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

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

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

The innate immune system is an evolutionarily conserved system that senses and defends against infection and irritation. Innate immune signaling is a complex cascade that quickly recognizes infectious threats through multiple germline-encoded cell surface or cytoplasmic receptors and transmits signals for the deployment of proper countermeasures through adaptors, kinases, and transcription factors, resulting in the production of cytokines. As the first response of the innate immune system to pathogenic signals, inflammatory responses must be rapid and specific to establish a physical barrier against the spread of infection and must subsequently be terminated once the pathogens have been cleared. Long-lasting and low-grade chronic inflammation is a distinguishing feature of type 2 diabetes and cardiovascular diseases, which are currently major public health problems. Cardiometabolic stress-induced inflammatory responses activate innate immune signaling, which directly contributes to the development of cardiometabolic diseases. Additionally, although the innate immune elements are highly conserved in higher-order jawed vertebrates, lower-grade jawless vertebrates lack several transcription factors and inflammatory cytokine genes downstream of the Toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs) pathways, suggesting that innate immune signaling components may additionally function in an immune-independent way. Notably, recent studies from our group and others have revealed that innate immune signaling can function as a vital regulator of cardiometabolic homeostasis independent of its immune function. Therefore, further investigation of innate immune signaling in cardiometabolic systems may facilitate the discovery of new strategies to manage the initiation and progression of cardiometabolic disorders, leading to better treatments for these diseases. In this review, we summarize the current progress in innate immune signaling studies and the regulatory function of innate immunity in cardiometabolic diseases. Notably, we highlight the immune-independent effects of innate immune signaling components on the development of cardiometabolic disorders.

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

There have been major advances in our knowledge of the contribution of DNA sequence variations to cardiovascular disease and stroke. However, the inner workings of the body reflect the complex interplay of factors beyond the DNA sequence, including epigenetic modifications, RNA transcripts, proteins, and metabolites, which together can be considered the "expressed genome." The emergence of high-throughput technologies, including epigenomics, transcriptomics, proteomics, and metabolomics, is now making it possible to address the contributions of the expressed genome to cardiovascular disorders. This statement describes how the expressed genome can currently and, in the future, potentially be used to diagnose diseases and to predict who will develop diseases such as coronary artery disease, stroke, heart failure, and arrhythmias., (© 2017 American Heart Association, Inc.)

3D-printed models fabricated from CT, MRI, or echocardiography data provide the advantage of haptic feedback, direct manipulation, and enhanced understanding of cardiovascular anatomy and underlying pathologies. Reported applications of cardiovascular 3D printing span from diagnostic assistance and optimization of management algorithms in complex cardiovascular diseases, to planning and simulating surgical and interventional procedures. The technology has been used in practically the entire range of structural, valvular, and congenital heart diseases, and the added-value of 3D printing is established. Patient-specific implants and custom-made devices can be designed, produced, and tested, thus opening new horizons in personalized patient care and cardiovascular research. Physicians and trainees can better elucidate anatomical abnormalities with the use of 3D-printed models, and communication with patients is markedly improved. Cardiovascular 3D bioprinting and molecular 3D printing, although currently not translated into clinical practice, hold revolutionary potential. 3D printing is expected to have a broad influence in cardiovascular care, and will prove pivotal for the future generation of cardiovascular imagers and care providers. In this Review, we summarize the cardiovascular 3D printing workflow, from image acquisition to the generation of a hand-held model, and discuss the cardiovascular applications and the current status and future perspectives of cardiovascular 3D printing.

