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Background: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. Methods: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. Results: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: 5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (−0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus −1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (−0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). Conclusions: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01178320.

Angina with no obstructive coronary artery disease (ANOCA) is a common entity. There is still under-recognition of this condition, but it is unclear if the referral patterns for chest pain diagnosis have changed. We aimed to determine if the prevalence of patients diagnosed with ANOCA by means of coronary angiography has changed over time.A population-based cohort of patients who had their first coronary angiogram for a chest pain syndrome in Alberta from 1995 to 2020 was extracted retrospectively from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. A temporal trend analysis was performed to compare patients with ANOCA vs obstructive coronary artery disease (CAD), and the predictors of ANOCA were investigated.In our analysis, 121,066 patients were included (26% ANOCA, 31% female, overall mean age 62 years). The percentages of ANOCA vs obstructive CAD ranged from 24.2% to 26.7% in all patients (P0.001), from 19.4% to 21.4% in patients with acute coronary syndromes (P = 0.002), and from 30.6% to 37.5% in patients with stable angina (P0.001). Independent predictors of ANOCA were female sex (odds ratio [OR] 3.34, 95% confidence interval [CI] 3.05-3.66), younger age (OR 0.96, 95% CI 0.95-0.96), history of atrial fibrillation (OR 2.18, 95% CI 1.73-2.73), and stable angina (vs myocardial infarction: OR 0.25, 95% CI 0.23-0.28; vs unstable angina: OR 0.79, 95% CI 0.70-0.89). Traditional cardiovascular risk factors were associated with obstructive CAD.There remained a high prevalence of ANOCA detected during invasive coronary angiography, which remained stable over time. This study demonstrates an opportunity to exclude obstructive CAD with less invasive testing, particularly in women.

Aims Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. Methods and results A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow‐up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan–Meier analyses compared to those with no remodelling, log‐rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. Conclusions Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long‐term outcomes whereas change in left ventricular ejection fraction did not.

A better understanding of the central role of inflammation in the development of coronary artery disease (CAD) has been the impetus for the evaluation of therapeutic strategies targeting the interleukin-1s/interleukin-6 cytokine signaling pathway, involved in both chronic atherogenesis and in triggering of atherosclerotic plaque rupture. As an inexpensive pharmacologic agent with relatively few adverse effects that tend to be mild and tolerable, the role of colchicine in secondary prevention of atherothrombotic events has been the focus of multiple recent large-scale randomized controlled trials involving patients with stable CAD (Low-Dose Colchicine [LoDoCo] and LoDoCo2 trials), a recent myocardial infarction (Colchicine Cardiovascular Outcome Trial [COLCOT], Colchicine in Patients With Acute Coronary Syndrome [COPS], and Colchicine and Spironolactone in Patients With Myocardial Infarction/Synergy Stent Registry [CLEAR SYNERGY] trials), and undergoing percutaneous coronary interventions (Colchicine in Percutaneous Coronary Intervention [COLCHICINE-PCI] trial). Based on this evidence, low-dose colchicine (0.5 mg once daily) should be considered in patients with recent myocardial infarctions—within 30 days and, ideally, within 3 days—or with stable CAD to improve cardiovascular outcomes. Colchicine should not be used in patients with severe renal or hepatic disease because of the risk of severe toxicity. No serious adverse effect was associated with the combined use of colchicine and high-intensity statin therapy in large trials. The impact of colchicine in high-risk populations of patients with peripheral arterial disease and in those with diabetes for the primary prevention of CAD remains to be established.

Background Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality worldwide. Data from Canadian populations regarding the burden of ASCVD are limited. Therefore, we describe the 5‐year period prevalence of ASCVD and subsequent major adverse cardiovascular event (MACE) outcomes among patients with ASCVD in Alberta, Canada. Methods A retrospective, observational study was conducted by linking provincial health services data, vital statistics, and pharmaceutical dispenses data. Five‐year period prevalence of clinical ASCVD was captured between 2011 and 2016, and a cohort of adult patients with an initial clinical ASCVD event were identified between 2012 and 2016. One‐year incidence rates (IRs) of subsequent MACE outcomes were calculated as composite and individual measures. A subgroup of patients with acute myocardial infarction (AMI) as their index event was examined. Results There were 198 573 patients (mean [standard deviation] age: 63.9 [15.6] years; 56.6% males) identified with clinical ASCVD between 2012 and 2016. Overall, the 5‐year period prevalence of ASCVD in Alberta was 89.9 per 1000 persons and the 1‐year IR for a primary MACE outcome was 6.15 (95% confidence interval [CI]: 6.03–6.26) per 100 person‐years. Among the ASCVD cohort, 9465 had an AMI as their index event and the IR for a primary MACE outcome was 14.30 (95% CI: 13.45–15.20) per 100 person‐years. Conclusions This study found that the prevalence of ASCVD and the rate of subsequent MACE outcomes 1 year following the initial ASCVD event are substantial, particularly among patients with an AMI. Secondary prevention strategies aimed at lowering this risk are needed for patients with ASCVD.

