[Show abstract][Hide abstract] ABSTRACT: Carotid endarterectomy is a standard vascular surgical procedure performed worldwide and encompasses multiple risks including cerebral hyperperfusion syndrome, stroke, carotid dissection and aneurysmal formation, all of which are well documented in the literature. However, neovascular glaucoma manifesting post carotid endarterectomy, is extremely rare and can have disastrous consequences if left undiagnosed. In this article, we present one such case of neovascular glaucoma manifesting post carotid endarterectomy and review the available literature on this uncommon entity.
Annals of Vascular Diseases 07/2015; 8(2). DOI:10.3400/avd.cr.14-00120
[Show abstract][Hide abstract] ABSTRACT: Experimental studies suggest that angiotensin II plays a central role in the pathogenesis of abdominal aortic aneurysm. This trial aims to evaluate the efficacy of the angiotensin receptor blocker telmisartan in limiting the progression of abdominal aortic aneurysm.
Telmisartan in the management of abdominal aortic aneurysm (TEDY) is a multicentre, parallel-design, randomised, double-blind, placebo-controlled trial with an intention-to-treat analysis. We aim to randomly assign 300 participants with small abdominal aortic aneurysm to either 40 mg of telmisartan or identical placebo and follow patients over 2 years. The primary endpoint will be abdominal aortic aneurysm growth as measured by 1) maximum infra-renal aortic volume on computed tomographic angiography, 2) maximum orthogonal diameter on computed tomographic angiography, and 3) maximum diameter on ultrasound. Secondary endpoints include change in resting brachial blood pressure, abdominal aortic aneurysm biomarker profile and health-related quality of life. TEDY is an international collaboration conducted from major vascular centres in Australia, the United States and the Netherlands.
Currently, no medication has been convincingly demonstrated to limit abdominal aortic aneurysm progression. TEDY will examine the potential of a promising treatment strategy for patients with small abdominal aortic aneurysms.
Australian and Leiden study centres: Australian New Zealand Clinical Trials Registry ACTRN12611000931976 , registered on 30 August 2011; Stanford study centre: clinicaltrials.gov NCT01683084 , registered on 5 September 2012.
[Show abstract][Hide abstract] ABSTRACT: Abdominal aortic aneurysm (AAA) and aortic occlusive disease (AOD) represent common causes of morbidity and mortality in elderly populations which were previously believed to have common aetiologies. The aim of this study was to assess the gene expression in human AAA and AOD. We performed microarrays using aortic specimen obtained from 20 patients with small AAAs (≤ 55mm), 29 patients with large AAAs (> 55mm), 9 AOD patients, and 10 control aortic specimens obtained from organ donors. Some differentially expressed genes were validated by quantitative-PCR (qRT-PCR)/immunohistochemistry. We identified 840 and 1,014 differentially expressed genes in small and large AAAs, respectively. Immune-related pathways including cytokine-cytokine receptor interaction and T-cell-receptor signalling were upregulated in both small and large AAAs. Examples of validated genes included CTLA4 (2.01-fold upregulated in small AAA, P = 0.002), NKTR (2.37-and 2.66-fold upregulated in small and large AAA with P = 0.041 and P = 0.015, respectively), and CD8A (2.57-fold upregulated in large AAA, P = 0.004). 1,765 differentially expressed genes were identified in AOD. Pathways upregulated in AOD included metabolic and oxidative phosphorylation categories. The UCP2 gene was downregulated in AOD (3.73-fold downregulated, validated P = 0.017). In conclusion, the AAA and AOD transcriptomes were very different suggesting that AAA and AOD have distinct pathogenic mechanisms.
[Show abstract][Hide abstract] ABSTRACT: Previous studies in rodent models and patients suggest that visceral adipose could play a direct role in the development and progression of abdominal aortic aneurysm (AAA). This study aimed to assess the association of visceral adiposity with AAA presence and growth. This study was a case-control investigation of patients that did (n=196) and did not (n=181) have an AAA who presented to The Townsville Hospital vascular clinic between 2003 and 2012. Cases were patients with AAA (infra-renal aortic diameter >30 mm) and controls were patients with intermittent claudication but no AAA (infra-renal aortic diameter <30 mm). All patients underwent computed tomography angiography (CTA). The visceral to total abdominal adipose volume ratio was estimated from CTAs by assessing total and visceral adipose deposits using an imaging software program. Measurements were assessed for reproducibility by repeat assessments on 15 patients. AAA risk factors were recorded at entry. Forty-five cases underwent two CTAs more than 6 months apart to assess AAA expansion. The association of visceral adiposity with AAA presence and growth was examined using logistic regression. Visceral adipose assessment by CTA was highly reproducible (mean coefficient of variation 1.0%). AAA was positively associated with older age and negatively associated with diabetes. The visceral to total abdominal adipose volume ratio was not significantly associated with AAA after adjustment for other risk factors. Patients with a visceral to total abdominal adipose volume ratio in quartile four had a 1.63-fold increased risk of AAA but with wide confidence intervals (95% CI 0.71-3.70; p=0.248). Visceral adiposity was not associated with AAA growth. In conclusion, this study suggests that visceral adiposity is not specifically associated with AAA presence or growth although larger studies are required to confirm these findings.
