Optimizing Post-Acute Coronary Syndrome Dyslipidemia Management: Insights from the North American Acute Coronary Syndrome Reflective III.

INTRODUCTION: Despite contemporary practice guidelines, a substantial number of post-acute coronary syndrome (ACS) patients fail to achieve guideline-recommended LDL-C thresholds. Our study aimed to investigate this guideline recommendations-to-practice care gap. Specifically, we aimed to identify opportunities where additional lipid-lowering therapies are indicated and explore reasons for the non-prescription of guideline-recommended therapies. METHODS: ACS patients with LDL-C ≥1.81 mmol/L (70 mg/dL) despite maximally tolerated statin ± ezetimibe therapy (including those intolerant of ≥2 statins) were enrolled 1-12 months post-event from 27 Canadian and US sites from September 2018 to October 2020 and followed up for three visits during the 12 months post-event. We determined the proportion of patients who did not achieve Canadian/US guideline-recommended LDL-C thresholds, the number of patients who would have been eligible for additional lipid-lowering therapies, and reasons behind lack of escalation in lipid-lowering therapies when indicated. Individual patient and aggregate practice feedback, including guideline-recommended intensification suggestions, were provided to each physician. RESULTS: Of the 248 patients enrolled in the pilot study (median age 64 [57, 73] years, 31.5% female and STEMI 27.4%), 75.4% were on high-intensity statins on the first visit. A total of 18.5% of those who attended all 3 visits had an LDL-C measured only at the first visit which was above the threshold. After 1 year of follow-up, 51.9% of patients achieved LDL-C thresholds at either visit 2 or 3. In the context of feedback reminding physicians about guideline-directed LDL-C-modifying therapy in their individual participating patients, we observed an increase in the use of ezetimibe and PCSK9 inhibitor therapy at 3-12 months. This was associated with a significant lowering of the mean LDL-C (from 2.93 mmol/L [baseline] to 2.09 mmol/L [3-6 months] to 1.87 mmol/L [6-12 months]) and a significantly greater proportion of patients (from 0% [baseline] to 38.6% [3-6 months] to 53.4% [6-12 months]) achieving guideline-recommended LDL-C thresholds. The most prevalent reasons behind the non-intensification of LDL-C-lowering therapy with ezetimibe and/or PCSK9i were LDL-C levels being close to target, the pre-existing use of other lipid-lowering therapies, patient refusal, and cost. CONCLUSION: Although most patients post-ACS were on high-intensity statin therapy, almost 50% failed to achieve guideline-recommended LDL-C thresholds by 1-year follow-up. Furthermore, additional lipid-lowering therapies in this high-risk group were underprescribed, and this might be linked to several factors including potential gaps in physician knowledge, treatment inertia, patient refusal, and cost.

Physical Activity in Renal Disease and the Effect on Hypertension: A Randomized Controlled Trial.

INTRODUCTION: Exercise is an effective strategy for blood pressure (BP) reduction in the general population, but its efficacy for the management of hypertension in chronic kidney disease (CKD) is not known. We evaluated the difference in 24-h ambulatory systolic BP (SBP) with exercise training in people with moderate to severe CKD. METHODS: Participants with an estimated glomerular filtration rate (eGFR) of 15-44 mL/min per 1.73 m2 and SBP >120 mm Hg were randomized to receive thrice-weekly moderate-intensity aerobic-based exercise over 24 weeks, or usual care. Phase 1 included supervised in-center and home-based sessions for 8 weeks. Phase 2 was 16 weeks of home-based sessions. BP, arterial stiffness, cardiorespiratory fitness, and markers of cardiovascular (CV) risk were analyzed using mixed linear regression. RESULTS: We randomized 44 people; 36% were female, the median age was 69 years, 55% had diabetes, and the median eGFR was 28 mL/min per 1.73 m2. Compared with usual care, there was no significant change in 24-ambulatory SBP at 8 weeks (2.96 mm Hg; 95% confidence interval (CI): -2.56, 8.49) or 24 weeks. Peak oxygen uptake improved by 1.9 mL/kg/min in the exercise group (95% CI: 0.03, 3.79) at 8 weeks with a trend toward higher body mass index 1.84 kg/m2 (95% CI: -0.10, 3.78) and fat free mass, but this was not sustained at 24 weeks. Markers of CV risk were unchanged. CONCLUSIONS: Despite an improvement in peak aerobic capacity and body composition, we did not detect a change in 24-h ambulatory SBP in people with moderate-to-severe CKD.