In patients with acute coronary syndromes (ACS), guidelines recommend the assessment of left-ventricular ejection fraction (LVEF). Many patients with ACS undergo multiple assessments of LVEF, the clinical value of which is unknown.Patients with ACS undergoing cardiac catheterization between 2012 and 2016 were evaluated and assessments of LV function identified. To evaluate changes in LVEF over time, available echocardiograms were reviewed in a subsample of patients with LVEF data available (n = 3221). Patients with ACS were classified into 3 groups: group 1 (LVEF50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF35%).Our cohort consisted of 8327 patients with ACS (76% men), presenting with a mean age of 62.4 ± 12.4 years. At index presentation, 66% of patients had an LVEF50%, 27% had an LVEF between 35% and 50%, and 7% had severely reduced LVEF of35%. More than half of the cohort (n = 4600) had follow-up assessment of LV function, performed over an average of 2.71 ± 1.31 years. In the subsample of 3221 patients, only 1.1% of those in group 1, and 5.1% of those in group 2, deteriorated to an LVEF35%.Patients with ACS often undergo multiple assessments of LV function. Those with initially preserved EF rarely demonstrate a decline in EF to35%. A reduction in low-value cardiac tests may be an important first step in improving the quality of care for patients with ACS.En cas de syndrome coronarien aigu (SCA), les lignes directrices recommandent d’évaluer la fraction d’éjection ventriculaire gauche (FEVG). Beaucoup de patients présentant un SCA subissent plusieurs évaluations de la FEVG, une pratique dont on ne connaît pas la valeur clinique.Nous avons examiné les dossiers de patients atteints d’un SCA ayant subi un cathétérisme cardiaque entre 2012 et 2016 afin de relever les évaluations de la fonction ventriculaire gauche. Pour évaluer l’évolution de la FEVG au fil du temps, nous avons examiné les échocardiogrammes d’un sous-échantillon de patients pour lesquels des données sur la FEVG étaient disponibles (n = 3 221). Les patients présentant un SCA ont été divisés en trois groupes : groupe 1 (FEVG50 %), groupe 2 (FEVG de 35 à 50 %) et groupe 3 (FEVG35 %).Notre cohorte comprenait 8 327 patients présentant un SCA (proportion d’hommes : 76 %), dont l’âge moyen était de 62,4 ± 12,4 ans. Au moment de la manifestation de référence, 66 % des patients avaient une FEVG50 %, 27 %, une FEVG de 35 à 50 % et 7 %, une FEVG gravement réduite35 %. Plus de la moitié des patients de la cohorte (n = 4 600) ont subi une évaluation de suivi de la fonction ventriculaire gauche, effectuée sur une période de 2,71 ± 1,31 ans en moyenne. Dans le sous-échantillon de 3 221 patients, seulement 1,1 % des patients du groupe 1 et 5,1 % de ceux du groupe 2 ont vu leur FEVG se détériorer à une valeur35 %.Les patients présentant un SCA subissent souvent plusieurs évaluations de la fonction ventriculaire gauche. Ceux dont la fraction d’éjection était initialement préservée ont rarement présenté une réduction de la fraction d’éjection en deçà de 35 %. Une réduction du nombre d’évaluations cardiaques offrant peu de valeur pourrait constituer un premier pas important vers l’amélioration de la qualité des soins prodigués aux patients présentant un SCA.

The Framingham Risk Score (FRS) and Pooled Cohort Equations (PCEs) overestimate risk in many contemporary cohorts.This study sought to determine if recalibration of these scores using contemporary population-level data improves risk stratification for statin therapy.Five-year FRS and PCEs were recalibrated using a cohort of Ontario residents alive January 1, 2011, who were 30 to 79 years of age without cardiovascular disease. Scores were externally validated in a primary care cohort of routinely collected electronic medical record data from January 1, 2010, to December 31, 2014. The relative difference in mean predicted and observed risk, number of statins avoided, and number needed to treat with statins to reduce a cardiovascular event at 5 years were reported.The FRS was recalibrated in 6,938,971 Ontario residents (51.6% women, mean age 48 years) and validated in 71,450 individuals (56.1% women, mean age 52 years). Recalibration reduced overestimation from 109% to 49% for women and 131% to 32% for men. The recalibrated FRS was estimated to reduce statin prescriptions in up to 26 per 1,000 low-risk women and 80 per 1,000 low-risk men, as well as reduce the number needed to treat from 61 to 47 in women and from 53 to 41 in men. In contrast, after recalibration of the PCEs, risk remained overestimated by 217% in women and 128% in men.Recalibration is a feasible solution to improve risk prediction but is dependent on the model being used. Recalibration of the FRS but not the PCEs reduced overestimation and may improve utilization of statins.

