for the treatment of hypertension; and (4) the blood pressure target for patients with nondiabetic chronic kidney disease has now been changed to < 140/90 mm Hg from < 130/80 mm Hg. We also reviewed the recent evidence on blood pressure targets for patients with hypertension and diabetes and continue to recommend a blood pressure target of less than 130/80 mm Hg.

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 patient's 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.

The KRESCENT Program: an initiative to match supply and demand for kidney research in Canada.

BACKGROUND: The prevalence of kidney disease is rising in Canada, and new approaches to prevention, diagnosis, and treatment are required. A kidney research training strategy, which enhances capacity while fostering collaboration and knowledge translation, may help to address this health care problem. PURPOSE: This manuscript describes the Kidney Research Scientist Core Education and National Training (KRESCENT) Program that was launched in 2004 with a major goal to enhance kidney research capacity in Canada. FEATURES: KRESCENT is an innovative training program, which recruits from a variety of research disciplines, and emphasizes multi-disciplinary research approaches, team-based collaboration and knowledge translation. The program provides salary support for post-doctoral fellows, new investigators and allied health doctoral trainees, and also offers core curriculum and mentorship support. The curriculum involves knowledge acquisition, application and integration and uses workshops and web-based problem modules to enhance research skills. Training in methodological approaches and career development is also included. Initial evaluation of KRESCENT suggests that kidney research capacity in Canada has increased, and trainees have a high success rate in obtaining academic positions (~88%) and peer-review grant support (~50%). SUMMARY: KRESCENT represents a novel collaborative approach to kidney research training in Canada that may serve as a suitable model for training in other countries, or in other medical disciplines.

The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part I - blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. EVIDENCE: MEDLINE searches were conducted from November 2008 to October 2009 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Changes to the recommendations for 2010 relate to automated office blood pressure measurements. Automated office blood pressure measurements can be used in the assessment of office blood pressure. When used under proper conditions, an automated office systolic blood pressure of 135 mmHg or higher or diastolic blood pressure of 85 mmHg or higher should be considered analogous to a mean awake ambulatory systolic blood pressure of 135 mmHg or higher and diastolic blood pressure of 85 mmHg or higher, respectively. VALIDATION: All recommendations were graded according to strength of the evidence and voted on by the 63 members of the Canadian Hypertension Education Program Evidence-Based Recommendations Task Force. To be approved, all recommendations were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.

The 2009 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 1--blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on appropriate blood pressure measurement, the timely assessment of serially elevated readings, the degree of blood pressure elevation, the method of measurement (office, ambulatory, home) and associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk and determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2007 to October 2008 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Key messages include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of global risk assessment and the need for ongoing monitoring of hypertensive patients to identify incident type 2 diabetes. 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 were required to be supported by at least 70% of task force members. These guidelines will continue to be updated annually.

The 2008 Canadian Hypertension Education Program recommendations for the management of hypertension: Part 1 - blood pressure measurement, diagnosis and assessment of risk.

OBJECTIVE: To provide updated, evidence-based recommendations for the diagnosis and assessment of adults with hypertension. OPTIONS AND OUTCOMES: The diagnosis of hypertension is dependent on appropriate blood pressure measurement, the timely assessment of serially elevated readings, degree of blood pressure elevation, method of measurement (office, ambulatory, home) and associated comorbidities. The presence of cardiovascular risk factors and target organ damage should be ascertained to assess global cardiovascular risk and determine the urgency, intensity and type of treatment required. EVIDENCE: MEDLINE searches were conducted from November 2006 to October 2007 with the aid of a medical librarian. Reference lists were scanned, experts were contacted, and the personal files of authors and subgroup members were used to identify additional studies. Content and methodological experts assessed studies using prespecified, standardized evidence-based algorithms. Recommendations were based on evidence from peer-reviewed, full-text articles only. RECOMMENDATIONS: Recommendations for blood pressure measurement, criteria for hypertension diagnosis and follow-up, assessment of global cardiovascular risk, diagnostic testing, diagnosis of renovascular and endocrine causes of hypertension, home and ambulatory monitoring, and the use of echocardiography in hypertensive individuals are outlined. Key messages in 2008 include continued emphasis on the expedited, accurate diagnosis of hypertension, the importance of global risk assessment and the need for ongoing monitoring of hypertensive patients to identify incident type 2 diabetes. 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 received at least 70% consensus. These guidelines will continue to be updated annually.