Outrunning the grim reaper: longevity of the first 200 sub-4 min mile male runners.

OBJECTIVES: To determine the impact of running a sub-4 min mile on longevity. It was hypothesised that there would be an increase in longevity for runners who successfully completed a sub-4 min mile compared with the general population. METHODS: As part of this retrospective cohort study, the Sub-4 Alphabetic Register was used to extract the first 200 athletes to run a sub-4 min mile. Each runner's date of birth, date of their first successful mile attempt, current age (if alive) or age at death was compared with the United Nations Life Tables to determine the difference in each runner's current age or age at death with their country of origin-specific life expectancy. RESULTS: Of the first 200 sub-4 min mile runners (100% male), 60 were dead (30%) and 140 were still alive. Sub-4 min mile runners lived an average of 4.7 years beyond their predicted life expectancy (95% CI 4.7 to 4.8). When accounting for the decade of completion (1950s, 1960s or 1970s), the longevity benefits were 9.2 years (n=22; 95% CI 8.3 to 10.1), 5.5 years (n=88; 95% CI 5.3 to 5.7) and 2.9 years (n=90; 95% CI 2.7 to 3.1), respectively. CONCLUSION: Sub-4 min mile runners have increased longevity compared with the general population, thereby challenging the notion that extreme endurance exercise may be detrimental to longevity.

Association Between Hemoglobin A1c and Development of Cardiovascular Disease in Canadian Men and Women Without Diabetes at Baseline: A Population-Based Study of 608 474 Adults.

BACKGROUND: We examined the association between hemoglobin A1c (HbA1c) and the development of cardiovascular disease (CVD) in men and women, without diabetes or CVD at baseline. METHODS AND RESULTS: This retrospective cohort study included adults aged 40 to <80 years in Alberta, Canada. Men and women were divided into categories based on a random HbA1c during a 3-year enrollment period. The primary outcome of CVD hospitalization and secondary outcome of combined CVD hospitalization/mortality were examined during a 5-year follow-up period until March 31, 2021. A total of 608 474 individuals (55.2% women) were included. Compared with HbA1c 5.0% to 5.4%, men with HbA1c of 5.5% to 5.9% had an increased risk of CVD hospitalization (adjusted hazard ratio [aHR], 1.12 [95% CI, 1.07-1.19]) whereas women did not (aHR, 1.01 [95% CI, 0.95-1.08]). Men and women with HbA1c of 6.0% to 6.4% had a 38% and 17% higher risk and men and women with HbA1c ≥6.5% had a 79% and 51% higher risk of CVD hospitalization, respectively. In addition, HbA1c of 6.0% to 6.4% and HbA1c ≥6.5% were associated with a higher risk (14% and 41%, respectively) of CVD hospitalization/death in men, but HbA1c ≥6.5% was associated with a 24% higher risk only among women. CONCLUSIONS: In both men and women, HbA1c ≥6.0% was associated with an increased risk of CVD and mortality outcomes. The association between CVD and HbA1c levels of 5.5% to 5.9%, considered to be in the "normal" range, highlights the importance of optimizing cardiovascular risk profiles at all levels of glycemia, especially in men.

Uptake of SGLT2i and Outcomes in Patients with Diabetes and Heart Failure: A Population-Based Cohort and a Specialized Clinic Cohort.

BACKGROUND: Sodium/glucose cotransporter 2 inhibitors (SGLT2i) are effective in adults with diabetes mellitus (DM) and heart failure (HF) based on randomized clinical trials. We compared SGLT2i uptake and outcomes in two cohorts: a population-based cohort of all adults with DM and HF in Alberta, Canada and a specialized heart failure clinic (HFC) cohort. METHODS: The population-based cohort was derived from linked provincial healthcare datasets. The specialized clinic cohort was created by chart review of consecutive patients prospectively enrolled in the HFC between February 2018 and August 2022. We examined the association between SGLT2i use (modeled as a time-varying covariate) and all-cause mortality or deaths/cardiovascular hospitalizations. RESULTS: Of the 4,885 individuals from the population-based cohort, 64.2% met the eligibility criteria of the trials proving the effectiveness of SGLT2i. Utilization of SGLT2i increased from 1.2% in 2017 to 26.4% by January 2022. In comparison, of the 530 patients followed in the HFC, SGLT2i use increased from 9.8% in 2019 to 49.1 % by March 2022. SGLT2i use in the population-based cohort was associated with fewer all-cause mortality (aHR 0.51, 95% CI 0.41-0.63) and deaths/cardiovascular hospitalizations (aHR 0.65, 95% CI 0.54-0.77). However, SGLT2i usage rates were far lower in HF patients without DM (3.5% by March 2022 in the HFC cohort). CONCLUSIONS: Despite robust randomized trial evidence of clinical benefit, the uptake of SGLT2i in patients with HF and DM remains low, even in the specialized HFC. Clinical care strategies are needed to enhance the use of SGLT2i and improve implementation.

