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Background: The majority of those diagnosed with aortic aneurysm in the UK are older, multi-morbid patients. Decision-making as to who may benefit from intervention (open or endovascular aneurysm repair) is highly variable across the NHS (as is the mode of intervention), in part because there are no detailed guidelines or consensus on preoperative assessment. Thus, there is likely to be significant variation in the pre-operative assessment and optimisation of these patients. Methods: A survey was designed to understand current practice and attitudes of vascular surgeons and vascular anaesthetists in the UK regarding preoperative assessment and optimisation of patients undergoing elective aortic aneurysm repair. The survey was reviewed and validated by an expert panel, then distributed electronically to all vascular surgical and vascular anaesthetic leads in the UK. Results: Overall, the response rate was 68%. The responses were varied between surgeons and anaesthetists, with differences reported in the preoperative assessment and optimisation of patients, the approach to shared decision-making, and the perioperative pathway. Conclusions: Despite initiatives such as Getting It Right First Time (GIRFT) and National Institute for Health and Care Excellence (NICE) guidelines, variation still exists between centres with some differences in opinion observed between surgeons and anaesthetists. These differences may be leading to duplication of work in the perioperative pathway, inconsistencies in how risk is assessed and communicated with consequent variation in patient care. Addressing these issues requires awareness and implementation of existing guidelines, transdisciplinary working, efficient data-driven pathways, and structured aortic aneurysm multi-disciplinary team to promote meaningful shared decision-making. [ABSTRACT FROM AUTHOR]

Although a growing number of studies have attempted to uncover the relationship between plasma lipids and the risk of aortic aneurysm (AA), it remains controversial. Meanwhile, the relationship between plasma lipids and the risk of aortic dissection (AD) has not been reported on. We conducted a two-sample Mendelian randomization (MR) analysis to evaluate the potential relationship between genetically predicted plasma levels of lipids and the risk of AA and AD. Summary data on the relationship between genetic variants and plasma lipids were obtained from the UK Biobank and Global Lipids Genetics Consortium studies, and data on the association between genetic variants and AA or AD were taken from the FinnGen consortium study. Inverse-variance weighted (IVW) and four other MR analysis methods were used to evaluate effect estimates. Results showed that genetically predicted plasma levels of low-density lipoprotein cholesterol, total cholesterol, or triglycerides were positively correlated with the risk of AA, and plasma levels of high-density lipoprotein cholesterol were negatively correlated with the risk of AA. However, no causal relationship was found between elevated lipid levels and the risk of AD. Our study revealed a causal relationship between plasma lipids and the risk of AA, while plasma lipids had no effect on the risk of AD. [ABSTRACT FROM AUTHOR]

Background: Sweden and the UK invite all 65-year-old men to a population-based ultrasound-based screening program to detect abdominal aortic aneurysms (AAA). First-degree relatives of patients with AAA are reported to have an increased risk to develop AAA, both women and men, but are not invited to screening. The "Detecting AAA in First Degree Relatives to AAA patients" (DAAAD) was designed to detect the true prevalence in adult offspring to AAA patients and to evaluate if national registries could be used for identification of index persons and their adult children with a high risk for the disease. The aim of this study is to summarize the design and methodology for this registry-based study. Methods: The study is based on a registry-based extraction and identification of a risk group in the population with a subsequent identification of their adult offspring. The targeted risk group suffers a heredity for a potentially lethal disease, AAA (n = 750) and matched control group without heredity for AAA is also identified and invited (n = 750). The participation rate in the population-based AAA screening program for men is 75% regionally. This population is younger and have a lower prevalence. A participation rate of 65% is considered clinically adequate. For the DAAAD study, a stratified analysis of the primary outcome, prevalence, will be performed for women and men separately. Two other planned projects are based on the material: firstly, evaluation of the anxiety for disease and health-related quality of life (HRQoL) and, secondly, the cost-effectiveness of the study. Discussion: In conclusion, this feasibility study will be instrumental in supporting the development of a possible new model to invite persons with high risk to develop hereditary rare diseases. To our knowledge, this is a unique, safe, and most likely to be a cost-efficient model to invite targeted risk groups for selected screening. If the study design and the results are shown to be cost-effective at the detected participation rate and prevalence, it should be further evaluated and adopted to a national screening program. The model also invites both women and men, which is unique for this specific patient group, considering that all population-based screening programs only include men. Trial registration: This trial is registered at the website of Clinical Trials. ClinicalTrials.gov identifier, NCT4623268 [ABSTRACT FROM AUTHOR]