Over the past 66 years, our knowledge of the role of the endothelium in the regulation of cardiovascular function and dysfunction has advanced from the assumption that it is a single layer of cells that serves as a barrier between the blood stream and vascular smooth muscle to an understanding of its role as an essential endocrine-like organ. In terms of historical contributions, we pay particular credit to (1) the Canadian scientist Dr. Rudolf Altschul who, based on pathological changes in the appearance of the endothelium, advanced the argument in 1954 that “one is only as old as one’s endothelium” and (2) the American scientist Dr. Robert Furchgott, a 1998 Nobel Prize winner in Physiology or Medicine, who identified the importance of the endothelium in the regulation of blood flow. This review provides a brief history of how our knowledge of endothelial function has advanced and now recognize that the endothelium produces a plethora of signaling molecules possessing paracrine, autocrine, and, arguably, systemic hormone functions. In addition, the endothelium is a therapeutic target for the anti-diabetic drugs metformin, glucagon-like peptide I (GLP-1) receptor agonists, and inhibitors of the sodium–glucose cotransporter 2 (SGLT2) that offset the vascular disease associated with diabetes.

Aims Measures of structural and functional remodelling of the left atrium (LA) are emerging as useful biomarkers in heart failure (HF). We hypothesized that LA volume and its contribution to stroke volume (SV) would predict a composite endpoint of HF hospitalization or death in patients with HF. Methods and results We recruited 57 controls and 86 patients with HF, including preserved and reduced left ventricular ejection fraction (LVEF). Cardiac magnetic resonance imaging was used to evaluate LA volumes and contribution to LV SV. Plasma mid-region pro-atrial natriuretic peptide (MR-proANP) was evaluated. LA volume was negatively correlated with LVEF (P = 0.001) and positively correlated with LV mass in HFrEF (P Conclusion We found different relationships between LA remodelling and biomarkers in HFrEF and HFpEF. Our results support the hypothesis that the pathophysiologic underpinnings of HFpEF and HFrEF are different, and atrial remodelling encompasses distinct components for each HF subtype.

BACKGROUND: Although accurate risk prediction is essential in guiding treatment decisions in primary prevention of atherosclerotic cardiovascular disease, the accuracy of the Framingham Risk Score (recommended by a Canadian guideline) and the Pooled Cohort Equations (recommended by US guidelines) has not been assessed in a large contemporary Canadian population. Our primary objective was to assess the calibration and discrimination of the Framingham Risk Score and Pooled Cohort Equations in Ontario, Canada. METHODS: We conducted an observational study involving Ontario residents aged 40 to 79 years, without a history of atherosclerotic cardiovascular disease, who underwent cholesterol testing and blood pressure measurement from Jan. 1, 2010, to Dec. 31, 2014. We compared predicted event rates generated by the Framingham Risk Score and the Pooled Cohort Equations with observed event rates at 5 years using linkages from validated administrative databases. RESULTS: Our study cohort included 84 617 individuals (mean age 56.3 yr, 56.9% female). Over a maximum follow-up period of 5 years, we observed 2162 (2.6%) events according to the outcome definition of the Framingham Risk Score, and 1224 (1.4%) events according to the outcome definition of the Pooled Cohort Equations. The predicted event rate of 5.78% by the Framingham Risk Score and 3.51% by the Pooled Cohort Equations at 5 years overestimated observed event rates by 101% and 115%, respectively. The degree of overestimation differed by age and ethnicity. The C statistics for the Framingham Risk Score (0.74) and Pooled Cohort Equations (0.73) were similar. INTERPRETATION: The Framingham Risk Score and Pooled Cohort Equations significantly overpredicted the actual risks of atherosclerotic cardiovascular disease events in a large population from Ontario. Our finding suggests the need for further refinement of cardiovascular disease risk prediction scores to suit the characteristics of a multiethnic Canadian population.

In this report, we describe the fabrication, characterization, and use of a massive array of closed bipolar ultramicroelectrodes (UMEs) in electrochemical imaging applications. The bipolar UME array is 1 cm

In this work, we describe the preparation and use of a thin metal film modified Indium Tin Oxide (ITO) electrode as a highly conductive, transparent, and electrocatalytically active electrode material for studying nanobubbles generated at the electrode/solution interface. Hydrogen and oxygen nanobubbles were generated from water electrolysis on the surface of a Au/Pd alloy modified ITO electrode. The formation of single H2 and O2 nanobubbles was imaged in real time during a potential scan using single-molecule fluorescence microscopy. Our results show that while O2 nanobubbles can be detected at an early stage in the oxygen evolution reaction (OER), the formation of H2 nanobubbles requires a significant overpotential. Our study shows that thin-film-coated ITO electrodes are simple to make and can be useful electrode substrates for (single molecule) spectroelectrochemistry research.