Outcomes of management strategies in patients with prior coronary artery bypass grafting presenting with an acute coronary syndrome.

BACKGROUND: Patients with prior coronary artery bypass grafting (CABG) presenting with an acute coronary syndrome (ACS) have poor outcomes and the optimal treatment strategy for this population is unknown. METHODS: Using linked administrative databases, we examined patients with an ACS between 2008 and 2019, identifying patients with prior CABG. Patients were categorized by ACS presentation type and treatment strategy. Our primary outcome was the composite of death and recurrent myocardial infarction at one year. RESULTS: Of 54,641 patients who presented with an ACS, 1670 (3.1%) had a history of prior CABG. Of those, 11.0% presented with an ST-elevation myocardial infarction (STEMI) of which, 15.3% were treated medically, 31.1% underwent angiography but were treated medically, 22.4% with fibrinolytic therapy and 31.1% with primary PCI. The primary outcome rate was the highest (36.8%) in patients who did not undergo angiography and was similar in the primary PCI (20.8%) and fibrinolytic group (21.9%). In patients presenting with a non-ST elevation acute coronary syndrome (NSTE-ACS) (89.0%), 33.2% were treated medically, 38.5% underwent angiography but were treated medically and 28.2% were treated with PCI. Compared to those who underwent PCI, patients treated conservatively demonstrated a higher risk of the composite outcome (14.8% vs 27.3%; adjusted hazard ratio 1.70, 95% confidence interval 1.22-2.37). CONCLUSIONS: Patients with prior CABG presenting with an ACS are often treated conservatively without PCI, which is associated with a higher risk of adverse events.

Iron Deficiency, Anemia, and Iron Supplementation in Patients With Heart Failure: A Population-Level Study.

BACKGROUND: Studies have shown an association between iron deficiency (ID) and clinical outcomes in patients with heart failure (HF), irrespective of the presence of ID anemia (IDA). The current study used population-level data from a large, single-payer health care system in Canada to investigate the epidemiology of ID and IDA in patients with acute HF and those with chronic HF, and the iron supplementation practices in these settings. METHODS: All adult patients with HF in Alberta between 2012 and 2019 were identified and categorized as acute or chronic HF. HF subtypes were determined through echocardiography data, and ID (serum ferritin concentration <100 µg/L, or ferritin concentration between 100 and 300 µg/L along with transferrin saturation <20%), and IDA through laboratory data. Broad eligibility for 3 clinical trials (AFFIRM-AHF [Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute HF and ID], IRONMAN [Intravenous Iron Treatment in Patients With Heart Failure and Iron Deficiency], and HEART-FID [Randomized Placebocontrolled Trial of Ferric Carboxymaltose as Treatment for HF With ID]) was determined. RESULTS: Among the 17 463 patients with acute HF, 38.5% had iron studies tested within 30 days post-index-HF episode (and 34.2% of the 11 320 patients with chronic HF). Among tested patients, 72.6% of the acute HF and 73.9% of the chronic HF were iron-deficient, and 51.4% and 49.0% had IDA, respectively. Iron therapy was provided to 41.8% and 40.5% of patients with IDA and acute or chronic HF, respectively. Of ID patients without anemia, 19.9% and 21.7% were prescribed iron therapy. The most common type of iron therapy was oral (28.1% of patients). Approximately half of the cohort was eligible for each of the AFFIRM-AHF, intravenous iron treatment in patients with HF and ID, and HEART-FID trials. CONCLUSIONS: Current practices for investigating and treating ID in patients with HF do not align with existing guideline recommendations. Considering the gap in care, innovative strategies to optimize iron therapy in patients with HF are required.

Relationships Between Measures of the Physical Activity-Related Built Environment and Excess Weight in Preschoolers: A Retrospective, Population-Level Cohort Study.