BACKGROUND. Spontaneous coronary artery dissection (SCAD) is a cause of myocardial infarction, especially in younger women without cardiovascular risk factors. Patient management and diagnostics are still largely based on retrospective and observational studies. Most patients with SCAD report chest pain and have elevated biomarkers with ECG findings. SCAD can lead to cardiogenic shock, ventricular arrhythmias and cardiac arrest, and is commonly associated with fibromuscular dysplasia (FMD). Genetic associations are still in their infancy with this disease process. METHODS. An Invitae 29 gene aortopathy panel was performed on a mother with a thoracic aortic aneurysm and her daughter who presented with SCAD and was noted to have FMD. RESULTS. The patient and her mother were both noted to have a heterozygous mutation of the Biglycan (BGN) gene (Variant c.1030T > G (p.Tyr344His)) of undetermined significance. An extensive literature review was performed, including a review of the UK Biobank. This is the first case to our knowledge showing a possible link between the BGN mutation and SCAD/FMD. CONCLUSIONS. The BGN mutation has been recognized to be correlated with aortic aneurysm and aortic dissection. It has not yet been explored to be associated with SCAD/FMD. This paper highlights the potential link between the BGN gene and SCAD/FMD. Further research looking at this association is warranted. [ABSTRACT FROM AUTHOR]

Endovascular aortic aneurysm repair has changed the management of patients affected by this condition, offering a minimally invasive solution with satisfactory outcomes. Constant evolution of this technology has expanded the use of endovascular devices to more complex cases. The purpose of this review article is to describe the current strategies, guidance, and technologies in this field, with a particular focus on practices in the United Kingdom. [ABSTRACT FROM AUTHOR]

Background: Thoracic aortic aneurysm (TAA) and abdominal aortic aneurysm (AAA) are known to have a strong genetic component. Methods and results: In a genome-wide association study (GWAS) using the UK Biobank, we analyzed the genomes of 1,363 individuals with AAA compared to 27,260 age, ancestry, and sex-matched controls (1:20 case:control study design). A similar analysis was repeated for 435 individuals with TAA compared to 8,700 controls. Polymorphism with minor allele frequency (MAF) >0.5% were evaluated. We identified novel loci near LINC01021, ATOH8 and JAK2 genes that achieved genome-wide significance for AAA (p-value <5x10-8), in addition to three known loci. For TAA, three novel loci in CTNNA3, FRMD6 and MBP achieved genome-wide significance. There was no overlap in the genes associated with AAAs and TAAs. Additionally, we identified a linkage group of high-frequency variants (MAFs ~10%) encompassing FBN1, the causal gene for Marfan syndrome, which was associated with TAA. In FinnGen PheWeb, this FBN1 haplotype was associated with aortic dissection. Finally, we found that baseline bradycardia was associated with TAA, but not AAA. Conclusions: Our GWAS found that AAA and TAA were associated with distinct sets of genes, suggesting distinct underlying genetic architecture. We also found association between baseline bradycardia and TAA. These findings, including JAK2 association, offer plausible mechanistic and therapeutic insights. We also found a common FBN1 linkage group that is associated with TAA and aortic dissection in patients who do not have Marfan syndrome. These FBN1 variants suggest shared pathophysiology between Marfan disease and sporadic TAA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the safety and cost-effectiveness of lengthening the time between surveillance ultrasound scans in the UK Abdominal Aortic Aneurysm (AAA) Screening Programme.Methods: A discrete event simulation model was used to evaluate the cost-effectiveness of AAA screening for men aged 65, comparing current surveillance intervals to 6 alternative surveillance interval strategies that lengthened the time between surveillance scans for 1 or more AAA size categories. The model considered clinical events and costs incurred over a 30-year time horizon and the cost per quality-adjusted life year (QALY). The model adopted the National Health Service perspective and discounted future costs and benefits at 3.5%.Results: Compared with current practice, alternative surveillance strategies resulted in up to a 4% reduction in the number of elective AAA repairs but with an increase of up to 1.6% in the number of AAA ruptures and AAA-related deaths. Alternative strategies resulted in a small reduction in QALYs compared to current practice but with reduced costs. Two strategies that lengthened surveillance intervals in only very small AAAs (3.0-3.9 cm) provided, at a cost-effectiveness threshold of £20 000 per QALY, the highest positive incremental net benefit. There was negligible chance that current practice is the most cost-effective strategy at any threshold below £40 000 per QALY.Conclusions: Lengthening surveillance intervals in the UK Abdominal Aortic Aneurysm Screening Programme, especially for small AAA, can marginally reduce the incremental cost per QALY of the program. Nevertheless, whether the cost savings from refining surveillance strategies justifies a change in clinical practice is unclear. [ABSTRACT FROM AUTHOR]

