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Background: Coronary artery bypass grafting (CABG) remains a cornerstone in the management of coronary artery disease (CAD). In non-urgent surgical revascularization cases, preoperative optimization of modifiable risk factors can improve outcomes. There is increasing interest in the relationship between lipoprotein(a) levels and the risk for ischemic cardiovascular disease, particularly how CABG outcomes are in turn affected. This review highlights the role of Lp(a) in the pathogenesis of CAD and CABG outcomes and discusses future directions for its optimal management in the perioperative period., Methods: A review of the PubMed/MEDLINE database until March 2024 was performed to capture publications that evaluated and/or described the relationship between lipoprotein(a) and CABG surgery or CAD outcomes., Results: The available literature supports lipoprotein(a) as a causal and independent risk factor for the pathogenesis of CAD. Elevated lipoprotein(a) levels are associated with an increased risk of adverse post-CABG outcomes, including graft occlusion incidence and major adverse cardiovascular events. Genetic variations influencing lipoprotein(a) levels play a role in disease progression and surgical outcomes. Several therapies aimed at reducing lipoprotein(a) levels, currently in phase III clinical trials, show promise for improving post-CABG prognosis., Conclusions: Among individuals undergoing surgical revascularization for CAD, lipoprotein(a) levels may help define risk and inform best practices for perioperative management. We advocate for the routine measurement of lipoprotein(a) in all patients undergoing CABG. Emerging lipoprotein(a)-lowering agents show promise for secondary prevention of cardiac events, though dedicated analyses in cardiac surgical sub-cohorts will be important to evaluate their role in improving CABG outcomes., (Copyright © 2025. Published by Elsevier Inc.)

Background: This exploratory analysis of the randomized controlled Aortic Surgery Cerebral Protection Evaluation CardioLink-3 trial sought to determine if cerebral oximetry desaturation during elective proximal arch repair is associated with detrimental postoperative neuroradiologic and neurofunctional outcomes., Methods: Cerebral oximetry and pre- and postoperative brain magnetic resonance imaging data from 101 participants were analyzed. Oximetry data from the trial allocation groups were compared; the relationships between cerebral oximetry indices and new ischemic cerebral lesions on magnetic resonance imaging and neurologic outcomes were also evaluated., Results: Total cerebral desaturation events (>20% decrease from baseline) on the left (median [interquartile range], 1 [1-3] vs 1.5 [0.5-3] with innominate and axillary cannulation; P = .80) were comparable to those on the right (1 [1-3] vs 1 [0-3]; P = .75) as were the total area under the curve of desaturation (left, P = .61; right, P = .84). Seventy patients had new ischemic lesions, among whom 36 had new severe lesions. Total desaturation events and area under the curve of desaturation were similar in patients with and without new ischemic lesions or severe lesions. The nadir regional cerebral saturation was lower on the left (49% [41-56]) than the right (53% [44-59]); left desaturation episodes were associated with lower postoperative cognitive test scores (P = .004)., Conclusions: The innominate and axillary cannulation techniques for elective proximal arch repair with unilateral antegrade cerebral perfusion were associated with similar occurrences of cerebral oximetry desaturation and neither were associated with new ischemic lesions., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: This study evaluated the use of a wearable, patch-based cardiac rhythm monitoring device in detecting postoperative atrial fibrillation (POAF) among cardiac surgical patients within 30 days after hospital discharge., Description: From the SEARCH-AF (The Post-Surgical Enhanced Monitoring for Cardiac Arrhythmias and Atrial Fibrillation) CardioLink-1 trial, this study examined rates of POAF according to surgery type and the incremental value of continuous cardiac rhythm monitoring among patients who underwent valve surgery. The primary outcome was cumulative atrial fibrillation or atrial flutter lasting for ≥6 minutes detected by continuous monitoring or atrial fibrillation or atrial flutter documented by a 12-lead electrocardiogram within 30 days of