Incorporating patient preferences into clinical trial design: results of the opinions of patients on treatment implications of new studies (OPTIONS) project.

BACKGROUND: Traditionally, clinical outcomes comprising composite end points in cardiovascular trials are assigned equal weights in statistical analyses. However, the importance of weighting outcomes according to their relative severity is now recognized. This study aimed to elicit patients' perceptions of the importance of cardiovascular outcomes and treatment complications and compare them with those of clinicians. METHODS AND RESULTS: Interviewer-administered surveys, including rating, ranking, point-allocation and trade-off exercises, were conducted in 52 adults with confirmed coronary disease or previous myocardial infarction. Patients viewed "death" as the most severe cardiovascular outcome, followed by cardiogenic shock, congestive heart failure (CHF), and repeat myocardial infarction (re-MI), the same pattern observed in clinician responses in a previous study. Most patients were willing to accept a 3-fold increase in risk of systemic bleed (SB) or nonfatal intracranial hemorrhage (ICH) for a 20% reduction in risk of cardiogenic shock or 60% reduction in risk of CHF, but only a 2-fold increase in the risk of SB or ICH for a 20% reduction in risk of CHF or 60% reduction in risk of re-MI and no increase in risk of SB or ICH for a 20% reduction in risk of re-MI. Similar patterns were seen in a previous study of trade-offs in clinicians. CONCLUSIONS: Although patients' preferences appear to be comparable with those of clinicians, patients may be less willing than clinicians to tolerate potential treatment complications. The methods used in this study offer a feasible approach to incorporating patient preferences into cardiovascular trials and warrant further investigation in broader patient populations.

Percutaneous revascularization improves outcomes in patients with prior coronary artery bypass surgery.

BACKGROUND: Although ACC/AHA guidelines recommend a low threshold for catheterization after coronary artery bypass surgery (CABG), in clinical practice repeat revascularization often appears unfeasible and data on outcomes are scarce. METHODS: Using APPROACH, a clinical data collection and outcome monitoring initiative in Alberta, Canada, we analyzed nonemergency repeat catheterization, revascularization, and mortality rates of all patients with previous CABG, grouped by indication (acute coronary syndromes [ACS], stable angina [SA]) and compared to those of the cohort without previous CABG. RESULTS: Of 7,127 patients, 31.5%, and 11% received percutaneous revascularization (PCI), or reoperation, respectively. Significantly more post-CABG patients were managed medically as compared with the overall APPROACH cohort of coronary disease patients (57.5% vs. 41.5%-P < 0.001). Post CABG patients with ACS received PCI more often than those with SA (36.4% vs. 24.8%). PCI was associated with improved both non-adjusted and adjusted mortality by 22 and 19%, respectively (P < 0.001) during a follow-up of up to 14 years. Patients with diabetes had a higher mortality rate than those without at 1-, 5-, and 10-year follow-up in every treatment group. However PCI was associated with a similar improvement in mortality (HR: 0.76 [95% SD: 0.65-0.90]) in diabetic patients (HR: 0.85 [95% SD: 0.75-0.96]) when compared to medical management. CONCLUSION: Significantly fewer post-CABG patients received repeat revascularization than all-comers however; PCI was associated with improved mortality in both the diabetic and the nondiabetic patient population. These findings support the practice of attempting revascularization in post-CABG patients, particularly in those with an ACS.

Exercise Rehabilitation for People With End-Stage Kidney Disease: Who Will Fill the Gaps?

Exercise rehabilitation is a well established therapy for reducing morbidity and mortality and improving quality of life and function across chronic conditions. People with dialysis-dependent kidney failure have a high burden of comorbidity and symptoms, commonly characterised as fatigue, dyspnoea, and the inability to complete daily activities. Despite more than 30 years of exercise research in people with kidney disease and its established benefit in other chronic diseases, exercise programs are rare in kidney care and are not incorporated into routine management at any stage. In this review, we describe the mechanisms contributing to exercise intolerance in those with end-stage kidney disease and outline the role of exercise rehabilitation in addressing the major challenges to kidney care: cardiovascular disease, symptom burden, and physical frailty. We also draw on existing models of exercise rehabilitation from other chronic conditions to inform the way forward and challenge the status quo of exercise rehabilitation in both practice and research.

