Search

Objective: The study was undertaken because it was unknown whether the duration of type 2 diabetes modifies the effects of sodium-glucose cotransporter 2 inhibitor canagliflozin on cardiovascular (CV) and kidney outcomes., Research Design and Methods: This post hoc analysis of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program (N = 10,142) and Evaluation of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Participants With Diabetic Nephropathy (CREDENCE) trial (N = 4,401) evaluated hazard ratios and 95% CIs using Cox proportional hazards for the effects of canagliflozin on CV and kidney outcomes, including progression and regression of albuminuria over 5-year intervals of disease duration., Results: Canagliflozin had ranges of benefit across intervals of diabetes duration, with no heterogeneity for major adverse CV events, CV death or heart failure hospitalization, and kidney failure requiring therapy or doubling serum creatinine. Furthermore, canagliflozin reduced albuminuria progression and increased albuminuria regression with no interaction across all diabetes duration subgroups., Conclusions: Our findings suggest that earlier treatment with canagliflozin confers consistent cardiorenal benefits to individuals with type 2 diabetes., (© 2024 by the American Diabetes Association.)

Competing Interests: Intérêts concurrents: Sheldon Tobe déclare avoir été rémunéré par la société Medtronic Canada. Andrew Dueck déclare avoir été rémunéré à titre de témoin expert au sujet de brevets portant sur des séquences d’imagerie par résonance magnétique pour l’évaluation de plaques des artères périphériques. Il est titulaire de la chaire Maggisano en chirurgie vasculaire. Mina Madan déclare avoir participé à un comité consultatif pour la société Medtronic Canada. Aucun autre intérêt concurrent n’a été déclaré.

Competing Interests: Competing interests: Sheldon Tobe reports payment from Medtronic Canada. Andrew Dueck reports payment for expert testimony, patents related to magnetic resonance imaging sequences for the evaluation of peripheral plaque. He holds the Maggisano chair in vascular surgery. Mina Madan reports participation on an advisory board for Medtronic Canada. No other competing interests were declared.

Background: The hypertension specialist often receives referrals of patients with young-onset, severe, difficult-to-control hypertension, patients with hypertensive emergencies, and patients with secondary causes of hypertension. Specialist hypertension care compliments primary care for these complex patients and contributes to an overall hypertension control strategy. The objective of this study was to characterize hypertension centres and the practice patterns of Canadian hypertension specialists., Methods: Adult hypertension specialists across Canada were surveyed to describe hypertension centres and specialist practice in Canada, including the following: the patient population managed by hypertension specialists; details on how care is provided; practice pattern variations; and differences in access to specialized hypertension resources across the country., Results: The survey response rate was 73.5% from 25 hypertension centres. Most respondents were nephrologists and general internal medicine specialists. Hypertension centres saw between 50 and 2500 patients yearly. A mean of 17% (± 15%) of patients were referred from the emergency department and a mean of 52% (± 24%) were referred from primary care. Most centres had access to specialized testing (adrenal vein sampling, level 1 sleep studies, autonomic testing) and advanced therapies for resistant hypertension (renal denervation). Considerable heterogeneity was present in the target blood pressure in young people with low cardiovascular risk and in the diagnostic algorithms for investigating secondary causes of hypertension., Conclusions: These results summarize the current state of hypertension specialist care and highlight opportunities for further collaboration among hypertension specialists, including standardization of the approach to specialist care for patients with hypertension., (© 2023 The Authors.)

Background: Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada., Methods: We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014-2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death., Results: We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63-0.69) and mortality (0.68, 0.64-0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77-0.88) and mortality (0.71, 0.66-0.78) outcomes than a result in the normoglycemic range., Conclusions: Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: To assess micro current to improve vision for dry age-related macular degeneration. Dry age-related macular degeneration is a major cause of blindness, disability, and severe erosion of quality of life, throughout the world. Beyond nutritional supplementation, there is no approved therapy., Methods: This was a prospective randomized sham controlled clinical trial for participants with confirmed dry AMD with documented visual loss. Participants were randomized three to one, to receive transpalpebral external micro current electrical stimulation with the MacuMira device. The Treatment group received four treatments in the first two weeks, and two further treatments at weeks 14 and 26. Differences in BCVA and contrast sensitivity (CS) were estimated with mixed-effects repeated measures analysis of variance., Results: Change of visual acuity with ETDRS assessment of number of letters read (NLR) and contrast sensitivity at week 4 and 30, compared to the first visit, between 43 treatment and 19 sham control participants. The Sham Control group had NLR of 24.2 (SD 7.1) at baseline, 24.2 (SD 7.2) at 4 weeks, and 22.1 (SD7.4) at 30 weeks. The Treatment group had NLR of 19.6 (SD 8.9) at baseline, 27.6 (SD 9.1) at 4 weeks, and 27.8 (SD 8.4) at 30 weeks. The change in NLR from baseline in the Treatment compared to the Sham control group was 7.7 (95% CI 5.7, 9.7, p < 0.001) at 4 weeks and 10.4 (95% CI 7.8, 13.1, p < 0.001) at 30 weeks. There were similar benefits in CS., Conclusions: This pilot study of transpalpebral microcurrent demonstrated improved visual measures and is very encouraging as a potential treatment for dry AMD., Trial Registration: NCT02540148, ClinicalTrials.gov., (© 2023. The Author(s).)

Background: Hypertensive disorders of pregnancy (HDPs) are a risk factor for future cardiovascular disease; therefore, follow-up and implementation of early interventions is recommended. We performed a qualitative study to assess the feasibility and user response to a mobile-health tool and virtual consultation aimed at educating people with an HDP on future cardiovascular risk, and at better understanding patients' priorities for postpartum care., Methods: Participants with a history of an HDP in the past 5 years had access to an online educational tool and participated in a virtual consultation to discuss their cardiovascular risks after experiencing an HDP. Participants were invited to a focus group to obtain feedback on their postpartum experience and the Her-HEART program., Results: A total of 20 female participants were enrolled in the study between January 2020 and February 2021. Of these, 16 participants took part in 1 of 5 focus groups. Participants reported a lack of awareness of future cardiovascular disease risks prior to participating in the program, and identified barriers to counselling, including traumatic birth experiences, inappropriate timing, and competing priorities. Participants reported that the virtual Her-HEART program was an effective avenue to provide counselling on long-term cardiovascular risks. They highlighted the importance of coordinated care pathways and mental health support in postpartum follow-up programs., Conclusion: We have shown the feasibility of providing an educational website and virtual consultation to facilitate counselling in people affected by HDPs. Our results shed light on patient-reported priorities related to the content and delivery of postpartum counselling after an HDP., (© 2023 The Authors.)

