Multiple arterial aneurysms in association with aberrant brachial arterial anatomy and hemodialysis fistulas.

This work describes two cases of multiple aneurysms of aberrant brachial arterial supply in association with ipsilateral hemodialysis fistulas. In the first case, a 38-year-old man presented with acute thrombosis of an aneurysmal left brachioradial artery. In the second case, a 34-year-old man was referred with the diagnosis of aneurysmal left brachiocephalic fistula. This turned out to be an aneurysmal brachioradial artery. In both patients, multiple true aneurysms of aberrant brachial arterial supply were observed. By nature, the brachioradial variation lies superficially in the arm. We discuss the pitfalls of such an anomaly in planning an ipsilateral arteriovenous fistula.

Endovascular repair of a mycotic thoracic aortic aneurysm in a patient with aortic coarctation.

This report describes the management of a 28-year-old female patient who presented with septicemia and mediastinal mass-effect secondary to a proximal mycotic aneurysm of the descending aorta. The patient had an infected bicuspid aortic valve, aortic coarctation, and a left vertebral artery arising directly from the aortic arch. Evidence of disseminated embolization affecting her posterior cerebral circulation, the left axillary, and the superior mesenteric arteries was noted. The patient had a considerably small aorta. An urgent thoracic endovascular aortic repair was performed successfully with a chimney stent to the left vertebral artery. The report discusses the planning and technique used in managing this complex case.

A variant in LDLR is associated with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is a common cardiovascular disease among older people and demonstrates significant heritability. In contrast to similar complex diseases, relatively few genetic associations with AAA have been confirmed. We reanalyzed our genome-wide study and carried through to replication suggestive discovery associations at a lower level of significance. METHODS AND RESULTS: A genome-wide association study was conducted using 1830 cases from the United Kingdom, New Zealand, and Australia with infrarenal aorta diameter≥30 mm or ruptured AAA and 5435 unscreened controls from the 1958 Birth Cohort and National Blood Service cohort from the Wellcome Trust Case Control Consortium. Eight suggestive associations with P<1×10(-4) were carried through to in silico replication in 1292 AAA cases and 30,503 controls. One single-nucleotide polymorphism associated with P<0.05 after Bonferroni correction in the in silico study underwent further replication (706 AAA cases and 1063 controls from the United Kingdom, 507 AAA cases and 199 controls from Denmark, and 885 AAA cases and 1000 controls from New Zealand). Low-density lipoprotein receptor (LDLR) rs6511720 A was significantly associated overall and in 3 of 5 individual replication studies. The full study showed an association that reached genome-wide significance (odds ratio, 0.76; 95% confidence interval, 0.70-0.83; P=2.08×10(-10)). CONCLUSIONS: LDLR rs6511720 is associated with AAA. This finding is consistent with established effects of this variant on coronary artery disease. Shared causal pathways with other cardiovascular diseases may present novel opportunities for preventative and therapeutic strategies for AAA.

Quantitative Determination of three Angiotensin-II-receptor Antagonists in Presence of Hydrochlorothiazide by RP-HPLC in their Tablet Preparations.

Losartan potassium, Valsartan , Telmisartan and Irbesartan are angiotensin-II-receptor antagonists (ARA II) group which used in treatment of hypertension alone or in combination with other drugs mainly Hydrochlorothiazide. RP- HPLC method was developed for the assay of three angiotensin-II-receptor antagonists (ARA-IIs) in presence of Hydrochlorothiazide. The method was performed by reversed phase high performance liquid chromatography using a mobile phase which is consisted of 0.025 M potassium dihydrogen phosphate (pH 6.0): acetonitrile = 65:35% with detection at 220 nm on an ACE C18 column (250 mm × 4.6 mm, 5 µm) at flow rate 1.5 mL/min in an isocratic manner. The proposed method was validated according to ICH guidline in terms of linearity, accuracy, precision , robustness, limit of detection and limit of quantitation.

Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1.

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.

Transverse minilaparotomy for open abdominal aortic aneurysm repair.

