Systematic review and meta-analysis of peak wall stress and peak wall rupture index in ruptured and asymptomatic intact abdominal aortic aneurysms

BACKGROUND: Prior studies have suggested aortic peak wall stress (PWS) and peak wall rupture index (PWRI) can estimate the rupture risk of an abdominal aortic aneurysm (AAA), but whether these measurements have independent predictive ability over assessing AAA diameter alone is unclear. The aim of this systematic review was to compare PWS and PWRI in participants with ruptured and asymptomatic intact AAAs of similar diameter. METHODS AND RESULTS: Web of Science, Scopus, Medline, and The Cochrane Library were systematically searched to identify studies assessing PWS and PWRI in ruptured and asymptomatic intact AAAs of similar diameter. Random-effects meta-analyses were performed using inverse variance-weighted methods. Leave-one-out sensitivity analyses were conducted to assess the robustness of findings. Risk of bias was assessed using a modification of the Newcastle-Ottawa scale and standard quality assessment criteria for evaluating primary research papers. Seven case-control studies involving 309 participants were included. Meta-analyses suggested that PWRI (standardized mean difference, 0.42; 95% CI, 0.14–0.70; P=0.004) but not PWS (standardized mean difference, 0.13; 95% CI, −0.18 to 0.44; P=0.418) was greater in ruptured than intact AAAs. Sensitivity analyses suggested that the findings were not dependent on the inclusion of any single study. The included studies were assessed to have a medium to high risk of bias. CONCLUSIONS: Based on limited evidence, this study suggested that PWRI, but not PWS, is greater in ruptured than asymptomatic intact AAAs of similar maximum aortic diameter

Whole genome expression analysis within the angiotensin II-apolipoprotein E deficient mouse model of abdominal aortic aneurysm

Abstract\ud Background: An animal model commonly used to investigate pathways and potential therapeutic\ud interventions relevant to abdominal aortic aneurysm (AAA) involves subcutaneous infusion of\ud angiotensin II within the apolipoprotein E deficient mouse. The aim of this study was to investigate\ud genes differentially expressed in aneurysms forming within this mouse model in order to assess the\ud relevance of this model to human AAA.\ud Results: Using microarrays we identified genes relevant to aneurysm formation within\ud apolipoprotein E deficient mice. Firstly we investigated genes differentially expressed in the\ud aneurysm prone segment of the suprarenal aorta in these mice. Secondly we investigated genes that\ud were differentially expressed in the aortas of mice developing aneurysms relative to those that did\ud not develop aneurysms in response to angiotensin II infusion. Our findings suggest that a host of\ud inflammation and extracellular matrix remodelling pathways are upregulated within the aorta in\ud mice developing aneurysms. Kyoto Encyclopedia of Genes and Genome categories enriched in the\ud aortas of mice with aneurysms included cytokine-cytokine receptor interaction, leukocyte\ud transendothelial migration, natural killer cell mediated cytotoxicity and hematopoietic cell lineage.\ud Genes associated with extracellular matrix remodelling, such as a range of matrix\ud metalloproteinases were also differentially expressed in relation to aneurysm formation.\ud Conclusion: This study is the first report describing whole genome expression arrays in the\ud apolipoprotein E deficient mice in relation to aneurysm formation. The findings suggest that the\ud pathways believed to be critical in human AAA are also relevant to aneurysm formation in this\ud mouse model. The findings therefore support the value of this model to investigate interventions\ud and mechanisms of human AAA

High ankle brachial index predicts high risk of cardiovascular events amongst people with peripheral artery disease