Competing Interests: Intérêts concurrents: James Stone déclare avoir reçu des honoraires et émoluments à titre de consultant pour Bayer Canada et Sanofi Canada. Le Dr Stone est directeur médical principal du Cardiovascular Health and Stroke Strategic Clinical Network des Services de santé de l’Alberta, et membre actif du conseil de gouvernance du Collège des médecins et chirurgiens de l’Alberta. Jason Andrade déclare avoir reçu une rémunération ou des honoraires de Medtronic, BiosenseWebster, Abbott, Biotronik, Bayer, Servier et BMS-Pfizer. Simon Bacon déclare avoir reçu des subventions de Moderna, versées à Respiplus pour la création de modules de formation sur la réticence aux vaccins et des honoraires de consultant et de conférencier de Respiplus. Il a fait partie de comités consultatifs pour Bayer, Sanofi, Respiplus et Lucilab, aucun n’étant en lien avec le présent article. Il est aussi titulaire d’une chaire en mentorat pour la Stratégie de recherche axée sur le patient des Instituts de recherche en santé du Canada (IRSC) (SMC-151518), et d’une chaire du Fonds de recherche du Québec (251618 et 309815). Harpreet Bajaj déclare avoir reçu des subventions de Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi et Tricida, et des honoraires de conférencier de Eli Lilly et Novo Nordisk. Mark Gelfer déclare avoir reçu des honoraires de consultation de Cliniques Telus Santé et occupe un poste bénévole de président du conseil de GenXys Health Care Systems, dont il détient des actions. Jeffrey Habert déclare avoir reçu des honoraires de consultation de MDBriefcase, Liv, MedPlan, Master Clinician Alliance, Academy, Bridge, Seacourses, Thrombose Canada, Meducom, Antibody, Canadian Heart Research Centre, CTC Communications, STA Healthcare Communications, Canadian Collaborative Research Network, CPD Network, Telus Santé, EOCI Pharmacomm et Operatic. Le Dr Habert a aussi reçu des honoraires de Pfizer, Amgen, BMS, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Purdue, Bausch, Allergan, AbbVie, AstraZeneca, Novartis, Lundbeck, CHEP+, Novo Nordisk, Janssen, Eisai, HLS, Otsuka, Sunovion et Jazz. Le Dr Habert a été coresponsable des Guides cliniques de Thrombose Canada (2018–2021). Karim Keshavjee déclare avoir reçu des honoraires de consultation de l’Université McMaster, Demers Professional Corporation et Normative. Darlene Kitty déclare avoir reçu une rémunération d’enseignante des facultés de médecine de l’Université d’Ottawa et de l’Université McGill pour des conférences occasionnelles et des bourses de voyage à titre de directrice du Programme autochtone de la Faculté de médecine de l’Université d’Ottawa. La Dre Kitty est présidente du Comité sur la santé autochtone du Collège des médecins de famille du Canada. David Lau déclare avoir reçu des subventions de Novo Nordisk, des honoraires de consultation de Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly, Novo Nordisk et Viatris, des honoraires de Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly et Novo Nordisk, et une rémunération en tant que témoin expert de l’Association canadienne de protection médicale. Le Dr Lau a occupé des postes de direction chez Obésité Canada et à l’Association canadienne des médecins et chirurgiens bariatriques. Laurent Macle déclare avoir reçu des subventions et des honoraires de BMS-Pfizer, Servier et Bayer. Michael McDonald déclare avoir reçu des honoraires de consultation de Boehringer Ingelheim, et des honoraires de Novartis et Servier. Le Dr McDonald a aussi fait partie du comité de surveillance de la sécurité des données pour l’essai IVVE. Kara Nerenberg déclare avoir fait partie des comités pour les lignes directrices de pratique clinique de la Fondation canadienne des maladies du cœur et de l’AVC, Obésité Canada, Hypertension Canada, Diabète Canada et la Société des obstétriciens et gynécologues du Canada. Glen Pearson déclare avoir reçu des honoraires de consultation de Novartis Canada en tant que participant à des comités consultatifs. Alexandre Poppe déclare avoir reçu une subvention de recherche de Stryker et des honoraires de Pfizer-BMS. Le Dr Poppe a aussi fait partie du comité de surveillance de la sécurité des données pour l’essai FLOW sur la fluoxétine après l’AVC et du comité de surveillance de l’innocuité pour l’essai AcT (Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke) sur le ténectéplase dans l’AVC aigu. Le Dr Poppe a reçu le soutien d’une bourse du programme de recherche de Servier. Diana Sherifali déclare avoir reçu un financement personnel par l’entremise de la chaire de recherche médicale interprofessionnelle de l’Institut de santé publique Heather M. Arthur et Hamilton Health Sciences. Peter Selby déclare avoir reçu des subventions du ministère ontarien de la Santé et de Pfizer (Bourses de recherche mondiale sur la dépendance à la nicotine). Il fait aussi partie du comité de rédaction C-CHANGE depuis 2010. Eric Smith déclare avoir reçu des honoraires de consultation de Bayer, Biogen, Alnylam et Cyclerion. Sol Stern déclare avoir reçu des émoluments et des honoraires de consultation de MDBriefcase.com et Sea Courses inc. George Thanassoulis déclare avoir reçu des subventions, des émoluments et des honoraires de consultation de Amgen, Sanofi, Novartis et Silence. Le Dr Thanassoulis a aussi été membre du Comité de rédaction de la Ligne directrice sur la dyslipidémie de la SCC. Kristin Terenzi déclare avoir reçu des honoraires de consultation pour des comités consultatifs, des honoraires de conférencière et un soutien pour sa participation à des réunions de AstraZeneca, Boehringer Ingelheim, Astellas, Allergan, Amgen, Aspen, Bayer, Lilly, Lundbeck, AbbVie, Aralez, GSK, Merck, Novo Nordisk, Pfizer et Novartis. Karen Tu déclare avoir reçu des subventions (versées à son établissement) des institutions suivantes: IRSC, Fondation de l’Hôpital St. Michael, Collège des médecins de famille du Canada, Fondation pour l’avancement de la médecine familiale, Fondation AMC, Fonds d’exploration de l’Hôpital général de North York, Fondations canadienne et ontarienne des maladies du cœur et de l’AVC, ministère de la Défense des États-Unis, Université de Toronto — Département de médecine familiale et communautaire, MaRS Innovation Fund, Fondation canadienne de dermatologie, Société canadienne de rhumatologie (Canadian Initiative for Outcomes in Rheumatology Care), PSI Foundation, Action Cancer Ontario, Toronto Rehab Institute Chair Fund, UTOPIAN, Société d’arthrite, Société canadienne de la SP, Réseau canadien vasculaire, Prix IMPACT ciblé de l’unité de soutien SPOR de l’Ontario et Fondation Rathlyn. La Dre Tu détient une bourse en tant que chercheuse au Département de médecine familiale et communautaire de l’Université de Toronto. Jacob Udell déclare avoir reçu des subventions de Boehringer Ingelheim, Janssen, Sanofi et Novartis, et des honoraires de AstraZeneca, GlaxoSmithKline et Sanofi. Le Dr Udell a aussi fait partie de comités consultatifs pour Boehringer Ingelheim, Sanofi et Novartis. Sean Virani déclare avoir reçu des subventions de Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka et Medtronic, des honoraires de consultation de Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Seriver et Otsuka, et des honoraires de Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka et Medtronic. Le Dr Virani a aussi fait partie de comités de surveillance de la sécurité des données ou de comités consultatifs pour Abbott et Medtronic. Richard Ward déclare avoir reçu des honoraires de consultation de Eisai et Lilly-Boehringer Ingelheim, et une rémunération ou des honoraires de Boehringer Ingelheim, AstraZeneca, Janssen, Amgen, Lilly, Pfizer et Takeda. Le Dr Ward agit aussi à titre de directeur de l’Association médicale albertaine. Sean Wharton déclare avoir reçu des subventions et des honoraires de Novo Nordisk, Eli Lilly, Bausch Health Canada et Boehringer Ingelheim; il a fait partie comités de surveillance de la sécurité des données pour Novo Nordisk, Eli Lilly, Bausch Health Canada et Boehringer Ingelheim; et il a bénéficié de matériel et de services, de rédaction ou autres, de Novo Nordisk, Eli Lilly et Bausch Health Canada. Le Dr Wharton a aussi occupé un poste de responsabilité auprès de l’Obesity Society et d’Obésité Canada. Jennifer Zymantas déclare avoir reçu des honoraires de Pfizer comme modératrice lors de conférences portant sur l’anticoagulation. Diane Hua-Stewart occupe le poste de directrice du programme CHEP+. Peter Liu déclare avoir reçu des subventions de Génome Canada, de la Fondation des maladies du cœur et de l’AVC et des IRSC. Le Dr Liu détient un brevet pour l’IGFBP7, un biomarqueur de l’insuffisance cardiaque et il est directeur scientifique de l’Institut de cardiologie de l’Université d’Ottawa. Sheldon Tobe déclare avoir reçu une subvention et un soutien non matériel pour l’étude Zero to Five, remis à l’Institut de recherche Sunnybrook, des honoraires de consultation de AstraZeneca, et une rémunération pour le programme éducatif CHEP+ de Amgen, AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer et Sanofi Genzyme. Le Dr Tobe agit aussi bénévolement auprès de l’American Hypertension Specialists Certification Program. Aucun autre intérêt n’a été déclaré.

Background: Hidradenitis suppurativa (HS) is associated with several comorbidities such as diabetes mellitus and cardiovascular diseases. These comorbidities are also risk factors for chronic kidney disease (CKD), yet little is known about the risk of CKD in HS patients., Objectives: The objective was to study the prevalence of CKD in HS patients., Methods: Cross-sectional population-based study using the United States National Inpatient Sample database between January 1, 2002 and December 31, 2012 was performed., Results: We identified 23,767 hospital admissions for HS patients and 95,068 admissions for age- and gender-matched controls. The prevalence of CKD in HS patients was 6.3% (1,497/23,767) compared to non-HS controls which was 4.3% (4,052/95,068). The association of CKD was strongest in HS patients, who were ≥60 years old, 16.9% (475/2,811), male 7.3% (695/9,556), obese 7.8% (407/5,209), diabetic 12.5% (890/7,105), hyperlipidemic 13.3% (416/3,126), and had cardiovascular diseases 12.5% (631/5,045). The crude odds ratio of CKD in HS patients was 1.5 (95% CI: 1.420-1.605) compared to non-HS patients. The association remained significant after adjusting for important covariates with adjusted odds ratio of CKD in HS patients of 1.1 (95% CI: 1.014-1.176) compared to non-HS patients., Conclusions: Our findings show that there is a possible association of HS with CKD. Any signs of CKD should be assessed by a nephrologist as early diagnosis can hopefully prevent further progression., (The Author(s). Published by S. Karger AG, Basel.)