Secondary Prevention and Rehabilitation for Spontaneous Coronary Artery Dissection: A Systematic Review.

BACKGROUND: Spontaneous coronary artery dissection (SCAD) is a serious, noniatrogenic and nontraumatic cardiac event that predominantly affects women, with a high risk of recurrence. Secondary prevention strategies are not well understood in this population. Therefore, the aim of this systematic review is to determine the current evidence on secondary prevention strategies and their effect on recurrent cardiac events and quality of life (QOL). METHODS: A literature search was conducted on August 21, 2021, of Ovid MEDLINE, Ovid Embase, CINAHL, Cochrane Library (via Wiley), Google Scholar, and ProQuest Dissertations & Theses Global. Literature on adult SCAD survivors who underwent secondary prevention measures with reported outcomes on major adverse cardiovascular events or QOL were included. Articles solely on pregnancy-associated SCAD or fibromuscular dysplasia were excluded. RESULTS: Thirty studies were included in this review. A variety of research methodologies were explored. There were no randomized controlled trials. Overall, the quality of the evidence was moderate. Although evidence on secondary prevention was limited, tailored medical management was shown to have the most effect on decreasing recurrent events. Cardiac rehabilitation (CR) was supported as a safe and effective program for SCAD patients, with no reported associations with recurrent SCAD events or major adverse cardiovascular events. CR along with psychosocial interventions showed promise in improving QOL in SCAD survivors. CONCLUSIONS: Medical management has the most effect in reducing recurrent events. CR, as a secondary prevention program, can provide interventions that might improve QOL. Randomized trial evidence on therapies for patients with SCAD are needed.

Comparing the Effectiveness of 2 Cardiac Rehabilitation Exercise Therapy Programs.

Cardiovascular diseases are among the leading causes of morbidity and mortality in Canada, highlighting the critical role of disease prevention and risk reduction programs. Cardiac rehabilitation (CR) is a key component of comprehensive cardiovascular care. Currently, more than 200 CR programs are established across the country, varying in duration, number of in-person supervised exercise sessions, and recommendations for exercise frequency at-home. In an increasingly cost-conscious healthcare environment, the effectiveness of healthcare services must be consistently reevaluated. This study evaluates the impact of 2 CR programs implemented by the Northern Alberta Cardiac Rehabilitation Program, by comparing peak metabolic equivalents achieved by study participants in each program. We hypothesize that our "hybrid" CR program, which is structured as an 8-week program with weekly in-person exercise sessions and a prescribed home exercise program, has patient outcomes similar to those of our "traditional" CR program, which required biweekly in-person exercise sessions over the course of 5 weeks. The results of this study may have implications for evaluating how to minimize barriers to both rehabilitation participation and long-term effectiveness of CR programs. The results may help inform the structuring and funding of future rehabilitation programs.

Les maladies cardiovasculaires (MCV) sont parmi les premières causes de morbidité et de mortalité au Canada d'où l'importance des programmes de prévention des MCV et de réduction du risque cardiovasculaire. La réadaptation cardiaque est un élément clé du continuum de soins cardiovasculaires. À l'heure actuelle, il existe plus de 200 programmes de réadaptation cardiaque au pays, qui diffèrent tant par leur durée, par le nombre de séances d'exercice supervisées en personne que par leurs recommandations sur la fréquence des exercices à domicile. Dans un contexte où le coût des soins de santé est de plus en plus préoccupant, l'efficience des services de santé doit constamment être réévaluée. Cette étude évalue les effets de deux programmes de réadaptation cardiaque instaurés par le Cardiac Rehabilitation Program du nord de l'Alberta en comparant l'équivalent métabolique maximal obtenu par les participants à l'étude pour chaque programme. L'hypothèse de départ était que notre programme de réadaptation cardiaque « hybride ¼, qui consiste d'une part en un programme de huit semaines de séances hebdomadaires d'exercices en personne et d'autre part en un programme d'exercices à domicile, donnerait des résultats semblables à ceux de notre programme « traditionnel ¼ de réadaptation cardiaque. Celui-ci se compose de deux séances d'exercices en personne par semaine, pendant cinq semaines. Les résultats de cette étude pourraient nous aider à réduire les obstacles qui nuisent à la participation aux programmes de réadaptation et à l'efficience à long terme de ces programmes. Nous espérons apporter un éclairage sur la structure et le financement des futurs programmes de réadaptation.