Accurate risk assessment of an individuals' propensity to develop cardiovascular diseases (CVDs) is crucial for the prevention of these conditions. Numerous published risk prediction models used for CVD risk assessment are based on conventional risk factors and include only a limited number of biomarkers. The addition of novel biomarkers can boost the discriminative ability of risk prediction models for CVDs with different pathogenesis. The present study reports the development of risk prediction models for a range of heterogeneous CVDs, including coronary artery disease (CAD), stroke, deep vein thrombosis (DVT), and abdominal aortic aneurysm (AAA), as well as for Type 2 diabetes mellitus (DM2), a major CVD risk factor. In addition to conventional risk factors, the models incorporate various blood biomarkers and comorbidities to improve both individual and population stratification. An automatic variable selection approach was developed to generate the best set of explanatory variables for each model from the initial panel of risk factors. In total, up to 254,220 UK Biobank participants (ranging from 215,269 to 254,220 for different CVDs and DM2) were included in the analyses. The derived prediction models utilizing Cox proportional hazards regression achieved consistent discrimination performance (C-index) for all diseases: CAD, 0.794 (95% CI, 0.787–0.801); DM2, 0.909 (95% CI, 0.903–0.916); stroke, 0.778 (95% CI, 0.756–0.801); DVT, 0.743 (95% CI, 0.737–0.749); and AAA, 0.893 (95% CI, 0.874–0.912). When validated on various subpopulations, they demonstrated higher discrimination in healthier and middle-age individuals. In general, calibration of a five-year risk of developing the CVDs and DM2 demonstrated incremental overestimation of disease-related conditions amongst the highest decile of risk probabilities. In summary, the risk prediction models described were validated with high discrimination and good calibration for several CVDs and DM2. These models incorporate multiple shared predictor variables and may be integrated into a single platform to enhance clinical stratification to impact health outcomes. [ABSTRACT FROM AUTHOR]

Objective. To evaluate the associations between GCA and vascular diseases and other comorbidities in patients with GCA compared with non-vasculitis patients. Methods. Using the UK-based Clinical Practice Research Datalink we identified 9778 newly diagnosed GCA patients in 1990-2014, and up to 10 non-vasculitis patients randomly matched to each case on age, sex, practice and years of history before cohort entry. We compared the distributions of 9 different preexisting vascular diseases and 11 other comorbidities, and risks of incident vascular diseases and other comorbidities after cohort entry between GCA and non-vasculitis patients. Results. Patients with GCA were more likely to have a history of vascular diseases and other comorbidities except myocardial infarction, type 2 diabetes, obesity and cancer, compared with non-vasculitis patients. Patients with GCA had increased risks for all types of incident vascular disease compared with non-vasculitis patients: adjusted hazard ratios were 1.57 (95% CI: 1.36, 1.82) for myocardial infarc-tion, 1.41 (95% CI: 1.29, 1.55) for stroke, 1.75 (95% CI: 1.49, 2.06) for peripheral vascular disease, 1.98 (95% CI: 1.50, 2.62) for aortic aneurysm and 2.03 (95% CI: 1.77, 2.33) for venous thromboembolism. Patients with GCA also had increased risks for other incident comorbidities (type 2 diabetes, depression, etc.), but not for cancer. Conclusion. Patients with GCA had more prior vascular diseases and other comorbidities before the diagnosis and they also had increased risks for incident vascular diseases and many other incident comorbidities after the diagnosis compared with non-vasculitis population. [ABSTRACT FROM AUTHOR]

