| 1. |
- Gretarsdottir, Solveig, et al.
(författare)
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Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:8, s. 71-692
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study on 1,292 individuals with abdominal aortic aneurysms (AAAs) and 30,503 controls from Iceland and The Netherlands, with a follow-up of top markers in up to 3,267 individuals with AAAs and 7,451 controls. The A allele of rs7025486 on 9q33 was found to associate with AAA, with an odds ratio (OR) of 1.21 and P = 4.6 x 10(-10). In tests for association with other vascular diseases, we found that rs7025486[A] is associated with early onset myocardial infarction (OR = 1.18, P = 3.1 x 10(-5)), peripheral arterial disease (OR = 1.14, P = 3.9 x 10(-5)) and pulmonary embolism (OR = 1.20, P = 0.00030), but not with intracranial aneurysm or ischemic stroke. No association was observed between rs7025486[A] and common risk factors for arterial and venous diseases-that is, smoking, lipid levels, obesity, type 2 diabetes and hypertension. Rs7025486 is located within DAB2IP, which encodes an inhibitor of cell growth and survival.
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| 2. |
- Helgadottir, Anna, et al.
(författare)
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Apolipoprotein(a) Genetic Sequence Variants Associated With Systemic Atherosclerosis and Coronary Atherosclerotic Burden But Not With Venous Thromboembolism
- 2012
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 60:8, s. 722-729
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Tidskriftsartikel (refereegranskat)abstract
- Objectives The purpose of this study is investigate the effects of variants in the apolipoprotein(a) gene (LPA) on vascular diseases with different atherosclerotic and thrombotic components. Background It is unclear whether the LPA variants rs10455872 and rs3798220, which correlate with lipoprotein(a) levels and coronary artery disease (CAD), confer susceptibility predominantly via atherosclerosis or thrombosis. Methods The 2 LPA variants were combined and examined as LPA scores for the association with ischemic stroke (and TOAST [Trial of Org 10172 in Acute Stroke Treatment] subtypes) (effective sample size [n(e)] = 9,396); peripheral arterial disease (n(e) = 5,215); abdominal aortic aneurysm (ne = 4,572); venous thromboembolism (ne = 4,607); intracranial aneurysm (ne = 1,328); CAD (n(e) = 12,716), carotid intima-media thickness (n = 3,714), and angiographic CAD severity (n = 5,588). Results LPA score was associated with ischemic stroke subtype large artery atherosclerosis (odds ratio [OR]: 1.27; p = 6.7 X 10(-4)), peripheral artery disease (OR: 1.47; p = 2.9 x 10(-14)), and abdominal aortic aneurysm (OR: 1.23; p = 6.0 x 10(-5)), but not with the ischemic stroke subtypes cardioembolism (OR: 1.03; p = 0.69) or small vessel disease (OR: 1.06; p = 0.52). Although the LPA variants were not associated with carotid intima-media thickness, they were associated with the number of obstructed coronary vessels (p = 4.8 x 10(-12)). Furthermore, CAD cases carrying LPA risk variants had increased susceptibility to atherosclerotic manifestations outside of the coronary tree (OR: 1.26; p = 0.0010) and had earlier onset of CAD (-1.58 years/allele; p = 8.2 x 10(-8)) than CAD cases not carrying the risk variants. There was no association of LPA score with venous thromboembolism (OR: 0.97; p = 0.63) or intracranial aneurysm (OR: 0.85; p = 0.15). Conclusions LPA sequence variants were associated with atherosclerotic burden, but not with primarily thrombotic phenotypes. (J Am Coll Cardiol 2012; 60: 722-9) (C) 2012 by the American College of Cardiology Foundation
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| 3. |
- Helgadottir, Anna, et al.
(författare)
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The same sequence variant on 9p21 associates with myocardial infarction, abdominal aortic aneurysm and intracranial aneurysm
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 40:2, s. 217-224
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Tidskriftsartikel (refereegranskat)abstract
- Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD)(1-4) and type 2 diabetes (T2D)(5-7), 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.
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| 4. |
- Jones, Gregory T., et al.
