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Concept: Aneurysm of sinus of Valsalva

18

Large vessel vasculitis (LVV) covers a spectrum of primary vasculitides predominantly affecting the aorta and its major branches. The two main subtypes are giant cell arteritis (GCA) and Takayasu arteritis (TA). Less commonly LVV occurs in various other diseases. Clinical manifestations result from vascular stenosis, occlusion, and dilation, sometimes complicated by aneurysm rupture or dissection. Occasionally LVV is discovered unexpectedly on pathological examination of a resected aortic aneurysm. Clinical evaluation is often unreliable in determining disease activity. Moreover, the diagnostic tools are imperfect. Acute phase reactants can be normal at presentation and available imaging modalities are more reliable in delineating vascular anatomy than in providing reliable information on degree of vascular inflammation. Glucocorticoids are the mainstay of therapy of LVV. Patients may develop predictable adverse effects from long-term glucocorticoid use. Several steroid-sparing agents have also shown some promise and are currently in use. Endovascular revascularization procedures and open surgical treatment for aneurysms and dissections are sometimes necessary, but results are not always favorable and relapses are common. This article, the first in a series of two, will be devoted to GCA and isolated (idiopathic) aortitis, while TA will be covered in detail in the next article.

Concepts: Inflammation, Atherosclerosis, Vasculitis, Aortic aneurysm, Aortic dissection, Aorta, Aneurysm of sinus of Valsalva, Giant cell arteritis

17

Abdominal aortic aneurysm (AAA) is an important vascular disease in older adults, but data on lifetime risk of AAA are sparse. We examined lifetime risk of AAA in a community-based cohort and prospectively assessed the association between midlife cardiovascular risk factors and AAAs.

Concepts: Epidemiology, Atherosclerosis, Cardiovascular disease, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

15

The UK abdominal aortic aneurysm (AAA) screening programmes currently invite only men for screening because the benefit in women is uncertain. Perioperative risk is critical in determining the effectiveness of screening, and contemporary estimates of these risks in women are lacking. The aim of this study was to compare mortality following AAA repair between women and men in the UK.

Concepts: Risk, Gender, Risk management, Aortic aneurysm, Aneurysm, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva, Uncertainty

11

Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl2-induced AAA at a dose comparable to human medical practice. Analysis of tissue extracts revealed that montelukast reduces the levels of matrix metalloproteinase-9 (MMP-9) and macrophage inflammatory protein-1α (MIP-1α) in the aortic wall. Furthermore, aneurysm progression was specifically mediated through CysLT1 signaling since a selective CysLT2 antagonist was without effect. A significantly reduced vessel dilatation is also observed when treatment with montelukast is started days after aneurysm induction, suggesting that the drug not only prevents but also stops and possibly reverts an already ongoing degenerative process. Moreover, montelukast reduced the incidence of aortic rupture and attenuated the AAA development in two additional independent models, i.e., angiotensin II- and porcine pancreatic elastase-induced AAA, respectively. Our results indicate that cys-LTs are involved in the pathogenesis of AAA and that antagonism of the CysLT1 receptor is a promising strategy for preventive and therapeutic treatment of this clinically silent and highly lethal disease.

Concepts: Inflammation, Enzyme, Aortic aneurysm, Aneurysm, Aortic dissection, Aorta, Aneurysm of sinus of Valsalva, Leukotriene

11

We determined the feasibility of abdominal aortic aneurysm (AAA) screening program led by family physicians in public primary healthcare setting using hand-held ultrasound device. The potential study population was 11,214 men aged ≥ 60 years attended by three urban, public primary healthcare centers. Participants were recruited by randomly-selected telephone calls. Ultrasound examinations were performed by four trained family physicians with a hand-held ultrasound device (Vscan®). AAA observed were verified by confirmatory imaging using standard ultrasound or computed tomography. Cardiovascular risk factors were determined. The prevalence of AAA was computed as the sum of previously-known aneurysms, aneurysms detected by the screening program and model-based estimated undiagnosed aneurysms. We screened 1,010 men, with mean age of 71.3 (SD 6.9) years; 995 (98.5%) men had normal aortas and 15 (1.5%) had AAA on Vscan®. Eleven out of 14 AAA-cases (78.6%) had AAA on confirmatory imaging (one patient died). The total prevalence of AAA was 2.49% (95%CI 2.20 to 2.78). The median aortic diameter at diagnosis was 3.5 cm in screened patients and 4.7 cm (p<0.001) in patients in whom AAA was diagnosed incidentally. Multivariate logistic regression analysis identified coronary heart disease (OR = 4.6, 95%CI 1.3 to 15.9) as the independent factor with the highest odds ratio. A screening program led by trained family physicians using hand-held ultrasound was a feasible, safe and reliable tool for the early detection of AAA.

Concepts: Epidemiology, Atherosclerosis, Heart, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

8

Abdominal aortic aneurysm (AAA) is a complex multifactorial disease associated with a high morbidity and mortality. Increased inflammation including T-helper 17 cell-mediated effects has been implicated in AAA pathogenesis. Psoriasis is considered to be a T-helper 17-driven chronic inflammatory disease and in view of potentially overlapping inflammatory mechanisms, we investigated the risk of AAA in patients with psoriasis in a nationwide cohort.

Concepts: Immune system, Asthma, Atherosclerosis, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

8

Contemporary population-based data on age-specific incidence and outcome from acute abdominal aortic aneurysm (AAA) events are needed to understand the impact of risk factor modification and demographic change, and to inform AAA screening policy.

Concepts: Epidemiology, Demography, Risk, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

8

Current abdominal aortic aneurysm (AAA) screening in men age 65 might have limited impact on overall AAA death rates if incidence is moving to older ages. Up-to-date population-based studies of age-specific incidence, risk factors, and outcome of acute AAA are needed to inform screening policy.

Concepts: Epidemiology, Death, Medical statistics, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

7

Endovascular sealing is a new technique for the repair of abdominal aortic aneurysms. Commercially available in Europe since 2013, it takes a revolutionary approach to aneurysm repair through minimally invasive techniques. Although aneurysm sealing may be thought as more stable than conventional endovascular stent graft repairs, post-implantation movement of the endoprosthesis has been described, potentially leading to late complications. The paper presents for the first time a model, which explains the nature of forces, in static and dynamic regimes, acting on sealed abdominal aortic aneurysms, with references to real case studies. It is shown that elastic deformation of the aorta and of the endoprosthesis induced by static forces and vibrations during daily activities can potentially promote undesired movements of the endovascular sealing structure.

Concepts: Stent, Aortic aneurysm, Aneurysm, Aortic dissection, Aorta, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva

7

Recent studies have confirmed a close association between various medical conditions (intracranial aneurysm, abdominal aortic aneurysm, temporal arteritis, autoimmune disorder, renal cysts), certain aortic anatomic variants (bovine aortic arch, direct origin of left vertebral artery from aortic arch, bicuspid aortic valve), and family history of aneurysm disease with thoracic aortic aneurysm and dissection. This paper reviews these associations. We propose to capitalise on these associations as powerful and expanding opportunities to diagnose the virulent but silent disease of thoracic aortic aneurysm. This can be accomplished by recognition of this ‘guilt by association’ with the other conditions. Thus, patients with associated diseases and anatomic variants should be investigated for silent aortic aneurysms. Such a paradigm holds substantial potential for reducing death from the silent killer represented by thoracic aortic aneurysm disease.

Concepts: Medicine, Disease, Infectious disease, Aortic aneurysm, Aneurysm, Aortic dissection, Abdominal aortic aneurysm, Aneurysm of sinus of Valsalva