randomization., Evaluation: The primary outcome occurred in 8.2%, 13.5%, and 21.2% of patients who underwent isolated coronary artery bypass grafting (CABG), isolated valve surgery, and combined CABG and valve surgery. Relative to patients who underwent isolated CABG, those patients who had valve surgery were more likely to experience POAF. A higher diagnostic yield was obtained when the patch-based cardiac rhythm monitor was applied in patients who underwent valve surgery., Conclusions: Use of a wearable, patch-based cardiac monitoring device was an effective detection strategy among patients undergoing valve surgery, given their higher risk of developing POAF., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Predischarge elevated mean mitral gradients (>5 mm Hg) may occur after repair for degenerative mitral regurgitation. We sought to identify risk factors associated with elevated gradients and to evaluate its impact on functional outcomes at 12 months in this subanalysis of the Canadian Mitral Research Alliance CardioLink-2 trial., Methods: One hundred four patients with degenerative mitral regurgitation undergoing mitral repair were randomized to either a leaflet resection or preservation strategy. Logistic regression was used to identify risk factors associated with an elevated gradient. Functional outcomes at 12 months were compared between participants with and without elevated gradients., Results: Elevated gradients was identified in 15 participants (14.4%), which was not significantly different based on allocation to each repair strategy (P = .10). Patients with elevated gradients were more likely to be women (odds ratio [OR], 4.28; 95% confidence interval [CI], 1.29-14.19; P = .02) and to have a lower preoperative hemoglobin level (OR, 0.93; 95% CI, 0.89-0.98; P = .01) and smaller intercommissural diameter (OR, 0.86; 95% CI, 0.76-0.97; P = .02) and mitral annuloplasty size (OR, 0.71; 95% CI, 0.57-0.87; P = .001). The ratio of intercommissural diameter-to-annuloplasty size was similar between those with and without elevated gradients (both 0.8 ± 0.1, P = .69). At 12 months those with elevated gradients had a worse New York Heart Association functional status (P = .0001), lower peak oxygen saturation in exercise test (P = .01), smaller body weight-walk distance product (P = .02), and higher Borg scale (P = .01) in the 6-minute walk test., Conclusions: Female gender, smaller mitral anatomy sizes, and lower preoperative hemoglobin levels were associated with postoperative elevated mitral gradients, which was in turn were associated with reduced functional status. Further research is warranted to investigate these potential risk factors., (Copyright © 2023. Published by Elsevier Inc.)

Background: Mitral valve repair is the gold standard treatment for degenerative mitral regurgitation (MR). The Canadian Mitral Research Alliance (CAMRA) CardioLink-2 trial showed no significant association between repair strategy, that is, leaflet resection vs preservation, and risk of functional mitral stenosis. In this subanalysis, we compared outcomes and functional tests at 12 months., Methods: CAMRA CardioLink-2 was a multicentre randomized controlled trial that allocated patients with degenerative MR and posterior leaflet prolapse to leaflet resection (n = 54) or preservation (n = 50). Stress echocardiography and functional status assessments, including the 6-minute walk test, were compared 12 months after repair., Results: Baseline demographics, stress echocardiographic findings, and mitral annuloplasty prosthesis size (33.0 ± 3.0 vs 33.6 ± 3.4 mm; P = 0.4) were similar between the two groups. There were no readmissions for heart failure or deaths during the follow-up period. At 12 months, a larger percentage of patients were in NYHA functional class ≥ 2 in the resection group compared with the preservation group (P = 0.01). Exercise capacity, rate-pressure product, 6-minute walk distance, and mean mitral valve gradients were not significantly different between the groups at 12 months. A more prominent increase in mean mitral gradient with smaller annuloplasty sizes was observed in the resection group at both rest (P = 0.03) and peak exercise (P = 0.005) in the linear regression model., Conclusions: At 12 months, there were no significant differences in mitral valve gradient, exercise capacity, and 6-minute walk test between repair strategies. Leaflet preservation may offer a larger mitral valve orifice with improved gradients in patients