(författare)
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Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci
- 2017
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Ingår i: Circulation Research. - 0009-7330 .- 1524-4571. ; 120:2, s. 341-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA. Objective: To identify additional AAA risk loci using data from all available genome-wide association studies. Methods and Results: Through a meta-analysis of 6 genome-wide association study data sets and a validation study totaling 10 204 cases and 107 766 controls, we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches, we observed no new associations between the lead AAA single nucleotide polymorphisms and coronary artery disease, blood pressure, lipids, or diabetes mellitus. Network analyses identified ERG, IL6R, and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9. Conclusions: The 4 new risk loci for AAA seem to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
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| 5. |
- Martufi, Giampaolo, et al.
(författare)
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Local Diameter, Wall Stress, and Thrombus Thickness Influence the Local Growth of Abdominal Aortic Aneurysms
- 2016
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Ingår i: Journal of Endovascular Therapy. - : Sage Publications. - 1526-6028 .- 1545-1550. ; 23:6, s. 957-966
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To investigate the influence of the local diameter, the intraluminal thrombus (ILT) thickness, and wall stress on the local growth rate of abdominal aortic aneurysms. Methods: The infrarenal aortas of 90 asymptomatic abdominal aortic aneurysm (AAA) patients (mean age 70 years; 77 men) were retrospectively reconstructed from at least 2 computed tomography angiography scans (median follow-up of 1 year) and biomechanically analyzed with the finite element method. Each individual AAA model was automatically sliced orthogonally to the lumen centerline and represented by 100 cross sections with corresponding diameters, ILT thicknesses, and wall stresses. The data were grouped according to these parameters for comparison of differences among the variables. Results: Diameter growth was continuously distributed over the entire aneurysm sac, reaching absolute and relative median peaks of 3.06 mm/y and 7.3%/y, respectively. The local growth rate was dependent on the local baseline diameter, the local ILT thickness, and for wall segments not covered by ILT, also on the local wall stress level (all p<0.001). For wall segments that were covered by a thick ILT layer, wall stress did not affect the growth rate (p=0.08). Conclusion: Diameter is not only a strong global predictor but also a local predictor of aneurysm growth. In addition, and independent of the diameter, the ILT thickness and wall stress (for the ILT-free wall) also influence the local growth rate. The high stress sensitivity of nondilated aortic walls suggests that wall stress peaks could initiate AAA formation. In contrast, local diameters and ILT thicknesses determine AAA growth for dilated and ILT-covered aortic walls.
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| 6. |
- Martufi, Giampaolo, 1980-, et al.
(författare)
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Multidimensional growth measurements of abdominal aortic aneurysms
- 2013
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 58:3, s. 748-755
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Tidskriftsartikel (refereegranskat)abstract
- Background: Monitoring the expansion of abdominal aortic aneurysms (AAAs) is critical to avoid aneurysm rupture in surveillance programs, for instance. However, measuring the change of the maximum diameter over time can only provide limited information about AAA expansion. Specifically, regions of fast diameter growth may be missed, axial growth cannot be quantified, and shape changes of potential interest for decisions related to endovascular aneurysm repair cannot be captured. Methods: This study used multiple centerline-based diameter measurements between the renal arteries and the aortic bifurcation to quantify AAA growth in 51 patients from computed tomography angiography (CTA) data. Criteria for inclusion were at least 1 year of patient follow-up and the availability of at least two sufficiently high-resolution CTA scans that allowed an accurate three-dimensional reconstruction. Consequently, 124 CTA scans were systematically analyzed by using A4clinics diagnostic software (VASCOPS GmbH, Graz, Austria), and aneurysm growth was monitored at 100 cross-sections perpendicular to the centerline. Results: Monitoring diameter development over the entire aneurysm revealed the sites of the fastest diameter growth, quantified the axial growth, and showed the evolution of the neck morphology over time. Monitoring the development of an aneurysm's maximum diameter or its volume over time can assess the mean diameter growth (r = 0.69, r = 0.77) but not the maximum diameter growth (r = 0.43, r = 0.34). The diameter growth measured at the site of maximum expansion was similar to 16%/y, almost four times larger than the mean diameter expansion of 4.4%/y. The sites at which the maximum diameter growth was recorded did not coincide with the position of the maximum baseline diameter (rho = 0.12; P = .31). The overall aneurysm sac length increased from 84 to 89 mm during the follow-up (P < .001), which relates to the median longitudinal growth of 3.5%/y. The neck length shortened, on average, by 6.2% per year and was accompanied by a slight increase in neck angulation. Conclusions: Neither maximum diameter nor volume measurements over time are able to measure the fastest diameter growth of the aneurysm sac. Consequently, expansion-related wall weakening might be inappropriately reflected by this type of surveillance data. In contrast, localized spots of fast diameter growth can be detected through multiple centerline-based diameter measurements over the entire aneurysm sac. This information might further reinforce the quality of aneurysm surveillance programs.