INTRODUCTION: Traditional open surgical repair for abdominal aortic aneurysm (AAA) is a major procedure with a relatively high risk of perioperative morbidity. This article describes the results of minimally invasive open AAA repair through a transverse left upper quadrant minilaparotomy. METHODS: Between January 2007 and June 2010, 83 consecutive patients (77 men) underwent elective or urgent repair of a nonruptured AAA through a horizontal transperitoneal left upper quadrant minilaparotomy. Postoperatively, patients were fast-tracked through a multidisciplinary recovery program. RESULTS: Repairs were urgent in 15 patients (18%), and 10 (12%) had aortoiliac aneurysms. American Society of Anesthesiologists (ASA) scores 1 to 4 were 3.6%, 44.6%, 42%, and 11%, respectively. Median (range) age was 73 (61-87) years, AAA size was 5.9 (5.1-10) cm, body mass index was 27 (19-39) kg/m(2), operation time was 150 (85-280) minutes, blood loss was 625 (200-4150) mL, critical care bed days was 1 (0-19), and hospital stay was 4 (2-88) days. Four (4.8%) patients returned to the operating theater within the same admission. No patients required conversion to full laparotomy and none had reintervention postdischarge. Two patients (2.4%) died in the hospital, and 18 (21.7%) had postoperative adverse events, ranging from urinary retention to myocardial infarction. New-onset atrial fibrillation was the commonest of these events (11, 13.3%). Respiratory tract infection incidence was low (4.8%). Incisional herniation developed in two patients (2.4%) at a median (range) follow-up of 10 (6-25) months. Correcting for age, cardiac complications were associated with increased odds of hospital stay >4 days (odds ratio [OR], 7.59; 95% confidence interval [CI], 1.12-52.42; P = .014). Correcting for ASA score, advancing age was associated with increased risk of cardiac complications (OR, 1.18; 95% CI, 1.08-1.28; P = .001), whereas AAA screening (patient identified through screening) and maintaining higher intraoperative systolic pressure were both protective (OR, 0.24; 95% CI, 0.07-0.87; P = .018) and (OR, 0.93; 95% CI, 0.89-0.98; P = .009), respectively. CONCLUSION: Left upper quadrant minilaparotomy is a feasible minimally invasive approach to open AAA repair. This technique is associated with low morbidity and mortality and short hospital stay, particularly in patients identified through AAA screening.

An analysis of drug modulation of abdominal aortic aneurysm growth through 25 years of surveillance.

BACKGROUND: A modest (41%) reduction in abdominal aortic aneurysm (AAA) growth rate is likely to delay AAA-related events (surgery or rupture) by 5 years, making the notion of AAA medical treatment very appealing. Randomized controlled trials of commonly used existing medications are expensive and ethically questionable. This study reviewed the independent associations of commonly used medications and AAA growth during a 25-year period of AAA surveillance. METHODS: The study included all patients monitored through an AAA screening and surveillance program. Records of AAA size, risk factors, outcomes, death, and medications were entered into a continually updated database. AAA growth rates were calculated using a flexible hierarchical model. A multivariate model was used to test for associations independent of confounders. RESULTS: The study comprised 1269 patients (94.1% men) who had a mean age of 67 years. The median starting diameter was 35 mm, the end diameter was 44 mm, and follow-up was 3.4 years. Drugs used in the treatment of diabetes were associated with a 56% reduction in AAA growth rate (P = .01) independent of confounding factors, including other therapeutic agents (P = .003). Angiotensin-receptor blockers and potassium-sparing diuretics were also associated with slower AAA growth rates, although these effects were not independent of all confounders. CONCLUSION: Diabetes or its medications, or both, have a negative effect on AAA growth. Because of polypharmacy, demonstrating the independent effects of individual drugs affecting the renin-angiotensin system was not possible. In light of this analysis, however, strong associations between angiotensin-receptor blockers and aldosterone-receptor blockers and slowed AAA progression are credible.

Assessment of the association between genetic polymorphisms in transforming growth factor beta, and its binding protein (LTBP), and the presence, and expansion, of Abdominal Aortic Aneurysm.

