A Method for Analysis of Oxidized Phospholipids from Biological Samples Using Mass Spectrometry.

Oxidized phospholipids (oxPLs) are generated during innate immunity and inflammation, where they play a variety of biological roles, including regulation of autoimmunity and coagulation. Some are generated by enzymatic reactions, leading to stereo- and regiospecificity, while many others can be formed through nonenzymatic oxidation and truncation and can be used as biomarkers of oxidative stress. Mass spectrometry methods have been developed over many years for oxPL analysis, which can provide robust estimations of molecular species and amounts, where standards are available. Here we present a method used for the analysis of enzymatically-generated oxPL (eoxPL), which allows quantification of mono-hydroxy oxylipin-containing species. We also show profiling of many other partially characterized structures in tissue samples and provide typical chromatograms obtained.

In-hospital outcomes of ad hoc versus planned PCI for unprotected left-main disease: An analysis of 8574 cases from British Cardiovascular Intervention Society database 2006-2018.

BACKGROUND: Although data suggests ad hoc percutaneous coronary intervention (PCI) results in similar patient outcomes compared to planned PCI in nonselected patients, data for ad hoc unprotected left main stem PCI (uLMS-PCI) are lacking. AIM: To determine if in-hospital outcomes of uLMS-PCI vary by ad hoc versus planned basis. METHODS: Data were analyzed from all patients undergoing uLMS-PCI in the United Kingdom 2006-2018, and patients grouped into uLMS-PCI undertaken on an ad hoc or a planned basis. Patients who presented with ST-segment elevation, cardiogenic shock, or with an emergency PCI indication were excluded. RESULTS: In total, 8574 uLMS-PCI procedures were undertaken with 2837 (33.1%) of procedures performed on an ad hoc basis. There was a lower likelihood of intervention for stable angina (28.8% vs. 53.8%, p < 0.001) and a higher rate of potent P2Y12 inhibitor use (16.4% vs. 12.1%, p < 0.001) in the ad hoc PCI group compared to the planned PCI group. Patients undergoing uLMS-PCI on an ad hoc basis tended to undergo less complex procedures. Acute procedural complications including slow flow (odds ratio [OR]: 1.70, 95% confidence interval [CI]: 1.01-2.86), coronary dissection (OR: 1.41, 95% CI: 1.12-1.77) and shock induction (OR: 2.80, 95% CI: 1.64-4.78) were more likely in the ad hoc PCI group. In-hospital death (OR: 1.65, 95% CI: 1.19-2.27) and in-hospital major adverse cardiac or cerebrovascular events (OR: 1.50, 95% CI: 1.13-1.98) occurred more frequently in the ad hoc group. In sensitivity analyses, these observations did not differ when several subgroups were separately examined. CONCLUSIONS: Ad hoc PCI for uLMS disease is associated with adverse outcomes compared to planned PCI. These data should inform uLMS-PCI procedural planning.

Thrombin Generation Is Associated With Extracellular Vesicle and Leukocyte Lipid Membranes in Atherosclerotic Cardiovascular Disease.

BACKGROUND: Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples. METHODS: Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics. RESULTS: External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients. CONCLUSIONS: The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.

Aspirin and cancer treatment: systematic reviews and meta-analyses of evidence: for and against.

Aspirin as a possible treatment of cancer has been of increasing interest for over 50 years, but the balance of the risks and benefits remains a point of contention. We summarise the valid published evidence 'for' and 'against' the use of aspirin as a cancer treatment and we present what we believe are relevant ethical implications. Reasons for aspirin include the benefits of aspirin taken by patients with cancer upon relevant biological cancer mechanisms. These explain the observed reductions in metastatic cancer and vascular complications in cancer patients. Meta-analyses of 118 observational studies of mortality in cancer patients give evidence consistent with reductions of about 20% in mortality associated with aspirin use. Reasons against aspirin use include increased risk of a gastrointestinal bleed though there appears to be no valid evidence that aspirin is responsible for fatal gastrointestinal bleeding. Few trials have been reported and there are inconsistencies in the results. In conclusion, given the relative safety and the favourable effects of aspirin, its use in cancer seems justified, and ethical implications of this imply that cancer patients should be informed of the present evidence and encouraged to raise the topic with their healthcare team.