requiring smaller annuloplasty sizes., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD)., Background: Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown., Methods: This was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2., Results: Baseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: -1.40%; 95% confidence interval [CI]: -2.60 to -0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: -1.5 ml/m 2 ; 95% CI: -2.6 to -0.5 ml/m 2 ; p = 0.006), with a trend toward reduction in iICV (adjusted difference: -1.7 ml/m 2 ; 95% CI: -3.8 to 0.3 ml/m 2 ; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2., Conclusions: In individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970)., Competing Interests: Funding Support And Author Disclosures This trial was supported by an unrestricted investigator-initiated study grant from Boehringer Ingelheim. The study sponsor was not involved in the study design; data collection, analysis and interpretation; writing of this report or in the decision to submit for publication. Dr. Mason was the recipient of a Boehringer Ingelheim Diabetes and Cardiovascular Disease Scholarship. Dr. Coelho-Filho was partially supported by a National Council for Scientific and Technological Development (CNPq) Productivity in Research award grant (303366/2015-0) and a Young Investigators Grant from The São Paulo Research Foundation (2015/15402-2). Dr. Verma holds a Canada Research Chair in Cardiovascular Surgery. Dr. Gilbert holds a Canada Research Chair in Diabetes Complications. Dr. Jüni holds a Canada Research Chair in Clinical Epidemiology of Chronic Diseases. Dr. Mazer is the recipient of a Merit Award from the University of Toronto Department of Anesthesia. Dr Connelly is supported by a Merit Award from the Department of Medicine, University of Toronto. Dr. Coelho-Filho has received research grants and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Shire, and Pfizer. Dr. Verma has received research grants and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EOCI Pharmacomm Ltd., HLS Therapeutics, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group; and is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization. Dr. Teoh has received honorarium from Boehringer Ingelheim and writing fees for unrelated manuscripts from Merck. Dr. Gilbert has received institutional research grants from AstraZeneca and Boehringer Ingelheim; served on advisory panels for AstraZeneca, Boehringer Ingelheim, and Janssen; received CME speaker honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, and Janssen; and owns stock in Certa, OccuRx, and Fibrocor Therapeutics. Dr. Leiter has received research grants from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, GlaxoSmithKline, Novo Nordisk, and Sanofi; served on advisory panels for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi; and received CME speaker honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Servier. Dr. Jüni has served as unpaid member of the steering group of trials funded by Abbott Vascular, AstraZeneca, Biotronik, Biosensors, St. Jude Medical, Terumo, and The Medicines Company; received institutional research grants from AstraZeneca, Biotronik, Biosensors International, Eli Lilly, and The Medicines Company; and received institutional honoraria for participation in advisory boards and/or consulting from Amgen, Ava, and Fresenius but has not received personal payments by any pharmaceutical company or device manufacturer. Dr. Zinman has received research grants and/or advisory board honorarium from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, and Sanofi. Dr. Mazer has received honoraria from Amgen, Boehringer Ingelheim, Octapharma, and AstraZeneca. Dr. Yan has received research support from AstraZeneca. Dr. Connelly is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure; has received institutional research grants from AstraZeneca, Servier, and Boehringer Ingelheim; has received support for travel to scientific meetings from Boehringer Ingelheim; has received honoraria for speaking engagements and ad hoc participation in advisory boards from Servier, Merck, Eli Lilly, AstraZeneca, Boehringer Ingelheim, Ferring, Novo Nordisk, Novartis, and Janssen; and is supported by a Merit Award from the Department of MEdicine, University of Toronto. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Aims: Doxorubicin (DOX) is a potent anticancer drug with severe dose-dependent cardiotoxicity. To address this issue, previous research primarily focused on DOX-induced toxicity on cardiomyocytes. However, more recent research has looked into the endothelium as a therapeutic target due to the emerging role of endothelial cells in the support of cardiomyocyte survival and function., Main Methods: We investigated a novel role of endothelial cell (EC) primary cilia in the prevention of DOX-mediated cardiotoxicity. Mice lacking EC primary cilia, via the deletion of EC-specific intraflagellar protein 88 (IFT88) expression, were administered DOX (20 mg/kg i.p.), and assessed for survival, cardiac function, cardiac structure changes, and indices of cardiomyocyte injury., Key Findings: DOX-treatment resulted in reduced survival and cardiac function (ejection fraction and fractional shortening) in EC-IFT88 -/- mice vs. their similarly treated wild-type littermates. Cardiomyocyte vacuolization, cardiac fibrosis, and serum CK-MB levels were also increased in DOX-treated mice compared to saline-treated controls. However, these parameters were not significantly different when comparing WT and EC-IFT88 -/- mice after DOX treatment., Significance: The loss of EC primary cilia accelerated DOX-mediated mortality and reduced cardiac function, suggesting pathways downstream of ciliary-mediated signal transduction as potential targets to promote EC support of cardiomyocyte function during DOX treatment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH., Competing Interests: Declaration of competing interest HT reports receiving honorarium from Boehringer Ingelheim and writing fees for unrelated diabetes-focussed manuscripts from Merck and Servier. DLB discloses the following relationships - Advisory Board: Cardax, Cereno Scientific, Elsevier Practice Update Cardiology, Medscape Cardiology, PhaseBio, Regado Biosciences; Board of Directors: Boston VA Research Institute, Society of Cardiovascular Patient Care, TobeSoft; Chair: American Heart Association Quality Oversight Committee; Data Monitoring Committees: Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Cleveland Clinic (including for the ExCEED trial, funded by Edwards), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo), Population Health Research Institute; Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Vice-Chair, ACC Accreditation Committee), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Medtelligence/ReachMD (CME steering committees), Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), Slack Publications (Chief Medical Editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), WebMD (CME steering committees); Other: Clinical Cardiology (Deputy Editor), NCDR-ACTION Registry Steering Committee (Chair), VA CART Research and Publications Committee (Chair); Research Funding: Abbott, Afimmune, Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Chiesi, CSL Behring, Eisai, Ethicon, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Idorsia, Ironwood, Ischemix, Lilly, Medtronic, PhaseBio, Pfizer, Regeneron, Roche, Sanofi Aventis, Synaptic, The Medicines Company; Royalties: Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); Site Co-Investigator: Biotronik, Boston Scientific, CSI, St. Jude Medical (now Abbott), Svelte; Trustee: American College of Cardiology; Unfunded Research: FlowCo, Merck, Novo Nordisk, PLx Pharma, Takeda. CDM reports receiving honoraria from Amgen, Boehringer Ingelheim and OctaPharma. KAC is listed as an inventor on a patent application by Boehringer Ingelheim on the use of dipeptidyl peptidase-4 inhibitors in heart failure; and reports receiving research grants to his institution from AstraZeneca and Boehringer Ingelheim; support for travel to scientific meetings from Boehringer Ingelheim and honoraria for speaking engagements and ad hoc participation in advisory boards from AstraZeneca, Boehringer Ingelheim and Janssen. SV holds a Canada Research Chair in Cardiovascular Surgery; and reports receiving research grants and/or speaking honoraria from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, EOCI Pharmacomm Ltd, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Sun Pharmaceuticals, and the Toronto Knowledge Translation Working Group. He is also the is the President of the Canadian Medical and Surgical Knowledge Translation Research Group, a federally incorporated not-for-profit physician organization.The other authors have no relevant conflicts of interest to declare., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: The pathophysiologic processes of abdominal