Competing Interests: Competing interests: James Stone reports receiving consulting fees and honoraria from Bayer Canada and Sanofi Canada. Dr. Stone is senior medical director, Cardiovascular Health and Stroke Strategic Clinical Network, Alberta Health Services; and member at large, Governing Council, College of Physicians and Surgeons of Alberta. Jason Andrade reports receiving payment or honoraria from Medtronic, Biosense-Webster, Abbott, Bio-tronik, Bayer, Servier and BMS-Pfizer. Simon Bacon reports receiving grants from Moderna, paid through Respiplus for the development of vaccine hesitancy education modules, and consultancy and speaker fees from Respiplus. Dr. Bacon has served on advisory boards for Bayer, Sanofi, Respiplus and Lucilab, none of which are related to the current article. Dr. Bacon also holds a Canadian Institutes of Health Research (CIHR) Strategy for Patient-Oriented Research Mentoring Chair (SMC-151518) and Fonds de recherche du Québec Chair (251618 and 309815). Harpreet Bajaj reports receiving grants from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, Janssen, Kowa Pharmaceuticals, Merck, Novo Nordisk, Pfizer, Sanofi and Tricida; and honoraria for lectures from Eli Lilly and Novo Nordisk. Mark Gelfer reports receiving consulting fees from Telus Health Care Centres and holding an unpaid role as board chair of GenXys Health Care Systems, in which Dr. Gelfer also holds stock options. Jeffrey Habert reports receiving consulting fees from MDBriefcase, Liv, MedPlan, Master Clinician Alliance, Academy, Bridge, Seacourses, Thrombosis Canada, Meducom, Antibody, the Canadian Heart Research Centre, CTC Communications, STA Healthcare Communications, Canadian Collaborative Research Network, CPD Network, Telus Health, EOCI Pharmacomm and Operatic. Dr. Habert has also received honoraria from Pfizer, Amgen, BMS, Bayer, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Purdue, Bausch, Allergan, AbbVie, AstraZeneca, Novartis, Lundbeck, Canadian Cardiovascular Health Education Program (CHEP+), Novo Nordisk, Janssen, Eisai, HLS, Otsuka, Sunovion and Jazz. Dr. Habert was the previous co-chair of the Thrombosis Canada Clinical Guides (2018–2021). Karim Keshavjee reports receiving consulting fees from McMaster University, Demers Professional Corporation and Normative. Darlene Kitty reports receiving teaching stipends from the University of Ottawa Faculty of Medicine and the McGill University Faculty of Medicine for occasional lectures, and travel support as director for the Indigenous Program of the University of Ottawa Faculty of Medicine. Dr. Kitty is the chair of the Indigenous Health Committee, College of Family Physicians of Canada. David Lau reports receiving grants from Novo Nordisk; consulting fees from Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly, Novo Nordisk and Viatris; honoraria from Amgen, Bayer, Boehringer Ingelheim, CME at Sea, HLS Therapeutics, Eli Lilly and Novo Nordisk; and payment for expert testimony from the Canadian Medical Protective Association. Dr. Lau has served in leadership roles with Obesity Canada and the Canadian Association of Bariatric Physicians and Surgeons. Laurent Macle reports receiving grants and honoraria from BMS-Pfizer, Servier and Bayer. Michael McDonald reports receiving consulting fees from Boehringer Ingelheim, and honoraria from Novartis and Servier. Dr. McDonald also participated in the data safety monitoring board for the IVVE Trial. Kara Nerenberg reports membership with the clinical practice guideline committees for the Heart and Stroke Foundation, Obesity Canada, Hypertension Canada, Diabetes Canada and the Society of Obstetricians and Gynaecologists of Canada. Glen Pearson reports receiving consulting fees from Novartis Canada as an advisory board participant. Alexandre Poppe reports receiving a research grant from Stryker and an honorarium from Pfizer-BMS. Dr. Poppe has also participated on a data safety monitoring board for the FLOW trial of fluoxetine after stroke and the safety committee for the Alteplase Compared to Tenecteplase in Patients With Acute Ischemic Stroke (AcT trial) of tenecteplase for acute stroke. Dr. Poppe has received fellowship program support from Servier. Diana Sherifali reports receiving personal funding through her Heather M. Arthur Population Health Institute/Hamilton Health Sciences Chair in Interprofessional Health Research. Peter Selby reports receiving grants from the Ontario Ministry of Health and Pfizer (Global Research Awards for Nicotine Dependence). Dr. Selby has also participated on the C-CHANGE guideline panel since 2010. Eric Smith reports receiving consulting fees from Bayer, Biogen, Alnylam and Cyclerion. Sol Stern reports receiving consulting fees and honoraria from MDBriefcase.com and Sea Courses Inc. George Thanassoulis reports receiving grants, consulting fees and honoraria from Amgen, Sanofi, Novartis and Silence. Dr. Thanassoulis has also been a member of the CCS Dyslipidemia Guideline committee. Kristin Terenzi reports receiving consulting fees for advisory boards of, honoraria for speaking events for, and support for attending meetings from AstraZeneca, Boehringer Ingelheim, Astellas, Allergan, Amgen, Aspen, Bayer, Lilly, Lundbeck, AbbVie, Aralez, GSK, Merck, Novo Nordisk, Pfizer and Novartis. Karen Tu reports receiving grants (payments to institution) from CIHR, St. Michael’s Hospital Foundation, The College of Family Physicians of Canada, Foundation for Advancing Family Medicine, Canadian Medical Association Foundation, North York General Hospital Exploration Fund, Heart and Stroke Foundation of Canada, Heart and Stroke Foundation of Ontario, United States Department of Defense, University of Toronto — Department of Family and Community Medicine, MaRS Innovation Fund, Canadian Dermatology Foundation, Canadian Rheumatology Association (Canadian Initiative for Outcomes in Rheumatology Care), PSI Foundation, Cancer Care Ontario, Toronto Rehab Institute Chair Fund, UTOPIAN, Arthritis Society, MS Society of Canada, The Canadian Vascular Network, Ontario SPOR Support Unit Targeted IMPACT Award and Rathlyn Foundation. Dr. Tu holds a Research Scholar Award from the Department of Family and Community Medicine at the University of Toronto. Jacob Udell reports receiving grants from Boehringer Ingelheim, Janssen, Sanofi and Novartis; and honoraria from AstraZeneca, GlaxoSmithKline and Sanofi. Dr. Udell has also participated on advisory boards for Boehringer Ingelheim, Sanofi and Novartis. Sean Virani reports receiving grants from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka and Medtronic; consulting fees from Abbott, Amgen, AstraZeneca, Boehringer Ingelheim, Bayer, Novartis, Seriver and Otsuka; and honoraria from Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bayer, Novartis, Servier, Otsuka and Medtronic. Dr. Virani has also participated in data safety monitoring boards or advisory boards for Abott and Medtronic. Richard Ward reports receiving consulting fees from Eisai and Lilly-Boehringer Ingelheim, and payment or honoraria from Boehringer Ingelheim, AstraZeneca, Janssen, Amgen, Lilly, Pfizer and Takeda. Dr. Ward also serves as director of the Alberta Medical Association. Sean Wharton reports receiving grants and honoraria from Novo Nordisk, Eli Lilly, Bausch Health Canada and Boehringer Ingelheim; has participated in data safety monitoring boards for Novo Nordisk, Eli Lilly, Bausch Health Canada and Boehringer Ingelheim; and has received equipment, medical writing or other services from Novo Nordisk, Eli Lilly and Bausch Health Canada. Dr. Wharton has also played a leadership role in The Obesity Society and Obesity Canada. Jennifer Zymantas reports receiving an honorarium from Pfizer for a moderator role during speaking engagements related to anticoagulation. Diane Hua-Stewart holds the role of director of CHEP+. Peter Liu reports receiving grants from Genome Canada, the Heart and Stroke Foundation and CIHR. Dr. Liu holds a patent for IGFBP7 as a biomarker for heart failure and is chief scientific officer with the University of Ottawa Heart Institute. Sheldon Tobe reports receiving a KMH clinic unrestricted grant and in-kind support for the Zero to Five study, paid to Sunnybrook Research Institute; consulting fees from AstraZeneca; and payment for the CHEP+ education program from Amgen, Astra-Zeneca, BMS, Bayer, Boehringer Ingelheim, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer and Sanofi Genzyme. Dr. Tobe also holds a volunteer role with the American Hypertension Specialists Certification Program. No other competing interests were declared.

Plasma exposure of the endothelin receptor antagonist atrasentan varies between individuals and is associated with nephroprotective effects and the risk of heart failure. We examined the influence of genetic polymorphisms on atrasentan plasma exposure and pharmacodynamic effects. We performed a substudy of the Study of Diabetic Nephropathy With Atrasentan (SONAR) trial which enrolled adults with type 2 diabetes and chronic kidney disease (estimated glomerular filtration rate: 25-75 mL/min/1.73 m 2 , and a urine albumin-to-creatinine ratio of 300-5,000 mg/g). Single nucleotide polymorphisms (SNPs) were determined for prespecified membrane transporters, metabolizing enzymes, and the endothelin-1 peptide. The associations among genotype, atrasentan plasma exposure, and the effect of atrasentan on the prespecified kidney and heart failure hospitalization (HHF) outcomes was assessed with Cox proportional hazards regression models. Of 3,668 patients randomized, 2,329 (63.5%) consented to genotype analysis. Two SNPs in the SLCO1B1 gene (rs4149056 and rs2306283), encoding the hepatic organic anion transporter 1B1 (OATP1B1), showed the strongest association with atrasentan plasma exposure. Based on their SLCO1B1 genotype, patients were classified into normal (atrasentan area under the plasma-concentration time curve from zero to infinity (AUC 0-inf ) 41.3 ng·h/mL) or slow (atrasentan AUC 0-inf 49.7 ng·h/mL, P < 0.001) OATP1B1 transporter phenotypes. Among patients with a normal OATP1B1 phenotype, the hazard ratio (HR) with atrasentan for the primary kidney and HHF outcomes were 0.61 (95% confidence interval (CI): 0.45-0.81) and 1.35 (95% CI: 0.84-2.13), respectively. In the slow transporter phenotype, HRs for kidney and HHF outcomes were 1.95 (95% CI: 0.95-4.03, P-interaction normal phenotype = 0.004), and 4.18 (95% CI: 1.37-12.7, P-interaction normal phenotype = 0.060), respectively. OATP1B1 gene polymorphisms are associated with significant between-patient variability in atrasentan plasma exposure and long-term efficacy and safety., (© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Heart failure (HF) often develops in patients with diabetes and is recognized for its role in increased cardiovascular morbidity and mortality in this population. Most existing models predict risk in patients with prevalent rather than incident diabetes and fail to account for sex differences in HF risk factors. We derived sex-specific models in Ontario, Canada to predict HF at diabetes onset and externally validated these models in the U.K., Research Design and Methods: Retrospective cohort study using international population-based data. Our derivation cohort comprised all Ontario residents aged ≥18 years who were diagnosed with diabetes between 2009 and 2018. Our validation cohort comprised U.K. patients aged ≥35 years who were diagnosed with diabetes between 2007 and 2017. Primary outcome was incident HF. Sex-stratified multivariable Fine and Gray subdistribution hazard models were constructed, with death as a competing event., Results: A total of 348,027 Ontarians (45% women) and 54,483 U.K. residents (45% women) were included. At 1, 5, and 9 years, respectively, in the external validation cohort, the C-statistics were 0.81 (95% CI 0.79-0.84), 0.79 (0.77-0.80), and 0.78 (0.76-0.79) for the female-specific model; and 0.78 (0.75-0.80), 0.77 (0.76-0.79), and 0.77 (0.75-0.79) for the male-specific model. The models were well-calibrated. Age, rurality, hypertension duration, hemoglobin, HbA1c, and cardiovascular diseases were common predictors in both sexes. Additionally, mood disorder and alcoholism (heavy drinker) were female-specific predictors, while income and liver disease were male-specific predictors., Conclusions: Our findings highlight the importance of developing sex-specific models and represent an important step toward personalized lifestyle and pharmacologic prevention of future HF development., (© 2022 by the American Diabetes Association.)