Phosphatidylthreonine is a procoagulant lipid detected in human blood and elevated in coronary artery disease.

Aminophospholipids (aPL) such as phosphatidylserine are essential for supporting the activity of coagulation factors, circulating platelets, and blood cells. Phosphatidylthreonine (PT) is an aminophospholipid previously reported in eukaryotic parasites and animal cell cultures, but not yet in human tissues. Here, we evaluated whether PT is present in blood cells and characterized its ability to support coagulation. Several PT molecular species were detected in human blood, washed platelets, extracellular vesicles, and isolated leukocytes from healthy volunteers using liquid chromatography-tandem mass spectrometry. The ability of PT to support coagulation was demonstrated in vitro using biochemical and biophysical assays. In liposomes, PT supported prothrombinase activity in the presence and absence of phosphatidylserine. PT nanodiscs strongly bound FVa and lactadherin (nM affinity) but poorly bound prothrombin and FX, suggesting that PT supports prothrombinase through recruitment of FVa. PT liposomes bearing tissue factor poorly generated thrombin in platelet poor plasma, indicating that PT poorly supports extrinsic tenase activity. On platelet activation, PT is externalized and partially metabolized. Last, PT was significantly higher in platelets and extracellular vesicle from patients with coronary artery disease than in healthy controls. In summary, PT is present in human blood, binds FVa and lactadherin, supports coagulation in vitro through FVa binding, and is elevated in atherosclerotic vascular disease. Our studies reveal a new phospholipid subclass, that contributes to the procoagulant membrane, and may support thrombosis in patients at elevated risk.

Predictors of 1- and 12-month mortality in bifurcation coronary intervention: a contemporary perspective.

Aim: Bifurcation-PCI is performed frequently, although without extensive evidence to back up a definitive solution for its complexity. We set out to identify factors associated with 1- and 12-month mortality after bifurcation-PCI between 2017 and 2021 in our tertiary center in Wales, UK. Results: Of 732 bifurcation PCI cases (mean age 69; 25% female), 67% were in ACS, 42% were left main PCI and 25.3% involved two-stent strategy. 30-day and 12-month mortality were 1.9 and 8.2%, respectively. Age, diabetes, smoking and renal failure are associated with mortality after bifurcation-PCI, while the choice between provisional and 2-stent strategies did not impact mortality/TLR. Conclusion: Awareness of 'real-world' outcomes of bifurcation-PCI should be used for appropriate patient selection, technique planning and procedural consent.

The impact of adopting low-molecular-weight heparin in place of aspirin as routine thromboprophylaxis for patients with hip fracture.

PURPOSE OF THE STUDY: In 2010, the National Institute for Health and Care Excellence (NICE) recommended the use of anticoagulants rather than aspirin as pharmacological thromboprophylaxis after hip fracture. We examine the impact of implementing this change in guidance on the clinical incidence of deep vein thrombosis (DVT). STUDY DESIGN: Demographic, radiographic and clinical data were retrospectively collected for 5039 patients admitted to a single tertiary centre in the UK for hip fracture between 2007 and 2017. We calculated rates of lower-limb DVT and examined the impact of the June 2010 change of departmental policy, from use of aspirin to use of low-molecular-weight heparins (LMWH) in hip fracture patients. RESULTS: Doppler scans were performed in 400 patients in the 180 days after a hip fracture, and identified 40 ipsilateral and 14 contralateral DVTs (p<0.001). The rate of DVT reduced significantly following the 2010 change in departmental policy from aspirin to LMWH in these patients (1.62% vs 0.83%, p<0.05). CONCLUSIONS: The rate of clinical DVT halved following the change from aspirin to LMWH for pharmacological thromboprophylaxis, but the number needed to treat was 127. A figure of <1% for the incidence of clinical DVT in a unit that routinely uses LMWH monotherapy following hip fracture provides a context for discussions of alternative strategies, and for power calculations for future research. These figures are important to policy makers and to researchers as they will inform the design of the comparative studies on thromboprophylaxis agents for which NICE has called.

Stent failure: the diagnosis and management of intracoronary stent restenosis.