Vascular Medicine 06/2014; 19(4). DOI:10.1177/1358863X14537883 · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aortic calcification and thrombus have been postulated to worsen outcome following endovascular abdominal aortic aneurysm repair (EVAR). The purpose of this study was to assess the association of abdominal aortic aneurysm (AAA) calcification and thrombus volume with outcome following EVAR using a reproducible, quantifiable computed tomography (CT) assessment protocol.
Patients with elective EVAR performed between January 2002 and 2012 at the Townsville Hospital, Mater Private Hospital (Townsville) and Royal Brisbane and Women's Hospital (RBWH) were included if preoperative CTAs were available for analysis. AAA calcification and thrombus volume were measured using a semiautomated workstation protocol. Outcomes were assessed in terms of clinical failure, endoleak (type I, type II) and reintervention. Univariate and multivariate analyses were performed. Median follow-up was 1.7 years and the interquartile range 1.0-3.8 years.
One hundred thirty-four patients undergoing elective EVAR were included in the study. Rates of primary clinical success and freedom from reintervention were 82.8 % and 88.9 % at the 24-month follow-up. AAA calcification and thrombus volume were not associated with clinical failure, type I endoleak, type II endoleak or reintervention.
AAA calcification and thrombus volume were not associated with poorer outcome after EVAR in this study.
• The association of calcification and thrombus volumes with EVAR outcome is unclear • Quantifiable methods for assessing calcification and thrombus were not used previously • This study used reproducible methods for assessing AAA calcification and thrombus volumes.
European Radiology 05/2014; 24(8). DOI:10.1007/s00330-014-3185-y · 4.01 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To document the incidence of geriatric syndromes (delirium, functional decline, falls, and pressure ulcers) in two surgical units and to determine the association between the occurrence of geriatric syndromes and admission type (elective vs nonelective), severity of surgery, and surgical subspecialty unit.
Retrospective cohort study.
One vascular surgical unit and one urology surgical unit in an Australian tertiary teaching hospital.
Individuals aged 65 and older admitted to a study unit for 3 days or more (N = 112).
Delirium was identified using a validated chart extraction tool. Functional decline from admission to discharge was identified from nursing documentation. Falls were identified according to documentation in the medical record cross-checked with the hospital incident reporting system. Pressure ulcers were identified according to documentation in the medical record.
Geriatric syndromes were present in 32% of participants. Delirium was identified in 21%, functional decline in 14%, falls in 8%, and pressure ulcers in 5%. Individuals admitted directly from the emergency or outpatient department and interhospital transfers (nonelective) were significantly more likely to develop any geriatric syndrome than those on an elective surgery list before admission to the hospital (41% vs 18%, P = .01). In multivariable analysis, nonelective admission (odds ratio (OR) = 3.3, 95% confidence interval (CI) = 1.6-4.7, P = .005), major surgery (OR = 3.1, 95% CI = 1.7-3.7, P = .004) and preexisting impairment in activities of daily living (OR 2.9, 95% CI 1.5-3.6, P = .007) increased the likelihood of geriatric syndromes.
Geriatric syndromes are common in older adults undergoing surgery, and nonelective admission and major surgery increase the likelihood of geriatric syndromes occurring during hospitalization. Baseline dependency in ADLs is an important risk factor for the occurrence of these conditions.
Journal of the American Geriatrics Society 05/2014; 62(6). DOI:10.1111/jgs.12827 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: AAA (abdominal aortic aneurysm) is an important cause of sudden death in older adults, but there is no current effective drug therapy for this disease. The UCNs (urocortins1–3) and their receptors: CRFR (corticotrophin-releasing factor receptor)-1 and -2 have been implicated in various CVDs (cardiovascular diseases). We assessed the relative expression of UCN1–3 in AAA by qRT-PCR (quantitative reverse transcription–PCR) and ELISA, and examined in vitro how UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation, pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range 1.14–4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76–2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease) (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95% confidence interval, 1.37–12.40) greater prevalence of AAA independent of other risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis.
