These guidelines refer to the management of elective infra-renal AAA onlye for cases that are amenable to treatment by a standard, commercially available endograft, or by open repair utilising an infra-renal aortic clamp placement. Cases that will require the use of branched/ fenestrated endografts, a suprarenal aortic clamp, suprarenal aneurysms and thoraco-abdominal aneurysms should be referred to units specialising in the treatment of these more complex, higher-risk cases.

Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

No abstract

Vitamin D (nutritional term for compounds with biological activity of 1α,25-dihydroxyvitamin D; also used to indicate summation of Vitamin D 2 and D 3 ) is a fat-soluble vitamin that functions as a steroid hormone. It plays a crucial role in mineral homeostasis and skeletal health and its deficiency classically leads to rickets in children and osteomalacia in adults. 1 Its primary action on the skeletal system is to regulate calcium and phosphorus metabolism by influencing intestinal absorption, bone resorption, and renal retention (Figure 1). Vitamin D metabolites also play an integral physiological role in nonskeletal tissues and have been implicated in a wide range of chronic pathology, including skin and autoimmune disease, cancer, diabetes mellitus, hypertension, and cardiovascular disease (CVD).2 Interest in the role of vitamin D in CVD arose from evidence of adverse cardiovascular effects of vitamin D deficiency in animal models, 3 and epidemiological studies reporting the increase in cardiovascular events in winter and at increasing distance from the equator. Various extrarenal tissues, including many cell types involved in CVD, also express CYP27B1 and are therefore able to produce 1,25(OH) 2 D. This local production and breakdown is not subject to the same feedback controls as renal production. Vitamin D Deficiency and ExcessThere is controversy about the definition of vitamin D deficiency (or hypovitaminosis D), the optimum serum level of 25(OH)D, and the dietary requirements of vitamin D.

Background-Abdominal aortic aneurysm is a multifactorial disorder in which inflammation is an important pathophysiological feature. In explant culture, aneurysm biopsies secrete large amounts of interleukin-6 (IL-6), and among aneurysm patients, the circulating concentration of IL-6 appears to be increased. Methods and Results-We investigated, in 19 patients, whether aneurysm wall was an important source of circulating IL-6.We also tested the hypotheses, in 466 patients with a small aneurysm, that (1) high concentrations of circulating IL-6 signaled rapid aneurysm growth and (2) the Ϫ174 G3 C polymorphism in the IL-6 promoter predicted survival. For 19 patients with large or inflammatory aneurysms, the concentration of IL-6 was higher in the iliac arteries than the brachial arteries (median difference 26.5 pg/mL, this difference increasing with aneurysm diameter, Pϭ0.01). In 466 patients with small aneurysms, the frequency of the Ϫ174 C allele (0.40) was similar to that in a normal healthy population. Patients of GG genotype had lower plasma concentrations of IL-6 than patients of GC and CC genotypes (medians 1.9, 4.8, and 15.6 pg/mL, respectively, Kruskal-Wallis Pϭ0.047). Cardiovascular and all-cause mortalities were lower for patients of GG genotype than for patients of GC and CC genotype: hazard ratios 0.32 (95% CI 0.12 to 0.93), Pϭ0.036, and 0.51 (95% CI 0.25 to 1.00), Pϭ0.05, respectively. There was no association between plasma IL-6 or IL-6 genotype and aneurysm growth. Conclusions-Aortic aneurysms appear to be an important source of circulating IL-6, the concentration being influenced by genotype. For patients with small aneurysms, the Ϫ174 G3 C IL-6 genotype predicts future cardiovascular mortality.

The endovascular-repair group had an early benefit with respect to aneurysm-related mortality, but the benefit was lost by the end of the study, at least partially because of fatal endograft ruptures (adjusted hazard ratio, 0.92; 95% CI, 0.57 to 1.49; P=0.73). By the end of follow-up, there was no significant difference between the two groups in the rate of death from any cause (adjusted hazard ratio, 1.03; 95% CI, 0.86 to 1.23; P=0.72). The rates of graft-related complications and reinterventions were higher with endovascular repair, and new complications occurred up to 8 years after randomization, contributing to higher overall costs. ConclusionThe results over a median follow-up period of 6 years confirm the previously published midterm findings that operative mortality associated with endovascular repair of abdominal aortic aneurysm was only a third of that associated with the open-repair procedure and that aneurysm-related mortality was reduced during the early years after endovascular repair. However, the early benefit was completely lost in the longer term, with substantially higher aneurysm-related mortality after 4 years in the endovascular-repair group than in the open-repair group and new graft-related complications and reinterventions continued to be reported for as long as 8 years after endovascular procedures were performed. Secondary rupture after aneurysm repair was reported only after endovascular repair and appeared to explain the long-term increase in aneurysm-related mortality. In contrast, open repair was very durable but was associated with higher operative mortality. These findings have implications for the selection of patients for endovascular repair, the choices for patients, surveillance after repair, and cost-effectiveness.

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10(-5)) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10(-5)). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10(-10), odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression.

Acute aortic syndrome (AAS) is a modern term to describe interrelated emergency aortic conditions with similar clinical characteristics and challenges. These conditions include aortic dissection, intramural haematoma (IMH), and penetrating atherosclerotic ulcer (PAU and aortic rupture); trauma to the aorta with intimal laceration may also be considered. The common denominator of AAS is disruption of the media layer of the aorta with bleeding within IMH, along the aortic media resulting in separation of the layers of the aorta (dissection), or transmurally through the wall in the case of ruptured PAU or trauma. Population-based studies suggest that the incidence of acute dissection ranges from 2 to 3.5 cases per 100 000 person-years; hypertension and a variety of genetic disorders with altered connective tissues are the most prevalent risk conditions. Patients with AAS often present in a similar fashion, regardless of the underlying condition of dissection, IMH, PAU, or contained aortic rupture. Pain is the most commonly presenting symptom of acute aortic dissection and should prompt immediate attention including diagnostic imaging modalities (such as multislice computed tomography, transoesophageal ultrasound, or magnetic resonance imaging). Prognosis is clearly related to undelayed diagnosis and appropriate surgical repair in the case of proximal involvement of the aorta; affection of distal segments of the aorta may call for individualized therapeutic approaches favouring endovascular in the presence of malperfusion or imminent rupture, or medical management.