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Atherosclerotic cardiovascular disease (ASCVD) is a significant health challenge, and apolipoprotein B (ApoB)-containing lipoproteins are increasingly recognized as central to its progression. Initially labelled as the "low-density lipoprotein hypothesis," our understanding of the etiology of ASCVD has evolved into the "ApoB principle," which highlights the causal and consistent role of all ApoB lipoproteins in ASCVD development. We review the large body of data from genetic studies, to epidemiologic studies, to clinical trials that support this foundational principle. We also provide an overview of the recommendations from guideline committees across the globe on dyslipidemia management and compare these with recent Canadian guidelines. With a few key differences, recent guidelines worldwide provide largely concordant recommendations for diagnosing and managing dyslipidemia with general consensus regarding the need for optimal control of low-density lipoprotein cholesterol and ApoB-containing lipoproteins to prevent cardiovascular events and improve patient care., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Because cholesterol-depleted Apo B particles are thought to be a hallmark of hypertriglyceridemia, American, Canadian and European Lipid Guidelines suggest screening for Apo B only in patients with hypertriglyceridemia. Accordingly, this study examines the relationship of triglycerides to the LDL-C/Apo B and non-HDL-C/Apo B ratios., Methods: The study cohort consisted of 6272 NHANES subjects adjusted for a weighted sample size of 150 million subjects without previously diagnosed cardiac disease. Data was reported by LDL-C/Apo B tertiles as weighted frequencies and percent. Sensitivity, specificity, negative predictive and positive predictive values were calculated for triglycerides thresholds of >150 mg/dL and >200 mg/dL. The range of values of Apo B for decisional levels of LDL-C and non-HDL-C were also determined RESULTS: Among patients with triglycerides >200 mg/dL, 75.9% were amongst the lowest LDL-C/Apo B tertile. However, this represents only 7.5% of the total population. Of patients with the lowest LDL-C/Apo B ratio, 59.8% had triglycerides <150 mg/dL. Moreover, there was an inverse relationship between non-HDL-C/Apo B such that elevated triglycerides were associated with the highest tertile of non-HDL-C/Apo B. Finally, the range of values of Apo B for decisional levels of LDL-C and non-HDL-C was determined and is so broad- 30.3-40.6 mg/dl Apo B for different levels of LDL-C and 19.5 to 27.6 mg/dl Apo B for different levels of non-HDL-C- that neither is an adequate clinical surrogate for Apo B., Conclusion: Plasma triglycerides should not be used to restrict the measurement of Apo B since cholesterol-depleted Apo B particles may be present at any level of triglyceride., (Copyright © 2023. Published by Elsevier Inc.)

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 The ODYSSEY OUTCOMES (Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome) trial demonstrated that alirocumab reduced major cardiovascular events. However, because of the hierarchical testing strategy used for the multiple outcomes examined, the observed reduction in all-cause mortality was labeled "nominally significant" which has clouded its interpretation. Methods and Results We re-analyzed data from ODYSSEY OUTCOMES using Bayesian methods and generated various prior probabilities by incorporating mortality data from previous similar PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitor trials. We first used data from the ODYSSEY OUTCOMES trial with a non-informative prior, then sequentially added data from ODYSSEY LONG TERM and the FOURIER trial, giving FOURIER full weight, 50% weight and 10%. The posterior probability of a mortality reduction using only the ODYSSEY OUTCOMES data was hazard ratio 0.85 (95% CI 0.74-0.99) which corresponded to a 98.4% probability of a mortality benefit. When the ODYSSEY LONG TERM data were added to the analysis, the posterior probability was hazard ratio 0.84 (95% CI 0.72-0.97) with a 99.9% probability of mortality reduction, and when the FOURIER data were added to the analysis the posterior probability was hazard ratio 0.94 (95% CI 0.85-1.04) with an 89.1% probability of a mortality reduction. When the FOURIER trial was given only 50% or 10% weight, the probability of a mortality reduction rose 95.4% and 98.7%, respectively. We estimate that the probability of >1% absolute risk reduction ranges from 8% to 24%, while the probability of >0.5% absolute risk reduction ranges from 66% to 89%. Conclusions Our analysis demonstrates a high likelihood that alirocumab confers a reduction in all-cause mortality, despite the equivocal interpretation of the data in the original ODYSSEY OUTCOMES publication.