[Show abstract][Hide abstract] ABSTRACT: Current efforts to identify the genetic contribution to abdominal aortic aneurysm (AAA) have mainly focused on the assessment of germ-line variants such as single nucleotide polymorphisms. The aim of the current study was to assess the presence of acquired chromosomal aberrations in human AAA. Microarray data of 10 biopsies obtained from the site of main AAA dilatation (AAA body) and 3 control biopsies obtained from the macroscopically non-dilated neck of the AAA (AAA neck) were initially compared to identify chromosomal aneuploidies using the ChARM software. A commonly deleted segment of chromosome bands 6 (q22.1-23.2) was predicted within AAA biopsies. This finding was confirmed by quantitative (qPCR)-based DNA copy number assessments where a fold-copy number change (∆KCt) of -1±0.35 suggesting the loss of one copy of the long interspersed nucleotide elements (LINE-1) mapped to 6 (q22.1-23.2) was identified using DNA from an independent set of 6 AAA body compared to 6 paired AAA neck biopsies. The median relative genomic content of LINE-1 DNA was also reduced in AAA body compared to AAA neck biopsies (1.540 vs. 3.159, P=0.031). A gene important for vascular homeostasis mapped to 6q23.1, CTGF, was assessed and found to be significantly downregulated within AAA bodies compared to AAA necks (0.261 vs 0.627, P=0.031) as determined by reverse transcription qPCR using total RNA as a template. Histology demonstrated marked staining for macrophages within AAA body biopsies. We found in vitro that the median relative genomic content of LINE-1 DNA in aortic vascular smooth muscle cell (AoSMC) exposed to pro-inflammatory media was ~1.5-times greater than that measured in control AoSMCs exposed to non-conditioned media (3.044 vs. 2.040, P=0.015). Our findings suggest that acquired chromosomal aberrations associated with retrotransposon propagation may predispose to sporadic AAA.
[Show abstract][Hide abstract] ABSTRACT: Objective
Abdominal aortic aneurysm (AAA) represents a common cause of morbidity and mortality in elderly populations but the mechanisms involved in AAA formation remain incompletely understood. Previous human studies have focused on biopsies obtained from the center of the AAA however it is likely that pathological changes also occur in relatively normal appearing aorta away from the site of main dilatation. The aim of this study was to assess the gene expression profile of biopsies obtained from the neck of human AAAs.
We performed a microarray study of aortic neck specimens obtained from 14 patients with AAA and 8 control aortic specimens obtained from organ donors. Two-fold differentially expressed genes were identified with correction for multiple testing. Mechanisms represented by differentially expressed genes were identified using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Some of the differentially expressed genes were validated by quantitative real-time PCR (qPCR) and immunohistochemistry.
We identified 1,047 differentially expressed genes in AAA necks. The KEGG analysis revealed marked upregulation of genes related to immunity. These pathways included cytokine-cytokine receptor interaction (P=8.67*10-12), chemokine signaling pathway (P=5.76*10-07), and antigen processing and presentation (P=4.00*10-04). Examples of differentially expressed genes validated by qPCR included the T-cells marker CD44 (2.16-fold upregulated, P=0.008) and the B-cells marker CD19 (3.14-fold upregulated, P=0.003). The presence of B-cells in AAA necks was confirmed by immunohistochemistry.
The role of immunity in AAA is controversial. This study suggests that immune pathways are also upregulated within the undilated aorta proximal to an AAA.
[Show abstract][Hide abstract] ABSTRACT: Previous studies have suggested that patients with peripheral artery disease (PAD) suffer from a high incidence of cardiovascular events (CVE). Visceral adiposity has been implicated in promoting CVEs. This study aimed to assess the association of relative visceral adipose volume with incident cardiovascular events in patients with peripheral artery disease.
This was a prospective cohort study including 260 patients with PAD who presented between 2003 and 2012. Cases were patients with diagnosed PAD including symptomatic lower limb athero-thrombosis and asymptomatic abdominal aortic aneurysm. All patients underwent computed tomography angiography (CTA). Abdominal visceral to total adipose volume ratio (relative visceral adipose volume) was estimated from CTAs using a previously validated workstation protocol. Cardiovascular risk factors were recorded at entry. The association of visceral adiposity with major CVEs (death, non-fatal myocardial infarction or stroke) was examined using Kaplan Meier and Cox proportional hazard analyses.