As the leading risk for death, population control of increased blood pressure represents a major challenge for all countries of the Americas. In the early 1990's, Canada had a hypertension control rate of 13%. The control rate increased to 68% in 2010, accompanied by a sharp decline in cardiovascular disease. The unprecedented improvement in hypertension control started around the year 2000 when a comprehensive program to implement annually updated hypertension treatment recommendations started. The program included a comprehensive monitoring system for hypertension control. After 2011, there was a marked decrease in emphasis on implementation and evaluation and the hypertension control rate declined, driven by a reduction in control in women from 69% to 49%. A coalition of health and scientific organizations formed in 2011 with a priority to develop advocacy positions for dietary policies to prevent and control hypertension. By 2015, the positions were adopted by most federal political parties, but implementation has been slow. This manuscript reviews key success factors and learnings. Some key success factors included having broad representation on the program steering committee, multidisciplinary engagement with substantive primary care involvement, unbiased up to date credible recommendations, development and active adaptation of education resources based on field experience, extensive implementation of primary care resources, annual review of the program and hypertension indicators and developing and emphasizing the few interventions important for hypertension control. Learnings included the need for having strong national and provincial government engagement and support, and retaining primary care organizations and clinicians in the implementation and evaluation.

Background: Early identification of people with diabetes or prediabetes enables greater opportunities for glycemic control and management strategies to prevent related complications. To identify gaps in screening for these conditions, we examined population trends in receipt of timely glucose testing overall and in specific clinical subgroups., Methods: Using linked administrative databases, we conducted a retrospective cohort study of people aged 40 years and older without diabetes at baseline. Our primary outcome was up-to-date glucose testing, defined as having received testing at least once in the 3 years before each index year from 2010 to 2017, using linked administrative databases of people residing in Ontario, Canada. We calculated rates of up-to-date testing by age group, sex, ethnicity (South Asian, Chinese, general population) and comorbidities (hypertension, hyperlipidemia, cardiovascular disease)., Results: Over the 8-year study period, up-to-date glucose testing rates were stable at 67% for men and 77% for women (both relative risk 1.00 per year; 95% confidence interval 1.00-1.00). Testing rates were significantly lower in men than in women (all age groups p < 0.001) and lower in younger than older age groups (except those aged ≥ 80 yr). South Asian people had the highest testing rates, although among people aged 70 years or older, testing was highest in the general population ( p < 0.001). Among people with hypertension, hyperlipidemia and cardiovascular disease, annual testing rates were also stable, but only 58% overall among people with hypertension., Interpretation: We found lower glucose testing rates in younger men and people with hypertension. Our findings reinforce the need for initiatives to increase awareness of glycemic testing., Competing Interests: Competing interests: Catherine Yu reports receiving research grants from the St. Michael’s Hospital Medical Services Association, St. Michael’s Hospital (Unity Health Toronto), the Ontario SPOR SUPPORT Unit and the Royal College of Physicians and Surgeons of Canada. Kim Connelly reports receiving research grants and payment for presentations from AstraZeneca, Servier, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk and Merck. Dr. Connelly also reports serving on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Servier, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk and Merck. Gillian Booth reports receiving grants or contracts from the Canadian Institutes of Health Research (CIHR), Juvenile Diabetes Research Foundation and the Thistledown Foundation. Karen Tu reports receiving payments (to institutions) from CIHR, St. Michael’s Hospital Foundation, The College of Family Physicians of Canada, Foundation for Advancing Family Medicine, Canadian Medical Association Foundation, North York General Hospital, Heart and Stroke Foundation of Canada, Heart and Stroke Foundation of Ontario, Department of Defense (United States), University of Toronto (Department of Family and Community Medicine), MaRS Innovation Fund, Canadian Dermatology Foundation, Canadian Rheumatology Association (Canadian Initiative for Outcomes in Rheumatology Care), PSI Foundation, Cancer Care Ontario, Toronto Rehabilitation Institute Chair Fund, University of Toronto Practice-Based Research Network, Arthritis Society, MS Society of Canada, The Canadian Vascular Network and the Ontario SPOR SUPPORT Unit Targeted IMPACT Award. Sheldon Tobe reports receiving a KMH clinic unrestricted grant and in-kind support for the Zero to Five study, and consulting fees from AstraZeneca (all paid to Sunnybrook Research Institute). Dr. Tobe also reports receiving payment from Amgen, Astra-Zeneca, Bristol Myers Squibb, Bayer, Boehringer Ingelheim, Janssen, Lilly, Novartis, Novo Nordisk, Pfizer and Sanofi Genzyme for the CHEPPLUS education program. Dr. Tobe has worked on a volunteer basis with the American Hypertension Specialists Certification Program. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Background: The endothelin receptor antagonist atrasentan reduced the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease (CKD) in the SONAR (Study of Diabetic Nephropathy with Atrasentan) trial, although with a numerically higher incidence of heart failure (HF) hospitalization., Objectives: The purpose of this study was to assess if early changes in B-type natriuretic peptide (BNP) and body weight during atrasentan treatment predict HF risk., Methods: Participants with type 2 diabetes and CKD entered an open-label enrichment phase to assess response to atrasentan 0.75 mg/day. Participants without substantial fluid retention (>3 kg body weight increase or BNP increase to >300 pg/mL), were randomized to atrasentan 0.75 mg/day or placebo. Cox proportional hazards regression was used to assess the effects of atrasentan vs placebo on the prespecified safety outcome of HF hospitalizations., Results: Among 3,668 patients, 73 (4.0%) participants in the atrasentan and 51 (2.8%) in the placebo group developed HF (HR: 1.39; 95% CI: 0.97-1.99; P = 0.072). In a multivariable analysis, HF risk was associated with higher baseline BNP (HR: 2.32; 95% CI: 1.81-2.97) and percent increase in BNP during response enrichment (HR: 1.46; 95% CI: 1.08-1.98). Body weight change was not associated with HF. Exclusion of patients with at least 25% BNP increase during enrichment attenuated the risk of HF with atrasentan (HR: 1.02; 95% CI: 0.66-1.56) while retaining nephroprotective effects (HR: 0.58; 95% CI: 0.44-0.78)., Conclusions: In patients with type 2 diabetes and CKD, baseline BNP and early changes in BNP in response to atrasentan were associated with HF hospitalization, highlighting the importance of natriuretic peptide monitoring upon initiation of atrasentan treatment. (Study Of Diabetic Nephropathy With Atrasentan [SONAR]; NCT01858532)., Competing Interests: Funding Support and Author Disclosures This study was conducted in the framework of the IMI BEAt-DKD program. The BEAt-DKD project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115974. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA. Dr Kohan has served as a consultant for AbbVie, AstraZeneca, Chinook Therapeutics, and Travere Therapeutics. Dr Bakris has received support from T32 National Institutes of Health grant DK07011; has served as a consultant to Merck, Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Horizon, and Novo Nordisk; and has served on the steering committee of trials for Bayer, Quantum Genomics, Alnylam, and Novo Nordisk. Dr Correa-Rotter has served on advisory boards for Boehringer and AstraZeneca; and has been a speaker for AstraZeneca, Boehringer Ingelheim, AbbVie, Takeda, Amgen, and Janssen. Dr Hou has served as a consultant for and received honoraria from AbbVie and AstraZeneca. Dr Januzzi is supported by the Hutter Family Professorship; is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and has participated in clinical endpoint committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr Kitzman has received grant funding from Novartis, Bayer, NovoNordisk, and AstraZeneca; honoraria for consulting from AbbVie, Bayer, Merck, Medtronic, Relypsa, Merck, Corvia Medical, Boehringer Ingelheim, NovoNordisk, AstraZeneca, Keyto, Pfizer, and Novartis; stock ownership in Gilead Sciences. Dr Kolansky has participated in clinical endpoint committees for ACI Clinical, George Clinical, and the Baim Institute for Clinical Research. Dr Makino has served on steering committees for AbbVie and Teijin; and has served on advisory boards for Boehringer Ingelheim and Travere Therapeutics. Dr Perkovic has served on steering committees for trials funded by AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Novo Nordisk, Retrophin, and Tricida; and has participated in scientific presentations or advisory boards with AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol Myers Squibb, Boehringer Ingelheim, Dimerix, Durect, Eli Lilly, Gilead, GlaxoSmithKline, Janssen, Merck, Mitsubishi Tanabe, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Retrophin, Sanofi, Servier, and Tricida. Dr Tobe has participated on a steering committee for Bayer Fidelio/Figaro studies; and has served on the Speakers Bureau of Servier and Pfizer. Dr Parving was the co-chair of the SONAR study steering committee; and has served as a consultant for AbbVie. Dr de Zeeuw has served on advisory boards and/or as a speaker for Bayer, Boehringer Ingelheim, Fresenius, Mitsubishi-Tanabe, and Travere Pharmaceuticals; has served on Steering Committees and/or as a speaker for AbbVie and Janssen; and has served on the Data Safety and Monitoring Committees for Bayer, with honoraria paid to the institution and consultant/speaker. Dr Heerspink is supported by a VIDI (917.15.306) grant from the Netherlands Organisation for Scientific Research; has served as a consultant for AbbVie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, CSL Pharma, Fresenius, Gilead, Janssen, Merck, Mundipharma, Mitsubishi Tanabe, and Retrophin; and has received grant support from AbbVie, AstraZeneca, Boehringer Ingelheim, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Atrasentan reduces the risk of kidney failure but increases the risk of edema and, possibly, heart failure. Patients with severe CKD may obtain greater absolute kidney benefits from atrasentan but may also be at higher risk of heart failure. We assessed relative and absolute effects of atrasentan on kidney and heart failure events according to baseline eGFR and urinary albumin-creatinine ratio (UACR) in a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial., Design, Setting, Participants, & Measurements: The effect of atrasentan versus placebo in 3668 patients with type 2 diabetes and CKD with elevated albuminuria was examined in the SONAR trial. We used Cox proportional hazards regression analysis to study effects on the primary kidney outcome (composite of doubling of serum creatinine, kidney failure, or kidney death) and heart failure hospitalization across subgroups of eGFR (<30, ≥30-45, and ≥45 ml/min per 1.73 m 2 ) and UACR (<1000, ≥1000-3000, and ≥3000 mg/g)., Results: Atrasentan reduced the relative risk of the primary kidney outcome (hazard ratio, 0.71; 95% confidence interval, 0.58 to 0.88) consistently across all subgroups of baseline eGFR and UACR (all P interaction >0.21). Patients in the highest UACR and lowest eGFR subgroups, in whom rates of the primary kidney outcome were highest, showed the largest absolute benefit (all P interaction <0.01). The risk of heart failure hospitalization was higher in the atrasentan group (hazard ratio, 1.39; 95% confidence interval, 0.97 to 1.99) and was consistent across subgroups, with no evidence that relative or absolute risks differed across eGFR or UACR subgroups (all P interaction >0.09)., Conclusions: Atrasentan reduced the relative risk of the primary kidney outcome consistently across baseline UACR and eGFR subgroups. The absolute risk reduction was greater among patients in the lowest eGFR and highest albuminuria category who were at highest baseline risk. Conversely, the relative and absolute risks of heart failure hospitalization were similar across baseline UACR and eGFR subgroups. Clinical Trial registry name and registration number: Study of Diabetic Nephropathy with Atrasentan (SONAR), NCT01858532., (Copyright © 2021 by the American Society of Nephrology.)