Endothelial dysfunction is characterized by impaired endothelium-dependent vasodilatation and is an independent predictor of adverse cardiovascular consequences. The ease with which endothelial function can be assessed has led to it becoming a useful marker of cardiovascular diseases in research studies. Obstructive sleep apnea (OSA) has been independently associated with endothelial dysfunction which may explain the increased risk for cardiovascular and all-cause mortality in this population. One possible mechanism for the development of endothelial dysfunction in OSA is through the cyclical pattern of hypoxia and re-oxygenation. This creates a haemostatic imbalance in which nitric oxide bio-availability is reduced and pro-inflammatory and pro-thrombotic forces prevail. Furthermore the repair capacity of the endothelium to protect itself against this increased damage is diminished. All of these pathways contribute to vascular disease which ultimately gives rise to adverse cardiovascular consequences. This review aims to provide a critical appraisal of the cross-sectional and interventional studies which have investigated micro- and macro-vascular endothelial dysfunction in OSA with emphasis on randomised controlled studies., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The burden of cardiovascular disease (CVD) in Canada and other developed countries is growing, in part because of the aging of the population and the alarming rise of obesity. Studying Canada's contribution to the global body of CVD research output will shed light on the effectiveness of investments in Canadian CVD research and inform if Canada has been responding to its CVD burden. Search was conducted using the Web-of-Science database for publications during 1981 through 2010 on major areas and specific interventions in CVD. Search was also conducted using Canadian and US online databases for patents issued between 1981 and 2010. Search data were used to estimate the proportions of the world's pool of research publications and of patents conducted by researchers based in Canada. The results indicate that Canada contributed 6% of global research in CVD during 1981 through 2010. Further, Canada's contribution shows a strong upward trend during the period. Based on patent data, Canada's contribution level was similar (5%-7%). Canada's contribution to the global pool of CVD research is on par with France and close to the UK, Japan, and Germany. Canada's contribution in global CVD research is higher than its average contribution in all fields of research (6% vs 3%). As the burden of chronic diseases including CVD rises with Canada's aging population, the increase in Canadian research into CVD is encouraging., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

The exosome is a secreted microvesicle that has been shown to contain genetic material and proteins and is involved in multiple levels of cellular communication. The cardiovascular exosome proteome is a promising subproteome that warrants investigation since a detailed understanding of its role in the heart should improve our comprehension of intercellular communication in the heart, and may even assist in biomarker discovery. Indeed, uncovering the role of the exosome in cardiovascular physiology could be accomplished with the application of scientific approaches and insights gained from studies of exosomes in other fields, such as cancer biology and immunology, where much of the established knowledge of the exosome has been generated. In the present review, we discuss the relevant literature and examine areas of investigation that would bring the cardiovascular exosome to the forefront of intercellular communication in the heart., (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Cardiovascular disease (CVD) is a leading cause of death in Canada and is a priority area for medical research. The research funding landscape in Canada has changed quite a bit over the last few decades, as have funding levels. Our objective was to estimate the magnitude of expenditures on CVD research for the public and charitable (not-for profit) sectors in Canada between 1975 and 2005., Methods: To estimate research expenditures for the public and charitable sectors, we compiled a complete list of granting agencies in Canada, contacted each agency and the Canadian Institutes of Health Research (CIHR), and extracted data from the organizations' annual reports and the Reference Lists of health research in Canada. Two independent reviewers scanned all grant and fellowship/scholarship titles (and summary/key words, when available) of all research projects funded to determine their inclusion in our analysis; only grants and fellowships/scholarships that focused on heart and peripheral vascular diseases were selected., Results: Public/charitable sector funding increased 7.5 times, from close to $13 million (in constant dollars) in 1975 to almost $96 million (in constant dollars) in 2005 (base year). The Medical Research Council of Canada (MRCC)/CIHR and the Heart & Stroke Foundation of Canada have been the main founders of this type of research during our analysis period; the Alberta Heritage Foundation for Medical Research and the Fonds de la recherche en santé du Quebec have played major roles at the provincial level. The Indirect Costs Research Program and Canada Foundation for Innovation have played major roles in terms of funding in the last years of our analysis., Conclusion: Public/charitable-funded research expenditures devoted to CVD have increased substantially over the last three decades. By international standards, the evidence suggests Canada spends less on health-related research than the UK and the US, at least in absolute terms. However, this may not be too problematic as Canada is likely to free-ride from research undertaken elsewhere. Understanding these past trends in research funding may provide decision makers with important information for planning future research efforts. Future work in this area should include the use of our coding methods to obtain estimates of funded research for other diseases in Canada.

The role of traditional risk factors in the development of cardiovascular disease has been well studied. However, the relationship between chronic inflammatory conditions and cardiovascular risk has only recently been appreciated. Expression of numerous pro-inflammatory cytokines is common to the pathogenesis of both atherosclerosis and other chronic inflammatory diseases and may suggest that systemic inflammation independently contributes to elevated risk. This article examines the magnitude of cardiovascular risk in several of the most common chronic inflammatory diseases and summarizes currently available data to discern whether this risk is largely due to the presence of co-existing traditional risk factors for cardiovascular disease or the effect of increased systemic inflammation. Evidence is summarized to show which therapies may positively or negatively impact cardiovascular risk. Evidence is discussed in context of practical patient management tools, appropriate treatment based on risk, and treatment targets for high-risk patients. Overall, patients with chronic inflammatory diseases are at an often underestimated increase in cardiovascular risk and require individualized therapy and specific patient management strategies to address the disease process, cardiovascular risk factors, and comorbidities.