Introduction: The coronavirus disease 2019 (COVID-19) pandemic has impacted cardiovascular (CV) outcomes and care globally, although to date, limited data exist on the Canadian experience. This study aimed to describe trends in major adverse cardiovascular events (MACE)/procedures during the COVID-19 pandemic in the Province of Alberta, Canada. Methods: A repeated cross-sectional study design compared MACE from inpatient and emergency department visits among Albertan adults between March 15, 2019, and September 14, 2020. The Alberta population was 4.4 million in 2020 and all residents are part of a single payer healthcare system. The percent change between each MACE reported in the control (2019) and COVID-19 restriction periods (2020) were calculated. MACE were defined individually and as a primary composite outcome (CV death, acute coronary syndrome [ACS], ischemic stroke, or coronary revascularization procedures). These preliminary data are part of an ongoing study, measuring outcomes throughout the first year of the pandemic. Results: Compared to March-June 2019, primary MACE during the initial COVID-19 restriction period (March-June 2020) decreased by 15.6% (n=739 patients), and by 7.3% (n=342 patients) during June-September 2020, when COVID-19 restrictions were eased. Most individual MACE followed similar patterns with reduced reported events/procedures during the initial restriction period and an increase towards previous rates thereafter (Figure 1): CV death (17.7% vs 10.2%), ACS (19.1% vs 8.4%), coronary revascularization (17.0% vs 9.2%). The exception was ischemic stroke, which was not notably impacted by pandemic restrictions. Conclusions: Declines in MACE/procedures during the COVID-19 pandemic are suggestive of a substantial gap in patient management and healthcare-seeking behaviour that may have negative downstream implications. Ongoing analyses will further explore reported MACE up to one year after the pandemic began.

On-treatment levels of high sensitivity C-reactive protein (hsCRP) in statin-treated patients predict plaque progression and the prospective risk of atherosclerotic cardiovascular events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors produce additional LDL-C lowering, reduce plaque burden and improve cardiovascular outcomes in statin-treated patients. It is unknown whether residual systemic inflammation attenuates their favorable effects on plaque burden.GLAGOV compared the effects of treatment for 78 weeks with evolocumab or placebo on progression of coronary atherosclerosis in statin-treated patients with coronary artery disease.Clinical demographics, biochemistry and changes in both the burden (percentage atheroma volume (PAV), total atheroma volume (TAV), n ​= ​413) and composition (n ​= ​162) of coronary plaque were evaluated in evolocumab-treated patients according to baseline hsCRP strata (1, 1-3,3 ​mg/L).The study cohort comprised 413 evolocumab-treated patients (32% low [1 ​mg/L], 41% intermediate [1-3 ​mg/L] and 27% high [3 ​mg/L] baseline hsCRP levels). Patients in the highest hsCRP stratum were more likely to be female and had a higher prevalence of diabetes, hypertension, and the metabolic syndrome. LDL-C levels were similar across the groups, however participants with higher hsCRP levels had higher triglyceride and lower HDL-C levels at baseline. At follow-up, the change in PAV from baseline (-0.87% [low] vs. -0.84% [intermediate] vs. -1.22% [high], p ​= ​0.46) and the proportion of patients experiencing any degree of regression (65.9% vs. 63.5% vs. 63.1%, p ​= ​0.88) was similar across hsCRP strata and when evaluated by levels of achieved LDL-C. There were no serial differences in plaque composition by hsCRP strata.The ability of evolocumab to induce regression in statin-treated patients is not attenuated by the presence of enhanced systemic inflammation. This underscores the potential benefits of intensive lipid lowering, even in the presence of heightened inflammatory states.

Statins are first line therapy in people with diabetes. Little is known about real-world statin intensity use and low-density lipoprotein cholesterol (LDL-C) levels achieved. We aimed to describe statin intensity used, achievement of LDL-C targets, and factors associated with achieving targets among adults with diabetes.This population based (∼4.3 million), retrospective observational study, used clinical and administrative databases. Statin use by intensity, adherence, and achievement of LDL-C targets in adults with diabetes were described. Multiple logistic regression assessed the factors associated with achieving targets.Out of 331,312 individuals with diabetes, 88% had an index LDL-C test. At follow up, 31% overall did not achieve LDL-C targets and overall adherence was 66%. Failure to achieve targets was 49%, 30%, and 25% in low-, moderate-, and high-intensity statin groups, respectively. Those who were older, males, had a history of myocardial infarction, stroke, congestive heart failure, renal disease, better adherence, and higher intensity statin users were more likely to achieve targets.One-third of people on statins did not achieve targets. Strategies to fill the gap between ideal and current levels of LDL-C achieved are needed if the benefits of statins demonstrated in trials are to be translated into practice.