aortic aneurysms (AAAs) and atherosclerosis often intersect. Given that anomalies in vascular smooth muscle cell (SMC) autophagy have been noted in models of atherosclerosis, we sought to evaluate the potential role that SMC autophagy may play in the initiation and progression of AAAs., Methods: Studies were conducted in ATG7 flx/flx SM22α-Cre tg/+ (SMC ATG7 knockout [SMC-ATG7-KO]) and ATG7 WT/WT ; SM22α-Cre tg/+ (SMC ATG7 wild-type [SMC-ATG7-WT]) littermates that were continuously infused with angiotensin II (Ang II; 1.5 mg/kg/d) for up to 12 weeks. Mortality, morbidity, hemodynamics, and aortic remodeling were documented., Results: During the 12-week observation window, all of the Ang II-treated SMC-ATG-WT mice (n = 6) survived, whereas 10 of the 19 Ang II-treated SMC-ATG-KO mice had died by week 7 (log-rank test, P < .001). Mean arterial pressure (128.07 ± 3.4 mm Hg for Ang II-treated SMC-ATG-KO vs 138.5 ± 5.87 mm Hg for Ang II-treated SMC-ATG-WT mice) and diastolic arterial pressure (109.7 ± 2.55 mm Hg for Ang II-treated SMC-ATG7-KO vs 119.4 ± 2.12 mm Hg for Ang II-treated SMC-ATG7-WT mice) were significantly different between the two groups (P < .01). Cardiac rupture, myocardial infarct, end-organ damage, pleural effusion, and venous distention were noted in Ang II-treated SMC-ATG7-KO but not in Ang II-treated SMC-ATG7-WT mice. Although the suprarenal aortic diameters of the Ang II-treated SMC-ATG7-KO group demonstrated a trending increase (at week 4, 1.26 ± 0.06 mm [n = 14] for Ang II-treated SMC-ATG-KO mice vs 1.09 ± 0.02 mm [n = 5] for Ang II-treated SMC-ATG-WT mice; P < .05), only 2 of the 19 developed abdominal aortic dissections., Conclusions: Mice with SMC ATG7 deficiency that are chronically infused with Ang II do not tend to develop dissecting AAA but do exhibit adverse aortic remodeling and appreciable cardiac failure-associated mortality., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Monocyte-derived microparticles (mono-MPs) are emerging as critical transducers of inflammatory signals, and have been suggested to link cardiovascular risk factors to vascular injury. Since adiponectin has been proposed to exert multiple anti-inflammatory and vasculoprotective effects, we hypothesized that it might serve to limit the production and/or action of mono-MPs., Methods: Flow cytometry and western blot studies were conducted on THP-1 cells, THP-1-derived MPs, human umbilical vein endothelial cells (HUVECs), peripheral blood CD14+ monocytes and mice to evaluate the effects of adiponectin on mono-MPs., Results: Adiponectin attenuated lipopolysaccharide (LPS)-evoked MP release from THP-1 monocytes (30% difference) and peripheral blood monocytes (both P < 0.05) as well as dampened LPS-induced mono-MP generation in vivo. Furthermore, peritoneal monocytes from Adipoq(-/-) mice generated significantly greater MPs than those from Adipoq(+/+) littermates in the absence (2.3 fold difference, P < 0.05) and presence (1.6 fold difference, P < 0.05) of LPS. LPS-induced MP expression of NLRP3 inflammasome and its key components, namely cleaved ASC, caspase-1 and IL-1β (pro- and cleaved), were markedly attenuated by adiponectin. HUVECs incubated with MPs from LPS-treated THP-1 cells exhibited increased VCAM-1 levels and adhesion to THP-1 cells. Adiponectin abrogated these effects. From a mechanistic standpoint, the effects of adiponectin on MP release and molecular signaling occurred at least in part through the AMPK, Akt and NFκB pathways., Conclusion: Adiponectin exerts novel effects to limit the production and action of mono-MPs, underscoring yet another pleiotropic effect of this adipokine., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Obesity is a multifactorial chronic disease characterized by an accumulation of visceral and subcutaneous fat, which leads to a predisposition toward cardiometabolic diseases. A plethora of mechanisms, including abnormalities in lipid metabolism, insulin resistance, inflammation, endothelial dysfunction, adipokine imbalance, and inflammasome activation have been suggested to underlie the relationship between obesity and atherosclerosis. More recent data point toward an emerging role of impaired autophagy and altered gut microbiome homeostasis as potentially contributing factors. This review provides an overview of this area., (Copyright © 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the risk assessment and management patterns employed by primary care physicians in patients at elevated