Impact of Canagliflozin on Kidney and Cardiovascular Outcomes by Type 2 Diabetes Duration: A Pooled Analysis of the CANVAS Program and CREDENCE Trials.

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.

Association of prior outpatient diabetes screening with cardiovascular events and mortality among people with incident diabetes: a population-based cohort study.

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.

Patient Perspectives on a Pilot Virtual Follow-up Program After Hypertensive Disorders of Pregnancy: A Qualitative Study.

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.

Contexte: Les troubles hypertensifs de la grossesse (THG) représentent un facteur de risque de maladies cardiovasculaires. Il est donc recommandé d'assurer un suivi et d'intervenir de façon précoce. Nous avons réalisé une étude qualitative pour évaluer la faisabilité et la réaction des utilisatrices à un outil de santé mobile et à une consultation virtuelle visant à informer les personnes atteintes d'un THG à propos de leur risque cardiovasculaire et à mieux comprendre leurs priorités en matière de soins post-partum. Méthodologie: Les participantes ayant présenté un THG au cours des cinq dernières années ont eu accès à un outil éducatif en ligne et ont participé à une consultation virtuelle pour discuter de leur risque cardiovasculaire. Elles ont été invitées à un groupe de discussion afin d'obtenir des commentaires sur leur expérience post-partum et sur le programme Her-HEART. Résultats: Au total, 20 participantes ont été sélectionnées entre janvier 2020 et février 2021. Parmi elles, 16 ont pris part à l'un des cinq groupes de discussion. Les participantes ont déclaré qu'elles connaissaient mal leur risque de maladies cardiovasculaires avant de participer au programme et ont fait état d'obstacles les faisant hésiter à consulter, notamment des expériences traumatisantes à l'accouchement, le manque de temps et des priorités conflictuelles. Les participants ont déclaré que le programme virtuel Her-HEART était un moyen efficace de fournir des conseils sur les risques cardiovasculaires à long terme. Elles ont souligné l'importance d'une trajectoire de soins coordonnée et d'un soutien psychologique dans les programmes de suivi post-partum. Conclusion: Nous avons démontré la pertinence d'un site Web éducatif et d'une consultation virtuelle pour faciliter l'accompagnement des patientes atteintes d'un THG. Les résultats mettent également en lumière les priorités des patientes ayant présenté un tel trouble en ce qui concerne les modalités d'un accompagnement post-partum.

Risk of Chronic Kidney Disease in Hospitalized Patients with Hidradenitis Suppurativa.

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.

Evaluation of visual acuity in dry AMD patients after microcurrent electrical stimulation.

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.

Characterizing Hypertension Specialist Care in Canada: A National Survey.

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.

Contexte: Le spécialiste de l'hypertension reçoit souvent des patients orientés pour une hypertension sévère, d'apparition précoce et difficile à maîtriser, pour une urgence hypertensive ou pour des causes secondaires de l'hypertension. Les soins spécialisés de l'hypertension complètent les soins primaires pour ces cas complexes et font partie d'une stratégie globale de maîtrise de l'hypertension. Cette étude avait pour objectif de caractériser les centres de traitement de l'hypertension et les habitudes de pratique des spécialistes canadiens qui traitent l'hypertension. Méthodologie: Un sondage a été mené auprès de spécialistes de l'hypertension adulte de l'ensemble du Canada afin de décrire les centres de traitement de l'hypertension et la pratique des spécialistes au Canada, notamment les éléments suivants : la population de patients prise en charge par des spécialistes de l'hypertension, les renseignements sur la façon dont les soins sont prodigués, les variations dans les habitudes de pratique ainsi que les différences relatives à l'accès aux ressources spécialisées en hypertension à l'échelle du pays. Résultats: Le taux de réponse au sondage a été de 73,5 % dans 25 centres de l'hypertension. La plupart des répondants étaient des néphrologues et des spécialistes en médecine interne générale. Les centres de l'hypertension recevaient entre 50 et 2500 patients par année. En moyenne, 17 % (± 15 %) des patients provenaient du service des urgences et 52 % (± 24 %) provenaient d'une unité de soins primaires. La plupart des centres avaient accès à des tests spécialisés (prélèvements veineux surrénaliens, études du sommeil de niveau 1, tests autonomes) et à des traitements avancés pour l'hypertension résistante (dénervation rénale). Une hétérogénéité considérable a été constatée en ce qui concerne la pression artérielle cible chez les jeunes présentant un faible risque cardiovasculaire et les algorithmes diagnostiques pour étudier les causes secondaires de l'hypertension. Conclusions: Ces résultats résument la situation actuelle des soins spécialisés de l'hypertension et font ressortir des occasions d'accroître la collaboration entre les spécialistes de l'hypertension, notamment en ce qui concerne une normalisation de l'approche des soins spécialisés pour les patients hypertendus.

Ups and downs of hypertension control in Canada: critical factors and lessons learned.

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.

La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta.En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

O controle populacional da hipertensão arterial ­ o maior fator de risco de morte ­ representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta.Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Derivation and External Validation of a Clinical Model to Predict Heart Failure Onset in Patients With Incident Diabetes.