Cardio-oncology and Cancer Rehabilitation: Is an Integrated Approach Possible?

With significant improvements in the understanding of cancer biology, improved detection, and the use of novel adjuvant therapies, each year more Canadians are surviving a cancer diagnosis. Despite their effectiveness these therapies often result in short- and long-term deleterious effects to major organ systems, particularly cardiovascular. Cardio-oncology is an emerging field of study with the aim to improve cardiovascular health across the oncology disease spectrum. International guidelines distinguish "cardio-oncology" rehabilitation from "cancer" rehabilitation, but how this is navigated is currently unknown. How such care should be assessed and integrated acutely or in the longer term remains unknown. Accordingly, the aim of this article is to consider the cancer patient's needs beyond the scope of cardio-oncology rehabilitation to holistically integrate cancer rehabilitation across the disease trajectory.

Participant Exercise-Session Attendance in Community-Based, Bridging, and Hospital-Based Cardiac Rehabilitation: A Retrospective Case-Control Study.

Background: A paucity of studies have investigated participant attendance in community-based and hybrid cardiac rehabilitation programs in the Canadian setting. We compared exercise-session attendance of community-based, bridging (hospital plus community-based), and hospital-based participants who attended a high-volume cardiac rehabilitation program in Alberta, Canada. Methods: Exercise sessions attended and participant characteristics were collected and analyzed from 230 records of patients who attended cardiac rehabilitation between 2016 and 2019. Community-based (n = 74) and bridging (n = 41) program participants were age- and sex-matched in a 1:1 ratio to hospital-based participants. The number of exercise sessions attended was compared among program groups, between female and male patients, and for patients with vs without cardiac surgery. The percentage of exercise sessions attended was also compared among program groups. Results: Bridging participants attended the greatest number of exercise sessions (median = 10.0 sessions) and demonstrated a significantly higher percentage of sessions attended (91%, 25th and 75th percentile interquartile range [IQR] = 64, 100%) than matched hospital participants (median = 6.0 sessions; 63%, 25, 75 IQR = 13, 94%; P = 0.01). Percentage of sessions attended did not differ for bridging and community-based participants (P = 0.30). Exercise-session attendance was similar for community-based participants (median = 6.0 sessions; 75%, 25, 75 IQR = 38%, 88%) vs their hospital matches (median = 6.0 sessions; 81%, 25, 75 IQR = 38%, 100%; P ≥ 0.37), as well as for female vs male patients (median = 7.0 sessions for both sexes; P = 0.66), and for surgical vs nonsurgical patients (median = 7.0 sessions; P = 0.48). Female patients in the bridging program attended significantly more exercise sessions in the community, compared with male patients in the bridging program (P = 0.02). Conclusions: Bridging participants attended the most exercise sessions overall and demonstrated a higher percentage attendance than hospital-based participants. These results suggest that a hybrid program consisting of hospital and community-based exercise was favourable for exercise-session attendance. Given modern approaches to de-medicalize cardiac rehabilitation, our findings further support the provision of community program offerings, without detriment to patient session attendance.