The under-utilization of cardiovascular preventative therapy with statins warrants novel interventions to optimize prescriptions in at-risk patients. We investigated the role of a laboratory generated Framingham Risk Score (FRS) provided to primary care clinicians in changing statin use in a primary care setting.Data was acquired from the electronic medical records of 1573 anonymized patients undergoing routine lipid testing. Follow-up statin use and low-density lipoprotein cholesterol levels were obtained for 2 years post intervention. FRS parameters were entered into a laboratory information system, and provided to ordering physicians along with the cholesterol profile and the appropriate current Canadian Dyslipidemia treatment recommendation in a single report. Statin prescription rates following the intervention were compared with historical use 6 months prior to the study.A total of 1283 participants (mean age of 60 ± 11 years) had an FRS report and were considered for analysis. Two hundred individuals filled a statin prescription in the 6 months prior to their index lipid test, and an additional 84 filled a statin prescription following the intervention (42% increase). The relative and absolute increase in statin prescription was 47.3% and 13.6% in the high-risk group p 0.001, 53.3% and 8.1% in the intermediate-risk group p 0.001, and 17.0% and 1.42% in the low-risk group p = 0.008, respectively.The use of the laboratory reported FRS was associated with a significant increase in the rate of statin prescription across all risk groups. The expansion of FRS reporting across other health regions would improve cardiovascular risk prevention.

NEW FINDINGS What is the central question of this study? Does treatment of obstructive sleep apnoea (OSA) with nocturnal oxygen or continuous positive airway pressure (CPAP) improve hypoxic vascular responses, which are reportedly impaired in OSA? What is the main finding and its importance? Cerebrovascular and cardiovascular hypoxic responses were not impaired in OSA patients free of overt cardiovascular disease and known risk factors, and were not altered by nocturnal oxygen or CPAP treatment. We conclude that this OSA patient phenotype has normal vascular responses to hypoxia and is unlikely to obtain long term cardiovascular benefits from nocturnal oxygen or CPAP therapy. ABSTRACT Cerebral blood flow (CBF) and cardiovascular responses to hypoxia are reportedly impaired in obstructive sleep apnoea (OSA) patients and corrected by continuous positive airway pressure (CPAP), beneficial effects that are ascribed to correction of OSA-related intermittent hypoxia (IH). However, CPAP corrects both IH and ancillary OSA features (i.e. intermittent hypercapnia, sympathetic activation, blood pressure surges, negative intrathoracic pressure swings and sleep fragmentation). Whether correction of these ancillary OSA features contribute to CPAP's beneficial effects on vascular hypoxic responses is unknown. Nocturnal oxygen corrects OSA-induced IH, but apnoeas and ancillary features persist. Thus, we examined the effects of nocturnal oxygen and CPAP on cerebrovascular and cardiovascular hypoxic responses in untreated OSA patients. Responses were assessed in 52 OSA patients free of overt cardiovascular disease and known risk factors at baseline, after 2 weeks of nocturnal oxygen (n = 26) or no treatment (n = 26), and after ∼4 weeks of CPAP treatment (n = 40). Twenty-two age-matched controls were assessed at baseline and follow-up visits. Resting, isocapnic euoxia mean blood pressure was decreased following nocturnal oxygen (-3.6 ± 6.0 mmHg; P = 0.006) and CPAP (-4.5 ± 7.5 mmHg; P

BACKGROUND Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality in Canada and worldwide. Laboratory tests, including troponin and low-density lipoprotein cholesterol (LDL-C), are important biomarkers of ASCVD risk. The objective of this study was to investigate patterns of testing for troponin and LDL-C test volumes among Alberta residents during the coronavirus disease 2019 (COVID-19) pandemic. METHODS AND RESULTS A repeated cross-sectional study design captured population-level laboratory test volumes between March 15, 2019 and December 14, 2020. Three-month cross-sections were derived to report laboratory test volumes by different COVID-19 restriction periods during 2020-2021 and using 2019-2020 as a preceding control period. Percent change for troponin and LDL-C test volumes were calculated for both control and COVID-19 periods among adult (≥18 years of age) Alberta residents, and stratified by age (18-49, 50-65, 66-79, and ≥80 years), sex, and geographic zones (urban, rural). This preliminary data is part of an ongoing study for which further troponin and LDL-C test volumes will be available up until March 14, 2021 (representing one year of data throughout the COVID-19 pandemic). Among the Alberta population, 292,836 troponin and 794,789 LDL-C tests were captured between March 15, 2020 and December 14, 2020 (Figure 1). Testing patterns during the COVID-19 restriction period showed marked reduction in test volumes from the previous year. The initial cross-section of the COVID-19 period (March-June 2020) was characterized by the largest overall reduction with troponin test volumes decreasing 18% and LDL-C test volumes decreasing 63%, compared to the year prior. As restrictions eased in the summer months of 2020, testing volumes rebounded to near pre-pandemic volumes for both tests. However, in the fall of 2020, troponin tests decreased again (-15%). Within these drops in utilization, slightly larger relative declines were observed for troponin test volumes in women (-20%) and patients ≥80 years-old (-25%) and for LDL-C test volumes among urban residents (-64%), women (-67%) and patients aged 18-49 (-66%) and 50-65 (-65%) years (Table 1). CONCLUSION This study describes declines in troponin and LDL-C test volumes in the initial and second COVID-19 lockdown periods. Women had overall smaller total troponin and LDL-C test volumes and larger relative declines during the pandemic compared to men. The decrease in these ASCVD-related laboratory test volumes during the pandemic may have been accompanied by other important changes in indicators of healthcare utilization and associated clinical outcomes. Ongoing analyses will further explore the impact of the pandemic.