Rationale: Dyslipidemia is common in Obstructive Sleep Apnea (OSA). Postprandial lipidemia (PPL) is a strong marker of cardiovascular risk. Evidence that OSA treatment improves PPL is lacking., Objectives: To investigate the effect of continuous positive airway pressure (CPAP) treatment on postprandial lipidemia (PPL) in patients with obstructive sleep apnea (OSA) in the upper moderate or severe range., Methods: In this randomized, placebo-controlled crossover trial, we compared the effects of 2 months each of therapeutic and placebo CPAP on PPL., Measurements and Main Results: PPL was determined from the area under the 24-hour triglyceride concentration curve (TAG-AUC(24)) using seven blood samples drawn across both the wake and sleep periods. Secondary outcomes were the difference in other 24-hour lipid profiles. Thirty-eight eligible patients were randomly assigned to a treatment order and 29 patients completed the trial. CPAP reduced PPL compared with placebo with a mean TAG-AUC(24) difference of -357 mmol/L/d (95% confidence interval [CI], -687.3 to -26.8; P = 0.035). During both the CPAP and placebo studies, TAG levels peaked during both wakefulness (2:00 p.m.) and sleep (3:00 a.m.). Both peaks were lower during CPAP than placebo: 2:00 p.m., -0.49 mmol/L (95% CI, -0.74 to -0.24; P < 0.0005) and 3:00 a.m., -0.40 mmol/L (95% CI, -0.65 to -0.15; P = 0.002). Moreover, mean 24-hour total cholesterol was -0.19 mmol/L lower on CPAP (95% CI, -0.27 to -0.11; P < 0.00001)., Conclusions: This randomized trial demonstrated that treatment of severe OSA with CPAP improves postprandial TAG and total cholesterol levels. These effects may reduce the risk for cardiovascular events. The results imply that the association between OSA and cardiovascular disease may, in part, be caused by direct effects on dyslipidemia. Clinical trial registered with the Australian and New Zealand Clinical Trials Registry at www.anzctr.org.au (ACTRN 12605000066684).

The concepts of "cardiometabolic risk," "metabolic syndrome," and "risk stratification" overlap and relate to the atherogenic process and development of type 2 diabetes. There is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. With the objectives of clarifying these concepts and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group reviewed the evidence related to emerging cardiovascular risk factors and Canadian guideline recommendations in order to present a detailed analysis and consolidated approach to the identification and management of cardiometabolic risk. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider risk factors related to ethnicity in order to appropriately evaluate everyone in their diverse patient populations., (Copyright © 2011 Elsevier Inc. All rights reserved.)

With the objectives of clarifying the concepts related to "cardiometabolic risk," "metabolic syndrome" and "risk stratification" and presenting practical strategies to identify and reduce cardiovascular risk in multiethnic patient populations, the Cardiometabolic Working Group presents an executive summary of a detailed analysis and position paper that offers a comprehensive and consolidated approach to the identification and management of cardiometabolic risk. The above concepts overlap and relate to the atherogenic process and development of type 2 diabetes. However, there is confusion about what these terms mean and how they can best be used to improve our understanding of cardiovascular disease treatment and prevention. The concepts related to cardiometabolic risk, pathophysiology, and strategies for identification and management (including health behaviours, pharmacotherapy, and surgery) in the multiethnic Canadian population are presented. "Global cardiometabolic risk" is proposed as an umbrella term for a comprehensive list of existing and emerging factors that predict cardiovascular disease and/or type 2 diabetes. Health behaviour interventions (weight loss, physical activity, diet, smoking cessation) in people identified at high cardiometabolic risk are of critical importance given the emerging crisis of obesity and the consequent epidemic of type 2 diabetes. Vascular protective measures (health behaviours for all patients and pharmacotherapy in appropriate patients) are essential to reduce cardiometabolic risk, and there is growing consensus that a multidisciplinary approach is needed to adequately address cardiometabolic risk factors. Health care professionals must also consider ethnicity-related risk factors in order to appropriately evaluate all individuals in their diverse patient populations., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Genomic and proteomic approaches to cardiovascular medicine promise to revolutionize our understanding of disease initiation and progression. This improved appreciation of pathophysiology may be translated into avenues of clinical utility. Gene-based presymptomatic prediction of illness, finer diagnostic subclassifications and improved risk assessment tools will permit earlier and more targeted intervention. Pharmacogenetics will guide our therapeutic decisions and monitor response to therapy. Personalized medicine will require the integration of clinical information, stable and dynamic genomics, and molecular phenotyping. Bioinformatics will be crucial in translating these data into useful applications, leading to improved diagnosis, prediction, prognostication and treatment. The present paper reviews the potential contributions of genomic and proteomic approaches in developing a more personalized approach to cardiovascular medicine.