Ankle-brachial pressure index (ABPI) is commonly measured in people referred to vascular specialists. This study aimed to assess the association of high ABPI (≥ 1.4) with cardiovascular events in people with peripheral artery disease (PAD). 1533 participants with PAD diagnosed by a vascular specialist were prospectively recruited from four out-patient clinics in Australia. ABPI was measured at recruitment and the occurrence of myocardial infarction (MI), stroke or cardiovascular death (major cardiovascular events; MACE) and any amputation were recorded over a median (inter-quartile range) follow-up of 3.3 (1.0-7.1) years. The association of high, compared to normal, low (0.5-0.9) or very low (<0.5), ABPI with clinical events was estimated using Cox proportional hazard analyses, adjusting for traditional risk factors and reported as hazard ratio with 95% confidence intervals. 596 (38.9%), 676 (44.1%), 157 (10.2%) and 104 (6.8%) participants had normal, low, very low and high ABPI, respectively. Participants with high ABPI had increased risk of MACE, MI and death by comparison to those with either normal ABPI [1.69 (1.07, 2.65), 1.93 (1.07, 3.46) and 1.67 (1.09, 2.56)] or either low or very low ABPI [1.51 (1.02, 2.23), 1.92 (1.16, 3.19) and 1.47 (1.02, 2.14)] after adjusting for other risk factors. Findings were similar in a sensitivity analysis excluding people with ABPI only measured in one leg (n = 120). Participants with high ABPI also had an increased risk of MACE and MI compared to those with very low ABPI alone. High ABPI is a strong indicator of excess risk of cardiovascular events amongst people with PAD

The reproducibility of measuring maximum abdominal aortic aneurysm diameter from ultrasound images

Background: Accurate repeat assessment of the diameter of an abdominal aortic aneurysm (AAA) is important. This study investigated the reproducibility of different methods of measuring AAA diameter from ultrasound images. Methods: Fifty AAA patients were assessed by ultrasound. Maximum AAA diameter was measured independently by three trained observers on two separate occasions using a standardised protocol. Five diameters were measured from each scan, three in the anterior-posterior (AP) and two in the transverse (TV) plane, including inner-to-inner (ITI), outer-to-outer (OTO) and leading edge-to-leading edge (LETLE). Intra- and inter-observer reproducibility were reported as reproducibility coefficients. Statistical comparison of methods was performed using linear mixed effects models. Results: Intra-observer reproducibility coefficients (AP LETLE 2.2 mm; AP ITI 2.4 mm; AP OTO 2.6 mm) were smaller than inter-observer reproducibility coefficients (AP LETLE 4.6 mm: AP ITI 4.5; and AP OTO 4.8 mm). There was no statistically significant difference in intra-observer reproducibility of three types of measurements performed in the AP plane. Measurements obtained in the TV plane had statistically significant worse intra-observer reproducibility than those performed in the AP plane. Conclusions: This study suggests that the comparison of maximum AAA diameter between repeat images is most reproducibly performed by a single trained observer measuring diameters in the AP plane

Association of computed tomographic leg muscle characteristics with lower limb and cardiovascular events in patients with peripheral artery disease

Background Poor lower extremity physical performance is an independent predictor of unfavorable outcome in patients with peripheral artery disease (PAD); however, few studies have assessed muscle characteristics on imaging directly. Method and Results A novel 3‐dimensional semi‐automated protocol was developed to estimate leg muscle volume and density (mean attenuation) from computed tomography images. Patients with PAD who underwent a lower extremity computed tomography scan at a tertiary vascular surgery center were included, and were followed up using hospital records and linked data as part of a retrospective cohort study. The primary outcomes were lower limb events (major amputation or peripheral revascularization) and cardiovascular events (myocardial infarction, stroke, or cardiovascular death). Two hundred and twenty‐three patients with PAD were included (median age 69.0 years; 73% men) and followed for a median of 4.9 [2.6–7.0] years. During this time there were 99 index lower limb events and 97 cardiovascular events. Low leg muscle density was associated with increased risk of lower limb (rate ratio 1.41 [1.11–1.80] per SD reduction) and cardiovascular events (rate ratio 1.60 [1.29–1.99] per SD reduction). Low muscle density remained an independent predictor of cardiovascular (but not lower limb) events, after adjusting for age, sex, traditional cardiovascular risk factors, and angiographic PAD severity (rate ratio 1.39 [1.09–1.77] per lower SD). In contrast, leg muscle volume was not associated with outcomes after adjusting for risk factors and PAD severity. Conclusions Low leg muscle density, but not volume, is a strong, independent predictor of major cardiovascular events among people with PAD. Further research is needed to understand the mechanisms underlying these associations