Background: The built environment can impact health outcomes. Our purpose was to examine relationships between built environment variables related to physical activity and excess weight in preschoolers. Methods: In this retrospective, population-level study of 4- to 6-year-olds, anthropometric measurements were taken between 2009 and 2017 in Calgary and Edmonton, Alberta, Canada. Based on BMI z-scores (BMIz), children were classified as normal weight (-2 ≤ BMIz <1) or excess weight (BMIz ≥1; overweight and obesity). Physical activity-related built environment variables were calculated (distances to nearest playground, major park, school; street intersection density; number of playgrounds and major parks within an 800 m buffer zone). Binomial logistic regression models estimated associations between physical activity-related built environment variables and excess weight. Results: Our analysis included 140,368 participants (females: n = 69,454; Calgary: n = 84,101). For Calgary, adjusted odds ratios (aORs) showed the odds of excess weight increased 1% for every 100-intersection increase [1.010 (1.006-1.015); p < 0.0001] and 13.6% when there were ≥4 playgrounds (vs. 0 or 1) within an 800 m buffer zone [1.136 (1.037-1.243); p = 0.0059]. For Edmonton, aORs revealed lower odds of excess weight for every 100 m increase in distances between residences to nearest major park [0.991 (0.986-0.996); p = 0.0005] and school [0.992 (0.990-0.995); p < 0.0001]. The odds of excess weight decreased as the number of major parks within the 800 m buffer zone increased from 0 to 1 [0.943 (0.896-0.992); p = 0.023] and from 0 to ≥3 [0.879 (0.773-0.999); p = 0.048]. Conclusion: The physical activity-related built environment was associated with excess weight in preschoolers, although relationships varied between cities that differed demographically and geographically.

Applicability and impact of the COMPASS trial in a Canadian population of patients with atherosclerotic disease.

BACKGROUND AND AIMS: In the COMPASS trial, low-dose rivaroxaban with aspirin improved cardiovascular outcomes in patients with atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the potential clinical implications of this therapy in a generalizable population. METHODS AND RESULTS: A retrospective cohort of adults with ASVCD was formed using healthcare administrative databases in Alberta, Canada (population 4.4 million). Patients with a new diagnosis between 2008 and 2019 formed the epidemiological cohort (n = 224,600) and those with long-term follow-up (>5 years) formed the outcomes cohort (n = 232,460). The primary outcome of major adverse cardiovascular events (MACE) was assessed and categorized based on the COMPASS trial eligibility. In the outcomes cohort, 77% had only coronary artery disease, 15% had only peripheral artery disease, and 8% had both. Of those, 37% met the COMPASS trial eligibility criteria, 36% met exclusion criteria and 27% did not meet inclusion criteria. Over a median of 7.8 years, the COMPASS exclusion group demonstrated the highest rate of MACE (5.9 per 100 person-years), following by the eligible group and the group that did not meet COMPASS inclusion criteria (3.1 and 1.4 per 100 person-years respectively). The expected net clinical benefit of antithrombotic therapy in the eligible group was 5.6 fewer events per 1000 person-years. CONCLUSIONS: In a real-world population of 4.4 million adults, there are roughly 20,000 new cases of ASVCD diagnosed yearly, with ∼40% being eligible for the addition of low-dose rivaroxaban therapy to antiplatelet therapy. The theoretical implementation of dual antithrombotic treatment in this population could result in a substantial reduction in cardiovascular morbidity and mortality.

Sex Differences in High-Cost Users of Healthcare for Atrial Fibrillation.

Background: Healthcare resource use for atrial fibrillation (AF) is high, but it may not be equivalent across all patients. We examined whether sex differences exist for AF high-cost users (HCUs), who account for the top 10% of total acute care costs. Methods: All patients aged ≥ 20 years who presented to the emergency department (ED) or were hospitalized with AF were identified in Alberta, Canada, between 2011 and 2015. The cohort was categorized by sex into HCUs and non-HCUs. Healthcare utilization was defined as ED, hospital, and physician visits, and costs included those for hospitalization, ambulatory care, physician billing, and drugs. All costs were inflated to 2022 Canadian dollars (CAD$). Results: Among 48,030 AF patients, 45.1% were female. Of these, 31.8% were HCUs, and the proportions of female and male patients were equal (31.9% vs 31.7%). Female HCUs were older, more likely to have hypertension and heart failure, and had a higher stroke risk than male HCUs. Mean healthcare utilization did not differ among HCUs by sex, except for number of ED visits, which was higher in male patients (12.7% vs 9.2%, P < 0.0001). Overall, HCUs accounted for 65.8% of the total costs (CAD$3.4 billion). Almost half of total HCU costs were attributable to female HCUs (CAD$966.1 million). Significant differences were present in the distributions of HCU-related costs (male patients: 74.6% hospitalization, 9.5% ambulatory care, 12.4% physician billing, 3.5% drugs; female patients: 77.7% hospitalization, 7.4% ambulatory care, 11.5% physician billing, 3.5% drugs, P < 0.0001). Conclusions: Despite having a lower AF prevalence, female patients represent an equal proportion of HCUs, and account for almost half the total HCU costs. Interventions targeted at reducing the number of AF HCU are needed, particularly for female patients.