Proteomics is the new systems biological approach to the study of proteins and protein variation on a large scale as a result of biological processes and perturbations. The field is undergoing a dramatic transformation, owing to the completion and annotation of the human genome as well as technological advances to study proteins on a large scale. The new science of proteomics can potentially yield novel biomarkers reflecting cardiovascular disease, establish earlier detection strategies, and monitor responses to therapy. Technological advances permit the unprecedented large-scale identification of peptide sequences in a biological sample with mass spectrometry, whereas gel-based techniques provide further refinement on the status of post-translational modification. The application of high throughput protein evaluation with a subset of predefined targets, identified through proteomics, microarray profiling, and pathway analysis in animal models and human tissues, is gaining momentum in research and clinical applications. Proteomic analysis has provided important insights into ischemic heart disease, heart failure, and cardiovascular pathophysiology. The combination of proteomic biomarkers with clinical phenotypes and genetic haplotype information can lead to a more precise diagnosis and therapy on an individual basis--the fundamental premise of "personalized medicine."

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that are regulated by inflammatory signals to mediate changes in extracellular matrix. Members of the MMP family share sequence homology, act on interstitial protein substrates, acutely participate in inflammatory processes and chronically mediate tissue remodelling. MMPs are important in vascular remodelling, not only in the overall vasculature architecture but also, more importantly, in the advancing atherosclerotic plaque. MMP activation modifies the architecture of the plaque and may directly participate in the process of plaque rupture. MMPs also participate in cardiac remodelling following myocardial infarction and development of dilated cardiomyopathy. Soluble MMPs are now potential biomarkers in delineating cardiovascular risk for plaque rupture and coronary risk. They also constitute innovative direct or indirect targets to modify cardiovascular tissue remodelling in atherosclerosis and heart failure.

Globally, cardiovascular disease will continue causing most human deaths for the foreseeable future. The consistent gender gap in life span of approximately 5.6 yr in all advanced economies must derive from gender differences in age-specific cardiovascular death rates, which rise steeply in parallel for both genders but 5-10 yr earlier in men. The lack of inflection point at modal age of menopause, contrasting with unequivocally estrogen-dependent biological markers like breast cancer or bone density, makes estrogen protection of premenopausal women an unlikely explanation. Limited human data suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases risk of cardiovascular death in men as it does in women. Alternatively, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis. Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in the progression of cardiovascular disease, highlighting the need to better understand androgen receptor (AR) coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity. Novel therapeutic targets may arise from understanding how androgens enhance early plaque formation and cause vasodilatation via nongenomic androgen effects on vascular smooth muscle, and how tissue-specific variations in androgen effects are modulated by AR coregulators as well as metabolic activation of testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor alpha/beta) the biological effects of testosterone on the vasculature. Observational studies show that blood testosterone concentrations are consistently lower among men with cardiovascular disease, suggesting a possible preventive role for testosterone therapy, which requires critical evaluation by further prospective studies. Short-term interventional studies show that testosterone produces a modest but consistent improvement in cardiac ischemia over placebo, comparable to the effects of existing antianginal drugs. By contrast, testosterone therapy has no beneficial effects in peripheral arterial disease but has not been evaluated in cerebrovascular disease. Erectile dysfunction is most frequently caused by pelvic arterial insufficiency due to atherosclerosis, and its sentinel relationship to generalized atherosclerosis is insufficiently appreciated. The commonality of risk factor patterns and mechanisms (including endothelial dysfunction) suggests that the efficacy of antiatherogenic therapy is an important challenge with the potential to enhance men's motivation for prevention and treatment of cardiovascular diseases.