AIM Limited data exist on the impact of contrast-enhanced echocardiography on treatment decisions in heart failure patients that require specific left ventricular ejection fraction (LVEF) criteria. This study assessed accuracy of contrast-enhanced echocardiography in identifying patients with LVEF >35% vs ≤35% with cardiac magnetic resonance (CMR) used as reference method. METHODS AND RESULTS Fifty-five patients from prospective Alberta HEART cohort with LVEF ≤50% on CMR were included. All patients had echocardiography performed within 2 weeks of CMR. Contrast agent was used when ≥2 contiguous LV endocardial segments were poorly visualized on echocardiography. LVEF was computed by Simpson's biplane method using non-contrast echocardiography and contrast-enhanced echocardiography and by outlining the endocardial contours in short-axis cine CMR images. Strong agreement in LV volumes and LVEF was seen between CMR and echocardiography with and without contrast (intra-class correlation coefficients >0.8) with less underestimation of LV volumes by contrast-enhanced echocardiography. Good agreement in LVEF ≤35% vs >35% was seen between CMR and non-contrast echocardiography with optimal images (κ 0.862) and contrast echocardiography (κ 0.769) while it was moderate for non-contrast echocardiography with suboptimal images (κ 0.491). The use of LV contrast in patients with suboptimal images (n = 39) resulted in correctly upgrading LVEF from ≤35% to >35% in 5 (13%) patients and downgrading LVEF from >35% to ≤35% in 2 (5%) patients using CMR as reference. CONCLUSIONS Contrast-enhanced echocardiography in heart failure patients with suboptimal images helps to more accurately assess eligibility for specific therapies and avoid need for further testing, therefore should be considered routine part of echocardiographic assessment.

Background: Incremental low-density lipoprotein (LDL) cholesterol lowering with the proprotein convertase subtilisin kexin type 9 inhibitor evolocumab regresses coronary atherosclerosis in statin-treated patients. Objectives: The purpose of this study was to evaluate the effect of adding evolocumab to statin therapy on coronary plaque composition. Methods: A total of 968 statin-treated coronary artery disease patients underwent serial coronary intravascular ultrasound imaging at baseline and following 76 weeks of treatment with placebo or evolocumab 420 mg monthly. Plaque composition changes were determined in 331 patients with evaluable radiofrequency analysis of the ultrasound backscatter signal. Results: Compared with statin monotherapy, evolocumab further reduced LDL cholesterol (33.5 mg/dl vs. 89.9 mg/dl; p < 0.0001) and induced regression of percent atheroma volume (−1.2% vs. +0.17%; p < 0.0001) and total atheroma volume (−3.6 mm3 vs. −0.8 mm3; p = 0.04). No difference was observed between the evolocumab and placebo groups in changes in calcium (1.0 ± 0.3 mm3 vs. 0.6 ± 0.3 mm3; p = 0.49), fibrous (−3.0 ± 0.6 mm3 vs. −2.4 ± 0.6 mm3; p = 0.49), fibrofatty (−5.0 ± 1.0 mm3 vs. −3.0 ± 1.0 mm3; p = 0.49), and necrotic (−0.6 ± 0.5 mm3 vs. −0.1 ± 0.5 mm3; p = 0.49) volumes. An inverse correlation was observed between changes in LDL cholesterol and plaque calcification (r = −0.15; p < 0.001). Conclusions: The addition of evolocumab to a statin did not produce differential changes in plaque composition compared with statin monotherapy. This suggests that evaluation of plaque morphology using virtual histology imaging may provide no incremental information about the plaque effects of evolocumab beyond measurement of plaque burden. (GLobal Assessment of Plaque reGression With a PCSK9 antibOdy as Measured by intraVascular Ultrasound [GLAGOV]; NCT01813422)

Accelerated trajectories of cognitive decline in older adults may increase the risk of developing Alzheimer disease and related dementias (ADRD). Physical activity has potential modifying effects on these changes that could prevent or delay ADRD. This review explores the hypothesis that multiple, mutually complimentary, and interacting factors explain the positive association between exercise and the optimization of cognition in older adults.

