Lipoprotein(a) (Lp(a)) is a low-density lipoprotein (LDL) cholesterol-like particle bound to apolipoprotein(a). Increased Lp(a) levels are an independent, heritable causal risk factor for atherosclerotic cardiovascular disease (ASCVD) as they are largely determined by variations in the Lp(a) gene (LPA) locus encoding apo(a). Lp(a) is the preferential lipoprotein carrier for oxidized phospholipids (OxPL), and its role adversely affects vascular inflammation, atherosclerotic lesions, endothelial function and thrombogenicity, which pathophysiologically leads to cardiovascular (CV) events. Despite this crucial role of Lp(a), its measurement lacks a globally unified method, and, between different laboratories, results need standardization. Standard antilipidemic therapies, such as statins, fibrates and ezetimibe, have a mediocre effect on Lp(a) levels, although it is not yet clear whether such treatments can affect CV events and prognosis. This narrative review aims to summarize knowledge regarding the mechanisms mediating the effect of Lp(a) on inflammation, atherosclerosis and thrombosis and discuss current diagnostic and therapeutic potentials.

Virtual reality (VR) and augmented reality (AR) are two contemporary simulation models that are currently upgrading medical education. VR provides a 3D and dynamic view of structures and the ability of the user to interact with them. The recent technological advances in haptics, display systems, and motion detection allow the user to have a realistic and interactive experience, enabling VR to be ideal for training in hands-on procedures. Consequently, surgical and other interventional procedures are the main fields of application of VR. AR provides the ability of projecting virtual information and structures over physical objects, thus enhancing or altering the real environment. The integration of AR applications in the understanding of anatomical structures and physiological mechanisms seems to be beneficial. Studies have tried to demonstrate the validity and educational effect of many VR and AR applications, in many different areas, employed via various hardware platforms. Some of them even propose a curriculum that integrates these methods. This chapter provides a brief history of VR and AR in medicine, as well as the principles and standards of their function. Finally, the studies that show the effect of the implementation of these methods in different fields of medical training are summarized and presented.

Although evidence indicates the association of lipoprotein(a) [Lp(a)] with atherosclerosis, the link with calcific aortic valve disease (CAVD) is unclear. This systematic review and meta-analysis explores the connection between Lp(a) and aortic valve calcification and stenosis (AVS). We included all relevant studies, indexed in eight databases, up to February 2023. A total of 44 studies (163 139 subjects) were included, with 16 of them being further meta-analysed. Despite considerable heterogeneity, most studies support the relationship between Lp(a) and CAVD, especially in younger populations, with evidence of early aortic valve micro-calcification in elevated-Lp(a) populations. The quantitative synthesis showed higher Lp(a) levels, by 22.63 nmol/L (95% CI: 9.98–35.27), for patients with AVS, while meta-regressing the data revealed smaller Lp(a) differences for older populations with a higher proportion of females. The meta-analysis of eight studies providing genetic data, revealed that the minor alleles of both rs10455872 and rs3798220 LPA gene loci were associated with higher risk for AVS (pooled odds ratio 1.42; 95% CI: 1.34–1.50 and 1.27; 95% CI: 1.09–1.48, respectively). Importantly, high-Lp(a) individuals displayed not only faster AVS progression, by a mean difference of 0.09 m/s/year (95% CI: 0.09–0.09), but also a higher risk of serious adverse outcomes, including death (pooled hazard ratio 1.39; 95% CI: 1.01–1.90). These summary findings highlight the effect of Lp(a) on CAVD initiation, progression and outcomes, and support the early onset of Lp(a)-related subclinical lesions before clinical evidence.