Health-related quality of life amongst people diagnosed with abdominal aortic aneurysm and peripheral artery disease and the effect of fenofibrate

The aims of this study were, firstly, to assess the effect of concurrent peripheral artery disease (PAD) on the health-related quality of life (QOL) of people diagnosed with a small abdominal aortic aneurysm (AAA); and secondly, to test whether the peroxisome proliferator-activated receptor alpha agonist fenofibrate improved QOL of people diagnosed with a small AAA, including those diagnosed with concurrent PAD. The study included both a cross-sectional observational study and a randomized placebo-controlled clinical trial. 140 people diagnosed with a 35-49 mm diameter AAA, 56 (40%) of whom had concurrent PAD, and 25 healthy controls were prospectively recruited. QOL was assessed with the short form (SF) 36. Findings in participants that were diagnosed with both AAA and PAD were compared separately with those of participants that had a diagnosis of AAA alone or who had neither AAA nor PAD diagnosed (healthy controls). All participants diagnosed with an AAA were then randomly allocated to 145 mg of fenofibrate per day or identical placebo. Outcomes were assessed by changes in the domains of the SF-36 and ankle brachial pressure Index (ABPI) from randomization to 24 weeks. Data were analyzed using Mann-Whitney U tests. Participants diagnosed with both AAA and PAD had significantly worse QOL than participants diagnosed with AAA alone or healthy controls. Fenofibrate did not significantly alter SF-36 scores or ABPI over 24 weeks. Fenofibrate does not improve QOL of people diagnosed with small AAA, irrespective of whether they have concurrent PAD.Trial registration: ACTN12613001039774 Australian New Zealand Clinical Trials Registry

Association between aortic peak wall stress and rupture index with abdominal aortic aneurysm–related events

Objective: The aim of this study was to assess whether aortic peak wall stress (PWS) and peak wall rupture index (PWRI) were associated with the risk of abdominal aortic aneurysm (AAA) rupture or repair (defined as AAA events) among participants with small AAAs. Methods: PWS and PWRI were estimated from computed tomography angiography (CTA) scans of 210 participants with small AAAs (≥ 30 and ≤ 50 mm) prospectively recruited between 2002 and 2016 from two existing databases. Participants were followed for a median of 2.0 (inter-quartile range 1.9, 2.8) years to record the incidence of AAA events. The associations between PWS and PWRI with AAA events were assessed using Cox proportional hazard analyses. The ability of PWS and PWRI to reclassify the risk of AAA events compared to the initial AAA diameter was examined using net reclassification index (NRI) and classification and regression tree (CART) analysis. Results: After adjusting for other risk factors, one standard deviation increase in PWS (hazard ratio, HR, 1.56, 95% confidence intervals, CI 1.19, 2.06; p = 0.001) and PWRI (HR 1.74, 95% CI 1.29, 2.34; p 0.562. PWRI, but not PWS, significantly improved the classification of risk of AAA events compared to the initial AAA diameter alone. Conclusion: PWS and PWRI predicted the risk of AAA events but only PWRI significantly improved the risk stratification compared to aortic diameter alone. Key Points: • Aortic diameter is an imperfect measure of abdominal aortic aneurysm (AAA) rupture risk. • This observational study of 210 participants found that peak wall stress (PWS) and peak wall rupture index (PWRI) predicted the risk of aortic rupture or AAA repair. • PWRI, but not PWS, significantly improved the risk stratification for AAA events compared to aortic diameter alone

Circulating biomarkers are not associated wtih endoleaks after endovascular repair of abdominal aortic aneurysms