Introduction: Peu d'études ont porté sur la participation des patients aux programmes communautaires ou hydrides de réadaptation cardiaque du Canada. Nous avons comparé la participation des patients aux séances d'entraînement en milieu communautaire, de transition (en milieu hospitalier et milieu communautaire) et en milieu hospitalier d'un programme de réadaptation cardiaque à volume élevé de l'Alberta, au Canada. Méthodes: Nous avons collecté et analysé les données sur les séances d'entraînement suivies et les caractéristiques des participants provenant de 230 dossiers de patients qui avaient participé à la réadaptation cardiaque entre 2016 et 2019. Les participants du programme en milieu communautaire (n = 74) et du programme de transition (n = 41) ont été appariés par âge et sexe aux participants du programme en milieu hospitalier selon un ratio 1:1. Le nombre de séances d'entraînement suivies a été comparé entre les groupes du programme, entre les patientes et les patients, et entre les patients qui avaient subi ou non une chirurgie cardiaque. Le pourcentage des séances d'entraînement suivies a aussi été comparé entre les groupes du programme. Résultats: Les participants du programme de transition ont assisté au plus grand nombre de séances d'entraînement (médiane = 10,0 séances) et ont démontré un pourcentage significativement plus élevé de séances suivies (91 %, 25e et 75e percentile [25, 75] intervalle interquartile [IIQ] = 64, 100 %) que les participants appariés du programme en milieu hospitalier (médiane = 6,0 séances; 63 %, 25, 75 IIQ = 13, 94 %; P = 0,01). Le pourcentage de séances suivies ne différait pas entre les participants du programme de transition et les participants du programme en milieu communautaire (P = 0,30). La participation aux séances d'entraînement était similaire entre les participants du programme en milieu communautaire (médiane = 6,0 séances; 75 %, 25, 75 IIQ = 38 %, 88 %) et les participants appariés du programme en milieu hospitalier (médiane = 6,0 séances; 81 %, 25, 75 IIQ = 38 %, 100 %; P ≥ 0,37), de même qu'entre les patientes et les patients (médiane = 7,0 séances pour les deux sexes; P = 0,66), et les patients opérés et les patients non opérés (médiane = 7,0 séances; P = 0,48). Les patientes du programme de transition ont participé à un nombre plus important de séances d'entraînement en milieu communautaire que les patients du programme de transition (P = 0,02). Conclusions: Les participants du programme de transition ont dans l'ensemble assisté à la plupart des séances d'entraînement et ont démontré un pourcentage plus élevé de participation que les participants du programme en milieu hospitalier. Ces résultats indiquent qu'un programme hybride qui consiste en un entraînement en milieu hospitalier et en milieu communautaire favorisait la participation aux séances d'entraînement. Compte tenu des approches contemporaines de démédicalisation de la réadaptation cardiaque, nos conclusions justifient d'autant plus la mise à disposition de programmes en milieu communautaire, et ce, sans compromettre la participation des patients aux séances.

HCV-specific T cells in HCV/HIV co-infection show elevated frequencies of dual Tim-3/PD-1 expression that correlate with liver disease progression.

Co-infection of HCV with HIV has been associated with more rapid progression of HCV-related disease. HCV-specific T-cell immune responses, which are essential for disease control, are attenuated in co-infection with HIV. T-cell exhaustion has recently been implicated in the deficient control of chronic viral infections. In the current study, we investigated the role of programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) expression in T-cell exhaustion during HCV/HIV co-infection. We show that in HCV/HIV co-infection, both total and HCV-specific T cells co-express Tim-3 and PD-1 in significantly higher frequencies, compared with HCV mono-infection. Co-expression of these two markers on HCV-specific CD8(+) T cells positively correlated with a clinical parameter of liver disease progression. HCV-specific CD8(+) T cells showed greater frequencies of Tim-3/PD-1 co-expression than HIV-specific CD8(+) T cells, which may indicate a greater degree of exhaustion in the former. Blocking Tim-3 or PD-1 pathways restored both HIV- and HCV-specific CD8(+) T-cell expansion in the blood of co-infected individuals. These data demonstrate that co-expression of Tim-3 and PD-1 may play a significant role in HCV-specific T-cell dysfunction, especially in the setting of HIV co-infection.

Human immunodeficiency virus type 1 escapes from interleukin-2-producing CD4+ T-cell responses without high-frequency fixation of mutations.