A total of 92 major CVEs were recorded in 76 patients during a median follow-up of 2.8 (IQR 1.2 to 4.8) years, including myocardial infarction (n = 26), stroke (n = 10) and death (n = 56). At 3 years the incidence of major CVEs stratified by relative visceral adipose volume quartiles were 15% [Quartile (Q) 1], 17% (Q2), 11% (Q3) and 15% (Q4) (P = 0.517). Relative visceral adipose volume was not associated with major CVEs after adjustment for other risk factors.
This study suggests that visceral adiposity does not play a central role in the predisposition for major CVEs in patients with PAD.
PLoS ONE 12/2013; 8(12):e82350. DOI:10.1371/journal.pone.0082350 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
There is a well-established link between exposure to hot and cold temperatures and an increased risk of cardiovascular hospitalization or death. There is also contrasting evidence of a seasonal increase in aortic ruptures related to atmospheric pressure, but an association with environmental temperature has never been formally modelled. Methods
Using a prospective database, we identified 295 patients who were operated in a single centre for ruptured abdominal aortic aneurysm in south-east Queensland between 1990 and 2010. We matched patients to their nearest weather station to estimate their exposure to temperature and air pressure in the days leading up to their rupture. We used the case–crossover method to estimate the risks of temperature, which we allowed to be non-linear (increased risks at high and low temperatures) and delayed by up to 25 days. ResultsThere was an immediate increase in risk after exposure to cold, and a delayed risk after exposure to heat. An increased risk after exposure to high pressures disappeared after adjusting for temperature. At a mean temperature of 19°C (66°F), the odds ratio for rupture was 1.73 (95% confidence interval: 1.09, 2.76) compared with the reference temperature of 24°C. Conclusion
This is the first study to demonstrate an association between temperature and risk of aortic aneurysm rupture in the Southern Hemisphere. The physiological changes caused by thermoregulation may be a trigger for those people with a fragile aneurysm.
ANZ Journal of Surgery 12/2013; 84(11). DOI:10.1111/ans.12446 · 1.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Abdominal aortic aneurysm (AAA) is a potentially life threatening late onset degenerative condition. MicroRNAs, the small non-coding RNA molecules that regulate gene expression, have been previously shown to be associated with a broad range of human pathologies, including cardiovascular diseases. The aim of this study was to identify AAA-associated microRNAs potentially contributing to AAA pathology. We analyzed the expression of 124 microRNAs within AAA biopsies and serum of 10 patients undergoing AAA repair, and serum from 10 age- and sex-matched subjects without AAA, using the FlexmiR™ MicroRNA Assay. RNA extracted from the site of main AAA dilatation (AAA body) was compared with that extracted from the macroscopically non-dilated neck of the AAA (AAA neck). Similarly, RNA extracted from the serum of AAA patients (AAA serum) was compared with that extracted from age and sex matched controls (control serum). Real-time quantitative PCR (qRT-PCR), western blot, and histology were performed using an independent set of 6 paired AAA body and neck biopsies to examine the validity of findings. Seven microRNAs were upregulated (>2-fold difference, FDR<0.5) within AAA biopsies, of which miR-155 was the most differentially expressed (11.32-fold, FDR=0.414). This finding was confirmed by qRT-PCR with median relative expression of miR-155 being 3.26 and 0.63 within AAA body and AAA neck biopsies, respectively (P=0.031). Circulating miR-155 was also increased in AAA patients compared to controls with a 2.67-fold upregulation at borderline significance (FDR=0.554). Two immunologically important miR-155 target genes, CTLA4 and SMAD2, were assessed and found to be significantly downregulated within AAA bodies compared to AAA necks (P=0.032 and P=0.026) as determined by qRT-PCR and western blotting, respectively. Histology demonstrated dense accumulation of T-lymphocytes within the adventitial and outer medial layers of AAA body but not neck tissue. This study suggests that miR-155 is overexpressed in AAA with potential implications in the pathogenesis of the condition.
[Show abstract][Hide abstract] ABSTRACT: Peripheral arterial disease (PAD) is characterised by atherosclerotic stenosis or occlusion of the arteries of the lower limbs, resulting in an impairment of blood flow to the legs. Patients with PAD have a significant reduction in their physical capacity and are limited during activities such as walking by intermittent claudication.
Synthesis of published work within the field of exercise training and peripheral arterial disease.
Supervised exercise training is considered the most effective treatment for increasing exercise tolerance in patients with PAD, and is also associated with improvements in daily physical activity and quality of life, and a reduction is cardiovascular disease risk. Exercise should be prescribed and progressed for patients individually, taking into consideration their disease severity, exercise tolerance and relevant comorbidities.