Background: Several studies have revealed the link between Coronavirus Disease 2019 (COVID-19) and endothelial dysfunction. To better understand the global pattern of this relationship, we conducted a meta-analysis on endothelial biomarkers related to COVID-19 severity. Methods: We systematically searched the literature up to March 10, 2021, for studies investigating the association between COVID-19 severity and the following endothelial biomarkers: Intercellular Adhesion Molecule 1 (ICAM-1), Vascular Cell Adhesion Molecule 1 (VCAM-1), E-selectin, P-selectin, Von Willebrand Factor Antigen (VWF-Ag), soluble Thrombomodulin (sTM), Mid-regional pro-adrenomedullin (MR-proADM), and Angiopoietin-2 (Ang-2). Pooled estimates and mean differences (PMD) for each biomarker were reported. Results: A total of 27 studies (n=2213 patients) were included. Critically ill patients presented with higher levels of MR-proADM (PMD: 0.71 nmol/L, 95% CI: 0.22 to 1.20 nmol/L, p=0.02), E-selectin (PMD: 13,32 pg/ml, 95% CI: 4,89 to 21,75 pg/ml, p=0.008), VCAM-1 (PMD: 479 ng/ml, 95% CI: 64 to 896 ng/ml, p=0.03), VWF-Ag (PMD: 110.5 IU/dl, 95% CI: 44.8 to 176.1 IU/dl, p=0.04) and Ang-2 (PMD: 2388 pg/ml, 95% CI: 1121 to 3655 pg/ml, p=0.003), as compared to non-critically ill ones. ICAM-1, P-selectin and thrombomodulin did not differ between the two groups (p>0.05). Conclusion: Endothelial biomarkers display significant heterogeneity in COVID-19 patients, with higher MR-proADM, E-selectin, VCAM-1, VWF-Ag, and Ang-2 levels being associated with increased severity. These findings strengthen the evidence on the key role of endothelial dysfunction in disease progress.

Background: Several studies have linked high Lipoprotein (a) [Lp(a)] concentrations to cardiovascular events, including the formation of Abdominal Aortic Aneurysms (AAA). We review and meta-analyze existing evidence on the association of Lp(a) levels with AAA. Methods: Studies evaluating the link of Lp(a) with AAA, up to December 27th 2021, were identified by a systematic search of PubMed, SCOPUS, and Web of Science databases. The results were qualitatively and quantitatively synthesized according to PRISMA guidelines. Results are presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: A total of 5,078 subjects (1,637 patients with AAA vs. 3,441 controls) from 11 studies were included in the meta-analysis, with a mean age of 69.9 years and a male sex prevalence of 85.8%. Based on the qualitative synthesis, high Lp(a) concentrations are linked to abdominal aortic wall degradation and extracellular matrix disarrangement. Moreover, despite the considerable variability among races, high Lp(a) levels are related to increased AAA risk, independently of race differences. Accordingly, patients with AAA displayed significantly higher Lp(a) levels compared to controls (SMD: 0.86, 95% CI: 0.55-1.17, p<0.001). The outcome was not affected in a sensitivity analysis excluding three outlying studies (SMD: 0.40, 95% CI: 0.22-0.58, p<0.001). Conclusion: This meta-analysis indicates the association between high Lp(a) levels and the presence of AAA, although existing literature presents high heterogeneity. Further studies are needed to standardize Lp(a) measurements and to conclude whether Lp(a) can be used as a sensitive biomarker of early presymptomatic AAA diagnosis.

The cardiovascular implications of non-alcoholic fatty liver disease (NAFLD) have been associated with heart failure with preserved ejection fraction (HFpEF). The purpose of this review was to conduct a bibliographic search regarding the correlation between NAFLD and the echocardiographic parameters of left ventricular diastolic function. A systematic literature search was conducted in PubMed and Embase for original research data reporting on the association of NAFLD with diastolic function markers [E/e′, left atrial volume index (LAVi), left ventricular mass index (LVMi)]. Meta-analysis was performed using the meta and dmetar packages in R studio v.1.4.1106, with p < 0.05 values being considered significant. Results are expressed as the standardized mean difference (SMD) for continuous variables and as the odds ratio (OR) for categorical variables, with respective 95% confidence intervals (CI). Heterogeneity between studies was expressed with index Ι². From the preliminary search, 2619 articles were found from which 31 studies were included in the final statistical analysis. The meta-analysis of 8 studies which reported on the prevalence of diastolic dysfunction showed that it was increased in patients with NAFLD (OR: 2.07, 95% CI 1.24–3.44 with p = 0.01, I²: 80% with p < 0.01). The meta-analysis of 21 studies showed significantly higher E/e′ in NAFLD patients (SMD 1.02, 95% CI 0.43–1.61 with p < 0.001, I²: 97% with p < 0.001). Individuals with NAFLD had increased LAVi (SMD: 0.87, 95% CI 0.38–1.37 with p < 0.001, I²: 96% with p < 0.001) and LVMi (SMD: 0.89, 95% CI 0.31–1.48 with p = 0.003, I²: 100% with p < 0.001). To conclude, in the meta-analysis of 31 observational studies, NAFLD patients were found to have affected left ventricular diastolic function, supporting the hypothesis of NAFLD being associated with HFpEF.