Contexte: L'utilisation des ressources en santé est élevée pour la fibrillation auriculaire (FA), mais elle n'est pas forcément équivalente pour tous les patients. Nous avons examiné s'il existait des différences entre les sexes pour ce qui est des cas très coûteux de FA, qui représentent les 10 % supérieurs des coûts totaux de soins de courte durée. Méthodologie: Tous les patients âgés de 20 ans et plus qui se sont présentés au service des urgences ou qui ont été hospitalisés pour une FA ont été répertoriés en Alberta, au Canada, entre 2011 et 2015. La cohorte a été divisée par sexe en fonction des utilisateurs très coûteux et des autres utilisateurs. L'utilisation des soins de santé était définie comme des consultations aux urgences, à l'hôpital ou chez le médecin, et les coûts comprenaient les hospitalisations, les soins ambulatoires, les honoraires des médecins et les médicaments. Tous les coûts ont été convertis en dollars canadiens ($ CA) de 2022. Résultats: Parmi les 48 030 patients atteints de FA, 45,1 % étaient des femmes et 31,8 % étaient des utilisateurs très coûteux, en proportions égales entre les femmes et les hommes (31,9 % vs 31,7 %). Parmi les utilisateurs très coûteux, les femmes étaient plus âgées, plus susceptibles de présenter de l'hypertension et une insuffisance cardiaque, et leur risque d'AVC était plus élevé comparativement aux hommes. L'utilisation moyenne des soins de santé n'affichait pas de différences chez les utilisateurs très coûteux selon le sexe, à l'exception des consultations aux urgences, qui étaient plus fréquentes chez les hommes (12,7 % vs 9,2 %, p < 0,0001). Dans l'ensemble, les utilisateurs très coûteux représentaient 65,8 % des coûts totaux, qui étaient de 3,4 milliards de dollars canadiens. Les femmes représentaient par ailleurs près de la moitié du total des utilisations très coûteuses (966,1 millions de dollars canadiens). Des différences significatives ont été observées quant à la répartition des coûts liés aux utilisateurs très coûteux (hommes : hospitalisations [74,6 %], soins ambulatoires [9,5 %], honoraires des médecins [12,4 %], médicaments [3,5 %]; femmes : hospitalisations [77,7 %], soins ambulatoires [7,4 %], honoraires des médecins [11,5 %], médicaments [3,5 %], p < 0,0001). Conclusions: Bien que la FA soit moins fréquente chez les femmes que chez les hommes, celles-ci représentent une proportion tout aussi importante des utilisations très coûteuses et comptent pour presque la moitié des coûts totaux attribuables aux utilisateurs très coûteux. Des interventions visant à réduire les utilisations très coûteuses pour la FA sont donc nécessaires, particulièrement chez les femmes.

Real-world Use and Outcomes of Sodium-glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada.

OBJECTIVES: Since 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure. METHODS: This retrospective, population-based cohort study, identified people with diabetes and heart failure between Jan 1, 2014 to Dec 31, 2017 in Alberta, Canada and followed them for a minimum of three years for SGLT2i dispensation and outcomes. Multivariate logistic regression assessed the factors associated with SGTL2i dispensation. Propensity scores were used with regression adjustment to estimate the effect of SGLT2i treatment on heart failure hospitalization. RESULTS: Among 22,025 individuals with diabetes and heart failure (43.4% women, mean age 74.7±11.8 years), only 10.2% were dispensed an SGLT2i. Male sex, age <65 years, a higher baseline A1C, no chronic kidney disease, presence of atherosclerotic cardiovascular disease, and urban residence were associated with SGLT2i dispensation. Lower heart failure hospitalization rates were observed in those with SGLT2i dispensation (548.1 per 100 person years) vs those without (813.5 per 1,000 person years; p<0.001) and lower all-cause mortality in those with an SGLT2i than those without (48.5 per 1,000 person years vs 206.1 per 1,000 person years; p<0.001). Regression adjustment found SGLT2i therapy was associated with a 23% reduction in hospitalization. CONCLUSIONS: SGLT2is were dispensed to only 10% of people with diabetes and established heart failure, underscoring a significant care gap. SGLT2i use was associated with a real-world reduction in heart failure hospitalization and all-cause death. This study highlights an important opportunity to optimize SGLT2i use.