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.

Trends in glucose testing among individuals without diabetes in Ontario between 2010 and 2017: a population-based cohort study.

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.

Ups and downs of hypertension control in Canada: critical factors and lessons learned

[ABSTRACT]. 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 unprece- dented 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 com- prehensive 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 imple- mentation and evaluation.

[RESUMEN]. La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisci- plinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la expe- riencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organi- zaciones de atención primaria y al personal médico en la implementación y la evaluación.

[RESUMO]. O controle populacional da hipertensão arterial – o maior fator de risco de morte – representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e aval- iação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hiper- tensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adap- tação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.

Organic Anion Transporter Gene Variants Associated With Plasma Exposure and Long-Term Response to Atrasentan in Patients With Diabetic Kidney Disease.

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 m2 , 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 (AUC0-inf ) 41.3 ng·h/mL) or slow (atrasentan AUC0-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.

Increase in BNP in Response to Endothelin-Receptor Antagonist Atrasentan Is Associated With Incident Heart Failure.

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).

Ups and downs of hypertension control in Canada: critical factors and lessons learned / Altibajos en el control de la hipertensión en Canadá: factores críticos y lecciones aprendidas / Altos e baixos no controle da hipertensão no Canadá: fatores críticos e lições aprendidas

ABSTRACT 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.

RESUMEN La hipertensión arterial representa el principal riesgo de muerte; controlarla a nivel de la población constituye un desafío importante para todos los países de la Región de las Américas. A principios de la década de 1990, Canadá presentaba una tasa de control de la hipertensión del 13%. La tasa de control aumentó al 68% en el 2010, lo que vino acompañado por una disminución importante de las enfermedades cardiovasculares. Esta mejora sin precedentes en el control de la hipertensión empezó alrededor del año 2000 cuando se inició un programa integral para aplicar las recomendaciones sobre el tratamiento de la hipertensión, actualizadas anualmente. El programa incluyó un sistema de monitoreo integral para el control de la hipertensión. Después del 2011, hubo una marcada disminución del énfasis en la implementación y la evaluación, y la tasa de control de la hipertensión disminuyó, impulsada por una reducción en el control en las mujeres, que pasó del 69% al 49%. En el 2011, se formó una coalición de organizaciones científicas y de salud con la prioridad de elaborar una campaña de defensa y promoción de las políticas alimentarias para prevenir y controlar la hipertensión. Para el año 2015, esta postura fue adoptada por la mayoría de los partidos políticos federales, aunque la implementación ha sido lenta. En este artículo se revisan los factores clave de éxito y las lecciones aprendidas. Algunos factores clave de éxito fueron tener una amplia representación en el comité directivo del programa; el compromiso multidisciplinario con la participación sustantiva del sector de la atención primaria; unas recomendaciones creíbles, imparciales y actualizadas; el desarrollo y la adaptación activa de recursos educativos basados en la experiencia en el terreno; la amplia implementación de los recursos de la atención primaria; la revisión anual del programa y de los indicadores de hipertensión; y el desarrollo y el énfasis en unas pocas intervenciones importantes para el control de la hipertensión. Entre las lecciones aprendidas se encontró la necesidad de contar con un fuerte compromiso y apoyo del gobierno nacional y provincial, y de mantener a las organizaciones de atención primaria y al personal médico en la implementación y la evaluación.

RESUMO O controle populacional da hipertensão arterial - o maior fator de risco de morte - representa um grande desafio para todos os países das Américas. No início da década de 1990, o Canadá tinha uma taxa de controle de hipertensão de 13%. Esse índice aumentou para 68% em 2010, acompanhado por um declínio acentuado das doenças cardiovasculares. A melhoria sem precedentes no controle da hipertensão começou por volta do ano 2000, quando teve início um programa abrangente para implementar recomendações de tratamento de hipertensão atualizadas anualmente. O programa incluía um sistema integral de monitoramento do controle da hipertensão. Após 2011, houve uma acentuada redução da ênfase na implementação e avaliação, e a taxa de controle de hipertensão caiu, principalmente às custas de uma redução deste controle em mulheres (de 69% para 49%). Uma coalizão de organizações científicas e de saúde formou-se em 2011 com a prioridade de desenvolver posições de defesa de políticas alimentares para prevenir e controlar a hipertensão. Até 2015, essas posições haviam sido adotadas pela maioria dos partidos políticos federais, mas a implementação tem sido lenta. Este manuscrito examina fatores-chave de sucesso e aprendizados. Alguns fatores-chave de sucesso incluíram uma ampla representatividade no comitê diretor do programa, engajamento multidisciplinar (com envolvimento significativo da atenção primária), recomendações imparciais e confiáveis, elaboração e adaptação ativa de recursos didáticos com base na experiência de campo, ampla implementação dos recursos da atenção primária, revisão anual do programa e dos indicadores de hipertensão e desenvolvimento e ênfase das poucas intervenções realmente importantes para o controle da hipertensão. As lições aprendidas incluíram a necessidade de ter forte envolvimento e apoio dos governos nacional e subnacionais e manter organizações e médicos da atenção primária engajados na implementação e avaliação.