The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings that have emerged since the 2016 guidelines. In patients with clinical atherosclerosis, abdominal aortic aneurysm, most patients with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol ≥ 5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with nonstatin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃ 1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein B are the preferred lipid parameter for screening, rather than low-density lipoprotein cholesterol. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.

A primary characteristic of obstructive sleep apnea (OSA) is chronic exposure to intermittent hypoxia (IH) due to repeated upper airway obstruction. Chronic IH exposure is believed to increase OSA severity over time by enhancing the acute ventilatory response to hypoxia (AHVR), thus promoting ventilatory overshoot when apnea ends and perpetuation of apnea during sleep. Continuous positive airway pressure (CPAP), the gold-standard treatment of OSA, reduces the AHVR, believed to result from correction of IH. However, CPAP also corrects ancillary features of OSA such as intermittent hypercapnia, negative intrathoracic pressure and surges in sympathetic activity, which may also contribute to the reduction in AHVR. Therefore, the objective of this study was to investigate the impact of nocturnal oxygen therapy (to remove IH only) and CPAP (to correct IH and ancillary features of OSA) on AHVR in newly diagnosed OSA patients. Fifty-two OSA patients and twenty-two controls were recruited. The AHVR was assessed using a 5 min iscopanic-hypoxic challenge before, and after, treatment of OSA by nocturnal oxygen therapy and CPAP. Following baseline measurements, OSA patients were randomly assigned to nocturnal oxygen therapy (Oxygen, n = 26) or no treatment (Air; n = 26). The AHVR was re-assessed following two weeks of oxygen therapy or no treatment, after which all patients were treated with CPAP. The AHVR was quantified following ~4 weeks of adherent CPAP therapy (n = 40). Both nocturnal oxygen and CPAP treatments improved hypoxemia (p 0.05), and, as expected, nocturnal oxygen therapy did not completely abolish respiratory events (i.e., apneas/hypopneas). Averaged across all OSA patients, nocturnal oxygen therapy did not change AHVR from baseline to post-oxygen therapy. Similarly, the AHVR was not altered pre- and post-CPAP (p 0.05). However, there was a significant decrease in AHVR with both nocturnal oxygen therapy and CPAP in patients in the highest OSA severity quartile (p 0.05). Nocturnal oxygen therapy and CPAP both reduce the AHVR in patients with the most severe OSA. Therefore, IH appears to be the primary mechanism producing ventilatory instability in patients with severe OSA via enhancement of the AHVR.

Background There remains no effective intervention capable of reversing most cases of dementia. Current research is focused on prevention by addressing risk factors that are shared between cardiovascular disease and dementia (e.g., hypertension) before the cognitive, functional, and behavioural symptoms of dementia manifest. A promising preventive treatment is exercise. This study describes the methods of a randomized controlled trial (RCT) that assesses the effects of aerobic exercise and behavioural support interventions in older adults at increased risk of dementia due to genetic and/or cardiovascular risk factors. The specific aims are to determine the effect of aerobic exercise on cognitive performance, explore the biological mechanisms that influence cognitive performance after exercise training, and determine if changes in cerebrovascular physiology and function persist 1 year after a 6-month aerobic exercise intervention followed by a 1-year behavioural support programme (at 18 months). Methods We will recruit 264 participants (aged 50–80 years) at elevated risk of dementia. Participants will be randomly allocated into one of four treatment arms: (1) aerobic exercise and health behaviour support, (2) aerobic exercise and no health behaviour support, (3) stretching-toning and health behaviour support, and (4) stretching-toning and no health behaviour support. The aerobic exercise intervention will consist of three supervised walking/jogging sessions per week for 6 months, whereas the stretching-toning control intervention will consist of three supervised stretching-toning sessions per week also for 6 months. Following the exercise interventions, participants will receive either 1 year of ongoing telephone behavioural support or no telephone support. The primary aim is to determine the independent effect of aerobic exercise on a cognitive composite score in participants allocated to this intervention compared to participants allocated to the stretching-toning group. The secondary aims are to examine the effects of aerobic exercise on a number of secondary outcomes and determine whether aerobic exercise-related changes persist after a 1-year behavioural support programme (at 18 months). Discussion This study will address knowledge gaps regarding the underlying mechanisms of the pro-cognitive effects of exercise by examining the potential mediating factors, including cerebrovascular/physiological, neuroimaging, sleep, and genetic factors that will provide novel biologic evidence on how aerobic exercise can prevent declines in cognition with ageing. Trial registration ClinicalTrials.gov NCT03035851. Registered on 30 January 2017

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery ( V ¯ P ); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V ¯ P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V ¯ P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans.