INTRODUCTION: Despite advances in stent technology for percutaneous coronary intervention (PCI) in the treatment of coronary disease, these procedures can be complicated by stent failure manifested as intracoronary stent restenosis (ISR). Even with advances in stent technology and medical therapy, this complication is reported to affect around 10% of all percutaneous coronary intervention (PCI) procedures. Depending on stent type (drug-eluting versus bare metal), ISR has subtle differences in mechanism and timing and offers different challenges in diagnosing etiology and subsequent treatment options. AREAS COVERED: This review will be visiting the definition, pathophysiology, and risk factors of ISR. EXPERT OPINION: The evidence behind management options has been illustrated with the aid of real life clinical cases and summarized in a proposed management algorithm.

Temporal Trends in In-Hospital Outcomes Following Unprotected Left-Main Percutaneous Coronary Intervention: An Analysis of 14 522 Cases From British Cardiovascular Intervention Society Database 2009 to 2017.

BACKGROUND: Percutaneous coronary intervention (PCI) is increasingly used as a treatment option for unprotected left main stem artery (unprotected left main stem percutaneous intervention) disease. However, whether patient outcomes have improved over time is uncertain. METHODS: Using the United Kingdom national PCI database, we studied all patients undergoing unprotected left main stem percutaneous intervention between 2009 and 2017. We excluded patients who presented with ST-segment-elevation, cardiogenic shock, and with an emergency indication for PCI. RESULTS: Between 2009 and 2017, in the study-indicated population, 14 522 unprotected left main stem percutaneous intervention procedures were performed. Significant temporal changes in baseline demographics were observed with increasing patient age and comorbid burden. Procedural complexity increased over time, with the number of vessels treated, bifurcation PCI, number of stents used, and use of intravascular imaging and rotational atherectomy increased significantly through the study period. After adjustment for baseline differences, there were significant temporal reductions in the occurrence of peri-procedural myocardial infarction (P<0.001 for trend), in-hospital major adverse cardiac or cerebrovascular events (P<0.001 for trend), and acute procedural complications (P<0.001 for trend). In multivariable analysis examining the associates of in-hospital major adverse cardiac or cerebrovascular events, while age per year (odds ratio, 1.02 [95% CIs, 1.01-1.03]), female sex (odds ratio, 1.47 [1.19-1.82]), 3 or more stents (odds ratio, 1.67 [05% [1.02-2.67]), and patient comorbidity were associated with higher rates of in-hospital major adverse cardiac or cerebrovascular events, by contrast use of intravascular imaging (odds ratio, 0.56 [0.45-0.70]), and year of PCI (odds ratio, 0.63 [0.46-0.87]) were associated with lower rates of in-hospital major adverse cardiac or cerebrovascular events. CONCLUSIONS: Despite trends for increased patient and procedural complexity, in-hospital patient outcomes have improved after unprotected left main stem percutaneous intervention over time.

Predictors of 30-day and 12-month mortality in left main stem percutaneous coronary intervention 2016-2020: A study from two UK centers.

INTRODUCTION: Left main stem percutaneous coronary intervention (LMS-PCI) is a complex high-risk procedure which can be performed as an alternative to coronary artery bypass graft (CABG) procedure in surgical turn-down patients or where there is equipoise in percutaneous versus surgical strategies. Current guidelines suggest that PCI is an appropriate alternative to CABG in patients with unprotected LMS disease and low SYNTAX score. However, "real world" data on outcomes of LMS-PCI remain limited. This study aims to quantify and determine predictors of mortality following LMS-PCI. METHODS: Using local coronary angioplasty registries from two UK centers, all LMS-PCI cases were identified from 2016 to 2020. Descriptive statistics and multivariate logistic regressions were used to examine the association between baseline and procedural characteristics with 30-day and 12-month mortality. RESULTS: We identified 484 cases of LMS-PCI between 2016 and 2020. There was a year-on-year increase in the number of LMS-PCI, the highest being in 2020. Covariates associated with higher 30-day mortality were age (OR 1.07, 95% CI: 1.02-1.12) and shock preprocedure (OR 23.88, 95% CI: 7.90-72.20). Covariates associated with higher 12-month mortality were age (OR 1.04, 95% CI: 1.01-1.08), acute coronary syndrome (ACS) (OR 2.50, 95% CI: 1.08-5.80), renal disease (OR 5.24, 95% CI: 1.47-18.68), and shock preprocedure (OR 7.93, 95% CI: 3.30-19.05). Overall, 30-day and 12-month mortality in this contemporary data set were 9.5% and 16.7%, respectively, with significantly lower rates in elective cases (p < 0.01). CONCLUSIONS: Older age and cardiogenic shock preprocedure were associated with increased 30-day mortality after LMS-PCI. Twelve-month mortality was associated with older age, ACS presentation, preexisting renal disease, and cardiogenic shock preprocedure.