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline., Methods: The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020., Recommendations: The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.

[Figure: see text].

Atrasentan, an endothelin receptor antagonist, showed clinically significant albuminuria reduction with minimal signs of fluid retention in phase II trials. We evaluated whether plasma exposure was associated with long-term outcomes for kidney protection and heart failure in the phase III SONAR trial (n = 3668) in type 2 diabetics with chronic kidney disease. A population pharmacokinetic model was used to estimate plasma exposure of atrasentan 0.75 mg/day. Parametric time-to-event models were used to quantify the association between plasma exposure and long-term outcomes. Mean atrasentan plasma exposure was 41.4 ng.h/mL (2.5th to 97.5th P: 14.2 to 139.9). Compared with placebo, a mean atrasentan exposure translated in a hazard ratio of 0.76 (95% confidence interval (CI): 0.28-0.85) for kidney events and 1.13 (95% CI: 1.03-2.20) for heart failure events. At the mean atrasentan exposure, the kidney protective effect was larger than the increase in heart failure supporting the atrasentan 0.75 mg/day dose in this population., (© 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Aim: To better understand the healthcare burden of people with type 2 diabetes (T2D) and estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m 2 in Ontario, Canada., Materials and Methods: We used administrative data to evaluate the prevalence of T2D, eGFR < 90 mL/min/1.73 m 2 and adverse cardiovascular co-morbidities in individuals aged ≥ 30 years living in Ontario, Canada. We also examined incremental healthcare costs and healthcare resource utilization (HCRU) for these patients with specific incident cardiovascular and renal outcomes, in comparison with controls without these outcomes., Results: While the prevalence of T2D in the general population aged ≥ 30 years in Ontario increased by 1.8% over a 5-year period (2011-2012 to 2015-2016), the prevalence of eGFR < 90 mL/min/1.73 m 2 among people with T2D increased by 35%. In comparison with corresponding controls without these outcomes, the per patient average total costs (Canadian dollars) over a 2-year analysis period were higher for patients with cardiovascular disease/chronic kidney disease related death ($69 827; n = 32 407), doubling of serum creatinine ($52 260; n = 22 825), those who started dialysis ($150 627; n = 3499) or received a kidney transplant ($50 664; n = 651). Similarly, HCRU was significantly greater for patients with these incident outcomes., Conclusions: This real-world retrospective study highlights an increasing prevalence of T2D, eGFR < 90 mL/min/1.73 m 2 , and the substantially higher healthcare costs and HCRU when these patients have adverse cardiovascular and renal outcomes. The existence of such a large economic burden underpins the importance of preventing these diabetes-related complications., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 Clinical Practice Guideline for the Management of Blood Pressure in Chronic Kidney Disease for patients not receiving dialysis represents an update to the KDIGO 2012 guideline on this topic. Development of this guideline update followed a rigorous process of evidence review and appraisal. Guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence. The strength of recommendations is based on the "Grading of Recommendations Assessment, Development and Evaluation" (GRADE) approach. The scope includes topics covered in the original guideline, such as optimal blood pressure targets, lifestyle interventions, antihypertensive medications, and specific management in kidney transplant recipients and children. Some aspects of general and cardiovascular health, such as lipid and smoking management, are excluded. This guideline also introduces a chapter dedicated to proper blood pressure measurement since all large randomized trials targeting blood pressure with pivotal outcomes used standardized preparation and measurement protocols adhered to by patients and clinicians. Based on previous and new evidence, in particular the Systolic Blood Pressure Intervention Trial (SPRINT) results, we propose a systolic blood pressure target of less than 120 mm Hg using standardized office reading for most people with chronic kidney disease (CKD) not receiving dialysis, the exception being children and kidney transplant recipients. The goal of this guideline is to provide clinicians and patients a useful resource with actionable recommendations supplemented with practice points. The burden of the recommendations on patients and resources, public policy implications, and limitations of the evidence are taken into consideration. Lastly, knowledge gaps and recommendations for future research are provided., (Copyright © 2021 KDIGO. Published by Elsevier Inc. All rights reserved.)

Aim: To evaluate whether atrasentan plasma exposure explains between-patient variability in urinary albumin-to-creatinine ratio (UACR) response, a surrogate for kidney protection, and B-type natriuretic peptide (BNP) response, a surrogate for fluid expansion., Methods: Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run-in period. Individual area under the concentration-time-curve (AUC) was estimated using a population pharmacokinetic model. The association between atrasentan AUC, other clinical characteristics, and UACR and BNP response, was estimated using linear regression., Results: The median atrasentan AUC was 43.8 ng.h/mL with a large variation among patients (2.5th-97.5th percentiles [P]: 12.6 to 197.5 ng.h/mL). Median UACR change at the end of enrichment was -36.0% and median BNP change was 8.7%, which also varied among patients (UACR, 2.5th-97.5th P: -76.2% to 44.5%; BNP, 2.5th-97.5th P: -71.5% to 300.0%). In the multivariable analysis, higher atrasentan AUC was associated with greater UACR reduction (4.88% per doubling in ng.h/mL [95% confidence interval {CI}: 6.21% to 3.52%], P < .01) and greater BNP increase (3.08% per doubling in ng.h/mL [95% CI: 1.12% to 4.11%], P < .01) independent of estimated glomerular filtration rate, haemoglobin or BNP. Caucasian patients compared with black patients had greater UACR reduction (7.06% [95% CI: 1.38% to 13.07%]) and also greater BNP increase (8.75% [95% CI: 1.65% to 15.35%]). UACR response was not associated with BNP response (r = 0.06)., Conclusion: Atrasentan plasma exposure varied among individual patients and partially explained between-patient variability in efficacy and safety response., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Introduction: First Nations communities are known to have high rates of diabetes. The rural First Nations communities in northwest (NW) Ontario are particularly affected. Regional studies in 1985 and 1994 found a high prevalence of diabetes. More recently, they are estimated to have the highest prevalence in Ontario at 19%, double the provincial norm. The purpose of this study is to examine the epidemiology and prevalence of diabetes in the total population and cardiovascular comorbidities in the adult population of 25 First Nations communities in NW Ontario., Methods: This retrospective diabetes prevalence study used primary care electronic medical record data for a 3-year period, 1 August 2014-31 July 2017. Diabetes prevalence was calculated for both the total and the adult (18+) populations and comorbid hypertension and dyslipidaemia were identified in adults., Results: The age-adjusted diabetes prevalence for the total population was 15.1% versus a Canadian prevalence of 8.8%. The age-adjusted adult prevalence was 14.1%, double Canada's average of 7.1%. The average age of adults with diabetes was 52 years (±14.9); 57% were female. Comorbid hypertension (58%) and dyslipidaemia (73%) were common. Metformin was the most commonly used medication (58%), followed by insulin/analogues (23%) and sulphonylureas (13%)., Conclusion: The diabetes prevalence in the First Nations population of NW Ontario is double Canada's norm. Addressing it will require addressing relevant social determinants of health, including poverty and food security., Competing Interests: None

Rationale: Hemodialysis patients are at significant risk from COVID-19 due to their frequent interaction with the health care system and medical comorbidities. We followed up the trajectory of the first COVID-19-positive maintenance hemodialysis patient at Sunnybrook Health Sciences Centre in Toronto. We present the lessons learned and changes in practices that occurred to prevent an outbreak in our center., Presenting Concerns of the Patient: The patient, a 66-year-old woman on in-center hemodialysis, initially presented with a 2-day history of a productive cough. She subsequently developed a fever, was placed on contact and droplet isolation, and admitted to hospital., Diagnoses: On March 13, 2020, the patient tested positive for COVID-19. Within the next 48 hours, she developed hypoxia and acute respiratory distress syndrome as a complication of her illness requiring an extended critical care stay. This extended critical care stay resulted in critical illness-associated secondary sclerosing cholangitis., Interventions: An interprofessional team was established, performing rapid Plan-Do-Study-Act quality improvement cycles to improve screening practices and promote the safety of patients and staff in the hemodialysis unit., Outcomes: We present here the lessons learned, the changes to our screening protocols, and the clinical course of our first in-center hemodialysis patient with SARS-CoV-2., Teaching Points: Regular review of the infection screening processes is paramount in preventing outbreaks of COVID-19, particularly in hemodialysis units. Hospital admission should be arranged if a patient exhibits any clinical signs of hemodynamic compromise or hypoxia. Early education for health care practitioners caring for patients with COVID-19 and refresher information regarding personal protective equipment helped promote the safety of staff and prevent health care-associated outbreaks., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2020.)