Impact of inherited bleeding disorders on maternal bleeding and other pregnancy outcomes: A population-based cohort study.

INTRODUCTION: Increasing rate of postpartum haemorrhage (PPH) has been observed between 2003 and 2010 in Canada. Inherited bleeding disorders contribute to the risk of PPH. AIM: To identify the trend in PPH in the last decade, assess the impact of bleeding disorders on pregnancy outcomes and evaluate their coagulation workup during pregnancy. METHODS: We conducted a population-based retrospective cohort study using the Alberta Pregnancy Birth Cohort from 2010 to 2018. We included women with von Willebrand disease (VWD) and haemophilia, identified by previously validated algorithm and matched with controls. Logistic regression was used to compute odds of PPH and other pregnancy outcomes. RESULTS: We identified 311,330 women with a total of 454,400 pregnancies with live births. The rate of PPH did not change significantly from 10.13 per 100 deliveries (95% CI 10.10-10.16) in 2010-10.72 (95% CI 10.69-10.75) in 2018 (p for trend = .35). Women with bleeding disorders were significantly more likely to experience PPH (odds ratio [OR] 2.3; 95% CI 1.5-3.6), antepartum haemorrhage (OR 2.9; 95% CI 1.5-5.9) and red cell transfusion (OR 2.8; 95% CI 1.1-7.0). We observed a nonsignificant rise in the rate of PPH in women with VWD and haemophilia. Only 49.5% pregnancies with bleeding disorders had third trimester coagulation factor levels checked. Higher odds of PPH and antepartum haemorrhage were observed even with factor levels ≥0.50 IU/mL in third trimester. CONCLUSION: Despite comprehensive care in women with bleeding disorders, they are still at higher risk of adverse pregnancy outcomes compared to population controls.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

INTRODUCTION: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. MATERIAL AND METHODS: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. RESULTS: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. CONCLUSIONS: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems.

Impact of a modified screening approach during the COVID-19 pandemic on the diagnosis and outcomes of gestational diabetes mellitus: A population-level analysis of 90,518 pregnant women.

AIMS: To provide real-world evidence on the uptake of and outcomes associated with the modified gestational diabetes mellitus (GDM) screening approach offered during the COVID-19 pandemic compared with the standard screening approach. METHODS: All pregnancies between 01 January 2020 and 31 December 2021, in Alberta, Canada, were included in the study. We examined GDM screening and diagnosis rates, and large-for-gestational-age (LGA) outcomes. RESULTS: Annual GDM screening rates were > 95% during the study time period. Overall, 84.7%, and 11.6% of the 92,505 pregnancies underwent standard and modified screening for GDM, respectively. The use of modified screening was the highest among deliveries in August 2020 (49.8%) which corresponded to the early first wave of the pandemic. GDM diagnosis rate was lower in the modified screening (7.4%) than in the standard screening (12.3%, p < 0.001) group. The LGA rates in the modified screening with GDM and the standard screening with GDM groups were 24.8% and 12.6%, respectively (p < 0.001). Women in the modified screening with GDM group were at a higher risk of having an LGA infant (adjusted odds ratio: 3.46; 95% confidence interval: 2.93, 4.08) compared to the standard screening with no GDM group. CONCLUSIONS: The COVID-19 epidemic had no impact on screening for GDM. Women who underwent modified screening, based on HbA1c/random plasma glucose, had lower rates of GDM cases.

Gestational diabetes: One size does not fit all-an observational study of maternal and neonatal outcomes by maternal glucose profile.

