Ottawa Heart Institute Research Corporation

OBJECTIVE: To study whether modification of LDL by methylglyoxal (MG), a potent arginine-directed glycating agent that is increased in diabetes, is associated with increased atherogenicity. RESEARCH DESIGN AND METHODS: Human LDL was isolated and modified by MG in vitro to minimal extent (MG(min)-LDL) as occurs in vivo. Atherogenic characteristics of MG(min)-LDL were characterized: particle size, proteoglycan-binding, susceptibility to aggregation, LDL and non-LDL receptor-binding, and aortal deposition. The major site of modification of apolipoprotein B100 (apoB100) modification was investigated by mass spectrometric peptide mapping. RESULTS: MG(min)-LDL contained 1.6 molar equivalents of MG modification-mostly hydroimidazolone-as found in vivo. MG(min)-LDL had decreased particle size, increased binding to proteoglycans, and increased aggregation in vitro. Cell culture studies showed that MG(min)-LDL was bound by the LDL receptor but not by the scavenger receptor and had increased binding affinity for cell surface heparan sulfate-containing proteoglycan. Radiotracer studies in rats showed that MG(min)-LDL had a similar fractional clearance rate in plasma to unmodified LDL but increased partitioning onto the aortal wall. Mass spectrometry peptide mapping identified arginine-18 as the hotspot site of apoB100 modification in MG(min)-LDL. A computed structural model predicted that MG modification of apoB100 induces distortion, increasing exposure of the N-terminal proteoglycan-binding domain on the surface of LDL. This likely mediates particle remodeling and increases proteoglycan binding. CONCLUSIONS: MG modification of LDL forms small, dense LDL with increased atherogenicity that provides a new route to atherogenic LDL and may explain the escalation of cardiovascular risk in diabetes and the cardioprotective effect of metformin.

OBJECTIVES: To map whether and how systematic reviews (SRs) with network meta-analysis (NMA) use presentation formats to report (a) structured evidence summaries - here defined as reporting of effects estimates in absolute effects with certainty ratings and with a method to rate interventions across one or more outcome(s) - and (b) NMA results in general. STUDY DESIGN AND SETTING: We conducted a systematic survey, searching MEDLINE (Ovid) for SRs with NMA published between January 1, 2020, and December 31, 2021. We planned to include a random sample of publications, with predefined mechanisms in place for saturation, and included SRs that met prespecified quality criteria and extracted data on presentation formats that reported: (a) estimates of effects, (b) certainty of the evidence, or (c) rating of interventions. RESULTS: The 200 eligible SRs, from 158 unique Journals, utilized 1133 presentation formats. We found structured evidence summaries in 10 publications (5.0%), with 3 (1.5%) reporting structured evidence summaries across all outcomes, including benefits and harms. Sixteen of the 133 SRs (11.7%) reporting dichotomous outcomes included estimates of absolute effects. Seventy-six SRs (38.0%) reported both benefits and harms and 26 SRs (13.0%) reported certainty ratings in presentation formats, 20 (76.9%) used Grading of Recommendations Assessment, Development and Evaluation and 6 (23.1%) used Confidence In Network Meta-analysis. Surface Under the Cumulative Ranking Curve was the most common method to rate interventions (69 SRs, 34.5%). NMA results were most often reported using forest plots (108 SRs, 54.0%) and league tables (93 SRs, 46.5%). CONCLUSION: Most SRs with NMA do not report structured evidence summaries and only rarely do such summaries include reporting of both benefits and harms; those that do offer effective user-friendly communication and provide models for optimal NMA presentation practice.

This article aims to bridge existing knowledge gaps that impact clinical cardiovascular care and outcomes for women in Canada. The authors discuss various aspects of women's heart health, emphasizing the efficacy of multidisciplinary care in promoting women's well-being. The article also identifies the impact of national women's heart health campaigns and the value of peer support in improving outcomes. The article addresses the particular risks that women face, such as pregnancy-related complications and hormone replacement therapy, all of which are associated with cardiovascular events, and highlights the differences in ischemic symptoms between men and women. Despite improvements in acute event outcomes, challenges persist in accessing timely ambulatory care, particularly for women. Canada has responded to these challenges by introducing Women Heart Programs, which offer tailored programs, support groups, and specialized testing. However, these programs remain few in number and are found only in urban settings. Overall, this review identifies sex and gender factors related to women's heart health, underscoring the importance of specialized programs and multidisciplinary care in improving women's cardiovascular health.