Background: "Gender" reflects social norms for women and men, whereas "sex" defines biological characteristics. Gender-related characteristics explain some differences in access to care for premature acute coronary syndrome (ACS); whether they are associated with cardiovascular outcomes is unknown., Objectives: This study estimated associations between gender and sex with recurrent ACS and major adverse cardiac events (MACE) (e.g., ACS, cardiac mortality, revascularization) over 12 months in patients with ACS., Methods: We studied 273 women and 636 men age 18 to 55 years from GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary SYndrome), a prospective observational cohort study, who were hospitalized for ACS between January 2009 and April 2013. Gender-related characteristics (e.g., social roles) were assessed using a self-administered questionnaire, and a composite measure of gender was derived. Outcomes included recurrent ACS and MACE over 12 months., Results: Feminine roles and personality traits were associated with higher rates of recurrent ACS and MACE compared with masculine characteristics. This difference persisted for recurrent ACS, after multivariable adjustment (hazard ratio from score 0 to 100: 4.50; 95% confidence interval: 1.05 to 19.27), and was a nonstatistically significant trend for MACE (hazard ratio: 1.54; 95% confidence interval: 0.90 to 2.66). A possible explanation is increased anxiety, the only condition that was more prevalent in patients with feminine characteristics and that rendered the association between gender and recurrent ACS nonstatistically significant (hazard ratio: 3.56; 95% confidence interval: 0.81 to 15.61). Female sex was not associated with outcomes post-ACS., Conclusions: Younger adults with ACS with feminine gender are at an increased risk of recurrent ACS over 12 months, independent of female sex., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Few contemporary data exist on traditional (TRF) and non-TRF (NTRF) burden in patients with premature acute coronary syndrome (ACS)., Methods: Prevalence of TRFs and NTRFs were measured in 1015 young (55 years old or younger) ACS patients recruited from 26 centres in Canada, the United States, and Switzerland. Risk factors were compared across sex and family history categories, and against a sample of the general Canadian population based on the 2000-2001 Canadian Community Health Survey. The 10- and 30-year risks of cardiovascular disease (CVD) were estimated using Framingham Risk Scores., Results: Risk factors were more prevalent in premature ACS patients compared with the general population. Young women with a family history of coronary artery disease showed the greatest risk factor burden including TRFs of hypertension (67%), dyslipidemia (67%), obesity (53%), smoking (42%), and diabetes (33%), and NTRFs of anxiety (55%), low household income (44%), and depression (37%). The estimated median 10-year risk of CVD was 7% (interquartile range [IQR], 3%-9%) in women and 13% (IQR, 7%-17%) in men, whereas the 30-year risk of CVD was 36% (IQR, 22%-49%) in women and 44% (IQR, 31%-57%) in men., Conclusions: Patients with premature ACS, especially women with a positive family history, are characterized by a very high risk factor burden that is poorly captured by 10-year risk estimates but better captured by 30-year estimates. Consideration of NTRFs and use of 30-year risk estimates might better estimate risk in young individuals and improve the prevention of premature ACS., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The association between depression and cardiovascular disease severity in younger patients has not been assessed, and sex differences are unknown. We assessed whether major depression and depressive symptoms were associated with worse cardiovascular disease severity in patients with premature acute coronary syndrome, and we assessed sex differences in these relationships., Methods: We enrolled 1023 patients (aged ≤ 55 years) hospitalized with acute coronary syndrome from 26 centers in Canada, the United States, and Switzerland, through the GENdEr and Sex determInantS of cardiovascular disease: From bench to beyond-Premature Acute Coronary Syndrome study. Left ventricular ejection fraction, Killip class, cardiac troponin I, and Global Registry of Acute Coronary Events score data were collected through chart review., Results: The sample comprised 248 patients with major depression and 302 women. In univariate analyses, major depression was associated with a lower likelihood of having an abnormal left ventricular ejection fraction (odds ratio, 0.70; 95% confidence interval, 0.51-0.97; P = .03) and lower troponin I levels (estimate, -4.04; 95% confidence interval, -8.01 to -0.06; P = .05). After adjustment for sociodemographic and clinical characteristics, neither major depression nor depressive symptoms were associated with disease severity indices, and there were no sex differences., Conclusion: The increased risk of adverse events in depressed patients with premature acute coronary syndrome is not explained by disease severity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Prescription plans frequently use restrictive strategies to control drug expenditures. Increased restrictions may reduce access to evidence-based therapy among patients with chronic disease. We sought to evaluate the impact of increased restrictions on medication use among heart failure (HF) patients., Methods and Results: We conducted a population-based cohort study of administrative data from 3 Canadian provinces. During 1998 to 2001, Quebec (QC) had a minimally restrictive plan, whereas Ontario (ON) and British Columbia (BC) had more restrictive prescription plans. We evaluated drug use at 30 days of discharge stratified by prescription plan. Provincial rates of filled prescriptions for HF drugs in QC, ON, and BC were 62%, 58%, and 47% for angiotensin-converting enzyme inhibitors; 34%, 22%, and 16% for beta-blockers; 9%, 5%, and 3% for angiotensin receptor blockers; and 79%, 76%, and 62% for loop diuretics, respectively. In multivariate analyses, patients residing in provinces with restrictive plans were less likely to be prescribed drugs that were restricted, such as beta-blockers (odds ratio, 0.53; 95% CI, 0.46 to 0.60; 0.36, 0.29 to 0.44, for ON and BC, respectively) and angiotensin receptor blockers (0.50, 0.45 to 0.56; 0.38, 0.32 to 0.46, for ON and BC, respectively), than drugs with no restrictions, such as loop diuretics (0.81, 0.74 to 0.88; 0.40, 0.36 to 0.45, for ON and BC, respectively) and angiotensin-converting enzyme inhibitors (0.80, 0.75 to 0.86; 0.47, 0.43 to 0.52, for ON and BC, respectively)., Conclusions: Among HF patients, residing in a province with a more restrictive prescription plan may be associated with lower use of restricted HF medications over and above the expected regional differences in HF drug use across provinces.