Abdominal aortic aneurysm (AAA) is a common disease with significant heritability. In this study, we performed a genome-wide association meta-analysis from 14 discovery cohorts and uncovered 144 independent associations, including 97 previously unreported loci. A polygenic risk score derived from meta-analysis was able to explain AAA beyond clinical risk factors. Genes at AAA risk loci indicate involvement of lipid metabolism, vascular development and remodeling, extracellular matrix dysregulation and inflammation as key mechanisms in the pathogenesis of AAA. We further integrated functional data to elucidate expression of genes associated with AAA. These genes also indicate crossover between the development of AAA and other monogenic aortopathies, particularly via TGF-beta signaling pathways. Motivated by the strong evidence for the role of lipid levels in AAA by PheWAS, we identified therapeutic opportunities using Mendelian Randomization and, in pre-clinical studies, we demonstrated that PCSK9 inhibition in mice prevented the development of AAA.

A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A Genomic Analysis (TAGA) study comprises 407 individuals related in 12 families. Each family was collected through a proband with AAA. We calculated heritability and genetic correlations between abdominal aortic diameter and clinical parameters. A genome-wide linkage scan was performed based on 4.6 million variants. A predictive model was calculated with conditional forest. Heritability of the abdominal aortic diameter was 34%. Old age, male sex, higher height, weight, creatinine levels in serum, and better lung capacity were the best predictors of aortic diameter. Linkage analyses suggested the implication of Epidermal Growth Factor Receptor (EGFR) and Betacellulin (BTC) genes with aortic diameter. This is the first study to evaluate genetic components of variation of the aortic diameter in a population of AAA high-risk individuals. These results reveal EGFR, a gene that had been previously implicated in AAA, as a determinant of aortic diameter variation in healthy genetically enriched individuals, and might indicate that a common genetic background could determine the diameter of the aorta and future risk of AAA.

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Introduction: Iliac artery endofibrosis (IAE) is an uncommon disease, poorly studied pathology with devastating effects and different therapeutic approaches affecting young people who practise intensive sports, especially cyclists. The evolution of the process not only depends on the diagnosis and therapeutic action, but also on the acceptance and attitude of the patient and subsequent professional guidance.Case description: This is the case description of a professional triathlon athlete that had one previous iliac surgical revascularization for an IAE Iliac and was admitted in our department five times with subacute lower limb ischemia affecting both legs between 2013 and 2016. Clinical findings and image tests are reported, as well as medical procedures performed. Indications based on clinical, functional and imaging ratings were clear, but his professional activity was not completely abandoned. Finally, after four endovascular procedures with good immediate results, he was warned of the seriousness of the process since the etiopathogenic reason. At the present moment patient is asymptomatic, under routine controls, working as successful triathlon coach. Discussion and conclusion:The fact that an external mechanical stress is the reason of repeated iliac artery injury suggests that an open surgical approach correcting the external muscular compression or arterial deformation should be a definitive but also aggressive solution according to literature. However, endovascular procedures and new endovascular devices are an increasingly promising option with a very low surgical risk. No matter the revascularization performed, the persistence of sports intensive practice carries a high risk of recurrence. Sport practise cessation is mandatory in some cases in order to assure revascularization long-term patency, but also a well conducted professional orientation is needed to complete the therapeutic action.