cardiometabolic risk., Methods: Between April 2011 and March 2012, multiple physicians from 9 Primary Care Teams (PCTs) and 88 physicians from traditional nonteam (Solo) practices completed a practice assessment on the management of 2461 patients > 40 years old with no clinical evidence of cardiovascular disease and diagnosed with at least 1 of the following: dyslipidemia, type 2 diabetes mellitus (T2DM), or hypertension., Results: Individuals with dyslipidemia, T2DM, or hypertension tended to have a body mass index ≥ 25 kg/m(2). Waist circumference measurements, obtained for only 392/829 (47.0%) Solo patients, revealed that 88.9% of these individuals were abdominally obese and that at least 52.2% of Solo patients had metabolic syndrome. Cardiovascular risk, determined by the physicians for 83.5% of all patients without T2DM and typically performed using traditional risk engines, was often miscalculated (43.2% PCTs, 58.8% Solo; P = 0.0007). Healthy behavioural modifications were infrequently recommended (< 50%). Pharmacotherapy was widely used (> 70%) but treatment targets were infrequently met. The composite outcome of guideline-recommended low-density lipoprotein cholesterol, glycemic, and blood pressure targets was met by 9.0% and 8.1% of patients managed by PCT and Solo physicians respectively., Conclusions: Obesity and cardiovascular risk were underassessed and the latter often underestimated. Patients were infrequently counselled on the benefits of healthy behavioural changes. A paradigm change in assessing and managing obesity and cardiovascular risk via aggressive lifestyle interventions is warranted in individuals at elevated cardiometabolic risk., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular (CV) risk stratification remains the cornerstone of preventive cardiology. This study was performed to gain insight into how Canadian primary care physicians (PCPs) incorporate traditional and emerging risk factors in determining risk., Methods: Using a tested questionnaire, this cross-sectional survey evaluated the perceptions of 846 PCPs (38% response rate) on CV risk assessment, treatment thresholds, and novel biomarkers of vascular risk., Results: Most physicians (74%) perform CV risk assessment in eligible patients annually with 69% using the Framingham Risk Score (FRS). Although 89% of the physicians knew that FRS estimates 10-year risk of coronary heart disease death and myocardial infarction, 30% could not characterize FRS thresholds for high risk. Only 44% correctly used a positive family history to double the FRS. Waist circumference was considered by 79% of the physicians as a vital sign but only 6% reported measuring this routinely. Carotid ultrasound was identified by 55% as the preferred imaging technique for screening in primary prevention. Although 99% had heard of high sensitivity C-reactive protein (hs-CRP), only 49% measured it for the purposes of assessing CV risk and 27% were unsure under what clinical scenarios the test is indicated., Conclusions: Our survey suggests that FRS is employed by approximately 2/3 of Canadian PCPs for risk stratification. Family history and central obesity are considered important additional CV risk markers. There are substantial knowledge gaps on the appropriate use of family history and hs-CRP in risk stratification, particularly in patients who may not present with hyperlipidemia., (Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

P53 protein levels are elevated by trastuzumab and the biologically similar rat ERBB2/HER2/NEU antibody; and that this coincides with enhanced apoptosis, increased cleaved caspase-3 levels and diminished cardiac function. We also demonstrate that MDM2 may be a regulatory target of anti-ERBB2 thereby implicating the MDM2/p53 axis as a potential molecular component for the undesirable cardiac outcomes noted with trastuzumab. Finally, we show that these MDM2/p53-mediated events are independent of both the ERK1/2 and Akt systems. In conclusion, our findings suggest that the adverse cardiac events observed with trastuzumab may stem from its negative regulation of MDM2 events which impairs p53 degradation resultantly promoting apoptosis leading to cardiac dysfunction. These observations may have important therapeutic implications since they suggest that anticancer agents that inhibit MDM2 and its downstream actions may curb tumor progression at the expense of increasing cardiac stress., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.)