OBJECTIVES: To examine obstetrical and neonatal outcomes across maternal glucose profiles at the population level and to explore insulin sensitivity and beta-cell function across profiles in an independent, well-phenotyped cohort for potential pathophysiologic explanation. RESEARCH DESIGN AND METHODS: Observational cohort study of all pregnancies with gestational diabetes screening between October 2008 and December 2018 resulting in live singleton birth in Alberta, Canada (n = 436,773) were categorized into seven maternal glucose profiles: (1) normal 50 g-glucose challenge test (nGCT), (2) normal 75-g OGTT (nOGTT), (3) isolated elevated 1 h post-load glucose (ePLPG1), (4) isolated elevated 2 h post-load glucose (ePLPG2), (5) elevated 1 and 2 h post-load glucose (ePLPG12), (6) isolated elevated FPG (eFPG), and (7) elevated FPG + elevated 1-h and/or 2-h PLG (Combined). Primary outcomes were large for gestational age (LGA) and neonatal intensive care unit (NICU) admission rates. An independent observational cohort of 1451 women was examined for measures of beta-cell function (ISSI-2, insulinogenic index/HOMA-IR) and insulin sensitivity/resistance (Matsuda index, HOMA-IR) by similar maternal glucose profiles. RESULTS: Pregnancies with elevated FPG, either isolated or combined, had higher adverse events and lower insulin sensitivity. The combination of elevated FPG + elevated 1-h and/or 2-h PLG had the highest rates of LGA(20.9%), NICU admissions (14.7%), and lowest insulin sensitivity as measured by Matsuda index and HOMA-IR, and beta-cell function as measured by ISSI-2 and Insulinogenic index/HOMA-IR. CONCLUSIONS: Elevated fasting plasma glucose, either alone or combined with post-load glucose elevation is associated with worse outcomes than isolated post-load glucose elevation, possibly due to higher degrees of insulin resistance. Future work is needed to better understand these differences, and explore whether tailored treatment of GDM can improve neonatal outcomes.

Lower Socioeconomic Status is Associated with an Increased Incidence and Spectrum of Major Congenital Heart Disease and Associated Extracardiac Pathology.

Several studies have suggested an inverse relationship between lower socioeconomic status (SES) and the incidence of congenital heart disease (CHD) among live births. We sought to examine this relationship further in a Canada-wide population study, exploring CHD subtypes, trends, and associated noncardiac abnormalities. Infants born in Canada (less Quebec) from 2008 to 2018 with CHD requiring intervention in the first year were identified using ICD-10 codes through the Canadian Institute for Health Information Discharge Abstract Database. Births of CHD patients were stratified by SES (census-based income quintiles) and compared against national birth proportions using X2 tests. Proportions with extracardiac defects (ED) and nonlethal genetic syndromes (GS) were also explored. From 2008 to 2018, 7711 infants born with CHD were included. The proportions of major CHD distributed across SES quintiles were 27.1%, 20.1%, 19.2%, 18.6%, and 15.0% from lowest to highest, with significant differences relative to national birth proportions (22.0%, 20.0%, 20.6%, 20.7%, and 16.7% from lowest (1) to highest (5)) (p < 0.0001). No temporal trends in the CHD proportions across SES categories were observed over the study period. The distribution across SES quintiles was different only for specific CHD subtypes (double-outlet right ventricle (n = 485, p = 0.03), hypoplastic left heart syndrome (n = 547, p = 0.006), heterotaxy (n = 224, p = 0.03), tetralogy of Fallot (n = 1007, p = 0.008), truncus arteriosus (n = 126, p < 0.0001), and ventricular septal defect (n = 1916, p < 0.0001)), with highest proportions observed in the lowest quintile. The proportion of the total population with ED but not GS was highest in lower SES quintiles (< 0.0001) commensurate with increased proportion of CHD. Our study suggests a negative association between SES and certain CHD lesions and ED.

Kidney function monitoring and trajectories in patients with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) and chronic kidney disease (CKD) frequently co-exist. The frequency of kidney monitoring and range of kidney function in patients with AF in clinical practice are uncertain. METHODS: All adult Albertans with AF between 2008 and 2017 were identified using ICD-9 and -10 codes 427.3 and I48. Kidney Disease Improving Global Outcomes (KDIGO) risk categories were defined using eGFR by the Chronic Kidney Disease Epidemiology Collaborative equation and albuminuria results within 6 months of eGFR measurement. eGFR trajectories were compared from baseline to maximum value within the following year. RESULTS: Among 105,946 patients with AF, 16.0% were KDIGO category G1 (eGFR ≥ 90), 49.0% G2 (60-89.9), 19.8% G3a (45-59.9), 11.4% G3b (30-44.9), and G4 3.8% (15-29.9). Albuminuria was normal/mild 83.4%, moderate 11.7%, and severe 4.9%. Kidney monitoring was more common among people with lower eGFR and worse albuminuria, from approximately twice annually for G1-2/A1-2 to 8 times annually in stage G4A3. Approximately 60-80% of patients received guideline-recommended monitoring, consistent across KDIGO stages. With lower baseline eGFR, annual change in eGFR decreased while the relative proportion of patients who worsened compared to improved increased: for baseline eGFR 60-89.9, 16.7% worsened vs 6.7% improved, but for eGFR 30-44.9, 8.8% worsened but only 1.0% improved. CONCLUSION: The frequency of kidney function monitoring in patients with AF increased with worsening KDIGO risk category and adhered to KDIGO guidelines in approximately three quarters of patients. A minority of patients had moderate to severe eGFR impairment, of whom most remained stable over 1 year.