• 11 overlapping genes associated with AAD were identified by integrative analysis. • Dysregulated gene expression plays an important role in AAD risk. • Extracellular matrix organization plays a vital role in AAD development. Aortic aneurysm and dissection (AAD) are a set of life-threatening diseases. This study aimed to investigate the genetic mechanisms of AAD by integrating transcriptome-wide association study (TWAS) and mRNA expression profile. The genome-wide association study (GWAS) summary data of AAD was obtained from the UK Biobank, which contains 452,264 White British individuals, including 1470 AAD patients. The TWAS analysis was performed by integrating expression quantitative trait loci (eQTL) data of aorta and the GWAS dataset of AAD using the FUSION software. The TWAS significant genes and differentially expressed genes (DEGs) identified by mRNA expression profile of aortic dissection were integrated to find common genes and biological process. For TWAS significant genes, protein–protein interaction (PPI) network analysis was further conducted based on STRING database. TWAS identified 423 genes with P < 0.05. After comparing the results of TWAS and mRNA expression profile, 11 overlapping genes (PDE8B, IKBKE, HMGA1, PKM, CHST1, DUS3L, S100A16, PTGS1, RAB38, PDLIM5, NOL6) and 15 common gene ontology (GO) terms (including extracellular matrix organization, external encapsulating structure organization, cell-substrate adhesion, actin filament-based process, focal adhesion, protein kinase activity) were identified. 9 hub genes of the TWAS results were identified via PPI network analysis, including RPS9, RPS18, RSRC1, DNAJC3, HBS1L, PRKCA, NCAM1, ITGB3, FTSJ3. Multiple candidate genes and biological processes associated with AAD were identified by the present integrative study of TWAS and mRNA expression profile. Further studies are needed to elucidate the genetic mechanisms of AAD. [ABSTRACT FROM AUTHOR]

Background--Fenestrated endovascular repair of abdominal aortic aneurysms has been proposed as an alternative to open surgery for juxtarenal and pararenal abdominal aortic aneurysms. At present, the evidence base for this procedure is predominantly limited to single-center or single-operator series. The aim of this study was to present nationwide early results of fenestrated endovascular repair in the United Kingdom. Methods and Results--All patients who underwent fenestrated endovascular repair between January 2007 and December 2010 at experienced institutions in the United Kingdom(>10 procedures) were retrospectively studied by use of the GLOBALSTAR database. Site-reported data relating to patient demographics, aneurysm morphology, procedural details, and outcome were recorded. Data from 318 patients were obtained from 14 centers. Primary procedural success was achieved in 99% (316/318); perioperative mortality was 4.1%, and intraoperative target vessel loss was observed in 5 of 889 target vessels (0.6%). The early reintervention (<30 days) rate was 7% (22/318). There were 11 deaths during follow-up; none were aneurysm-related. Survival by Kaplan-Meier analysis was 94% (SE 0.01), 91% (0.02), and 89% (0.02) at 1,2, and 3 years, respectively. Freedom from target vessel loss was 93% (0.02), 91% (0.02), and 85% (0.06), and freedom from late secondary intervention (>30 days) was 90% (0.02), 86% (0.03), and 70% (0.08) at 1, 2, and 3 years. Conclusions--In this national sample, fenestrated endovascular repair has been performed with a high degree of technical and clinical success. Late survival and target vessel patency are satisfactory. These results support continued use and evaluation of this technique for juxtarenal aneurysms, but illustrate the need for a more robust evidence base. [ABSTRACT FROM AUTHOR]

Focuses on various ways in treating abdominal aortic aneurysms in Great Britain. List of diagnostic technique in detecting aneurysms; Process of elective surgery; Significance of clinical examination before operation.