Background Global longitudinal strain (GLS), most commonly measured at the endocardium, has been shown to be superior to left ventricular (LV) ejection fraction (LVEF) for the identification of systolic dysfunction and prediction of outcomes in heart failure (HF). We hypothesized that strains measured at different myocardial layers (endocardium = ENDO, epicardium = EPI, average = AVE) will have distinct diagnostic and predictive performance for patients with HF. Methods Layer-specific GLS, layer-specific global circumferential strain (GCS) and global radial strain (GRS) were evaluated by cardiovascular magnetic resonance imaging (CMR) feature tracking in the Alberta HEART study. A total of 453 subjects consisted of healthy controls (controls, n = 77), at-risk for HF (at-risk, n = 143), HF with preserved ejection fraction (HFpEF, n = 87), HF with mid-range ejection fraction (HFmrEF, n = 88) and HF with reduced ejection fraction (HFrEF, n = 58). For outcomes analysis, CMR-derived imaging parameters were adjusted with a base model that included age and N-terminal prohormone of b-type natriuretic peptide (NT-proBNP) to test their independent association with 5-year all-cause mortality. Results GLS_EPI distinguished all groups with preserved LVEF (controls − 16.5 ± 2.4% vs. at-risk − 15.5 ± 2.7% vs. HFpEF − 14.1 ± 3.0%, p Conclusion Global strains measured on endocardium, epicardium or averaged across the wall thickness are not equivalent for the identification of systolic dysfunction or outcomes prediction in HF. The endocardium-specific strains were shown to have poorest all-around performance. GLS_AVE and GRS were the only CMR parameters to be significantly associated with 5-year all-cause mortality in multivariable analysis. GLS_EPI and GRS, as well as the difference in endocardial and epicardial strains, were sensitive to systolic dysfunction among HF patients with normal LVEF (> 55%), in whom lower strains were associated with increased concentricity.

Background: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare form of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis characterized by small to medium size vessel vasculitis. Here, we present a case of newly diagnosed EGPA presenting as non-ST segment elevation myocardial infarction (NSTEMI). Case: A 53-year-old male with a history of asthma and nasal polyps presented with acute onset anginal chest pain, rising troponin T and CKMB without ischemic changes on electrocardiogram. He was admitted for NSTEMI. Cardiac catheterization showed non-obstructive coronary artery disease (Figure 1). Given his past medical history along with eosinophilia and pulmonary opacities seen on CT chest, there was concern for EGPA. Lung wedge resection biopsy showed parenchymal eosinophilia, granulomatous inflammation, and vasculitis that confirmed the diagnosis (Figure 2). Figure 1 Figure 2 Discussion: Cardiac involvement is known to be a major contributor to disease-related death, totaling up to 50% of cases, and therefore poses an important aspect of this rare disease. Recent reports, particularly concerning clinical differences given ANCA status, have shown that these patients might represent a heterogeneous group. For instance, ANCA-negative patients, such as our patient, more frequently develop heart conditions. We cultivate such discussion not only to bring attention to EGPA as an uncommon entity to the practice of many cardiologists, but also to point out that early recognition of cardiac involvement could reduce morbidity and mortality.

ObjectiveThe objective of our study was to explore the perspectives of patients and general practitioners (GPs) regarding interventions to increase initiation of cholesterol lowering medication (or statins), including a proposed laboratory-based facilitated relay intervention.DesignQualitative descriptive study using interviews and focus groups for data collection, and thematic analysis for data analysis.SettingPrimary care providers and patients in Calgary, Alberta, Canada.Participants17 GPs with primarily community-based, non-academic practices with at least 1 year of practice experience participated in semistructured interviews. 14 patients at high risk of cardiovascular disease participated in focus groups.Main outcome measuresExploration of strategies that might be used to enhance the prescription of, and adherence to statin therapy for patients with statin-indicated conditions.ResultsGPs proposed a variety of interventions to improve statin prescription, including electronic record audit solutions, GP directed education, and patient-oriented campaigns. Patients expressed that they may benefit from being provided access to their laboratory test results, as well as targeted education. Both parties provided positive feedback on the proposed laboratory-based facilitated relay intervention, while pointing out areas for improvement. Notably, GPs were concerned that the patient-directed component of the intervention might jeopardise therapeutic relationships, and patients were concerned about accidental disclosure of personal health information. Important considerations for the design of facilitated relay messaging should include brevity, simplicity and the provision of contact information for inquiries.ConclusionsGPs and patients described several suggestions for increasing statin initiation and welcomed the proposal of a laboratory-based facilitated relay strategy. These findings support further testing of this intervention which may enhance GPs’ ability to successfully engage patients in cardiovascular risk reduction through statin therapy.