Aspirin and cancer: biological mechanisms and clinical outcomes.

Evidence on aspirin and cancer comes from two main sources: (1) the effect of aspirin upon biological mechanisms in cancer, and (2) clinical studies of patients with cancer, some of whom take aspirin. A series of systematic literature searches identified published reports relevant to these two sources. The effects of aspirin upon biological mechanisms involved in cancer initiation and growth appear to generate reasonable expectations of effects upon the progress and mortality of cancer. Clinical evidence on aspirin appears overall to be favourable to the use of aspirin, but evidence from randomized trials is limited, and inconsistent. The main body of evidence comes from meta-analyses of observational studies of patients with a wide range of cancers, about 25% of whom were taking aspirin. Heterogeneity is large but, overall, aspirin is associated with increases in survival and reductions in metastatic spread and vascular complications of different cancers. It is important that evaluations of aspirin used as an adjunct cancer treatment are based upon all the available relevant evidence, and there appears to be a marked harmony between the effects of aspirin upon biological mechanisms and upon the clinical progress of cancer.

The Impact of Intracoronary Imaging on PCI Outcomes in Cases Utilising Rotational Atherectomy: An Analysis of 8,417 Rotational Atherectomy Cases from the British Cardiovascular Intervention Society Database.

Introduction: There is increasing evidence supporting the use of intracoronary imaging to optimize the outcomes of percutaneous coronary intervention (PCI). However, there are no studies examining the impact of imaging on PCI outcomes in cases utilising rotational atherectomy (RA-PCI). Our study examines the determinants and outcomes of using intracoronary imaging in RA-PCI cases including 12-month mortality. Methods: Using the British Cardiac Intervention Society database, data were analysed on all RA-PCI procedures in the UK between 2007 and 2014. Descriptive statistics and multivariate logistic regressions were used to examine baseline, procedural, and outcome associations with intravascular imaging. Results: Intracoronary imaging was used in 1,279 out of 8,417 RA-PCI cases (15.2%). Baseline covariates associated with significantly more imaging use were number of stents used, smoking history, previous CABG, pressure wire use, proximal LAD disease, laser use, glycoprotein inhibitor use, cutting balloons, number of restenosis attempted, off-site surgery, and unprotected left main stem (uLMS) PCI. Adjusted rates of in-hospital major adverse cardiac/cerebrovascular events (IH-MACCE), its individual components (death, peri-procedural MI, stroke, and major bleed), or 12-month mortality were not significantly altered by the use of imaging in RA-PCI. However, subgroup analysis demonstrated a signal towards reduction in 12-month mortality in uLMS RA-PCI cases utilising intracoronary imaging (OR 0.67, 95% CI 0.44-1.03). Conclusions: Intracoronary imaging use during RA-PCI is associated with higher risk of baseline and procedural characteristics. There were no differences observed in IH-MACCE or 12-month mortality with intracoronary imaging in RA-PCI.

The role of procoagulant phospholipids on the surface of circulating blood cells in thrombosis and haemostasis.

Phospholipids (PLs) are found in all cell types and are required for structural support and cell activation signalling pathways. In resting cells, PLs are asymmetrically distributed throughout the plasma membrane with native procoagulant aminophospholipids (aPLs) being actively maintained in the inner leaflet of the membrane. Upon platelet activation, aPLs rapidly externalize to the outer leaflet and are essential for supporting the coagulation cascade by providing binding sites for factors in the cell-based model. More recent work has uncovered a role for enzymatically oxidized PLs (eoxPLs) in facilitating coagulation, working in concert with native aPLs. Despite this, the role of aPLs and eoxPLs in thrombo-inflammatory conditions, such as arterial and venous thrombosis, has not been fully elucidated. In this review, we describe the biochemical structures, distribution and regulation of aPL externalization and summarize the literature on eoxPL generation in circulating blood cells. We focus on the currently understood role of these lipids in mediating coagulation reactions in vitro, in vivo and in human thrombotic disease. Finally, we highlight gaps in our understanding in how these lipids vary in health and disease, which may place them as future therapeutic targets for the management of thrombo-inflammatory conditions.