Background: We previously found large variation among family physicians in adherence to the C anadian C ardiovascular H armonization of N ational G uidelines E ndeavour (C-CHANGE). We assessed the role of patient- and physician-level factors in the variation in adherence to recommendations for managing cardiovascular disease risk factors., Methods: We conducted a retrospective study using multilevel logistic regression analyses with the E lectronic M edical R ecord A dministrative data L inked D atabase (EMRALD) housed at ICES in Ontario. Five quality indicators based on C-CHANGE guidelines were modelled. Effects of clustering and between-group variation, patient-level (sociodemographics, comorbidities) and physician-level characteristics (demographic and practice information) were assessed to determine odds ratios of receiving C-CHANGE recommended care., Results: In all, 324 Ontario physicians practicing in 41 clinics who provided care to 227,999 adult patients were studied. We found significant variation in quality indicators, with 15% to 39% of the total variation attributable to nonpatient factors. The largest variation was in performing 2-hour plasma glucose testing in prediabetic patients. Patient-level factors most frequently associated with recommendation adherence included sex, age, and multi-comorbidities. Women were more likely than men to have their body mass index measured, and their blood pressure controlled, but less likely to receive antiplatelet medications and liver-enzyme testing if overweight or obese., Conclusions: The majority of variations in adherence were attributable to patient attributes, but a substantial proportion of unexplained variation was due to differences among physicians and clinics. This finding may signal suboptimal processes or structures and warrant further investigation to improve the quality of primary care management of cardiovascular disease in Ontario., (© 2020 Canadian Cardiovascular Society. Published by Elsevier Inc.)

Hypertension Canada's 2020 guidelines for the prevention, diagnosis, risk assessment, and treatment of hypertension in adults and children provide comprehensive, evidence-based guidance for health care professionals and patients. Hypertension Canada develops the guidelines using rigourous methodology, carefully mitigating the risk of bias in our process. All draft recommendations undergo critical review by expert methodologists without conflict to ensure quality. Our guideline panel is diverse, including multiple health professional groups (nurses, pharmacy, academics, and physicians), and worked in concert with experts in primary care and implementation to ensure optimal usability. The 2020 guidelines include new guidance on the management of resistant hypertension and the management of hypertension in women planning pregnancy., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

We present Hypertension Canada's inaugural evidence-based recommendations for the diagnosis and management of resistant hypertension. Hypertension is present in 21% of the Canadian population, and among those with hypertension, resistant hypertension has an estimated prevalence from 10% to 30%. This subgroup of hypertensive individuals is important, because resistant hypertension portends a high cardiovascular risk. Because of its importance, Hypertension Canada formed a Guidelines Committee to conduct a review of the evidence and develop recommendations for the diagnosis and management of resistant hypertension. The Hypertension Canada Guidelines Committee recommends that patients with blood pressure above target, despite use of 3 or more blood pressure-lowering drugs at optimal doses, preferably including a diuretic, be identified as those with apparent resistant hypertension. Patients identified with apparent resistant hypertension should be assessed for white coat effect, nonadherence, and therapeutic inertia, investigated for secondary hypertension, and referred to a provider with expertise in hypertension. There is no randomized controlled trial evidence for better cardiovascular outcomes with any class of antihypertensive agent at this time, so recommendations for a preferred drug class cannot be made. Furthermore, we provide a summary of the current evidence concerning the role of device therapy in the management of resistant hypertension. We will continue updating the guidelines as additional high-quality evidence with relevance to daily practice becomes available., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: DREAM-GLOBAL (Diagnosing hypertension-Engaging Action and Management in Getting Lower Blood Pressure in Indigenous and low- and middle-income countries) studied a SMS text messaging-based system for blood pressure measurement and hypertension management in Canadian Aboriginal and Tanzanian communities. The use of SMS text messages is an emerging point of interest in global health care initiatives because of their scalability, customizability, transferability, and cost-effectiveness., Objective: The study aim was to assess the effect on the difference in blood pressure reduction of active hypertension management messages or passive health behavior messages. The system was designed to be implemented in remote areas with wireless availability. This study described the implementation and evaluation of technical components, including quantitative data from the transmission of blood pressure measurements and qualitative data collected on the operational aspects of the system from participants, health care providers, and community leadership., Methods: The study was implemented in six remote Indigenous Canadian and two rural Tanzanian communities. Blood pressure readings were taken by a community health worker and transmitted to a mobile phone via Bluetooth, then by wireless to a programmed central server. From the server, the readings were sent to the participant's own phone as well. Participants also received biweekly tailored SMS text messages on their phones. Quantitative data on blood pressure reading transmissions were collected from the study central server. Qualitative data were collected by surveys, focus groups, and key informant interviews of participants, health care providers, and health leadership., Results: In Canada, between February 2014 and February 2017, 2818 blood pressure readings from 243 patients were transmitted to the central server. In Tanzania, between October 2014 and August 2015, 1165 readings from 130 patients were transmitted to the central server. The use of Bluetooth technology enabled the secure, reliable transmission of information from participants to their health care provider. The timing and frequency were satisfactory to 137 of 187 (73.2%) of participants, supporting the process of sending weekly messages twice on Mondays and Thursdays at 11 am. A total of 97.0% (164/169) of the participants surveyed said they would recommend participation in the DREAM-GLOBAL program to a friend or relative with hypertension., Conclusions: In remote communities, the DREAM-GLOBAL study helped local health care providers deliver a blood pressure management program that enabled patients and community workers to feel connected. The technical components of the study were implemented as planned, and patients felt supported in their management through the SMS text messaging and mobile health program. Technological issues were solved with troubleshooting. Overall, the technical aspects of this research program enhanced clinical care and study evaluation and were well received by participants, health care workers, and community leadership., Trial Registration: Clinicaltrials.gov NCT02111226; https://clinicaltrials.gov/ct2/show/NCT02111226., (©Jordan Andrea Barsky, Rebekah Hunter, Colin McAllister, Karen Yeates, Norm Campbell, Peter Liu, Nancy Perkins, Diane Hua-Stewart, Marion A Maar, Sheldon W Tobe. Originally published in JMIR mHealth and uHealth (http://mhealth.jmir.org), 09.12.2019.)