Background: Despite the well-established benefits of strategies to reduce low-density lipoprotein cholesterol (LDL-C), many patients fail to achieve the guideline recommended targets. The objective of this study was to evaluate the impact of an enhanced 26-week algorithm-based treatment optimization strategy, involving titration of statin monotherapy and/or combination therapy with statin and ezetimibe, on achievement of guideline-based LDL-C targets in patients at high risk for atherosclerotic disease., Methods and Results: In this national (172-physician) quality enhancement research initiative involving 2334 Canadian men and women (median age, 65 years) at high vascular risk who were not at the guideline-recommended LDL-C target despite statin therapy, 36.6% and 45.5% of patients achieved an LDL-C <2.0 mmol/L at visit 2 and visit 3, respectively, using the treatment optimization algorithm. The percentage of patients achieving the 2009 Canadian Cardiovascular Society (CCS)-recommended target of either LDL-C <2.0 mmol/L or a 50% or greater reduction from baseline increased from 6.8% at visit 1 to 43.3% at visit 2 and to 52.1% at visit 3. Attainment of LDL-C targets increased significantly with consecutive visits (P < .001). Use of ezetimibe in combination with statin therapy was associated with greater target achievement., Conclusions: Use of a structured treatment optimization algorithm, based on titration of statin dosages and incorporation of ezetimibe therapy when required, enabled the majority of high-risk patients to achieve guideline-recommended targets, thereby narrowing the care gap that exists in dyslipidemia management., (Copyright © 2011. Published by Elsevier Inc.)

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.)

Objectives: To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association's recommended targets in ambulatory patients with type 2 diabetes., Methods: Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success - defined as the achievement of a blood pressure (BP) of 13080 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmolL and total cholesterolhigh-density lipoprotein cholesterol ratio lower than 4.0 - are reported., Results: Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association's recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose- lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterolhigh-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C., Interpretation: A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence- based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.

DNA turnover through damage and repair is normal homeostatic process in viable cells. DNA damage induces sequential responses to either repair the damage or activate a programmed cell death process. Defects in this critical response to DNA damage underpin a wide array of human pathologies that include cancer predisposition, immune dysfunction, radiosensitivity, and neurodegeneration. Recent experimental and clinical studies have suggested that oxidative stress leading to catastrophic DNA damage is enhanced in failing hearts as well as other cardiovascular diseases. Accordingly, targeting the genotoxic effects of oxidative stress may prove to be a novel avenue in the development of rational therapies for cardiovascular diseases. A platform introduction to DNA repair/response are integrated, and insights into the future directions of this exciting field are offered.

Increasing evidence suggests that the inflammatory biomarker, C-reactive protein (CRP), may play a causal role in the development and progression of atherothrombosis. Since endothelial dysfunction is an early and integral component of atherosclerosis, we hypothesized that endothelial homeostasis would be impaired in CRP-overexpressing CRP transgenic (CRPtg) mice. Male CRPtg and wild-type mice were injected thrice over 2 weeks with vehicle or turpentine to induce the inflammation-sensitive CRP transgene. Serum human CRP levels in turpentine-treated CRPtg mice was 276.28 +/- 95.7 microg/ml. Human CRP was undetectable in the sera of wild-type mice and present at only low levels (1.41 +/- 0.2 microg/ml) in vehicle-treated CRPtg mice (n=6-8 mice/group). Aortic segments from turpentine-induced CRP-overexpressing CRPtg mice demonstrated impaired endothelium-dependent responses to acetylcholine vs. those from vehicle-treated CRPtg controls (57.1 +/- 9.5% vs. 85.0 +/- 5.0%, P<0.05, n=6). Nitric oxide release as well as phosphorylated eNOS protein expression from isolated aortic segments of CRPtg mice overexpressing CRP were markedly reduced compared to that from vehicle-treated controls. Masson's trichrome staining revealed increased perivascular fibrosis in CRP-overexpressing CRPtg mice. CRP overexpression was also associated with augmented aortic endothelial staining for VCAM-1 and MCP-1 and enhanced macrophage infiltration. Mice overexpressing the human CRP gene exhibit endothelial dysfunction, possibly via reduced NO bioavailability, with resultant changes in vascular structure. These data further support a role for CRP in mediating endothelial dysfunction.