The SARS-CoV2 envelope differs from host cells, exposes procoagulant lipids, and is disrupted in vivo by oral rinses.

The lipid envelope of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an essential component of the virus; however, its molecular composition is undetermined. Addressing this knowledge gap could support the design of antiviral agents as well as further our understanding of viral-host protein interactions, infectivity, pathogenicity, and innate immune system clearance. Lipidomics revealed that the virus envelope comprised mainly phospholipids (PLs), with some cholesterol and sphingolipids, and with cholesterol/phospholipid ratio similar to lysosomes. Unlike cellular membranes, procoagulant amino-PLs were present on the external side of the viral envelope at levels exceeding those on activated platelets. Accordingly, virions directly promoted blood coagulation. To investigate whether these differences could enable selective targeting of the viral envelope in vivo, we tested whether oral rinses containing lipid-disrupting chemicals could reduce infectivity. Products containing PL-disrupting surfactants (such as cetylpyridinium chloride) met European virucidal standards in vitro; however, components that altered the critical micelle concentration reduced efficacy, and products containing essential oils, povidone-iodine, or chlorhexidine were ineffective. This result was recapitulated in vivo, where a 30-s oral rinse with cetylpyridinium chloride mouthwash eliminated live virus in the oral cavity of patients with coronavirus disease 19 for at least 1 h, whereas povidone-iodine and saline mouthwashes were ineffective. We conclude that the SARS-CoV-2 lipid envelope i) is distinct from the host plasma membrane, which may enable design of selective antiviral approaches; ii) contains exposed phosphatidylethanolamine and phosphatidylserine, which may influence thrombosis, pathogenicity, and inflammation; and iii) can be selectively targeted in vivo by specific oral rinses.

Defining Percutaneous Coronary Intervention Complexity and Risk: An Analysis of the United Kingdom BCIS Database 2006-2016.

OBJECTIVES: The authors used the BCIS (British Cardiovascular Intervention Society) database to define the factors associated with percutaneous coronary intervention (PCI) procedural complexity. BACKGROUND: Complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) is an emerging concept that is poorly defined. METHODS: The BCIS (British Cardiovascular Intervention Society) database was used to study all PCI procedures in the United Kingdom 2006-2016. A multiple logistic regression model was developed to identify variables associated with in-hospital major adverse cardiac or cerebrovascular events (MACCE) and to construct a CHIP score. The cumulative effect of this score on patient outcomes was examined. RESULTS: A total of 313,054 patients were included. Seven patient factors (age ≥80 years, female sex, previous stroke, previous myocardial infarction, peripheral vascular disease, ejection fraction <30%, and chronic renal disease) and 6 procedural factors (rotational atherectomy, left main PCI, 3-vessel PCI, dual arterial access, left ventricular mechanical support, and total lesion length >60 mm) were associated with increased in-hospital MACCE and defined as CHIP factors. The mean CHIP score/case for all PCIs increased significantly from 1.06 ± 1.32 in 2006 to 1.49 ± 1.58 in 2016 (P < 0.001 for trend). A CHIP score of 5 or more was present in 2.5% of procedures in 2006 increasing to 5.3% in 2016 (P < 0.001 for trend). Overall in-hospital MACCE was 0.6% when the CHIP score was 0 compared with 1.2% with any CHIP factor present (P < 0.001). As the CHIP score increased, an exponential increase in-hospital MACCE was observed. The cumulative MACCE for procedures associated with a CHIP score 4+ or above was 3.2%, and for a CHIP score 5+ was 4.4%. All other adverse clinical outcomes were more likely as the CHIP score increased. CONCLUSIONS: Seven patient factors and 6 procedural factors were associated with adverse in-hospital MACCE and defined as CHIP factors. Use of a CHIP score might be a future target for risk modification.

Endoscopy findings in patients on dual antiplatelet therapy following percutaneous coronary intervention.

