Mini-Review: Immunogenic epitopes in apolipoprotein B-100 for atheroprotective immunization.

Here, we provide a concise overview of recent developments in the identification of immunogenic epitopes in human apolipoprotein B-100 for immunization against atherosclerotic cardiovascular disease. Major steps forward toward a clinical application of vaccines include the design of humanized mouse models, tetramer-based identification of antigen-specific T cells, and novel analysis tools, such as single-cell RNA sequencing and cytometry by time of flight, to assess temporal and spatial changes in immune cells in atherosclerotic cardiovascular disease.

Dipeptidyl peptidase 3 plasma levels predict cardiogenic shock and mortality in acute coronary syndromes.

Background And Aims: Dipeptidyl peptidase 3 (DPP3) is a protease involved in the degradation of angiotensin II which disturbs peripheral blood pressure regulation and compromises left ventricular function. This study examined the relationship of circulating DPP3 (cDPP3) with cardiogenic shock (CS) and mortality in patients presenting with acute coronary syndromes (ACS).

Methods: Plasma cDPP3 levels were assessed at baseline and 12-24 h after presentation in patients with ACS prospectively enrolled into the multi-centre SPUM-ACS study (n = 4787).

Short and medium chain acylcarnitines as markers of outcome in diabetic and non-diabetic subjects with acute coronary syndromes.

Background: Carnitine metabolism produces numerous molecular species of short-, medium-, and long-chain acylcarnitines, which play important roles in energy homeostasis and fatty acid transport in the myocardium. Given that disturbances in the carnitine metabolism are linked to cardiometabolic disease, we studied the relationship of circulating acylcarnitines with outcomes in patients with acute coronary syndromes (ACS) and evaluated differences in circulating levels of these metabolites between diabetic and non-diabetic patients.

Methods: Harnessing a prospective multicentre cohort study (SPUM-ACS; NCT01000701), we measured plasma levels of acylcarnitines, carnitine, and carnitine metabolites to assess their relationship with adjudicated major adverse cardiac events (MACE), defined as composite of myocardial infarction, stroke, clinically indicated revascularization, or death of any cause.

Initial systolic blood pressure associates with systemic inflammation, myocardial injury, and outcomes in patients with acute coronary syndromes.

Aims: Outcomes after acute coronary syndromes (ACS) are determined by baseline risk profiles, including initial systolic blood pressure (sBP) levels. Herein, we aimed to characterize ACS patients stratified by initial sBP levels and study their relation to inflammation, myocardial injury and post-ACS outcomes.

Methods And Results: We analysed 4724 prospectively recruited ACS patients according to invasively assessed sBP (<100, 100-139, and ≥140 mmHg) at admission.

Clinical outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary interventions later than 48 h after symptom onset.

Aims: Routine revascularization in patients with ST-segment elevation myocardial infarction (STEMI) presenting >48 h after symptom onset is not recommended.

Methods And Results: We compared outcomes of STEMI patients undergoing percutaneous coronary intervention (PCI) according to total ischaemic time. Patients included in the Bern-PCI registry and the Multicenter Special Program University Medicine ACS (SPUM-ACS) between 2009 and 2019 were analysed.

History of peripheral artery disease and cardiovascular risk of real-world patients with acute coronary syndrome: Role of inflammation and comorbidities.

Background: Patients with acute coronary syndromes (ACS) remain at risk of cardiovascular disease (CVD) recurrences. Peripheral artery disease (PAD) may identify a very high risk (VHR) group who may derive greater benefit from intensified secondary prevention.

Methods: Among ACS-patients enrolled in the prospective multi-center Special Program University Medicine (SPUM), we assessed the impact of PAD on major cardiovascular events (MACE: composite of myocardial infarction, stroke and all-cause death) and major bleeding.

Use of serial changes in biomarkers vs. baseline levels to predict left ventricular remodelling after STEMI.

Aims: Cellular communication network factor 1 (CCN1) is an independent predictor of MACE after ACS and elevated levels correlated with infarct size after STEMI. We compared the prognostic accuracy of baseline levels of CCN1, NT-proBNP, hsTnT, and ST2 and changes in levels over time to predict the development of structural and functional alterations typical of LV remodelling.

Methods: Serial 3-T cMRI scans were performed to determine LVEF, LVEDV, LVESV, infarct size, and relative infarct size, which were correlated with serial measurements of the four biomarkers.

Mammalian Target of Rapamycin Inhibition in Patients With ST-Segment Elevation Myocardial Infarction.

Background: Early inflammation following acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) affects myocardial infarct (MI) size and left ventricular remodeling. The mammalian target of rapamycin (mTOR) is involved in the enhanced inflammatory response and its inhibition has exerted beneficial effects on MI size in preclinical models of acute MI.

Objectives: The CLEVER-ACS (Controlled Level Everolimus in Acute Coronary Syndromes) trial evaluated the effects of targeting inflammation by mTOR inhibition in patients with STEMI undergoing PCI.

Long-term effects of systematic smoking cessation counselling during acute coronary syndrome, a multicentre before-after study.