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| 7. |
- Nchimi, Alain, et al.
(författare)
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Multifactorial Relationship Between F-18-Fluoro-Deoxy-Glucose Positron Emission Tomography Signaling and Biomechanical Properties in Unruptured Aortic Aneurysms
- 2014
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Ingår i: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 7:1, s. 82-91
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Tidskriftsartikel (refereegranskat)abstract
- Background The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations and F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography. Methods and Results The study included 53 patients (45 men) with aortic aneurysms, 47 infrarenal (abdominal aortic) and 6 thoracic (thoracic aortic), who had 1 F-18-FDG positron emission tomography/computed tomography. During a 30-month period, more clinical events occurred in patients with increased F-18-FDG uptake on their last examination than in those without (5 of 18 [28%] versus 2 of 35 [6%]; P=0.03). Wall stress and stress/strength index computed by finite element simulations and F-18-FDG uptake were evaluated in a total of 68 examinations. Twenty-five (38%) examinations demonstrated 1 aneurysm wall area of increased F-18-FDG uptake. The mean number of these areas per examination was 1.6 (18 of 11) in thoracic aortic aneurysms versus 0.25 (14 of 57) in abdominal aortic aneurysms, whereas the mean number of increased uptake areas colocalizing with highest wall stress and stress/strength index areas was 0.55 (6 of 11) and 0.02 (1 of 57), respectively. Quantitatively, F-18-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). F-18-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. Conclusions Increased F-18-FDG positron emission tomographic uptake in aortic aneurysms is strongly related to aneurysm location, wall stress as derived by finite element simulations, and patient risk factors such as acquired and inherited susceptibilities.
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| 8. |
- Parker, Louis P., et al.
(författare)
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Proximal false lumen thrombosis is associated with low false lumen pressure and fewer complications in type B aortic dissection
- 2022
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Ingår i: Journal of Vascular Surgery. - : Elsevier BV. - 0741-5214 .- 1097-6809. ; 75:4, s. 1181-1190.e5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Improved risk stratification is a key priority for type B aortic dissection (TBAD). Partial false lumen thrombus morphology is an emerging predictor of complications. However, partial thrombosis is poorly defined, and its evaluation in clinical studies has been inconsistent. Thus, we aimed to characterize the hemodynamic pressure in TBAD and determine how the pressure relates to the false lumen thrombus morphology and clinical events. Methods: The retrospective admission computed tomography angiograms of 69 patients with acute TBAD were used to construct three-dimensional computational models for simulation of cyclical blood flow and calculation of pressure. The patients were categorized by the false lumen thrombus morphology as minimal, extensive, proximal or distal thrombosis. Linear regression analysis was used to compare the luminal pressure difference between the true and false lumen for each morphology group. The effect of morphology classification on the incidence of acute complications within 14 days was studied using logistic regression adjusted for clinical parameters. A survival analysis for adverse aortic events at 1 year was also performed using Cox regression. Results: Of the 69 patients, 44 had experienced acute complications and 45 had had an adverse aortic event at 1 year. The mean +/- standard deviation age was 62.6 +/- 12.6 years, and 75.4% were men. Compared with the patients with minimal thrombosis, those with proximal thrombosis had a reduced false lumen pressure by 10.1 mm Hg (95% confidence interval [CI], 4.3-15.9 mm Hg; P = .001). The patients who had not experienced an acute complication had had a reduced relative false lumen pressure (-6.35 mm Hg vs -0.62 mm Hg; P = .03). Proximal thrombosis was associated with fewer acute complications (odds ratio, 0.17; 95% CI, 0.04-0.60; P = .01) and 1-year adverse aortic events (hazard ratio, 0.36; 95% CI, 0.16-0.80; P = .01). Conclusions: We found that proximal false lumen thrombosis was a marker of reduced false lumen pressure. This might explain how proximal false lumen thrombosis appears to be protective of acute complications (eg, refractory hypertension or pain, aortic rupture, visceral or limb malperfusion, acute expansion) and adverse aortic events within the first year.
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