Long-term Clinical Outcomes Following Cardiac Stress Testing After Percutaneous Coronary Intervention.

BACKGROUND: Cardiac stress testing (CST) is commonly performed after percutaneous coronary intervention (PCI), yet little is known whether such ischemic testing is associated with improved clinical outcomes. METHODS: We studied patients who underwent their first PCI procedure from October 2008 to December 2016 in Ontario, Canada. Patients who underwent CST from 60 days to 1 year after PCI were compared with those who did not undergo CST. The primary outcome was a composite of cardiovascular death or hospitalisation for myocardial infarction (MI) at 3 years after CST. Inverse probability of treatment weighting was used to adjust for potential differences between the study groups. RESULTS: Among the 86,150 included patients, 40,988 (47.6%) underwent CST within 60 days to 1 year after PCI. Patients who underwent CST had higher prescription rates of cardiac medications. At 1 year after CST, rates of cardiac catheterisation and coronary revascularisation were more than double those observed in the nontested group (13.4% vs 5.9%, standardised difference [SD] 0.26, for cardiac catheterisation; 6.6% vs 2.7%, SD 0.19, for PCI). The CST group had a significantly lower primary event rate at 3 years compared without CST (3.9% vs 4.5%, hazard ratio 0.87, 95% confidence interval 0.81-0.93). CONCLUSIONS: This population-based study of PCI patients found a small but significantly lower risk of cardiovascular events among patients who received CST. Further studies are needed to confirm these findings and determine the specific aspects of care that may be associated with the modestly improved outcomes.

Association Between Maternal Glucose Levels in Gestational Diabetes Screening and Subsequent Hypertension.

BACKGROUND: We assessed the association between maternal glucose levels in pregnancy and subsequent hypertension. METHODS: This population-level, retrospective cohort study examined women aged 12 to 54 years with singleton pregnancies completed at ≥29 weeks of gestation from October 1, 2008 to December 1, 2018 followed until March 31, 2019 in Alberta, Canada. Women were stratified by results in the 50-gram glucose challenge test and by 75-gram oral glucose tolerance test subtypes (normal oral glucose tolerance test, elevated fasting plasma glucose only [elevated fasting], elevated postload glucose only, or both elevated fasting and postload glucose [combined]. Time to development of hypertension was modeled using Cox proportional hazards models. RESULTS: Of 313 361 women, 231 008 (79.1%) underwent a glucose challenge test only while 60 909 (20.9%) underwent either an oral glucose tolerance test only or both. Nine thousand five hundred eighty (3.1%) developed hypertension, and 2824 (0.9%) developed cardiovascular disease over a median follow-up of 5.7 years. Every 1-mmol/L increase in glucose in the glucose challenge test increased the risk of subsequent hypertension by 15% (adjusted hazard ratio and 95% CI, 1.15 [1.14-1.16]). Among those who underwent the oral glucose tolerance test, the combined group conferred the highest risk of subsequent hypertension, followed by elevated fasting, then elevated postload glucose only (reference: glucose challenge test ≤7.1 mmol/L, adjusted hazard ratio [95% CI]: elevated postload glucose only, 1.83 [1.68-2.00]; elevated fasting 2.02 [1.70-2.40]; combined, 2.65 [2.33-3.01]). No significant associations between maternal glucose levels and cardiovascular disease were observed. CONCLUSIONS: Increasing maternal glucose levels in pregnancy were associated with increasing risk of subsequent hypertension. These findings may help identify higher-risk women who should be targeted for earlier postpartum cardiovascular risk reduction.

The Association of Sodium-Glucose Cotransporter 2 Inhibitors With Cardiovascular Outcomes in Anthracycline-Treated Patients With Cancer.