Objective: Endoleak is a common complication of endovascular repair (EVAR) for abdominal aortic aneurysm (AAA), but can only be detected through prolonged follow-up with repeated aortic imaging. This study examined the potential for circulating matrix metalloproteinase-9 (MMP9), osteoprotegerin (OPG), D-dimer, homocysteine (HCY) and C-reactive protein (CRP) to act as diagnostic markers for endoleak in AAA patients undergoing elective EVAR. Methods: Linear mixed effects models were constructed to assess differences in AAA diameter after EVAR, between groups of patients who did, and did not develop endoleak during follow-up, adjusting for potential confounders. Circulating MMP9, OPG, D-dimer, HCY and CRP concentrations were measured in pre- and post-operative plasma samples. The association of these markers with endoleak diagnosis was assessed using linear mixed effects adjusted as above. The potential for each marker to diagnose endoleak was assessed using receiver operator characteristic (ROC) curves. Results: Seventy-five patients were included in the current study, 24 of whom developed an endoleak during follow-up. Patients with an endoleak had significantly large AAA sac diameters than those that did not have an endoleak. None of the assessed markers showed a significant association with endoleak. This was confirmed through ROC curve analyses indicating poor diagnostic ability for all markers. Conclusions: Circulating concentrations of MMP9, OPG, D-dimer, HCY and CRP were not associated with endoleak in patients undergoing EVAR in this study

A Cross-Sectional Study Investigating Canadian and Australian Adolescents' Perceived Experiences of COVID-19: Gender Differences and Mental Health Implications

The coronavirus (COVID-19) disease pandemic has been associated with adverse psychological outcomes. This cross-cultural study (N = 1326, 71% female) aimed to investigate Canadian and Australian adolescents’ subjective experiences of COVID-19, gender differences, and psychological implications. Mixed-methods analyses were used to examine differences in COVID-19 experiences and mental health outcomes between country and gender in a Canadian (N = 913, 78% fe-male) and an Australian sample (N = 413, 57% female) of adolescents. Canadian adolescents reported increased COVID-19 discussions and more concerns related to their COVID-19 experiences compared to Australian adolescents. Girls consistently reported more concerns related to COVID-19 and poorer psychological outcomes compared to boys. School lockdown for the Canadian sample may have played a role in these country differences. Further, girls might be at significantly more risk for mental health concerns during COVID-19, which should be considered in adolescent mental health initiatives during the pandemic. Although school disruption and separation of peers due to the pandemic likely have a role in adolescent perceived stressors and mental health, the differences between Canadian and Australian adolescents were less clear and future investigations comparing more objective pre-COVID-19 data to current data are needed

Association of lower extremity performance with cardiovascular and all-cause mortality in patients with peripheral artery disease: A systematic review and meta-analysis

Background: Peripheral artery disease (PAD) is associated with impaired mobility and a high rate of mortality. The aim of this systematic review was to investigate whether reduced lower extremity performance was associated with an increased incidence of cardiovascular and all‐cause mortality in people with PAD. Methods and Results: A systematic search of the MEDLINE, EMBASE, SCOPUS, Web of Science, and Cochrane Library databases was conducted. Studies assessing the association between measures of lower extremity performance and cardiovascular or all‐cause mortality in PAD patients were included. A meta‐analysis was conducted combining data from commonly assessed performance tests. The 10 identified studies assessed lower extremity performance by strength tests, treadmill walking performance, 6‐minute walk, walking velocity, and walking impairment questionnaire (WIQ). A meta‐analysis revealed that shorter maximum walking distance was associated with increased 5‐year cardiovascular (unadjusted RR=2.54, 95% CI 1.86 to 3.47, P&lt;10&minus;5, n=1577, fixed effects) and all‐cause mortality (unadjusted RR=2.23 95% CI 1.85 to 2.69, P&lt;10&minus;5, n=1710, fixed effects). Slower 4‐metre walking velocity, a lower WIQ stair‐climbing score, and poor hip extension, knee flexion, and plantar flexion strength were also associated with increased mortality. No significant associations were found for hip flexion strength, WIQ distance score, or WIQ speed score with mortality. Conclusions: A number of lower extremity performance measures are prognostic markers for mortality in PAD and may be useful clinical tools for identifying patients at higher risk of death. Further studies are needed to determine whether interventions that improve measures of lower extremity performance reduce mortality