Trial Design: In the Special Program University Medicine-Acute Coronary Syndromes (SPUM-ACS) observational study (clinical trial registration: NCT01000701), a multicentre before-after clinical trial, we assessed 5-year outcome after acute coronary syndrome, comparing a systematic with an opportunistic smoking cessation counselling phase.

Methods: We studied smokers who were hospitalised for acute coronary syndromes (ACS), and we assessed self-reported smoking cessation, incidence of cardiovascular events and mortality 5 years after hospital discharge. In the observational phase, from August 2009 to October 2010, only smokers who requested smoking cessation counselling received it during hospitalisation.

Smoking cessation and depression after acute coronary syndrome.

Smoking and depression are risk factors for acute coronary syndrome (ACS) that often co-exist. We investigated the evolution of depression according to smoking cessation one-year after ACS. Data from 1822 ACS patients of the Swiss multicenter SPUM-ACS cohort study were analyzed over a one-year follow-up.

Rapid Inflammasome Activation Is Attenuated in Post-Myocardial Infarction Monocytes.

Inflammasomes are crucial gatekeepers of the immune response, but their maladaptive activation associates with inflammatory pathologies. Besides canonical activation, monocytes can trigger non-transcriptional or rapid inflammasome activation that has not been well defined in the context of acute myocardial infarction (AMI). Rapid transcription-independent inflammasome activation induced by simultaneous TLR priming and triggering stimulus was measured by caspase-1 (CASP1) activity and interleukin release.

Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS) - A phase II, randomized, double-blind, multi-center, placebo-controlled trial.

Background: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size.

Design: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.

Circulating Monocyte Subsets Are Associated With Extent of Myocardial Injury but Not With Type of Myocardial Infarction.

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations.

Extracellular vesicle species differentially affect endothelial cell functions and differentially respond to exercise training in patients with chronic coronary syndromes.

Background: Extracellular vesicles are released upon cellular activation and mediate inter-cellular communication. Individual species of extracellular vesicles might have divergent roles in vascular homeostasis and may show different responses to therapies such as exercise training.

Aims: We examine endothelial effects of medium-size and small extracellular vesicles from the same individual with or without chronic coronary syndrome, and in chronic coronary syndrome patients participating in a four-week high-intensity interval training intervention.

Cysteine-Rich Angiogenic Inducer 61 Improves Prognostic Accuracy of GRACE (Global Registry of Acute Coronary Events) 2.0 Risk Score in Patients With Acute Coronary Syndromes.

Background It remains unclear whether the novel biomarker cysteine-rich angiogenic inducer 61 (CCN1) adds incremental prognostic value to the GRACE 2.0 (Global Registry of Acute Coronary Events) risk score and biomarkers high-sensitivity Troponin T, hsCRP (high-sensitivity C-reactive protein), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) in patients with acute coronary syndromes. Methods and Results Patients referred for coronary angiography with a primary diagnosis of acute coronary syndromes were enrolled in the Special Program University Medicine - Acute Coronary Syndromes and Inflammation cohort.

CCN family member 1 (CCN1) is an early marker of infarct size and left ventricular dysfunction in STEMI patients.

Background And Aims: CCN family member 1 (CCN1) has recently been proposed as a novel biomarker of myocardial injury, improving prediction of 30-day and one-year mortality following acute coronary syndromes. Among ST-elevation myocardial infarction (STEMI) patients, we evaluated the utility of CCN1 measured immediately before primary percutaneous coronary intervention (PPCI) as a predictor of two earlier endpoints: final myocardial infarct size and post-infarction left ventricular ejection fraction (LVEF). Furthermore, we evaluated the impact of CCN1 on the discriminatory power of the CADILLAC score.

Improving 1-year mortality prediction in ACS patients using machine learning.

Background: The Global Registry of Acute Coronary Events (GRACE) score is an established clinical risk stratification tool for patients with acute coronary syndromes (ACS). We developed and internally validated a model for 1-year all-cause mortality prediction in ACS patients.

Methods: Between 2009 and 2012, 2'168 ACS patients were enrolled into the Swiss SPUM-ACS Cohort.

Prognostic value of total testosterone levels in patients with acute coronary syndromes.

Background: Endogenous testosterone levels decrease in men with aging. Controversies persist regarding the screening and treatment of low testosterone levels in patients with acute coronary syndromes (ACS).

Methods And Results: Total serum testosterone levels were measured in 1054 men hospitalized for ACS that were part of a Swiss prospective cohort.

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines.

Aims: The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes.

Methods And Results: We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes.

Prognostic value of inflammatory biomarkers and GRACE score for cardiac death and acute kidney injury after acute coronary syndromes.

Aims: The aim of this study was to analyse the role of inflammation and established clinical scores in predicting acute kidney injury (AKI) after acute coronary syndromes (ACS).

Methods And Results: In a prospective multicentre cohort including 2034 patients with ACS undergoing percutaneous coronary intervention, high-sensitivity C-reactive protein (hsCRP), neutrophil count, neutrophil-to-lymphocyte ratio (NL-ratio), and creatinine were measured at the index procedure. AKI (n = 39, defined according to RIFLE criteria) and major cardiovascular and cerebrovascular events were adjudicated after 1 year.