Background: Sodium glucose cotransporter-2 inhibitors (SGLT2is) are hypothesized to reduce the risk of anthracycline-associated cardiotoxicity. Objectives: This study sought to determine the association between SGLT2is and cardiovascular disease (CVD) after anthracycline-containing chemotherapy. Methods: Using administrative data sets, we conducted a population-based cohort study of people >65 years of age with treated diabetes and no prior heart failure (HF) who received anthracyclines between January 1, 2016, and December 31, 2019. After estimating propensity scores for SGLT2i use, the average treatment effects for the treated weights were used to reduce baseline differences between SGLT2i-exposed and -unexposed controls. The outcomes were hospitalization for HF, incident HF diagnoses (in- or out-of-hospital), and documentation of any CVD in future hospitalizations. Death was treated as a competing risk. Cause-specific HRs for each outcome were determined for SGLT2i-treated people relative to unexposed controls. Results: We studied 933 patients (median age 71.0 years, 62.2% female), 99 of whom were SGLT2i treated. During a median follow-up of 1.6 years, there were 31 hospitalizations for HF (0 in the SGLT2i group), 93 new HF diagnoses, and 74 hospitalizations with documented CVD. Relative to controls, SGLT2i exposure was associated with HR of 0 for HF hospitalization (P < 0.001) but no significant difference in incident HF diagnosis (HR: 0.55; 95% CI: 0.23-1.31; P = 0.18) or CVD diagnosis (HR: 0.39; 95% CI: 0.12-1.28; P = 0.12). There was no significant difference in mortality (HR: 0.63; 95% CI: 0.36-1.11; P = 0.11). Conclusions: SGLT2is may reduce the rate of HF hospitalization after anthracycline-containing chemotherapy. This hypothesis warrants further testing in randomized controlled trials.

Temporal Trends in Type 1, Type 2, and Gestational Diabetes in Pregnancy: Impact of Rural Residence, Ethnicity, and Material Deprivation.

OBJECTIVE: Our aim in this study was to implement a newly validated algorithm to identify pregnant women with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM), and to identify temporal trends in rates over the last decade. We also compared obstetric and neonatal outcomes of pregnancies with and without diabetes mellitus (DM). METHODS: Among women with live births between 2005 and 2018 in Alberta, we calculated yearly rates of T1DM, T2DM, and GDM, overall, and stratified by ethnicity, urban or rural residence, material deprivation score, and maternal age. RESULTS: Between 2005 and 2018, GDM rates increased from 42.3 to 101.8 per 1,000 deliveries (p<0.0001), T2DM rates increased from 2.6 to 6.4 per 1,000 deliveries (p<0.0001), whereas T1DM remained constant at 3.0 per 1,000 deliveries each year (p=0.4301). Higher GDM and T2DM rates were observed among Chinese and South Asian women, respectively, and among women who were materially deprived and living in urban areas. Women with T2DM were older and had the highest rates of pre-existing hypertension (16%). In contrast, women with T1DM were younger and had the highest rates of gestational hypertension (12%), pre-eclampsia (12%), and cesarean section deliveries (62%). Children of women with T1DM had the highest rates of large for gestational age (46%), neonatal hypoglycemia (41.1%), respiratory distress syndrome (7.7%), and jaundice (29.3%). CONCLUSIONS: Diabetes-in-pregnancy rates have more than doubled over the last decade, driven primarily by increases in GDM and T2DM. These trends may have significant implications for the future health of mothers and children in Alberta.

Validity of Alternative Claims-based Algorithms for Type 1, Type 2, and Gestational Diabetes in Pregnancy.

OBJECTIVE: Our aim in this study was to evaluate the accuracy of alternative algorithms for identifying pre-existing type 1 or 2 diabetes (T1DM or T2DM) and gestational diabetes mellitus (GDM) in pregnant women. METHODS: Data from a clinical registry of pregnant women presenting to an Edmonton diabetes clinic between 2002 and 2009 were linked and administrative health records. Three algorithms for identifying women with T1DM, T2DM, and GDM based on International Classification of Diseases---tenth revision (ICD-10) codes were assessed: delivery hospitalization records (Algorithm #1), outpatient clinics during pregnancy (Algorithm #2), and delivery hospitalization plus outpatient clinics during pregnancy (Algorithm #3). In a subset of women with clinic visits between 2005 and 2009, we examined the performance of an additional Algorithm #4 based on Algorithm #3 plus outpatient clinics in the 2 years before pregnancy. Using the diabetes clinical registry as the "gold standard," we calculated true positive rates and agreement levels for the algorithms. RESULTS: The clinical registry included data on 928 pregnancies, of which 90 were T1DM, 89 were T2DM, and 749 were GDM. Algorithm #3 had the highest true positive rate for the detection of T1DM, T2DM, and GDM of 94%, 72%, and 99.9%, respectively, resulting in an overall agreement of 97% in diagnosis between the administrative databases and the clinical registry. Algorithm #4 did not provide much improvement over Algorithm #3 in overall agreement. CONCLUSIONS: An algorithm based on ICD-10 codes in the delivery hospitalization and outpatient clinic records during pregnancy can be used to accurately identify women with T1DM, T2DM, and GDM.