Background: Timely and appropriate care is critical for patients with ST-elevation myocardial infarction (STEMI). Effective communication and prompt sharing of test results, particularly electrocardiograms (ECGs), between the referring emergency medicine (EM) physician or emergency medical service (EMS) paramedic and the interventional cardiologist (IC) are essential. This exchange relies on fax or SMS text messages. The SmartAMI-ACS (Strategic Management of Acute Reperfusion and Therapies in Acute Myocardial Infarction) App was developed to streamline communication. It is user friendly and privacy compliant, and enables rapid, secure ECG sharing to support faster, informed clinical decision-making. Objective: This paper details the results of targeted preimplementation surveys to establish barriers and enablers of using a smartphone app to transmit ECG images among ICs, EM physicians, and EMS paramedics to help tailor implementation interventions. Methods: To assess the proposed acceptability and uptake of the app, preimplementation surveys were disseminated to ICs, EM physicians, and EMS paramedics in one region of Ontario, Canada. Questions were generated based on selected components of the Consolidated Framework for Implementation Research, results from a pilot study carried out at a regional hospital where the SmartAMI-ACS app was previously implemented, and predicted barriers based on expert guidance. The preimplementation surveys consisted of 7-point Likert scale questions (1=strongly disagree and 7=strongly agree) and open-ended questions. Open-ended data were extracted verbatim and analyzed using an inductive qualitative approach, with transcripts coded into descriptive qualitative codes and then collapsed into themes. Results: Survey uptake was acceptable, with 9 of the invited 10 ICs, 51 of the invited 223 EM physicians, and 93 of the invited 1138 EMS paramedics responding. All groups recognized that current practices for sharing ECGs allowed room for improvement, accepting that fax can be inconvenient and SMS text messages may not be secure. When asked whether there was a need for a smartphone app to transmit ECGs, ICs (mean 6.67, SD 0.5), EM physicians (mean 5.57, SD 1.3), and EMS paramedics (mean 5.79, SD 1.45) consistently agreed. Commonly reported barriers were concerns over technological challenges, privacy issues, and cell phone reception strength. Through the identification of the barriers in each stakeholder group, implementation strategies were developed that facilitated the scale-up of this system-change intervention. Conclusions: Results from the 3 web-based preimplementation surveys to identify key barriers and enablers to the implementation of the app helped inform the selection of tailored implementation strategies to support the rollout of the app across the health region. The surveys identified key barriers around technology, privacy, and access to required Wi-Fi that needed to be addressed during app implementation to facilitate uptake and use. Results from the surveys, and ongoing evaluation of effectiveness, are informing the expansion of the app intervention to local ambulance services and other health regions.

PURPOSE OF REVIEW: Women undergoing coronary artery bypass grafting (CABG) continue to experience worse perioperative and long-term outcomes than men despite advances in surgical techniques and perioperative care. This review summarizes contemporary evidence on sex-related differences in coronary artery disease (CAD), surgical outcomes, and secondary prevention. Gaps in the current evidence are identified and priorities for optimizing outcomes and informing sex-specific clinical practice are highlighted. RECENT FINDINGS: Women present with distinct patterns of CAD, including higher prevalence of microvascular dysfunction and nonobstructive disease, contributing to delayed diagnosis and referral for surgical revascularization. Women are less likely to receive guideline-recommended revascularization strategies, including multiple arterial grafting. Women also experience higher rates of graft failure, mortality, and stroke after CABG. Emerging observational evidence suggests that off-pump and minimally invasive CABG approaches may reduce the disparities in female patients, although randomized sex-specific data remains limited. Secondary prevention remains suboptimal, with persistent gaps in implementation of guideline-directed therapies. SUMMARY: Significant disparities persist across the continuum of care for women undergoing CABG, from diagnosis through long-term secondary prevention. Improving equitable implementation of evidence-based surgical strategies, increasing representation of women in randomized clinical trials, and developing sex-specific evidence are essential to optimize outcomes and inform future clinical guidelines.