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

The coronavirus disease 2019 (COVID-19) pandemic has affected health and economy worldwide on an unprecedented scale. Patients have diverse clinical outcomes, but those with preexisting cardiovascular disease, hypertension, and related conditions incur disproportionately worse outcome. The high infectivity of severe acute respiratory syndrome coronavirus 2 is in part related to new mutations in the receptor binding domain, and acquisition of a furin cleavage site in the S-spike protein. The continued viral shedding in the asymptomatic and presymptomatic individuals enhances its community transmission. The virus uses the angiotensin converting enzyme 2 receptor for internalization, aided by transmembrane protease serine 2 protease. The tissue localization of the receptors correlates with COVID-19 presenting symptoms and organ dysfunction. Virus-induced angiotensin converting enzyme 2 downregulation may attenuate its function, diminish its anti-inflammatory role, and heighten angiotensin II effects in the predisposed patients. Lymphopenia occurs early and is prognostic, potentially associated with reduction of the CD4+ and some CD8+ T cells. This leads to imbalance of the innate/acquired immune response, delayed viral clearance, and hyperstimulated macrophages and neutrophils. Appropriate type I interferon pathway activation is critical for virus attenuation and balanced immune response. Persistent immune activation in predisposed patients, such as elderly adults and those with cardiovascular risk, can lead to hemophagocytosis-like syndrome, with uncontrolled amplification of cytokine production, leading to multiorgan failure and death. In addition to the airways and lungs, the cardiovascular system is often involved in COVID-19 early, reflected in the release of highly sensitive troponin and natriuretic peptides, which are all extremely prognostic, in particular, in those showing continued rise, along with cytokines such as interleukin-6. Inflammation in the vascular system can result in diffuse microangiopathy with thrombosis. Inflammation in the myocardium can result in myocarditis, heart failure, cardiac arrhythmias, acute coronary syndrome, rapid deterioration, and sudden death. Aggressive support based on early prognostic indicators with expectant management can potentially improve recovery. Appropriate treatment for heart failure, arrhythmias, acute coronary syndrome, and thrombosis remain important. Specific evidence-based treatment strategies for COVID-19 will emerge with ongoing global collaboration on multiple approaches being evaluated. To protect the wider population, antibody testing and effective vaccine will be needed to make COVID-19 history. [ABSTRACT FROM AUTHOR]

ABSTRACT Background and objective: Sleep disordered breathing (SDB) is highly prevalent but under-recognized. Evidence is accumulating for its role as a predictor of mortality independent of cardiovascular risk factors. The role of hypercapnia in SDB is not known systematically, and between 11 and 43% of patients with SDB develop chronic hypercapnia. Hypercapnia predicts mortality in other respiratory conditions. The role of hypercapnia in independently predicting mortality in patients with SDB after assessing for the presence of airways disease and obesity was investigated. Methods: The records of 396 consecutive patients were examined retrospectively. Univariate and multivariate analyses were performed using Cox proportional hazards regression to determine the association between gas exchange and polysomnography (PSG) variables and all-cause mortality, adjusted for potential confounders, including age, gender and presence of co-morbidity and airways disease. Results: The mean age of our patient population was 55 ± 15 years, and the mean body mass index (BMI) was 30.6 ± 6.2 kg/m2. Out of the 322 patient population, 258 were men. After 10 years, 25% had died, following a maximum follow-up of 16.7 years. Mortality among patients with SDB was predicted by a difference between evening and morning PaCO2 (ΔPaCO2) of ≥7 mm Hg and evening hypoxaemia (PaO2 < 65 mm Hg), independent of age and the presence of co-morbidity and airways disease. There was a significant correlation between minimum oxygen saturation (SpO2) and ΔPaCO2 ≥ 7 mm Hg ( P = 0.002) and evening PaO2 < 65 mm Hg ( P < 0.001). Conclusions: An overnight increase in CO2 and evening hypoxaemia are independent mortality predictors in SDB. A low minimum SpO2 identifies patients in whom morning and evening arterial blood gases are beneficial. [ABSTRACT FROM AUTHOR]

The article discusses the harmonization of the clinical practice guidelines that prevent and treat cardiovascular disease in Canada. It states that the Canadian Cardiovascular Harmonization of National Guidelines Endeavour (C-CHANGE) initiative was developed to harmonize the 400 recommendations into 89 key recommendations through using a consensus model. It mentions that the initiative proposes an outcome evaluation plan for tracking of clinical and health system outcomes.