OBJECTIVES: Abdominal Aortic Aneurysm (AAA) has a strong genetic predisposition. Transforming growth factor beta 1 (TGF-beta1) is a causal factor in ascending aortic dilatation; however, a role in AAA pathology is unclear. The aim of the study was to determine whether genes coding TGF-beta and its binding protein are associated with the presence and expansion of AAA. METHODS: Four geographically distinct case control studies, totaling 1890 AAA cases and 3785 controls, were genotyped and compared to the presence, size and growth rate of AAA. 26 single nucleotide polymorphisms (SNPs) in 5 genes were genotyped in the UK cohort and the result was replicated in 3 independent cohorts. RESULTS: No associations between genotypes or haplotypes and the presence of AAA disease were confirmed. Five SNPs in Latent TGF-beta Binding Protein (LTBP4) and an allelic variant of TGFB3 were associated with a significant decrease in AAA growth (p< or =0.02), in the UK cohort. Altered growth was demonstrated in carriers of two common haplotypes of LTBP4 (+0.38 mm/year, p=0.003; -0.41 mm/year, p=0.02, per haplotype copy) and a single haplotype of TGFB3 (-0.53 mm/year, p=0.05). This association with AAA growth could not be demonstrated in two other independent cohorts. Meta-analysis of AAA size and growth rates in larger AAA (> or =45 mm), in all four cohorts, demonstrated a significant association with the LTBP4 21011A>T genotype (a 2% decrease in AAA diameter, or a 0.53 mm/year reduction in AAA growth rate, per T allele [p=0.03, p=0.01]). CONCLUSION: This study suggests that the LTBP4 gene may contribute to AAA progression.

Sequence variant on 9p21 is associated with the presence of abdominal aortic aneurysm disease but does not have an impact on aneurysmal expansion.

Abdominal aortic aneurysm (AAA) is among a number of vascular disorders to be recently associated with a common allelic variant situated on chromosome 9p21. To further assess the significance of this region of the genome in AAA development, we genotyped the sequence variation tagged by rs10757278 in two geographically independent cohorts of patients and compared them to matched controls. We also assessed the impact of this variant on AAA growth rate in cohorts with a median surveillance period of 3.2 and 4.5 years. Using meta-analysis to combine the findings of both cohorts, we found a significant association between rs10757278-G and the presence of AAA (OR (95%CI) 1.38 (1.04-1.82) P=0.03), an effect size completely consistent with that originally reported. rs10757278 was not significantly associated with altered AAA growth rate in either cohort.

Angiotensin II type 1 receptor 1166C polymorphism is associated with abdominal aortic aneurysm in three independent cohorts.

OBJECTIVE: Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small sample sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA. METHODS AND RESULTS: The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the AGTR1 1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93, P=1.1x10(-6)). Overall, the ACE ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67, P<0.02). The AGT 268T allele appeared to have an epistatic effect on large aneurysm size. CONCLUSIONS: This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.

Screening and ultrasound surveillance of large abdominal aortic aneurysms do not improve suitability for endovascular repair.

OBJECTIVE: The effect of population screening for abdominal aortic aneurysm (AAA) disease on morbidity and mortality has been comprehensively studied and reported. However, the effect of early AAA detection on suitability for endovascular aneurysm repair (EVAR) remains unknown. Considering the importance of such an effect on future health economics, we sought to assess the possible effect of AAA ultrasound surveillance on suitability for EVAR. METHODS: This was a prospective cohort study. From January 2002 to August 2003, consecutive AAA patients selected for open elective repair were placed into one of two groups according to mode of presentation. The first group included patients referred from a local well-established AAA ultrasound screening and surveillance program (ultrasound surveillance [AAA-S] group). The second group included patients referred from neighboring unscreened regions with incidentally diagnosed AAA (incidental [AAA-I] group). All patients underwent preoperative computed tomographic angiography. By using three-dimensional reconstruction software, computed tomographic images were assessed by two blinded observers for suitability for EVAR by using the criteria for a modular endovascular device. RESULTS: Of 74 patients included in the study, 41 were in the AAA-S group, and 31 were in the AAA-I group. The median aneurysm diameter was 72.3 mm (range, 50.7-83.7 mm) for AAA-I and 65 mm (range, 50.7-79.2 mm) for AAA-S (P < .47). Suitability for EVAR was 41% in the AAA-S group and 45% in the AAA-I group (P < .47). CONCLUSIONS: Early detection and surveillance of AAA does not seem to increase suitability for EVAR. Suitability for EVAR seems to be determined early on in an aneurysm's life. On the basis of current device technology, referral for intervention from an AAA surveillance program may need to be initiated at a size well below 5.5 cm if an increase in EVAR suitability is to be expected.