PURPOSE OF STUDY: This study examines the associations between dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) and gastrointestinal bleeding (GIB), to explore possible predictors of outcomes. STUDY DESIGN: Retrospective analysis of 3342 patients who underwent PCI between 1 August 2011 and 31 December 2018 in a single centre was carried out. Oesophagogastroduodenoscopies (OGDs) for patients 12 months post-PCI were analysed. RESULTS: Blood loss occurred in 2% of all (3342) patients post-PCI within 12 months. 128 patients (63% male, mean age (SD) of 69.8 (10) years) who had PCI subsequently underwent an OGD within 12 months of the index PCI procedure. GIB occurred within the first 30 days of DAPT in 36% (n=13/36) of cases. There were no thrombotic events associated with cessation of one antiplatelet agent. Increased age, haemoglobin (Hb) ≤109 g/L and Glasgow-Blatchford score ≥8 were associated with increased 12-month mortality. An Hb drop of ≥30 g/L was a sensitive and specific marker for significant pathology and evidence of bleeding on OGD (sensitivity=0.83, specificity=0.81). CONCLUSIONS: GIB bleeding occurred infrequently in the patients post-PCI on DAPT. Risk assessment scores (such as Glasgow-Blatchford and Rockall scores) are useful tools to assess the urgency of OGD and need for endoscopic therapy.

Comparison of an e-learning package with lecture-based teaching in the management of supraventricular tachycardia (SVT): a randomised controlled study.

INTRODUCTION: To compare the impact of an e-learning package with theoretical teaching on the ability of both graduate and undergraduate medical students to learn the management of supraventricular tachycardia. METHODS: We conducted a randomised, controlled, study at two Welsh medical schools. Participants were graduate-entry and undergraduate medical students, who were randomised (in a 1:1 ratio) to either 1 hour of training using an e-learning package or an hour of lecture-based teaching. The outcome was a comparison, within each group and between groups, of median scores achieved in assessments of knowledge through completion of preintervention, immediate post intervention and 2 weeks postintervention questionnaires. RESULTS: Of the 97 participants available for randomisation, 47 underwent teaching using the e-learning package and 50 were taught in the lecture group. Median scores were higher in the e-learning package group than the lecture group, though this difference was not statistically significant (4.00 vs 3.00; p=0.08) immediately after intervention. At 2 weeks post intervention, median scores in the e-learning package group were significantly higher than the median scores in the lecture group (4.00 vs 3.00; p=0.002). This was despite a subanalysis of the results demonstrating that subjects in the lecture group reported having seen more cases compared with those in the e-learning group (32 vs 13; p=0.002). Further, there was a significant fall in score over 2 weeks in the group receiving lecture-based teaching, but no such decrease in those using the e-learning package. CONCLUSION: E-learning seems to be the preferred method of learning and the method that confers longer retention time for both postgraduate and undergraduate medical students.

Relationship between lipoproteins, thrombosis, and atrial fibrillation.

The prothrombotic state in atrial fibrillation (AF) occurs as a result of multifaceted interactions, known as Virchow's triad of hypercoagulability, structural abnormalities, and blood stasis. More recently, there is emerging evidence that lipoproteins are implicated in this process, beyond their traditional role in atherosclerosis. In this review, we provide an overview of the various lipoproteins and explore the association between lipoproteins and AF, the effects of lipoproteins on haemostasis, and the potential contribution of lipoproteins to thrombogenesis in AF. There are several types of lipoproteins based on size, lipid composition, and apolipoprotein category, namely: chylomicrons, very low-density lipoprotein, low-density lipoprotein (LDL), intermediate-density lipoprotein, and high-density lipoprotein. Each of these lipoproteins may contain numerous lipid species and proteins with a variety of different functions. Furthermore, the lipoprotein particles may be oxidized causing an alteration in their structure and content. Of note, there is a paradoxical inverse relationship between total cholesterol and LDL cholesterol (LDL-C) levels, and incident AF. The mechanism by which this occurs may be related to the stabilizing effect of cholesterol on myocardial membranes, along with its role in inflammation. Overall, specific lipoproteins may interact with haemostatic pathways to promote excess platelet activation and thrombin generation, as well as inhibiting fibrinolysis. In this regard, LDL-C has been shown to be an independent risk factor for thromboembolic events in AF. The complex relationship between lipoproteins, thrombosis and AF warrants further research with an aim to improve our knowledge base and contribute to our overall understanding of lipoprotein-mediated thrombosis.