The article argues against the roadmap of long noncoding RNAs for cardiovascular development and disease.

Chronic kidney disease (CKD) is normally related to proteinuria, a common finding in a compromised glomerular filtration barrier (GFB). GFB is a structure composed of glomerular endothelial cells, the basement membrane, and the podocytes. CKD with podocyte damage may be associated with actin cytoskeleton reorganization, resulting in podocyte effacement. Gelsolin plays a critical role in several diseases, including cardiovascular diseases and cancer. Our current study aimed to determine the connection between gelsolin and podocyte, and thus the mechanism underlying podocyte injury in CKD. Experiments were carried out on Drosophila to demonstrate whether gelsolin had a physiological role in maintaining podocyte. Furthermore, the survival rate of gelsolin-knocked down Drosophila larvae was extensively reduced after AgNO3 exposure. Secondly, the in vitro podocytes treated with puromycin aminonucleoside (PAN) enhanced the gelsolin protein expression, as well as small GTPase RhoA and Rac1, which also regulated actin dynamic expression incrementally with the PAN concentrations. Thirdly, we further demonstrated in vivo that GSN was highly expressed inside the glomeruli with mitochondrial dysfunction in a CKD mouse model. Our findings suggest that an excess of gelsolin may contribute to podocytes damage in glomeruli. [ABSTRACT FROM AUTHOR]

Abstract: Natriuretic peptide (NP) levels (B-type natriuretic peptide (BNP) and N-terminal proBNP) are now widely used in clinical practice and cardiovascular research throughout the world and have been incorporated into most national and international cardiovascular guidelines for heart failure. The role of NP levels in state-of-the-art clinical practice is evolving rapidly. This paper reviews and highlights ten key messages to clinicians: [•] NP levels are quantitative plasma biomarkers of heart failure (HF). [•] NP levels are accurate in the diagnosis of HF. [•] NP levels may help risk stratify emergency department (ED) patients with regard to the need for hospital admission or direct ED discharge. [•] NP levels help improve patient management and reduce total treatment costs in patients with acute dyspnoea. [•] NP levels at the time of admission are powerful predictors of outcome in predicting death and re-hospitalisation in HF patients. [•] NP levels at discharge aid in risk stratification of the HF patient. [•] NP-guided therapy may improve morbidity and/or mortality in chronic HF. [•] The combination of NP levels together with symptoms, signs and weight gain assists in the assessment of clinical decompensation in HF. [•] NP levels can accelerate accurate diagnosis of heart failure presenting in primary care. [•] NP levels may be helpful to screen for asymptomatic left ventricular dysfunction in high-risk patients. [Copyright &y& Elsevier]

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3D-printed models fabricated from CT, MRI, or echocardiography data provide the advantage of haptic feedback, direct manipulation, and enhanced understanding of cardiovascular anatomy and underlying pathologies. Reported applications of cardiovascular 3D printing span from diagnostic assistance and optimization of management algorithms in complex cardiovascular diseases, to planning and simulating surgical and interventional procedures. The technology has been used in practically the entire range of structural, valvular, and congenital heart diseases, and the added-value of 3D printing is established. Patient-specific implants and custom-made devices can be designed, produced, and tested, thus opening new horizons in personalized patient care and cardiovascular research. Physicians and trainees can better elucidate anatomical abnormalities with the use of 3D-printed models, and communication with patients is markedly improved. Cardiovascular 3D bioprinting and molecular 3D printing, although currently not translated into clinical practice, hold revolutionary potential. 3D printing is expected to have a broad influence in cardiovascular care, and will prove pivotal for the future generation of cardiovascular imagers and care providers. In this Review, we summarize the cardiovascular 3D printing workflow, from image acquisition to the generation of a hand-held model, and discuss the cardiovascular applications and the current status and future perspectives of cardiovascular 3D printing. [ABSTRACT FROM AUTHOR]