While walking programs are beneficial and frequently prescribed, other forms of aerobic exercise such as cycling or arm-cranking may also be incorporated as tolerated by patients. Forty minutes of accumulated aerobic activity, three times per week, is recommended for most patients. Patients should be encouraged to commence exercise at a moderate intensity, and should stop and rest if claudication pain becomes severe. Resistance training should also be included on at least two days per week with the goal of improving muscular strength and endurance. Comorbidities such as musculoskeletal complaints, hypertension, diabetes and peripheral neuropathy are common in patients with PAD and may exacerbate their functional limitations. Given the high cardiovascular risk associated with PAD, it is important that patients are appropriately monitored during exercise.
[Show abstract][Hide abstract] ABSTRACT: Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared to healthy control subjects. Twenty-one PAD patients and 17 aged controls were randomly assigned to either a passive movement or an active exercise study. Interstitial fluid microdialysate and tissue samples were obtained from the thigh skeletal muscle. Muscle dialysate vascular endothelial growth factor (VEGF) levels were modestly increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor trombospondin-1 protein (TSP-1) was markedly higher (P<0.05) in PAD patients compared to the control subjects, whereas soluble VEGF receptor-1 dialysate levels were similar in the two groups. The basal VEGF protein content in the muscle tissue samples was ~27% lower (P<0.05) in the PAD patients compared to the control subjects. Analysis of mRNA expression for a range of angiogenic and angiostatic factors revealed a modest change with active exercise and passive movement in both groups, except for an increase (P<0.05) in the ratio of angiopoietin2/angiopoietin1 mRNA in the PAD group with both interventions. PAD patients and aged individuals showed a similar limited angiogenic response to active exercise and passive movement. The limited increase in muscle extracellular VEGF combined with an elevated basal level of TSP-1 in muscle extracellular fluid of PAD patients may restrict capillary growth in these patients.
[Show abstract][Hide abstract] ABSTRACT: Peripheral artery disease (PAD) is a strong predictor of cardiovascular morbidity and mortality yet it is under-recognised and undertreated. General practitioners (GPs) are best positioned to detect patients with PAD. This article investigates awareness of PAD by GPs; the prevalence of screening for PAD and tools used for screening and diagnosis, in particular the ankle-brachial index (ABI); and the barriers to PAD screening and measurement of the ABI in the general practice setting. A cross-sectional survey of primary care practitioners was conducted between September 2011 and March 2012. A mail-out survey was distributed to 1120 GPs practising in Queensland, Australia: 287 (26%) responded; 61% of GPs reported screening for PAD; 58% of GPs reported 'never' measuring the ABI; and 70% reported using arterial duplex ultrasound as their first-line diagnostic tool. Equipment availability, time constraints and lack of training and skills were identified as the most significant barriers to screening and ABI testing. In conclusion, there are deficits in the utilisation of guideline recommendations relating to PAD screening and diagnosis by Australian GPs. Our data suggest that earlier detection of PAD may be achieved through GP education combined with increased access to ABI equipment or the availability of a more time-efficient test.
Vascular Medicine 10/2013; 18(6). DOI:10.1177/1358863X13505673 · 1.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Most abdominal aortic aneurysms (AAAs) contain intraluminal thrombus (ILT), which has been demonstrated to contain proteolytic enzymes and proinflammatory cytokines implicated in AAA progression and rupture. In animal models, anticoagulants have been shown to limit AAA progression. Whether ILT plays a role in AAA rupture is unknown. The aim of this study was to compare the volume of ILT in patients with ruptured and intact AAAs.
We matched by maximum axial diameter alone, on a 1:2 basis, 28 patients with ruptured AAAs and 56 patients with intact AAAs. Total infrarenal aortic volume and ILT volume were measured from computed tomography angiograms using a previously validated and reproducible semiautomated workstation protocol. Clinical risk factors were also recorded. The Mann-Whitney U test was used to compare ILT volumes between patients with ruptured and intact AAAs.
Median (interquartile range [IQR]) maximum AAA diameter (84.0 [77.5-93.9] mm vs 82.6 [77.1-93.3] mm; P = .769) and median (IQR) total AAA volume (372.8 [277.4-486.1] cm(3) vs 358.4 [289.1-563.4] cm(3); P = .977) were similar in patients with ruptured and intact AAAs. Median (IQR) AAA ILT volume was similar in patients with ruptured (152.7 [84.8-252.4] cm(3)) and intact (180.1 [89.9-254.8] cm(3); P = .414) AAAs.
This study suggests that ILT volume is not different in ruptured and intact AAAs.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 10/2013; 59(2). DOI:10.1016/j.jvs.2013.08.036 · 3.02 Impact Factor