The presence of interleukin-2 (IL-2)-producing human immunodeficiency virus type 1 (HIV-1)-specific CD4(+) T-cell responses has been associated with the immunological control of HIV-1 replication; however, the causal relationship between these factors remains unclear. Here we show that IL-2-producing HIV-1-specific CD4(+) T cells can be cloned from acutely HIV-1-infected individuals. Despite the early presence of these cells, each of the individuals in the present study exhibited progressive disease, with one individual showing rapid progression. In this rapid progressor, three IL-2-producing HIV-1 Gag-specific CD4(+) T-cell responses were identified and mapped to the following optimal epitopes: HIVWASRELER, REPRGSDIAGT, and FRDYVDRFYKT. Responses to these epitopes in peripheral blood mononuclear cells were monitored longitudinally to >1 year postinfection, and contemporaneous circulating plasma viruses were sequenced. A variant of the FRDYVDRFYKT epitope sequence, FRDYVDQFYKT, was observed in 1/21 plasma viruses sequenced at 5 months postinfection and 1/10 viruses at 7 months postinfection. This variant failed to stimulate the corresponding CD4(+) T-cell clone and thus constitutes an escape mutant. Responses to each of the three Gag epitopes were rapidly lost, and this loss was accompanied by a loss of antigen-specific cells in the periphery as measured by using an FRDYVDRFYKT-presenting major histocompatibility complex class II tetramer. Highly active antiretroviral therapy was associated with the reemergence of FRDYVDRFYKT-specific cells by tetramer. Thus, our data support that IL-2-producing HIV-1-specific CD4(+) T-cell responses can exert immune pressure during early HIV-1 infection but that the inability of these responses to enforce enduring control of viral replication is related to the deletion and/or dysfunction of HIV-1-specific CD4(+) T cells rather than to the fixation of escape mutations at high frequencies.

Correction: The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

[This corrects the article DOI: 10.1371/journal.pone.0211032.].

Rehabilitation Needs in Cancer Treatment-Related Cardiotoxicity.

OBJECTIVES: To examine and summarize current international guidelines regarding cardiovascular risk reduction before and during cancer therapy, and to discuss the emerging role of cardio-oncology as a subspecialty in cancer care and the role of cardio-oncology rehabilitation. DATA SOURCES: Published articles and guidelines. CONCLUSION: With improvements in cancer detection and the use of novel adjuvant therapies, an increasing number of individuals now survive a cancer diagnosis. However, for some the cost is high - many survivors are now at higher risk of death from cardiovascular disease than from recurrent cancer. Cardiovascular morbidity and mortality are common and associated with common cancer therapies serially administered in adult oncology care. IMPLICATIONS FOR NURSING PRACTICE: Timely risk-reduction interventions hold promise in reducing cardiovascular morbidity and mortality. Oncology nurses are the key providers to identify baseline risks, perform necessary referrals, provide individualized teaching, and support the patient within the family and community.

Underutilization of clopidogrel and glycoprotein IIb/IIIa inhibitors in non-ST-elevation acute coronary syndrome patients: the Canadian global registry of acute coronary events (GRACE) experience.

BACKGROUND: There are limited contemporary data on the early use of clopidogrel or glycoprotein (Gp) IIb/IIIa inhibitors, alone versus combination therapies, in non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: This study included 5,806 Canadian NSTE-ACS patients with elevated cardiac biomarker and/or ST deviation on presentation in the prospective GRACE between 2003-2007. We stratified the study population according to the management strategy (non-invasive vs invasive) and into low-(GRACE risk score or=141). RESULTS: Overall, 3,893 patients (67.1%) received early (

Physical Activity In Renal Disease (PAIRED) and the effect on hypertension: study protocol for a randomized controlled trial.