Objectives: For patients with type 2 diabetes, newer antihyperglycaemic agents (AHA), including the dipeptidyl peptidase IV inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA) and sodium glucose co-transporter 2 inhibitors (SGLT2i) offer a lower risk of hypoglycaemia relative to sulfonylurea or insulin. However, it is not clear how AHA compare to placebo on risk of any hypoglycaemia. This study evaluates the risk of any and severe hypoglycaemia with AHA and metformin relative to placebo., Design: A systematic review and meta-analysis was conducted of randomized, placebo-controlled trials ≥12 weeks in duration. MEDLINE, Embase and the Cochrane Library were searched up to April 16, 2019. Studies allowing use of other diabetes medications were excluded. Mantel-Haenszel risk ratio with 95% confidence intervals were used to pool estimates based on class of AHA and number of concomitant therapies used., Patients: Eligible studies enrolled patients with type 2 diabetes ≥18 years of age., Results: 144 studies met our inclusion criteria. Any hypoglycaemia was not increased with AHA when used as monotherapy (DPP4i (RR 1.12; 95% CI 0.81-1.56), GLP1RA (1.77; 0.91-3.46), SGLT2i (1.34; 0.83-2.15)), or as add-on to metformin (DPP4i (0.95; 0.67-1.35), GLP1RA (1.24; 0.80-1.91), SGLT2i (1.29; 0.91-1.83)) or as triple therapy (1.13; 0.67-1.91). However, metformin monotherapy (1.73; 1.02-2.94) and dual therapy initiation (3.56; 1.79-7.10) was associated with an increased risk of any hypoglycaemia. Severe hypoglycaemia was rare not increased for any comparisons., Conclusions: Metformin and the simultaneous initiation of dual therapy, but not AHA used alone or as single add-on combination therapy, was associated with an increased risk of any hypoglycaemia relative to placebo., Competing Interests: Ms Kamalinia initiated her Master's degree while an employee of Merck Canada Inc. with educational support but has since left to focus on her studies. Merck Canada Inc did not play any role in the conception of the research question, protocol development, data synthesis or interpretation. Dr RGJ reports personal fees from Merck, AZ, Novo Nordisk, Lilly/BI and Janssen, outside the submitted work. Ms LL, Mr PJD and Dr BRS declare no competing interests. Dr SWT reports grants from Eli Lilly, Astra Zeneca, AbbVie and Bayer for participation in international contract research studies as well as honoraria for speaker's bureaus from Servier and Valeant during the conduct of the study and has had travel reimbursed by the Novartis Foundation., (© 2019 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: There is a paucity of controlled clinical trial data based on research with Indigenous peoples. A lack of data specific to Indigenous peoples means that new therapeutic methods, such as those involving electronic health (eHealth), will be extrapolated to these groups based on research with other populations. Rigorous, ethical research can be undertaken in collaboration with Indigenous communities but requires careful attention to culturally safe research practices. Literature on how to involve Indigenous peoples in the development and evaluation of eHealth or mobile health apps that responds to the needs of Indigenous patients, providers, and communities is still scarce; however, the need for community-based participatory research to develop culturally safe technologies is emerging as an essential focus in Indigenous eHealth research. To be effective, researchers must first gain an in-depth understanding of Indigenous determinants of health, including the harmful consequences of colonialism. Second, researchers need to learn how colonialism affects the research process. The challenge then for eHealth researchers is to braid Indigenous ethical values with the requirements of good research methodologies into a culturally safe research protocol., Objective: A recent systematic review showed that Indigenous peoples are underrepresented in randomized controlled trials (RCTs), primarily due to a lack of attention to providing space for Indigenous perspectives within the study frameworks of RCTs. Given the lack of guidelines for conducting RCTs with Indigenous communities, we conducted an analysis of our large evaluation data set collected in the Diagnosing Hypertension-Engaging Action and Management in Getting Lower Blood Pressure in Indigenous Peoples and Low- and Middle- Income Countries (DREAM-GLOBAL) trial over a period of five years. Our goal is to identify wise practices for culturally safe, collaborative eHealth and RCT research with Indigenous communities., Methods: We thematically analyzed survey responses and qualitative interview/focus group data that we collected over five years in six culturally diverse Indigenous communities in Canada during the evaluation of the clinical trial DREAM-GLOBAL. We established themes that reflect culturally safe approaches to research and then developed wise practices for culturally safe research in pragmatic eHealth research., Results: Based on our analysis, successful eHealth research in collaboration with Indigenous communities requires a focus on cultural safety that includes: (1) building a respectful relationship; (2) maintaining a respectful relationship; (3) good communication and support for the local team during the RCT; (4) commitment to co-designing the innovation; (5) supporting task shifting with the local team; and (6) reflecting on our mistakes and lessons learned or areas for improvement that support learning and cultural safety., Conclusions: Based on evaluation data collected in the DREAM-GLOBAL RCT, we found that there are important cultural safety considerations in Indigenous eHealth research. Building on the perspectives of Indigenous staff and patients, we gleaned wise practices for RCTs in Indigenous communities., Trial Registration: ClinicalTrials.gov NCT02111226; https://clinicaltrials.gov/ct2/show/NCT02111226., (©Marion A Andrea Maar, Valerie Beaudin, Karen Yeates, Lisa Boesch, Peter Liu, Kian Madjedi, Nancy Perkins, Diane Hua-Stewart, Faith Beaudin, Mary Jo Wabano, Sheldon W Tobe. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 04.11.2019.)

Background: The prevalence of adult chronic kidney disease and cardiovascular comorbidities in Canadian Indigenous communities is largely unknown. We conducted a study to document the prevalence of chronic kidney disease and concurrent diabetes mellitus, hypertension and dyslipidemia in a First Nations population in northwest Ontario., Methods: In this observational study, we used retrospective data collected from regional electronic medical records of 16 170 adults (age ≥ 18 yr) from 26 First Nations communities in northwest Ontario from May 2014 to May 2017. Demographic and laboratory data included age, gender, prescribed medications, estimated glomerular filtration rate, urine albumin:creatinine ratio, low-density lipoprotein cholesterol (LDL-C) level and glycated hemoglobin (HbA 1c ) concentration. We identified patients with diabetes by an HbA 1c concentration of 6.5% or higher, or the use of a diabetic medication, those with dyslipidemia by an elevated LDL-C level (≥ 2.0 mmol/L) or use of lipid-lowering medication, and those with hypertension by use of antihypertensive medication., Results: Of the 16 170 adults residing in the communities, 5224 unique patients (32.3%) had renal testing (albumin:creatinine ratio and/or estimated glomerular filtration rate). The age-adjusted prevalence of chronic kidney disease was 14.5%, and the prevalence of stage 3-5 chronic kidney disease (estimated glomerular filtration rate < 60 mL/min) was 7.0%. Most patients with chronic kidney disease (1487 [80.0%]) had at least 1 cardiovascular comorbidity. A total of 1332 patients (71.6%) had diabetes, 1313 (70.6%) had dyslipidemia, and 1098 (59.1%) had hypertension; all 3 comorbidities were present in 716 patients (38.5%)., Interpretation: We document a high prevalence of advanced chronic kidney disease in this First Nations population, 7.0%, double the rate in the general population. High rates of cardiovascular comorbidities were also common in these patients with chronic kidney disease, which places them at increased risk for cardiovascular disease., Competing Interests: Competing interests: None declared., (Copyright 2019, Joule Inc. or its licensors.)

Africa is experiencing an increasing prevalence of noncommunicable diseases (NCD). However, few reliable data are available on their true burden, main risk factors, and economic impact that are needed to inform implementation of evidence-based interventions in the local context. In Malawi, a number of initiatives have begun addressing the NCD challenge, which have often utilized existing infectious disease infrastructure. It will be crucial to carefully leverage these synergies to maximize their impact. NCD-BRITE (Building Research Capacity, Implementation, and Translation Expertise) is a transdisciplinary consortium that brings together key research institutions, the Ministry of Health, and other stakeholders to build long-term, sustainable, NCD-focused implementation research capacity. Led by University of Malawi-College of Medicine, University of North Carolina, and Dignitas International, NCD-BRITE's specific aims are to conduct detailed assessments of the burden and risk factors of common NCD; assess the research infrastructure needed to inform, implement, and evaluate NCD interventions; create a national implementation research agenda for priority NCD; and develop NCD-focused implementation research capacity through short courses, mentored research awards, and an internship placement program. The capacity-building activities are purposely designed around the University of Malawi-College of Medicine and Ministry of Health to ensure sustainability. The NCD BRITE Consortium was launched in February 2018. In year 1, we have developed NCD-focused implementation research capacity. Needs assessments will follow in years 2 and 3. Finally, in year 4, the generated research capacity, together with findings from the needs assessments, will be used to create a national, actionable, implementation research agenda for NCD prioritized in this consortium, namely cardiovascular disease, diabetes mellitus, and asthma and chronic obstructive pulmonary disease., (Copyright © 2019. Published by Elsevier B.V.)

Recent studies have found an increasing burden of noncommunicable diseases in sub-Saharan Africa. A compressive search of PubMed, Medline, EMBASE, and the World Health Organization Global Health Library databases was undertaken to identify studies reporting on the prevalence, risk factors, and interventions for hypertension and diabetes in Malawi. The findings from 23 included studies revealed a high burden of hypertension and diabetes in Malawi, with estimates ranging from 15.8% to 32.9% and from 2.4% to 5.6%, respectively. Associated risk factors included old age, tobacco smoking, excessive alcohol consumption, obesity, physical inactivity, high salt and sugar intake, low fruit and vegetable intake, high body mass index, and high waist-to-hip ratio. Certain antiretroviral therapy regimens were also associated with increased diabetes and hypertension risk in human immunodeficiency virus patient populations. Nationwide, the quality of clinical care was generally limited and demonstrated a need for innovative and targeted interventions to prevent, control, and treat noncommunicable diseases in Malawi., (Copyright © 2019 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.)

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes., Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18-85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25-75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g who had received maximum labelled or tolerated renin-angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532., Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4-2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49-0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85-2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75-1·59]; p=0·65)., Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease., Funding: AbbVie., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Clinical practice guidelines serve an important role in the primary and secondary prevention of cardiovascular disease. There is variability among guideline groups in the methods used to assess and grade clinical evidence, resulting in discrepancies in various guidelines. Multiple guidelines focused on different aspects of cardiovascular care can lead to recommendations that are out of sync. Discrepancies between a practice recommendation from 2 different Canadian guideline groups can lead to confusion among clinicians and patients, reducing the likelihood that the practice recommendation will be carried out. Assisting cardiovascular-focused guideline groups to align, to harmonize, and to score highly on appraisal has been a main function of the Canadian Cardiovascular Harmonized National Guidelines Endeavour (C-CHANGE). Validated appraisal tools, harmonized guideline initiatives, and continuous evaluation of the impact of guidelines on quality indicators and practice outcomes are crucial for improving cardiovascular care for all Canadians., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