Tissue inhibitor of metalloproteinases 4 (TIMP4) is expressed highly in heart and found dysregulated in human cardiovascular diseases. It controls extracellular matrix remodeling by inhibiting matrix metalloproteinases (MMPs) and is implicated in processes including cell proliferation, apoptosis, and angiogenesis. Timp4-deficient mice (Timp4-/-) were generated to assess TIMP4 function in normal development and in models of heart disease. We deleted exons 1-3 of the Timp4 gene by homologous recombination. Timp4-/- mice are born healthy, develop normally, and produce litters of normal size and gender distribution. These mice show no compensation by overexpression of Timp1, Timp2, or Timp3 in the heart. Following cardiac pressure overload by aortic banding, Timp4-/- mice have comparable survival rate, cardiac histology, and cardiac function to controls. In this case, Timp4 deficiency is compensated by increased cardiac Timp2 expression. Strikingly, the induction of myocardial infarction (MI) leads to significantly increased mortality in Timp4-/- mice primarily due to left ventricular rupture. The post-MI mortality of Timp4-/- mice is reduced by administration of a synthetic MMP inhibitor. Furthermore, combining the genetic deletion of Mmp2 also rescues the higher post-MI mortality of Timp4-/- mice. Finally, Timp4-/- mice suffer reduced cardiac function at 20 months of age. Timp4 is not essential for murine development, although its loss moderately compromises cardiac function with aging. Timp4-/- mice are more susceptible to MI but not to pressure overload, and TIMP4 functions in its capacity as a metalloproteinase inhibitor after myocardial infarction. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) and subsequent adverse remodeling cause heart failure. Previously we demonstrated a role for Kit ligand (KL) in improving cardiac function post-MI. KL has two major isoforms; KL-1 is secreted whereas KL-2 is predominantly membrane bound. We demonstrate here first that KL-2-deficient mice have worse survival and an increased heart/bodyweight ratio post-MI compared to mice with reduced c-Kit receptor expression. Next we synthesized recombinant lentiviral vectors (LVs) that engineered functional expression of murine KL-1 and KL-2. For in vivo analyses, we directly injected these LVs into the left ventricle of membrane-bound KL-deficient Sl/Sld or wild-type (WT) mice undergoing MI. Control LV/enGFP injection led to measurable reporter gene expression in hearts. Injection of LV/KL-2 attenuated adverse left ventricular remodeling and dramatically improved survival post-MI in both Sl/Sld and WT mice (from 12 to 71% and 35 to 73%, respectively, versus controls). With regard toward beginning to understand the possible salutary mechanisms involved in this effect, differential staining patterns of Sca-1 and Ly49 on peripheral blood (PB) cells from therapeutically treated animals was found. Our data show that LV/KL-2 gene therapy is a promising treatment for MI.Molecular Therapy (2009) 17 2, 262–268 doi:10.1038/mt.2008.244 [ABSTRACT FROM AUTHOR]

Background: The importance of heart failure with preserved ejection fraction is increasingly recognized. We conducted a study to evaluate the epidemiologic features and outcomes of patients with heart failure with preserved ejection fraction and to compare the findings with those from patients who had heart failure with reduced ejection fraction. Methods: From April 1, 1999, through March 31, 2001, we studied 2802 patients admitted to 103 hospitals in the province of Ontario, Canada, with a discharge diagnosis of heart failure whose ejection fraction had also been assessed. The patients were categorized in three groups: those with an ejection fraction of less than 40 percent (heart failure with reduced ejection fraction), those with an ejection fraction of 40 to 50 percent (heart failure with borderline ejection fraction), and those with an ejection fraction of more than 50 percent (heart failure with preserved ejection fraction). Two groups were studied in detail: those with an ejection fraction of less than 40 percent and those with an ejection fraction of more than 50 percent. The main outcome measures were death within one year and readmission to the hospital for heart failure. Results: Thirty-one percent of the patients had an ejection fraction of more than 50 percent. Patients with heart failure with preserved ejection fraction were more likely to be older and female and to have a history of hypertension and atrial fibrillation. The presenting history and clinical examination findings were similar for the two groups. The unadjusted mortality rates for patients with an ejection fraction of more than 50 percent were not significantly different from those for patients with an ejection fraction of less than 40 percent at 30 days (5 percent vs. 7 percent, P=0.08) and at 1 year (22 percent vs. 26 percent, P=0.07); the adjusted one-year mortality rates were also not significantly different in the two groups (hazard ratio, 1.13; 95 percent confidence interval, 0.94 to 1.36; P=0.18). The rates of readmission for heart failure and of in-hospital complications did not differ between the two groups. Conclusions: Among patients presenting with new-onset heart failure, a substantial proportion had an ejection fraction of more than 50 percent. The survival of patients with heart failure with preserved ejection fraction was similar to that of patients with reduced ejection fraction. N Engl J Med 2006;355:260-9. [ABSTRACT FROM AUTHOR]