BACKGROUND: The prevalence of hypertension among people with chronic kidney disease is high with over 60% of people not attaining recommended targets despite taking multiple medications. Given the health and economic implications of hypertension, additional strategies are needed. Exercise is an effective strategy for reducing blood pressure in the general population; however, it is not known whether exercise would have a comparable benefit in people with moderate to advanced chronic kidney disease and hypertension. METHODS: This is a parallel-arm trial of adults with hypertension (systolic blood pressure greater than 130 mmHg) and an estimated glomerular filtration rate of 15-45 ml/min 1.73 m2. A total of 160 participants will be randomized, with stratification for estimated glomerular filtration rate, to a 24-week, aerobic-based exercise intervention or enhanced usual care. The primary outcome is the difference in 24-h ambulatory systolic blood pressure after 8 weeks of exercise training. Secondary outcomes at 8 and 24 weeks include: other measurements of blood pressure, aortic stiffness (pulse-wave velocity), change in the Defined Daily Dose of anti-hypertensive drugs, medication adherence, markers of cardiovascular risk, physical fitness (cardiopulmonary exercise testing), 7-day accelerometry, quality of life, and adverse events. The effect of exercise on renal function will be evaluated in an exploratory analysis. The intervention is a thrice-weekly, moderate-intensity aerobic exercise supplemented with isometric resistance exercise delivered in two phases. Phase 1: supervised, facility-based, weekly and home-based sessions (8 weeks). Phase 2: home-based sessions (16 weeks). DISCUSSION: To our knowledge, this study is the first trial designed to provide a precise estimate of the effect of exercise on blood pressure in people with moderate to severe CKD and hypertension. The findings from this study should address a significant knowledge gap in hypertension management in CKD and inform the design of a larger study on the effect of exercise on CKD progression. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03551119 . Registered on 11 June 2018.

The effect of exercise on blood pressure in chronic kidney disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Management of hypertension in chronic kidney disease (CKD) remains a major challenge. We conducted a systematic review to assess whether exercise is an effective strategy for lowering blood pressure in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We searched MEDLINE, EMBASE, the Cochrane Library, CINAHL and Web of Science for randomized controlled trials (RCTs) that examined the effect of exercise on blood pressure in adults with non-dialysis CKD, stages 3-5. Outcomes were non-ambulatory systolic blood pressure (primary), other blood pressure parameters, 24-hour ambulatory blood pressure, pulse-wave velocity, and flow-mediated dilatation. Results were summarized using random effects models. RESULTS: Twelve studies with 505 participants were included. Ten trials (335 participants) reporting non-ambulatory systolic blood pressure were meta-analysed. All included studies were a high risk of bias. Using the last available time point, exercise was not associated with an effect on systolic blood pressure (mean difference, MD -4.33 mmHg, 95% confidence interval, CI -9.04, 0.38). The MD after 12-16 and 24-26 weeks of exercise was significant (-4.93 mmHg, 95% CI -8.83, -1.03 and -10.94 mmHg, 95% CI -15.83, -6.05, respectively) but not at 48-52 weeks (1.07 mmHg, 95% CI -6.62, 8.77). Overall, exercise did not have an effect on 24-hour ambulatory blood pressure (-5.40 mmHg, 95% CI -12.67, 1.87) or after 48-52 weeks (-7.50 mmHg 95% CI -20.21, 5.21) while an effect was seen at 24 weeks (-18.00 mmHg, 95% CI -29.92, -6.08). Exercise did not have a significant effect on measures of arterial stiffness or endothelial function. CONCLUSION: Limited evidence from shorter term studies suggests that exercise is a potential strategy to lower blood pressure in CKD. However, to recommend exercise for blood pressure control in this population, high quality, longer term studies specifically designed to evaluate hypertension are needed.

Cardiac rehabilitation and its effects on cognition in patients with coronary artery disease and heart failure.

INTRODUCTION: Cardiac rehabilitation program is an evidence-based intervention and established model of exercise delivery following myocardial infarction and heart failure. Although it forms an important part of recovery and helps to prevent future events and complications, there has been little focus on its potential cognitive benefits. Areas covered: Coronary artery disease and heart failure are common heart problems associated with significant morbidity and mortality, and cognitive decline is commonly seen in affected individuals. Cognitive impairment may influence patient self-management by reducing medication adherence, rendering patients unable to make lifestyle modifications and causing missed healthcare visits. Cognitive assessment in cardiac rehabilitation as an outcome measure has the potential to improve clinical, functional and behavioral domains as well as help to reduce gaps in the quality of care in these patients. Expert commentary: Limited evidence at present has shown that cardiac rehabilitation and exercise has potential in preventing cognitive decline. Cardiac prehabilitation, a rehabilitation-like program delivered before cardiac surgery, may also play a role in preventing postoperative cognitive dysfunction, but needs future research studies to support it.

Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents, but more precise estimates of their effects on major adverse cardiovascular events (MACE), mortality, and safety are needed. We systematically reviewed and meta-analyzed randomized controlled trials with durations ≥ 6 months comparing MACE, mortality, and safety with PCSK9 inhibitors vs control. We searched CENTRAL, Embase, MedLine and the grey literature to November 7, 2018. From 2048 articles, we included 23 trials (n = 60,723). PCSK9 inhibitors reduced MACE (relative risk, 0.83; 95% confidence interval, 0.78-0.88), but did not clearly reduce mortality (relative risk, 0.93; 95% confidence interval, 0.85-1.02) or increase adverse events. In conclusion, PCSK9 inhibitors reduce nonfatal MACE, are well tolerated, but effects on mortality remain unclear.

Cardiac Rehabilitation in Patients With Lymphoma Undergoing Autologous Hematopoietic Stem Cell Transplantation: A Cardio-oncology Pilot Project.

BACKGROUND: Worldwide > 50,000 hematopoietic stem cell transplants (HSCTs) are performed annually. HSCT patients receive multiple cardiotoxic therapies (chemotherapy and radiation therapy) in addition to severe physical deconditioning during hospital admission. We hypothesized that guided exercise in a cardiac rehabilitation (CR) program following autologous HSCT is a safe and feasible intervention. METHODS: Pilot project to assess for safety, feasibility and impact of 8 weeks of CR in HSCT patients following transplant. Consecutive patients with lymphoma underwent standard activity protocol testing before HSCT, at 6 weeks following HSCT (prior to CR), and at 14 weeks following HSCT (at completion of CR), consisting of grip strength (GS), gait speed (GtS), timed up-and-go (TUG), and 6-minute walk test (6MWT). CR consisted of 8 weekly visits for guided exercise. RESULTS: Activity tolerance protocol data of 30 patients (24 male, 6 female) from December 2014 to December 2016 were analyzed using repeated measures (analysis of variance [ANOVA]) to observe for changes in GS, GtS, TUG, and 6MWT. Statistically significant improvements were found in GS (P < 0.005), GtS (P = 0.02), and 6MWT (P = 0.001). These improvements show that guided CR-based exercise may assist HSCT survivors to meet or even surpass baseline exercise levels and improve physical functioning. There were no adverse events (ie, death or injury) during the study period. Fifty-seven percent of referred patients participated in CR, exceeding documented CR adherence in cardiac populations. CONCLUSIONS: The addition of CR-based exercise programming in HSCT survivorship care of patients with lymphoma is a safe and feasible intervention to assist in recovery following transplant.

The Effect of Nurse Practitioner-Led Intervention in Diabetes Care for Patients Admitted to Cardiology Services.

OBJECTIVE: To determine the benefits of diabetes nurse practitioner (DNP) intervention on glycemic control, quality of life and diabetes treatment satisfaction in patients with type 2 diabetes (T2DM) admitted to cardiology inpatient services at a tertiary centre. PATIENTS AND METHODS: Patients admitted to the cardiology service with T2DM who had suboptimal control (HbA1c >6.5%) were approached for the study. Diabetes care was optimized by the DNP through medication review, patient education and discharge care planning. Glycemic control was evaluated with 3-month post-intervention HbA1c. Secondary outcomes of lipid profiles, quality of life and treatment satisfaction were evaluated at baseline and at 3 months with fasting lipids, Audit of Diabetes-Dependent Quality of Life questionnaires (ADDQoL) and Diabetes Treatment Satisfaction Questionnaires (DTSQ) respectively. RESULTS: With almost 49% of patients admitted to the Mazankowski Alberta Heart Institute having HbA1c <6.5%, only 23 patients completed the study over a 12-month period. We found a significant decrease in HbA1c values at 3 months post-intervention from 8.0% (SD=1. 2) to 6.9% (SD=0.7), p=0.002. LDL showed a significant decrease at 3 months from 1.7 mmol/L (SD=0.7) to 1.1 mmol /L (SD=0.6), p=0.011. Overall median ADDQoL impact scores improved at follow up, from -1.4 to -0.4, p = 0.0003. Overall no significant changes in DTSQ scores were seen. CONCLUSIONS: Short-term DNP intervention in T2DM patients admitted to the inpatient cardiology service was associated with benefits in areas of glycemic control and various domains of QoL. Our study provides support for the involvement of DNP in the care of cardiology inpatients at tertiary centres.