In September 2017, KDIGO (Kidney Disease: Improving Global Outcomes) convened a Controversies Conference titled Blood Pressure in Chronic Kidney Disease (CKD). The purpose of the meeting was to consider which recommendations from the 2012 KDIGO Clinical Practice Guideline for the Management of Blood Pressure in CKD should be reevaluated based on new evidence from clinical trials. Participants included a multidisciplinary panel of clinical and scientific experts. Discussions focused on the optimal means for measuring blood pressure (BP) as well as managing BP in CKD patients. Consistent with the 2012 Guideline, the conference did not address BP management in patients on maintenance dialysis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Data derived from the Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) study were analyzed in an effort to employ machine learning methods to predict the composite endpoint described in the original study., Methods: We identified 573 CORAL subjects with complete baseline data and the presence or absence of a composite endpoint for the study. These data were subjected to several models including a generalized linear (logistic-linear) model, support vector machine, decision tree, feed-forward neural network, and random forest, in an effort to attempt to predict the composite endpoint. The subjects were arbitrarily divided into training and testing subsets according to an 80%:20% distribution with various seeds. Prediction models were optimized within the CARET package of R., Results: The best performance of the different machine learning techniques was that of the random forest method which yielded a receiver operator curve (ROC) area of 68.1%±4.2% (mean ± SD) on the testing subset with ten different seed values used to separate training and testing subsets. The four most important variables in the random forest method were SBP, serum creatinine, glycosylated hemoglobin, and DBP. Each of these variables was also important in at least some of the other methods. The treatment assignment group was not consistently an important determinant in any of the models., Conclusion: Prediction of a composite cardiovascular outcome was difficult in the CORAL population, even when employing machine learning methods. Assignment to either the stenting or best medical therapy group did not serve as an important predictor of composite outcome., Clinical Trial Registration: ClinicalTrials.gov, NCT00081731., Competing Interests: Disclosure KRT has received grants from the NHLBI and the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). She has received consulting fees from Eli Lilly and Company, Amgen, and Noxxon Pharma, as well as research support from Eli Lilly and Company. LDD has received grants from the National Institutes of Health (NIH) and research support from Pfizer, Astra Zeneca, and Johnson & Johnson. BAG and MS have received grants from the NIH. ST has received personal fees from AbbVie. KJ has received grants from the Medical College of Toledo. KP has received grants from the NHLBI. JMM has received personal fees from the Harvard Clinical Research Institute and grants from the NHLBI. RBD Sr has received grants from the NHLBI. DEC has received grants from the NHLBI and research support from Medtronic, Boston Scientific, and Abbott Vascular. CJC has received research funding from Cordis, study drugs from AstraZeneca, and study drugs and research funding from Pfizer. JIS has received grants from the NIH, BrickStreet Insurance Endowment, and the Huntington Foundation Endowment. The authors report no other conflicts of interest in this work.

Background: Geographic factors may influence cardiovascular disease outcomes in Canada. Circulatory diseases are a major reason for higher population mortality rates in Northern Ontario, but it is unknown if hospitalized patients with cardiovascular disease experience differential outcomes compared with those in the South., Methods: We examined 30-day and 1-year mortality and readmissions for patients hospitalized with acute myocardial infarction (AMI), heart failure (HF), atrial fibrillation (AF), or stroke in Northern compared with Southern Ontario, using the Canadian Institute for Health Information Discharge Abstract Database (2005-2016). Northern patients were defined as those residing and hospitalized in the Northwest or Northeast Local Health Integration Network regions. We used multiple Cox proportional hazards regression analysis for time-to-first event and Prentice-Williams-Peterson method to evaluate repeat and multiply admitted patients., Results: A total of 47,745 Northern and 465,353 Southern patients hospitalized with AMI (n = 182,158), HF (n = 130,770), AF (n = 72,326), or stroke (n = 127,844) were studied. Rates of first readmission were higher among Northern patients for AMI (adjusted hazard ratio [HR], 1.32), HF (HR, 1.16), AF (HR, 1.21), and stroke (HR, 1.27) compared with Southern patients (all P < 0.001). Repeat readmission rates among Northern patients for AMI (HR, 1.23), HF (HR, 1.13), AF (HR, 1.18), and stroke (HR, 1.22) were also increased (all P < 0.001 vs Southern). Thirty-day mortality did not differ significantly between Northern and Southern patients., Conclusions: Readmissions were increased in those residing and hospitalized in the North. To reduce readmissions in the North, the quality of postacute transitional care should be examined further., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Hypertension, the leading cause of cardiovascular morbidity and mortality, affects more than 1 billion people globally. The rise in mobile health in particular the use of mobile phones and short message service (SMS) to support disease management provides an opportunity to improve hypertension awareness, treatment, and control, in remote and vulnerable patient populations. The primary objective of this randomized controlled study was to assess the effect of active (with hypertension specific management SMS) or passive (health behaviors SMS alone) on the difference in blood pressure (BP) reduction between the active and passive SMS groups in hypertensive Canadian First Nations people from six rural and remote communities. Pragmatic features of the study included shifting of BP measures to non-medical health workers. Despite an overall reduction in BP over the study, there was no difference in the BP change between groups from baseline to final for systolic 0.8 (95% CI -4.2 to 5.8 mm Hg) or diastolic -1.0 (95% CI -3.7 to 1.8 mm Hg, P = 0.5) BP. Achieved BP control was 37.5% (25.6%-49.4%, 95% CI) in the active group and 32.8% (20.6%-44.8%, 95% CI) in the passive group (difference in proportions -4.74% (-21.7% to 12.2%, 95% CI, P = 0.6). The study looked at changes in health services delivery, mobile health technologies, and patient engagement to support better management of hypertension in Canadian First Nations communities. The active hypertension specific SMS did not lead to improvements in BP control., (©2018 Wiley Periodicals, Inc.)

Background: Curcumin, a popular herbal supplement from the plant turmeric, has prevented ischemic reperfusion and toxin-induced injury in many animal studies and a single-centre randomized human trial. We sought to test whether perioperative oral curcumin (compared with placebo) affects the inflammatory response and risk of postrepair complications after elective abdominal aortic aneurysm repair in humans., Methods: We conducted a parallel-group, randomized, placebo-controlled trial of patients from 10 hospitals in Canada who were scheduled to undergo elective repair of an unruptured abdominal aortic aneurysm (November 2011 to November 2014). Patients in the treatment group received perioperative oral curcumin (2000-mg doses 8 times over 4 d). Patients, health care providers and local research staff were unaware of the treatment assignment. The primary outcomes were median concentrations of 4 bio markers indicating injury and inflammation (postoperative urine interleukin-18 and perioperative rise in serum creatinine, plasma N -terminal pro-B-type natriuretic peptide and plasma high-sensitivity C-reactive protein)., Results: Baseline characteristics were similar in the 2 groups (606 patients overall; median age 76 yr). More than 85% of patients in each group took more than 80% of their scheduled capsules. Neither curcumin nor placebo significantly affected any of the 4 biomarkers ( p > 0.05 for all comparisons). Regarding the secondary outcomes, there was a higher risk of acute kidney injury with curcumin than with placebo (17% v. 10%, p = 0.01), but no between-group difference in the median length of hospital stay (5 v. 5 days, p > 0.9) or the risk of clinical events (9% v. 9%, p = 0.9)., Interpretation: Curcumin had no beneficial effects when used in elective abdominal aortic aneurysm repair. These findings emphasize the importance of testing turmeric and curcumin before espousing their health benefits, as is currently done in the popular media., Trial Registration: ClinicalTrials.gov, no. NCT01225094., Competing Interests: Competing interests: P.J. Devereaux has received grants from Abbott Diagnostics, Boehringer Ingelheim, Covidien, Octopharma, Philips Healthcare, Roche Diagnostics amd Stryker for projects outside the work reported here. Matthew James is the principal investigator on an investigator-initiated research grant funded by Amgen Canada outside the work reported here. No other competing interests were declared., (© 2018 Joule Inc. or its licensors.)

Competing Interests: Competing interests: Todd Anderson reports receiving grants from Amgen and DalCor, and personal fees from Sanofi, Merck, and Amgen, outside the submitted work. Alice Cheng reports personal fees from Abbott, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier and Takeda, outside the submitted work. Gord Gubitz reports receiving personal fees from Bayer, Pfizer and Boehringer Ingelheim, outside the submitted work. David Lau reports receiving research funding and speaker fees from AstraZeneca and Novo Nordisk and has received speaker fees and/or served as consultant from Amgen, Akcea, Boehringer Ingelheim, Janssen, Merck, Shire and Valeant, outside the submitted work. Lawrence Leiter has received research funding from, has provided CME on behalf of, or has acted as an adviser to Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion, GlaxoSmithKline, Janssen, Kowa, the Medicines Company, Merck, Novartis, Novo Nordisk, Resverlogix, Sanofi, Servier and The Medicines Company, outside the submitted work. Peter Selby reports receiving grants from Pfizer Inc., Bhasin Consulting Fund, Patient-Centered Outcomes Research Institute, Pfizer Canada Inc.; personal fees from Bristol-Myers Squibb, Pfizer Canada Inc., Evidera Inc., Johnson & Johnson Group of Companies, Medcan Clinic, Miller Medical Communications, NVision Insight Group, Myelin & Associates; and is a vendor of record for providing smoking cessation pharmacotherapy (free or discounted) for research studies for Pfizer, Novartis, Johnson & Johnson, and Med-Plan Communications, outside the submitted work. Simon Bacon has received consultancy fees from Schering-Plough, Merck and Sygesa, speaker fees from Novartis, and investigator-initiated grants from GlaxoSmithKline and Abb Vie. Sheldon Tobe reports grants from Eli Lilly, Astra Zeneca, AbbVie and Bayer, as well as personal fees from Servier and Valeant, during the conduct of the study. He has also had travel reimbursed by the Novartis Foundation. Sean Wharton reports personal fees from Novo Nordisk, Janssen and Eli Lilly, outside the submitted work. Eileen O’Meara reports clinical trial and national leader function fees paid to her institution from Novartis; clinical trial and national leader function fees paid to her instution, as well as consulting fees from Astra Zeneca; clinical trial fees paid to her institution from Merck; clinical trial fees paid to her institution and consulting fees from Bayer; and clinical trial and steering committee fees paid to her institution from Amgen. James Stone reports personal fees from Astra Zeneca, Bayer, Lilly, Sanofi, Novo-Nordisk and Servier, as well as personal fees for a clinical research trial from Sanofi, outside the submitted work. No other competing interests were declared.